PN F Manual For Primary Healthcare Final

i
ii
Philippine National Formulary
Manual for
Primary Healthcare
8th Edition
Department of Health
Manila, Philippines
2014
iii
PNF new 4 new.pdf 1 1/8/15 3:06 PM

',6&/$,0(5
This Manual which is intended for the Primary Healthcare prescribers contains
the list of medicines, their therapeutic information, and other data that were collated
as meticulously as possible through the collaborative efforts of the Formulary Execu-
tive Council, medical specialists, specialty societies, and pharmacists applying the
standard clinical practice current at the time of the undertaking. Thus, the contents
are the most recent only insofar as the dates of the actual collaboration are con-
cerned. There is no guarantee that after the final drafting for this edition, the new in-
formation that may subsequently become available will be included.
While diligent effort has been made to ensure the accuracy of the information
for each medicine included in this volume, the data presented here is a synopsis of
key points in the official product labeling. The complete labeling contains additional
precautionary information that may be of significance in specific cases. Thus, the edi-
tors do not warrant that the information contained herein is in every aspect accurate.
The editors have included only the information that they consider to be essen-
care level. It is the
tial, relevant and useful for the prescribers at the Primary HealthCare
hope of the editors that this Manual will be a readily accessible, easily understanda-
ble, up-dated source of independent medicine information for these prescribers.
Nevertheless, readers should refer to more recent and comprehensive materials and
publications to supplement this Manual.
Moreover, the recommendations incorporated into the clinical practice guide-

lines are intended to serve only as guides that will supplement and not replace the
best clinical judgment of the prescribing clinicians. Readers are enjoined to confirm
the information contained herein with other sources, particularly with regard to the
newest or the latest information.
All rights reserved 2014
The Formulary Executive Council

National Center for Pharmaceutical Access and Management
Department of Health
San Lazaro Compound, Rizal Ave., Sta. Cruz, Manila, Philippines, 1003
ISBN 978-971-92174-9-7
The completion of this publication was made possible through the financial and technical sup-
port from the World Health Organization-Western Pacific Regional Office and Office of the
WHO Representative in the Philippines.
Any part of the book or its entirety may be reproduced or transmitted without any alteration, in
any form or by any means, with permission from DOH provided it is not used for commercial
purposes.
iv
PHILIPPINE NATIONAL FORMULARY
MANUAL for
PRIMARY HEALTHCARE
8th Edition
2014
DEPARTMENT OF HEALTH
Enrique T. Ona, MD, FPCS, FACS
Secretary of Health
Madeleine De Rosas-Valera, MD, MScIH (Heidelberg)

Former Undersecretary of Health
Health Policy Finance and Research Development Cluster
NATIONAL CENTER FOR PHARMACEUTICAL

ACCESS AND MANAGEMENT
Ma. Virginia G. Ala, MD, MPH, CESO III
Immediate Past Director IV and Program Manager
Anna Melissa S. Guerrero, MD, MPH (HTA)

OIC – Program Manager
FORMULARY EXECUTIVE COUNCIL

Alex J. Bienvenido Alip Jr., MD, FPAFP
Ma. Minerva P. Calimag, MD, MSc, PhD, DPBA, FPSECP
Bu C. Castro, MD, LIB, FPSP
Marita B. Dantes, MD, FPNA
Raul E. Echipare, MD, MPH
Cecilia A. Jimeno, MD, FPCP, FPSEDM
Hilton Y. Lam, MHA, PhD
Cecilia C. Maramba-Lazarte, MD, MScID, FPIDSP
Imelda G. Peña, RPh, MS, DrPH
Genesis C. Rivera, MD, FPPS, FPSECP
Isidro C. Sia, MD, PhD, FPSECP
FEC Chair (2011-2012)
Madeleine De Rosas-Valera, MD, MScIH (Heidelberg)
FEC Chair (2013)
Kenneth Y. Hartigan-Go, MD, MD (UK), FPCP, FPSECP, FPSCOT, FICD, FACP
FEC Chair (2014)
v
PHILIPPINE NATIONAL FORMULARY
MANUAL for
PRIMARY HEALTHCARE
8th Edition
2014
EDITORIAL TEAM

Editor-in-Chief
Mac Ardy J. Gloria, RPh

Associate Editor
Isidro C. Sia, MD, PhD

Irene V. Florentino-Fariñas, RPh, MD
Joyce Anne D. Ceria, RPh
Roderick L. Salenga, RPh, MPH
Anne Julienne M. Genuino, RPh
Johanna B. Mallari, RPh
Members of the Editorial Team
Ermalyn M. Magturo
Technical Assistant
vi
PNF new 7 new .pdf 1 1/6/15 6:25 PM
&2175,%87256
&2175,%87256
Dr. Ma. Teresa B. Abola
Dr. Ma. Teresa B. Abola
&DUGLRORJ\6SHFLDOW\([SHUW
&DUGLRORJ\6SHFLDOW\([SHUW
Research Institute for Tropical Medicine
Dr. Celiafor
Research Institute C.Tropical
Carlos Medicine
Dr. Celia
Head, Antimicrobial C. Carlos
Resistance Surveillance Program
Head, Antimicrobial Resistance Surveillance Program
National Center for Mental Health
National Dr.Center
Venus for Serra-Arain
Mental Health
Venus Serra-Arain
Dr. Beverly A. Azucena
Dr.Dr.Beverly
AldenA. C.Azucena
Cuyos
Dr. Alden C. Cuyos
National Poison Management and Control Center
Dr. Nelia
National Poison P. Cortes-Maramba
Management and Control Center
Dr.Nelia
Dr. Carissa P. Cortes-Maramba
Paz C. Dioquino
Dr.Dr.
Carissa
Lynn C. Paz C. Dioquino
Panganiban
Dr. Lynn C. Panganiban
Philippine Academy of Ophthalmology
Dr. Harvey
Philippine Academy ofS. Uy
Ophthalmology
Dr. Harvey S. Uy
Philippine Academy of Pediatric Pulmonologists
Philippine2012 PAPP of
Academy Task Force on
Pediatric pCAP
Pulmonologists
2012 PAPP Task Force on pCAP
Philippine College of Chest Physicians
Dr. Celeste
Philippine College MaeofL.Chest
Campomanes
Physicians
Dr. Celeste MaePast
Immediate L. Campomanes
President
Dr. Immediate
Chad Rey PastV. Carungin
President
Dr.
Dr.Chad Rey
Ma. Bella V.
R.Carungin
President Siasoco
Dr.Chair,
Ma. Council
Bella R. Siasoco
on Asthma
Dr. Tim
Chair, S. on
Council Trinidad
Asthma
Dr. Tim
Chair, S. Trinidad
Council on COPD
Dr. Rizal
Chair,Alberto B.COPD
Council on Nolido, Jr.
Dr. Rizal
Chair, Alberto
Council B. Nolido,
on Pulmonary Jr.
Infections
Chair, Council on Pulmonary Infections
Philippine Dermatological Society
Dr. Blossom
Philippine Tian Chan
Dermatological Society
Dr. Blossom Tian Chan
Philippine Heart Association
Dr. Joel
Philippine HeartM. Abanilla
Association
Dr. Joel M. Abanilla
President
Dr. Federick C. Cheng
President
Dr. Federick
Chair, Council onC. Cheng
Hypertension
Dr. Ma.
Chair, Teresa
Council B. Abola
on Hypertension
Dr.
Dr.Ma. TeresaB.B.Reyes
Eugenio Abola
Dr. Eugenio B. Reyes
Dr. Irma Marie P. Yape
Dr. Irma Marie P. Yape

vii
vii
CONTRIBUTORS
Philippine Neurological Association
Dr. Artemio A. Roxas
Dr. Wilfredo C. Calma
Philippine Nutrition Society

Dr. Yasmin Laura Marie C. Zuñiga
Philippine Obstetrical and Gynecological Society

Dr. Godofreda Vergeire-Dalmacion
Philippine Psychiatric Association

Dr. Edgardo Juan L. Tolentino, Jr.
Dr. Ponciano Z. Jerez Jr.
Dr. Maria Teresa Aguilar-Icasiano
Philippine Rheumatology Association
Dr. Inocencio P. Alejandro
Philippine Society of Endocrinology and Metabolism
Dr. Cecilia A. Jimeno
Philippine Society of Gastroenterology
Dr. Joseph C. Bocobo
Dr. Augusto Jose G. Galang
Philippine Society of Hematology and Blood Transfusion

Dr. Ma. Angelina L. Mirasol
Philippine Society for Microbiology and Infectious Diseases
Dr. Ludovico L. Jurao, Jr.
Philippine Society of Nephrology
Dr. Delia V. Bayog
Dr. Susan Anonuevo-de la Rama
Philippine Society of Otolaryngology, Head and Neck Surgery
Dr. Natividad A. Almazan
Philippine Urological Association
Dr. Ulysses T. Quanico
Dr. Rufino T. Agudera
viii
Department of Health – Office of the Secretary
MESSAGE
th
It has been six years since the 7 edition of the Philippine National For-
mulary (PNF) Manual for Primary Healthcare has been utilized in the rational
selection and use of essential medicines. With the development of its “new and
improved” version, the Department of Health is very proud to present a more
relevant tool to promote the safe, effective and rational use of medicines (RUM)
in the grass roots.
The existence of a national formulary is very essential in providing

objective, unbiased drug information to various healthcare providers and oth-
er stakeholders. The PNF, previously known as the Philippine National Drug
Formulary (PNDF), has been evaluated, assessed and updated to ensure its
relevance to the people’s health needs. More importantly, it aims to remain
as a significant primary reference for prescribing, and to facilitate adherence
to the principles of RUM by all of the practitioners, most especially those in
primary healthcare facilities. Unlike previous editions, this publication con-
tains a wealth of information on a list of essential medicines as well as the
current clinical practice guidelines for a selected group of common diseases
intended for use by the country’s primary healthcare providers.
I would like to commend and thank all the members of the Formulary
Executive Council, the editorial team, PNFS Secretariat, medical societies,
and resource persons who have provided their precious time and expertise in
order to make this project a success.
I urge each individual to be one with us in the achievement of univer-

sal healthcare through the provision of safe, quality and cost-effective essen-
tial medicines for all Filipinos.
Enrique T. Ona, MD, FPCS, FACS

Secretary of Health
ix
National Center for Pharmaceutical Access and Management
MESSAGE
Essential medicines are necessary tools to address diseases that
cause the greatest morbidity and mortality in the country. For this reason, the
National Center for Pharmaceutical Access and Management (NCPAM) of
th
the Department of Health (DOH) presents the 8 Edition of the Philippine
National Formulary Manual for Primary Healthcare (PHC).
The Manual provides an adequate list of essential medicines neces-

sary to address not only the priority diseases and health care needs of the
country but the endemic diseases in a particular locality as well. The selec-
tion was based on the current clinical practice guidelines which also consid-
ered the affordability and cost-effectiveness of the medicines when imple-
mented at the primary level of health care. Antibiotics for the treatment of the
common communicable diseases (e.g., urinary tract infection and infectious
diarrheal diseases) and medications for hypertension and diabetes mellitus
have also been added.
The PHC Formulary is intended to serve as the primary reference

and guidance for healthcare workers in the primary level given the vital func-
tions that they carry out. The Manual contains information not only on the
rational selection and use of medicines, but also drug management in its en-
tirety. It contains prescribing information validated by specialty experts and
based on current local standards of practice. Discussions on the rising global
and local problems such as antimicrobial resistance are also incorporated.
Antimicrobial Resistance Alerts are added to the prescribing information on
the anti-infective medicines, to warn against the dangers of inappropriately
using antibiotics.
I commend the NCPAM, the Formulary Executive Council, the edito-

rial team, and everyone else who devoted their time and effort in the prepara-
tion and completion of this publication.
Thank you and mabuhay!
Lilibeth C. David, MD, MPH, MPM, CESO III

OIC – Cluster Head
Health Policy Finance and Research Development Cluster
Director IV, Health Policy Development and Planning Bureau
x
INTRODUCTION TO THE PNF 8TH EDITION:
MANUAL FOR PRIMARY HEALTHCARE
“A Timely Challenge”
The Formulary Executive Council’s primary goal in the revision of the Manu-
al for Primary Healthcare was to empower the primary health physicians by
further capacitating them through the provision of comprehensive knowledge
on sound, evidence-based pharmacologic interventions that will merge conformi-
ty to current clinical practice standards with cost-effectiveness. This aims to
address the specific health concerns and needs of the mostly low-resource
communities they serve.
To explicitly define these needs, a situational analysis of the practices per-

taining to the utilization of the national formulary was carried out in several public
health facilities. At the primary level, the foremost problem that hindered the use
of the Formulary was the perception of many doctors that the Primary Care List
of Medicines was very limited and already outdated for which a more sufficient
list of medicines, prescriber information and practice guidelines were called for.
Other pertinent problems and their underlying causes were elucidated, many of
which were deep-rooted and beyond the scope of the healthcare providers and
the FEC. Nevertheless, the revision of the Formulary was set in the context of
these needs.
To meet these needs, the following specific strategies were enhanced and
applied:
a. Provision of a comprehensive list of medicines that will allow the pri-

mary healthcare physicians to administer the adequate pharmacother-
apeutic management of the diseases frequently encountered at their
facilities.
The physician can select the appropriate medicine from a wider range of
pharmacotherapeutic agents. This will also help ease the problem of out-of-
pocket payment of patients and their families in the mostly low-resource are-
as served by the primary care providers.
Medicines included in the manual are indicated for the priority diseases and
health needs in the country or for diseases endemic in a particular locality.
Further selection processes for each of the medicines considered efficacy,
safety, and comparative cost-effectiveness. These were based on sound
scientific evidence on optimum clinical benefits of the medicine for a given
indication (efficacy), and the minimum production of adverse effects (safety).
In comparing the costs of the medicines, the total treatment costs and not
only the unit costs were considered. The evidence-based Clinical Practice
Guideline or the current standard of practice served as the main frame of
reference in the final selection of the medicines.
The medicines that were added included antibiotics needed for treatment of
the common communicable diseases (e.g., community acquired pneumonia,
urinary tract infection, and infectious diarrheal diseases), additional medica-
xi
tions to address the rising trend in low-income communities of hypertension
and diabetes mellitus, vaccines, antibacterial ophthalmic and otic prepara-
tions, and psychopharmacologic medications. Moreover, medicines needed
for the emergency management of serious diseases in patients awaiting
transfer to a hospital were included.
b. Provision of a readily accessible, and updated rapid reference on the

medicines that is based on sound scientific evidence, and that con-
tains all necessary prescribing information validated by specialty ex-
perts and checked against current local standards of practice.
The medicines list, the monographs, and cross-references were integrated

into a single manual. Succinct explanations of the reasons behind drug in-
teractions, precautions, and adverse events were added to the prescribing
information to emphasize the scientific basis for using the medicines. The
prescribing information and practice guidelines were submitted to the medi-
cal and surgical specialty societies for review and validation.
Clinical practice guidelines on the management of hypertension, diabetes

mellitus, community-acquired pneumonia in adults and children, urinary tract
infection, and poisoning based on the most current local guidelines were in-
cluded. Moreover, management of the diarrheal diseases based on WHO
recommendations was added. Algorithms were provided to further guide the
physicians. “Essential Practice Points” to emphasize focal points in the prac-
tice guidelines were integrated into the algorithms. In addition, steps in the
administration of medicines for the treatment of leptospirosis, and control of
H. pylori infection in peptic ulcer disease and rabies were detailed in the pre-
scribing information. The latest vaccination schedule, general information on
methicillin-resistant Staphylococcus aureus and the recommended treatment
regimen for tuberculosis based on the 2014 National TB Control Program
were also included.
c. Provision of strategies to implement the rational and responsible use

of medicines and to ensure patient safety.
Sections on the Rational Use of Medicines and a review of proper prescrib-

ing were integrated into the General Guidance. Apart from the dose adjust-
ments, drug adverse events and interactions, the prescribing information in-
cluded a more comprehensive listing of the precautions and the precepts to
be followed in the use of antibiotics. The link to the FDA website was also
included for more prompt reporting of adverse drug reactions.
Discussions on the growing global and local problems of antimicrobial re-

sistance were included together with the recommendations from the Antimi-
crobial Resistance Surveillance Program of the DOH based on its most cur-
rent data. Moreover, Antimicrobial Resistance Alerts based on local data
were incorporated into the prescribing information on the anti-infective medi-
cines to signal an alarm to be mindful of the detrimental consequences of
using antibiotics to which organisms have shown an emerging or increasing
non-susceptibility.
xii
d. Provision for a dialogic, inclusive process of communication for en-
hancement of the Formulary and improvement of the patient-doctor re-
lationship.
A situational analysis of the problems in the use of the National Formulary

was initially conducted among primary healthcare providers. The needs elu-
cidated in the study served as the primary bases for the revisions. A phase 1
utilization study (pilot-testing) of the draft of the new volume was subse-
quently undertaken among the municipal and city health officers prior to fina-
lization, using a monitoring tool that had been specifically developed for the
assessment of the formulary. A directory of the hotlines and other contact
numbers of pertinent DOH and FDA offices is provided. Guidelines are also
in place to assist in the establishment of a dynamic interaction between the
primary healthcare physician and the patients or their families.
The current Council did not depart from the two-fold objectives of the previ-
ous Formulary committees. It continues to be governed by the need to espouse
the principles of the rational use of medicines and the need to reconcile provision
of optimum healthcare for all with the wise and efficient channeling of limited
funds of both government and individuals. The crafting, then, of a reliable, re-
sponsive and relevant formulary has remained to be a constant challenge. For
the Council, the fundamental strategy to meet this challenge was to effectively
restructure the formulary in order to augment the knowledge of the primary health
care physicians and the armamentarium available to them.
The Formulary remains as an integral part of the rational and responsible

use of medicines, serving as the basis for rational prescribing that can effect op-
timal health outcomes for all, particularly the underprivileged Filipinos. However,
enhancement of the Formulary alone cannot ensure these.
It is our turn to challenge the healthcare practitioners to utilize the Na-

tional Formulary effectively and faithfully. Only then will it become the vehicle
for rational use of medicines. Only then can it effect the wiser use of finite funds
of both individuals and government that, in turn, will help ensure access to medi-
cines by all, especially the poor.

Mac Ardy J. Gloria, RPh
xiii
$&.12:/('*0(176
This Formulary is adapted from the WHO Model Formulary (2008) with the publisher’s
permission. We acknowledge and fully appreciate the work of the World Health Organization in
developing the WHO Model List of Essential Medicines that has
will assisted countriesininestablishing
assist countries establishing
their own national essential medicines list.
For their invaluable contribution to the current edition of the Philippine National Formu-
lary Manual for Primary Healthcare, sincere gratitude is also due to the following:
Members of the Formulary Executive Council who reviewed the prescribing infor-
mation and related data on the medicines used for their specialties: Dr. Minerva Calimag (anes-
thetic agents, analgesics), Dr. Marita Dantes (anticonvulsants, anti-inflammatory, anti-vertigo
and anti-Parkinson medicines), Dr. Raul Echipare (primary care medicines), Dr. Kenneth Harti-
gan-Go (antidotes), Dr. Cecilia Jimeno (anti-diabetes medicines, thyroid hormones and anti-
thyroid medicines, steroids, and the Clinical Practice Guidelines for Diabetes Mellitus), Dr. Cecil-
ia Maramba-Lazarte (antibiotics, herbal medicines, and medicines for the pediatric patients), Dr.
Genesis Rivera (medicines for the pediatric patients), Dr. Isidro Sia (pharmacology and herbal
medicines). Contributions from the other members are also acknowledged: Dr. Alex Alip, Jr.
(community medicine), Dr. Bu C. Castro (medico-legal), Dr. Hilton Lam (health economics), and
Dean Imelda Peña (pharmacy);
Dr. Myrna T. Mendoza who gave timely comments and provided the latest manuals on
the Philippine Clinical Practice Guidelines for the management of infectious diseases; Drs. Celia
Carlos, Raquel Ecarma, Joseph Michael Jaro, Ernesto Que, Felix Domingo, Jr. and Ronald
Cuyco who gave additional indispensable comments and corrections of the prescribing infor-
mation and clinical guidelines; and the residents of the Department of Internal Medicine of the
National Kidney and Transplant Institute who helped provide further clinical details on the use of
the medicines;
Drs. Nelia Cortes-Maramba, Lynn Panganiban, and Carissa Dioquino of the National
Poison Management and Control Center and Dr. Cristan Cabanilla of the PAPP for allowing the
FEC to incorporate the guidelines in the management of common poisoning and pCAP, respec-
tively; and members of the National Antibiotic Guidelines Committee;
Dr. Ma. Teresa Abola, a member of the Specialty Experts assisting the FEC, for her
untiring efforts in helping polish the prescribing information for the cardiovascular medicines and
guidelines in hypertension;
Mr. Roderick Salenga of the WHO Philippines for his technical assistance in the de-
velopment of the evaluation tool for the pilot test of the Manual;
Dr. Klara Tisocki, Team Leader for Essential Medicines and Health Technologies at
WHO-WPRO for her technical assistance and continuous support for the development of this
Formulary Manual;
Mr. Frederick Pereña who prepared the cover design;
Municipal and City Health Officers and Dentists, and medical officers of the Naval Ed-
ucation and Training Command who generously participated in the initial situational analysis and
the Phase 1 utilization study (pilot test): Drs. Mirian Abadilla, Leonardo Afable, Rodelin Agbulos,
Jr., Veena Aguinaldo, Lorigrace Austria, Jennylin Badiola, Emmeline Baltar, Mirabelle Benjamin,
Dante Brosas, Minerva Cazenas, Elmira Dizon, Irish Fernandez, Benbenato Garcia, Edwin Guin-
to, Ne Hora, Fernando Igrobay, Ma. Linda Llaguno, Evangeline Manzo, Ureka Mariano, Loida
Martin, Ma. Lourdes Pakoy, Luz Pang, Antonette Rico, Soledad Salinas-Villajin, Lenario Santos,
Jhayson de los Santos, Wilfredo Sevilla, Marie Therese Sumbillo, Edna Tabo-oy, Myrna
Trongcoso, Marion Zaragoza-Sengco and NETC Chief Nurse Erlyn Esperas.
xiv
TABLE OF CONTENTS
GENERAL GUIDE ............................................................................................................. xxi
GENERAL GUIDE ON THE USE OF THIS MANUAL .......................................................................... xxii
MEDICINE MONOGRAPH KEY ............................................................................................................ xxiv
GENERAL GUIDE TO PRESCRIBING ................................................................................................. 1
A. RATIONAL APPROACH TO THERAPEUTICS ........................................................................ 1
B. VARIATION IN DOSE-RESPONSE.......................................................................................... 2
1. MEDICINE FORMULATION ..................................................................................... 2
2. BODY WEIGHT AND AGE ....................................................................................... 2
3. DOSE CALCULATION IN CHILDREN ..................................................................... 3
4. PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES .................................. 3
5. MEDICINE DISTRIBUTION ...................................................................................... 4
6. MEDICINE METABOLISM AND EXCRETION......................................................... 4
7. PHARMACODYNAMIC VARIABLES ....................................................................... 5
8. DISEASE VARIABLES ............................................................................................. 5
9. ENVIRONMENTAL VARIABLES .............................................................................. 5
C. ADHERENCE TO, COMPLIANCE WITH AND MAINTENANCE OF MEDICINE TREATMENT ....... 5
1. PATIENT-RELATED REASONS .............................................................................. 6
2. DISEASE-RELATED REASONS .............................................................................. 6
3. DOCTOR-RELATED REASONS .............................................................................. 6
4. DOCTOR-PATIENT INTERACTION ........................................................................ 6
5. PRESCRIPTION-RELATED REASONS .................................................................. 6
6. PHARMACIST-RELATED REASONS...................................................................... 6
7. RECOMMENDATIONS TO THE PRESCRIBERS ................................................... 6
D. ADVERSE EFFECTS AND INTERACTIONS ........................................................................... 7
1. ADVERSE DRUG REACTIONS (ADR) .................................................................... 7
2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS ............................ 7
a. EXTREMES OF AGE ....................................................................................... 7
b. INTERCURRENT ILLNESSES/COMORBIDITIES .......................................... 7
c. MEDICINE INTERACTIONS ............................................................................ 7
d. INCOMPATIBILITIES BETWEEN MEDICINES AND IV FLUIDS ................... 8
e. ADVERSE EFFECTS CAUSED BY TRADITIONAL MEDICINES .................. 8
f. EFFECT OF FOOD ON MEDICINE ABSORPTION ........................................ 8
E. PRESCRIPTION WRITING ...................................................................................................... 8
1. PRESCRIPTION FORM ........................................................................................... 8
2. INCORRECT PRESCRIPTIONS .............................................................................. 9
3. NARCOTICS AND CONTROLLED SUBSTANCES ................................................ 9
F. PATIENT COUNSELING .......................................................................................................... 9
1. WHAT TO COUNSEL ............................................................................................... 10
2. WHO AND WHEN TO COUNSEL ............................................................................ 10
3. COUNSELING: PROCESS STEPS ......................................................................... 10
ANTIMICROBIAL RESISTANCE ........................................................................................................... 12
RELEVANT LAWS, REGULATIONS AND POLICIES ......................................................................... 19
MEDICINE AND THERAPEUTIC INFORMATION ............................................................... 22
ALLERGY AND IMMUNE SYSTEM ...................................................................................................... 23
ANTIHISTAMINES .......................................................................................................................... 23
CETIRIZINE ....................................................................................................................... 23
DIPHENHYDRAMINE ........................................................................................................ 23
LORATADINE .................................................................................................................... 24
STEROIDS ...................................................................................................................................... 25
HYDROCORTISONE ......................................................................................................... 25
PREDNISONE.................................................................................................................... 25
ANTIDOTES ........................................................................................................................................... 26
ACTIVATED CHARCOAL, USP...................................................................................................... 26
ATROPINE ...................................................................................................................................... 26
COBRA ANTIVENIN ....................................................................................................................... 27
PYRIDOSTIGMINE ......................................................................................................................... 28
xv
ANTI-INFECTIVES (SYSTEMIC) ........................................................................................................... 29
ANTIBACTERIALS (Oral and Parenteral)....................................................................................... 29
AMOXICILLIN..................................................................................................................... 29
AMPICILLIN ....................................................................................................................... 30
AZITHROMYCIN ................................................................................................................ 31
CEFALEXIN ....................................................................................................................... 32
CEFIXIME .......................................................................................................................... 33
CEFTRIAXONE .................................................................................................................. 33
CEFUROXIME ................................................................................................................... 35
CHLORAMPHENICOL ....................................................................................................... 36
CIPROFLOXACIN .............................................................................................................. 37
CLARITHROMYCIN ........................................................................................................... 38
CLINDAMYCIN................................................................................................................... 39
CLOXACILLIN .................................................................................................................... 41
CO-AMOXICLAV (Amoxicillin + Potassium Clavulanate) .................................................. 41
COTRIMOXAZOLE (Trimethoprim + Sulfamethoxazole) .................................................. 42
DOXYCYCLINE.................................................................................................................. 44
ERYTHROMYCIN .............................................................................................................. 45
GENTAMICIN ..................................................................................................................... 46
METRONIDAZOLE ............................................................................................................ 47
PENICILLIN G BENZATHINE (Benzathine benzylpenicillin)............................................. 48
PENICILLIN G CRYSTALLINE (Benzylpenicillin) .............................................................. 49
PHENOXYMETHYLPENICILLIN (Penicillin V) .................................................................. 49
ANTI-H. PYLORI INFECTION IN PEPTIC ULCER DISEASE .......................................... 50
AMOXICILLIN ........................................................................................................... 50
CLARITHROMYCIN ................................................................................................. 50
METRONIDAZOLE ................................................................................................... 51
OTHER ANTIBACTERIALS ............................................................................................................ 51
ANTI-LEPROSY ................................................................................................................. 51
CLOFAZIMINE .......................................................................................................... 51
DAPSONE ................................................................................................................ 52
RIFAMPICIN ............................................................................................................. 52
ANTITUBERCULOSIS ....................................................................................................... 53
SINGLE DOSE FORMULATIONS ............................................................................ 53
ETHAMBUTOL .................................................................................................. 53
ISONIAZID......................................................................................................... 53
PYRAZINAMIDE ............................................................................................... 54
RIFAMPICIN ...................................................................................................... 55
STREPTOMYCIN .............................................................................................. 56
FIXED-DOSE COMBINATIONS ............................................................................... 57
ISONIAZID + RIFAMPICIN ............................................................................... 57
ISONIAZID + RIFAMPICIN + ETHAMBUTOL .................................................. 57
ISONIAZID + RIFAMPICIN + PYRAZINAMIDE + ETHAMBUTOL ................... 57
URINARY ANTISEPTIC ..................................................................................................... 57
NITROFURANTOIN .................................................................................................. 57
ANTI-PARASITICS .......................................................................................................................... 58
ANTHELMINTICS .............................................................................................................. 58
FOR COMMON ROUND WORM INFECTIONS ...................................................... 58
ALBENDAZOLE ................................................................................................ 58
ANTIFILARIALS ........................................................................................................ 59
ALBENDAZOLE ................................................................................................ 59
DIETHYLCARBAMAZINE ................................................................................. 59
ANTISCHISTOSOMA ............................................................................................... 60
PRAZIQUANTEL ............................................................................................... 60
ANTIPROTOZOAL ............................................................................................................. 61
ANTIAMEBIASIS, ANTIGIARDIASIS and ANTITRICHOMONIASIS ....................... 61
METRONIDAZOLE ........................................................................................... 61
ANTIMALARIALS...................................................................................................... 61
ARTEMETHER + LUMEFANTRINE ................................................................. 61
xvi
CHLOROQUINE ................................................................................................ 62
DOXYCYCLINE ................................................................................................. 63
PRIMAQUINE .................................................................................................... 63
ANTIVIRAL ...................................................................................................................................... 64
ACICLOVIR / ACYCLOVIR ................................................................................................ 64
OSELTAMIVIR ................................................................................................................... 65
CARDIOVASCULAR SYSTEM .............................................................................................................. 66
ADRENERGICS .............................................................................................................................. 66
DOPAMINE ........................................................................................................................ 66
EPINEPHRINE ................................................................................................................... 67
ANTI-ANGINALS ............................................................................................................................. 68
ISOSORBIDE DINITRATE (ISDN)..................................................................................... 68
DILTIAZEM......................................................................................................................... 69
ANTIDYSLIPIDEMIA ....................................................................................................................... 70
FENOFIBRATE .................................................................................................................. 70
ROSUVASTATIN ............................................................................................................... 70
SIMVASTATIN ................................................................................................................... 72
ANTIHYPERTENSIVES .................................................................................................................. 73
AMLODIPINE ..................................................................................................................... 73
CAPTOPRIL ....................................................................................................................... 73
CLONIDINE ........................................................................................................................ 75
DILTIAZEM......................................................................................................................... 76
ENALAPRIL ........................................................................................................................ 76
HYDROCHLOROTHIAZIDE .............................................................................................. 78
LOSARTAN ........................................................................................................................ 79
METHYLDOPA................................................................................................................... 80
METOPROLOL .................................................................................................................. 80
ANTITHROMBOTICS...................................................................................................................... 82
ASPIRIN ............................................................................................................................. 82
CLOPIDOGREL ................................................................................................................. 83
CARDIOACTIVE ............................................................................................................................. 84
DIGOXIN ............................................................................................................................ 84
DERMATOLOGY.................................................................................................................................... 86
ANTI-ALLERGY .............................................................................................................................. 86
HYDROCORTISONE ......................................................................................................... 86
ANTIBACTERIAL TOPICAL PREPARATIONS .............................................................................. 86
FUSIDIC ACID ................................................................................................................... 86
MUPIROCIN ....................................................................................................................... 87
SILVER SULFADIAZINE.................................................................................................... 87
ANTIFUNGAL, ANTI-LICE and ANTI-SCABIES ............................................................................. 88
AKAPULKO [Senna alata L. (Fam. Fabaceae)] ................................................................ 88
CLOTRIMAZOLE ............................................................................................................... 88
PERMETHRIN.................................................................................................................... 89
ANTIPRURITIC ............................................................................................................................... 89
CALAMINE ......................................................................................................................... 89
EARS, NOSE and THROAT .................................................................................................................. 90
ANTIBACTERIAL OTIC PREPARATION ....................................................................................... 90
NEOMYCIN + POLYMYXIN B + FLUOCINOLONE ACETONIDE .................................... 90
ENDOCRINE SYSTEM and STEROIDS ............................................................................................... 91
ANTIDIABETIC AGENTS ................................................................................................................ 91
GLICLAZIDE ...................................................................................................................... 91
METFORMIN ...................................................................................................................... 92
INSULINS ........................................................................................................................... 92
REGULAR INSULIN (Recombinant DNA, Human) .................................................. 94
NPH HUMAN INSULIN / ISOPHANE INSULIN HUMAN (Recombinant DNA origin) ....... 94
CORTICOSTEROIDS ..................................................................................................................... 95
HYDROCORTISONE ......................................................................................................... 95
PREDNISONE.................................................................................................................... 96
xvii
THYROID HORMONES and ANTITHYROID ................................................................................. 97

LEVOTHYROXINE ............................................................................................................. 97
METHIMAZOLE ................................................................................................................. 98
(<(6
OPHTHALMIC ANTIBACTERIAL PREPARATION ........................................................................ 100
ERYTHROMYCIN .............................................................................................................. 100
TOBRAMYCIN ................................................................................................................... 100
*$6752,17(67,1$/6<67(0
ANTACID ......................................................................................................................................... 101
ALUMINUM HYDROXIDE + MAGNESIUM HYDROXIDE ................................................ 101
ANTI-EMETICS ............................................................................................................................... 101
METOCLOPRAMIDE ......................................................................................................... 101
ANTI-PEPTIC ULCER ..................................................................................................................... 102
PROTON PUMP INHIBITOR ............................................................................................. 102
OMEPRAZOLE ......................................................................................................... 102
ANTISPASMODICS ........................................................................................................................ 103
DICYCLOVERINE .............................................................................................................. 103
HYOSCINE ......................................................................................................................... 104
*(1,7285,1$5<6<67(0
ANTI-UROLITHIASIS ...................................................................................................................... 106
SAMBONG [Blumea balsamifera L. DC (Fam. Asteraceae)] ............................................ 106
DIURETICS ..................................................................................................................................... 106
FUROSEMIDE ................................................................................................................... 106
HYDROCHLOROTHIAZIDE .............................................................................................. 107
FOR BENIGN PROSTATIC HYPERTROPHY ............................................................................... 107
TAMSULOSIN .................................................................................................................... 107
*<1(&2/2*<$1'2%67(75,&6
FOR ECLAMPSIA ........................................................................................................................... 109
MAGNESIUM SULFATE .................................................................................................... 109
HORMONES ................................................................................................................................... 109
ETHINYLESTRADIOL + LEVONORGESTREL ................................................................ 109
MEDROXYPROGESTERONE .......................................................................................... 111
OXYTOCIC ...................................................................................................................................... 112
OXYTOCIN ......................................................................................................................... 112
+(0$72/2*,&6<67(0
ANTIANEMIC .................................................................................................................................. 113
FERROUS SALT ................................................................................................................ 113
ANTIFIBRINOLYTIC ....................................................................................................................... 113
TRANEXAMIC ACID .......................................................................................................... 113
COAGULANT .................................................................................................................................. 114
PHYTOMENADIONE ......................................................................................................... 114
1(592866<67(0DQG086&8/26.(/(7$/6<67(0
ANALGESICS/ANTIPYRETICS..........................
...................................................................................................... 116
PARACETAMOL ................................................................................................................ 116
TRAMADOL ....................................................................................................................... 116
LOCAL(LOCAL)
ANESTHETIC ANESTHETIC ........... ........................................................................................................ 118
LIDOCAINELIDOCAINE ........................................................................................................................ 118
ANTICHOLINERGICS ..................................................................................................................... 119
BIPERIDEN ........................................................................................................................ 119
DIPHENHYDRAMINE ........................................................................................................ 120
ANTICONVULSANTS ..................................................................................................................... 120
CARBAMAZEPINE ............................................................................................................ 120
DIAZEPAM ......................................................................................................................... 122
VALPROATE ...................................................................................................................... 123
ANTI-INFLAMMATORY AGENTS ................................................................................................... 124
CELECOXIB ....................................................................................................................... 124
IBUPROFEN ...................................................................................................................... 126
MEFENAMIC ACID ............................................................................................................ 127
NAPROXEN ....................................................................................................................... 128
xviii
PREDNISONE.................................................................................................................... 129
ANTITHROMBOTICS...................................................................................................................... 130
ASPIRIN ............................................................................................................................. 130
CLOPIDOGREL ................................................................................................................. 130
ANTI-VERTIGO and ANTI-MOTION SICKNESS ........................................................................... 130
MECLIZINE (MECLOZINE) ............................................................................................... 130
PSYCHOPHARMACOLOGIC AGENTS ......................................................................................... 131
ANTIDEPRESSANTS ........................................................................................................ 131
FLUOXETINE ........................................................................................................... 131
SERTRALINE ........................................................................................................... 132
ANTIPSYCHOSIS .............................................................................................................. 133
CHLORPROMAZINE ................................................................................................ 133
HALOPERIDOL ........................................................................................................ 134
OLANZAPINE ........................................................................................................... 136
RISPERIDONE ......................................................................................................... 137
MOOD STABILIZERS ........................................................................................................ 139
CARBAMAZEPINE ................................................................................................... 139
VALPROATE ............................................................................................................ 139
RESPIRATORY SYSTEM ...................................................................................................................... 141
ANTITUSSIVE ................................................................................................................................. 141
BUTAMIRATE .................................................................................................................... 141
BRONCHODILATORS .................................................................................................................... 141
SALBUTAMOL ................................................................................................................... 141
FLUTICASONE + SALMETEROL ..................................................................................... 142
FOR CHRONIC OBSTRUCTIVE PULMONARY DISEASE ........................................................... 143
IPRATROPIUM .................................................................................................................. 143
IPRATROPIUM + SALBUTAMOL ...................................................................................... 144
CORTICOSTEROIDS ..................................................................................................................... 145
HYDROCORTISONE ......................................................................................................... 145
PREDNISONE.................................................................................................................... 145
EXPECTORANT ............................................................................................................................. 146
LAGUNDI [Vitex negundo L. (Fam. Verbenaceae)] .......................................................... 146
LEUKOTRIENE RECEPTOR ANTAGONIST ................................................................................. 146
MONTELUKAST ................................................................................................................ 146
VITAMINS and MINERALS ................................................................................................................... 148
CALCIUM + VITAMIN D .................................................................................................................. 148
FERROUS SALT ............................................................................................................................. 148
FERROUS SALT + FOLIC ACID .................................................................................................... 149
MICRONUTRIENT POWDER ......................................................................................................... 150
MULTIVITAMINS for INFANTS, CHILDREN, and ADULTS ........................................................... 151
RETINOL (Vitamin A) ...................................................................................................................... 152
VITAMIN B1 B6 B12........................................................................................................................ 152
ZINC ................................................................................................................................................ 153
MISCELLANEOUS ................................................................................................................................. 154
ANTISEPTICS ................................................................................................................................. 154
ETHYL ALCOHOL ............................................................................................................. 154
GLUTARALDEHYDE ......................................................................................................... 154
HYDROGEN PEROXIDE ................................................................................................... 154
POVIDONE-IODINE ........................................................................................................... 154
FLUIDS and ELECTROLYTES ....................................................................................................... 155
0.9% SODIUM CHLORIDE ................................................................................................ 155
5% GLUCOSE (DEXTROSE) IN WATER ......................................................................... 155
5% GLUCOSE (DEXTROSE) IN 0.3% SODIUM CHLORIDE ........................................... 156
5% GLUCOSE (DEXTROSE) IN 0.9% SODIUM CHLORIDE ........................................... 156
5% GLUCOSE (DEXTROSE) IN LACTATED RINGER’S ................................................. 157
50% GLUCOSE SOLUTION .............................................................................................. 158
BALANCED MULTIPLE REPLACEMENT SOLUTION ..................................................... 159
LACTATED RINGER’S SOLUTION (RINGER’S LACTATE) ............................................ 159
ORAL REHYDRATION SALTS (ORS 75-replacement) .................................................... 160
xix
SODIUM CHLORIDE ......................................................................................................... 161
STERILE WATER FOR INJECTION ................................................................................. 162
VACCINES and IMMUNOLOGICALS ................................................................................................... 163
ANTI-RABIES SERUM .................................................................................................................... 163
ANTI-TETANUS SERUM ................................................................................................................ 163
BCG VACCINE ................................................................................................................................ 164
DIPHTHERIA-TETANUS TOXOID and PERTUSSIS VACCINE ................................................... 164
HEPATITIS B VACCINE (Recombinant DNA) ................................................................................ 165
INFLUENZA POLYVALENT VACCINE .......................................................................................... 166
LIVE ATTENUATED MEASLES VACCINE .................................................................................... 167
LIVE ATTENUATED MEASLES, MUMPS and RUBELLA VACCINE ............................................ 167
LIVE ATTENUATED TRIVALENT ORAL POLIO VACCINE .......................................................... 168
PENTAVALENT VACCINE ............................................................................................................. 169
RABIES IMMUNOGLOBULIN (EQUINE) – ERIG purified ............................................................. 169
RABIES IMMUNOGLOBULIN (HUMAN) – HRIG ........................................................................... 170
RABIES VACCINE .......................................................................................................................... 171
TETANUS IMMUNOGLOBULIN ..................................................................................................... 172
TETANUS TOXOID ......................................................................................................................... 173
APPENDICES…….. ............................................................................................................. 176
US FDA PREGNANCY RISK CATEGORIES........................................................................................ 177
SYMBOLS and ABBREVIATIONS........................................................................................................ 178
MEASUREMENTS ................................................................................................................................. 179
DRUGS AND CYP ENZYMES ............................................................................................................... 180
CLINICAL PRACTICE GUIDELINES ................................................................................... 184
CLINICAL PRACTICE GUIDELINES (CPG) USER GUIDE ................................................................. 185
INFECTIOUS DISEASES ....................................................................................................................... 186
COMMUNITY ACQUIRED PNEUMONIA (CAP) ............................................................................ 186
IN IMMUNOCOMPETENT ADULTS…………………………………………………………..186
PEDIATRIC……………………………………………………………………………………….195
URINARY TRACT INFECTION....................................................................................................... 201
TUBERCULOSIS ............................................................................................................................ 215
NONCOMMUNICABLE DISEASES ...................................................................................................... 219
HYPERTENSION IN ADULTS ........................................................................................................ 219
DIABETES MELLITUS .................................................................................................................... 232
COMMON POISONING .................................................................................................................. 248
CAUSTICS: ACIDS ............................................................................................................ 248
CAUSTICS: ALKALI – SODIUM HYPOCHLORITE .......................................................... 251
KEROSENE ....................................................................................................................... 253
N-METHYL CARBAMATES ............................................................................................... 255
ORGANOCHLORINE ......................................................................................................... 256
ORGANOPHOSPHATES................................................................................................... 258
WATUSI (DANGEROUS FIRECRACKERS) ..................................................................... 262
ETHANOL .......................................................................................................................... 263
COBRA BITE...................................................................................................................... 267
PARALYTIC SHELLFISH POISONING ............................................................................. 269
DIARRHEA AND DEHYDRATION ........................................................................................................ 272
VACCINATION SCHEDULES .............................................................................................. 278
DIRECTORY………................................................................................................................................... 282
REFERENCES…….............................................................................................................. 284
xx
GENERAL
GUIDE
xxi
GENERAL GUIDE ON THE USE
OF THIS MANUAL
The Philippine National Formulary Manual for Primary Healthcare allows primary
healthcare prescribers – physicians and dentists – to quickly find important medicine information
and practice guidelines for diseases and other health conditions commonly encountered in the
primary care setting.
In this current edition of the PNF, the essential medicines list, monographs, and cross-
reference index have been integrated into a single manual. The initial section emphasizes the
fundamental points in the rational approach to the use of medicines and summarizes the physio-
logic and pharmacologic variables that affect response to pharmacotherapeutic agents and that
are necessary factors in the determination of dosage and frequency of administration. A review
of the guidelines on proper prescription writing, adequate patient counselling and a timely report
on the emerging problems due to Antimicrobial Resistance were included under this General
Guide.
The main section contains the essential medicines for the primary care facilities. The
medicines are arranged using the Anatomical Therapeutic Chemical (ATC) Classification Sys-
tem, but listed alphabetically (Refer to Table of Contents for the categories). Medicines with
more than one therapeutic indication appear in more than one category. Each monograph con-
sists of:
• Generic Name
• Dosage Form/Strength
• Indications
• Antimicrobial Resistance Alert (for the Anti-Infectives)
• Contraindications
• Dosage (weight and/or age-specific dosage recommendations)
• Dose Adjustments (for patients with renal or hepatic disease; or the elderly patients)
• Precautions/Warnings
• Adverse Drug Reactions
• Drug Interactions
• Recommendations on Proper Intake
• Pregnancy Category
Succinct explanations accompany the precautions, adverse events, and drug interac-
tions to emphasize the scientific bases for using the medicines. In addition, concise guidelines
on the pharmacotherapeutic management of leptospirosis, rabies, eradication of H. pylori infec-
tion in peptic ulcer disease, and dehydration in children as well as general information on methi-
cillin-resistant Staphylococcus aureus (MRSA) and precepts in the use of antibiotics were incor-
porated into the prescribing information of the medicines primarily used to treat these diseases.
The succeeding section of this Formulary contains the most recently published clinical
practice guidelines (CPGs) in the management of CAP in adults and children, UTI in adults,
hypertension, diabetes mellitus, and common poisoning that were developed by the relevant
specialty societies. These were enhanced and adapted to the current needs at the primary
xxii
healthcare facilities by the editors. A summary of the WHO guidelines for the management of
diarrheal diseases and the 2014 DOH recommended treatment regimen for tuberculosis were
also included. The final section contains the latest local vaccination schedules.
References
The general guide and the therapeutic information in this Formulary have been
adapted from various current and comprehensive references with the WHO Model Formulary
(2008) and the WHO Model List of Essential Medicines 18th List (2013) serving as the primary
materials. Notable references include the latest Philippine FDA-approved product information,
the Philippine National Drug Formulary Volume II, 3rd Edition (2006), the locally published Ra-
tional Antibiotic Use in Pediatrics (2010), the British National Formulary (2013-2014), the British
National Formulary for Children (2013-2014), and the Australian Medicines Handbook (2012),
among others. The complete list of the sources and materials cited are found in the section on
References.
The entries were compiled, reviewed and updated by the Formulary Executive Coun-
cil, a group of experts drawn from different expertise/medical fields tasked to select the medi-
cines to be included in the PNF using sound evidence-based processes. The therapeutic infor-
mation was submitted to various medical and surgical specialty societies for review and valida-
tion.
The Clinical Practice Guidelines on the management of CAP in adults and children,
UTI in adults, hyperten-sion, diabetes mellitus, common poisoning, leptospirosis, and rabies
were primarily based on the most recently published Philippine national guidelines developed by
the relevant task forces composed of members from various medical and other specialty
societies. The WHO and IMCI guidelines served as the bases for the management of diarrheal
diseases while the 2014 DOH Manual of Procedures for the National Tuberculosis Control
Program was used for the tabulated guidelines on the management of TB.
xxiii
MEDICINE MONOGRAPH KEY
The medicine monograph key summarizes and describes the types of information con-
tained in this edition that the physicians and dentists can utilize in prescribing medicines for the
patients in primary healthcare facilities. Other healthcare professionals can also derive infor-
mation regarding the rational use of medicines from this Manual. The key also shows the format
of how the prescribing information is arranged. The information contained in this Manual has
been validated against the current locally and internationally published clinical practice guide-
lines available at the time of the undertaking and the reviews made by specialty experts and the
medical and surgical specialty societies.
INTRODUCTION OF THE MEDICINE
GENERIC NAME
DOSAGE FORM/STRENGTH: (for oral or parenteral administration)
INDICATION/S: This section only includes Philippine FDA-approved indications. Notably, the
indications included in this edition are limited to the more commonly encountered conditions
at the primary healthcare facilities. Thus, indications for conditions requiring more specialized
care or hospitalization (e.g., acute bacterial meningitis, high-risk pneumonia) are not included.
Indications that will require a referral to a higher level of healthcare facility or to the specialist
(e.g., diabetes in children and in pregnant women) will be written as such. In addition, the indica-
tions listed for the Anti-Infective Agents are restricted to those included in the most current local
clinical practice guidelines that were made available to the editors and/or the latest published
recommendations of the Philippine Antimicrobial Resistance Surveillance Program.
ANTIMICROBIAL RESISTANCE ALERT! This section lists precautions and recommendations

based on available local clinical practice guidelines and the Philippine Antimicrobial Resistance
Surveillance Program regarding the use of antibiotics to which pathogens have been found to
have emerging or increasing antimicrobial resistance.
CONTRAINDICATION/S: This section details disease states where and patient populations for
whom the medicine should not be used.
DOSE: This section lists dosages of the medicines for adult, child and elderly patients, if speci-
fied, as indicated in the official FDA-approved labeling and/or other main references.
DOSE ADJUSTMENT/S: This section gives dosage adjustment recommendations for the elder-
ly, or for patients with renal or hepatic impairment.
PRECAUTIONS: This section details (1) harmful conditions related to the use of the medicine
(e.g., exacerbations, increased risk of adverse effects), and (2) disease states or patient popula-
tions where caution is advised. This may also include precautions for breastfeeding mothers and
nursing infants. Black Box Warnings are included.
xxiv
ADVERSE DRUG REACTIONS: This section denotes side effects and adverse drug reactions
(ADRs) listed in the official FDA-approved labeling. These are enumerated based on the occur-
rence or frequency (i.e., Common – ≥1%; Less Common – ≥0.1% and <1%; and Rare
≥0.01% and <0.1%). Under the Less Common and Rare ADRs, only those deemed significant
based on the clinical judgments of the editors (e.g., serious or life-threatening or potentially irre-
versible ADRs) are listed. For complete prescribing information, readers are enjoined to refer to
the official Philippine FDA-approved labeling.
DRUG INTERACTION/S: This section includes the effects and implications of the concomitant
administration of different medicines, or their use together with food, based on official Philippine
FDA-approved labeling and other references. Moreover, the included entries are categorized
based on: (1) which combinations should be monitored closely, and (2) which should be avoid-
ed.
ADMINISTRATION: This section lists recommendations on the proper intake or administration

of the medicines.
PREGNANCY CATEGORY: This section is based on the US FDA Pregnancy Risk Categories.
(Please refer to the Appendix for the complete listing and description of the risk categories).
xxv
GENERAL GUIDE TO PRESCRIBING
A. RATIONAL APPROACH TO THERAPEUTICS
Rational use of medicines (RUM) is the fundamental concept where patients receive
medicines, when these are needed, that are appropriate for the clinical needs, in doses that
meet the individual requirements, for an adequate period of time, at the lowest possible cost,
and administered correctly by the right person.
1. The problem of irrational use of medicines concerns the following:
a. This is one of the most critical causes of unsuccessful treatment outcomes,
health hazards that include antimicrobial resistance, wastage of resources, and
increased health costs.
b. Worldwide, 50% of medicines are prescribed, dispensed or sold inappropriately;
moreover, half of the patient population fails to take them correctly.
c. In the Philippines, many irrational practices are prevalent such as rationing (of-
ten termed as “diby-diby”), prescribing of inappropriate alternative medicines,
“shotgun” therapy, misuse and overuse of antibiotics, dispensing of antibiotics
without a prescription, self-medication, buying medicines piecemeal (“tingi”),
and failure to complete treatment.
d. The problems that underlie the irrational practices are far-reaching and include
inadequate supplies of medicines that are in turn due to the sheer number of
patients coming for consultation, the lack of funds or poor support from the gov-
ernment officials, poverty, inherent limitations of the National Formulary,
anomalous transactions, geographical isolation and poor health literacy of pa-
tients and even some health care providers.
2. The solutions for many of the causes of irrational practices are often beyond the con-
trol of the primary care physicians. However, the physicians, as stewards of the peo-
ple’s health, must lead by example the efforts to adhere faithfully to the principles of
RUM.
3. The basic tenets of RUM include:
a. Prescribing medicines only when these are necessary;
b. Prescribing appropriately; and
c. Considering the benefits of administering medicines in relation to the risks in-
volved.
4. The key points of the systematic processes that will assist in determining the proper
treatment are:
a. Defining the patient’s problem.
b. Specifying the therapeutic objective.
c. Selecting the therapeutic strategy.
The selected strategy for achieving a health outcome should be agreed
upon with the patient. The total costs for all therapeutic options should be con-
sidered. Strategies can either be non-pharmacologic and/or pharmacologic.
1.) Non-pharmacologic Treatment
• This implies that patients do not always need medicine for the
treatment of their conditions.
• This includes changes in lifestyle or diet, use of physiotherapy or
exercise, provision of adequate psychological support, and other
non-pharmacologic treatments.
• This is of equal importance as prescription medicines; instructions
for such treatments must be written, explained, and monitored in
the same way.
1
2.) Pharmacologic Treatment
a) Selecting the correct group of medicines:
There are two fundamental principles for rational therapeutics:
i. Knowledge about the pathophysiology involved in the clinical
situation of each patient
ii. Pharmacodynamics of the chosen group of medicines
b) Verifying the suitability of the chosen pharmaceutical treat-
ment:
i. Is the active substance chosen suitable for the patient?
ii. Is the dosage form suitable for the patient?
iii. Is the standard dosage schedule suitable for the patient?
iv. Is the standard duration of treatment suitable for the patient?
c) Prescription Writing:
i. This serves as the link between the prescriber, the pharma-
cist (or dispenser), and the patient.
ii. This is vital to the successful management of presenting
medical conditions (see detailed Prescription Writing below).
iii. In the Philippines, only validly registered medical doctors
and dentists (as well as veterinarians) are allowed to pre-
scribe.
d) Giving information, instructions, and warnings:
This is essential in ensuring patient adherence.
e) Monitoring treatment:
i. The evaluation of the follow-up and the outcome of treatment
allows for possible termination of treatment (if the patient’s
problem is solved), or its reformulation when necessary.
ii. This step gives rise to important information about the ef-
fects of medicines, contributing to the pool of knowledge on
pharmacovigilance; that in turn is needed to promote the ra-
tional use of medicines.
B. VARIATION IN DOSE-RESPONSE
Correct dose regimen is necessary for the success in medicine treatment. The use of
standard doses in the marketing literature suggests that standard responses are the rule, but
in reality there is considerable variation in medicine response. The reasons for the variation
include: adherence (see Adherence with Medicine Treatment), medicine formulation, body
weight and age, composition, variation in medicine absorption, distribution, metabolism, and
excretion, variation in pharmacodynamics, disease variables, and genetic and environmental
variables.
1. MEDICINE FORMULATION
a. Poorly formulated medicines may fail to disintegrate or to dissolve.
b. Enteric-coated medicines may pass through the GI tract intact.
Changes in absorption can produce sudden changes in medicine concentrations of
medicines with a narrow therapeutic-to-toxic ratio. For such medicines, quality control
surveillance should be carried out.
2. BODY WEIGHT AND AGE

Although the concept of varying the dose with the body weight or age of chil-
dren has long been a tradition, adult doses have been assumed to be the same irre-
spective of size or shape. However, adult weights vary 2- to 3-folds. Furthermore, a
2
patient with a large fat mass can store large excesses of highly lipid soluble medicines
compared with a lean patient of the same weight.
Age can also be important. Adolescents may metabolize some medicines rela-
tively more rapidly than adults, while the elderly may have reduced renal function and
eliminate some medicines more slowly.
3. DOSE CALCULATION IN CHILDREN
Many children’s doses are standardized by weight (and therefore require multi-
plying by the body-weight in kilograms to determine the child’s dose). Occasionally,
the doses have been standardized by body surface area (BSA) in m2.
To calculate a child’s medication based on BSA, use the formula:
𝑐ℎ𝑖𝑖𝑖′𝑠 𝐵𝐵𝐵
𝑥 𝑎𝑎𝑎𝑎𝑎 𝑑𝑑𝑑𝑑 = 𝑐ℎ𝑖𝑖𝑖′𝑠 𝑑𝑑𝑑𝑑
1.73
with the BSA computed as follows:
𝑊 ×𝐻
𝐴= �
3600
where:
A – Patient’s BSA (m2)
W – Patient’s weight in (kg)
H – Patient’s height (cm)
3600 – Conversion/correction factor (kg/m3)
If the weight is expressed in pounds (lbs) and the height in inches (in):
𝑊 ×𝐻
𝐴= �
3131
• Young children may require a higher dose for each kilogram than adults because
of their higher metabolic rates.
• Calculation by body weight in an overweight child may result in higher than neces-
sary doses being administered. In such cases, doses should be calculated using
an ideal weight, related to height and age.
• Nomograms can also be used to calculate body surface values based on a child’s
height and weight.
• Where the dose for children is not readily available, prescribers should seek
specialist advice before prescribing for a child.
4. PHYSIOLOGICAL AND PHARMACOKINETIC VARIABLES
a. Pharmacokinetics
• This area of study deals with changes of concentration in the drug prod-
uct, or in a drug and its metabolites, in the body, after it has been admin-
istered. This includes the time course of drug absorption, distribution, me-
tabolism and elimination.
• A basic understanding of the factors which control drug concentration at
the site of action (e.g., bioavailability, area under the curve and half-life)
is important for the optimal use of drugs.
1.) Bioavailability
• This refers to the amount of medicine from an administered
dosage form which enters the systemic circulation, and the
rate at which it appears in the bloodstream.
3
x Changes in a drug’s bioavailability may be thought of in

terms of changes in exposure to the drug which, if substan-
tial, can relate to safety and efficacy concerns.
2.) Bioequivalence

x This indicates that a drug in two or more similar dosage

forms reaches the general circulation at the same relative
rate and the same relative extent (i.e., that the plasma level
profiles of the drug obtained using the two dosage forms are
the same).
x This is an important consideration in several key situations
involving lot-to-lot consistency, innovator to generic product
therapeutic equivalence, and situations where a marketed
product undergoes changes in certain aspects (formulation,
manufacturing process, and dosage strength).
3.) Half-life
x This indicates the time required to reduce the amount of
medicine in the body or the plasma concentration by 50%.
x This is a clinically useful pharmacokinetic parameter be-
cause this indicates when the next dose of a medicine
needs to be administered, and thus helpful in determining
an optimal dosing regimen.
b. 0HGLFLQH DEVRUSWLRQ UDWHV may vary widely among individuals and in the
same individual at different times and in different physiological states.
x Medicines taken after a meal are delivered to the small intestine more
slowly than in the fasting state, leading to much lower medicine concen-
trations.
x In pregnancy, gastric emptying is also delayed, while some medicines
may increase or decrease gastric emptying, and affect absorption of oth-
er medicines.
5. MEDICINE DISTRIBUTION
a. Fat-soluble medicines (vitamins A, D, E and K) are stored in adipose tissues.
b. Water-soluble medicines are distributed chiefly in the extracellular space.
c. Acidic medicines bind strongly to plasma albumin.
d. Basic medicines go to muscle cells.
e. Hence, variations in plasma albumin concentration, fat content, or muscle mass
may all contribute to dose variation.
6. MEDICINE METABOLISM AND EXCRETION
a. Medicine metabolism is affected by genetic, environmental, and disease-state
factors.
b.
b. Medicine acetylation shows genetic polymorphism, where individuals fall clearly
into either fast or slow acetylator types. This means that some patients can me-
tabolize medicines more rapidly (fast acetylators) than the others (slow acetyla-
tors).
c. Medicine oxidation, however, is polygenic.
x Although a small proportion of the population can be classified as very
slow oxidizers of some medicines, there is a normal distribution of medi-
cine-metabolizing capacity for most medicines and most subjects.
d. Many medicines are eliminated by the kidneys without being metabolized.
4
PNF new 30 .pdf 1 1/9/15 9:44 AM
1. PATIENT-RELATED REASONS
a. Women tend to be more adherent than men.
b. Younger patients and the very elderly tend to be less adherent.
c. People living alone are less adherent than those living with partners or spouses.
d. Specific education interventions have been reported and shown to improve ad-
herence and compliance.
e. Some patient disadvantages include illiteracy, poor eyesight, or cultural atti-
tudes.
f. Cultural attitudes include preference for traditional or alternative medicines, and
distrust of modern medicines.
g. Economic factors affect patient adherence, compliance and maintenance.
2. DISEASE-RELATED REASONS
Conditions with a known worse prognosis (e.g., cancer) or painful conditions
(e.g., rheumatoid arthritis) elicit better adherence than asymptomatic “perceived as
benign” conditions such as hypertension.
3. DOCTOR-RELATED REASONS
a. Failure to inspire confidence in the treatment offered
b. Little or no explanation provided
c. Too many medicines prescribed
d. Errors in prescribing
e. Overall attitude to the patient
4. DOCTOR-PATIENT INTERACTION
a. Quality of the doctor–patient interaction is crucial to adherence and compliance.
b. “Satisfaction with the interview” is one of the best predictors of good adherence.
c. If they are in doubt or dissatisfied, they may turn to alternative options, including
complementary medicine.
5. PRESCRIPTION-RELATED REASONS
a. Illegible or inaccurate prescriptions may discourage patients to adhere to medi-
cations.
b. Lost prescriptions may delay patients to start or continue medications.
c. Prescriptions not refilled as intended or instructed for a chronic disease may re-
duce maintenance.
d. Too complex prescriptions (greater number of different medicines, poorer ad-
herence).
e. Multiple doses decrease adherence and compliance especially if more than two
doses per day are given.
f. Adverse effects, like drowsiness, impotence, or nausea, reduce adherence.
6. PHARMACIST-RELATED REASONS
a. Manner and professionalism
b. Pharmacist information and counseling can serve as a valuable reinforcement,
as long as they agree with the physician’s advice.
7. RECOMMENDATIONS TO THE PRESCRIBERS

a. Review the prescription to make sure it is correct.
b. Spend time explaining the health problem and the reason for the medicine.
c. Establish good rapport with the patient.
6
d. Explore problems, such as difficulty with reading the label or getting the pre-
scription filled.
e. Encourage patients to bring their medication to the clinic so that tablet counts
can be done to monitor compliance.
f. Encourage patients to learn the names of their medicines, and review their reg-
imen with them. Write notes for them.
g. Keep treatment regimens simple.
h. Communicate with other healthcare professionals to develop a team approach
and to collaborate on helping and advising the patient.
i. Involve the partner or another family member.
j. Listen to the patient.
D. ADVERSE EFFECTS AND INTERACTIONS
1. ADVERSE DRUG REACTIONS (ADR)
• Any response to a medicine which is noxious, unintended and occurs at doses
normally used for prophylaxis, diagnosis, or therapy.
• These reactions are different from accidental/deliberate excessive dosage or
medicine maladministration.
2. MAJOR FACTORS PREDISPOSING TO ADVERSE EFFECTS
a. EXTREMES OF AGE
1.) The very old and the very young populations are more susceptible to
ADRs.
• Examples of which are: hypnotics, antihypertensives, Non-
Steroidal Anti-inflammatory Drugs (NSAIDs), psychotropics, diuret-
ics and digoxin.
2.) All children, particularly neonates, differ from adults in their response to
medicines.
• Some medicines are likely to cause problems in neonates, but are
generally tolerated in children.
• Other medicines are associated with increased risk of ADRs in
children of all ages.
b. INTERCURRENT ILLNESSES/COMORBIDITIES
• This occurs when a patient suffers from another disease aside from the
current condition being treated (kidney, liver or heart disease). The genetic
make-up of the individual patient plays a role.
c. MEDICINE INTERACTIONS
• These may occur among medicines which compete for the same recep-
tor, or which act on the same physiological system.
1.) These may occur indirectly when a medicine-induced disease, or a
change in fluid/electrolyte balance, alters the response to another medi-
cine.
2.) These may occur when one medicine alters the absorption, distribution,
or elimination of another medicine, such that the amount which reaches
the site of action is either increased or decreased.
Drug–drug interactions are some of the most common causes of
adverse effects. When two medicines are administered to a patient, they may
either act independently of each other, or interact with each other. Interaction
may increase or decrease the effects of the medicines concerned and may
cause unexpected toxicity. As newer and more potent medicines become avail-
able, the frequency of serious drug interactions is likely to increase.
7
NOTE: Interactions which modify the effects of a medicine may involve

non-prescription medicines, non-medicinal chemical agents, and social drugs
such as alcohol, marijuana and tobacco, and traditional remedies, as well as
certain types of food. The physiological changes in individual patients, caused
by such factors as age and sex, also influence the predisposition to ADRs re-
sulting from drug interactions.
d. INCOMPATIBILITIES BETWEEN MEDICINES AND IV FLUIDS
x Medicines should not be added to blood, amino acid solutions, or fat
emulsions.
o Certain medicines, when combined with intravenous fluids, may be
inactivated by pH changes, precipitation, or chemical reaction.
e. ADVERSE EFFECTS CAUSED BY TRADITIONAL MEDICINES
Patients who have been, or are taking, traditional herbal remedies may
develop ADRs. In these types of preparation, it is not always easy to identify the
responsible constituents. Refer to the medicine and toxicology information ser-
vice if available or to suitable literature.
f. EFFECT OF FOOD ON MEDICINE ABSORPTION
Food delays gastric emptying and reduces the rate of absorption of many
medicines; however, the total amount of medicine absorbed may or may not be
reduced. On the other hand, some medicines are taken with food, either to in-
crease absorption or to decrease the irritant effect on the stomach.
E. PRESCRIPTION WRITING
1. PRESCRIPTION FORM
Administrative Order No. 62 (series of 1989) on the rules and regulations to im-
plement prescribing requirements under the Generics Act defines a prescription as a
written order and instruction of a validly-registered physician, dentist or veterinarian
for the use of a specific medicine (or medical device) for a specific patient.
The most important requirement for a prescription is that it should be clear. It
should be legible and indicate precisely what should be given. The language used
may be in English, Filipino, or the local dialect.
In accordance with R.A. 5921, or the Pharmacy Act as amended, all prescrip-
tions should contain the following information:
x The patient’s name, age and sex;
x The prescriber’s name, office address, professional registration number, and
professional tax receipt number; and
x Date of the prescription
In addition, Section 3 of the Generics Act lists the following specific guidelines
to prescribing:
x Generic names shall be used in all prescriptions. For drugs with a single active
ingredient, the generic name of that active ingredient shall be used in prescrib-
ing. For drugs with two or more active ingredients, the generic name as deter-
mined by the Philippine FDA shall be used.
x The generic name must be written in full, but the salt or chemical form may be
abbreviated. (The symbol Rx means prescription which originated in medieval
manuscripts as an abbreviation of the Latin verb recipe. The imperative form is
recipere which means “to take” or “take thou
thus.”)
x The generic name must be clearly written immediately after the R x symbol or on
the order chart.
x A brand name may also be included. If written on a prescription pad, the brand
name must be enclosed in parentheses and written below the generic name. If
8
1.1.1. 1.WHAT
WHAT
WHAT
WHAT
TO
TO
TO
COUNSEL
COUNSEL
TO
COUNSEL
COUNSEL
Routinely,
Routinely,
Routinely,
Routinely,
effectively
effectively
effectively
effectively
and
and
andappropriately
and
appropriately
appropriately
appropriately
educate
educate
educate
educate
patients
patients
patients
patients
onon
on
the
the
on
the
following:
the
following:
following:
following:
(1)
(1)
(1)(1)
when
when
when
when
dispensing
dispensing
dispensing
dispensing
prescription
prescription
prescriptionand
prescription
and
andnon-prescription
and
non-prescription
non-prescriptiondrugs,
non-prescription
drugs,
drugs,(2)
drugs, when
(2)
(2)when
(2)
whencounseling
when
counseling
counseling on
counseling on dis-
ondis-
on
dis-dis-
charge
charge
charge medications,
charge
medications, and
medications,
medications,
and(3)
andand
(3)when
(3) when
(3)
when providing
when
providingrecommendations
providing
providing
recommendations
recommendations
recommendations about
about management
about
about
management
management
management ofofof of
specific
specificdrug-related
specific
specific
drug-relatedproblems:
drug-related
drug-related
problems:
problems:
problems:
a.a.a. a.The
Themedication’s
TheThe
medication’sname
medication’s
medication’s
name
name(generic),
name
(generic),indication
(generic),
(generic),
indicationand
indication
indication
andwhen
andand
when
whenappropriate
when
appropriatetotouse
appropriate
appropriatetouse
use
to use
b.b.b. b.The
Themedication’s
TheThe
medication’sexpected
medication’s
medication’s
expectedonset
expected
expected
onsetofofof
onset
onset action
action and
action
of action
andwhat
andand
whattototo
what
whatdodoif ifthe
do
to do
iftheifaction
the action
the does
action
action
doesnot
does
does
not
notnot
occur
occur
occur
occur
c.c.c. c.The
The
The
medication’s
The
medication’s
medication’sroute,
medication’sroute, dosage
route,
route,
dosage
dosageform,
dosage
form, dosage
form,
form,
dosageand
dosage
dosage
andadministration
andand
administrationschedule
administration
administration
schedule(in-
schedule
schedule
(in-
(in-(in-
cluding
cluding duration
cluding
cluding
durationofoftherapy)
duration
durationoftherapy)
therapy)
of therapy)
d.d.d. d.Directions
Directions for
Directions
Directions
foruse
for
use
forincluding
useuse
including education
including
including
educationabout
education
education
aboutdrug
about
about
drugdevices
drug
drug
devices
devices
devices
e.e.e. e.Proper
Properstorage
Proper
Proper
storage requirements
storage
storage
requirements
requirements
requirements
f.f.f. f.Common
Commonororor
Common
Common important
importantdrug-drug
important
or important
drug-drugororor
drug-drug
drug-drugdrug-food
drug-food
or interactions
drug-food
drug-food
interactions
interactions
interactions
g.g.g. g.Potential
Potentialcommon
Potential
Potential
common
common and
common
and severe
andand
severeadverse
severe
severe
adverseeffects,
adverse
adverse
effects,and
effects,
effects,
and
andactions
and
actionstototo
actions
actionsprevent
prevent
to ororor
prevent
preventmini-
mini-
or
mini-
mini-
mize
mizetheir
mize
mize
theiroccurrence
their
their
occurrence
occurrence
occurrence
h.h.h. h.What
What
Whatthe
What
the patient
thethe
patientshould
patient
patient
shoulddo
should
should
do toto
do domonitor
tomonitor
to his/her
monitor
monitor
his/her therapeutic
his/her
his/her
therapeutic response
therapeutic
therapeutic
response
responseororor
response when
when
or
when
when
side
sideeffects
side
side
effects develop
effects
effects
develop
develop
develop
i. i. i. i.What
What
Whatactions
What
actions
actions the
actions the patient
the patient
the should
patient
patient
should take
should
should
takeiftake
take ifthe
iftheifintended
the intended
the therapeutic
intended
intended
therapeuticresponse
therapeutic
therapeutic
responseisisnot
response
responseisnot
not
is not
obtained
obtained
obtainedororor
obtained if ifside
or if effects
ifside
side side
effectsdevelop
effects
effects
develop
develop
develop
j. j. j. j.Proper
Properdisposal
Proper
Proper
disposal ofofcontaminated,
disposal
disposal discontinued
ofcontaminated,
contaminated,
of contaminated,
discontinuedororor
discontinued
discontinuedunused
unused
or medications
unused
unused
medications
medications
medications
2.2.2. 2.WHO
WHOAND
WHO
WHO
ANDWHEN
AND
AND
WHENTO
WHEN
WHEN
TOCOUNSEL
TOCOUNSEL
TO
COUNSEL
COUNSEL
a.a.a. a.Patients
Patientswho
Patients
Patients
who
whoshould
who
shouldalways
should
should
alwaysbe
always
always
be counseled
becounseled
be together
counseled
counseled
together with
together
together
withtheir
with
with
theirfamilies
their
their
familiesand
families
families
andcare-
andand
care-
care-
care-
givers:
givers:
givers:
givers:
x x x x Confused
Confusedpatients
Confused
Confused
patients
patients
patients
x x x x Patients
Patientswho
Patients
Patients
who
whoare
who
aresight-
aresight-
are ororor
sight- hearing-impaired
sight-hearing-impaired
or
hearing-impaired
hearing-impaired
x x x x Patients
Patientswith
Patients
Patients
withpoor
with
with
poor literacy
poor
poor
literacy
literacy
literacy
x x x x Patients
Patientswhose
Patients
Patients
whoseprofiles
whose
whose
profilesshow
profiles
profiles
show
showaachange
showachangeininmedications/dosing
change
a changeinmedications/dosing
medications/dosing
in medications/dosing
x x x x New
Newpatients,
New
New
patients,ororor
patients,
patients,those
those
or receiving
those
those
receivingaamedication
receiving
receiving
amedicationfor
medication
a medication
forthe
for
thefirst
for
thefirst
the time
firstfirst
time
time
time
x x x x Patients
Patientswho
Patients
Patients
whohave
who
who
havemedications
have
have
medicationswith
medications
medications
withsignificant
with
with
significant side
significant
significant
side effects,
side
side
effects,specific
effects,
effects,
specificstor-
specific
specific
stor-
stor-
stor-
age
agerequirements,
agerequirements,
age and
requirements,
requirements,
andcomplicated
andand
complicateddirections
complicated
complicated
directions
directions
directions
b.b.b. Patients
atPatients
b. who
who
Patients should
should
who bebecounseled
should counseled
be atatcertain
counseled certain
at intervals
intervals
certain together
together
intervals with
with
together their
their
with families
families
their and
and
families
caregivers:
caregivers:
and caregivers:
x x x Asthmatic
Asthmatic
patients
x Asthmatic patients
Asthmatic
patients
patients
x x x Diabetic
Diabetic
patients
x Diabetic patients
patients
Diabetic patients
x Patients
x x x Patients
Patientstaking
taking
taking
Patients four
four
four
taking (4)
(4) oror
(4)
four or
(4)more
more
moreprescribed
prescribed
prescribed
or more medications
medications
medications
prescribed medications
x Patients
x x x Patients
Patientswho
whowho
Patients are
are
are
who mentally
mentally
are illillill ill
mentally
mentally
x Epileptic
x x x Epileptic
Epilepticpatients
patients
patients
Epileptic patients
x Patients
x x x Patients
Patientswith
with
with
Patients skin
skin
skin
with complaints
complaints
complaints
skin complaints
3.3.3. 3.COUNSELING:
COUNSELING:
COUNSELING:PROCESS
PROCESS
PROCESS
COUNSELING: STEPS
STEPS
STEPS
PROCESS STEPS
Steps
Steps
Steps ininin
Steps patient
patient
in
patienteducation
patient
education and
education
education
and
andcounseling
and
counseling
counseling process
counseling
process will
process
process
willvary
willwill
varyaccording
vary
vary
according
according tototo
according the
the
to
thethe
health
health
health system’s
health
system’s
system’s policies
system’s policies and
policies
policies
andprocedures,
andand
procedures,
procedures, environment,
procedures,
environment,
environment,and
environment,
andpractice
andand
practice
practicesetting.
practice
setting.Generally,
setting.
setting.
Generally,
Generally,
Generally,
the
the following
the following
the
following steps
following
steps
steps are
steps
areappropriate
areare
appropriatefor
appropriate
appropriate
forpatients
forpatients
for receiving
patients
patients
receiving
receivingnew
receiving
newmedications
newnew
medications
medicationsororor
medications returning
returning
or
returning
returning
for
forrefills:
forrefills:
for
refills:
refills:
a.a.a. a.Establish
Establish
Establishcaring
Establish
caring relationship
caring
caring
relationship
relationshipwith
relationship
with the
withwith
the patient
thepatient
the asasas
patient
patient appropriate
appropriate
as tototo
appropriate
appropriatethe
the
to practice
the practice
the
practiceset-
practice
set-
set-set-
ting,
ting,and
ting,
ting,
and
andstage
and
stage ininin
stage
stagethe
the
in patient’s
thethe
patient’shealth
patient’s
patient’s
health
healthcare
health
caremanagement.
care
care
management.
management. Show
management.Show
Show interest
Showinterest
interestininin
interestthe
the
in
thethe
patient
patient verbally
patient
patient
verbally and
verbally
verbally
and
andnon-verbally.
and
non-verbally.
non-verbally.
non-verbally.
101010 10
• Explain the purpose and expected length of sessions.
• Obtain the patient’s agreement to participate.
b. Assess the patient’s knowledge about his or her health problems, medications,
physical and mental capability to use the medications appropriately, and attitude
towards the health problems and medications.
• Ask why the patient is being prescribed with the medication (if known), or
the medication’s use, expected benefits and action.
• Provide information orally, and use demonstrations or visual aids to fill
the patient’s gaps in knowledge and understanding.
• Open the medication containers and show patient what the medication
looks like, or demonstrate use.
• Explain how to take the medication.
• Discuss when to take, and how long to take the medication.
• Plan what to do if a dose is missed.
• Determine any special precautions to heed and follow.
• Explain how to store the medication.
• Demonstrate if the prescription can be refilled, and if so, determine when
it is done.
• Give specific details on how the patient will know if the medication is
working.
c. Verify patient’s knowledge and understanding of medication use.
• Ask the patient to describe (or show) how the medication should be used,
and its effects.
• Ask the patient if they have any questions.
11
$17,0,&52%,$/5(6,67$1&(
$17,0,&52%,$/5(6,67$1&(
$17,0,&52%,$/5(6,67$1&(
A.A.A. DEFINITION
DEFINITION
DEFINITION
OF
OFOF
ANTIMICROBIAL
ANTIMICROBIAL
ANTIMICROBIAL
RESISTANCE
RESISTANCE
RESISTANCE
1.1. 1. $QWLPLFURELDO
$QWLPLFURELDO
$QWLPLFURELDO 5HVLVWDQFH
5HVLVWDQFH
5HVLVWDQFH (AMR)
(AMR)
(AMR)
refers
refers
refers
totothe
to
thethe
resistance
resistance
resistanceofofaof
amicroorganism
microorganism
a microorganism
(including
(including
(including bacteria,
bacteria,
bacteria,
viruses
viruses
virusesand
andand
some
some
some
parasites)
parasites)
parasites) totoan
toanan
antimicrobial
antimicrobial
antimicrobialagent
agent
agent
toto to
which
which
which
it itwas
was
it was
previously
previously
previously sensitive.
sensitive.
sensitive.
Resistant
Resistant
Resistant
organisms
organisms
organisms withstand
withstand
withstandattack
attack
attack
bybyanti-
by
anti-
anti-
bacterials,
bacterials,
bacterials, antivirals,
antivirals,
antivirals,
ororantimalarials.
orantimalarials.
antimalarials.
Thus,
Thus,
Thus,
standard
standard
standard treatments
treatments
treatments become
become
become inef-
inef-
inef-
fective,
fective,
fective,
allowing
allowing
allowing
infections
infections
infectionstotopersist
to
persist
persist
and
and
and
spread.
spread.
spread.
2.2. 2. AMR
AMR which
AMR which
which
isisais
aconsequence
consequence
a consequenceofofthe
of
thethe
use
useuse
orormisuse
or
misuse
misuse
ofofantimicrobials
of
antimicrobials
antimicrobials
develops
develops
develops
when
when
when
the
thethe
organism
organism
organismmutates
mutates
mutates
ororacquires
or
acquires
acquires
a aresistance
resistance
a resistance
gene.
gene.
gene.
B.B.B. CAUSES
CAUSES
CAUSES
OF
OFOF
ANTIMICROBIAL
ANTIMICROBIAL
ANTIMICROBIAL
RESISTANCE
RESISTANCE
RESISTANCE
1.1. 1. Although
Although
Although the
thethe
ultimate
ultimate
ultimate
causes
causes
causes
ofofAMR
of
AMRAMR
are
areare
microbial,
microbial,
microbial,
clinical
clinical
clinical
and
andand
programmatic
programmatic
programmatic
inin in
nature,
nature,
nature,
it itisis
itessentially
is
essentially
essentially
a aman-made
man-made
a man-made occurrence.
occurrence.
occurrence.
2.2. 2. The
TheThe
proliferation
proliferation
proliferation
ofofdrug-resistant
ofdrug-resistant
drug-resistantstrains
strains
strains
isisassociated
isassociated
associated
with
with
with
various
various
various
manage-
manage-
manage-
ment,
ment,
ment,
healthcare
healthcare
healthcare
provider,
provider,
provider,
and
andand
patient-related
patient-related
patient-related issues.
issues.
issues.
Table
Table 1 1enumerates
Table enumerates
1 enumerates
sev-
sev-
sev-
eral
eral
eral
ofofthe
of
thethe
causes
causes
causes
leading
leading
leading
totodrug
to
drug
drug
resistance.
resistance.
resistance.
3.3. 3. The
The general
The general
general
categories
categories
categories ofofthe
of
thethe
causes,
causes,
causes,
i.e.,
i.e.,
i.e.,
therapeutic
therapeutic
therapeutic
protocols,
protocols,
protocols,
drug
drug
drug
charac-
charac-
charac-
teristics,
teristics,
teristics,
and
andand
drug
drug
drug
selling
selling
selling
and
and and
purchasing
purchasing
purchasing
practices,
practices,
practices,
provide
provide
provide
opportunities
opportunities
opportunities
where
where
where
potential
potential
potential
strategies
strategies
strategies
totocombat
to
combat
combat AMR
AMR
AMR
arise.
arise.
arise.
7DEOHCauses
7DEOHCauses
7DEOHCauses ofofinadequate
of
inadequate
inadequate
treatment
treatment
treatment
which
which
which
maymaymay
contribute
contribute
contribute
totoemergence
to
emergence
emergence ofofdrug
of
drug
drug
resistance
resistance
resistance
Healthcare
Healthcare
Healthcareproviders:
providers:
providers: Drugs:
Drugs:
Drugs: Patients:
Patients:
Patients:
Inadequate
Inadequate
Inadequate regimens
regimens
regimens Inadequate
Inadequate
Inadequatesupply/quality
supply/quality
supply/quality Inadequate
Inadequate
Inadequate drug
drug
drug
intake
intake
intake
Inappropriate
Inappropriate
Inappropriate guidelines
guidelines
guidelines Poor PoorPoor
quality
quality
quality Poor
Poor
Poor
adherence
adherence
adherence
Noncompliance
Noncompliance
Noncompliance with
withwith
guide-
guide-
guide- Unavailability
Unavailability
Unavailability
ofofcertain
of
certain
certain
drugs
drugs
drugs (or (orpoor
(or
poor
poor
directly
directly
directly
observed
observed
observed
therapy)
therapy)
therapy)
lines
lines
lines (stock-outs
(stock-outs
(stock-outs
orordelivery
or
delivery
delivery Lack
Lack
Lack
ofofinformation
of
information
information
Absence
Absence
Absence ofofguidelines
of
guidelines
guidelines disruptions)
disruptions)
disruptions) Lack
Lack
Lack
ofofmoney
of
money
money
Poor
PoorPoor
training
training
training Poor
PoorPoor
storage
storage
storage
conditions
conditions
conditions (no
(notreatment
(no
treatment
treatment available
available
available
free
freefree
ofof of
NoNotreatment
Notreatment
treatment
monitoring
monitoring
monitoring Wrong Wrong
Wrong
dose
dose
dose
ororcombinations
or
combinations
combinations charge) charge)
charge)
Poorly
Poorly
Poorly
organized
organized
organized
ororfunded
or
funded
funded Lack
Lack
Lack
ofoftransportation
of
transportation
transportation
control
control
control
programmes
programmes
programmes Adverse
Adverse
Adverse effects
effects
effects
Social
Social
Social
barriers
barriers
barriers
Malabsorption
Malabsorption
Malabsorption
Substance
Substance
Substance dependency
dependency
dependency disorders
disorders
disorders
Source:
Source:
Source:
Final
Final
Final
Report,
Report,
Report,
Country
Country
Country
Situation
Situation
Situation
Analysis
Analysis
Analysis
onon
Antimicrobial
on
Antimicrobial
Antimicrobial
Resistance, Philippines,
2012.
2012.
2012.
C.C.C. ANTIMICROBIAL
ANTIMICROBIAL
ANTIMICROBIAL
RESISTANCE:
RESISTANCE:
RESISTANCE:
AAGROWING
A
GROWING
GROWING
GLOBAL
GLOBAL
GLOBAL
CONCERN
CONCERN
CONCERN
1.1. 1. The The
The WHO
WHOWHO
cites
cites
cites
the
thethe
following
following
following
alarming
alarming
alarming
reasons
reasons
reasons
why
whywhy
AMR
AMR
AMRisisalready
is
already
already
a aglobal
aglobal
global
concern:
concern:
concern:AMR
AMR AMRkills;
kills;
kills;
AMR
AMRAMRchallenges
challenges
challenges control
control
control
ofofinfectious
of
infectious
infectious disease;
disease;
disease;AMR
AMR
AMR
threatens
threatens
threatens
a areturn
return
a returntotothe
to
thethe
pre-antibiotic
pre-antibiotic
pre-antibiotic
era;
era;
era;
AMR
AMRAMR
increases
increases
increasesthe
thethe
costs
costs
costs
ofofhealth
of
health
health
care;
care;
care;
AMR
AMR
AMRjeopardizes
jeopardizes
jeopardizes healthcare
healthcare
healthcaregains
gains
gains
totosociety;
tosociety;
society;
and,
and,
and,
AMR
AMRAMRcompromises
compromises
compromises
health
health
health
security,
security,
security,
and
andand
damages
damages
damagestrade
trade
trade
and
and
and
economy.
economy.
economy.
2.2. 2. Furthermore,
Furthermore,
Furthermore,
the
thethe
following
following
following
facts
facts
facts
collated
collated
collated
bybyWHO
by
WHOWHO(Country
(Country
(Country
Situational
Situational
Situational
Analysis,
Analysis,
Analysis,
2012)
2012)clearly
clearly
2012) clearly
demonstrate
demonstrate
demonstrate the
thethe
potential
potential
potential
and
andand
real
real
real
dangers
dangers
dangers
that
that
that
AMR
AMR
AMRcauses
causes
causes
and
and
and
has
has
has
caused:
caused:
caused:
a.a. a. About
About
AboutQHZFDVHVRIPXOWLGUXJUHVLVWDQW7%
QHZFDVHVRIPXOWLGUXJUHVLVWDQW7%
QHZFDVHVRIPXOWLGUXJUHVLVWDQW7% HPHUJHDQQXDO
HPHUJHDQQXDO
HPHUJHDQQXDO
O\,O\,causing
O\,
causing
causing
atatleast
at
least
least
150,000
150,000
150,000 deaths.
deaths.
deaths.
MDR-TB
MDR-TB
MDR-TBisisdefined
is
defined
defined
asasresistance
asresistance
resistance
toto to
rifampicin
rifampicin
rifampicin
and
andand
isoniazid.
isoniazid.
isoniazid.
ItsItstherapy
Its
therapy
therapy
requires
requires
requires
18-24
18-24
18-24
months
months
monthsofoftreatment
of
treatment
treatment
with
withwith
expensive
expensive
expensivesecond-line
second-line
second-linedrugs,
drugs,
drugs,
like
like
like
capreomycin
capreomycin
capreomycin and
andand
kanamycin.
kanamycin.
kanamycin.
b.b. b. Extensively
Extensively
Extensively drug-resistant
drug-resistant
drug-resistant TBTBTBororXDR-TB
orXDR-TB
XDR-TB (defined
(defined
(defined
asasasMDR
MDRMDR plus
plus
plus
re-
re-re-
sistance
sistance
sistance
totoany
to
anyany
member
member
member ofofthe
of
thethe
quinolone
quinolone
quinolone
family
family
family
and
and
and
atatleast
at
least
least
totoany
to
anyany
sec-
sec-sec-
ond-line
ond-line
ond-line
anti-TB
anti-TB
anti-TB
injectable,
injectable,
injectable,
such
such
such
asaskanamycin,
askanamycin,
kanamycin,capreomycin
capreomycin
capreomycin ororamikacin)
or
amikacin)
amikacin)
isisais
aglobal
global
a global
threat
threat
threat
with
witha aFDVHIDWDOLW\UDWHRI
with FDVHIDWDOLW\UDWHRI
a FDVHIDWDOLW\UDWHRI XDR-TB
XDR-TB
XDR-TB isisais
abig
big
a big
prob-
prob-
prob-
121212
lem because there are very few options for treatment, which probably ac-
counts for the high mortality rate among the XDR-TB patients.
c. Resistance to earlier generation antimalarial medicines such as chlo-
roquine and sulfadoxine-pyrimethamine is widespread in most malaria-
endemic countries. Falciparum malaria parasites resistant to artemisinins
are emerging in Southeast Asia; infection showed delayed clearance af-
ter the start of treatment (indicating resistance).
d. Ciprofloxacin is the only antibiotic currently recommended by WHO for
the management of bloody diarrhea due to Shigella, now that widespread
resistance has developed to any previously effective antibiotics. But rap-
idly increasing prevalence of resistance to Ciprofloxacin in Shigello-
sis is reducing the options for safe and efficacious treatment especially
for children. New antibiotics suitable for oral use are badly needed.
e. AMR has become a serious problem for treatment of gonorrhea (caused
by Neisseria gonorrhoeae), which is increasing in prevalence worldwide.
The problem involves even the “last-line” oral cephalosporins. In multi-
drug-resistant N. gonorrhoeae, resistance is found against tetracy-
clines, macrolides (including azithromycin), sulfonamide and trimethoprim
combinations and more recently, to quinolones. Untreatable gonococcal
infections will result in higher rates of illness and death thus reversing the
gains made in the control of the sexually transmitted infection.
f. Extended-spectrum beta-lactamases or ESBLs are resistant to third-
generation cephalosporins (ceftazidime, cefotaxime and cefpodoxime)
as well as monobactams (aztreonam); common in the Enterobacteri-
aceae, particularly E.coli and K. pneumoniae.
g. New resistance mechanisms, such as the beta-lactamase NDM-1
(New Delhi metalo-beta-lactamase 1), have emerged among several
gram-negative bacilli. These bacilli are considered as new superbugs that
have resistance to broad spectrum antibiotics that are often the last de-
fense against multi-resistant bacterial strains.
h. A high percentage of hospital acquired infections is caused by highly re-
sistant bacteria such as methicillin-resistant Staphylococcus aureus
(MRSA) and vancomycin resistant enterococci.
i. Resistance is an emerging concern for treatment of HIV infection, follow-
ing the rapid expansion in access to anti-retroviral medicines in recent
years.
D. STATUS OF ANTIMICROBIAL RESISTANCE IN THE PHILIPPINES
1. There is a need to approach the problem of AMR in the Philippines with a
heightened sense of urgency. This is clearly elucidated by several evidences of
the dangers it poses.
a. The most dreaded recognized AMR gene, the NDM-1, was identified in
the Escherichia coli isolated from the urine of a 33 year old female in 2011.
The gene can render even the most powerful antibiotics ineffective.
b. Many of the causative bacterial pathogens that cause infections included
in the top ten causes of morbidity in the Philippines have already become
resistant to multiple antibiotics. At the forefront is TB, with MDR-TB and
even XDR-TB already present in the Philippines which ranked 6th among
27 identified countries with MDR-TB. In 2006, the occurrence of MDR-TB
was 4% among new cases and a high 27% among previously treated pa-
tients.
2. The DOH established in 1988 the Antimicrobial Resistance Surveillance
Program (ARSP) to determine the current status and developing trends of an-
timicrobial resistance of selected bacteria to specific antimicrobials. The ARSP,
13
which
whichnow
nowhas
has2222active
activesentinel
sentinelsites
sitesinin tertiary
tertiary or
or regional
regional hospitals
hospitals in 14 re-
gions,
gions,submits
submitsand
andpublishes
publishesannual
annualsummary
summaryreports.
reports.
Although
Althoughthe theinterpretation
interpretation ofof the
the antimicrobial
antimicrobial resistance
resistance data
data must be ap-
proached
proachedwith withcaution
cautiondue
duetotofactors
factorsthat
thatcan
canintroduce
introduce bias
bias and
and influence anal-
ysis
ysis(e.g.,
(e.g.,area
areaand
andpopulation
populationcoverage,
coverage,sampling,
sampling, and
and laboratory
laboratory routines and
capacities),
capacities),the thesurveillance
surveillanceprogram
program focuses
focuses onon aerobic
aerobic bacterial
bacterial pathogens
causing
causingcommon
commoninfectious
infectiousdiseases
diseasesthat thatare
areof
of public
public health importance. Thus,
health importance.
allallprimary
primaryhealthcare
healthcareprescribers
prescribersmustmust keep
keep abreast
abreast ofof the
the new
new antimicrobial
susceptibility
susceptibilitydatadatatotoenable
enablethem
themtotoselect
selectappropriate
appropriate treatment
treatment options.
All
Allreaders
readersare
areenjoined
enjoinedtotorefer
referto
tothe
theyearly
yearly published
published ARSP
ARSP surveillance
data
dataforformore
moreupdated
updatedinformation
informationand andproper
proper guidance
guidance (see
(see Directory for
the
thecomplete
completecontact
contactdetails)
details)
3.3. The
TheARSP
ARSPfound
foundthe
thefollowing
following alarming
alarming rates
rates of resistance among various
of resistance
bacterialpathogens.
bacterial pathogens.
a.a. The(6%/HQ]\PH,
The (6%/HQ]\PH,which
whichcan canrender
render pathogens
pathogens resistant
resistant to many anti-
biotics,
biotics,has
hasbeen
beenidentified
identifiedininEscherichia coli and
Escherichiacoli and Klebsiella
Klebsiella spp.

b.b. 0XOWLGUXJ
0XOWLGUXJUHVLVWDQW
UHVLVWDQWPseudomonas aeruginosa DQG
Pseudomonas aeruginosa DQG Acinetobacter
spp.which
spp. whichaccount
account for
for 43%
43% ofof all
all hospital-acquired
hospital-acquired pneumonia
pneumonia have
been
beenidentified.
identified.
c.c. Theresistance
The resistancerate
rateofofStreptococcus pneumoniae (which
Streptococcuspneumoniae (which causes acute
respiratory
respiratorytracttractinfections)
infections)totopenicillin
penicillin was
was 5%
5% compared
compared to 0% in 2010
ininallallARSP
ARSPsites
sitesfrom
fromJanuary-December
January-December 2013.2013. Resistance
Resistance to cotrimox-
azole
azolewas was20%
20%inin2013.
2013.
d.d. The
Theresistance ratesofofQRQW\SKRLGDO
resistancerate QRQW\SKRLGDO Salmonella
Salmonella species
species from January-
December
December20132013totoampicillin
ampicillinand
and cotrimoxazole
cotrimoxazole were
were 56%
56% and 34%, re-
spectively.
spectively.There
Therewaswasincreasing
increasingresistance
resistance to
to ciprofloxacin
ciprofloxacin which was at
18%
18%inin2013
2013compared
comparedtoto14% 14%inin2012.
2012.
e.e. Combined
Combined2012-2013
2012-2013data datarevealed
revealedhigh
high rates
rates of resistance of 6KLJHOODH
of resistance
totoprevious
previousfirst
firstline
lineagents,
agents,with
withresistance
resistance rates
rates at
at 67%
67% against ampicil-
lin,
lin,67%
67%against
againstcotrimoxazole,
cotrimoxazole,and
and49%
49% against
against chloramphenicol.
chloramphenicol.
f. f. Emergingresistance
Emerging resistance ofof 6KLJHOODH
6KLJHOODHagainst
against the
the quinolones
quinolones is seen with
cumulative
cumulativerates
ratesofofresistance
resistance for
for 2011-2013
2011-2013 at at 15%
15% against
against ciprofloxa-
cin;
cin;resistance
resistancewas
wasatat13%
13%against
againstnalidixic
nalidixic acid.
acid.
g.g. Thereisisaasteady
There steadyincrease
increase inin the
the resistance
resistance rates
rates of
of Staphylococcus
Staphylococcus
aureusand
aureus andconsequently
consequentlyhigher
higher prevalence
prevalence ofof 056$
056$ which is also an
important
importantcause
causeofofhospital
hospitalacquired
acquiredinfections.
infections.
h.h. Forthe
For theperiod
periodofof 2012-2013,
2012-2013, very
very high
high resistance
resistance rates
rates of Neisseria
gonorrhoeaetotociprofloxacin
gonorrhoeae ciprofloxacin (74%),
(74%), penicillin
penicillin (80%),
(80%), and tetracycline
(55%)
(55%)were
werenoted.
noted.
4.4. Thesealarming
These alarmingincreasing
increasingtrends
trendsofofAMR
AMRininthe
the country
country are
are clearly
clearly demonstrat-
ededininTable
Table2 2which
whichsummarized
summarizedthetheresults
resultsof
ofaa comparison
comparison ofof the antimicrobial
resistance
resistanceofofselected
selectedorganisms
organismsinin1993
1993and
and2011.
2011.
14
14
Table 2. Summary of Antimicrobial Resistance Patterns for Selected Organisms and Antimicrobials in
1993 and 2011
Percent (%) Resistance
Organism/Antimicrobials
1993 2011 Remark
Enteric Infections/Gram-negative Pathogens
1. E. coli
Ampicillin 67.5 80.0 Increased
NDM: identified ESBLs – VERY ALARMING
increasing
2. Non-typhoidal Salmonella
Ampicillin 33.4 30.0 Decreased
Cotrimoxazole 34.3 21.0
Chloramphenicol 25.7 7.0
3. Salmonella typhi
Ampicillin 5.4 0.6 Decreased
Cotrimoxazole 10.2 0
Chloramphenicol 5.5 0
4. Shigella flexneri/spp.
Ampicillin 62.5
Cotrimoxazole 30.3 79.0 Increased
Chloramphenicol 53.1
Nalidixic acid 4.0 Emerging
Ciprofloxacin 3.0
5. Klebsiella spp.
Cephalothin (Cefazolin) 36.6 ESBL confirmed (from 18 VERY ALARMING
tertiary sentinel sites)
Gentamicin 26.9
6. Vibrio cholerae
Cotrimoxazole 43.0
Tetracycline 5.1 5.0 (zero in 2010) NOT GOOD
7. Neisseria gonorrhoeae
Ofloxacin 81.0 VERY ALARMING
Ciprofloxacin 82.0
Penicillin 91.7
Tetracycline 44.1
Acute Respiratory Infections/Gram-positive Pathogens
1. Streptococcus pneumoniae
Cotrimoxazole 6.5/8.7 16.0 Increased
Chloramphenicol 7.7 2.0 Decreased
Penicillin 24.4 4.0 Decreased
2. Staphylococcus aureus
Cotrimoxazole 13.4
Erythromycin 20.0
Methicillin/Oxacillin 18.5 53.0 VERY ALARMING
3. S. epidermidis
Cotrimoxazole 35.2 52.0 VERY ALARMING
Erythromycin 42.0 51.0
Methicillin/Oxacillin 38.4 66.0
Multidrug Resistant / Hospital-Acquired Pathogens
1. Acinetobacter baumannii 50% of isolates are MDR
(resistant to at least 3 classes
VERY, VERY
No data of antimicrobials; 13% to ALL
ALARMING
but 1 or 2 classes as reported
by 21 sentinel sites; 43%
associated with HAI)
2. Pseudomonas aeruginosa
Amikacin 26.8 Resistant to at least 3 classes VERY, VERY
of antimicrobials; 43% associ- ALARMING
ated with HAI
Gentamicin 53.7
Source: Final Report, Country Situation Analysis on Antimicrobial Resistance, Philippines, 2012.
15
E. RECOMMENDATIONS OF THE PHILIPPINE ANTIMICROBIAL RESISTANCE
SURVEILLANCE PROGRAM
Below are the recommendations of the ARSP regarding antibiotic treatment for
aerobic bacterial pathogens of public health importance based on the reported anti-
microbial resistance surveillance data for 2013 (Carlos, C, 2013):
1. Respiratory Bacterial Pathogens:
a. Infections secondary to Streptococcus pneumoniae can still be
covered with penicillin or one of the anti-pneumococcal macrolides,
although there is a need to closely monitor the changing trends of
resistance among pneumococci. Improved local data on serotype
distribution will allow for better surveillance information especially
needed for vaccination recommendations.
b. Due to high resistance rate of Haemophilus influenzae to ampi-
cillin, this antibiotic is no longer recommended for empiric thera-
py for infections secondary to the pathogen.
Recommended empiric treatment for suspected H. influenzae in-

fections may consist of beta-lactam-beta-lactamase inhibitor com-
binations, extended spectrum oral cephalosporins and the newer
macrolides.
2. Bacterial Enteric Pathogens:
a. For suspected uncomplicated enteric fever, empiric treatment
can still consist of either chloramphenicol or cotrimoxazole or
amoxicillin/ampicillin. There are increasing reports of nalidixic acid
resistance and ciprofloxacin non-susceptibility which may result to
clinical treatment failures when treating enteric fever using fluoro-
quinolones. Microbiological data is recommended for pathogen-
directed therapy.
b. In Salmonella gastroenteritis, increasing rates of ciprofloxacin

resistance should remind clinicians to use antibiotics judiciously as
this is usually a self-limiting disease.
c. Due to the emerging resistance of Shigellae to the quinolones and

limited data available, more vigilant surveillance of the resistance
pattern of this organism should be pursued by encouraging clini-
cians to send specimens for culture.
d. For cholera, tetracycline, chloramphenicol and cotrimoxazole re-
main to be good treatment options.
3. Sexually-Transmitted Bacterial Pathogens:
a. Limited data is available on N. gonorrhoeae in recent years, but
based on reported isolates, ceftriaxone remains as empiric antibi-
otic of choice for gonococcal infections. More vigilant surveillance
of the resistance patterns of this organism must be pursued by en-
couraging clinicians to send specimens for culture.
4. Gram-positive Cocci:
a. In view of the continued high rates of methicillin/oxacillin resistance
among staphylococci, there may be an indication to shift empiric
treatment of suspected staphylococcal infections from oxacillin to
alternative agents such as cotrimoxazole, doxycycline, clindamy-
cin, linezolid or vancomycin.
16
5. Gram-negative Bacilli:
a. Hospitals should base their treatment recommendations for the En-
terobacteriaceae on their institution’s prevailing resistance pat-
terns as these have been found to be variable from hospital to
hospital. The high percentage of possible ESBL-producing isolates
complicates treatment of serious infections caused by these organ-
isms and may lead to the increased use of carbapenems that may
favor the spread of the carbapenem-resistant Enterobacteriaceae.
b. Increasing resistance among the bacterial organisms Pseudomo-
nas aeruginosa and Acinetobacter baumannii continues to be a
concern as both carry intrinsic resistance to a number of antimicro-
bial classes and acquisition of additional resistance severely limits
the available treatment options.
c. Prudent antimicrobial use, monitoring of resistance patterns and
antimicrobial use, and improved standards of infection control are
essential in addressing the clinical and public health concerns.
All readers are enjoined to refer to the yearly published ARSP surveillance data for
more updated information and proper guidance (see Directory for complete contact
details).
F. DRIVING FORCES BEHIND ANTIMICROBIAL RESISTANCE

1. The inappropriate and irrational use of medicines provides favorable condi-
tions for resistant microorganisms to emerge and spread. WHO enumerates
the following as the underlying factors that drive AMR:
a. Inadequate national commitment to a comprehensive, coordinated re-
sponse, ill-defined accountability, and insufficient engagement of com-
munities;
b. Weak or absent surveillance and monitoring systems;
c. Inadequate systems to ensure quality and uninterrupted supply of medi-
cines;
d. Inappropriate and irrational use of medicines, in both clinical practice
and animal husbandry, and aquaculture;
e. Poor infection prevention and control practices; and
f. Depleted arsenals of diagnostics, medicines and vaccines as well as in-
sufficient research and development of new products.
G. THE RESPONSE OF THE NATIONAL GOVERNMENT TO THE RISING
ANTIMICROBIAL RESISTANCE
1. Creating an Inter-Agency Committee on AMR (ICAMR).
2. Developing a National Plan that will include, but not limited to, the following
strategies:
a. Establishing short and long term programs to address the different as-
pects of response to AMR;
b. Strengthening the surveillance system and laboratory detection capacity
of AMR in both humans and animals;
c. Ensuring accessibility, affordability, availability and quality of antimicro-
bial drugs for humans and its appropriate use in food producing animals
including banning the use of antibiotics as growth promoters;
d. Developing relevant and utilizable essential medicines list for human
and veterinary use;
17
e. Monitoring the rational use of antimicrobials in humans, animal hus-
bandry and aquaculture;
f. Advocating the rational use of antimicrobials to consumers and commu-
nity through media and the academe;
g. Training and educating on, and promotion of infection prevention and
control measures in health care facilities and the community;
h. Conducting researches to develop new antimicrobials and innovative
technology to improve diagnosis and treatment;
i. Monitoring and evaluating compliance to existing policies and on the
proper implementation of the AMR control plan;
j. Engaging all relevant stakeholders such as government agencies,
healthcare providers, non-government institutions, professional organi-
zations, drug industry, veterinary and aquaculture groups, consumer
groups, researchers and civil societies; and
k. Ensuring that activities are well financed for sustainability.
H. ACTION PLANS THE PRIMARY PHYSICIANS AND DENTISTS CAN ADOPT TO
HELP COMBAT ANTIMICROBIAL RESISTANCE
1. First and foremost is assuring the judicious use of antimicrobial agents through
faithful adherence to the principles of rational use of medicines and utilizing an-
timicrobial agents only for the appropriate indications as recommended by
the Antimicrobial Resistance Surveillance Program (ARSP) or the task force for
Clinical Practice Guidelines and included in the Philippine National Formulary.
The choice of antibiotics must strictly conform to the best standard treatment
guidelines or clinical practice guidelines, and guided by the latest findings and
recommendations of the ARSP;
2. Keeping abreast of the latest information on AMR through review of the latest
antibiotic susceptibility data published by the ARSP, literature search, attend-
ance in seminars, and participation in continuing medical education programs;
3. Devoting sufficient time to educate the patients and their families and caregivers
about the appropriate use of antibiotics and the reasons behind the need for
strict adherence to the prescribed dosage schedule and completion of full
course of treatment as well as to educate them on the prevention of AMR;
4. Careful monitoring of the patient’s compliance and response to the antimicrobial
agents;
5. Submitting specimen for culture when indicated (e.g. for suspected gonococcal
infections);
6. Complying with the rules on prescribing, and other regulations in the Pharmacy
Law;
7. Developing better communication with pharmacists and other dispensers;
8. Educating the other healthcare providers (nurses, midwives, barangay health
workers) about the RUM and prevention of AMR; and,
9. Educating the community continually on the need for and proper ways of main-
taining good personal hygiene and sanitation, avoidance of vices or unhealthy
habits, sanitation and prevention of infections, including maintaining cleanliness
of their surroundings.
18
RELEVANT LAWS, REGULATIONS AND
POLICIES
The 1987 Philippine Constitution mandates the right of every Filipino to health. It enunci-
ates the policy that “the State shall protect and promote the health of the people and instill health
consciousness among them” (Article II Section 15). Furthermore, it provides the adoption by the
State of an “integrated and comprehensive approach to health development which shall en-
deavor to make essential goods, health and other social services accessible to all the people at
affordable cost.”
In pursuit of these goals, several policies and laws have been enacted. A clear under-
standing of the statutes and conformity to regulations by all healthcare providers underpin the
attainment of optimal heath management. The important ones that pertain to the Formulary and
the mandatory prescribing practices are summarized in the subsequent sections. Of particular
relevance are the National Health Insurance Act of 2013 and Administrative Order 2012-0023
and its amendments, which included provisions that relate to the objectives of this current vol-
ume of the Formulary.
• Republic Act No. 6675, known as the Generics Act of 1988 which declared as the
policy of the State, among others, “to promote, encourage and require the use of
generic terminology in the importation, manufacture, distribution, marketing, adver-
tising and promotion, prescription and dispensing of drugs; to ensure the adequate
supply of drugs with generic names at the lowest possible cost; to emphasize the
scientific basis for the use of drugs, in order that the health professional may be-
come more aware and cognizant of their therapeutic effectiveness; and to promote
drug safety.”
As contained in Section 6 of RA 6675 those required to use the generic

terminology are as follows: (a) all government health agencies and their personnel
as well as other government agencies in all their transactions related to purchasing,
prescribing, dispensing, and administering of drugs and medicines; (b) all medical,
dental, and veterinary practitioners, and including private practitioners, who may
include brand names, if they so desire; (c) any organization or company involved in
the manufacture, importation, repacking and/or distribution of drugs and medicines;
and (d) drug outlets, including drugstores, hospital and non-hospital pharmacies
and non-traditional outlets such as supermarkets and stores that shall inform any
buyer about drug products having the same generic names, together with their
prices, to allow the buyers to exercise their options.
The Generics Act further states that “in the promotion of the generic names
for pharmaceutical products, special consideration shall be given to drugs and med-
icines which are included in the Essential Drugs List that will be prepared and up-
dated regularly by the Department of Health.
• Executive Order No. 49 enacted on January 21, 1993 directed the mandatory use
of the Philippine National Drug Formulary (Volume 1 or the Essential Drugs List) as
the basis for procurement of drug products by all concerned government entities.
This strengthened the advocacy of the Generics Act by ensuring that only essential
medicines identified in their generic names will be procured by all government insti-
tutions.
19
• Administrative Order No. 163 s. 2002 (entitled “Implementing Guidelines and
Procedures in the Procurement and Requisition of Drugs and Medicines by the De-
partment of Health pursuant to Executive Order No. 49”) provided the procedural
bases that ensure requisition of essential medicines by the government sector and
the decision system for the inclusion and deletion of medicines in the Philippine Na-
tional Drug Formulary (PNDF). This also set the necessary requirements to be
submitted for the procurement of non-Formulary medicines as well as the criteria for
the approval of applications for exemptions from E.O. No. 49.
• The more recent Republic Act 9502 enacted in 2008 provides additional power to
the President of the Philippines to impose, upon the recommendation of the Secre-
tary of Health, maximum retail prices over medicines that include, among others,
the “drugs and medicines that are included in the Philippine National Drug Formu-
lary Essential Drug List.”
• The Philippine Health Insurance Corporation Board Resolution No. 265 (dated
July 15, 1999) provides that the PNDF Volume I shall be the basis for claims reim-
bursements for medicines.
• The National Health Insurance Act of 2013 (Republic Act No. 7875 as amended
by R.A. No. 9241 and RA No. 10606) declared as a guiding principle the provision
of comprehensive health care services to all Filipinos through a socialized National
Health Insurance Program that prioritizes the needs of the underprivileged, the sick,
the elderly, persons with disabilities (PWDs), women and children as well as pro-
vides for a full national subsidy for the indigent families identified by the Department
of Social Welfare and Development. To ensure the quality of the health services
that will be rendered to members by the accredited providers, the Republic Act
states in Section 37 that all concerned health care practitioners should assure that
“the performance of medical procedures and the administration of drugs are appro-
priate, necessary, and unquestioningly consistent with accepted standards of medi-
cal practice and ethics” as well as “respectful of local cultures.” Moreover, it reiter-
ated the previous requirement that medicines for which payment will be made by
PhilHealth shall be those included in the Philippine National Drug Formulary except
for explicit exemptions granted by the Corporation.
• Administrative Order No. 2012-0023 entitled “Revised Implementing Guidelines

for the Philippine National Formulary System” signed in 2012 reviewed and en-
hanced the previous implementing guidelines (AO No. 2006-002 and its two adden-
da). The notable changes pertinent to this current volume of the Philippine National
Formulary Manual include the following: replacement of the name Philippine Na-
tional Drug Formulary (PNDF) by Philippine National Formulary (PNF); revision of
the name of the National Formulary Committee to Formulary Executive Council
(FEC); further detailing of the selection processes for the inclusion and deletion of
the medicines in the Formulary and exemption from E.O. No. 49; the provision for
Evidence Review Groups that will assist the FEC in the selection of medicines; and
the development of multi-tiered volumes of the PNF adapted to the needs and ca-
pacities of the different levels of healthcare and which shall now include full pre-
scribing information and succinct clinical practice guidelines that will be incorpo-
rated in a single manual.
20
• Administrative Order No. 2012-0023-A amending the above A.O. addressed the
need for establishing systems for the following: price negotiation through the timely
creation of the Medicine Price Board that is tasked to negotiate for the most cost-
effective price for government; and health technology and economic evaluation
through the inclusion of more stringent criteria for accreditation of the Evidence Re-
view Groups as well as enhancement of the processes for exemption and the inclu-
sion and deletion of medicines in the Formulary.
• An additional amendment to A.O. 2012-0023, the Department Order No. 2014-

0088 provides the processes that will allow more prompt responses to applications
for exemption from E.O. No. 49 of the medicines that will be utilized for national
health programs, where the cost of the medicines for the program will exceed PhP
500,000.
• Administrative Order No. 2014-0009 entitled “Implementing Guidelines of the Phil-

ippine Medicines Strategic Directions on Access to Medicines for Filipinos (2011-
2016) for the Rational Use of Medicines Pillar” was enacted this year to set the
guiding principles and key strategies that will institutionalize the Rational Use of
Medicines. Integrating RUM into the healthcare system will ensure that only the
most necessary and scientifically proven, efficacious, and cost-effective medicines
are used in situations where there are clear and valid indications for them.
• The Rational Use of Medicines (RUM) forms an integral part of the Philippine Med-
icines Strategic Directions on Access to Medicines for Filipinos for 2011-2016,
that will set the roadmap for a national medicine policy. This policy will serve as the
guideline for the development of a framework that will provide the directions for im-
proving access to essential medicines by all Filipinos in all levels of healthcare at all
times. This incorporates the principles embodied in the SARAH Medicines Access
Framework that refers to five complementary and mutually reinforcing pillars: Safe-
ty, efficacy and quality; Affordability and availability; Rational use of medicines; Ac-
countability, transparency and good governance; and Health system support.
21
MEDICINE
and
THERAPEUTIC
INFORMATION
22

$GYHUVH'UXJ5HDFWLRQV
$//(5*<$1',0081(6<67(0 Common: Dizziness, drowsiness, dryness of
mouth, fatigue, headache, insomnia, malaise,
nausea, pharyngitis, somnolence.
$17,+,67$0,1(6 Less Common: Abdominal pain, anorexia, arthral-
gia, chest pain, diarrhea, dyspepsia, dyspnea,
elevated liver enzymes, epistaxis, fever, flush-
CETIRIZINE ing, increased appetite, myalgia, tachycardia,
thirst, vomiting, weight gain.
2UDO10 mg tablet (as dihydrochloride) Rare: Dystonias, hemolytic anemia, hepatitis, hy-
10 mg/mL drops, 10 mL persensitivity, including anaphylaxis and bron-
(as dihydrochloride) chospasm; hypotension, rash, thrombocyto-
1 mg/mL solution, 30 mL and 60 mL penia.
(as dihydrochloride) 'UXJ,QWHUDFWLRQV
5 mg/5 mL syrup, 30 mL Monitor closely with:
(as dihydrochloride) Acetylcholinesterase Inhibitors (central) – these
A piperazine-derived, long-acting, second- may diminish the therapeutic effect of cetiriz-
generation H 1 receptor antagonist, which is ine.
often better tolerated than sedating antihista- Analgesics (opioids) – their adverse effects may be
mines due to less sedating and less anticho- enhanced by cetirizine, specifically constipa-
linergic effects. tion and urinary retention.
Anticholinergics (e.g., ipratropium, tiotropium) –
,QGLFDWLRQV Perennial and seasonal allergic rhini- their anticholinergic effect may be enhanced
tis, and other allergic symptoms such as hay by cetirizine.
fever, conjunctivitis, and chronic idiopathic ur- CNS Depressants (e.g., alcohol, sedatives) – these
ticaria. may potentiate the sedative effect of cetirizine;
&RQWUDLQGLFDWLRQV Known hypersensitivity reac- cetirizine may also enhance the adverse effect
tions to cetirizine, levocetirizine or hydroxyzine of other CNS depressants.
(cetirizine is hydroxyzine’s active metabolite) Warfarin – risk of increased INR and epistaxis.
or any component of the formulation; severe Avoid concomitant use with:
renal impairment. Doxylamine- combination increases risk for CNS
depression and psychomotor retardation.
'RVH
Symptomatic relief of allergy, by mouth, $'8/7, 10 $GPLQLVWUDWLRQ It may be administered with or
mg once daily or 5 mg twice daily (may be in- without food.
creased as necessary to the maximum rec- 3UHJQDQF\&DWHJRU\ B
ommended daily dose of 20 mg); &+,/' >6
years, 10 mg/day or 5 mg twice daily; &+,/'
2-6 years, 5 mg once daily or 2.5 mg twice
daily; &+,/' 1-2 years, oral drops, 0.25 DIPHENHYDRAMINE
mg/kg twice daily.
'RVH$GMXVWPHQWV 2UDO 25 mg and 50 mg capsule (as HCl)
Elderly ൒77 years of age: 12.5 mg/5 mL syrup, 60 mL and 120 mL
Use lower dose (5 mg/day). (alcohol-free) (as HCl)
Renal DQGHepatic Impairment: ,QM 50 mg/mL, 1 mL ampul (IM, IV) (as HCl)
For mild-to-moderate impairment, dose reduction is A monoethanolamine-derived, first-generation H 1
warranted (5 mg/day); receptor antagonist that exhibits antimusca-
Contraindicated for severe renal impairment. rinic and pronounced sedative property, with
3UHFDXWLRQV low incidence of GI side effects.
:$51,1*: May cause CNS depression which may impair ,QGLFDWLRQVRelief of allergic symptoms caused by
physical or mental abilities; patients should be cau- histamine release, including rhinitis, cough,
tioned about performing tasks that require mental
alertness, such as operating machinery or driving. conjunctivitis and allergic dermatoses; moder-
ate to severe angioedema and anaphylaxis
CNS stimulation may occur with antihistamines, (adjunct to epinephrine).
especially in children (caution is advised in pa-
tients suffering from epilepsy); children and &RQWUDLQGLFDWLRQV Known hypersensitivity to
the elderly (risk of sedation and anticholinergic diphenhydramine or any component of the
effects are increased). formulation; acute asthma; neonates or prem-
Renal impairment; hepatic impairment; excess ature infants (increased susceptibility to anti-
alcohol intake, and use of other sedative muscarinic effects); breastfeeding; use of the
drugs should be avoided. parenteral form as a local anesthetic.

Not recommended for children <12 months, or for 'RVH
breastfeeding mothers (cetirizine is excreted Allergic reactions, by mouth, $'8/7, 25-50 mg
into breast milk). every 6-8 hours; &+,/' >12 years, 25-50 mg
23
every 4-6 hours (maximum, 300 mg daily); Drug Interactions:
CHILD 6 to <12 years, 12.5-25 mg every 4-6 Monitor closely with:
hours (maximum, 150 mg daily); CHILD 2 to Beta blockers (e.g., labetalol, metoprolol, proprano-
<6 years, 6.25 mg every 4-6 hours (maxi- lol) – their plasma concentration and cardio-
mum, 37.5 mg daily). vascular effects are increased by diphenhy-
Allergic reactions, by IM or IV injection, ADULT, 10- dramine.
50 mg/dose, single doses up to 100 mg may CNS depressants (e.g., alcohol, anxiolytic seda-
be used if needed (not to exceed 400 tives, barbiturates, hypnotics, neuroleptics,
mg/day); CHILD, 5 mg/kg/ day or 150 opioid analgesics) – these may potentiate the
mg/m2/day in divided doses every 6-8 hours sedative effect of diphenhydramine.
(not to exceed 300 mg/day).
Administration: May be taken with or without food.
Dose Adjustments:
Pregnancy Category: B
Advanced age:
If used, consider lower doses.
Renal Impairment:
Same dosage as in patients with normal renal func-
tion may be used in patients with mild-to- LORATADINE
moderate renal impairment.
Hepatic Impairment: Oral: 10 mg tablet and 10 mg film-coated tablet
Same dosage as in patients with normal hepatic 5 mg/5 mL syrup, 30 mL
function may be used in patients with mild-to- A piperidine-derived, non-sedating, second-
moderate hepatic impairment; for severe im- generation H 1 receptor antagonist, which is
pairment, the patient should be referred to a extensively converted into a metabolite having
specialist (due to increased risk for coma). a longer half-life.
Elderly:
For emergency allergic reactions only; use only Indications: Relief of nasal and non-nasal symp-
smallest effective dose, 25 mg oral or IV every toms of seasonal allergic rhinitis; hay fever;
8-12 hours (advanced age associated with re- chronic idiopathic urticaria, and other allergic
duced clearance of drug). dermatological disorder.
Precautions: Contraindications: Known hypersensitivity to

WARNING: May cause sedation; serious adverse drug loratadine or any component of the formula-
interactions are quite common, potentially fatal in tion; children <2 years of age; pregnancy;
some; antihistamines can cause hypersensitivity reac- breastfeeding.
tions themselves.
Dose:
CNS depression (caution in performing tasks requir- Chronic idiopathic urticaria and seasonal allergic
ing mental alertness); prostatic hypertrophy, rhinitis, by mouth, ADULT, 10 mg once daily
urinary retention, susceptibility to angle- (not to exceed 10 mg per day); CHILD >30 kg
closure glaucoma, and pyloroduodenal ob-
or >6 years, 10 mg once daily; CHILD <30 kg
struction; advanced age (associated with re-
or 2-5 years, 5 mg once daily
duced drug clearance, and increased risk of NOTE: Safety and efficacy is not established for allergic
confusion, dryness of mouth, constipation or rhinitis in CHILD <2 years, and for urticaria in CHILD
other anticholinergic effects, and toxicity); <6 years.
asthma; thyroid dysfunction; cardiovascular
disease; pediatrics (may cause excitation; Dose Adjustments:
more susceptible to side-effects); epilepsy. Renal and Hepatic Impairment:
Latter part of third trimester pregnancy (may cause For mild-to-moderate impairment, the dose frequen-
irritability, paradoxical excitability, and tremor cy is reduced to alternate days; for severe im-
in neonates). pairment, the patient should be referred to a
specialist.
Adverse Drug Reactions:
Common: Anxiety, blurred vision, constipation, Precautions:
cough, diarrhea, dizziness, dryness of mouth, Renal or hepatic impairment; the elderly (loratadine
nose and throat, epigastric discomfort, eupho- may be inappropriate in certain comorbidities,
ria, incoordination, insomnia, nausea, nerv- such as dementia and delirium; increased risk
ousness, psychomotor impairment, sedation, of sedation and anticholinergic effects);
sleepiness, thickening of bronchial secretions, breastfeeding; prostatic hypertrophy, urinary
tinnitus, tremor, vomiting. retention, susceptibility to angle-closure glau-
Less Common: Hallucinations, headache, hypo- coma and pyloroduodenal obstruction; and
tension, palpitations, psychosis, restlessness, epilepsy.
urinary retention, vertigo. Adverse Drug Reactions:
Rare: Agranulocytosis, arrhythmias, blood dyscra- Common: Abdominal pain, blurred vision, conjunc-
sias, convulsions, EPS, hemolytic anemia, tivitis, drowsiness, dryness of mouth, dyspho-
hepatitis, hypersensitivity reactions, leukopenia, earache, epistaxis, fatigue, GI disturb-
nia, liver disorders, excitation, hallucination, ances, headache, hyperkinesia, impaired con-
seizures, paralysis. centration, influenza-type symptoms, laryngi-
tis, malaise, nausea, nervousness, psychomo-
24
tor impairment, somnolence, stomatitis, upper Dose:
respiratory tract infection, urinary retention, vi- Anaphylaxis, by IV or IM injection, ADULT, 200 mg;
ral infection, wheezing. by IV injection, CHILD, 2-4 mg/kg.
Less Common: Elevated liver enzymes, increased
appetite, insomnia, weight gain. See under Corticosteroids for other information.
Rare: Abnormal hepatic function, agitation, alope-
cia, amnesia, angle-closure glaucoma, blood
disorders, bronchitis, chest pain, confusion,
convulsions, depression, dermatitis, dizziness, PREDNISONE
erythema multiforme, EPS, hemoptysis, he-
patic necrosis, hepatitis, hypotension, hyper- Oral: 5 mg, 10 mg and 20 mg tablet
sensitivity reactions, including anaphylaxis; 10 mg/5 mL suspension, 60 mL
hypertension, impotence, palpitation, periph- A corticosteroid having glucocorticoid and anti-
eral edema, purpura, seizures, sleep disturb- inflammatory effects that is rapidly converted
ance, supraventricular tachyarrhythmias, syn- to prednisolone – the active product – in the
cope, tachycardia, thrombocytopenia, urticar- body.
ia, vertigo.
Indications: For the treatment of allergy and as
Drug Interactions: adjuvant for anaphylaxis.
NOTE: Sedative interactions apply to a lesser extent to the
non-sedating antihistamines. Interactions do not gen- Contraindications: See under Corticosteroids.
erally apply to antihistamines used for topical action,
as well as inhalation. Dose:
Monitor closely with: Allergy, by mouth, ADULT, initially up to 10-20 mg
Alcohol – its CNS depressant effect may be en- daily as a single dose in the morning (in se-
hanced by loratadine. vere allergy, up to 60 mg daily as a short-
Analgesics (opioids) – their adverse effects may be course of 5-10 days); CHILD, 1-2 mg/kg/day
enhanced by loratadine, specifically constipa- in 2-3 divided doses. Taper dose over the next
tion and urinary retention. few days.
Azithromycin- loratadine increases level or effect of Anaphylaxis (adjunctive treatment), by mouth,
this drug. ADULT, 0.5 mg/kg.
CYP3A4 inhibitors (see Appendix) – these may
significantly increase the plasma concentra- See under Corticosteroids for other information.
tion of loratadine, thereby increasing the risk
of adverse effects.
Estradiol and estrogens conjugated synthetic- lo-
ratadine increases the level or effect of these
drugs.
SSRIs – their adverse effects may be enhanced by
loratadine, specifically the risk of psychomotor
impairment.
STEROIDS
HYDROCORTISONE
Inj.: 50 mg/mL, 2 mL vial (IM, IV)

(as sodium succinate)
125 mg/mL, 2 mL and 4 mL vial (IV)
Powder, 100 mg, 250 mg vial (IV)
A glucocorticoid used on a short-term basis for the
emergency management of conditions, such
as anaphylaxis.
Indication: Adjunct in the emergency treatment of
anaphylaxis.
Contraindications: See under Corticosteroids.
25
stances, cyanides, malathion, metal salts, in-
ANTIDOTES cluding those of iron and lithium.
Common: Black stools, blackening of teeth and
ACTIVATED CHARCOAL, USP mouth; colicky abdominal pain (discomfort,
swelling), constipation, nausea, vomiting.
Oral: Powder, USP grade given as slurry Less Common: Diarrhea, hypotension.
Rare: Bowel obstruction, charcoal embolism; hypo-
A fine, smooth, odorless, tasteless, black powder, glycemia, hypothermia, pneumonitis (due to
prepared from the carbonization of organic aspiration).
matter, which reduces drug or poison absorp-
tion either by binding to it in the GI tract or by Drug Interactions:
interrupting it in the enterohepatic recircula- Monitor closely with:
tion. Laxatives (e.g., mannitol, sorbitol) – these may
cause volume depletion and electrolyte ab-
Indications: Gastrointestinal decontamination for normalities.
specific drug or poison ingestion associated Avoid concomitant use with:
with significant risk of toxicity (reducing ab- Anti-epileptics, oral contraceptives and other char-
sorption of drugs and poisons in the GI sys- coal interactants (e.g., digoxin, paracetamol,
tem); acute, oral poisoning. furosemide, salicylates, sulfonylureas, sul-
Contraindications: Bowel obstruction; poisoning fones, tetracyclines, theophylline, tricyclic an-
by hydrocarbons (e.g., petroleum distillates) tidepressants) – their absorption is reduced,
with high potential for harm if aspirated; poi- and they may eventually be removed from
soning by corrosive substances (this may pre- systemic circulation (may result to treatment
vent visualization of lesions caused by the failure).
poison); GI tract not anatomically intact; un- Food (e.g., milk, ice cream, sherbet) – this decreas-
protected airway. es the adsorptive capacity of activated char-
coal.
Dose:
Poisoning (for reduction of absorption), by mouth, Administration: In preparing lavage, ensure that
ADULT and CHILD >12 years, 50-100 g in the patient is in trendelenberg and left lateral
100-150 mL distilled water as a slurry given as decubitus position.
a single dose, as soon as possible after inges- Administer as a slurry (thick suspension) to increase
tion of poison; CHILD 1-12 years, 25 g as sin- adsorptive capacity; should not be adminis-
gle-dose (50 g in severe poisoning) in 50-100 tered with food due to decreased efficacy;
mL distilled water; INFANT, 1 g/kg as single- when given orally, the smallest dose should
dose (maximum, 50 g). NOTE: May repeat lavage be given slowly to avoid vomiting; adsorptive
every 6 hours for 48-72 hours. To produce effective effectiveness is time-dependent (greatest
adsorption, a ratio of about 10 parts activated char- benefit is observed when administered within
coal to one part poison is needed. one hour after poison ingestion).
Poisoning (for active elimination), by mouth, NOTE: If the patient is conscious and cooperative, a slurry
ADULT, 50 g every 4 hours (in case of intol- form of the activated charcoal may be orally adminis-
erance, 25 g every 2 hours); CHILD >1 year, tered. But in cases where NGT may be obstructed,
further dilution is allowed.
25-50 g every 4-6 hours; INFANT, 1 g/kg eve-
See under CPG on Common Poisoning for other
ry 4-6 hours.
information.
Dose Adjustments:
In uremic adult patients:
By mouth, 20-50 g once daily.
Precautions:
WARNING: Electrolyte abnormalities (hypernatremia, ATROPINE
hypokalemia, and hypermagnesemia) have been re-
ported to occur with the concomitant use of cathartics, Oral: 600 microgram tablet (as sulfate)
namely sorbitol, in the charcoal. Inj.: 1 mg/mL ampul (IM, IV) (as sulfate)
Not generally recommended in children <1 year.
Monitor for active bowel sounds before administer- An alkaloid from Atropa belladonna that competi-
ing; drowsy, unconscious or comatose patient tively blocks acetylcholine action in central
(risk of aspiration – ensure that airway is pro- and peripheral muscarinic autonomic recep-
tected); decreased peristalsis (administer tors.
within 1 hour of ingestion); caution during mul- Indications: Poisoning with organophosphate and
tiple doses due to danger of intestinal impac- n-methyl carbamate pesticides.
tion (reduce initial dose to half to prevent im-
paction; lavage should be followed by sodium Contraindications: Hypersensitivity to atropine or
sulfate cathartic). any component of the formulation; angle-
Do not use for poisoning with the following sub- closure glaucoma; severe inflammatory GI
stances: alcohols (e.g., ethanol, methanol), disease or GI obstruction; prostatic hypertro-
clofenotane (dicophane, DDT), corrosive sub- phy; prostatism and urinary obstruction; myas-
26
thenia gravis; thyrotoxicosis; organochlorine Drug Interactions:
poisoning; pyloric stenosis; poisoning caused Monitor closely with:
by CNS adrenergic stimulants, phenothia- Alcohol – enhanced CNS effects/CNS depression.
zines, tricyclic antidepressants and other anti- Antacids – these may delay or reduce oral absorp-
cholinergics. tion of atropine.
NOTE: No contraindications exist in the treatment of life- Beta blockers (e.g., metoprolol) – their retention
threatening organophosphate or carbamate insecti- time may be increased by atropine; it may al-
cides, and nerve agent poisoning.
so enhance their dissolution and bioavailabil-
Dose: ity.
Organophosphate and carbamate poisoning, by IM Chlorpromazine – increased antimuscarinic adverse
or IV injection (depending on the severity of effects (but reduced plasma chlorpromazine
poisoning), ADULT, 1-2 mg, and CHILD, 20 concentration).
micrograms/kg, repeated every 5-10 minutes Nitrates (e.g., isosorbide dinitrate) – atropine may
as necessary until full atropinization is ob- reduce the effects of sublingual tablets (failure
served (skin becomes flushed and dry, pupils to dissolve under the tongue due to dry
dilate ≥4 mm, pulse rate >120/minute, or, in mouth).
the elderly >70/minute, and hypoactive bowel Avoid concomitant use with:
sounds); gradually decrease interval of dosing Anticholinergic drugs or other drugs with anticholin-
and amount per dose after 12-24 hours; con- ergic effects (see Appendix – Table A) – these
tinue for 2-3 days in carbamate poisoning and increase the therapeutic effect and risk of ad-
longer in cases of organophosphates, or until verse effects of atropine (including central an-
the patient can be transferred to a hospital. ticholinergic delirium); avoid these combina-
tions if possible (if required, monitor the pa-
Dose Adjustment: tient, and reduce dose if necessary).
Renal Impairment: Anticholinesterases (e.g., neostigmine, pyridostig-
For mild-to-moderate renal impairment, dose reduc- mine) – combining anticholinergics with these
tion, or less frequent doses, after initial atro- drugs, which increase acetylcholine concen-
pinization is warranted (since atropine may be tration, will antagonize the anticholinergic ef-
eliminated more slowly); for severe impair- fect.
ment, the patient should be referred to a spe- Digoxin – atropine may increase serum digoxin
cialist. levels, resulting in enhanced actions and risk
Precautions: of toxicity.
Children; elderly; GI disorders (see Contraindica- Haloperidol – schizophrenic symptoms may worsen
tion); Down syndrome; prostatic enlargement; due to decreased plasma concentration of
cardiac disorders; hypoxia; constipation, delir- haloperidol.
ium, tachycardia and fever from any cause (all Metoclopramide – atropine antagonizes the effects
these may be worsened by atropine); pyrexia of metoclopramide on GI activity.
and in warm environments (monitor tempera- Norepinephrine – enhanced pressor effect; its reflex
ture and keep patients cool). bradycardia is blocked by atropine.
Pregnancy (crosses the placenta and may cause Phenylephrine – atropine increases the risk of se-
tachycardia); breastfeeding (small amount vere hypertension with phenylephrine eye
present in milk; may cause antimuscarinic ef- drops (use the combination cautiously and
fects in infants). monitor BP).
NOTE: Since atropine has a short duration, late unopposed Administration: See under Clinical Practice Guide-
bradycardia may result. Therefore, close monitoring is
necessary. lines – Common Poisoning.
NOTE: Parenteral drug products should be inspected visual-
Adverse Drug Reactions: ly for particulate matter and any possible discoloration
NOTE: Adverse effects following single or repeated doses of prior to administration; use only if solution is clear and
atropine are most often the result of excessive dos- seal intact.
age.
Pregnancy Category: C
Common: Blurred vision, constipation, cycloplegia,
delirium, dryness of mouth, nose and skin, dif-
ficulty in micturition and swallowing, fever,
flushing, mydriasis, palpitations, photophobia,
thirst, transient bradycardia followed by tachy- COBRA ANTIVENIN
cardia, urinary retention.
Less Common: Agitation, arrhythmias, ataxia, Inj.: 800 IU/5 mL ampul (IM, IV)
confusion (in elderly), disorientation, excite- A monovalent purified fraction of immunoglobulin
ment, headache, heat prostration, hyperpyrex- fragments from the plasma of animals immun-
ia, hypertension, paralytic ileus, psychosis, ized against a snake venom or a snake ven-
rapid respiration, rash, restlessness, vomiting. om mixture; its use is limited to a few closely-
Rare: Angle-closure glaucoma, myocardial infarc- related species whose venoms show clinically
tion, seizures. effective cross-neutralization.
Indications: Management of patients with Naja
spp. envenomations (e.g., N. philippinensis,
N. samarensis and N. sumatrana); signs of
27
neurotoxicity or swelling involving more than hours of envenomation; monitor for 1 hour fol-
half the bitten extremity. lowing the infusion.
Contraindications: Allergy to horse-based prod- Pregnancy Category: C
ucts, or antivenin by history or as a result of
an appropriate sensitivity test; hypersensitivity
to any component of the formulation, including PYRIDOSTIGMINE
papaya or papain; cross allergenicity with dust
mite and latex allergens. Oral: 60 mg tablet
Dose: Pyridostigmine is a cholinesterase inhibitor with
Naja spp. envenomations, ADULT and CHILD, comparatively long duration and gradual de-
usual dose is 0.5 mL IM; severe cases: initial cline of its cholinergic action.
dose of 5-10 vials IV and repeated every 1-2
hours until local manifestations, coagulation Indications: Initial treatment of snake bites due to
tests, and systemic signs are observed to be the Philippine cobra (predominantly causes
normal. The antivenin can be diluted in 500 neuromuscular paralysis) when cobra antiven-
mL isotonic fluid to run for 1-2 hours, or given in is not available (see under Common Poi-
undiluted IV over 10-15 minutes. soning – Cobra Bites).
NOTE: Begin infusion slowly, watching carefully for adverse
Contraindications: Mechanical obstruction of the
effects. Stop the infusion temporarily if these occur. If
there is no adverse reaction, increase the rate, aiming intestinal or urinary tract and known allergy to
to give the entire infusion over about 15-20 minutes. the preparation and bromide sensitive pa-
tients.
Precautions:
Dose:
WARNING: Antivenins should never be administered
prophylactically to asymptomatic patients. Pain and Cobra bite when cobra antivenin is not available:
fang marks are not intrinsically signs of enven- given through nasogastric tube, 60 mg 2-4
omation. times daily (see under Common Poisoning –
Cobra bites) while awaiting transfer of the pa-
Patients sensitive to antivenin or horse serum may
tient to the hospital and with dose titration
develop anaphylaxis. Prior to IV or IM antiven-
done depending on side effects.
in administration, proper skin test should be
performed and interpreted (therapy may be Precautions:
modified if indicated). Overdosage may result in cholinergic crisis, with
In life threatening situations, pre-treat with antihis- increasing muscle weakness which through
tamine (diphenhydramine, 50-100 mg IV), fol- involvement of respiratory muscles may lead
lowed by slow IV infusion of very dilute anti- to death. Pyridostigmine is discontinued in this
venin. At the first sign of hypersensitivity reac- case. (See below for Treatment); caution in
tion, stop infusion and administer subcutane- epilepsy, asthma, COPD, recent MI, hyper-
ously 0.5-1.0 mL epinephrine (1:1000); pre- tension, vagotonia, hyperthyroidism,
existing renal, hepatic, cardiac, or respiratory dysrhythmia.
treatment with anticoagulant or antiplatelet Pregnancy (no controlled studies in pregnant wom-
drugs (increased risk of serious outcomes, in- en); should be used strictly as directed.
cluding death, from snakebite); the elderly
(may require more vigorous treatment); chil- Adverse Drug Reactions:
NOTE: Most of these are due to undesirable functional
dren (should not be given weight-adjusted
effects on the autonomic nervous system.
doses; the amount required depends on the
Frequency not defined:
amount of venom to be neutralized).
Muscarine-type ADRs – nausea, vomiting, diarrhea,
Refer to Clinical Practice Guidelines – Common
abdominal cramps, increased peristalsis and
Poisoning for further information.
bronchial secretions, salivation, lacrimation,
STORAGE. Cold-chain management in hospitals.
bradycardia and miosis.
Adverse Drug Reactions: Nicotine-type ADRs – muscle spasms including
Common: Anaphylaxis or anaphylactoid reactions, laryngospasms, muscle twitches and muscle
chest discomfort, chills, dizziness, dyspnea, weakness.
edema of the face, tongue, and throat, fever, Also, urticaria and transient rash in bromide-
flushing, headache, hypotension, pruritus, sensitive patients.
rash, serum sickness, tachypnea, urticaria. Rare: Cholinergic crisis due to overdosage (see
Less Common: Abdominal pain, angioedema, Precautions and Treatment of Overdosage),
arthralgia, bradycardia, bronchospasm, col- cardiac standstill.
lapse, myalgia, nausea, neurological impair- Treatment of Overdosage:
ment, pain at the infusion site, sweating, tach- For cholinergic crisis, discontinue pyridostigmine
ycardia, vertigo, vomiting, wheezing. and give by slow IV 1-2 mg of atropine sulfate;
Rare: Cardiac arrest. then, depending on the pulse rate, may repeat
at intervals of 2-4 hours if required.
Drug Interactions: No information found.
Administration: Given through nasogastric tube in
Administration: The treatment should begin as
patients with cobra bites.
soon as possible and preferably within 4-6
28
1.3. The lowest incidence of, or least seri-
ANTI-INFECTIVES (SYSTEMIC) ous, adverse reactions.
2. Avoid the use of:
2.1. Topical antimicrobials - topical antisep-
ANTIBACTERIALS (Oral and Parenteral)
tics often suffice except for proven in-
dications such as vaginitis, conjunctivi-
PRECEPTS TO BE CONSIDERED BEFORE
tis and impetigo;
STARTING THERAPYa
2.2. Antimicrobial combinations except in
1. Establish a presumptive diagnosis of bacterial specific proven circumstances (tuber-
infection and if possible, a specific etiologic diag- culosis, neonatal sepsis, etc.)
nosis. Viral infections should not be treated with 2.3. Prophylactic antibiotics, unless they
antibiotics. There are few viral infections respon- are proven to be of benefit (e.g., post-
sive to anti-viral therapy. exposure prophylaxis meningococ-
2. Samples of blood and/or body fluids and dis- cemia and anthrax)
charges should be taken for gram-staining, and
whenever possible, submission of specimen to a a
Turnidge J. Principles of Appropriate Prescribing of Antimi-
higher healthcare level for culture and sensitivity crobials. Australian Journal of Hospital Pharmacy, 1994;
24:533-536
test.
3. An up-to-date knowledge of prevalent organisms
and their current susceptibility is of great help in
empirically choosing an antibacterial drug before AMOXICILLIN
bacteriological confirmation is available.
4. The choice of a suitable antibiotic, the dose, Oral: 250 mg and 500 mg capsule (as trihydrate)
route and duration of therapy will depend on 100 mg/mL granules/powder for drops (sus-
pension), 10 mL (as trihydrate)
three factors:
125 mg/5 mL and 250 mg/5 mL gran-
4.1. Suspected/proven causative organism ules/powder for suspension, 60 mL
and its susceptibility pattern (as trihydrate)
4.2. Host/patient factors such as:
A penicillinase-susceptible aminopenicillin having
• Age
extended spectrum of activity; oral absorption
• Nature, severity and site of infec- is not impaired by food, and is more rapidly
tion and completely absorbed, with higher bioa-
• History of allergy and other con- vailability and less GI irritation than ampicillin.
comitant diseases Indications: Upper and lower respiratory tract
• Renal and hepatic functions infections (including low-risk community-
• Immunologic status acquired pneumonia) due to susceptible bac-
• Genetic factors teria; exacerbations of chronic bronchitis; bac-
terial otitis media; dental abscess and other
• Pregnancy and lactation
oral infections; osteomyelitis; uncomplicated
4.3. Drug factors such as: enteric or typhoid fever; prophylaxis of bacte-
• Antimicrobial spectrum and anti- rial endocarditis during dental surgery; Helico-
bacterial efficacy (pharmacody- bacter pylori eradication (with either clarithro-
namics) mycin or metronidazole; see under H. pylori
• Pharmacokinetics eradication); as alternative antibiotic for mild
leptospirosis.
• Adverse effects
• Cost of therapy Antimicrobial Resistance ALERT!
Amoxicillin should not be used for the empiric
• Stability at anticipated local condi-
treatment of Acute Uncomplicated Cystitis and
tions, acceptability, ease and ac- Acute Uncomplicated Pyelonephritis due to
curacy of dosing the relatively poor efficacy and very high
prevalence of antimicrobial resistance.
Rules of Thumb
Contraindication: Known hypersensitivity to peni-
Some basic principles that should serve as cillins, or any component of the formulation.
guides to antimicrobial therapy: Dose:
Community-Acquired Pneumonia, low-risk (CAP-
1. Choose the agent with: LR), or non-severe, by mouth, ADULT, 500
1.1. The narrowest spectrum which will mg three times a day (for uncomplicated CAP-
cover the likely or proven pathogen(s); LR, the duration is 5-7 days) - see Clinical
Practice Guidelines – CAP for further infor-
1.2. The least expensive if efficacy and
mation; CHILD, 40-50 mg/kg/day in 3 divided
safety are otherwise equal;
29
PNF new 55 new.pdf 1 1/12/15 3:46 PM
doses, maximum of 1,500 mg/day, for at most 'UXJ,QWHUDFWLRQV

7 days- see Guidelines - Pediatric CAP. Monitor closely with:
Dental abscess (short-course), by mouth, $'8/7, 3 Allopurinol – when combined with amoxicillin, there
g repeated once after 8 hours. is increased risk of rash occurrence.
Endocarditis prophylaxis, by mouth, $'8/7, 2 g Contraceptives, Oral – their efficacy may be re-
single dose 1 hour before procedure; &+,/', duced by amoxicillin.
50 mg/kg (maximum, 2 g) single dose 1 hour Tetracyclines (e.g., doxycycline, minocycline, and
before procedure. tetracycline) – these could reduce the thera-
Enteric or typhoid fever (uncomplicated), by mouth, peutic and pharmacologic action of amoxicil-
$'8/7, 75-100 mg/kg thrice daily for 14 lin.
days, or 4-6 g once daily divided every 8 Vitamin K antagonists (e.g., warfarin) – penicillins
hours for 14 days; &+,/' and ,1)$17, 100 may enhance the anticoagulant effect of these
mg/kg divided every 8 hours for 14 days. drugs.
Otitis media, by mouth, $'8/7, 1 g every 8 hours; Avoid concomitant use with:
&+,/', 40 mg/kg daily in 3 divided doses Chloramphenicol– this may decrease the effects of
(maximum, 3 g daily). amoxicillin.
Leptospirosis, mild (as alternative treatment)a, by
mouth, $'8/7, 500 mg every 6 hours or 1 g $GPLQLVWUDWLRQ May be taken with or without food
every 8 hours for 7 days. (may be given without regard to meals); best
Other infections due to sensitive organisms, by taken at the start of meals for better absorp-
mouth, $'8/7 and &+,/' >10 years, 250 tion, and reduction of GI discomfort.

mg every 8 hours (double the dose in severe 3UHJQDQF\&DWHJRU\ B
infections); &+,/' up to 10 years, 125 mg
every 8 hours (double the dose in severe in-
fections).
a
The Philippine Clinical Practice Guidelines in the Diagno- AMPICILLIN
sis, Treatment and Prevention of Leptospirosis in
Adults, 2010, PSMID, Quezon City. ,QM 125 mg, 250 mg, 500 mg and 1 g vial (IM, IV)
'RVH$GMXVWPHQW (as sodium salt)
Renal Impairment: An extended-spectrum aminopenicillin useful for
Patients with impaired renal function do not general- treating serious conditions not amenable to
ly require dose reduction unless impairment is oral therapy, or infections caused by penicillin-
severe, in which case, the patient should be susceptible bacteria, such as anaerobes, en-
referred to a specialist. terococci, and beta lactamase-negative
3UHFDXWLRQV strains of gram-negative cocci and bacilli. This
History of allergy to penicillins; renal impairment is given parenterally because only less than
(risk of crystalluria with high doses); high inci- half of the oral dose is absorbed (absorption is
dence of erythematous rash in glandular fe- further decreased by food).
ver, acute lymphoblastic leukemia, infectious ,QGLFDWLRQV Sepsis neonatorum (with gentamicin);
mononucleosis, chronic lymphocytic leukemia, enteric fever.
CMV infection, HIV infection; risk of crystal-
luria (maintain adequate hydration with high Antimicrobial Resistance ALERT!
doses); superinfection (prolonged use may re- Due to high resistance of Haemophilus pneu-
sult in fungal or bacterial superinfection). moniae to ampicillin, this antibiotic is not rec-
Pregnancy (not known to be harmful); breastfeeding ommended as empiric therapy for infections
(monitor infant; trace amounts found in milk, caused by this pathogen.
but appropriate to use). &RQWUDLQGLFDWLRQV Known hypersensitivity to
$GYHUVH'UXJ5HDFWLRQV penicillins or any component of the formula-
Common: Diarrhea, headache, nausea. tion; patients with glandular fever or acute
Less Common: Abdominal pain, antibiotic- lymphatic leukemia.
associated colitis, vomiting. 'RVH
Rare: Allergic reactions including anaphylaxis, Enteric fever (typhoid fever), by IV push over 3-5
angioneurotic edema, CNS disorders, includ- minutes or IV infusion over 15-30 minutes,
ing convulsions (associated with high doses, $'8/7, 50-100 mg/kg/day divided every 6
or impaired renal function); coagulation disor- hours for 1-2 weeks; &+,/', 100 mg/kg/day
ders, hemolytic anemia, interstitial nephritis, divided every 6 hours for 1-2 weeks. Once
mucocutaneous candidiasis, neutropenia, with clinical improvement and oral medication
pustular drug eruption, rash, serum sickness- is tolerated, the antibiotic may be shifted to
like reactions, thrombocytopenia, urticaria. oral amoxicillin (See under Amoxicillin).
127(: A widespread, erythematous maculopapular rash
(pseudoallergic) is common; often occurs after >7 Sepsis neonatorum (with gentamicin), by IV push
days treatment and resolves 1-7 days after treatment over 3-5 minutes or IV infusion over 15-30
is stopped, or after 6-14 days if it continues (although minutes, 1(21$7( < GD\V, ൑2 kg weight:
not immune-mediated, consider skin testing to check 25 mg/kg/dose
25-50 mg/kg/doseevery 1212hours;
every >2kg
hours;>2 kg weight:
weight:
for hypersensitivity before using penicillin again). 75-150mg/kg/dose
25-50 mg/kg/doseevery
every 88 hours; 1(21$7(
hours; NEONATE
30
>GD\V, ൑1.2 kg weight: 25 mg/kg/dose eve-

>GD\V, ൑1.2 kg weight: 25 mg/kg/dose eve-
ry 12 hours; >1.2 to 2 kg weight: 25 AZITHROMYCIN
ry 12 hours; >1.2 to 2 kg weight: 25 AZITHROMYCIN
mg/kg/dose every 8 hours; >2 kg weight: 25
mg/kg/dose every 8 hours; >2 kg weight: 25
mg/kg/dose every 6 hours. 2UDO 250 mg capsule (as base*/as dihydrate)
5(&2167,787,21 every
mg/kg/dose 6 hours.
$1' $'0,1,675$7,21. According to 2UDO 250 mg capsule (as base*/as dihydrate)
500 mg tablet (as base*/as dihydrate/as mon-
5(&2167,787,21 $1' $'0,1,675$7,21. According to 500 mg tablet (as base*/as dihydrate/as mon-
manufacturer’s directions. ohydrate)
manufacturer’s directions. ohydrate)
'RVH$GMXVWPHQW 200 mg/5 mL powder for suspension, 15 mL,
'RVH$GMXVWPHQW 200 mg/5 mL powder for suspension, 15 mL,
Renal Impairment: 22.5 mL and 30 mL (as base*/as dihy-
Renal Impairment: 22.5 mL and 30 mL (as base*/as dihy-
For mild-to-moderate renal impairment, dose reduc- drate/as monohydrate)
For mild-to-moderate renal impairment, dose reduc- drate/as monohydrate)
tion or dose interval extension is warranted; A macrolide antibiotic with slightly less activity than
tion or dose interval extension is warranted; A macrolide antibiotic with slightly less activity than
for severe impairment, the patient should be erythromycin against gram-positive bacteria,
for severe impairment, the patient should be erythromycin against gram-positive bacteria,
referred to a specialist. but enhanced activity against some gram-
referred to a specialist. but enhanced activity against some gram-
3UHFDXWLRQV negative organisms, including H. influenzae
3UHFDXWLRQV negative organisms, including H. influenzae
In patients with history of allergy; renal impairment and C. trachomatis.
In patients with history of allergy; renal impairment and C. trachomatis.
(if severe, refer to a specialist); high incidence ,QGLFDWLRQV Suspected uncomplicated genital
(if severe, refer to a specialist); high incidence ,QGLFDWLRQV Suspected uncomplicated genital
of erythematous rash in glandular fever, infec- chlamydial infections (e.g., urethritis, cervicitis,
of erythematous rash in glandular fever, infec- chlamydial infections (e.g., urethritis, cervicitis,
tious mononucleosis, chronic lymphocytic leu- trachoma); low-risk community-acquired
tious mononucleosis, chronic lymphocytic leu- trachoma); low-risk community-acquired
kemia, acute lymphoblastic leukemia, CMV in- pneumonia (CAP-LR) in adults, when atypi-
kemia, acute lymphoblastic leukemia, CMV in- pneumonia (CAP-LR) in adults, when atypi-
fection, HIV infection. cal organisms are suspected, or when there
fection, HIV infection. cal organisms are suspected, or when there
In elderly patients, particularly those with concomi- is hypersensitivity to the beta-lactams; non-
In elderly patients, particularly those with concomi- is hypersensitivity to the beta-lactams; non-
tant cardiac diseases especially arrhythmias. severe CAP in child with hypersensitivity to
tant cardiac diseases especially arrhythmias. severe CAP in child with hypersensitivity to
Pregnancy (not known to be harmful); breastfeeding amoxicillin. See Guidelines- pCAP.
Pregnancy (not known to be harmful); breastfeeding amoxicillin. See Guidelines- pCAP.
(trace amounts in milk, but appropriate to use;
(trace amounts in milk, but appropriate to use; &RQWUDLQGLFDWLRQV Known hypersensitivity to
monitor infant). &RQWUDLQGLFDWLRQV Known hypersensitivity to
monitor infant).
127(: Rash (hypersensitivity or toxic response) may be azithromycin or any macrolide and ketolide
127(: Rash (hypersensitivity or toxic response) may be
indicative of a serious reaction (discontinue treatment azithromycin or any macrolide and ketolide
indicative of a serious reaction (discontinue treatment antibiotic, or any component of the formula-
if it occurs). antibiotic, or any component of the formula-
if it occurs). tion; with history of cholestatic jaundice or he-
tion; with history of cholestatic jaundice or he-
$GYHUVH'UXJ5HDFWLRQV patic impairment associated with prior
$GYHUVH'UXJ5HDFWLRQV patic impairment associated with prior
Common: Diarrhea, increased transaminase levels, azithromycin use.
Common: Diarrhea, increased transaminase levels, azithromycin use.
nausea, pain at the site of injection, pruritus, 'RVH
nausea, pain at the site of injection, pruritus, 'RVH
rash, urticaria, vomiting. Suspected uncomplicated genital chlamydial infec-
rash, urticaria, vomiting. Suspected uncomplicated genital chlamydial infec-
Less Common: Coagulation disorders, erythema tions, trachoma, by mouth, $'8/7 >45 kg, 1
Less Common: Coagulation disorders, erythema tions, trachoma, by mouth, $'8/7 >45 kg, 1
multiforme, GI upset, hemolytic anemia, inter- g as a single dose; $'8/7 <45 kg, 20 mg/kg
multiforme, GI upset, hemolytic anemia, inter- g as a single dose; $'8/7 <45 kg, 20 mg/kg
stitial nephritis, leukopenia, serum sickness- as a single dose; &+,/' >6 months, 20
stitial nephritis, leukopenia, serum sickness- as a single dose; &+,/' >6 months, 20
like reactions, thrombocytopenia, toxic epi- mg/kg as a single dose (maximum, 1 g).
like reactions, thrombocytopenia, toxic epi- mg/kg as a single dose (maximum, 1 g).
dermal necrolysis. Community-Acquired Pneumonia in adults, low-risk
dermal necrolysis. Community-Acquired Pneumonia in adults, low-risk
Rare: Anaphylaxis, angioedema, antibiotic-
Rare: Anaphylaxis, angioedema, antibiotic- (CAP-LR), for atypical organisms, by mouth,
associated colitis, crystalluria, electrolyte im- (CAP-LR), for atypical organisms, by mouth,
associated colitis, crystalluria, electrolyte im- $'8/7, 500 mg once a day for 5 days. See
balance, pustular drug eruption. $'8/7, 500 mg once a day for 5 days. See
balance, pustular drug eruption. Clinical Practice Guidelines – CAP for further
Clinical Practice Guidelines – CAP for further
'UXJ,QWHUDFWLRQV information.
'UXJ,QWHUDFWLRQV information.
Monitor closely with: Community-Acquired Pneumonia in children,
childrennonsevere
(pCAP
Monitor closely with: Community-Acquired Pneumonia in children (pCAP
Allopurinol – when combined with ampicillin, there is (pCAP
A or AB),
or B) for those with hypersensitivity to
Allopurinol – when combined with ampicillin, there is A or B), for those with hypersensitivity to
increased risk of rash occurrence. amoxicillin, by mouth, &+,/', 10 mg/kg sin-
increased risk of rash occurrence. amoxicillin, by mouth, &+,/', 10 mg/kg sin-
Aminoglycosides (e.g., amikacin, gentamicin) – gle dose, maximum of 500 mg/day, for 3
Aminoglycosides (e.g., amikacin, gentamicin) – gle dose, maximum of 500 mg/day, for 3
these may be rendered inactive by ampicillin. days or 10 mg/kg/day at day 1 then 5
these may be rendered inactive by ampicillin. days or 10 mg/kg/day at day 1 then 5
Anticoagulants (e.g., warfarin) – their bleeding risks mg/kg/day for days 2 to 5 with maximum dose
Anticoagulants (e.g., warfarin) – their bleeding risks mg/kg/day for days 2 to 5 with maximum dose
may be increased by ampicillin (due to possi- of 500 mg/day. See Guidelines - pCAP.
may be increased by ampicillin (due to possi- of 500 mg/day.
ble prolongation of bleeding time). 'RVH$GMXVWPHQWV
ble prolongation of bleeding time). 'RVH$GMXVWPHQWV
Contraceptives, Oral – their efficacy may be re-
Contraceptives, Oral – their efficacy may be re- Renal Impairment:
duced by ampicillin; there may also be an in- Renal Impairment:
duced by ampicillin; there may also be an in- Mild impairment- same dose
creased risk of breakthrough bleeding. Mild impairment- same dose
creased risk of breakthrough bleeding. Severe impairment- refer to specialist
Heparin – the risk of bleeding may be increased by Severe impairment- refer to specialist
Heparin – the risk of bleeding may be increased by Hepatic Impairment (except for Contraindications
ampicillin. Hepatic Impairment (except for Contraindications
ampicillin. stated above)
Avoid concomitant use with: stated above)
Avoid concomitant use with: Mild-to-moderate impairment- same dose
Atenolol – its antihypertensive and anti-anginal Mild-to-moderate impairment- same dose
Atenolol – its antihypertensive and anti-anginal Severe impairment- reduce dose
effects may be impaired by ampicillin. Severe impairment- reduce dose
effects may be impaired by ampicillin.
Chloramphenicol – this may decrease the effects of 3UHFDXWLRQV
Chloramphenicol – this may decrease the effects of 3UHFDXWLRQV
ampicillin. Cardiac conditions: prolongation of QT interval
ampicillin. Cardiac conditions: prolongation of QT interval
$GPLQLVWUDWLRQ Use freshly prepared solutions. IV (ventricular tachycardia reported); congenital
$GPLQLVWUDWLRQ Use freshly prepared solutions. IV (ventricular tachycardia reported); congenital
and IM solutions should be used within 1 hour long QT syndrome and family history of QT
and IM solutions should be used within 1 hour long QT syndrome and family history of QT
after preparation. Do not exceed a rate of 100 prolongation; torsades de pointes; ventricular
after preparation. Do not exceed a rate of 100 prolongation; torsades de pointes; ventricular
mg/minute. arrhythmia and other arrhythmias; congestive
mg/minute. arrhythmia and other arrhythmias; congestive
heart failure; recent MI.
3UHJQDQF\&DWHJRU\ B heart failure; recent MI.
3UHJQDQF\&DWHJRU\ B Proarrhythmic conditions (e.g., hypokalemia, hypo-
Proarrhythmic conditions (e.g., hypokalemia, hypo-
magnesemia).
magnesemia).
31
31
Elderly patients (may be more susceptible to drug- against gram-positive cocci, such as pneumo-
associated QT prolongation). cocci, streptococci and staphylococci, but is
Renal impairment; exacerbations of myasthenia less active than the other first-generation
gravis; diabetes (oral liquid contains sucrose cephalosporins against penicillinase-
3.87 g/5 mL). producing staphylococci.
Pregnancy; breastfeeding (limited drug information
available – use only if adequate alternatives Indications: Restricted for asymptomatic bacteriu-
are not available). ria and acute uncomplicated cystitis in preg-
nancy only for urine isolates susceptible to
Adverse Drug Reactions: cefalexin as demonstrated on urine culture
Common: Abdominal pain, arthralgia, cramping, and sensitivity.
diarrhea, dizziness, dyspepsia, flatulence,
headache, malaise, nausea, pruritus, rash, Antimicrobial Resistance ALERT!
vaginitis, vomiting. Due to increasing resistance to cefalexin, its
Less Common: Abnormal heart rhythm, allergic use in UTI is confined to asymptomatic bacte-
reaction, anorexia, anxiety, chest pain, con- riuria and acute cystitis in pregnancy where
junctivitis, constipation, drowsiness, edema, isolates are shown to be susceptible to it.
enteritis, fatigue, gastritis, hyperkinesia, hyp- Contraindications: Known hypersensitivity to
esthesia, hypotension, insomnia, leukopenia, cefalexin and any cephalosporins, or any
liver disorders, myasthenia gravis, neutro- component of the formulation; previously ex-
penia, palpitations, pancreatitis, paresthesia, perienced major allergy to penicillins.
photosensitivity, rash, sleep disturbances,
somnolence, thrombocytopenia, tinnitus, urti- Dose:
caria, vertigo. Asymptomatic bacteriuria in pregnancy for suscep-
Rare: Acute renal failure, agitation, angioedema, tible organisms demonstrated on urine c/s,
cholestatic jaundice, convulsions, disturb- by mouth, ADULT, 500 mg twice daily for 7
ances in taste and vision, hemolytic anemia, days. See Clinical Practice Guidelines – UTI
hepatic necrosis and failure, interstitial nephri- for further information.
tis, seizures, syncope. Acute uncomplicated cystitis in pregnancy for sus-
ceptible organisms demonstrated on urine
Drug Interactions: c/s, by mouth, ADULT, 500 mg 4 times daily
NOTE: Macrolides inhibit P-glycoprotein, which may lead to for 7 days. See Clinical Practice Guidelines –
drug interactions (see Appendix).
UTI for further information
Monitor closely with:
Antacids (e.g., aluminum or magnesium hydroxide) Dose Adjustments:
– these may reduce the absorption of Renal Impairment:
azithromycin. Dosage should be reduced.
Contraceptives, Oral – their efficacy may be re-
duced by azithromycin. Precautions:
Avoid concomitant use with: In patients allergic to penicillins (there is partial
Amiodarone – increases QTc interval; may cause cross-allergenicity of penicillins and cephalo-
possible serious or life-threatening interaction. sporins; if an allergic reaction occurs, the drug
Artemether + Lumefantrine – these may result to should be discontinued); marked renal im-
potentially hazardous interactions when given pairment (increases the risk of nephrotoxicity
concomitantly with azithromycin. and neurotoxicity – seizures or coma – with
Digoxin – the serum levels of digoxin may be in- high doses); patients should be monitored
creased by azithromycin, resulting in en- carefully so that any side effects or unusual
hanced actions and risk of toxicity. manifestations of drug idiosyncrasy may be
detected; elevated INR (may be associated
Administration: Capsules should be taken at least with increased INR, especially in nutritionally-
1 hour before, or 2 hours after, food; oral sus- deficient patients, those with prolonged treat-
pension can be taken with food to reduce GI ment, hepatic or renal disease);
discomfort and increase tolerability. Prolonged use may result in the overgrowth of non-
NOTE: Oral suspensions (100 mg/5 mL and 200 mg/5 mL) susceptible organisms, or fungal or bacterial
may be stored for 10 days post-reconstitution and superinfections; in individuals with a history of
taken without regard to food.
GI disease, particularly colitis (possible risk of
Pregnancy Category: B antibiotic-associated pseudomembranous coli-
tis).
Pregnancy (not known to be harmful); breastfeeding
(present in milk in low concentrations, but ap-
CEFALEXIN propriate to use; may cause loose bowel ac-
tions in child).
Oral: 250 mg and 500 mg capsule (as monohydrate) Adverse Drug Reactions:
1 g tablet (as monohydrate) Common: Abdominal pain, allergy, C. difficile-
associated disease, dizziness, diarrhea,
A first-generation cephalosporin that is intended for
headache, hypersensitivity, increased trans-
oral administration because it is almost com-
aminases, rash.
pletely absorbed from the GI tract; it is active
32
Less Common or Rare: Anemia, cholestatic hepa- and infants <6 months (efficacy and safety
titis, erythema multiforme, nausea, neutro- have not been established); superinfection
penia, Stevens-Johnson syndrome, toxic epi- (prolonged use may result in fungal or bacte-
dermal necrolysis, vomiting. rial superinfection).
Pregnancy (not known to be harmful; use only if
Drug Interactions:
clearly needed); breastfeeding (monitor infant;
probably present in milk, but safe in usual
Metformin – its serum concentration may be in-
dosage).
creased by cefalexin.
Vitamin K Antagonists (e.g., warfarin) – cephalo- Adverse Drug Reactions:
sporins may enhance their anticoagulant ef- Common: Abdominal pain, diarrhea, dyspepsia,
fect. flatulence, loose stools, nausea, vomiting.
Avoid concomitant use with: Less Common: Dizziness, headache.
Drugs causing renal impairment (e.g., aminoglyco- Rare: Agranulocytosis, allergic reactions, including
sides, furosemide and gentamicin) – cephalo- serum sickness-like reactions, fever, arthral-
sporins can cause renal impairment; there gia, and anaphylaxis; antibiotic-associated co-
may be an increased risk of nephrotoxicity litis, aplastic anemia, cholestatic jaundice,
when given concomitantly with these drugs. confusion, erythema multiforme, hallucina-
Drugs delaying peristalsis (e.g., opiates and diphe- tions, hemolytic anemia, hepatitis, hyperactivi-
noxylate with atropine) – these may prolong ty, hypertonia, leukopenia, nervousness, re-
and/or worsen the condition. versible interstitial nephritis, sleep disturb-
Zinc salts – these may decrease the absorption of ances, thrombocytopenia, toxic epidermal
cefalexin. necrolysis.
Administration: Administer without regard to food. Drug Interactions:
Anticoagulants (e.g., warfarin) – increased pro-
thrombin time, with or without clinical bleed-
ing; there may be an increased risk of hemor-
rhage.
CEFIXIME Carbamazepine – its levels are elevated when
administered concomitantly with cefixime.
Oral: 100 mg and 200 mg capsule Nephrotoxic drugs (e.g., ethacrynic acid, furo-
20 mg/mL granules for drops (suspension), semide, gentamicin and vancomycin) – there
10 mL may be an increased risk of nephrotoxicity
100 mg/5 mL granules for suspension, when these drugs are administered with cefix-
30 mL and 60 mL ime (since cephalosporins may possibly cause
An orally-active, third-generation cephalosporin that renal impairment).
has greater activity against gram-negative Probenecid – this increases half-life and prolongs
bacteria; possesses longer duration of action the activity of cefixime (since this competes
than the other orally-active cephalosporins. with cephalosporins for secretion via renal tu-
bules).
Indications: Uncomplicated anogenital gonorrhea- Avoid concomitant use with:
for use only when ceftriaxone is unavailable. Contraceptives, Oral – the contraceptive effect of
Contraindication: Known hypersensitivity to cefix- estrogens may be reduced by cefixime.
ime and other cephalosporins, or any compo- Administration: May be taken with food or milk to
nent of the formulation. reduce GI discomfort.
NOTE: Absorption delayed in the presence of food.
Dose:
Uncomplicated anogenital gonorrhea, by mouth, Pregnancy Category: B
ADULT AND CHILD >12 years, 400 mg as a
single dose.
Dose Adjustments:
Elderly:
CEFTRIAXONE
May be given the same dose recommended for
adults. Inj.: 250 mg vial + 2 mL 1% solution of lidocaine
Renal Impairment: (IM) (as disodium/sodium salt)
For mild-to-moderate renal impairment, dose reduc- 500 mg vial + 2 mL 1% solution of lidocaine
tion is warranted (maximum, 200 mg once dai- (IM) (as disodium/sodium salt)
ly); for severe impairment, the patient should 1 g vial + 3.5 mL 1% solution of lidocaine (IM)
be referred to a specialist. (as disodium/sodium salt)
250 mg vial + 5 mL diluent (IV) (as disodi-
Precautions: um/sodium salt)
Avoid use if with known history of immediate hyper- Each duplex III container consists of: 1 g
sensitivity reactions to Beta Lactam antibacte- ceftriaxone (as sodium) powder for injec-
rials (shock and fatalities have been reported); tion with 3.74% dextrose solution for injec-
renal failure (avoid use); GI diseases; children tion
33
A sterile, third-generation cephalosporin antibiotic failure (injection contains 83 mg Na+/g); chron-
whose spectrum of activity is wide, and has ic disease and malnutrition (risk of bleeding
enhanced potency against gram-negative or- due to low vitamin K stores); treatment >14
ganisms. days, renal failure, dehydration, immobilized
or concomitant TPN (risk of ceftriaxone pre-
Indications: Uncomplicated gonorrhea; pelvic
cipitation in gallbladder; consider discontinua-
inflammatory disease; neonatal gonococcal
tion if symptomatic).
conjunctivitis (Ophthalmia Neonatorum).
NOTE: Refer patients with disseminated gonococcal infec-
tion, or those with bacteremia or arthritis, to the hospi- (excreted in low concentration, but safe in
tal physician. usual dosage; monitor infant).
Contraindications: Known hypersensitivity to Adverse Drug Reactions:
cephalosporins or any component of the for- Common: Allergic skin reactions, including dermati-
mulation; porphyria; neonates less than 41 tis, exanthema and urticaria; edematous
weeks post-menstrual age; neonates more swelling of skin and joints, elevated serum liv-
than 41 weeks post-menstrual age with jaun- er enzymes, nausea, pain at the site of injec-
dice, hypoalbuminemia, acidosis or impaired tion, phlebitis, pruritus, rash, symptomatic
bilirubin binding; concomitant treatment with precipitation of ceftriaxone calcium salt in the
IV calcium (including TPN) in neonates over urine or gallbladder, vomiting.
41 weeks postmenstrual age (due to risk of Less Common: Abdominal discomfort, anorexia,
precipitation in urine and lungs). confusion, diaphoresis, diarrhea, dizziness,
emesis, flushing, glossitis, headache, in-
Dose: creased serum creatinine, mycosis of the gen-
Neonatal gonococcal conjunctivitis (Ophthalmia ital tract, stomatitis, nausea, oliguria, vertigo.
neonatorum), by deep IM injection or slow IV, Rare: Agranulocytosis, anaphylaxis, anemia, antibi-
NEONATE, 25-50 mg/kg as a single dose otic-associated colitis, cholestatic jaundice,
(maximum, 125 mg). coagulation disorders, erythema multiforme,
Uncomplicated gonorrhea, by deep IM injection or fever, granulocytopenia, hallucinations, hepa-
IV over 10-30 minutes, ADULT, ≥45 kg, 250 titis, leukopenia, nephritis, pancreatitis, pro-
mg as a single dose; for <45 kg, 125 mg as a longation of prothrombin time, serum sick-
single dose (also used with doxycycline and ness-like reactions, thrombocytopenia, toxic
metronidazole to treat pelvic inflammatory epidermal necrolysis.
disease).
Uncomplicated gonococcal vulvovaginitis, cervicitis, Drug Interactions:
urethritis, pharyngitis, or proctitis, by deep IM Monitor closely with:
injection, CHILD <45 kg, 125 mg as a single Alcohol – this results in a disulfiram-like reaction
dose. (abdominal pain, flushing, headache, nausea,
vomiting and tachycardia).
RECONSTITUTION AND ADMINISTRATION. According to
manufacturer’s directions. IM doses >1 g should be Aminoglycosides – ceftriaxone may enhance their
divided between more than one site. Administer by IV bactericidal activity against certain pathogens;
infusion over 60 minutes in neonates. there may also be an increased risk of ototox-
NOTE: The duration of therapy varies according to the icity and nephrotoxicity.
course of the disease. As with antibiotic therapy in Contraceptives, Oral – their efficacy may be re-
general, administration should be continued for a min- duced by ceftriaxone.
imum of 48-72 hours after the patient has become
afebrile, or signs of bacterial eradication have been
Avoid concomitant use with:
obtained. Synergy between the drug and aminoglyco- Bacteriostatic antibiotics (e.g., tetracyclines, chlo-
sides has been demonstrated with many gram- ramphenicol) – these may antagonize the ac-
negative bacilli under experimental conditions. Alt- tivity of ceftriaxone.
hough enhanced activity of such combinations is not
always predictable, it should be considered in severe, Administration: Dosages >1 g of ceftriaxone
life-threatening infections. Because of physical in- should be divided and injected on more than
compatibility, the two drugs should be administered one site. The reconstituted solution should be
separately at the recommended dosages. shaken up to 1 minute to ensure complete
Dose Adjustments: dissolution of ceftriaxone. For IV, reconstitute
Elderly: to approximately 100 mg/mL, then dilute fur-
Same dosage as in adult patients may be used in ther to 10-40 mg/mL. For IM, dilute with com-
the case of geriatric patients. patible fluid (NSS, D5W) to 250-350 mg/mL.
Renal and Hepatic Impairment: Reconstituted solutions should be inspected visual-
For combined mild-to-moderate impairment, dose ly; only the clear solution which is free from
reduction is warranted; for severe impairment, visible particles should be used. They should
the patient should be referred to a specialist. be used immediately after preparation.
NOTE: Reconstituted solutions retain their physical and
Precautions: chemical stability for 6 hours at room temperature (or
Avoid if there is history of immediate hypersensitivi- 24 hours at 5°C). They range from pale yellow to am-
ty Beta Lactams; severe renal and hepatic im- ber in color, depending on the concentration and the
length of storage.
pairment (monitor plasma concentration);
premature neonates (may displace bilirubin Pregnancy Category: B
from serum albumin); Na+ restriction, heart
34
old, 250 mg every 12 hours for 10 days.
CEFUROXIME CHILD, 3 months to 12 years old, 20
mg/kg/day suspension divided every 12 hours
Oral: 250 mg and 500 mg tablet (as axetil) for 10 days, (maximum, 500 mg/day).
125 mg/5 mL granules for suspension, 50 mL Acute bacterial exacerbation of chronic bronchitis,
and 70 mL (as axetil) by mouth, ADULT, 250-500 mg twice daily for
125 mg granules for suspension, per sachet 10 days; for secondary bacterial infections in
(as axetil) chronic bronchitis, ADULT, same dose for 5-
250 mg/5 mL granules for suspension, 60 mL 10 days.
Uncomplicated skin infection, ADULT, 250-500 mg
A second-generation cephalosporin with less activi- every 12 hrs for 10 days.
ty against gram-positive bacteria as compared
with the first-generation, but has greater sta- Dose Adjustments:
bility to hydrolysis by beta-lactamases; active Elderly:
against beta-lactamase-producing H. influen- No dosage reduction is necessary in elderly patients
zae, S. aureus, S. pneumoniae, Klebsiella at recommended dosages.
spp., and penicillin-resistant pneumococci. Renal Impairment:
For marked impairment, dose should not exceed
Indications: Respiratory tract infections: as alter- 500 mg/day, by mouth, or 750 mg twice daily
native treatment in low risk community ac- IM or IV. For severe impairment, the patient
quired pneumonia (CAP-LR) in patients with should be referred to a specialist.
stable co-morbid illnesses or with recent anti-
biotic therapy where Gram-negative bacilli Precautions:
can coexist; acute exacerbations of chronic History of hypersensitivity to cephalosporins (seri-
bronchitis, or acute bronchitis; alternative drug ous and occasionally fatal; discontinue if aller-
for infections due to susceptible organisms, gic reaction occurs); may result in Candida
such as in otitis media, orbital cellulitis; overgrowth; prolonged administration of ce-
asymptomatic bacteriuria; alternative oral furoxime may result in overgrowth of non-
treatment of Acute Uncomplicated Cystitis and susceptible microorganisms; history of colitis
Acute Uncomplicated Pyelonephritis; skin and or diarrhea in association with antibiotic treat-
soft tissue, bone and joint infections. ment (increased risk of antibiotic-associated
colitis); renal or hepatic impairment, or poor
Contraindications: Known hypersensitivity to nutritional state, patients receiving a protract-
cefuroxime and other cephalosporins, or any ed course of antimicrobial therapy and pa-
component of the formulation. tients previously stabilized with anticoagulant
Dose: therapy (may be associated with a fall in pro-
Asymptomatic bacteriuria, by mouth, ADULT, in thrombin activity).
non-pregnant patient, 125-250 mg twice daily Pregnancy (given only if such use is considered
for 7-14 days; in pregnant patient, 500 mg essential); breastfeeding (excreted in human
twice daily for 7 days. See Clinical Practice milk; use with caution when administered to a
Guidelines – UTI for further information. nursing mother).
SKILLED TASKS. May impair ability to perform skilled
Acute uncomplicated cystitis, as alternative treat-
tasks, e.g., machinery or driving.
ment, by mouth, ADULT, 250 mg twice daily
for non-pregnant patients, and 500 mg twice Adverse Drug Reactions:
daily for pregnant women, for 7 days. See Common: Diarrhea or loose stools, elevation in
Clinical Practice Guidelines – UTI for further AST, ALT and LDH; nausea, vomiting.
information. Less Common: Abdominal pain and cramps, ano-
Acute uncomplicated pyelonephritis, as alternative rexia, chest pain, chills, dizziness, dyspepsia,
treatment, by mouth, ADULT, 500 mg twice dysuria, flatulence, headache, itch, mouth ul-
daily for 14 days. See Clinical Practice Guide- cers, pain and inflammation at the injection
lines – UTI for further information. site, positive Coombs’ test, rash, shortness of
Community-Acquired Pneumonia, low-risk (CAP- breath, sleepiness, somnolence, superinfec-
LR) with co-existing Gram-negative bacilli, tion, swollen tongue, tachycardia, thirst, vagi-
by mouth, ADULT, 500 mg twice a day for 5-7 nitis, vulvar itch.
days. See Clinical Practice Guidelines – CAP Rare: Agranulocytosis, allergic reactions, including
for further information. pruritus, serum sickness-like reactions, rash,
Otitis media, by mouth, CHILD, 125 mg twice daily; urticaria, fever, arthralgia and anaphylaxis; an-
if necessary, double the dose in child >2 tibiotic-associated colitis, aplastic or hemolytic
years with otitis media. anemia, bleeding, cholestatic jaundice, confu-
Acute bacterial maxillary sinusitis, by mouth, sion, encephalopathy, erythema multiforme,
ADULT, 250 mg twice a day for 10 days; hepatitis, leukopenia, seizures, sleep disturb-
CHILD, >12 years old, 250 mg every 12 hours ances, thrombocytopenia, toxic epidermal
for 10 days. CHILD, 3 months to 12 years old, necrolysis.
30 mg/kg/day suspension divided every 12
Drug Interactions:
hours for 10 days, (maximum, 1,000 mg/day).
Pharyngitis, tonsillitis, by mouth, ADULT, 250 mg Monitor closely with:
twice a day for 10 days; CHILD, >12 years Anticoagulants (e.g., warfarin) – increased pro-
thrombin time, with or without clinical bleed-
35
ing; there may be an increased risk of hemor- Dose Adjustments:
rhage. Renal and Hepatic Impairment:
Nephrotoxic drugs (e.g., ethacrynic acid, furo- For mild-to-moderate impairment, dose reduction is
semide, gentamicin and vancomycin) – there warranted; for severe impairment, the patient
may be an increased risk of nephrotoxicity should be referred to a specialist (due to
when these drugs are administered with ce- dose-related depression of hematopoiesis).
furoxime (since cephalosporins may possibly Children with immature metabolic processes:
cause renal impairment). A dose of 25 mg/kg/day will usually produce thera-
Probenecid – this increases half-life, and prolong peutic chloramphenicol concentration in the
the activity of cefuroxime (since this competes blood; the serum drug concentration should
with cephalosporins for secretion via renal tube monitored by microbiological techniques
bules). wherever possible.
Ranitidine – may result in lower bioavailability of
Precautions:
cefuroxime as compared with that of the fast-
ing state. WARNING: Serious and fatal blood dyscrasias, including
Avoid concomitant use with: anemia, thrombocytopenia and granulocytopenia,
have occurred after short-term and prolonged thera-
Contraceptives, Oral – the contraceptive effect of
py. Monitor CBC frequently in all patients. Use only in
estrogens may be reduced by cefuroxime. serious infections.
Administration: Swallow the tablet whole; it is Typhoid (Jarisch-Herxheimer reaction may occur at
absorbed best if taken with a light meal. Con- start of treatment); avoid repeated courses
stituted suspensions or solutions shall be and prolonged use; severe renal and hepatic
used immediately. impairment; breastfeeding (the concentration
Pregnancy Category: B in milk is usually insufficient to cause “grey”
syndrome; but, use alternative drug if possi-
ble; may cause bone marrow toxicity in in-
fants); G6PD deficiency (hemolysis may oc-
cur).
CHLORAMPHENICOL
Oral: 250 mg and 500 mg capsule Common: Headache, nausea, reversible bone
125 mg/5 mL suspension, 30 mL and 60 mL marrow suppression, vomiting.
(as palmitate) Less Common: C. difficile-associated disease,
dryness of mouth, confusion, diarrhea, glossi-
A potent, broad-spectrum, microbial protein synthe- tis, mild depression, stomatitis.
sis inhibitor (50S subunit), which is active Rare: Anaphylaxis, aplastic anemia, grey syndrome
against most gram-negative and gram-positive (abdominal distension, ashen grey skin, circu-
bacteria; it is associated with serious hemato- latory collapse, cyanosis, greenish diarrhea);
logical side-effects when given systemically, hypersensitivity reactions, hypothermia, leu-
and should therefore be reserved for the kopenia, optic neuritis, peripheral neuropathy,
treatment of life-threatening infections. thrombocytopenia.
Indications: For uncomplicated typhoid fever (ty- Drug Interactions:
phoidal Salmonella infections); choleraa with NOTE: Chloramphenicol inhibits liver microsomal enzymes
severe diarrheal disease and dehydration. (CYP2C9), and may affect concentration of drugs
a
Carlos, C, Antimicrobial Resistance Surveillance Program 2013 Data which are metabolized by the enzyme (see Appen-
Summary Report. dix).
Contraindications: Known hypersensitivity to Anticoagulants (e.g., warfarin) – their anticoagulant
chloramphenicol or any component of the effect can be enhanced by chloramphenicol.
formulation; acute porphyria; anemia or Phenobarbital – this increases the metabolism of
thrombocytopenia; neonates <1 week and chloramphenicol, thereby reducing its concen-
premature infants; pregnancy (third trimester: tration and antibacterial activity.
neonatal “grey” syndrome), and breastfeeding. Phenytoin – chloramphenicol impairs its metabo-
Dose: lism, thereby increasing its concentration and
Cholera (with severe diarrheal disease and dehy- risk of toxicity.
dration), by mouth, ADULT, 500 mg every 6 Avoid concomitant use with:
hours for a total of 12 doses or 6 g for a total Bactericidal antibiotics – chloramphenicol (bacterio-
of 3 days. static) can antagonize the bactericidal action
Typhoid fever, and enteritis, by mouth, ADULT and of penicillins and aminoglycosides.
CHILD, 25 mg/kg three times a day for 10-14 Iron – chloramphenicol increases serum concentra-
days (maximum dose for child, 750 mg). tion of iron, and induces bone marrow toxicity
NOTE: Plasma concentration monitoring is required in (if myelosuppression occurs, monitor iron
neonates, and is preferred in those <4 years of age, stores and decrease iron as needed).
in the elderly, and in hepatic impairment. Lurasidone- chloramphenicol increases the levels of
lurasidone by affecting enzyme CYP3A4 me-
tabolism. Never use in combination.
36
Rifampicin – this accelerates the metabolism of Dose:
chloramphenicol, thereby decreasing its plas- Asymptomatic bacteriuria, by mouth, ADULT, in
ma concentration. non-pregnant patients, 250 mg twice daily for
7-14 days.
Administration: Take on an empty stomach 1 hour Acute uncomplicated pyelonephritis, by mouth,
before, or 2 hours, after meals. ADULT, 500 mg twice daily for 7-10 days.
Pregnancy Category: C Acute uncomplicated cystitis, as alternative treat-
ment, by mouth, ADULT, 250 mg twice daily
for 3 days. See Clinical Practice Guidelines –
UTI for further information.
CIPROFLOXACIN Chancroid, by mouth, ADULT, 500 mg twice daily
for 3 days.
MDR Typhoid, by mouth, ADULT, 500 mg every 12
Oral: 250 mg and 500 mg tablet (as HCl)
hours (7-14 days typically).
A broad-spectrum, second-generation carboxyquin- Pelvic inflammatory disease, by mouth, ADULT,
olone that can be used against gram-negative 500 mg twice daily (in combination with
bacteria, including Neisseria, Salmonella, Shi- doxycycline and metronidazole)..
gella, Campylobacter and Pseudomonas. Prophylaxis of meningococcal meningitis, by mouth,
ADULT, 500 mg as a single dose.
Indications: Restricted use for treatment of severe Shigella dysentery, by mouth, ADULT, 500 mg
infections of the GI tract including MDR ty- twice daily for 3 days; CHILD, 15 mg/kg/day
phoid fever and Shigella dysentery; chancroid; twice a day for 3 days (See Precautions).
pelvic inflammatory disease (in combination
with doxycycline and metronidazole); asymp- Dose Adjustments:
tomatic bacteriuria (in non-pregnant adults); Renal Impairment:
Acute Uncomplicated Pyelonephritis (in non- For mild-to-moderate renal impairment, dose reduc-
pregnant women); alternative treatment for tion is warranted; for severe impairment, the
Acute Uncomplicated Cystitis; meningococcal patient should be referred to a specialist.
meningitis prophylaxis. Hepatic Impairment:
Same dosage as in patients with normal hepatic
Antimicrobial Resistance ALERT! function may be used in patients with mild-to-
• Antimicrobials such as ciprofloxacin moderate hepatic impairment; for severe im-
should not be administered to patients with pairment, refer to a specialist.
Salmonella gastroenteritis since this is
usually a self-limited disease.a Precautions:
WARNING: Associated with an increased risk of tendinitis
• Due to emerging resistance of Shigellae to and tendon rupture; this risk is further increased in
quinolones, judicious use based on surveil- older patients, usually those older than 60 years; in
lance findings is urged.b kidney, heart, and lung transplant recipients; and with
the concomitant use of steroid therapy.
• The ARSP reported that in 2012-2013, for May exacerbate muscle weakness in patients with myasthe-
Neisseria gonorrhoeae isolates, resistance nia gravis; avoid quinolones with known history of
to Ciprofloxacin was very high at 74%.b myasthenia gravis.
This increased dramatically from 48% in
History of epilepsy or conditions that predispose to
2008.c
seizures; myasthenia gravis; G6PD deficiency
• Fluoroquinolones should not be used as (increased risk of hemolytic anemia); risk of
first-line antibiotic for Acute Uncomplicated crystalluria (avoid excessive alkalinity of urine
Cystitis due to its high propensity for collat- and ensure adequate fluid intake); renal im-
eral damage. Local studies have shown pairment; avoid exposure to excessive sun-
that ciprofloxacin is now significantly less light (discontinue if photosensitivity occurs);
effective therapy in tuberculosis.d children or adolescents (see below); rarely
tendon damage (see below).
a
Antimicrobial Resistance Surveillance Program Data, 2012 Pregnancy (avoid use; arthropathy reported in
b
Antimicrobial Resistance Surveillance Program Presentation, 2013 animal studies; safer alternatives are availa-
c
Country Situation Analysis on Antimicrobial Resistance, 2012 ble), and breastfeeding (amount too small to
d
Urinary Tract Infection Guidelines, 2013 be harmful; use alternative drugs if possible).
USE IN CHILDREN: Ciprofloxacin causes arthropathy in
Contraindications: Known hypersensitivity to weight-bearing joints of immature animals, and
quinolones or any component of the formula- is therefore generally not recommended for use in
tion; history of tendon disorders related to children and growing adolescents. However, the sig-
nificance of this effect in humans is uncertain and in
quinolone use; not recommended in children some specific circumstances, short-term use of ciprof-
and growing adults (<18 years of age) due to loxacin in children may be justified.
possible risk of arthropathy; concurrent tizani- TENDON DAMAGE: Tendon damage, including rupture, has
dine use. been reported rarely in patients receiving quinolones.
Tendon rupture can possibly occur within 48 hours of
starting treatment. Healthcare workers should always
be aware that:
37
• Quinolones are contraindicated in patients with a en concomitantly with ciprofloxacin (ciproflox-
history of tendon disorders related to quinolone acin may cause seizures).
use. Sucralfate – this chelates ciprofloxacin, thereby
• Elderly patients are more prone to tendinitis.
reducing its absorption and activity.
• The risk of tendon rupture is increased by the con-
comitant use of corticosteroids. Thyroid hormones – their absorption may be inter-
• If tendinitis is suspected, the quinolone should be fered by ciprofloxacin, thereby resulting in hy-
discontinued immediately. pothyroidism (acquire thyroid function tests if
SKILLED TASKS. May impair ability to perform skilled needed).
tasks, e.g., operating machinery or driving. Zinc salts – these bind to ciprofloxacin in the GI
Adverse Drug Reactions: tract, thereby reducing its absorption and ac-
Common: Abdominal pain, diarrhea, dyspepsia, tivity (take ciprofloxacin at least 2 hours before
flatulence, itch, nausea, rash, vomiting. zinc).
Less Common: Abnormal liver function tests, Administration: May be taken with or without food;
agitation, anorexia, arthralgia, arthritis, confu- do not take with antacids, iron or dairy prod-
sion, decreased appetite and food intake, de- ucts.
pression, dizziness, drowsiness, hallucina-
tions, fever, headache, myalgia, superinfec- Pregnancy Category: C
tions, restlessness, sleep and taste disorders,
urticaria.
Rare: Agranulocytosis, anaphylaxis, bone marrow
depression, C. difficile-associated disease, CLARITHROMYCIN
dyspnea, edema, erythema multiforme, ery-
thema nodosum, fixed drug eruptions, hearing Oral: 250 mg and 500 mg base tablet
loss, hematuria, hemolytic anemia, hepatitis, 500 mg MR tablet
hyperglycemia, hypoglycemia, hypotension, 125 mg/5 mL granules/powder for suspension,
interstitial nephritis, jaundice, leukopenia, neu- 60 mL
tropenia, pancreatitis, pancytopenia, petechi-
An erythromycin-derived, macrolide antibiotic, which
ae, photosensitivity reactions, psychotic reac-
can be used in regimens for Helicobacter py-
tions, renal impairment, seizures, serum sick-
lori eradication, and for low-risk CAP when in-
ness-like reactions, Stevens-Johnson syn-
dicated.
drome, syncope, tachycardia, tendonitis,
thrombocytopenia, toxic epidermal necrolysis, Indications: Low risk community-acquired pneu-
vasculitis. monia in adults (CAP-LR) due to atypical or-
ganisms; non-severe CAP in children with
Drug Interactions:
NOTE: Ciprofloxacin inhibits CYP1A2, and may affect drugs hypersensitivity to amoxicillin; anti-
metabolized by this enzyme (see Appendix). Helicobacter pylori infection.
Monitor closely with: Contraindications: Known hypersensitivity to
Ibuprofen – this may increase the risk of convul- clarithromycin or any component of the formu-
sions. lation; severe hepatic failure; hypokalemia;
Phenytoin – its concentration and therapeutic effect patients with history of QT prolongation or
may be decreased by ciprofloxacin. ventricular cardiac arrhythmias; cholestatic
Theophylline – its metabolism may be inhibited by jaundice or hepatic dysfunction with prior clar-
ciprofloxacin, thereby increasing its concentra- ithromycin use.
tion and toxicity (more likely in the elderly).
Warfarin – its effect may be enhanced by ciproflox- Dose:
acin, thereby increasing risk of bleeding (mon- Community-Acquired Pneumonia in adults, low-risk
itor INR). (CAP-LR) when atypical organisms are
Avoid concomitant use with: suspected, by mouth, ADULT, 500 mg twice
Antacids (e.g., aluminum or magnesium hydroxide) daily for 5-7 days; See Clinical Practice
– these bind to ciprofloxacin in the GI tract, Guidelines – CAP for further information.
thereby reducing its absorption and activity Community-Acquired Pneumonia in children, (pCAP
(give it at least 2 hours, before, or 4-6 hours A and pCAP B), for those with hypersensitiv-
after, the antacid). ity to amoxicillin, CHILD, 15 mg/kg/day,
Artemether + Lumefantrine – these may result to maximum of 1,000 mg/day, in 2 divided doses
potentially hazardous interactions when given for 7 days. See Guidelines – pCAP.
concomitantly with ciprofloxacin. Eradication of H. pylori, by mouth, See under Anti-
Calcium – this binds to ciprofloxacin in the GI tract; H. pylori Infection for further information.
reducing its absorption and activity (separate
Dose Adjustment:
doses by at least 2 hours).
Renal Impairment:
Iron – this binds to ciprofloxacin in the GI tract;
For mild-to-moderate renal impairment, dose reduc-
reducing its absorption and activity (take
tion is warranted; for severe impairment, the
ciprofloxacin at least 2 hours before iron).
patient should be referred to a specialist.
Seizure-inducing drugs (see Table C for other drugs
which may cause seizures) – there may be an Precautions:
increased risk of seizures when these are giv-
WARNING: Increased risk of cardiac deaths.
38
In patients with a predisposition to QT interval pro- Avoid concomitant use with:
longation, including electrolyte disturbances Calcineurin inhibitors – their metabolism is inhibited
(e.g., uncorrected hypokalemia or hypomag- by clarithromycin, increasing their concentra-
nesemia) and concomitant use of drugs that tion, and the risk of nephrotoxicity and neuro-
prolong QT interval (see Appendix – Table B). toxicity.
Elderly patients may be more susceptible to drug- Ergot alkaloids (e.g., ergotamine) – increased risk of
associated QT prolongation. ergot toxicity.
History of ischemic heart disease, severe cardiac HMG-CoA reductase inhibitors (e.g., lovastatin and
insufficiency, ventricular arrhythmia including simvastatin) – their concentration is possibly
torsades de pointes, bradycardia (treatment increased by clarithromycin, thus increasing
risk-benefit should be considered). the risk of toxicity (rhabdomyolysis).
Hepatic dysfunction (discontinue immediately if
Administration: The regular tablet and liquid can
signs and symptoms of hepatitis occur).
Antibiotic-associated colitis; myasthenia gravis (may be taken with or without food; whereas, the
long-acting tablet is usually taken with food.
be aggravated).
Pregnancy (avoid use unless there is no appropriate The tablet should be taken with a full glass of
alternative therapy); breastfeeding (safety has water; while the long-acting tablet is swal-
not been established). lowed whole (do not split, chew or crush).
NOTE: Macrolides inhibit P-glycoprotein, which may lead to Shake the suspension well before use.
drug interactions; CYP3A-based interactions: clar-
ithromycin (a CYP3A inhibitor) may increase or pro-
long both therapeutic and adverse effects of drugs
primarily metabolized by CYP3A enzymes (see Ap-
pendix).

CLINDAMYCIN
Common: Taste disturbance.
Oral: 150 and 300 mg capsule (as hydrochloride)
Less Common: Abdominal discomfort, diarrhea,
hepatotoxicity (including cholestatic jaundice), 75 mg/5 mL granules for suspension, 60 mL
nausea, rash, tinnitus, vomiting. (as palmitate hydrochloride)
Rare: Antibiotic-associated colitis, arrhythmias, A semisynthetic derivative of lincomycin that is
pancreatitis, pulmonary infiltration with QT ineffective for susceptible streptococci, Staphy-
terval prolongation, Stevens-Johnson syn- lococcus aureus, and Bacteroides spp. 90
drome, torsades de pointes, toxic epidermal percent of clindamycin hydrochloride is ab-
necrolysis. sorbed from the gastrointestinal tract.
Drug Interactions: Clindamycin palmitate must be hydrolyzed in
the GIT before it becomes an active drug. It
has no significant levels in the cerebrospinal
Anticoagulants (e.g., warfarin) – potential risk of
fluid.
serious hemorrhage and significant elevations
in INR and prothrombin time. Indications: Skin and soft tissue infections caused
Benzodiazepines (e.g., midazolam) – their metabo- by community-associated methicillin-resistant
lism may be inhibited by clarithromycin, and Staphylococcus aureus (MRSA); alternative
may prolong the sedative and respiratory de- for anaerobic infections.
pressant effects.
CYP3A4/5 inducers (see Appendix) – these may a
induce metabolism of clarithromycin; may re- General information on MRSA Infections:
sult in subtherapeutic levels leading to re- MRSA is a staphylococcal bacterium that has de-
duced efficacy. veloped resistance to several antibiotics, in-
Class IA or Class III antiarrhythmics or drugs which cluding methicillin. In the general community,
prolong QT interval (see Appendix – Table B) it causes mostly skin and soft tissue infections
– QT interval may be prolonged if given with as well as other infections. In a hospital, nurs-
the stated drugs, increasing the risk of ar- ing home, or other healthcare settings, MRSA
rhythmia. can cause severe infections such as pneumo-
Hypoglycemic agents and insulin – can result in nia, bloodstream and surgical site infections.
significant hypoglycemia. How is MRSA spread in the community?
NNRTIs – these decrease concentration of clar- MRSA can affect anyone through transmission via
ithromycin, and increase the concentration of direct contact with an open wound or sharing
its active metabolite. personal items, such as towels and razors that
Phosphodiesterase inhibitors (e.g., sildenafil and have touched infected skin. The risk for the in-
tadalafil) – their concentration may be infection is increased in places or during situa-
creased by clarithromycin. tions where there is crowding, skin-to-skin
Rifampicin – this may increase clarithromycin me- contact, and shared equipment or supplies
tabolism, thus reducing its antibacterial effect. (e.g., in schools, daycare centers, and among
Theophylline – possibly increased serum theophyl- patients with recent in-patient hospital care.
line concentration.
39
How can MRSA be prevented? Precautions:
Good personal hygiene is the most basic step in WARNING: Clostridium difficile-associated diarrhea (CDAD)
preventing the disease. has been reported and may range in severity from
For patients with MRSA, give the following addition- mild diarrhea to fatal colitis. This may occur during
al instructions: Cover the wounds with clean, treatment or for >2 months after discontinuation of
treatment. The antibiotic alters the colon flora, leading
dry bandages; never prick or pop the infected
to C. difficile overgrowth. C. difficile produces toxins A
sores; always wash the hands properly, espe- and B which contribute to CDAD; hypertonic produc-
cially after contact with the infected site; do ing C. difficile strains increase morbidity and mortality
not reuse or share personal items; wash used (more likely to be refractory to antimicrobial therapy
sheets, towels, and clothes properly; and strict and may require colectomy).
compliance with instructions regarding use of Reserve clindamycin for serious infection where less toxic
antibiotics are inappropriate.
antibiotics if these will become necessary.
Avoid use for non-bacterial infection including most upper
What are the symptoms of MRSA? respiratory tract infections.
Most staphylococcal skin infections, including Risk of potentially fatal pseudomembranous colitis,
MRSA, appear as a sore or infected area that fungal or bacterial superinfection on prolonged
may show: redness, swelling, pain and use; discontinue therapy if significant ab-
warmth at the site, presence of pus or other dominal cramps, diarrhea or passage of blood
discharge; fever may or may not be present. and mucus occur.
What is the out-patient treatment of MRSA skin and Severe skin reactions (e.g., toxic epidermal necroly-
soft tissue infections? sis), some with fatal outcome, have been re-
The primary treatment of the focal skin and soft ported; permanently discontinue in these situ-
tissue caused by community-associated ations.
MRSA is incision and drainage when mature Parenteral product contains benzyl alcohol which
(e.g., sore is fluctuant). may cause “gasping syndrome” and death in
The need for antibiotic treatment will depend on the newborn.
several considerations that include: rapid May increase the risk for antimicrobial-resistant
progression with cellulitis, severe or more ex- bacteria if used in the absence of proven or
tensive disease or presence at multiple sites, strongly suspected susceptible bacteria.
signs and symptoms of systemic disease, ab- Lactation: possibly unsafe.
scess in an area that is hard to drain (face, Adverse Drug Reactions:
hand, or genitalia), failure to respond to inci- Common: Abdominal pain, diarrhea, hypotension,
sion and drainage, and presence of comor- jaundice, nausea, pruritus, rash, urticaria,
bidities (immunosuppression, age extremes, vomiting.
etc.). Local resistance to antibiotics needs to Frequency not defined: Agranulocytosis, C. dif-
be considered also. ficile-associated diarrhea, eosinophilia (transi-
Antibiotics that can be used in the local outpatient ent), esophagitis, fungal overgrowth, granulo-
setting may include: clindamycin, cotrimoxa- cytopenia, hypersensitivity, neutropenia, poly-
zole or doxycycline. arthritis, pseudomembranous colitis, Stevens-
Patients with a major abscess or wound infection, Johnson syndrome, thrombocytopenia, renal
infected ulcer, or a serious co-morbid condi- dysfunction.
tion have to be hospitalized.
a Drug Interactions:
Centers for Disease Control and Prevention. (2013). Methi-
cillin-resistant Staphylococcus aureus (MRSA) infec- Monitor closely with:
tions. Retrieved from http://cdc.gov/mrsa/. Conjugated estrogens or estradiol or ethinylestradiol
– oral clindamycin decreases level or effect of
Contraindications: Hypersensitivity to clindamycin, these drugs by altering intestinal flora.
lincomycin, or any component of the formula- Digoxin – oral clindamycin increases level or effect
tion; history of ulcerative or pseudomembra- of digoxin through altering intestinal flora.
nous colitis. Neuromuscular blockers (e.g., pancuronium) –
Dose: clindamycin increases effects by pharmaco-
Skin and soft tissue infections due to methicillin- dynamic synergism; possible serious or life-
resistant Staphylococcus aureus (MRSA), by threatening interaction; risk of respiratory de-
mouth, ADULT, 150-450 mg/dose every 6-8 pression; use alternatives if possible.
hours with maximum dose of 1.8 g/day; Warfarin – clindamycin increases effects of warfarin
CHILD and INFANT, 10-30 mg/kg/day in 3-4 (decreased vitamin-K producing intestinal flora
divided doses with maximum dose of 1.8 may increase INR after a few days).
g/day. Avoid concomitant use with:
Typhoid vaccine, live – clindamycin decreases
Dose Adjustment: effect of vaccine through pharmacodynamic
Renal Impairment: antagonism; high likelihood of serious or life-
No dosage adjustment necessary. threatening interaction.
Hepatic Impairment: BCG vaccine, live – clindamycin decreases effect of
Use with caution in hepatic impairment, monitor for vaccine through pharmacodynamic antago-
hepatic abnormalities. nism; high likelihood of serious or life-
threatening interaction.
40
Erythromycin - antagonism may occur due to com- Pregnancy (not known to be harmful); breastfeeding
petition at the binding sites. (trace amounts found in milk, but safe in usual
dosage; monitor infant).
Administration: May be taken with food. Do not
refrigerate reconstituted oral solution since the Adverse Drug Reactions:
solution will thicken; reconstituted solution is Common: Abdominal pain, diarrhea, flatulence,
stable for 2 weeks at room temperature. nausea.
Less Common: Fever, hypersensitivity reactions,
including joint pain, rash and urticaria; sore
tongue and mouth.
Rare: Agranulocytosis, antibiotic-associated colitis,
blood in stools, black hairy tongue, cholestatic
CLOXACILLIN jaundice, electrolyte disturbances, hemolytic
anemia, hepatitis, interstitial nephritis, neutro-
Oral: 250 mg and 500 mg capsule (as sodium salt) penia, renal failure, thrombocytopenia, serum
125 mg/5 mL powder for syrup/suspension, 60 sickness-like reactions.
mL (as sodium salt)
250 mg/5 mL powder for oral solution, 60 mL Drug Interactions:
A penicillinase-resistant, isoxazolyl penicillin having Contraceptives, Oral – their efficacy may be re-
high potency against staphylococci, which are duced by cloxacillin.
resistant to benzylpenicillin. Methotrexate – cloxacillin may increase serum
Indications: Infections due to beta-lactamase- concentration of methotrexate and risk of tox-
producing staphylococci including impetigo, icity.
cellulitis, and other skin and soft tissue infec- Mycophenolate – cloxacillin may decrease the
tions, including infected wounds from animal serum concentration of mycophenolate and its
bites; otitis externa; pyomyositis; infected active metabolites.
wounds from animal bites. Probenecid – this decreases cloxacillin excretion,
and prolongs its activity (through competitive
Antimicrobial Resistance ALERT! renal tubule secretion).
Due to the high prevalence of methicillin re- Avoid concomitant use with:
sistant Staphylococcus aureus (MRSA), clox- Bacteriostatic antibiotics (e.g., tetracycline, chlo-
acillin should not be used for empiric treat- ramphenicol) – these may antagonize the ac-
ment of moderate to severe infections sus- tivity of cloxacillin.
pected to be secondary to S. aureus. (See
section on MRSA under Clindamycin for fur- Administration: Should be taken on an empty
ther information). stomach 1 hour before, or 2 hours, after meals
(intake of food further reduces its absorption).
Contraindication: Known hypersensitivity to peni-
cillins or any component of the formulation. Pregnancy Category: B
Dose:
Localized purulent skin lesions and impetigo, by
mouth, ADULT, 250-500 mg every 6 hours for CO-AMOXICLAV (Amoxicillin +
5-7 days; CHILD, 12.5-25 mg/kg (maximum, Potassium Clavulanate)
500 mg) every 6 hours for 5-7 days. Oral: 250 mg amoxicillin (as trihydrate) + 125 mg
Other infections due to susceptible beta-lactamase-
potassium clavulanate per tablet
producing staphylococci, by mouth, ADULT,
500 mg amoxicillin (as trihydrate) + 125 mg
500 mg 4 times daily (double the dose in se-
vere infections); CHILD, 15-25 mg/kg/day in 4
doses.
manufacturer’s directions. 125 mg amoxicillin (as trihydrate) + 31 mg
potassium clavulanate per 5 mL gran-
Dose Adjustments: ules/powder for suspension, 30 mL and 60
Renal and Hepatic Impairment: mL
Same dosage as in patients with normal function 200 mg amoxicillin (as trihydrate) + 28.5 mg
may be used in patients with mild-to-moderate potassium clavulanate per 5 mL gran-
impairment; for severe impairment, the patient ules/powder for suspension, 70 mL
should be referred to a specialist. 250 mg amoxicillin (as trihydrate) + 62.5 mg
Precautions: potassium clavulanate per 5 mL gran-
ules/powder for suspension,
History of allergy to penicillins (if skin rash develops,
60 mL and 100 mL
the patient should be prescribed a different
class of antimicrobial); heart failure; renal im-
potassium clavulanate per 5 mL gran-
pairment; hepatic impairment (cholestatic
ules/powder for suspension,
jaundice may occur up to several weeks after
30 mL and 70 mL
the treatment has been stopped; administra-
tion for more than two weeks and increasing
age are risk factors).
41
A combination of an extended-spectrum aminopeni- Dose Adjustments:
cillin and a beta-lactamase inhibitor, which Renal and Hepatic Impairment (except for Contra-
has increased antibacterial activity against indications stated above):
amoxicillin-resistant and beta-lactamase- For mild-to-moderate impairment, dose reduction is
producing strains of bacteria. warranted; for severe impairment, the patient
should be referred to a specialist.
Indications: Infections due to beta-lactamase-
producing bacteria and where amoxicillin Precautions:
alone is not appropriate, including respiratory History of allergy to penicillins; renal impairment
tract infections such as low-risk CAP (CAP- (risk of crystalluria with high doses; maintain
LR) in patients with co-morbid illness or with adequate hydration); hepatic impairment
recent antibiotic therapy where Gram- (monitor liver function; duration of treatment
negative bacilli can coexist; otitis media and should not exceed 14 days since cholestatic
sinusitis due to susceptible microorganisms; jaundice has been reported during, or shortly
treatment for Acute Uncomplicated Pyelone- after, the treatment; it is more common in pa-
phritis where Gram stain shows Gram- tients over the age of 65 years and in males);
positive organisms; asymptomatic bacteriu- erythematous rash (common in glandular fe-
ria; alternative treatment in Acute Uncompli- ver, CMV infection); chronic lymphatic leuke-
cated Cystitis and Acute Uncomplicated Pye- mia; and possibly HIV infection.
lonephritis (in non-pregnant women); animal Pregnancy (not known to be harmful); breastfeeding
bites; severe dental infections with spreading (trace amounts in milk).
cellulitis or those not responding to first-line
antibiotics.
Common: Diarrhea.
Contraindications: Known hypersensitivity to Less Common: Candidiasis, dizziness, flatulence,
amoxicillin, clavulanic acid or penicillins; histo- headache, loose stool, mycosis, nausea, rash,
ry of penicillin- or amoxicillin with clavulanic superficial staining of teeth (with suspension),
acid-associated jaundice or hepatic dysfunc- vaginitis, vomiting.
tion. Rare: Abdominal discomfort, agranulocytosis, ana-
phylaxis, angioedema, cholestatic jaundice,
Dose:
convulsions, elevation of ALT/AST, erythema
Asymptomatic bacteriuria, by mouth, ADULT, in
multiforme, exfoliative dermatitis, hemolytic
non-pregnant patients, 625 mg twice daily for anemia, hepatitis, hepatotoxicity, hypersensi-
7-14 days; in pregnant women, 625 mg twice tivity reactions, leukopenia, neutropenia,
daily for 7 days. See Clinical Practice Guide- pseudomembranous colitis, rash, serum sick-
lines – UTI for further information ness-type reactions, Stevens-Johnson syn-
Acute uncomplicated cystitis, alternative treatment, drome, thrombocytopenia, toxic epidermal
by mouth, ADULT, 625 mg twice daily for 7 necrolysis, vasculitis
days. See Clinical Practice Guidelines – UTI
for further information Drug Interactions:
Acute uncomplicated pyelonephritis due to gram- Monitor closely with:
positive organisms only, by mouth, ADULT, Allopurinol – when combined with co-amoxiclav,
625 mg thrice daily for 14 days. See Clinical there is increased risk of rash occurrence.
Practice Guidelines – UTI for further infor- Contraceptives, Oral – their efficacy may be re-
mation. duced by co-amoxiclav.
Community-Acquired Pneumonia, low-risk (CAP-
LR) with coexisting gram-negative bacilli, Administration: Administer at the start of a meal
by mouth, ADULT, 625 mg thrice a day or 1 g (to minimize potential GI intolerance, and op-
twice a day for 5-7 days. See Clinical Practice timize absorption).
NOTE: Two 500 mg amoxicillin/125 mg clavulanate tablets
Guidelines – CAP for further information. should not be taken at one time since the double
Infections due to susceptible beta-lactamase- dose of clavulanate is more likely to cause GI tract
producing organisms, by mouth, ADULT and adverse effects.
CHILD ≥12 years, 250 mg every 8 hours
(double the dose in severe infections); CHILD
<12 years, 20-40 mg/kg/ day in 3 divided
doses using the 125 mg/5 mL or 250 mg/5 mL COTRIMOXAZOLE (Trimethoprim +
preparation; or 25-45 mg/kg/day in 2 divided Sulfamethoxazole)
doses using the 200 mg/5 mL or 400 mg/5 mL
preparation. Oral: 400 mg sulfamethoxazole + 80 mg trime-
Severe dental infections, by mouth, ADULT, 375 thoprim tablet/capsule
mg every 8 hours for 5 days. 800 mg sulfamethoxazole + 160 mg trime-
RECONSTITUTION AND ADMINISTRATION. According to thoprim tablet
manufacturer’s directions. 200 mg sulfamethoxazole + 40 mg trime-
NOTE: Patients with dysphagia – may substitute 250 mg/5 thoprim/5 mL suspension,
mL suspension for 625 mg tablet; and 200 mg/5 mL 30 mL, 60 mL, 70 mL and 100 mL
or 400 mg/5 mL suspension for 1 g tablet. 400 mg sulfamethoxazole + 80 mg trime-
thoprim/5 mL suspension,
30 mL and 60 mL
42
A combination of a sulfonamide (5 parts) and an risk of crystalluria (sulfamethoxazole is poorly
inhibitor of dihydrofolate reductase (1 part), soluble at low pH; maintain adequate fluid in-
which provides synergistic antimicrobial activi- take to prevent crystalluria).
ty against many gram-positive and gram- Hepatic impairment (avoid if severe).
negative organisms because of its sequential Blood disorders (avoid unless under specialist
inhibition of folate synthesis. supervision; monitor blood count and discon-
tinue immediately if blood disorder develops);
Indications: Uncomplicated typhoid or enteric
rash (discontinue treatment immediately);
fever; choleraa (with severe diarrhea and de- asthma; G6PD deficiency (increased risk of
hydration); MRSA. hemolysis).
a
Carlos, C, Antimicrobial Resistance Surveillance Program 2013 Data
Summary Report. Pregnancy (first trimester: teratogenic effects which
include anencephaly, hypoplastic left heart
Antimicrobial Resistance ALERT! syndrome, choanal atresia, transverse limb
• Use of cotrimoxazole is not recommended for defect, diaphragmatic hernia; third trimester:
CAP due to continuing increase in rate of re- neonatal hemolysis and methemoglobinemia);
sistance of S. pneumoniae and H. influenzae. breastfeeding (monitor infant for jaundice:
• In UTI, among the Enterobacteriaceae, re- there is small risk of kernicterus in jaundiced
sistance rates of E. coli to cotrimoxazole have infants); G6PD-deficient infants (risk for he-
been increasing. molysis due to sulfamethoxazole); caution in ill
Contraindications: Known hypersensitivity to or premature infants; avoid in infants <6
sulfonamides, trimethoprim or any component weeks.
of the formulation; infants <2 months of age; Adverse Drug Reactions:
severe renal or hepatic failure; megaloblastic Common: Anorexia, diarrhea, fever, hyperkalemia,
anemia (due to folic acid deficiency); blood hyponatremia, itch, nausea, rash, sore mouth,
dyscrasias; acute porphyria; late pregnancy thrombocytopenia, vomiting.
(due to risk of neonatal kernicterus, hemolytic Less Common: Drowsiness, headache, neutro-
anemia and jaundice). penia, photosensitivity.
Dose: Rare: Arthralgia, aseptic meningitis, Clostridium
NOTE: Doses are expressed as 800/160 mg = 800 mg difficile-associated disease, convulsions, de-
sulfamethoxazole with 160 mg trimethoprim (equiva- pression, erythema, hallucinations, hepatic
lent to one double strength tablet); 40/8 mg is equiva- necrosis, hepatitis, hypoglycemia, jaundice,
lent to 1 mL of oral liquid. lowered mental acuity, megaloblastic anemia,
Typhoid fever, by mouth, ADULT, 320-480 mg/day myalgia, myocarditis, pancreatitis, peripheral
of Trimethoprim in 2 divided doses; CHILD, 8- neuropathy, pulmonary infiltrates, Stevens-
10 mg/kg/day of Trimethoprim in 2 divided Johnson syndrome, SLE, toxic epidermal
doses. necrolysis, urinary obstruction with anuria or
Cholera (with severe diarrheal disease and dehy- oliguria, uveitis, vasculitis, vertigo.
dration), by mouth, CHILD > 2 months old, 5-
10 mg/kg/day (based on trimethoprim compo- Drug Interactions:
nent) in two divided doses for 3 days, not to Monitor closely with:
exceed 320 mg/day of trimethoprim and 1.6 Digoxin – possibly increased plasma digoxin con-
g/day of sulfamethoxazole. centration.
DILUTION AND ADMINISTRATION. According to manufac- Drugs causing potassium retention (e.g., ACE inhib-
turer’s directions. itors) – greater risk of hyperkalemia.
Dose Adjustments: Other nephrotoxic drugs (e.g., gentamicin and
streptomycin) – cotrimoxazole can cause ne-
Renal Impairment:
phrotoxicity; giving with other nephrotoxic
tion is warranted; contraindicated for severe drugs may cause additional renal adverse ef-
impairment. fects.
Hepatic Impairment: Phenytoin – antifolate effect and increased plasma
Contraindicated in significant hepatic impairment. phenytoin concentration.
Rifampicin – this may decrease cotrimoxazole
Precautions: concentration when used for prophylaxis in
HIV infection (increased frequency of allergic reac- HIV-positive patients, decreasing its efficacy.
tions); photosensitivity; slow acetylator pheno-
Administration: Should be taken with food; this is
type (increased risk of adverse effects with
sulfonamide); treatment with oral typhoid vac- best taken after meals with an adequate
cine (cotrimoxazole is active against S. typhi, amount of fluid.
and may inactivate the vaccine); systemic lu- Pregnancy Category: C
pus erythematosus (may worsen).
Elderly (increased risk of blood dyscrasias and skin
disorders).
Renal impairment (impairment increases risk of
hyperkalemia or hypoglycemia; avoid if severe
and if plasma sulfamethoxazole concentration
cannot be monitored); low urine pH increases
43
symptoms, by mouth, for 7 days, ADULT, 100
DOXYCYCLINE mg twice daily; CHILD >8 years old, 2-4
mg/kg in 2 divided doses, not to exceed 200
Oral: 50 mg and 100 mg capsule (as base*/hyclate) mg/day. (For alternative antibiotic treatment,
see under Amoxicillin).
A broad-spectrum and long-acting tetracycline
antibiotic that is used for infections caused by For moderate to severe leptospirosis, refer im-
chlamydia, spirochetes and other pathogens, mediately to a higher level of healthcare facili-
and for malarial prophylaxis. ty or the hospital.
Indications: Infections caused by susceptible rick- For pre-exposure prophylaxis ONLY for individu-
ettsiae, Chlamydia, Brucella and Mycoplasma; als who intend to visit highly endemic
leptospirosis (see Dose below for important as and are likely to get exposed (e.g., travel-
notes on specific indications); alternative ers, soldiers), for short term exposures, by
treatment for syphilis. mouth, for ADULT MALES and NON-
PREGNANT, NON-LACTATING FEMALES,
Contraindications: Known hypersensitivity to 200 mg once weekly to begin 1-2 days before
tetracyclines or any component of the formula- exposure and continued throughout the period
tion; should not be given to children <8 years of exposure. Currently, there is NO recom-
of age (deposition of tetracyclines in growing mended pre-exposure prophylaxis that is safe
bones and teeth, causing deformation and infor pregnant or lactating women.
hibiting bone growth) except for cholera or
leptospirosis (for these two infections, doxycy- For post-exposure prophylaxis:
cline should not be given >7 days); pregnan- - In Low-Risk Exposure (defined as single his-
cy (first trimester: effects on skeletal develop- tory of wading in flood or contaminated water
ment in animal studies; 2nd and 3rd trimesters: and the absence of wounds, cuts, or open le-
dental discoloration; maternal hepatotoxicity sions of the skin), by mouth, ADULT, 200 mg
with large doses); breastfeeding; porphyria; within 24-72 hours from exposure.
SLE. - In Moderate-Risk Exposure (defined as sin-
gle history of wading in flood or contaminated
Dose: water and the presence of wounds, cuts, or
Bacterial infections, general dose, by mouth, open lesion in the skin, OR, the accidental in-
ADULT, 200 mg in two doses on the first day, gestion of contaminated water), by mouth,
then 100 mg daily; for severe infections, 100 ADULT, 200 mg once daily for 3-5 days to be
mg twice daily (maximum, 200 mg daily); started immediately within 24-72 hours from
CHILD >8 years, 2 mg/kg twice daily on Day exposure.
1 (maximum, 200 mg daily) then 2 mg/kg once - In High-Risk Exposure (defined as continu-
daily (maximum, 100 mg daily); round the ous exposure – more than a single exposure
dose to the nearest 25 mg; for severe infec- or several days exposure – of wading in flood
tions, 4 mg/kg daily (maximum, 200 mg) in 1 or contaminated water with or without the
or 2 doses. presence of wounds, cuts, or open lesions of
Early syphilis, by mouth, ADULT, 100 mg twice the skin; swimming in flooded waters especial-
daily for 14 days; late latent syphilis, 100 mg ly in areas infested with domestic/sewer rats
twice daily for 28 days. and ingestion of contaminated water), by
Leptospirosisa: mouth, ADULT, 200 mg once weekly until the
Clinical manifestations that should lead a end of the exposure.
health practitioner to consider suspected lep- - For Pediatrics: by mouth, CHILD, > 8 years
tospirosis: any individual with acute febrile old, 4 mg/kg as single dose (maximum, 200
illness of at least 2 days duration AND resid- mg); if child is exposed for more than 7 days,
ing in a flooded area or has high-risk exposure repeat the dose after one week.
(defined as wading in floods and contaminat-
NOTE: Antibiotic prophylaxis in the prevention of leptospiro-
ed water, contact with animal fluids, swimming
sis is NOT 100% effective. The most effective preven-
in flood water or ingestion of contaminated tive measure remains to be avoidance of high-risk ex-
water, with or without cuts or wounds) AND posure. There is currently no recommended pre-
with at least 2 of the following symptoms: my- exposure prophylaxis that is safe for pregnant or lac-
algia, calf tenderness, conjunctival suffusion, tating women.
chills, abdominal pain, headache, jaundice, ol- Pelvic inflammatory disease, by mouth, ADULT,
iguria. 100 mg twice daily for 14 days.
Suspected uncomplicated genital chlamydia and
For mild leptospirosis (defined as acute febrile non-gonococcal urethritis, by mouth, ADULT,
illness and various manifestations BUT with 100 mg twice daily for 1-3 weeks depending
stable vital signs, anicteric sclera, good urine on the site and severity of the infection.
output and NO evidence of meningismus / a
The Philippine Clinical Practice Guidelines on the Diagnosis, Treatment
meningeal irritation, sepsis / septic shock, dif- and Prevention of Leptospirosis in Adults 2010, PSMID, Quezon City.
ficulty of breathing and jaundice that can be
managed at the out-patient setting with close
monitoring) as first line agent to be started as
soon as the diagnosis is suspected regardless
of the phase of the disease or duration of
44
Dose Adjustments: Oral Retinoids (e.g., isotretinoin, acitretin) – may
Renal Impairment: increase the risk of benign intracranial hyper-
Doxycycline can be used without dose adjustment tension.
(does not lead to excessive accumulation Penicillins – being bacteriostatic, doxycycline may
when used at the usual recommended doses). interfere with the bactericidal action of penicil-
Hepatic Impairment: lins.
Avoid high doses (hepatotoxicity more likely to Zinc Salts – these form poorly-soluble chelates with
occur in hepatic impairment). doxycycline, thus reducing its absorption and
anti-infective capacity (separate administration
Precautions:
by at least 2 hours).
Tetracyclines may increase muscle weakness in
patients with myasthenia gravis and may ex- Administration: Capsules should be swallowed
acerbate SLE; overgrowth of non-susceptible whole with plenty of fluid (a full glass of wa-
organisms (including fungi); hepatic impair- ter); remain sitting or standing (for at least
ment; photosensitivity (avoid exposure to sun- ½ hour) to prevent esophageal irritation or
light or sunlamps); intracranial hypertension; damage; it may be given with food to counter
tissue hyperpigmentation; breastfeeding (use gastric irritation. Do not give with milk.
other alternative drugs if possible); probable
Pregnancy Category: D
absorption and discoloration of teeth in infants
may usually be prevented by chelation with
calcium from milk.
Adverse Drug Reactions: ERYTHROMYCIN
Common: Abdominal pain, diarrhea, enamel dys-
plasia, epigastric burning, headache, nausea, Oral: 250 mg tablet (as stearate)
photosensitivity, reduced bone growth (in chil- 200 mg/5 mL granules/powder for suspension,
dren <8 years), tooth discoloration, vaginitis, 60 mL (as ethyl succinate)
vomiting.
Less Common: Anorexia, bone deformity, dental A macrolide antibiotic that is effective in treating
hypoplasia, flushing, fungal overgrowth, rash, infections caused by Chlamydia, Mycoplasma,
stomatitis. Pneumococcus and Campylobacter spp.
Rare: Allergic reactions including Stevens-Johnson Indications: Alternative to penicillin in hypersensi-
syndrome and anaphylaxis; benign intracrani- tive patients; sinusitis; otitis externa; oral in-
al hypertension, blood disorders, C. difficile- fections; acne vulgaris and rosacea; respirato-
associated disease, esophageal ulcers, hepa- ry tract infections due to organisms suscepti-
titis, hepatotoxicity, nail discoloration, pancre- ble to erythromycin; syphilis; chancroid; chla-
atitis, serum sickness-like reactions, toxic epi- mydia; neonatal chlamydial conjunctivitis; non-
dermal necrolysis, visual disturbances, tinni- gonococcal urethritis; chronic prostatitis; skin
tus. infections; Campylobacter enteritis; diphtheria;
Drug Interactions: diphtheria and whooping cough prophylaxis; Q
Monitor closely with: fever in children.
Contraceptives, Oral – their efficacy may be re- Contraindications: Known hypersensitivity to
duced by doxycycline. erythromycin and other macrolides, or any
Rifampicin – this may increase the metabolism of component of the formulation; porphyria; se-
doxycycline, thereby reducing its efficacy. vere hepatic impairment; QT prolongation and
Avoid concomitant use with: ventricular cardiac arrhythmias.
Antacids (e.g., aluminum and magnesium hydrox-
ide) – these form poorly-soluble chelates with Dose:
doxycycline, thus reducing its absorption and Acne rosacea, by mouth, ADULT and CHILD >12
anti-infective capacity (separate administration years, 250-500 mg twice daily.
by at least 2 hours). Campylobacter enteritis, by mouth, ADULT, 500 mg
Calcium – this forms poorly-soluble chelates with 4 times a day for 5-7 days; CHILD, 10 mg/kg
doxycycline, thus reducing its absorption and 4 times a day for 5-7 days.
anti-infective capacity (separate administration Pertussis prevention and treatment, by mouth,
by at least 2 hours). ADULT, 250 mg every 6 hours for 14 days;
Ferric Salts – these form poorly-soluble chelates CHILD, 10 mg/kg/dose (maximum, 250 mg)
with doxycycline, thus reducing its absorption every 6 hours for 14 days.
and anti-infective capacity (separate admin- Recurrent rheumatic fever prophylaxis, by mouth,
istration by as long as possible, at least 2 ADULT and CHILD, 250 mg every 12 hours
hours); doxycycline also significantly reduce for at least 10 years.
iron absorption. Syphilis (early), by mouth, ADULT, 500 mg 4 times
Magnesium – this forms poorly-soluble chelates daily for 14 days; for syphilis (late latent), by
with doxycycline, thus reducing its absorption mouth, ADULT, 500 mg 4 times daily for 30
and anti-infective capacity (separate admin- days.
istration by at least 2 hours). Uncomplicated genital chlamydia, non-gonococcal
urethritis, chancroid, by mouth, ADULT, 500
45
mg 4 times daily for 7 days (14 days in lym- Verapamil – this may increase erythromycin con-
phogranuloma venereum). centration, thus increasing the risk of serious
Other infections due to sensitive organisms, by prolongation of the QT interval.
mouth, ADULT, 250-500 mg every 6 hours;
CHILD, 30-50 mg/kg/day in 3-4 divided doses. Administration: Tablets and capsules should be
swallowed whole; best taken on an empty
Dose Adjustment: stomach 1 hour before, or 2 hours, after
Renal Impairment: meals.
Precautions:
Risk of sudden cardiac death from cardiac causes GENTAMICIN
when oral erythromycin used concomitantly
with drugs that inhibit CYP3A4 (see Appen- Inj.: 10 mg/mL, 1 mL ampul and 2 mL vial (IM, IV)
dix). (as sulfate)
Caution in ventricular cardiac arrhythmia and QT 40 mg/mL, 1 mL, 1.5 mL and 2 mL ampul/ vial
prolongation. (IM, IV) (as sulfate)
Hepatic impairment (may cause idiosyncratic hepa-
totoxicity) and renal impairment (may cause An aminoglycoside that is not absorbed from the
ototoxicity); predisposition to QT interval pro- gut, and should therefore be administered by
longation, including electrolyte disturbances injection for systemic infections caused by
and concomitant use of drugs that prolong the some gram-positive and many gram-negative
QT interval (see Appendix – Table B). strains, including Pseudomonas aeruginosa.
Pregnancy (not known to be harmful); breastfeeding Indications: Sepsis neonatorum (with ampicillin);
(small amounts found in milk – not known to pelvic inflammatory disease (with clindamy-
be harmful; may cause loose bowel actions in cin).
infant).
Contraindications: Known hypersensitivity to
Adverse Drug Reactions: aminoglycosides or any component of the
Common: Abdominal pain, candidal infections, formulation; perforated ear drum; hepatic im-
cramps, diarrhea, nausea, vomiting. pairment; myasthenia gravis.
Less Common: Headache, rash, urticaria.
Rare: Blood dyscrasias, cardiac effects, including Dose:
prolonged QT interval; cholestatic jaundice, C. NOTE: If the patient is >20% over ideal weight, the ideal
weight is generally used to calculate the dose. How-
difficile-associated disease, hypersensitivity
ever, some practitioners prefer to use the adjusted
reactions including anaphylaxis; infantile hy- weight (adjusted weight = 0.4 𝑥 (actual weight ⎼ ideal
pertrophic pyloric stenosis, myasthenia-like weight) + ideal weight).
syndrome, pancreatitis, psychiatric disturb- Pelvic inflammatory disease (with clindamycin), by
ances, ototoxicity, toxic epidermal necrolysis. IV injection, ADULT, loading dose of 2 mg/kg,
Frequency not defined: Torsades de pointes, then 1.5 mg/kg every 8 hours; alternate thera-
ventricular arrhythmias, ventricular tachycar- py: 4.5 mg/kg once daily.
dia. Sepsis neonatorum, IM or slow IV infusion over 30-
Drug Interactions: 60 minutes, NEONATE <7 days, 1.2 up to 2
NOTE: Macrolides inhibit P-glycoprotein, which may lead to kg weight: 2.5 mg/kg/dose IV every 12 to 18
drug interactions (see Appendix). hours; >2 kg weight: 2.5 mg/kg/dose every 12
Monitor closely with: hours, IM or slow IV infusion over 30-60
Contraceptives, Oral – their efficacy may be re- minutes.
duced by erythromycin. NOTE: Treatment for <48 hours in people with normal renal
Digoxin – its plasma concentration may be in- function does not require gentamicin concentration
monitoring.
creased by erythromycin, thus increasing the DILUTION AND ADMINISTRATION. According to manufac-
risk of toxicity. turer’s directions.
Artemether + Lumefantrine – these may result to Dose Adjustments:
potentially hazardous interactions when given Neonates and Infants:
concomitantly with erythromycin. Adjust dosage; avoid prolonged use.
CYP3A4 inhibitors (see Appendix) – these may Obese patients:
increase the concentration of erythromycin To avoid excessive dosage, use ideal weight for
and the risk of QT prolongation. height to calculate dose and monitor serum-
HMG-CoA reductase inhibitors (e.g., atorvastatin, gentamicin concentration closely.
simvastatin) – their concentration may be in- Elderly:
creased by erythromycin, thus increasing the For mild-to-moderate renal impairment, dose reduc-
risk of myopathy and rhabdomyolysis (stop tion or dose interval extension is warranted;
medication temporarily). for severe impairment, the patient should be
Hydrocortisone – its metabolism may be inhibited by referred to a specialist.
erythromycin.
46
Renal Impairment:
For mild-to-moderate renal impairment, dose reduc- METRONIDAZOLE
patient should be referred to a specialist. Oral: 250 mg and 500 mg base tablet
Precautions: 125 mg base/5 mL (200 mg/5 mL as benzo-
ate) suspension, 60 mL
WARNING: Neurotoxicity, manifested as both bilateral
auditory and vestibular ototoxicity, can occur in pa- A nitroimidazole, antiprotozoal drug, which has
tients with pre-existing renal damage and in patients potent antibacterial activity against anaerobes,
with normal renal function treated at higher doses
including Bacteroides and Clostridium spp.
and/or for periods longer than those recommended.
Aminoglycosides are potentially nephrotoxic. Risk is greater Indications: Anaerobic bacterial infections, includ-
in patients with impaired renal function and in those
ing gingivitis and other oral infections; skin
who receive high doses or prolonged therapy.
Use with caution in premature infants and neonates because and soft tissue infections; bacterial vaginosis;
of renal immaturity and the resulting prolongation of for H. pylori eradication, see under Anti-H. py-
serum half-life of the drug. lori infection; for amoebiasis and giardiasis,
Neuromuscular blockade and respiratory paralysis have see under Antiamebiasis, Antigiardiasis and
been reported following parenteral injection of amino-
Antitrichomoniasis.
glycosides.
Neuromuscular diseases (e.g., myasthenia gravis) Contraindications: Known hypersensitivity to
or conditions characterized by muscle weak- metronidazole or any component of the formu-
ness (gentamicin may impair neuromuscular lation; chronic alcohol dependence.
transmission, increasing risk of muscle weak- Dose:
ness and respiratory depression); renal im- Acute oral infections, by mouth, ADULT, 200 mg
pairment; neonates (half-life prolonged; de- every 8 hours for 3-7 days; CHILD, 30-50
crease dose), infants, and the elderly; obesity mg/kg/day in 4 divided doses for 3-7 days.
(use ideal body weight to calculate dose and Acute ulcerative gingivitis, by mouth, ADULT, 200-
monitor serum gentamicin concentration 250 mg every 8 hours for 3 days; CHILD, 30-
closely). 50 mg/kg/day in 4 divided for 3 days.
Pregnancy (second and third trimesters: auditory or Anaerobic infections (usually treated for 7 days), by
vestibular nerve damage; reserve for severe mouth, ADULT, 800 mg initially, then 500 mg
or life-threatening infections for which safer every 8 hours; CHILD, 7.5 mg/kg every 8
drugs are inappropriate; if administered, moni- hours.
tor serum-gentamicin concentration); breast- Bacterial vaginosis, by mouth, ADULT, 2 g as a
feeding (amount probably too small to be single dose or 500 mg twice daily for 5-7 days.
harmful; monitor infant for thrush and diar-
rhea). Dose Adjustments:
Renal Impairment:
Adverse Drug Reactions: Dose adjustment is not usually necessary. Howev-
Common: Edema, gait instability, ototoxicity (audi- er, consider reducing dose during long-term
tory and vestibular damage), nephrotoxicity, therapy. For severe impairment, the patient
reddening of the skin, skin itching. should be referred to a specialist (as metabo-
Less Common: Rash. lites may accumulate, possibly causing ad-
Rare: Anaphylaxis, antibiotic-associated colitis, verse effects).
blood disorders, bronchospasm, CNS effects, Hepatic impairment:
electrolyte disturbances, nausea, neuromus- For severe liver disease, reduce total daily dose to
cular blockade, oliguria, peripheral neuropa- one-third or one-half, and give once daily (risk
thy, photosensitivity, stomatitis, vomiting. of drug accumulation and toxicity in severe
Drug Interactions: impairment, especially if renal impairment is
Monitor closely with: also present).
Digoxin – the serum levels of digoxin may be in- Precautions:
creased by gentamicin, resulting in enhanced Treatment with disulfiram may cause psychotic
actions and risk of toxicity. reactions; treatment with fluorouracil (avoid
Ototoxic and nephrotoxic drugs (e.g., streptomycin) combination); disulfiram-like reaction with al-
– possibly increased risk of ototoxicity and cohol.
nephrotoxicity. Hepatic impairment and hepatic encephalopathy.
Avoid concomitant use with: Renal impairment; congestive heart failure; history
Diuretics (e.g., furosemide) – these may enhance of blood dyscrasias; history of CNS disorders,
aminoglycoside toxicity, increasing risk of oto- and seizures (nitroimidazoles are neurotoxic
toxicity. and may aggravate existing neurological dis-
Administration: Infuse gentamicin over 30-60 ease); clinical and laboratory monitoring rec-
minutes; doses <120 mg may be given as IV ommended in courses lasting longer than 10
injection over 3-5 minutes. Final concentration days.
of IV infusion should not exceed 10 mg/mL. Pregnancy (avoid use in early pregnancy; if this is to
be administered, avoid high-dose regimens;
Pregnancy Category: D take in divided doses if possible); breastfeed-
ing (significant amounts in milk; may cause
47
bitterness in milk; use in divided doses if given Dose:
after breastfeeding rather than single daily Group A streptococcal infection, by deep IM injec-
doses; avoid large doses; use an alternative tion, ADULT and CHILD >27 kg, 1.2 million
drug if possible). units as a single dose; CHILD <27 kg,
600,000 units as a single dose.
Rheumatic fever prophylaxis (prevent recurrence of
Common: Abdominal pain, anorexia, CNS effects
fever), by deep IM injection, ADULT and
(e.g., dizziness), constipation or diarrhea, GI
CHILD, 25,000-50,000 units/kg (maximum
disturbances, headache, metallic taste, nau-
dose, 1.2 million units) for high-risk patients,
sea, vomiting.
every 3 weeks, for at least 10 years.
Less Common: Drowsiness, furry tongue (due to
Syphilis, congenital (where there is no evidence of
growth of Candida), glossitis, paresthesia,
CSF involvement), by deep IM injection,
stomatitis.
CHILD <2 years, 50,000 units/kg as a single
Rare: Agranulocytosis, anaphylactic shock, angi-
dose.
oedema, aplastic anemia, cholestatic hepati-
Syphilis, primary, by deep IM injection, ADULT, 1.2
tis, C. difficile-associated disease, darkening
million units as a single dose, divided between
of urine, seizures, hypersensitivity reactions,
2 sites.
jaundice, leukopenia (on prolonged or high
Syphilis, secondary latent, by deep IM injection,
dosage regimens), myalgia, myopia, optic
ADULT, 2.4 million units once weekly for 3
neuritis, pancreatitis, peripheral neuropathy,
consecutive weeks, divided between 2 sites.
psychotic disorder, raised liver enzyme, Ste- RECONSTITUTION AND ADMINISTRATION. According to
vens-Johnson syndrome, thrombocytopenia, manufacturer’s directions.
urethral discomfort.
Dose Adjustment:
Drug Interactions: Renal Impairment:
Monitor closely with: For mild-to-moderate renal impairment, dose reduc-
Contraceptives, Oral – their efficacy may be re- tion is warranted; for severe impairment, the
duced by metronidazole. patient should be referred to a specialist.
Phenobarbital – this may increase metabolism of
metronidazole, and reduce its concentration Precautions:
with possible treatment failure (monitor clinical WARNING:
effect as there may be a need to increase its Not for IV use.
dose, possibly by 2-3 times). Do not inject IV or admix with other IV solutions.
Reports of inadvertent IV administration associated with
Avoid concomitant use with: cardiorespiratory arrest and death.
Alcohol – this results in a disulfiram-like reaction Prior to administration, carefully read the warnings, adverse
(abdominal pain, flushing, headache, nausea, reactions, and dosage and administration sections of
vomiting, tachycardia); (avoid alcoholic drinks the labeling.
during, and for at least 24 hours after treat- History of allergy to penicillins; renal failure (neuro-
ment). toxicity; high doses may cause convulsions);
Administration: Tablets should be swallowed and pregnancy (not known to be harmful),
whole with water, during or after a meal; oral breastfeeding (trace amounts in milk; safe in
suspension should be taken one hour before a usual dosage; monitor infant).
meal or on an empty stomach. Adverse Drug Reactions:
Pregnancy Category: B Common: Pain and sterile inflammation at injection
site.
Less Common: Diarrhea.
Rare: CNS toxicity, convulsions, hemolytic anemia,
PENICILLIN G BENZATHINE hypersensitivity reactions, including anaphy-
(Benzathine benzylpenicillin) laxis; interstitial nephritis, Jarisch-Herxheimer
reaction, neutropenia, non-allergic (embolic-
Inj.: 1,200,000 units vial (MR) (IM) toxic) reactions, thrombocytopenia.
A beta lactamase-sensitive penicillin having a simi- Drug Interactions:
lar spectrum of activity with penicillin G crys- Monitor closely with:
talline; but provides a tissue depot from which Anticoagulants (e.g., warfarin) – penicillins may
the drug is slowly absorbed over a period of enhance their anticoagulant effect.
12 hours to several days. Contraceptives, Oral – their efficacy may be re-
NOTE: Peak plasma concentrations are reached within 13- duced by benzathine benzylpenicillin.
24 hours; detectable in the urine for 3-4 weeks. Avoid concomitant use with:
Indications: Streptococcal pharyngitis/tonsilitis; Probenecid – this may increase the serum concen-
diphtheria; rheumatic fever prophylaxis; syphi- tration of penicillins.
lis. Tetracycline – this may antagonize the bactericidal
effect of benzathine benzylpenicillin.
penicillins or any component of the formula- Administration: Administer by deep IM injection
tion; neurosyphilis; intravascular injection. only in the upper, outer quadrant of the but-
tock or mid-lateral aspect of the thigh; avoid
48
PNF new 74 new .pdf 1 1/8/15 2:52 PM
PDMRU QHUYHV DQG EORRG YHVVHOV as severe dosage; monitor infant); syphilis (Jarisch-
neurovascular damage may occur. Give dos- Herxheimer reaction can occur after starting
es >900 mg as 2 injections at separate sites. treatment).
PDMRU QHUYHV DQG EORRG YHVVHOV as severe dosage; monitor infant); syphilis (Jarisch-
3UHJQDQF\&DWHJRU\B
neurovascular damage may occur. Give dos- $GYHUVH'UXJ5HDFWLRQV
Herxheimer reaction can occur after starting
es >900 mg as 2 injections at separate sites. Common: Pain and sterile inflammation at injection
treatment).
site, phlebitis.
3UHJQDQF\&DWHJRU\B $GYHUVH'UXJ5HDFWLRQV
Less Common: Antibiotic-associated colitis, diar-
PENICILLIN G CRYSTALLINE rhea, Pain
Common: and nausea,
glossitis, sterile inflammation at injection
stomatitis, vomiting.
(Benzylpenicillin) Rare: site,
CNSphlebitis.
toxicity, electrolyte disturbances, hemo-
,QM 500,000 and 1,000,000 units (IM, IV)
Less lytic anemia,Antibiotic-associated
Common: hypersensitivity reactionscolitis,includ-
diar-
PENICILLIN G CRYSTALLINE rhea, glossitis, nausea, stomatitis, vomiting.
(as sodium or potassium salt) ing anaphylaxis; interstitial nephritis, Jarisch-
(Benzylpenicillin) CNS toxicity,
Rare:Herxheimer electrolyte
reaction, disturbances,
neutropenia, hemo-
non-allergic
A beta500,000
,QM lactamase-sensitive
500,000 and 1,000,000
units, penicillin
1,000,000units that
(IM,
units IV)is
and given by
5,000,000 lytic anemia, hypersensitivity
(embolic-toxic) reactions includ-
reaction, thrombocytopenia.
injection
(asvialfor
sodium infections caused
or potassium by streptococci,
salt) ing anaphylaxis; interstitial nephritis, Jarisch-
units (IM, IV) (as Sodium Salt) 'UXJ,QWHUDFWLRQ
neisseria, actinomycetes, spirochetes, and Herxheimer reaction, neutropenia, non-allergic
A betasome
lactamase-sensitive
anaerobes. penicillin that is given by Monitor closely with:
(embolic-toxic) reaction, thrombocytopenia.
127(:injection for infections
Peak plasma caused
concentrations by streptococci,
are reached within 15- Anticoagulants (e.g., warfarin) – penicillins may
neisseria,
30 minutes. actinomycetes, spirochetes, and 'UXJ,QWHUDFWLRQ
enhance their anticoagulant effect.
some anaerobes. Contraceptives,
Monitor closely Oral with: – their efficacy may be re-
,QGLFDWLRQV Neurosyphilis, pneumonia; throat Anticoagulants (e.g., warfarin) – penicillins may
duced by benzylpenicillin.
127(: Peak plasma concentrations are reached within 15-
infections;
30 minutes. otitis media. Avoidenhance their anticoagulant
concomitant use with: effect.
127(: This is also indicated for more serious infections, Contraceptives,
Probenecid – thisOral
may–increase
their efficacy mayconcen-
the serum be re-
,QGLFDWLRQV Neurosyphilis,
such as streptococcal pneumonia;
endocarditis, throat
meningococcal
duced by benzylpenicillin.
meningitis tration of penicillins.
infections;and
otitissepticemia,
media. osteomyelitis, cellulitis,
congenital syphilis, gas gangrene and leptospirosis
127(: This is also indicated for more serious infections,
Tetracycline – this may
Avoid concomitant useantagonize
with: the bactericidal
for
suchwhich
as treatment is instituted
streptococcal in the hospital.
endocarditis, meningococcal
Probenecid – this
effect of may increase the serum concen-
benzylpenicillin.
meningitis and septicemia, osteomyelitis, cellulitis, tration of penicillins.
&RQWUDLQGLFDWLRQV Known hypersensitivity to $GPLQLVWUDWLRQ
Tetracycline – this Reconstituted
may antagonize solutions should be
the bactericidal
congenital syphilis, gas gangrene and leptospirosis
penicillins or anyis component
for which treatment ofhospital.
instituted in the the formula- inspected visually; only clear solutions, free of
effect of benzylpenicillin.
tion; DYRLG intrathecal route. visible particles, should be used. Freshly-
&RQWUDLQGLFDWLRQV Known hypersensitivity to $GPLQLVWUDWLRQ Reconstituted
prepared solutions solutionsorshould
for injection be
infusion
'RVH
penicillins or any component of the formula- inspected visually; only clear solutions, free of
should be used immediately.
tion;(streptococcal)
Bacterial DYRLG intrathecal endocarditis,
route. by slow IV visible particles, should be used. Freshly-
injection or by IV infusion, $'8/7, 5-24 mil- 3UHJQDQF\&DWHJRU\
prepared solutions B for injection or infusion
'RVH
lion units/day divided every 4-6 hours; ,1 should be used immediately.
Bacterial
)$17 (streptococcal)
and &+,/' endocarditis,
<45 kg,by 250,000
slow IV
injection or by
units/kg/day divided every 4 $'8/7,
IV infusion, hours. 5-24 mil- 3UHJQDQF\&DWHJRU\ B
lion units/day
Mild-to-moderate divideddue
infections every 4-6 hours;
to sensitive ,1
organ- PHENOXYMETHYLPENICILLIN
)$17by IM
isms, &+,/'
andinjection, <45 IV kg,
by slow 250,000
injection or by (Penicillin V)
units/kg/day
IV divided every
infusion, $'8/7, 2-24 4million
hours.units/day in
2UDO250 PHENOXYMETHYLPENICILLIN
mg and 500 mg tablet/capsule
Mild-to-moderate infections
4-6 divided doses, withdue to sensitive
higher organ-
doses in severe (as potassiumV)
(Penicillin salt)
isms, by IM injection,
infections; &+,/', IV injection or by
by slow 100,000-400,000
125 mg/5 mL granules/powder for syrup/
IV infusion, $'8/7,
units/kg/day 2-24 million
in 4-6 divided dosesunits/day
(maximum in 2UDO250suspension,
mg and 50060mg mLtablet/capsule
(as potassium salt)
4-6 divided
dose, doses, units/day);
24 million with higher 1(21$7(
doses in severe 1-4 250(as potassium
mg/5 salt)
mL granules/powder for syrup/
infections;
weeks, &+,/',
50,000 units/kg/day 100,000-400,000
in 3 divided dos- 125suspension,
mg/5 mL granules/powder for syrup/
60 mL (as potassium salt)
units/kg/day
es; 1(21$7( in <14-6 week,
divided50,000
dosesunits/kg/day
(maximum suspension,
50,000 units/mL60 mL (as potassium
granules/powder for salt)
drops
dose,
in doses. units/day); 1(21$7( 1-4
24 million
2 divided 250(syrup/suspension),
mg/5 mL granules/powder
30 mL (asforpotassium
syrup/
weeks, 50,000
Neurosyphilis, units/kg/day
by IV injection, in 3 18-24
$'8/7, divided dos-
million suspension, 60 mL (as potassium salt)
salt)
es; 1(21$7(
units/day for 10-14 week, 50,000 units/kg/day
<1 days. 50,000 units/mL granules/powder for drops
in 2 divided doses.
5(&2167,787,21 $1' $'0,1,675$7,21. According to A beta lactamase-sensitive
(syrup/suspension),penicillin
30 mL (as having a simi-
potassium
Neurosyphilis,
manufacturer’s
by IVdirections.
injection, IV$'8/7, 18-24 million
route is preferred for ne- lar salt)
antimicrobial action and spectrum of activi-
onates andfor
units/day infants;
10-14 doses
days.over 1.2 g should be given ty with Penicillin G crystalline; but is less ac-
by the IV route$1'
5(&2167,787,21 only. $'0,1,675$7,21. According to A betativelactamase-sensitive penicillin having a simi-
and is suitable for oral administration.
manufacturer’s directions. IV route is preferred for ne- lar antimicrobial action and spectrum of activi-
'RVH$GMXVWPHQW
onates and infants; doses over 1.2 g should be given ,QGLFDWLRQV Streptococcal
ty with Penicillin pharyngitis;
G crystalline; but is cellulitis;
less ac-
Renalby Impairment:
the IV route only. mouth
tive andinfections;
is suitableS.
forpyogenes tonsillitis; sec-
oral administration.
'RVH$GMXVWPHQW ondary and primary prophylaxis of rheumatic
tion is warranted; for severe impairment, the ,QGLFDWLRQV
Renalpatient fever. Streptococcal pharyngitis; cellulitis;
Impairment:
mouth infections; S. pyogenes tonsillitis; sec-
&RQWUDLQGLFDWLRQV
ondary and primary Known hypersensitivity
prophylaxis of rheumatic to
3UHFDXWLRQV
tion is warranted; for severe impairment, the penicillins
fever. or any component of the formula-
History of allergy
patient shouldto be
penicillins;
referred torenal failure (maxi-
a specialist. tion; serious infections; infectious mononucle-
mum, 6 g daily; neurotoxicity – high doses &RQWUDLQGLFDWLRQV
3UHFDXWLRQV osis; should not Knownbe used hypersensitivity
for meningococcal to
may cause cerebral irritation, convulsions, or penicillins or any component of the formula-
History of allergy to penicillins; and gonococcal infections.
coma); sodium restriction, renal
heart failure
failure(maxi-
(con- tion; serious infections; infectious mononucle-
mum, approximately
tains 6 g daily; neurotoxicity
78 mg Na– per high1.2doses
g); 'RVHosis; should not be used for meningococcal
false-positive
may cause cerebralurinary irritation,
glucose (if tested for re-
convulsions, or Infections due to sensitive
and gonococcal organisms, by mouth,
infections.
ducing sodium restriction, heart failure (con-
coma); substances). $'8/7, 500 mg every 6 hours increased up
Pregnancy
tains (not known to be78harmful),
approximately mg Nabreastfeeding
per 1.2 g); 'RVHto 1 g every 6 hours in severe infections;
false-positive
(trace amounts urinary
foundglucose
in milk;(if safe
testedin for re-
usual Infections
&+,/' due6-12
to sensitive
years, 250 organisms,
mg everyby6 mouth,hours;
ducing substances). $'8/7, 500 mg every 6 hours increased up
Pregnancy (not known to be harmful), breastfeeding 49
to 1 g every 6 hours in severe infections;
(trace amounts found in milk; safe in usual &+,/' 6-12 years, 250 mg every 6 hours;
49
PNF new 75 new .pdf 1 1/8/15 2:25 PM
&+,/' 1-5 years, 125 mg every 6 hours; ANTI-H. PYLORI INFECTION IN

&+,/' up to 1 year, 62.5 mg every 6 hours. PEPTIC ULCER DISEASE
Presumed S. pyogenes tonsillitis or pharyngitis, by
mouth, $'8/7 and &+,/' >10 years, 500 Helicobacter pylori treatment should be preceded by
mg twice daily for 10 days; &+,/' <10 years, H. pylori diagnostic testing. Eradication treat-
250 mg twice daily for 10 days. ment includes the standard triple regimen re-
Primary prophylaxis of rheumatic fever, by mouth, flected on Table A. Antibiotics should not be
$'8/7, 500 mg 2-3 times daily for 10 days; used singly (i.e., should use 2-3 antibiotic
&+,/', 250 mg 2-3 times daily for 10 days. combination) because of risk of emergence of
Secondary prophylaxis of rheumatic fever, by drug resistance.
mouth, $'8/7, 500 mg twice daily; &+,/' 1-
5 years, 125 mg twice daily; &+,/' 6-12
years, 250 mg twice daily.

'RVH$GMXVWPHQWV AMOXICILLIN
Renal and Hepatic Impairment:
For mild-to-moderate impairment, dose reduction, or 2UDO250 mg and 500 mg capsule (as trihydrate)
extension of dose interval may be warranted; 100 mg/mL granules/powder for drops (sus-
for severe impairment, the patient should be pension), 10 mL (as trihydrate)
referred to a specialist. 125 mg/5 mL and 250 mg/5 mL granules/
powder for suspension, 60 mL (as trihy-
3UHFDXWLRQV drate)
History of allergy to penicillins; renal and hepatic
impairment; pregnancy (not known to be A penicillinase-susceptible aminopenicillin having
harmful); breastfeeding (trace amounts in extended spectrum of activity; oral absorption
milk, but safe in usual dosage; monitor infant is not impaired by food, and is more rapidly
regularly). and completely absorbed, with higher bioa-
vailability and less GI irritation than ampicillin.
Common: Black hairy tongue, diarrhea, epigastric ,QGLFDWLRQEradication of H. pylori.
distress, nausea, vomiting. &RQWUDLQGLFDWLRQ Known hypersensitivity to peni-
Less Common: Fever. cillins, or any component of the formulation.
Rare: Hemolytic anemia, hypersensitivity reactions
including anaphylaxis; leukopenia, interstitial 'RVH
nephritis, seizure, thrombocytopenia. Eradication of H. pylori, by mouth, $'8/7, 1 g
twice daily for 7 days with clarithromycin (500
'UXJ,QWHUDFWLRQ mg twice daily), inorcombination treatment
with levofloxacin (500 mg
Monitor closely with: once Table
(see daily).A).
Anticoagulants (e.g., warfarin) – penicillins may
enhance their anticoagulant effect. See under Antimicrobial (Oral and Parenteral) for
Contraceptives, Oral – their efficacy may be re- other information.
duced by phenoxymethylpenicillin.
Probenecid – this may increase the serum concen-
tration of penicillins. CLARITHROMYCIN
Tetracycline – this may antagonize the bactericidal
effect of phenoxymethylpenicillin. 2UDO250 mg and 500 mg base tablet
500 mg MR tablet
$GPLQLVWUDWLRQ Should be taken on an empty
125 mg/5 mL granules/powder for suspension,
stomach, and at least 30 minutes before, or 2
60 mL
hours after, food.
An erythromycin-derived, macrolide antibiotic, which
3UHJQDQF\&DWHJRU\ B can be used in regimens for H. pylori eradica-
tion, and in patients with H. pylori-associated
ulcers, or gastroduodenitis.
,QGLFDWLRQV Anti-Helicobacter pylori; for gastric
ulcer and duodenal ulcer relapse (in conjunc-
tion with other medications).
&RQWUDLQGLFDWLRQV Known hypersensitivity to
clarithromycin or any component of the formu-
lation; severe hepatic failure; hypokalemia;
patients with history of QT prolongation or
cardiac arrhythmias.
'RVH
Eradication of H. pylori, by mouth, $'8/7, 500 mg
twice daily for 7 days in a combination treat-
ment (see Table A).
50
PNF new 76 new .pdf 1 1/8/15 2:29 PM
See under Antimicrobial (Oral and Parenteral) for 50 mg twice a week and, 100 mg once a
other information. month); continue treatment for 12 months.
Type 2 lepra reactions, by mouth, $'8/7 and
7DEOH$. Standard triple
triple H. pylori eradication regimens
&+,/', 200-300 mg daily in 2 or 3 divided
Regimen Dosage Duration doses for a maximum of 3 months; 4-6 weeks
If non-Penicillin allergic: treatment may be required before any effect is
Omeprazole Standard dose seen.
Clarithromycin 500 mg twice a day 10-14
Amoxicillin 1 g twice a day days 'RVH$GMXVWPHQWV
If Penicillin allergic Renal DQGHepatic Impairment:
Omeprazole Standard dose Use drug with caution for mild-to-moderate impair-
Metronidazole 500 mg thrice a day 10-14 ment; for severe impairment, the patient
Clarithromycin 500 mg twice a day days should be referred to a specialist.
3UHFDXWLRQV
Patients with pre-existing GI symptoms and prob-
METRONIDAZOLE lems (reduce the dose, increase the dose in-
terval or discontinue if symptoms develop dur-
2UDO 250 mg and 500 mg base tablet ing treatment); avoid use if abdominal pain
125 mg base/5 mL (200 mg/5 mL as benzo- and diarrhea persist; renal impairment; hepat-
ate) suspension, 60 mL ic impairment; may discolor soft contact
lenses; avoid treatment with daily doses ex-
A nitroimidazole, antiprotozoal drug, which can be
ceeding 100 mg.
used in regimens for H. pylori eradication, and
Pregnancy (use with caution during first trimester);
in patients with H. pylori-associated ulcers, or
breastfeeding (crosses placental barrier and
gastroduodenitis.
excreted in breast milk; can cause reversible
,QGLFDWLRQV Eradication of H. pylori. skin discoloration in nursing infant).

&RQWUDLQGLFDWLRQV Known hypersensitivity to $GYHUVH'UXJ5HDFWLRQV

metronidazole or any component of the formu- Common: Abdominal pain, conjunctival discolora-
lation; chronic alcohol dependence. tion, diarrhea, dryness of skin, eye irritation,
ichthyosis, itch, nausea, pink to brownish-
'RVH black discoloration of skin, rash, red-brown
Eradication of H. pylori, by mouth, $'8/7, 500 mg coloration of body fluids, vomiting.
three times a day (in combination with other Less Common: Constipation, dizziness, drowsi-
drugs).(see Table A). ness, eosinophilic enteritis, GI bleeding,
See under Antimicrobial (Oral and Parenteral) for splenic infarction, taste disturbance.
other information. Rare: Enteropathy (due to the deposition of clo-
fazimine crystals in the GI mucosa and lymph
nodes), phototoxicity.
'UXJ,QWHUDFWLRQV
27+(5$17,%$&7(5,$/6 Monitor closely with:
Isoniazid – this increases the plasma and urinary
ANTI-LEPROSY concentration of clofazimine; decreases its
skin concentration.
Rifampicin – its rate of absorption may be de-
creased by clofazimine, possibly increasing
CLOFAZIMINE the time to peak plasma level.
2UDO 50 mg and 100 mg capsule Dapsone – this may reduce the anti-inflammatory
effect of clofazimine for Lepra type 2 reac-
A phenazine dye, which preferentially binds to tions.
mycobacterial DNA at the guanine base to in-
hibit its growth; given for sulfone-resistant lep- $GPLQLVWUDWLRQ Medicines used in the treatment of
rosy. leprosy should always be used in combination
(essential to prevent the emergence of re-
,QGLFDWLRQV Multibacillary leprosy; type 2 lepra sistance); Clofazimine is best absorbed when
reactions (Erythema Nodosum Leprosum). given right after a meal.
&RQWUDLQGLFDWLRQ Known hypersensitivity to clo- 3UHJQDQF\&DWHJRU\ C
fazimine or any component of the formulation.
'RVH
Multibacillary leprosy (in combination with dapsone
and rifampicin), by mouth, $'8/7, 50 mg
once daily and 300 mg once a month; &+,/'
10-14 years, 50 mg on alternate days, and
150 mg once a month; &+,/' <10 years, re-
quires appropriate dosage adjustments (e.g.,
51
BLOOD DISORDERS. On long-term treatment, patients and
their caregivers should be told how to recognize blood
DAPSONE disorders, and advised to seek immediate medical at-
tention if symptoms, such as fever, sore throat, rash,
Oral: 100 mg tablet mouth ulcers, purpura, bruising, or bleeding develop.
A sulfonamide with a broad spectrum of activity Adverse Drug Reactions:
against many bacteria, but is mainly used for Common: Asymptomatic methemoglobinemia, GI
its antileprosy properties of which it is bacteri- symptoms, hemolytic anemia (occurs in most
ostatic; competitively inhibits paraaminoben- patients taking more than 200 mg daily); rash
zoic acid and folic acid synthesis. (in HIV patients).
Indications: Paucibacillary and multibacillary lepro- Less Common: Allergy, anorexia, fever, headache,
insomnia, nausea, nervousness, vomiting.
sy; dermatitis herpetiformis.
Rare: Agranulocytosis, albuminuria, aplastic ane-
Contraindications: Known hypersensitivity to mia, blurred vision, Dapsone syndrome (re-
dapsone, sulfonamides, and sulfones, or any sembling mononucleosis), hepatitis, Jarisch-
component of the formulation; severe anemia; Herxheimer reactions, neutropenia, paresthe-
porphyria. sia, peripheral neuropathy (with doses more
than 200 mg daily); psychosis, severe skin re-
Dose:
actions (e.g., exfoliative dermatitis).
Dermatitis herpetiformis, by mouth, ADULT, start at
50 mg daily, increase to 300 mg daily (or Drug Interactions:
higher to achieve full control). Monitor closely with:
NOTE: reduce dosage to minimum level as soon as Cotrimoxazole – plasma concentration of both
possible. dapsone and cotrimoxazole may increase with
Multibacillary leprosy (in combination with rifampicin concomitant use.
and clofazimine), by mouth, continued for 12 Rifampicin – this may reduce plasma dapsone
months, ADULT, 100 mg daily; CHILD 10-14 concentration.
years, 50 mg daily; CHILD <10 years, 50 mg Avoid concomitant use with:
every other day. Antimalarial agents (chloroquine and/or primaquine)
Paucibacillary leprosy (in combination with rifampic- – these may enhance the toxic effect; con-
in), by mouth, continued for 6 months, comitant use of these drugs with dapsone
ADULT, 100 mg daily; CHILD 10-14 years, 50 may increase the risk of hemolytic reactions.
mg daily; CHILD <10 years, 50 mg every oth- Clofazimine – its anti-inflammatory effect for Lepra
er day. type 2 reactions may be reduced by dapsone.
Dose Adjustments: Administration: This may be administered with
Renal and Hepatic Impairment: meals if GI upset occurs; do not administer
Use drug with caution for mild to moderate impair- with antacids, alkaline foods, or drugs.
ment; for severe impairment, the patient NOTE: Stop dapsone if a serious skin reaction or muscle
should be referred to a specialist. weakness occurs.
Precautions: Pregnancy Category: C

Sulfonamide allergy (may predispose to dapsone
allergy; begin with low dose of dapsone and
monitor closely for adverse effects); cardio-
pulmonary disease or HIV and PCP (tolerate RIFAMPICIN
hemolytic anemia and methemoglobinemia
poorly); anemia (treat severe anemia before Oral: 150 mg, 300 mg, 450 mg and 600 mg tablet/
the commencement of therapy and monitor capsule
blood counts during treatment; dapsone caus- 100 mg/5 mL suspension, 30 mL, 60 mL and
es hemolytic anemia and methemoglo- 120 mL
binemia); susceptibility to hemolysis, including 200 mg/5 mL suspension, 30 mL, 60 mL and
G6PD deficiency, or in patients receiving 120 mL
drugs capable of inducing hemolysis (includ-
ing breastfeeding affected infants); hemoglo- A rifamycin-derived bactericidal agent active that is
bin M deficiency; methemoglobin reductase against gram-positive and gram-negative coc-
deficiency; in patients with hepatic or renal ci, some enteric bacteria, mycobacteria and
disease; dermatologic reactions (serious reac- chlamydia.
tions are rare, but potentially occurring); pe- Indication: Leprosy (paucibacillary and multibacil-
ripheral neuropathy (motor loss and muscle lary).
weakness have been reported with use); pro-
longed use may result in fungal or bacterial Contraindications: See under Antituberculosis.
superinfection. Dose:
Pregnancy (supplementation with folic acid may be Multibacillary leprosy (in combination with dapsone
necessary if use is warranted; possible risk of and clofazimine), by mouth, ADULT, 600 mg
hyperbilirubinemia in neonates); breastfeeding once a month under supervision; CHILD 10-
(avoid use; dapsone is excreted in substantial 14 years, 450 mg once a month under super-
amounts in breast milk). vision; CHILD <10 years, 10 mg/kg/dose
52
once a month for 12 months under supervi- NOTE: Patients should report visual disturbances immedi-
sion; continue treatment for 12 months. ately and discontinue treatment; children who are in-
capable of reporting symptomatic visual changes ac-
Paucibacillary leprosy (in combination with dap-
curately should be given alternative therapy, as
sone), by mouth, ADULT, 600 mg once a should, if possible, any patient who cannot under-
month; CHILD 10-14 years, 450 mg once a stand warnings about visual adverse effects.
month; CHILD <10 years, 10 mg/kg/dose
once a month for 6 months; continue treat- Adverse Drug Reactions:
ment for 6 months. Common: Retrobulbar neuritis (resulting in loss of
visual acuity and red-green color blindness).
See under Antituberculosis for other information. Less Common: Abdominal pain, anorexia, confu-
sion, disorientation, hallucinations, headache,
malaise, nausea, vomiting.
ANTITUBERCULOSIS Rare: Acute gout, hypersensitivity reaction including
anaphylaxis, hyperuricemia, neutropenia, pe-
For details on the recommended dosing, please refer to the ripheral neuritis, renal failure, thrombocytope-
National Tuberculosis Control Program Manual of Proce- nia.
dures, 5th Edition, 2014.
Drug Interaction:
SINGLE DOSE FORMULATIONS Monitor closely with:
Thiazide diuretics – serum uric acid levels may be
elevated.
ETHAMBUTOL Aluminum salts – may delay and reduce the absorp-
tion of ethambutol.
Oral: 200 mg and 400 mg tablet (as HCl)
A water-soluble, heat-stable, bacteriostatic agent Administration: Tablets should be taken with food.
used in combination with other drugs as first- Pregnancy Category: C
line agents for the treatment of tuberculosis.
Indication: Tuberculosis (especially in cases of
allergy to a fixed-dose combination where a
drug is introduced separately, or in the pres- ISONIAZID
ence of renal or hepatic impairment).
Oral: 100 mg, 300 mg and 400 mg tablet
Contraindications: Known hypersensitivity to 200 mg/5 mL syrup, 60 mL and 120 mL
ethambutol or any component of the formula-
tion; optic neuritis; children <6 years (unable A hydrazide of isonicotinic acid, which is a bacteri-
to report symptomatic visual disturbances). cidal agent used in combination with other
drugs as first-line agents for treating tubercu-
Dose: losis.
NOTE: Doses may need adjustment if significant weight gain
occurs during treatment. Use doses below for the first Indications: Tuberculosis (especially in cases of
2 months of the 6-month multidrug regimen). allergy to a fixed-dose combination where a
Tuberculosis, by mouth, ADULT, 15 mg/kg (range: drug is introduced separately, or in the pres-
15-20 mg/kg) daily, not to exceed 1.2 g daily; ence of renal or hepatic impairment).
CHILD, 20 mg/kg (range: 15-25 mg/kg) daily, NOTE: Preventive therapy for specific situations: close
not to exceed 1.2 g daily. Refer to the Tables family contacts of open/active tuberculosis cases es-
in the section on Recommended Treatment pecially in those <5 years; for latent TB infection; for
Regimen for Tuberculosis. the prevention of recurrence of infection in patients at
risk of reactivation.
Dose Adjustment:
Renal Impairment: Contraindications: Known hypersensitivity to
For adult patients with creatinine clearance <30 isoniazid or any component of the formulation;
mL/minute or for adult patients receiving he- drug-induced hepatic disease.
modialysis: 15-25 mg/kg per dose three times Dose:
per week (not daily). Refer to the Tables in Tuberculosis, treatment, by mouth, ADULT, 5 mg/
the section on Recommended Treatment Reg- kg (range: 4-6 mg/kg) daily, not to exceed 400
imen for Tuberculosis. mg daily; CHILD, 10 mg/kg (range: 10-15
Precautions: mg/kg) daily, not to exceed 300 mg daily. Re-
Ocular examination is recommended before, and fer to the Tables in the section on Recom-
during, treatment; warn patients to report vis- mended Treatment Regimen for Tuberculosis.
NOTE: Patients at risk of developing peripheral neuropathy
ual changes; elderly; young children; further as a result malnutrition, alcoholism or diabetes melli-
deterioration in vision may occur where there tus should additionally receive pyridoxine, 10 mg
are visual defects (e.g., diabetic retinopathy, daily. Pregnant and patients with renal failure should
cataract); renal impairment (monitor plasma also receive pyridoxine while on isoniazid therapy.
ethambutol concentration); gout (acute attack
Dose Adjustment:
may occur).
Renal Impairment:
For adult patients with creatinine clearance <30
(amount too small to be harmful).
mL/minute or for adult patients receiving he-
53
modialysis: not to exceed 300 mg once daily, Phenytoin – its concentration is increased by isoni-
or 900 mg three times per week. Prophylactic azid, possibly increasing risk of toxicity (de-
pyridoxine recommended. Refer to the Tables crease dose as required).
in the section on Recommended Treatment Rifampicin – increased risk of hepatotoxicity.
Regimen for Tuberculosis. Avoid concomitant use with:
Antacids (e.g., aluminum or magnesium hydroxide)
Precautions: – these reduce the absorption of isoniazid.
WARNING: Severe and sometimes fatal hepatitis may be Diazepam – its metabolism may be inhibited by
associated with isoniazid therapy which is age-
isoniazid.
related. Very high doses can induce CNS adverse ef-
fects (e.g., seizures, ataxia, stupor, psychosis). Ketoconazole – its metabolism may be increased by
isoniazid, thus decreasing its antifungal effect.
Malnutrition; chronic alcohol dependence; diabetes
mellitus and HIV infection (risk of peripheral Administration: Absorbed best if taken on an
neuritis); elderly patients; hepatic impairment empty stomach (1 hour before, or 2 hours af-
(increased risk of hepatotoxicity, monitor liver ter, a meal).
function regularly, and frequently in the first 2 Pregnancy Category: C
months); renal impairment (risk of ototoxicity
and peripheral neuropathy); epilepsy (isonia-
zid may cause seizures; ensure adequate
control); slow acetylator status (increased risk PYRAZINAMIDE
of adverse effects); history of psychosis; por-
phyria. Oral: 500 mg tablet
250 mg/5 mL suspension, 60 and 120 mL
(monitor infant for possible toxicity; theoretical
500 mg/5 mL suspension
risk of convulsions and neuropathy);
LIVER DISORDERS. Patients or their caregivers should be A nicotinamide-related bactericidal agent, which is
told how to recognize signs of liver disorder, and ad- used in combination with other drugs as first-
vised to discontinue treatment and seek immediate
line agents for treating tuberculosis.
medical attention if symptoms such as nausea, vomit-
ing, malaise or jaundice develop. Indications: Tuberculosis (especially in cases of
Adverse Drug Reactions: allergy to a fixed-dose combination where a
Common: Acne, fever, GI disorders (e.g., nausea, drug is introduced separately, or in the pres-
vomiting, diarrhea), hepatitis, increased ami- ence of renal or hepatic impairment); active
notransferases, raised antinuclear antibodies, against bacteria within macrophages.
NOTE: Bactericidal against M. tuberculosis in acidic pH.
rash, reduced alertness, skin eruptions, tired-
Activity declines with time (pH increases as inflamma-
ness. tion decreases).
Less Common: Atrophy, dryness of mouth, optic
neuritis, memory impairment, peripheral neuri- Contraindications: Known hypersensitivity to
tis, seizures, toxic encephalopathy, toxic psy- pyrazinamide or any component of the formu-
chosis. lation; severe hepatic impairment; porphyria;
Rare: Agranulocytosis, amenorrhea, aplastic ane- acute gout.
mia, arthritic symptoms, convulsions, difficulty Dose:
with micturition, gynecomastia, hemolytic Tuberculosis, by mouth, ADULT, 25 mg/kg (range:
anemia, hyperglycemia, hypersensitivity reac-
20-30 mg/kg) daily, not to exceed 2 g daily;
tions, lupus-like syndrome, pancreatitis, pella- CHILD, 30 mg/kg (range: 20-40 mg/kg) daily,
gra, pure red cell aplasia, thrombocytopenia,
not to exceed 2 g daily. Refer to the Tables in
urinary retention.
the section on Recommended Treatment Reg-
Drug Interactions: imen for Tuberculosis.
Monitor closely with: Dose Adjustments:
Carbamazepine – its metabolism is inhibited by
Renal Impairment:
isoniazid, thus increasing its concentration
For adult patients with creatinine clearance <30
and risk of toxicity (decrease dose if neces-
mL/minute or for adult patients receiving he-
sary).
modialysis: 25-35 mg/kg per dose three times
Drugs increasing blood glucose concentration (e.g.,
per week (not daily). Monitor for gout. Refer to
glucocorticoids, antipsychotics, calcineurin in-
the Tables in the section on Recommended
hibitors, and high-dose thiazide diuretics) –
Treatment Regimen for Tuberculosis.
their activity may be affected by isoniazid
(isoniazid can decrease blood glucose con- Precautions:
centration). Acute gout (it inhibits the renal excretion of urate
Oral Contraceptives – few cases of contraceptive and raises uric acid concentration); hepatic
failures reported. impairment (monitor hepatic function: idiosyn-
Paracetamol – potential toxicity of Paracetamol cratic hepatotoxicity more common); renal im-
when used with isoniazid (more studies need- pairment; diabetes mellitus (monitor blood
ed). glucose; may change suddenly).
54
Pregnancy (use it only if potential benefits outweigh Leprosy, see under Anti-Leprosy Medicines.
risks); and breastfeeding (amount too small to
Dose Adjustments:
be harmful).
LIVER DISORDERS. Patients or their caregivers should be Renal Impairment:
told how to recognize signs of liver disorder, and ad- Must not exceed recommended maximum dose.
vised to discontinue treatment and seek immediate Refer to the Tables in the section on Recom-
medical attention if symptoms, such as persistent mended Treatment Regimen for Tuberculosis.
nausea, vomiting, malaise or jaundice, develop. Hepatic Impairment:
Adverse Drug Reactions: Dose reduction is warranted (maximum, 8
Common: Hyperuricemia, nausea, polyarthralgia, mg/kg/day).
vomiting. Precautions:
Less Common: Allergic reactions, anorexia, diar- Monitor liver function and blood count in liver disor-
rhea, fever, flushing, hepatotoxicity (including ders, alcohol dependency, the elderly, and in
hepatomegaly, jaundice, liver tenderness, liver prolonged therapy; daily alcohol intake (may
failure, malaise, and splenomegaly), itch, increase the risk of drug-induced hepatotoxici-
rash, urticaria. ty); renal impairment; hepatic impairment (im-
Rare: Acute gout, acute porphyric crisis, dysuria, paired elimination; monitor liver function); por-
pellagra, photosensitivity, sideroblastic ane- phyria; it discolors soft lenses.
mia, thrombocytopenia. Pregnancy (first trimester: very high doses are
Drug Interactions: teratogenic in animal studies; third trimester:
Monitor closely with: risk of neonatal bleeding may be increased);
Anti-gout drugs (e.g., allopurinol, colchicine) – pyra- and breastfeeding (amount too small to be
zinamide may increase serum uric acid con- harmful; may cause loose bowel actions in the
centration and decrease the efficacy of anti- baby).
IMPORTANT: Advise patient on hormonal contraceptives to
gout therapy.
use additional means (effectiveness is reduced); al-
Rifampicin – pyrazinamide may enhance its hepato- ternative family planning advice should be offered.
toxic effects (severe, or even fatal, liver injury LIVER DISORDERS. Patients or their caregivers should be
has been reported in patients using these two told how to recognize signs of liver disorders and ad-
drugs as a 2-month treatment regimen for la- vised to discontinue treatment and seek immediate
tent TB infection). medical attention if symptoms such as persistent nau-
sea, vomiting, malaise, or jaundice develop.
Administration: Should be taken with food. NOTE: Resumption of rifampicin treatment after a long
interval may cause serious immunological reactions,
Pregnancy Category: C resulting in renal impairment, hemolysis, or thrombo-
cytopenia – discontinue permanently if serious ad-
verse effects occur.
RIFAMPICIN Common: Anorexia, cramps, diarrhea, epigastric
distress, flatulence, increased hepatic en-
Oral: 150 mg, 300 mg, 450 mg and 600 mg tablet/ zymes, nausea, orange-red coloration of body
capsule fluids (urine, tears, saliva and sputum), pan-
100 mg/5 mL suspension, 30 mL, 60 mL and creatitis, rash, staining of soft contact lenses,
120 mL vomiting.
200 mg/5 mL suspension, 30 mL, 60 mL and Less Common: Ataxia, behavioral changes, dizzi-
120 mL ness, edema, fatigue, flu-like syndrome (char-
acterized by fever, chills, myalgia), flushing,
A rifamycin-derived bactericidal agent active that is headache, heartburn, menstrual disturbances,
against gram-positive and gram-negative coc- numbness.
ci, some enteric bacteria, mycobacteria and
Rare: Acute renal failure, cerebral hemorrhage, C.
chlamydia, and is used in combination with
difficile-associated disease, collapse, exfolia-
other drugs as first-line agents for treating tu-
tive dermatitis, hemolytic anemia, hepatitis,
berculosis.
jaundice, leukopenia, myopathy, pemphigoid
Indications: Tuberculosis (especially in cases of reactions, psychosis, respiratory symptom,
allergy to a fixed-dose combination where a shock, thrombocytopenic purpura, toxic epi-
drug is introduced separately, or in the pres- dermal necrolysis.
ence of renal or hepatic impairment); leprosy. Drug Interactions:
NOTE: Enzyme induction (See Appendix): accelerates the
metabolism of various substrates, thus possibly de-
rifamycins, or any component of the formula- creasing their effects.
tion; jaundice. Monitor closely with:
Dose: ACE inhibitors (e.g., captopril, enalapril) – isolated
Tuberculosis, by mouth, ADULT, 10 mg/kg (range: reports of interaction with rifampicin but minor
8-12 mg/kg) daily, not to exceed 600 mg daily; clinical significance.
CHILD, 15 mg/kg (range: 10-20 mg/kg) daily, Analgesics – rifampicin increases clearance of
not to exceed 600 mg daily. Refer to the Ta- paracetamol, decreases levels of diclofenac
bles in the section on Recommended Treat- and opioids.
ment Regimen for Tuberculosis.
55
Anti-retroviral agents – levels of efavirenz, ritonavir turbances and impaired hearing); myasthenia
and nevirapine are decreased; clearance of gravis (due to neuromuscular blocking activi-
zidovudine is increased. ty).
Anti-epileptics – levels of phenytoin and valproic
acid are reduced. Dose:
Azoles (e.g., ketoconazole) – their metabolism is Tuberculosis, by deep IM injection, ADULT, 15
increased by rifampicin, thus decreasing their mg/kg (range: 12-18 mg/kg) daily, not to ex-
antifungal effect. ceed 1 g daily (patients over 60 years, or
Beta blockers (e.g., metoprolol, propranolol) – their those weighing <50 kg may not tolerate doses
metabolism is increased by rifampicin, thus above 500-750 mg daily); CHILD, 30 mg/kg
decreasing their concentration and reducing (range: 20-40 mg/kg) daily, not to exceed 1 g
the clinical effects. daily. Refer to the Tables in the section on
Calcium channel blockers (e.g., Amlodipine) – their Recommended Treatment Regimen for Tu-
levels are markedly reduced by rifampicin. berculosis.
Corticosteroids (e.g., hydrocortisone, prednisone manufacturer’s directions.
and prednisolone) – their metabolism is in-
creased by rifampicin, possibly reducing their Dose Adjustment:
activity. Renal Impairment:
Cotrimoxazole – when used for prophylaxis in a For adult patients with creatinine clearance <30
HIV-positive patient, its concentration and effi- mL/minute or for adult patients receiving he-
cacy may be decreased by rifampicin. modialysis: 12-15 mg/kg per dose two or three
Digoxin – possible reduction in the plasma concen- times per week. Refer to the Tables in the
tration of digoxin, reducing the clinical effects. section on Recommended Treatment Regi-
Doxycycline – possible reduction in the plasma men for Tuberculosis.
concentration of doxycycline, reducing the ef- If possible, streptomycin should be avoided in pa-
fects. tients with renal failure.
Theophylline – its concentration and therapeutic
Precautions:
effects are decreased by rifampicin.
Thyroid hormones (e.g., thyroxine) – rifampicin may WARNING: May cause nephrotoxicity and neurotoxicity.
Avoid concurrent use of nephrotoxic/neurotoxic drugs;
accelerate its metabolism (this may increase may cause neuromuscular blockade and respiratory
thyroxine requirements in a state of hypothy- paralysis, especially when given after anesthesia or
roidism). muscle relaxants.
Antacids (e.g., aluminum and magnesium hydrox- Children (painful injection, avoid use if possible);
ide) – these may reduce the absorption of ri- renal impairment (monitor plasma concentra-
fampicin. tion), infants, and the elderly (adjust dose and
Contraceptives, Oral – accelerated metabolism of monitor renal, auditory, and vestibular func-
estrogens and progestogens, reducing the tion, and plasma streptomycin concentra-
contraceptive effect. tions).
Praziquantel – its metabolism is increased by rifam- Pregnancy (second and third trimester: auditory and
picin, reducing its concentration to ineffective vestibular damage in the fetus; avoid unless
levels. essential; if given, serum-streptomycin con-
centration monitoring is essential), and breast-
Administration: Take dose at least 30 minutes feeding (present in milk; continue breastfeed-
before a meal (absorption is reduced when ing and monitor infant for thrush and diar-
taken with food). rhea).
Pregnancy Category: C Adverse Drug Reactions:
Common: Fever, hearing loss, hypersensitivity
reactions, nausea, rash, sterile abscess and
pain at injection site, vertigo, vomiting.
STREPTOMYCIN Less Common: Albuminuria, high frequency range
hearing impairment, numbness around mouth,
Inj.: 1 g vial (IM) (as sulfate) tinnitus, urinary casts, vestibular damage and
An aminoglycoside antibiotic that is used when an toxicity.
injectable drug is needed or desirable; princi- Rare: Agranulocytosis, anaphylactic shock, aplastic
pally used in patients with severe life- anemia, C. difficile-associated disease, exfoli-
threatening forms of TB, and sensitive gram- ative dermatitis, hemolytic anemia, hypomag-
negative infections. nesemia, nephrotoxicity, paresthesia of the
mouth, tubular necrosis, thrombocytopenia.
Indication: Tuberculosis (especially in cases of
allergy to a fixed-dose combination where a Drug Interactions:
drug is introduced separately, or in the pres- Monitor closely with:
ence of renal or hepatic impairment). Magnesium sulfate – there is additive neuromuscu-
lar blocking effect with aminoglycosides and
Contraindications: Known hypersensitivity to parenteral magnesium sulfate (monitor respir-
streptomycin or any component of the formu- atory function).
lation; hearing disorders (e.g., vestibular dis-
56
Ototoxic and nephrotoxic drugs (e.g., other amino- Dose:
glycoside antibiotics, furosemide, cephalo- Tuberculosis, by mouth, ADULT, refer to the Tables
sporins and vancomycin) – there are inin the section on Recommended Treatment
creased risks of nephrotoxicity and ototoxicity. Regimen for Tuberculosis.
H 1 -receptor blockers – these may mask early signs Dose Adjustments, Precautions, Adverse Drug
of ototoxicity. Reactions, and Drug Interactions: See un-
der Single Dose Formulation: Isoniazid, Ri-
Administration: Solutions should be inspected fampicin and Ethambutol
visually; only clear solutions, free of visible
Administration: Take on an empty stomach with
particles, should be used.
NOTE: Solutions retain their potency for 48 hours after full glass of water.
reconstitution at room temperature, and for up to 14
days when refrigerated.
ISONIAZID + RIFAMPICIN +
FIXED-DOSE COMBINATIONS PYRAZINAMIDE + ETHAMBUTOL
Oral: 75 mg + 150 mg + 400 mg + 275 mg tablet
ISONIAZID + RIFAMPICIN A fixed combination of isoniazid, rifampicin, pyra-

zinamide and ethambutol, which offers ease
Oral: 75 mg + 150 mg tablet of administration and facilitates patient com-
pliance in the treatment of tuberculosis.
A fixed combination of isoniazid and rifampicin,
which is used for treating tuberculosis and Indication: Tuberculosis.
serves as an aid to patient compliance. Contraindications: Combined preparations may
Indication: Tuberculosis. not be suitable for use in children; see under
Single Dose Formulation: Ethambutol, Isonia-
Contraindications: Combined preparations may zid, Pyrazinamide and Rifampicin.
not be suitable for use in children; see under
Single Dose Formulation: Isoniazid and Ri- Dose:
fampicin. Tuberculosis, by mouth, ADULT, refer to the Tables
in the section on Recommended Treatment
Dose: Regimen for Tuberculosis.
Tuberculosis, by mouth, ADULT, refer to the Tables
on Recommended Treatment for Tuberculo- Dose Adjustments:
sis. Renal and Hepatic Impairment:
For severe impairment, dose reduction may be
Dose Adjustments, Precautions, Adverse Drug warranted.
Reactions, and Drug Interactions: See un-
der Single Dose Formulation: Isoniazid and Precautions, Adverse Drug Reactions, and Drug
Rifampicin for other information. Interactions: See under Ethambutol, Isonia-
zid, Pyrazinamide, and Rifampicin.
Administration: Take on an empty stomach with
full glass of water. Administration: Should be taken on an empty
stomach; take 1 hour before, or 2 hours after,
Pregnancy Category: C meals.
ISONIAZID + RIFAMPICIN +
ETHAMBUTOL URINARY ANTISEPTIC
Oral: 75 mg + 150 mg + 275 mg tablet
A fixed combination of isoniazid, rifampicin and NITROFURANTOIN
ethambutol, which offers ease of administra-
tion and facilitates patient compliance in the Oral: 50 mg and 100 mg capsule (as macrocrystals)
treatment of tuberculosis.
Nitrofurantoin is bacteriostatic and bactericidal for
Indication: Tuberculosis. many gram-negative and gram-positive organ-
Contraindications: Combined preparations may isms, but may not affect P. aeruginosa and
not be suitable for use in children; see under many strains of proteus; the macrocrystalline
Single Dose Formulation: Isoniazid, Rifampic- form is absorbed and excreted slowly, and is
in and Ethambutol. better tolerated with lower incidence of GI side
effects.
Indications: Treatment of acute, uncomplicated
cystitis in non-pregnant women; asymptomatic
57
bacteriuria; recurrent urinary tract infection in the elderly, particularly females receiving long-
non-pregnant women (for asymptomatic bac- term prophylaxis for recurrent UTIs, has also
teriuria in pregnancy, urine culture is neces- been associated with an increased risk of he-
sary). patic toxicity and peripheral neuropathy; moni-
tor closely for toxicities during use).
Contraindications: Known hypersensitivity to Pregnancy (when given during the 2nd trimester until
nitrofurantoin or any component of the formu- 32 weeks age of gestation) may cause birth
lation; anuria, oliguria, or significant impair-
defects and complications (see under Guide-
ment of renal function; previous history of cho-
lines on UTI).
lestatic jaundice or hepatic dysfunction asso- NOTE: During long-term treatment, monitor:
ciated with prior nitrofurantoin use; for infants • Pulmonary function
<1 month of age (increased risk of hemolytic • Liver function every month for 3 months, then eve-
anemia); G6PD-deficiency, including breast- ry 3 months, since onset of hepatotoxicity may be
feeding of affected infants (only small insidious
amounts in milk but may be enough to pro- • Renal function since peripheral neuropathy is
more likely to occur if this is impaired
duce hemolysis in G6PD-deficient infants);
• For the development of paresthesia as stopping
pregnancy at term (third trimester: may pro- treatment early can prevent severe neuropathy
duce neonatal hemolysis if used at term); por-
phyria. Adverse Drug Reactions:
Common: Abdominal pain, allergic skin reactions,
Dose: anorexia, diarrhea, headache, nausea, vomit-
Asymptomatic bacteriuria, by mouth, ADULT, in ing.
non-pregnant patients, 100 mg 4 times daily Less Common: Dizziness, drowsiness, vertigo.
for 7-14 days; in pregnant women, 100 mg 4 Rare: Alopecia, anaphylaxis, arthralgia, benign
times daily for 7 days. intracranial hypertension; blood disorders,
Acute uncomplicated cystitis in non-pregnant wom- drug fever, cholestatic jaundice, erythema
en, by mouth, ADULT, 100 mg 4 times daily multiforme, exfoliative dermatitis, hepatotoxici-
for 5 days; in pregnant women, 100 mg 4 ty, lupus-like syndrome, pancreatitis, periph-
times daily for 7 days; CHILD >1 year, 5-7 eral neuropathy, pulmonary reactions, Ste-
mg/kg/day divided in 4 doses (maximum dose, vens-Johnson syndrome.
400 mg/day). See Clinical Practice Guidelines
– Urinary Tract Infection for further infor- Drug Interactions:
mation. NOTE: The bioavailability of nitrofurantoin is usually in-
creased by medicines that reduce gastric emptying
Recurrent urinary tract infection in non-pregnant
time, such as diphenoxylate and atropine.
women, by mouth, ADULT (women), 100 mg
at bedtime for 6-12 months either continuously
Aldosterone-blocking agents (eplerenone and spi-
or as post-coital prophylaxis.
ronolactone) – their hyperkalemic effect may
Dose Adjustments: be enhanced by nitrofurantoin.
Renal Impairment: Sedatives (e.g., alcohol) – their effect may be po-
Avoid use (peripheral neuropathy; ineffective be- tentiated when taken with nitrofurantoin.
cause of inadequate urine concentrations). Avoid concomitant use with:
Hepatic Impairment: Antacids – these reduce absorption of nitrofuranto-
Avoid use (cholestatic jaundice and chronic active in, thus decreasing its clinical effect.
hepatitis have been reported).
Administration: Take with meals or milk to improve
Precautions: absorption and decrease adverse effects
This is not indicated for the treatment of pyelone- (e.g., nausea).
phritis; it is ineffective in alkaline urine.
Pulmonary toxicity and disorders (monitor lung and
liver function on long-term therapy; discontin-
ue use if the lung function deteriorates; acute,
subacute or chronic pulmonary reactions have
ANTI-PARASITICS
been observed); susceptibility to peripheral
neuropathy (rare; risk may be increased in pa- ANTHELMINTICS
tients with anemia, renal impairment, diabe-
tes, vitamin B deficiency, debilitating disease,
or electrolyte disturbance); risk of optic neuri- FOR COMMON ROUND WORM INFECTIONS
tis; hepatic reactions (rare, but severe and
sometimes fatal reactions have been associ-
ated with its use; monitor liver function tests ALBENDAZOLE
periodically); hemolytic anemia; neurological
or allergic disorders; folate deficiency; pro- Oral: 400 mg chewable tablet
longed use may result in fungal or bacterial 200 mg/5 mL suspension, 10 mL, 15 mL, 30
superinfection; urine may be colored yellow or mL and 60 mL
brown.
The elderly (avoid use for long-term suppression A benzimidazole-derived, broad-spectrum, oral
due to potential for pulmonary toxicity; use in anthelmintic, which is used for long-term
58
treatment of tissue helminth infections, includ- signs of hepatic toxicity and blood count
ing hydatid disease and cysticercosis. should be monitored before a longer-term
Indications: Echinococcus multilocularis and E. treatment (twice during each cycle).
granulosus infections prior to surgery or infec- Exclude pregnancy before starting the treatment
tions not amenable to surgery; neurocysticer- (advise patients to use non-hormonal contra-
cosis; nematode infections, including ascaria- ception during and for one month after treat-
sis, capillariasis, enterobiasis, hookworm in- ment); breastfeeding.
fections, strongyloidiasis, trichostrongyliasis, Adverse Drug Reactions:
trichuriasis; filariasis. Common: Abdominal pain, headache, nausea,
Contraindications: Known hypersensitivity to vomiting.
albendazole or any component of the formula- Less Common: Abnormal liver function tests,
tion; pregnancy (first trimester: avoid in nema- diarrhea, dizziness, fever, increased intracra-
tode infections); hepatic cirrhosis; cestode in- nial pressure, meningeal signs, vertigo.
fections due to Taenia solium occurring during Rare: Agranulocytosis, allergic shock (if with cyst
pregnancy; ocular cysticercosis (severe eye leakage), aplastic anemia, bone marrow sup-
damage due to death of parasites may occur). pression, jaundice, convulsions, erythema
Dose:
multiforme, hepatitis, hypersensitivity reac-
Alveolar echinococcosis, by mouth, ADULT, as for
tions, proteinuria, Stevens-Johnson syn-
cystic echinococcosis, but treatment cycles
drome.
may need to be continued for months or
years. Drug Interactions:
Ascariasis, hookworm infections, enterobiasis, and Monitor closely with:
trichostrongyliasis, by mouth, ADULT and Phenobarbital – this may increase the metabolism
CHILD >2 years, 400 mg as a single dose; of albendazole, decreasing its concentration
CHILD 12 months-2 years, 200 mg as a single and possibly its efficacy.
dose. Phenytoin – this may increase the metabolism of
Capillariasis, by mouth, ADULT and CHILD >2 albendazole, decreasing its concentration and
years, 400 mg daily for 10 days. possibly its efficacy.
Cystic echinococcosis, by mouth, ADULT >60 kg, Praziquantel – this may increase plasma concentra-
800 mg daily in 2 divided doses for 28 days tion levels of the active metabolite of albend-
(followed by 14 tablet-free days); ADULT <60 azole.
kg, 15 mg/kg daily in 2 divided doses (maxi-
mum daily dose, 800 mg) for 28 days followed Administration: Taken with food; oral absorption
by 14 tablet-free days; up to 3 courses may be may be increased 4-5 times with fatty meal.
given. Pregnancy Category: C
Filariasis (mass drug administration for individuals
2 yrs old and over living in all established
endemic areas), by mouth, 6 mg/kg body ANTIFILARIALS
weight diethylcarbamazine citrate (DEC) and
400 mg albendazole as single dose given
once annually for at least 5 yrs. ALBENDAZOLE
Filariasis (selective treatment for patients positive for
microfilariae in nocturnal blood examination, 12 Oral: 500 mg chewable tablet
day treatment), by mouth, Day 1: 6 mg/kg body
weight diethylcarbamazine citrate (DEC) in 3 See under Anthelmintic for other information.
divided doses and 400 mg albendazole; Day
2 to Day 12: 6 mg/kg body weight of DEC only,
given in 3 divided doses daily.
DIETHYLCARBAMAZINE
NOTE: Refer to DOH National Filariasis Elimination
Program for more details
Oral: 50 mg tablet (as citrate)
Trichuriasis, by mouth, ADULT and CHILD >2
years, 400 mg as a single dose (for moderate A piperazine-derived, filarial medicine, which ren-
infections) or 400 mg daily for 3 days (for se- ders microfilariae susceptible to destruction by
vere infections); CHILD 12 months-2 years, the host’s defense mechanism through para-
200 mg as a single dose (for moderate infec- site immobilization, normal habitat dislocation
tions) or 200 mg initially, then 100 mg twice and surface membrane alteration.
daily for 3 days (for severe infections). Indications: Prophylaxis and treatment of systemic
Strongyloidiasis, by mouth, ADULT and CHILD >2 lymphatic filariasis and occult filariasis; loiasis;
years, 400 mg once or twice daily for 3 days. nematode infections, particularly, visceral lar-
Dose Adjustment: va migrans.
Hepatic Impairment:
Consider dose reduction during extended treatment. Contraindications: Known hypersensitivity to
diethylcarbamazine or any component of the
Precautions: formulation; pregnancy (delay medication until
Liver disease (patients may be more at risk for after delivery).
adverse effects); liver function tests, clinical
59
PNF new 86 new .pdf 1 1/8/15 2:17 PM
'RVH smaller doses for 2-3 days to avoid potential

Loiasis, treatment, by mouth, $'8/7, 1 mg/kg as a risk of immunological reactions; rigorous hy-
single dose on the first day, doubled on two giene is essential.
successive days, then adjusted to 2-3 mg/kg 3
times daily for a further 18 days. 3UHJQDQF\&DWHJRU\X
Loiasis, prophylaxis, by mouth, $'8/7, 300 mg

weekly for as long as exposure occurs. $17,6&+,672620$
Filariasis (mass drug administration for individuals
2 yrs old and over living in all established PRAZIQUANTEL
endemic areas), by mouth, 6 mg/kg body
weight diethylcarbamazine citrate (DEC) and 2UDO600 mg tablet
400 mg albendazole as single dose given 600 mg/5 mL suspension
once annually for at least 5 yrs.
A quinoline-derived, broad-spectrum anthelmintic,
Filariasis (selective treatment for patients positive for which is effective, as a single dose, in the
microfilariae in nocturnal blood examination, 12 treatment of schistosome infections of all spe-
day treatment), by mouth, Day 1: 6 mg/kg body cies, and other trematode and cestode infec-
weight diethylcarbamazine citrate (DEC) in 3 tions, including cysticercosis.
divided doses and 400 mg albendazole; Day
2 to Day 12: 6 mg/kg body weight of DEC only, ,QGLFDWLRQV Intestinal schistosomiasis; urinary
schistosomiasis; intestinal, liver, and lung
given in 3 divided doses daily, usually after meals.
fluke infections; cestode infections.
127(: Before treatment with diethylcarbamazine citrate
&RQWUDLQGLFDWLRQV Known hypersensitivity to
(DEC), patients should be assessed for co-infection
with Loa loa and Onchocerca
Loa loa Onchocerca volvulus
volvulus because
praziquantel or any component of the formula-
DEC can cause serious reactions in these patients. tion; ocular cysticercosis.

127(: Refer to DOH National Filariasis Elimination

'RVH
Program for more details Intestinal fluke infections, by mouth, $'8/7 and
&+,/' > 4 years, 25 mg/kg as a single dose.
3$7,(17 $'9,&(. Complete the prescribed course as Liver and lung fluke infections, by mouth, $'8/7
directed to minimize allergic reactions to dying para- and &+,/' >4 years, 25 mg/kg 3 times daily
sites. for 2 consecutive days; alternatively, 40 mg/kg
127(: Dexamethasone (to reduce intensity of Mazzotti as a single dose; treatment may need to be
reactions): 0.8 mg/kg/day administer prior to initiating
diethylcarbamazine and maintained for 5 days prior to
extended for several days in paragonimiasis.
gradual withdrawal. ;
Schistosomiasis, by mouth, $'8/7 and &+,/' >4
years, 40-60 mg/kg as a single dose; or in 3
'RVH$GMXVWPHQW divided doses of 20 mg/kg at intervals of 4-6
Renal Impairment: hours.
Consider reducing dose since plasma half-life is 'RVH$GMXVWPHQW
prolonged, and urinary excretion is considera- Hepatic Impairment:
bly reduced. Consider reducing dose due to increased concen-
tration and half-life.
3UHFDXWLRQV

Cardiac disorders; other severe acute diseases 3UHFDXWLRQV
(delay treatment until after recovery); treat- Cardiovascular disease; cerebral cysticercosis (it is
ment should be well supervised since allergic recommended to hospitalize patients for the
reaction is common and
- usually severe (espe- duration of treatment); Ocular cysticercosis
cially in onchocerciasis and loiasis); monitor (severe eye damage due to death of parasites
for eye changes (reactions may modified by may occur); in undiagnosed neurocysticerco-
concomitant steroid administration). sis (seizures may result if praziquantel is used
to treat another systemic infection); Paragon-
$GYHUVH'UXJ5HDFWLRQV imus infections (treatment in hospital as there

Common: Allergic reactions. may be CNS involvement); patients with se-
Less Common: Anorexia, asthmatic attacks, dizzi- vere hepatic disease; areas endemic for cysti-
ness, drowsiness, fever, headache, joint pain, cercosis (possible risk of edematous reaction);
malaise, transient hematuria, urticaria, vomit- reduced liver drug metabolism may result in
ing. higher and longer lasting plasma concentra-
tion of unmetabolized praziquantel.
Rare: Convulsions, exacerbation of lymphedema, Pregnancy (Taenia solium infections should be
transient lymphangitis. treated immediately; benefit of treatment in
'UXJ,QWHUDFWLRQV No information found. schistosomiasis outweighs the risk; if treat-
ment is not considered essential, it should be
$GPLQLVWUDWLRQ Tablets should be taken after delayed until after delivery); breastfeeding
meals; total cumulative dose of 72 mg/kg for (there is low excretion in breast milk; avoid
W. bancrofti infections; best initiated with breastfeeding during, and for 72 hours, after
60
PNF new 86 NEW .pdf 1 1/6/15 5:57 PM
PNF new 86 new.pdf
NEW .pdf 11 1/6/15
1/6/15 7:02
5:57PM
PM
treatment; considered
treatment; considered safe
safe to
to continue
continue breast-
breast- 'RVH
'RVH
feeding during
feeding during treatment
treatment for
for schistosomiasis).
schistosomiasis). Amoebiasis, by
Amoebiasis, by mouth,
mouth, forfor 77 consecutive
consecutive days,days,
6.,//(' 7$6.6. May impair ability to perform skilled
6.,//(' 7$6.6. May impair ability to perform skilled $'8/7, 1.5
$'8/7, 1.5 gg daily
daily in
in 33 divided
divided doses;
doses;
tasks, e.g., operating machinery or driving (warn pa- &+,/', 30-40
30-40 mg/kg/day
mg/kg/day in in 33 divided
divided doses.
doses.
tasks, e.g., operating machinery or driving (warn pa- &+,/',
tient not to operate machinery nor drive during treat-
tient not to operate machinery nor drive during treat- Giardiasis, by
Giardiasis, by mouth, $'8/7, 500
mouth, $'8/7, 500 mg mg twice
twice daily
daily
ment or for 24 hours after treatment).
ment or for 24 hours after treatment). for 5-7
5-7 days; &+,/', 15
days; &+,/', 15 mg/kg/day
mg/kg/day in in 33 divid-
divid-
for
$GYHUVH'UXJ5HDFWLRQV ed doses
ed doses for
for 55 days.
days.
Abdominal pain,
Common: Abdominal
Common: pain, anorexia,
anorexia, appetite
appetite loss,
loss, Urethritis and
Urethritis and vaginitis
vaginitis due
due toto Trichomonas,
Trichomonas, by by
colic, diarrhea,
colic, diarrhea, dizziness,
dizziness, drowsiness,
drowsiness, fever,
fever, :20(1, aa single
mouth, :20(1,
mouth, single 22 gg dose
dose oror 500
500
headache, malaise,
headache, malaise, myalgia,
myalgia, nausea,
nausea, reversi-
reversi- mg/day in
mg/day in 22 divided
divided doses
doses for
for 10
10 days; 0(1,
days; 0(1,
ble rises
ble rises in
in aminotransferases
aminotransferases (hepatic),
(hepatic), som-
som- aa single
single 22 gg dose
dose or
or 500
500 mg/day
mg/day in in 22 divided
divided
nolence, urticaria,
nolence, urticaria, vertigo,
vertigo, vomiting.
vomiting. doses for
doses for 10
10 days.
days.
Arrhythmias, bloody
Rare: Arrhythmias, bloody diarrhea,
diarrhea, hypersensitivity
hypersensitivity
Rare:
reactions (e.g.,
(e.g., fever,
fever, pruritus),
pruritus), rectal
rectal bleed-
bleed- See under
See under Antimicrobial (Oral and
Antimicrobial (Oral and Parenteral) for
Parenteral) for
reactions other information.
information.
ing, seizures.
ing, seizures. other
'UXJ,QWHUDFWLRQV
'UXJ,QWHUDFWLRQV
Monitor closely
with: $17,0$/$5,$/6
$17,0$/$5,$/6
Albendazole –– increased
Albendazole increased plasma
plasma concentration
concentration ofof
active metabolite
active metabolite of of albendazole.
albendazole.
Carbamazepine –– this
Carbamazepine this increases
increases metabolism
metabolism of of ARTEMETHER +
+ LUMEFANTRINE
LUMEFANTRINE
praziquantel, reducing
reducing its its concentration
concentration andand ARTEMETHER
praziquantel,
therapeutic effect
therapeutic effect 2UDO20 mg mg artemether
artemether + + 120
120 mg mg lumefantrine
lumefantrine
Chloroquine –– this
this may
may increase
increase metabolism
metabolism of of 2UDO20
Chloroquine tablet
tablet
praziquantel, reducing its its concentration
concentration andand A fixed-dose,
fixed-dose, antimalarial
antimalarial combination
combination of of an
an oil-
oil-
therapeutic effect.
effect. A
therapeutic soluble, artemisinin
soluble, artemisinin analog
analog andand aa fluorene-
fluorene-
Dexamethasone –– this
Dexamethasone this may
may increase
increase metabolism
metabolism of of derived aryl
aryl alcohol
alcohol that
that is
is used
used for
for uncompli-
uncompli-
concentration andand derived
praziquantel, cated P.
cated P. falciparum malaria.
falciparum malaria.
therapeutic effect.
therapeutic effect.
Phenytoin –– this
this increases
increases metabolism
metabolism of of pra-
pra- ,QGLFDWLRQV For
,QGLFDWLRQV For acute,
acute, uncomplicated
uncomplicated malaria
malaria
Phenytoin
ziquantel, reducing
concentration andand ther-
ther- caused by
caused by P.P. falciparum, alone or
falciparum, alone or with
with other
other
ziquantel,
apeutic effect.
effect. Plasmodium spp., spp., in
in areas
areas with
with significant
significant
apeutic Plasmodium
Avoid concomitant
concomitant use use with:
with: drug resistance.
drug resistance.
Avoid
Strong CYP450
Strong CYP450 inducers
inducers (e.g.,
(e.g., rifampicin)
rifampicin) –– these
these &RQWUDLQGLFDWLRQV Known Known hypersensitivity
hypersensitivity to to
increase metabolism
metabolism of of praziquantel,
reducing &RQWUDLQGLFDWLRQV
increase lumefantrine, halofantrine
halofantrine or or artemether,
artemether, and and
its plasma
plasma concentration
concentration to to ineffective
ineffective levels.
levels. lumefantrine,
its other artemisinin
artemisinin compounds;
compounds; family family history
history ofof
other
$GPLQLVWUDWLRQ Swallow
Swallow itit with
with water,
water, without
without sudden death
sudden death or or congenital
congenital prolongation
prolongation of of
$GPLQLVWUDWLRQ
chewing, to
to lessen
lessen its
its bitter
bitter taste.
taste. QT interval;
QT interval; history
history ofof arrhythmias,
arrhythmias, clinically-
clinically-
chewing,
relevant bradycardia,
relevant bradycardia, or or CHF
CHF accompanied
accompanied by by
3UHJQDQF\&DWHJRU\ B
3UHJQDQF\&DWHJRU\ B reduced leftleft ventricular
ventricular ejection
ejection fraction;
fraction; preg-
preg-
reduced
nancy (QRW
nancy (QRW forfor use
use in in thethe first
first trimester);
trimester);
breastfeeding (discontinue
breastfeeding (discontinue breastfeeding
breastfeeding dur- dur-
ANTIPROTOZOAL
ANTIPROTOZOAL ing and
and forfor 11 week
week after
after stopping
stopping treatment;
treatment;
ing
present in
present in milk
milk inin animal
animal studies).
studies).
$17,$0(%,$6,6$17,*,$5',$6,6DQG
$17,$0(%,$6,6$17,*,$5',$6,6DQG

'RVH
'RVH
$17,75,&+2021,$6,6
$17,75,&+2021,$6,6 Treatment of of uncomplicated
uncomplicated falciparum
falciparum malaria,malaria, by by
Treatment
mouth,ForFor
for 13
for 13 years
years old
old and
and overover oror body
body weight
weight

mouth,
over 35
over 35 kg,
kg, give
give 44 tablets
tablets onon day
day 11 then
then 44 tablets
tablets
METRONIDAZOLE
METRONIDAZOLE 88 hrs
hrs after
after 1st
1st dose
dose then
then 44 tablets
tablets twice
twice daily
daily on
on
day 22 and
day and day
day 3;
3; For
For 99 -- 13
13 yrsyrs old
old oror 25
25 to
to less
less
2UDO250 mg
2UDO250 mg and
and 500
500 mg
mg base
base tablet
tablet than 35
35 kg,
kg, give
give 33 tablets
tablets onon day
day 11 then
then 33 tablets
tablets
125 mg
mg base/5
base/5 mL
mL (200
(200 mg/5
mg/5 mLmL as
as benzo-
benzo- than
125
ate) suspension,
suspension, 60
60 mL
mL 88 hrs
hrs after
after 1st
1st dose
dose then
then 33 tablets
tablets twice
twice daily
daily on
on
ate) day 22 and
day and day
day 3;3; For
For 44 -- 88 yrs
yrs old
old oror 15
15 to
to less
less
than 25
than 25 kg,
kg, give
give 22 tablets
tablets onon day
day 11 then
then 22 tablets
tablets
A nitroimidazole,
A nitroimidazole, antiprotozoal
antiprotozoal drug,
drug, which
which has
has
potent antibacterial
antibacterial activity
activity against
against anaerobes,
anaerobes, 88 hrs
hrs after
after 1st
1st dose
dose then
then 22 tablets
tablets twice
twice daily
daily on
on
potent day 22 and
and day
day 3; 3; For
For 66 months
months up up toto 33 yrs
yrs old
old
including Bacteroides
Bacteroides andand Clostridium spp.
Clostridium spp. day
including or 55 to
to less
less than
than 15 15 kg,
kg, give
give 11 tablet
tablet on on day
day 11
or
,QGLFDWLRQV Acute invasive amebic
,QGLFDWLRQV Acute invasive amebic dysentery;dysentery; then 11 tablet
then tablet 88 hrs
hrs after
after 1st
1st dose
dose thenthen 11 tablet
tablet
trichomonal vaginitis,
trichomonal vaginitis, amoebiasis
amoebiasis and
and giardia-
giardia- twice daily
twice daily onon day
day 22 and
and dayday 3. 3.
sis.
sis. On day
On day 4,
4, give
give Primaquine
Primaquine (See (See under
under Primaquine
Primaquine
for dosing).
for dosing).
&RQWUDLQGLFDWLRQV: Known
&RQWUDLQGLFDWLRQV: hypersensitivity to
Known hypersensitivity to
metronidazole or
metronidazole or any
any component
component of
of the
the formu-
formu- 'RVH$GMXVWPHQWV
'RVH$GMXVWPHQWV
lation; chronic
lation; chronic alcohol
alcohol dependence.
dependence. Renal DQGHepatic Impairment:
Renal DQGHepatic Impairment:
Same dosage
Same dosage as
as in
in patients
patients with
with normal
normal function
function
may be
may be used
used in
in patients
patients with
with mild-to-moderate
mild-to-moderate
61
61
impairment; for severe impairment, the patient (followed in P. vivax and P. ovale infections by
should be referred to a specialist. primaquine to eliminate intrahepatic forms).
Precautions: Contraindications: Known hypersensitivity to 4-
Patients with cardiac conduction defects (including aminoquinoline compounds (e.g., hy-
congenital QT prolongation, arrhythmias, or droxychloroquine and chloroquine) or any
other conditions that may prolong the QT in- component of the formulation; in patients with
terval); concomitant administration of drugs history of epilepsy; retinal damage or impaired
that prolong the QT interval; avoid in acute visual field.
porphyria, severe and/or complicated malaria
Dose:
and first trimester of pregnancy; electrolyte
NOTE: All doses are in terms of chloroquine base.
disturbances; monitor patients unable to take Prophylaxis, by mouth, ADULT, 300 mg weekly;
food (greater risk of recrudescence); severe CHILD, 5 mg/kg weekly.
renal and hepatic impairment (monitor ECG NOTE: This regimen should be started one week before
and plasma potassium concentration). exposure, and be maintained for at least 4 weeks af-
SKILLED TASKS. Dizziness may impair ability to perform ter the last risk of exposure in the case of non-
skilled tasks, e.g., operating machinery or driving. immune individuals.
Treatment of acute malaria, by mouth, ADULT and
CHILD, 10 mg/kg followed by 5 mg/kg 6-8
Common: Abdominal pain, anorexia, arthralgia,
hours later, then 5 mg/kg daily on the next 2
asthenia, cough, diarrhea, dizziness, fatigue,
days or 10 mg/kg for 2 days, followed by 5
headache, itch, myalgia, nausea, palpitations,
prolonged QT interval, pruritus, pyrexia, rash, mg/kg daily on day 3 (total dose, 25 mg/kg
sleep disorder, vomiting, weakness. over 3 days).
Less Common: Ataxia, clonus, hypesthesia, pares- Dose Adjustment:
thesia. Renal Impairment:
Rare: Hepatitis, hypersensitivity reactions. For mild-to-moderate renal impairment, dose reduc-
Drug Interactions: tion is warranted; for severe impairment, the
Drugs which prolong QT interval (see Appendix – Precautions:
Table B) and other Antimalarials – QT interval G6PD deficiency (potential risk of hemolysis); Por-
may be prolonged when given concomitantly phyria cutanea tarda (treating this condition
with this combination, increasing the risk of ar- with higher doses of chloroquine has caused
rhythmia. hepatotoxicity); psoriasis may be worsened;
Hormonal Contraceptives – their effectiveness may epilepsy (tonic-clonic seizures have been re-
be reduced by this combination (use an addi- ported); risk factors for prolonged QT interval
tional method of birth control). (may prolong QT interval and increase the risk
Avoid concomitant use with: of arrhythmias); may aggravate myasthenia
CYP3A4 inducers (see Appendix) – can result in gravis; neurological disorders; renal impair-
decreased concentration of artemether and/or ment; hepatic impairment (avoid concurrent
lumefantrine, and potential loss of anti- therapy with hepatotoxic drugs); severe GI
malarial efficacy. disorders.
Drugs metabolized by CYP2D6 (see Appendix) – Pregnancy (in the first trimester of pregnancy, qui-
potential risk for QT prolongation. nine in combination with clindamycin for 7
Administration: Take the tablets with food or high- days is the treatment of choice – this combi-
fat meal to increase absorption. If patient vom- nation can be used throughout pregnancy; in
its out the dose within 1 to 2 hours, give an- acute malaria and third trimester: benefit of
other dose. prophylaxis and treatment outweighs risk).
NOTE: If clindamycin is not available, then quinine should be
Pregnancy Category: C given as monotherapy.
Breastfeeding (at doses used for malaria prophylax-
is; amount in milk is probably too small to be
harmful, and inadequate for reliable protection
CHLOROQUINE against malaria in the breastfed infant; avoid
breastfeeding when used for rheumatic dis-
Oral: 250 mg (150 mg base) tablet (as phosphate/ ease).
NOTE: If patient continues to deteriorate after chloroquine
diphosphate) medication – suspect resistance and administer qui-
nine IV as emergency measure.
An aminoquinoline antimalarial, which has rapid
schizontocidal activity against blood forms of Adverse Drug Reactions:
Plasmodium ovale and P. malariae, and Common: GI disturbances, itch, lack of appetite,
against susceptible strains of P. vivax and P. pruritus, skin eruptions, weight loss.
falciparum. Less Common: Anxiety, confusion, dizziness,
Indications: Prophylaxis of malaria; treatment of drowsiness, headache, hypotension, irreversi-
non chloroquine-resistant acute malaria ble retinopathy, paresthesia, personality
caused by P. malariae, P. vivax, and P. ovale changes, psychotic episodes, reversible cor-
62
PNF new 88 NEW .pdf 1 1/6/15 7:07 PM
neal
nealopacities,
opacities,sleep
sleepdisorders,
disorders,vertigo,
vertigo, visual
visual Supplement
Supplement to malaria treatment,
treatment, by mouth,$'8/7
by mouth, $'8/7
disturbances.
disturbances. and &+,/' over 8 years,
and years, 100
100 mg
mg twice
twice daily
daily
Rare:Agranulocytosis,
Rare: Agranulocytosis, arrhythmias,
arrhythmias, bleaching
bleaching of of for
for 7-10 days.
hair,
hair,blood
blooddyscrasias,
dyscrasias, blue-black
blue-black pigmenta-
pigmenta-
tion
tionofofmucous
mucous membranes
membranes and and skin,
skin, bone
bone See
See under
under Antimicrobial (Oral
(Oral and Parenteral) for
and Parenteral) for
marrow
marrowsuppression,
suppression, convulsions,
convulsions, hair
hair loss,
loss, other
other information.
hearing
hearingloss,
loss,hypersensitivity
hypersensitivity reactions,
reactions, pan-
pan-
cytopenia,
cytopenia,porphyria,
porphyria, prolonged
prolonged QT QT interval,
interval,
psoriasis,
psoriasis,neuromyopathy,
neuromyopathy,seizure,
seizure, rash,
rash, Ste-
Ste-
vens-Johnson
vens-Johnson syndrome,
syndrome, thrombocytopenia,
thrombocytopenia, PRIMAQUINE
tinnitus,
tinnitus,toxic
toxicepidermal
epidermalnecrolysis.
necrolysis.
2UDO
2UDO 26.3
26.3 mg (15 mg base)
base) tablet
tablet (as
(as diphosphate)
diphosphate)
'UXJ,QWHUDFWLRQV
'UXJ,QWHUDFWLRQV
127(:
127(:Chloroquine
Chloroquinehas hasa along
longhalf-life;
half-life; consequently,
consequently, the
the An
An aminoquinoline
aminoquinoline antimalarial
antimalarial used
used for
for the
the radical
radical
potential
potentialforfordrug
druginteractions
interactionsmay
maypersist
persist for
for weeks
weeks cure
cure and terminal prophylaxis
prophylaxis of of infections
infections
after
afterit ithas
hasbeen
beenstopped.
stopped. with
with P. vivax and P. ovale.
ovale.
Monitor
Monitorclosely
closelywith:
with:
Antacids
Antacids(e.g.,
(e.g.,aluminum
aluminumorormagnesium
magnesium hydroxide)
hydroxide) ,QGLFDWLRQV
,QGLFDWLRQV Radical cure
cure in
in relapsing
relapsing infections
infections ofof
– –these
thesemaymayreduce
reducethe theabsorption
absorption of of chloro-
chloro- P. vivax and P. ovale
P. ovale malaria;
malaria; elimination
elimination ofof
quine.
quine. intrahepatic
intrahepatic forms of
of P. vivax and
P. vivax and P. ovale(af-
P. ovale (af-
Digoxin
Digoxin– –the theserum
serumlevels
levels ofof digoxin
digoxin may
may be be in-
inter
ter standard chloroquine
chloroquine therapy);
therapy); elimination
elimination
creased
creasedbybychloroquine.
chloroquine. of
of P. falciparum gametocytes
gametocytes (after
(after standard
standard
Praziquantel
Praziquantel– –itsitsmetabolism
metabolismmay maybe beincreased
increased by by therapy
therapy with a blood schizontocide).
schizontocide).
chloroquine,
chloroquine, reducing
concentration and and &RQWUDLQGLFDWLRQV
&RQWUDLQGLFDWLRQV Known
Known hypersensitivity
hypersensitivity toto
therapeutic
therapeuticeffects
effects(increase
(increasethe the dose
dose ifif nec-
nec- primaquine
primaquine or any component
component of of the
the formula-
formula-
essary).
essary). tion;
tion; G6PD deficiency
deficiency in
in infants
infants (risk
(risk of
of he-
he-
Avoid
Avoidconcomitant
concomitantuse usewith:
with: molysis);
molysis); infants <1 <1 year
year (methemoglo-
(methemoglo-
Artemether
Artemether+ +Lumefantrine
Lumefantrine –– these these may
may result
result toto binemia);
binemia); patients with
with conditions
conditions thatthat predis-
predis-
potentially
potentiallyhazardous
hazardousinteractions
interactions when
when given
given pose
pose to granulocytopenia
granulocytopenia (including
(including active
active
concomitantly
concomitantlywith withchloroquine.
chloroquine. rheumatoid
rheumatoid arthritis and
and systemic
systemic lupus lupus ery-
ery-
Drugs
Drugswhich
whichprolong
prolongQT QTinterval
interval (see
(see Appendix
Appendix –– thematosus);
thematosus); pregnancy
pregnancy (treatment
(treatment with with pri-
pri-
TableB)B)and
Table andother
otherAntimalarials
Antimalarials––QT QT interval
interval maquine
maquine should be delayed
delayed until
until after
after deliv-
deliv-
may
maybebeprolonged
prolongedwhenwhengiven given concomitantly
concomitantly ery;
ery; third trimester: neonatal
neonatal hemolysis
hemolysis and and
with
withchloroquine,
chloroquine, increasing
increasing the the risk
risk ofof ar-
ar- methemoglobinemia),
methemoglobinemia), and and breastfeeding.
breastfeeding.
rhythmia.
rhythmia.
'RVH
'RVH
$GPLQLVWUDWLRQ
$GPLQLVWUDWLRQ ToTo avoid
avoid nausea
nausea and
and vomiting,
vomiting, 127(:
127(: All
All doses are in terms
terms of
of primaquine
primaquine base.
base.
tablets
tabletsshould
shouldbe
beadministered
administeredafter
aftermeals.
meals. Radical
Radical treatment of P. vivax and
and P.
vivaxPlasmodium
P. ovale
Plasmodium ovale malaria
malaria
falciparum
falciparum
127(:
127(:If Ifpart
partororallallofofa adose
doseisisvomited,
vomited, same
same amount
amount (after
(after standard chloroquine
chloroquine therapy),
therapy), by by
should
shouldimmediately
immediatelybe bereadministered.
readministered.
mouth, $'8/7, 250
mouth, 250 micrograms/kg
micrograms/kg daily daily (or
(or
3UHJQDQF\&DWHJRU\C
3UHJQDQF\&DWHJRU\C 15
15 mg daily) for 14 days; &+,/',
14 days; &+,/', 250 250 mi-mi-
crograms/kg
crograms/kg daily for
for 14
14 days;
days; dd in
in G6PD
G6PD defi-
defi-
ciency, $'8/7, 750
ciency, 750 micrograms/kg
micrograms/kg once once aa
week weeks; &+,/',
week for 8 weeks; &+,/', 500-750500-750 mi- mi-
DOXYCYCLINE
DOXYCYCLINE crograms/kg
crograms/kg once a week
week for
for 88 weeks.
weeks.
Gametocytocidal
Gametocytocidal treatment
treatment of
of P. falciparum malaria
P. falciparum malaria
2UDO
2UDO5050mg
mgand
and100
100mg
mgcapsule
capsule(as
(asbase*/hyclate)
base*/hyclate) (after
(after therapy of standard
standard blood
blood schizonto-
schizonto-
cide), by mouth, $'8/7
cide), $'8/7 andand &+,/',
&+,/', 50-500
50-500
broad-spectrum and
A A broad-spectrum and long-acting
long-acting tetracycline
tetracycline micrograms/kg
micrograms/kg as a single
single dose.
dose.
antibiotic
antibioticused
usedfor
forinfections
infectionscaused
caused byby chla-
chla-
mydia,
mydia,spirochetes
spirochetesand andother
otherpathogens,
pathogens, and
and 'RVH$GMXVWPHQW
'RVH$GMXVWPHQW
forformalarial
malarialprophylaxis.
prophylaxis. Renal
Renal Impairment:
Same
Same dosage as in patients
patients with
with normal
normal function
function
,QGLFDWLRQV
,QGLFDWLRQV Prophylaxis
Prophylaxis and and treatment
treatment (supple-
(supple- may
may be used in patients
patients with
with mild-to-moderate
mild-to-moderate
ment
menttotoquinine
quinineororartesunate)
artesunate) ofof multidrug-
multidrug- renal
renal impairment; for
for severe
severe impairment,
impairment, the
the
resistant
resistantP.P.falciparum
falciparummalaria.
malaria. patient
patient should be referred
referred to
to aa specialist.
specialist.
&RQWUDLQGLFDWLRQV
&RQWUDLQGLFDWLRQVSeeSeeunder
under Antimicrobial
Antimicrobial (Oral
(Oral 3UHFDXWLRQV
3UHFDXWLRQV
and
andParenteral).
Parenteral). G6PD
G6PD deficiency (exclude
(exclude before
before radical
radical treatment
treatment
'RVH
'RVH for
for P. vivax and P. ovale
ovale malaria;
malaria; but,
but, this
this isis
Short-term prophylaxis
Short-term prophylaxis ofof malaria,
malaria, by by mouth,
mouth, not
not necessary before
before single-dose
single-dose gametocy-
gametocy-
$'8/7,
$'8/7,100 100 mg mg daily
daily for
for up
up toto 88 weeks;
weeks; tocidal
tocidal treatment); for
for patients
patients receiving
receiving other
other
&+,/'
&+,/'over
over88years,
years,1.5 1.5mg/kg
mg/kgdaily
dailyfor
for up
up to
to potentially
potentially hemolytic
hemolytic drugs
drugs that
that depress
depress mye-
mye-
8 8weeks;
weeks;doxycycline
doxycyclineshould shouldbebestarted
startedonon the
the loid
loid elements of the the bone
bone marrow
marrow (monitor
(monitor
day
day before
before exposure
exposure and and continued
continued for for 44 blood
blood count: if either
either methemoglobinemia
methemoglobinemia or or
weeks
weeksafter
afterlast
lastrisk
riskofofexposure.
exposure. hemolysis
hemolysis occurs, withdraw
withdraw treatment
treatment and and
consult
consult a physician).
physician).
63
63
Adverse Drug Reactions: Prevention of genital herpes simplex, HIV-positive,
Common: Abdominal pain, anorexia, dizziness, by mouth, ADULT, 400-800 mg 2 or 3 times
headache, leukocytosis, nausea, vomiting. daily.
Less Common: Hemolytic anemia, methemoglo- Prevention of recurrent herpes simplex, by mouth,
binemia. ADULT, 200 mg 4 times daily or 400 mg twice
Rare: Agranulocytosis, anemia, arrhythmias, granu- daily, reduced to 200 mg 2-3 times daily if
locytopenia, hemoglobinuria, hypertension, in- possible and interrupted every 6-12 months
terference with visual accommodation, leuko- for reassessment.
penia, pruritus. Prophylaxis of herpes simplex in the immunocom-
promised, by mouth, ADULT and CHILD >2
Drug Interactions:
years or >40 kg, 20 mg/kg/ dose 4 times a
day for 5 days or 200-400 mg 4 times daily;
Chloroquine – its metabolism may be inhibited by
CHILD <2 years, half of the adult dose.
primaquine.
Treatment of chickenpox, by mouth, ADULT, 800
mg 4-5 times daily for 5-7 days; CHILD >2
Artemether + Lumefantrine – these may result to
years, 20 mg/kg/dose 5 times a day (maxi-
potentially hazardous interactions when given
mum dose, 3.2 g/day).
concomitantly with primaquine.
Treatment of herpes zoster, by mouth, ADULT, 800
Administration: Take with food to avoid stomach mg 5 times daily for 7-10 days.
upset and pain. NOTE: Therapy should be initiated as soon as possible after
a diagnosis of chickenpox or herpes zoster, or at the
Pregnancy Category: C first sign or symptoms of an outbreak of genital her-
pes.
manufacturer’s directions. In obese patients, paren-
ANTIVIRALS teral dose should be calculated on the basis of ideal
weight for height (to avoid excessive dosage).
Dose Adjustment:
ACICLOVIR / ACYCLOVIR
Renal impairment:
Oral: 200 mg, 400 mg and 800 mg tablet
200 mg/5 mL suspension, 60 and 120 mL
An acyclic, purine nucleoside analogue, which has a
Precautions:
high degree of specificity, and is active
against herpes simplex virus and varicella- WARNING: May aggravate renal insufficiency due to intra-
tubular obstruction with aciclovir microcrystals.
zoster virus.
Use with caution in patients with dehydration, renal
Indications: Initial treatment and prophylaxis of
disease, electrolyte abnormalities, underlying
recurrent mucosal and cutaneous herpes
neurologic diseases or hepatic dysfunction;
(HSV1, HSV2) infections; acute chickenpox
maintain adequate hydration (especially with
(varicella zoster) in immunocompromised pa-
infusion or high doses, or during renal impair-
tients; herpes zoster infections (shingles).
ment) to minimize renal adverse effects (crys-
Contraindications: Known hypersensitivity to tals may precipitate in renal tubules and im-
aciclovir, valaciclovir, or any other compo- pair renal function); renal impairment (in-
nents of the formulation; serious adverse re- creased risk of nephrotoxicity and neurological
actions to individual drug or metabolite; should adverse effects); suppressive therapy of geni-
not be used to treat severe HSV infections in tal herpes should be considered only if patient
children with low resistance to disease. is severely affected (periodic evaluation is
recommended); and cross-resistance may oc-
Dose: cur between agents due to their similar mech-
Treatment of initial infection of genital herpes sim- anisms of action and activation pathways.
plex, by mouth, ADULT, 400 mg 3 times daily Prolonged or repeated courses of aciclovir in se-
for 5-7 days; CHILD >2 years, 40-80 mg/kg/ verely immunocompromised patients may re-
day in 3-4 divided doses, usually for 5 days sult in selection of resistant viruses associated
(longer if new lesions appear during treatment with infections which may not respond; the el-
or if healing is incomplete; CHILD <2 years, derly (at increased risk of neurological ad-
half the adult dose. verse effects; likely to have reduced renal
Treatment of recurrent infection of genital herpes function); pediatrics (safety and effectiveness
simplex, by mouth, ADULT, 400 mg 3 times in children <2 years of age have not been ad-
daily (or 800 mg twice daily) for 5 days; or 800 equately studied).
mg 3 times daily for 2 days. Pregnancy (not known to be harmful; use only when
Treatment of recurrent infection of genital herpes potential benefit outweighs risk); breastfeed-
simplex, by mouth, ADULT, 400 mg 3 times ing (significant amount found in milk after sys-
daily (or 800 mg twice daily) for 5 days; or 800 temic administration; not known to be harm-
mg 3 times daily for 2 days. ful).
64
Adverse Drug Reactions: with these doses given for at least 7 days or
Common: Diarrhea, hallucinations (high dose), for up to 6 weeks during epidemics..
headache, nausea, vomiting. Treatment of influenza (must be given within 2
Less Common: Abdominal pain, agitation, arthral- days of onset of flu symptoms), by mouth,
gia, confusion, constipation, dizziness, drows- ADULT, 75 mg every 12 hours for 5 days;
iness, edema, fatigue, pruritus, photosensitivi- CHILD >12 years, 75 mg twice daily for 5
ty, rash, renal impairment, sore throat, urticar- days; CHILD >1-12 years, if <15 kg, give 2
ia, vertigo, weakness. mg/kg/dose twice daily for 5 days, (maximum,
Rare: Acute renal failure, anaphylaxis, anemia, 30 mg/dose); if >15-23 kg, give 45 mg/dose
anorexia, coma, crystalluria, dyspnea, fatigue, twice a day for 5 days; if >23-40 kg, give 60
fever, hepatitis, jaundice, leukopenia, neutro- mg/dose twice a day for 5 days; if >40 kg, give
penia, psychosis, seizures, Stevens-Johnson 75 mg/dose twice a day for 5 days.
syndrome, thrombocytopenia, toxic epidermal
Dose Adjustments:
necrolysis, tremor.
Renal impairment:
Drug Interactions: Administer with caution in moderate to severe renal
Monitor closely with: impairment.
Probenecid – this increases the half-life and AUC of Precautions:
aciclovir. Most effective when used within 24-48 hours of
Theophylline – aciclovir may increase its concentra- onset of symptoms.
tion and risk of adverse effects. Age <1 year: safety and efficacy for prophylaxis of
Zidovudine – increased effect of aciclovir. influenza has not been established.
Avoid concomitant use with: Age <2 weeks: safety and efficacy for treatment of
Zoster Vaccine – its therapeutic effect may be di- influenza has not been established.
minished by aciclovir. Increased risk of serious skin reactions.
Reports of potentially fatal neuropsychiatric adverse
Administration: For dosage taken 5 times daily, events in patients with flu.
take every 4 hours during waking hours. Make
sure that the patient drinks plenty of fluids (at Adverse Drug Interactions:
least 1.5-2 L daily). This medication may Common: Abdominal pain, conjunctivitis, ear disor-
make the patient feel dizzy or confused; ad- der, epistaxis, insomnia, nausea, vomiting,
vise not to drive or operate machinery if the vertigo.
patient is affected. Less common: Aggravation of diabetes, anemia,
arrhythmia, confusion, delirium, hemorrhagic
colitis, hepatitis, humerus fracture, peritonsillar
abscess, pneumonia, pseudomembranous co-
litis, pyrexia, rash, seizure, increased trans-
aminase, toxic epidermal necrolysis, unstable
OSELTAMIVIR angina, swelling of face or tongue. Hypother-
mia also reported.
Oral: 75 mg capsule (as phosphate)
Drug Interactions:
This inhibits influenza virus neuraminidase, resulting Monitor drug closely with:
in the inability of the virus to spread in the Clopidogrel – this decreases levels of oseltamivir.
respiratory tract. It is active against both Influ- Probenecid – this increases levels of oseltamivir,
enza A and B. It inhibits amantadine- and resulting in a 2-fold increase in exposure to
rimantadine-resistant influenza A virus. oseltamivir carboxylate (active metabolite).
Indications: Prophylaxis of influenza A and B (not a Administration: May be taken with meals to reduce
substitute for flu vaccination); treatment of un- GI side effects. Capsule may be opened and
complicated acute illness due to influenza A mixed with sweetened food products. To pre-
and B infection in patients who have been pare 100 mL of 6 mg/mL suspension, put 7
symptomatic for no more than 2 days. mL of distilled water into a glass or polyethyl-
Contraindication: Known hypersensitivity to osel- eneterephthalate (PET) bottle then empty con-
tamivir or any component, or other sialic acid- tents of eight 75 mg capsules (= 600 mg) into
the bottle. Swirl the suspension for at least 2
based neuraminidase inhibitor.
minutes then slowly add 91 mL of syrup,
Dose: sweetened condensed milk, or yogurt. Shake
Post-exposure prophylaxis of influenza (should be well for 30 minutes. Instruct patient to shake
given within 2 days of exposure), by mouth, mixture well before using. Swallow mixture
ADULT, 75 mg/dose twice a day for at least 7 immediately after preparation. Suspension
days or for up to 6 weeks during community can remain stable for 5 days at room tempera-
outbreaks or epidemics; CHILD >12 years, 75 ture or 5 weeks if refrigedrated at 2-8 degrees
mg twice daily; CHILD >1-12 years, if <15 kg, centigrade.
give 2 mg/kg/dose twice daily, (maximum, 30
mg/dose); if >15-23 kg, give 45 mg/dose twice
a day; if >23-40 kg, give 60 mg/dose twice a
day; if >40 kg, give 75 mg/dose twice a day,
65
Close monitoring of arterial and venous pressure
CARDIOVASCULAR SYSTEM and continuous ECG should be performed;
treatment with sympathomimetics should be
guided by hemodynamic monitoring (individu-
ADRENERGICS alize treatment depending on clinical re-
sponse); use low dose in cardiogenic shock
due to MI; prolonged use of sympathomimet-
DOPAMINE ics may result in diminution of therapeutic ef-
fect (downregulation of receptors); dispropor-
Inj.: 40 mg/mL, 5 mL vial/ampul (IV) (as HCl) tionate increase in diastolic pressure.
80 mg/mL, 5 mL vial (IV) (as HCl) Correct hypovolemia before, and maintain blood
800 micrograms/mL, 250 mL D5W (pre- volume during the treatment; correct hypoxia,
mixed) (IV) (as HCl) hypercapnia, and metabolic acidosis before or
1.6 mg/mL, 250 mL D5W (pre-mixed) at the same time that treatment is started
(IV) (as HCl) (may possibly reduce the effectiveness and/or
3.2 mg/mL, 250 mL D5W (pre-mixed) increase the incidence of adverse effects of
(IV) (as HCl) dopamine); pulmonary hypertension (may be
worsened due to dopamine-induced pulmo-
A direct-acting sympathomimetic which acts on
nary vasoconstriction); suppresses pituitary
beta 1 receptors in cardiac muscles, leading to
secretion of thyroid-stimulating hormone,
increased contractility with little effect on rate,
and may be given for short periods in the growth hormone and prolactin.
treatment of severe heart failure; it also has Elderly; pregnancy (limited human data available).
an advantage over others by causing renal Adverse Drug Reactions:
vasodilation, thus preserving renal perfusion Common: Anginal pain, chest pain, dyspnea, ec-
and renal function. topic beats, flushing, headache, hypotension
Indications: Hypovolemic shock and hemorrhagic with dizziness, nausea, palpitations, peripher-
al vasoconstriction, vomiting, tachycardia.
shock as adjuvant therapy to volume re-
Less Common: Abnormal ventricular conduction,
placement; cardiogenic shock (where systolic
bradycardia, extravasation (this may cause
BP <90 in adults).
necrosis and sloughing of surrounding tissue),
Contraindications: Known hypersensitivity to fainting, gangrene, hypertension, mydriasis,
dopamine or any of the excipients; ischemic piloerection, uremia.
heart disease; tachyarrhythmias, ventricular Rare: Allergic reactions, ventricular arrhythmia.
fibrillation; pheochromocytoma; hyperthyroid-
Drug Interactions:
ism.
Dose: Alpha-adrenergic blocking agents – peripheral
Hypovolemic and hemorrhagic shock as adjuvant vasoconstriction caused by high doses of do-
therapy to volume replacement, by IV infusion pamine is antagonized.
into a large vein, ADULT, initially 5 mi- MAO Inhibitors (e.g., linezolid, phenelzine, and
crograms/kg per minute, gradually increased tranylcypromine) – these inhibit metabolism of
by 5 to 10 micrograms/kg per minute accord- dopamine; they may prolong and intensify its
ing to blood pressure, cardiac output, and effects.
urine output (seriously-ill patients, up to 20 Phenytoin – co-administration in patients with do-
micrograms/kg per minute); CHILD, 2 to 10 pamine has resulted in hypotension and brad-
micrograms/kg per minute depending on pa- ycardia.
tient response. Avoid concomitant use with:
DILUTION AND ADMINISTRATION. See Administration. Beta-adrenergic blocking agents (e.g., propranolol
and metoprolol) – the cardiac effects of do-
Dose Adjustments:
pamine are antagonized.
Chlorpromazine – antagonism of hypertensive
For mild-to-moderate impairment, drug should be
effect.
used with caution, and dose reduction may be
Fluphenazine – antagonism of hypertensive effect.
warranted; for severe impairment, the patient
Haloperidol – antagonism of hypertensive effect.
Metoclopramide – this decreases level of dopamine
Precautions: by inhibiting GI absorption.
WARNING: This may cause peripheral ischemia in patients Vasoconstrictors (e.g., ergot alkaloids) – these may
with history of occlusive vascular disease (e.g., ather- increase peripheral vasoconstriction and the
osclerosis and Raynaud’s syndrome). In case of ex- risk of peripheral ischemia.
travasation causing peripheral ischemia, use phen-
tolamine for local infiltration. Administration: The solution should be diluted
before administration (usual dilution is 1.6 or
NOTE: Dosage is critical – at low doses, it stimulates
myocardial contractility and increases cardiac output; 3.2 mg/mL) in dextrose 5% or sodium chloride
however, higher doses (more than 5 mi- 0.9%. Alkaline solutions, such as sodium bi-
crograms/kg/minute) cause vasoconstriction, which carbonate (NaHCO 3 ), should not be added
increases blood pressure and may also cause wors- (since the drug will be inactivated). Utilize a
ening of heart failure.
66
large vein high up in the limb, preferably the Precautions:
arm, to avoid tissue necrosis. Cerebrovascular disease (increased risk of periph-
eral ischemia or stroke); hypovolemia (correct
before using epinephrine); acidosis, hyper-
capnia, or hypoxia (may reduce the effective-
ness, and increase the incidence of adverse
effects of epinephrine); heart diseases (e.g.,
EPINEPHRINE ischemic heart disease, heart failure, other ar-
rhythmias; increased risk of arrhythmias, an-
Inj.: 1:1000 (1 mg/mL) (SC, IM, IV) or 1:10,000 (1 gina and myocardial ischemia); aortic stenosis
mg/10 mL) (IV) and hypertrophic cardiomyopathy (possibly in-
A direct-acting, mixed alpha- and beta-adrenoceptor creased outflow obstruction); arrhythmias (re-
agonist; a sympathomimetic catecholamine, duce dose; monitor closely); pulmonary hyper-
which is a potent cardiac stimulant vasocon- tension (may worsen due to pulmonary vaso-
strictor and bronchodilator. constriction);
NOTE: Vasodilator at low dose (beta 2 receptors); but, Elderly; hyperthyroidism, diabetes mellitus (adverse
vasoconstrictor at high dose (alpha receptors). reactions are more likely to occur); second
stage of labor.
Indications: Severe anaphylactic reactions; severe
angioedema with laryngeal swelling or airway Adverse Drug Reactions:
obstruction; cardiac arrest. Common: Anxiety, dizziness, dyspnea, fear, head-
ache, hyperglycemia, nausea, pallor, palpita-
tions, restlessness, sweating, tachycardia,
epinephrine or any of the excipients; pheo- tremor, vomiting, weakness.
chromocytoma; use in local anesthesia of fin- Less Common: Angina, cerebral hemorrhage,
gers, toes, ears, nose or genitalia; shock; or- excessive increase in blood pressure, hyper-
ganic heart disease or cardiac dilatation; tension, peripheral ischemia and necrosis (at
closed-angle glaucoma; labor. infusion site), pulmonary edema, ventricular
NOTE: However, there are no absolute contraindications to
the use of epinephrine in life-threatening allergic reac- arrhythmias.
tions. Rare: Allergic reactions.
Dose: Drug Interactions:
Anaphylaxis, by IM or SC injection of 1:1,000 epi- NOTE: Alpha-adrenergic blockers antagonize vasoconstrict-
ing and hypertensive effects of epinephrine.
nephrine injection, ADULT and ADOLES-
CENT, 500 micrograms (0.5 mL); INFANT <6 Monitor closely with:
months, 50 micrograms (0.05 mL); CHILD 6 Drugs causing potassium loss (e.g., corticosteroids,
potassium-depleting diuretics, aminophylline,
months-6 years, 120 micrograms (0.12 mL),
theophylline) – these may potentiate the
6-12 years, 250 micrograms (0.25 mL) or for
hypokalemic effect of epinephrine.
CHILDREN, 10 micrograms (0.01 mL of
Ergot Alkaloids – these may reverse the pressor
1:1,000 solution)/kg bodyweight SC, repeated
effects of epinephrine.
if necessary at intervals of 20 minutes to four
Oxytocin – there is risk of hypertension due to en-
(4) hours depending on the response of the
hanced vasopressor effect of epinephrine.
patient and the severity of the condition. Sin-
Tricyclic Antidepressants – these block the uptake
gle pediatric doses should not exceed 500
of catecholamines; can intensify and prolong
micrograms.
epinephrine’s effects (since uptake is one
Anaphylaxis, by slow IV injection of 1:10,000 (given
mechanism by which catecholamines are ter-
at a rate of 1 mL/minute) epinephrine injec-
minated); patients having TCAs are more sus-
tion; this route should be reserved for severely
ceptible to arrhythmias (reduced dose of epi-
ill patients when there is doubt about the ade-
nephrine may be necessary).
quacy of circulation and absorption from the
IM site, ADULT, 500 micrograms (5 mL);
Alpha-blockers – these can prevent receptor activa-
CHILD, 10 micrograms/kg (0.1 mL/kg), given
tion by epinephrine (antagonize vasoconstrict-
over several minutes.
ing and hypertensive effects of epinephrine).
Cardiac arrest (asystole), ADULT, the recommend-
Beta-blockers – these can prevent receptor activa-
ed dose is 1 mg IV, using 10 mL of the
tion by epinephrine; vasoconstrictor effect of
1:10,000 solution. This may be repeated every
epinephrine predominates; hypertension fol-
3-5 minutes. If given through a peripheral line,
lowed by bradycardia may occur.
each dose should be followed by a flush of 20
Hypoglycemic agents – may lead to loss of blood
mL of IV fluid to ensure delivery of the drug to
sugar control in diabetic patients when taken
the central compartment. Intracardiac admin-
concomitantly with these drugs (epinephrine
istration is no longer recommended; CHIL-
induces hyperglycemia).
DREN, the recommended dose is 10 mi-
crograms (0.1 mL of the 1:10,000 solution)/kg Administration: Epinephrine is best administered
body weight administered IV. This may be reas an SC or IM injection into the anterolateral
peated every 3-5 minutes. aspect of the middle third of the thigh for ana-
phylaxis, IV for cardiac arrest or emergency
Dose Adjustment: No information found.
situations
67
NOTE: If central line is used, infusion pump required. Do not Dose Adjustments:
mix with alkaline solutions. Discard after 24 hours or if Renal Impairment:
solution is discolored or contains precipitate.
Single oral doses of the drug, in patients with renal
Pregnancy Category: C impairment, are not different from those with
normal renal function; but, consider reducing
dose for chronic use (since significant accu-
ANTI-ANGINALS mulation of the active metabolites may occur).
Hepatic Impairment:
Consider reducing dose since ISDN is, in part,
ISOSORBIDE DINITRATE (ISDN) metabolized by the liver.
Precautions:
Oral: 5 mg, 10 mg and 20 mg tablet Severe hepatic impairment; renal impairment; hypo-
20 mg and 40 mg MR tablet/capsule thyroidism; recent history of MI; malnutrition;
Sublingual: 5 mg tablet hypothermia.
Inj.: 1 mg/mL, 10 mL ampul (IV) Pregnancy (may cross placenta – avoid medication
unless potential benefit outweighs risk).
An organic nitrate vasodilator whose stability in
TOLERANCE. Patients taking ISDN for long-term manage-
storage is better than glyceryl trinitrate, and is ment of angina may often develop tolerance to the an-
useful in patients who require nitrates infre- ti-anginal effect; this can be avoided by giving the
quently; it has a slower onset of action, but second of 2 daily doses of longer-acting oral presen-
longer duration. tations after an 8-hour rather than a 12-hour interval,
thus ensuring a nitrate-free interval each day.
Indications: Prophylaxis and treatment of angina;
left ventricular failure. Adverse Drug Reactions:
Common: Dizziness, fainting, flushing, hypoten-
Contraindications: Known hypersensitivity to sion, including orthostatic hypotension; palpi-
nitrates or any of the excipients; hypotension; tations, peripheral edema, tachycardia, throb-
hypovolemia; hypertrophic obstructive cardi- bing headache.
omyopathy, aortic stenosis, cardiac tam- Less Common: Heartburn, hypoxemia, nausea,
ponade, constrictive pericarditis, mitral steno- rash, rebound angina, syncope, vomiting.
sis; marked anemia; head trauma; cerebral Rare: Angle-closure glaucoma.
hemorrhage; angle-closure glaucoma.
For extended release formulation: GI hyper- Drug Interactions:
motility, malabsorption syndrome. Monitor closely with:
Atropine – possibly reduced effect of sublingual
Dose: ISDN tablets (failure to dissolve under the
Angina (acute attack), sublingually, ADULT, 2.5 to 5 tongue owing to dry mouth).
mg, repeated every 5-10 minutes as required Drugs which reduce blood pressure (see Appendix
for 3 doses. NOTE: Inability to relieve chest – Table D) – nitrates cause hypotension and,
pain after 3 doses may signal acute myocar- if given with these drugs, may have enhanced
dial infarction which will need immediate hos- hypotensive effects.
pitalization. IV infusion may be started, while Avoid concomitant use with:
awaiting transfer to the hospital, at 1 mg/hour Phosphodiesterase Inhibitors (e.g., sildenafil) –
and titrated upward to 4 mg/hour. nitrates potentiate the hypotensive effects of
Angina prophylaxis, by mouth, ADULT, for regular phosphodiesterase inhibitors; combinations
release tablet, start at 5-20 mg twice to thrice may result in profound hypotension or myo-
daily, usual maintenance dose is 10-40 mg cardial infarction.
twice to thrice daily, (maximum, 240 mg); Contraceptives, Oral – antagonism of hypotensive
for extended release tablet, 40-80 mg once or effect.
twice daily, space twice daily dose 6 hours Dexamethasone – antagonism of hypotensive ef-
apart, (maximum, 160 mg/day). NOTE: Pro- fect.
vide nitrate-free interval daily (14 hours for Hydrocortisone – antagonism of hypotensive effect.
regular release and 18 hours for extended re- Ibuprofen – antagonism of hypotensive effect.
lease) to avoid development of tolerance. Prednisolone – antagonism of hypotensive effect.
Prevention of acute angina before a precipitating
activity, sublingually, ADULT, 5-10 mg taken Administration: Should be taken on an empty
10 minutes before activity. stomach ½ hour before meals. For sublingual
Prevention of chronic angina, by mouth, ADULT, tablets, sit or lie down before use (as the tab-
10-40 mg up to 3 times daily. let may cause dizziness); place the appropri-
Treatment of acute heart failure, sublingually, ate dose under the tongue; do not swallow; af-
ADULT, 5-10 mg every 2 hours or as needed. ter the pain has been relieved, the patient may
Treatment of chronic heart failure, by mouth, spit out or swallow what is left of the tablet to
ADULT, 20-40 mg 4 times daily (with hydrala- avoid adverse effects, such as headache. For
zine). IV infusion, mix 10 mL (equivalent to 10 mg) in
90 mL NSS.
68
tory effect on intestinal motility; may be asso-
DILTIAZEM ciated with mood changes); diabetes mellitus
(diltiazem influences insulin secretion and its
Oral: 30 mg and 60 mg tablet (as hydrochloride) peripheral action).
60 mg, 90 mg, 120 mg and 180 mg MR cap- Elderly (greater hypotensive response).
sule (as hydrochloride) Lactation (enters breast milk; not recommended).
90 mg, 120 mg and 180 mg MR tablet (as Adverse Drug Reactions:
hydrochloride)
Common: Abdominal pain, bradycardia, dizziness,
A nondihydropyridine, calcium-channel blocker, dyspnea, congestion, fatigue, flushing, head-
which has a negative chronotropic effect, thus ache, nausea, nervousness, pain, palpitations,
decreasing the workload of the heart, and peripheral edema, vasodilation, vomiting.
consequently reducing its oxygen require- Less Common: AV block, gout.
ments. Rare: Depression, EPS, gum hyperplasia, gyneco-
mastia, hepatitis, hypersensitivity reactions,
Indications: Prophylaxis and treatment of angina; photosensitivity reactions, rash.
hypertension.
Drug Interactions:
Contraindications: Known hypersensitivity to NOTE: Diltiazem can inhibit CYP-3A4; it may increase the
diltiazem or any component of the formulation; concentration of other drugs metabolized by this en-
marked bradycardia (below 40 beats/minute); zyme, possibly increasing their toxicity.
sick sinus syndrome (except in the presence Monitor closely with:
of a pacemaker); severe hypotension (<90 Carbamazepine – its concentration and risk of
mmHg systolic); congestive heart failure; toxicity are increased by diltiazem.
acute porphyria; second- or third-degree atrio- Digoxin – its concentration and risk of toxicity may
ventricular block (without pacemaker); Wolff- be increased by diltiazem.
Parkinson-White syndrome; acute MI and Drugs causing hypotension, bradycardia or slow
pulmonary congestion; pregnancy. cardiac conduction (e.g., amlodipine, diaze-
pam, hydrochlorothiazide, methyldopa) – can
Dose: result in increased risk of bradycardia and hy-
Angina, by mouth, ADULT, initially 30 mg 3 or 4 potension.
times daily; increase as required or at 1-2 day Midazolam – its metabolism is inhibited by dilti-
interval until optimum response is obtained azem, thus prolonging its sedative and respir-
(maximum dose, 360 mg daily in 3-4 divided atory depressant effects.
doses); doses of up to 360 mg/day may be Phenytoin – its concentration and risk of toxicity
needed in unstable angina. may be increased by diltiazem.
Angina (controlled-release products), by mouth Rifampicin – its metabolism may be increased by
ADULT, initially 180 mg once daily; increase diltiazem, decreasing its therapeutic effect.
as required up to 360 mg once daily. Ritonavir – its concentration and risk of adverse
NOTE: Dose should not be increased if heart rate drops to
effects may be increased by diltiazem.
50 beats/minute.
Hypertension, (see section below under Anti-
Colchicine – its concentration may be increased by
Hypertensives).
diltiazem, with consequent toxicity.
Dose Adjustments: HMG-CoA reductase inhibitors (e.g., atorvastatin,
Elderly: simvastatin) – their concentration and the risk
Start treatment at a lower dose. of rhabdomyolysis/myopathy may be in-
Renal Impairment: creased by diltiazem (use the lowest effective
Start treatment at a lower dose. Use caution. dose if use cannot be avoided).
Hepatic Impairment:
Administration: Normal release preparations may
For mild-to-moderate hepatic impairment, dose
be taken with or without food. For IR, adminis-
reduction may be warranted; for severe im-
ter before meals and at bedtime. For long-
pairment, the patient should be referred to a
acting dosage forms, do not open, chew, or
specialist.
crush; swallow whole.
Precautions: NOTE: Serum levels may be elevated if taken with food.
WARNING: All calcium channel blockers have some degree Pregnancy Category: C
of negative inotropic effect and may, in excessive
doses or in combination with other drugs, produce
myocardial depression especially after MI.
Avoid abrupt withdrawal (has been associated with
severe angina) and long-term use.
May worsen first-degree AV block and exacerbate
bradycardia; in heart failure or impaired left
ventricular function; hepatic and renal impair-
ment; in patients taking beta-blockers or digi-
talis (at risk of AV block, bradycardia, asystole
or sinus arrest); in patients at risk to develop
intestinal obstruction (diltiazem has an inhibi-
69
ANTIDYSLIPIDEMIA Increase in serum creatinine may occur – monitor
renal function.
Patients at high risk for biliary tract disease, such as
FENOFIBRATE women and obese individuals (modest in-
crease in the risk of cholesterol gallstones, re-
Oral: Micronized: 67M (67 mg) capsule, 200M (200 flecting an increase in the cholesterol content
mg) capsule of bile – may cause cholelithiasis).
Non-micronized: 100 mg, 160 mg tablet and Patients at risk for venous thromboembolism (asso-
200 mg tablet ciated with pulmonary embolism and deep ve-
nous thrombosis).
A peroxisome proliferator receptor alpha (PPARα) Avoid exposure of skin to sun, wear protective
activator, which modulates lipoprotein synthe- clothing and use sunscreen.
sis and catabolism. It reduces plasma triglyc- Lack of optimal response (therapy should be with-
eride, moderately increases high-density lipo- drawn if an adequate response is not obtained
protein (HDL) and has a variable effect on after 2-3 months of therapy at the maximal
LDL concentrations. daily dose).
Indications: Hypertriglyceridemia; dyslipidemia Elderly (due to a higher incident of renal impair-
ment).
associated with type 2 diabetes; hypercholes-
terolemia (second-line). Adverse Drug Reactions:
Contraindications: Known hypersensitivity to a Common: Arthralgia, bronchitis, cough, dizziness,
fatigue, GI disturbances (e.g., dyspepsia, ab-
fibrate or any component of the formulation;
dominal pain); headache, hypertension, in-
photosensitivity to ketoprofen; pancreatitis,
somnia, nausea, rhinitis, infections (e.g., uri-
unless due to hypertriglyceridemia; severe re-
nary tract, respiratory tract).
nal impairment, including patients receiving
Less Common: Pancreatitis, photosensitivity,
dialysis; when hepatic impairment, primary bil-
pulmonary embolism, VTE.
iary cirrhosis, gallstones or gall bladder dis-
ease are present; unexplained, persistent liver Rare: Agranulocytosis, anemia, arrhythmias, cho-
function abnormality; pregnancy (embryotoxi- lestatic jaundice, gallstones, hepatitis, hyper-
city in animal studies); lactation. sensitivity reactions (e.g., angioedema, ana-
phylaxis, exfoliative dermatitis); hypokalemia,
Dose: leukopenia, myopathy, rhabdomyolysis,
NOTE: At least 2-3 months of therapy is required to deter- thrombocytopenia.
mine efficacy.
By mouth (for micronized formulations), ADULT, 67 Drug Interactions:
mg up to 3 capsules/day, or 200 mg once dai- Monitor closely with:
ly (dose should be adjusted according to pa- Insulins – fenofibrate may increase effects of insu-
tient response); lin.
By mouth (for non-micronized formulations), Statins – fenofibrate may increase the risk of myo-
ADULT, 200-300 mg once daily in divided pathy or rhabdomyolysis with statins.
doses; usual range: 200-400 mg daily; Sulfonylureas – fenofibrate may enhance their
By mouth, CHILD, >10 years old, up to maximum of hypoglycemic effect.
5 mg/kg daily. Avoid concomitant use with:
Anticoagulants (e.g., warfarin) – fenofibrate may
Dose Adjustments: increase their anticoagulant effect and risk of
Renal Impairment: bleeding (monitor INR and decrease warfarin
For mild-to-moderate renal impairment, dose reduc- dose if necessary).
tion is warranted (initial dose of 40-50 mg Bile Acid Sequestrants – these may decrease ab-
once daily in adults, refer child to pediatrician); sorption of fenofibrate.
for severe impairment, fenofibrate is contrain- Administration: Best taken with food (food in-
dicated. creases the bioavailability of fenofibrate).
Elderly:
Use with caution; may need dose adjustment. Pregnancy Category: C
Precautions:
NOTE: Fenofibrate has a uricosuric effect; may reduce uric
acid concentrations by about 25%.
Hyperlipidemia (secondary causes of hyperlipidemia ROSUVASTATIN
should be ruled out prior to therapy).
Myopathy, myositis and rhabdomyolysis have been Oral: 10 mg, 20 mg and 40 mg tablet
reported in patients taking fenofibrate (con- (as calcium salt)
comitant HMG-CoA reductase inhibitor may An active HMG-CoA reductase inhibitor, which is
potentiate rhabdomyolysis and lead to acute effective in reducing LDL-cholesterol concen-
renal failure). tration, and has been considered to be effica-
Increase in hepatic transaminases – monitor regu- cious in severe hypercholesterolemia.
larly and discontinue if enzyme levels persist 3
times above the upper limit of normal. Indications: Prevention of cardiovascular events in
patients at high risk of a first cardiovascular
event; in adults, for treatment of primary hy-
70
percholesterolemia (heterozygous familial and increased risk for rhabdomyolysis especially
non-familial hypercholesterolemia); mixed at the highest approved dose of 40 mg/day;
dyslipidemia, or homozygous familial hyper- reserve highest dose only for patients who fail
cholesterolemia in patients who have not re- to achieve desired cholesterol level at 20
sponded adequately to diet and other appro- mg/day.
priate measures; in children and adolescents Severe intercurrent illness, such as infection, trau-
10-17 years of age, for treatment of heterozy- ma, metabolic disorder, endocrine and elec-
gous familial hypercholesterolemia. trolyte disturbances, or uncontrolled seizures,
(increases risk of myopathy; rhabdomyolysis
and renal failure; consider withholding statin).
rosuvastatin or any component of the formula- Risk for diabetes mellitus (small increases in HbA 1c
tion; pregnancy (its use during first trimester
and fasting blood glucose have been report-
has been associated with fetal malformation;
ed); hematuria and proteinuria.
decreased synthesis of cholesterol may pos-
Hypothyroidism (should be managed adequately
sibly affect fetal development); breastfeeding;
before starting treatment with a statin).
women who are planning to conceive or those
Elderly (risk of myopathy is higher especially if the
using inadequate contraception; severe renal
patient is frail, age >80 years or multiple dis-
impairment; active liver disease; unexplained
eases are present); children (it is important to
persistent elevation in serum transaminases.
establish a healthy lifestyle to reduce cardio-
Dose: vascular risk, particularly for those with familial
NOTE: Doses should be individualized according to the hypercholesterolemia).
baseline LDL-cholesterol levels, the recommended Treatment with systemic sodium fusidate (may
goal of therapy, and patient response; adjustments increase the risk of rhabdomyolysis with a
should be made at intervals of 4 weeks or more.
NOTE: Pharmacokinetic studies indicate that people of
statin, particularly if the person is already at
Asian ancestry may need lower doses (should start risk).
with 5 mg and should not receive 40 mg dose). These Rare reports of immune-mediated necrotizing myo-
individuals may build up higher drug levels. pathy.
High cardiovascular risk, by mouth, ADULT (men
>50 years, women >60 years), 20 mg once
Common: Abdominal pain, arthralgia, constipation,
daily.
Hypercholesterolemia, by mouth, ADULT, initially, 5 diabetes mellitus, dizziness, elevated creatine
kinase or aminotransferase concentrations,
or 10 mg once daily (may increase the dose to
headache, flu-like illness, insomnia, mild GI
20 mg if necessary at intervals of at least 4
symptoms, myalgia, nausea, UTI, weakness.
weeks); usual range, 5-20 mg once daily
(maximum dose, 40 mg once daily); CHILD Less Common: Pruritus, rash, urticaria.
Rare: Myopathy (including myositis), alopecia,
10-18 years, initially 5 mg once daily (maxi-
amnesia, anaphylaxis, angioedema, gyneco-
mum dose, 20 mg once daily); for child < 10
mastia, hematuria, hepatitis, hypersensitivity
years, safety and efficacy not established.
(rash, pruritus, urticaria); impotence, interstitial
Dose Adjustments: lung disease, jaundice, liver failure, pancreati-
Renal Impairment: tis, paresthesia, peripheral neuropathy, pro-
For mild-to-moderate renal impairment, dose reduc- teinuria, rhabdomyolysis, renal failure, toxic
tion is warranted (initially 5 mg once daily; epidermal necrolysis.
maximum, 10 mg once daily); contraindicated
Drug Interactions:
in severe impairment.
NOTE: Rosuvastatin is not significantly metabolized by CYP
Elderly: enzymes.
Use cautiously and start at low dosage (initially 5 Monitor closely with:
mg once daily) Antacids (e.g., aluminum or magnesium hydroxide)
Asian ancestry (may build up higher drug levels – these may decrease rosuvastatin concentra-
and be at higher risk to develop myopathy): tion (give antacid 2 hours after rosuvastatin).
Consider 5 mg as starting dose in adults. Fibrates – these increase risk of myopathy or rhab-
Patients at risk for myopathy: domyolysis with statins (the risk is less for
Consider lower initial dose (e.g., 5 mg/day in fenofibrate than with gemfibrozil since it does
adults). not affect the concentration of statins).
Precautions: Oral Contraceptives – rosuvastatin may increase
Renal impairment (may reduce elimination of rosu- their serum levels.
vastatin; impairment increases risk of myopa- Avoid concomitant use with:
thy). Bile acid binding resins – shown to reduce GI ab-
Hepatic side effects (hepatic impairment may impair sorption of simvastatin (give statin at least 1
elimination of rosuvastatin) – monitor liver en- hour before, or 4 hours after, the resin).
zymes before initiating therapy and if signs Niacin – increased toxicity due to pharmacodynamic
and symptoms of liver disease occur, history synergism; increased risk of rhabdomyolysis
of liver disease and alcoholism. at >1 g/day niacin.
Myopathy may occur with lipid lowering agent; Warfarin – rosuvastatin may increase the INR and
monitor creatine kinase (CK) levels and dis- risk of bleeding (consider using other alterna-
continue if these are markedly elevated; with tives).
71
$GPLQLVWUDWLRQ
$GPLQLVWUDWLRQ May be May taken
be taken
with orwith without
or without
food; food; RenalRenalImpairment:
Impairment:
may be may takenbe taken
at anyattime anyoftimethe of
day.the day. For mild-to-moderate
For mild-to-moderate renal impairment,
renal impairment, dose reduc-dose reduc-
tion istionwarranted;
is warranted; for severe for severeimpairment,impairment,the the
3UHJQDQF\&DWHJRU\X
3UHJQDQF\&DWHJRU\X
patientpatient
shouldshould be referred be referredto a specialist.
to a specialist.
Hepatic
Hepatic
Impairment:
Impairment:
Use cautiously
Use cautiously and start and at start
lowatdose;low dose; contraindicat-
contraindicat-
ed in edactive in active
liver disease
liver disease or persistent
or persistent abnor-abnor-
SIMVASTATIN
SIMVASTATIN mal liver
malfunction
liver functiontests. tests.
Restricted
Restricted
Dosing Dosing
for 80for mg: 80 mg:
2UDO10
2UDO10
mg, 20 mg, mg, 2040 mg, mg40 and mg80 andmg80 tablet
mg tablet Due toDue thetoincreased
the increased risk ofrisk myopathy,
of myopathy, includingincluding
An HMG-CoA
An HMG-CoA reductase reductaseinhibitor,inhibitor,
whichwhichis effective
is effective rhabdomyolysis,
rhabdomyolysis, particularly particularlyduringduring the firstthe first
in reducing
in reducing LDL-cholesterol
LDL-cholesterol concentration,
concentration, year year
of treatment,
of treatment, the use the of use80-mg of 80-mg dose dose
and hasand been has been reported reported
to reduce
to reducethe inci-
the inci- shouldshould be restricted
be restricted to patients
to patients who have who have
dencedenceof fatal of andfatal non-fatal
and non-fatal MI, strokeMI, stroke
and and been been takingtaking simvastatin simvastatin 80 mg 80 chronically
mg chronically
mortality,
mortality,
and the andneed the need
for coronary
for coronary
and non-and non- (e.g., (e.g.,
for 12for months
12 months or more) or more)
without without
evidence evidence
coronary
coronary
revascularization
revascularization procedures.
procedures. of muscle
of muscletoxicity. toxicity.
AsianAsian Ancestry Ancestry (on (on lipid-modifying
lipid-modifying niacin-niacin-
,QGLFDWLRQV
,QGLFDWLRQV For prevention
For prevention of cardiovascular
of cardiovascular containing
containing drugs): drugs):
eventsevents
in patientsin patients
with high withcardiovascular
high cardiovascular risk risk ConsiderConsider
lower lower doses.doses.
due todue atherosclerotic
to atherosclerotic cardiovascular
cardiovascular diseasedisease
or DM; or hypercholesterolemia
DM; hypercholesterolemia (primary);
(primary);
ho- ho- 3UHFDXWLRQV
3UHFDXWLRQV
mozygous
mozygous familial familial
hypercholesterolemia,
hypercholesterolemia, or or Muscle Muscle
Effects. Effects.
Monitor Monitor
creatine creatine
kinasekinase (CK); (CK);dis- dis-
combined
combined hyperlipidemia
hyperlipidemia in patients
in patients
who havewho have continuecontinueif myopathy
if myopathy is suspected
is suspected and CK andisCK is
not yetnotresponded
yet responded adequatelyadequately
to diettoordiet other
or other elevatedelevatedmore more than 5than times 5 times
the upper the upperlimit oflimit of
appropriate
appropriatemeasures; measures; in children
in children
and adoles-
and adoles- normal, normal,
or if severe
or if severe muscular muscularsymptoms symptoms are are
with heterozygous
cents cents with heterozygous familialfamilial
hypercholes-
hypercholes- present.present.
Simvastatin
Simvastatin shouldshould not benot started
be started
if if
terolemia.
terolemia. CK is CK elevated
is elevatedin patients in patientsat high at risk
highofrisk mus-
of mus-
cle effects.
cle effects.ThereThere is an increased
is an increased risk ofrisk myo-
of myo-
&RQWUDLQGLFDWLRQV
&RQWUDLQGLFDWLRQV KnownKnown hypersensitivity
hypersensitivity to to pathy pathy
if simvastatin
if simvastatin is given is given
at high atdosage
high dosage or or
simvastatin
simvastatinor anyorcomponentany component of theofformula-
the formula- with awith fibrate,
a fibrate, with lipid-lowering
with lipid-lowering dosesdoses of of
tion; active
tion; activeliver disease,
liver disease, or persistently
or persistently
ab- ab- nicotinic
nicotinic
acid, acid, or with or immunosuppressants
with immunosuppressants
normalnormal
liver function
liver function tests; tests;
porphyria;
porphyria;
preg- preg- (monitor(monitor
liver function
liver function and creatine
and creatine kinasekinasein in
nancynancy(congenital(congenital anomalies anomaliesreported;reported;
de- de- symptomatic
symptomatic patients). patients).
Risk of Riskrhabdomyolysis
of rhabdomyolysis
creasedcreased
synthesis synthesis
of cholesterol
of cholesterol possiblypossibly
af- af- (rare) (rare)
may be may increased
be increased in renal in renal
impairment impairment
fects fetal
fectsdevelopment);
fetal development); breastfeeding.
breastfeeding. and hypothyroidism.
and hypothyroidism.
'RVH
'RVH SevereSevere
intercurrent
intercurrent illnessillness (infection,
(infection,trauma, trauma,
or or
metabolic
metabolic disorder disorder
– increased– increasedrisk ofrisk myopa-
of myopa-
Homozygous
Homozygous familial familial
hypercholesterolemia, by by
$'8/7,
mouth,mouth, $'8/7, initiallyinitially
40 mg40daily mg at daily
night,
at night, thy, rhabdomyolysis
thy, rhabdomyolysis and renal and renalfailure;failure;
adviseadvise
patientspatients
to report to report unexplainedunexplained muscle muscle
pain); pain);
adjusted
adjusted
at intervals
at intervalsof at least
of at 4 least
weeks4 weeks
(see (see
hypothyroidism
hypothyroidism (should (should
be managedbe managed beforebefore
Restricted
RestrictedDosing with 80
Dosing withmg80once mg oncedaily daily
at at
startingstarting
treatment treatmentwith awith statin);
a statin);
surgery surgery
(pos- (pos-
night).night).
sibly increased
sibly increased risk ofrisk acute of acute
renal impairment,
renal impairment,
Prevention
Prevention
of cardiovascular
of cardiovascular events, events,
by mouth,
by mouth,
$'8/7, $'8/7,initiallyinitially
10-4010-40 mg once mg daily
once at daily
night,
at night, whichwhich increases increases the likelihood
the likelihood of myopathyof myopathy
adjusted
adjusted
at intervals
at intervalsof at least
of at 4 least
weeks 4 weeks
with with and rhabdomyolysis);
and rhabdomyolysis); the elderly
the elderly(risk of (risk
myo-
of myo-
recommended
recommended starting starting
dose doseof 40ofmg 40 formg for pathy pathy
is higher).is higher).
those those
at highatrisk highofrisk cardiovascular
of cardiovascular events. events. History
History
of liver of disease,
liver disease, or a or higha alcohol
high alcohol intakeintake
(avoid(avoiduse inuse active
in active liver disease
liver disease or unex- or unex-
Primary
Primary
hypercholesterolemia, combined combinedhyper-hyper-
lipidemia,
lipidemia,
by mouth, by mouth, $'8/7, $'8/7,
10-2010-20 mg dailymg daily plained plained
persistent persistent elevations elevationsin serum in serumtrans-trans-
aminases);
aminases); monitor monitor
liver function
liver functionat initiation
at initiation
of of
at night,
at night,
adjusted adjustedat intervals
at intervals
of at of least
at least
4 4
treatment,
treatment, after 4after to 12 4 weeks
to 12 weeks and periodically
and periodically
weeksweeks(see (see Restricted RestrictedDosing Dosingwith 80 withmg 80 mg
thereafter,
thereafter,e.g., at e.g., 6-month
at 6-month intervals intervals
or when or when
once daily
once at daily
night).
at night).
clinically
clinically
indicated;indicated; discontinuediscontinueif serum if serum
trans-trans-
Heterozygous
Heterozygous familial familial
hypercholesterolemia, by by
&+,/'
mouth,mouth, &+,/'
10-1810-18 years,years,
initiallyinitially
10 mg10atmg at aminase aminase concentration
concentration rises rises
to, and to, persists
and persists
at, 3 at,times 3 times
the upper the upper limit of limittheofreference
the reference
night increased,
night increased, if necessary,
if necessary,
at intervals
at intervals
of at of at
range.range.
least least
4 weeks 4 weeks to a maximum
to a maximum of 40 ofmg 40atmg at
&+,/'
night; night; &+,/'
<10 years, <10 years, safetysafety and efficacyRenalRenal
and efficacy impairment.
impairment.
not established.
not established. $GYHUVH'UXJ5HDFWLRQV
127(:127(:
MaximumMaximum
simvastatin
simvastatin
dose dosewith concomitant
with concomitantCommon:
Common:Abdominal
Abdominal
pain, pain,
atrial atrial
fibrillation,
fibrillation,
consti-consti-
verapamil
verapamil
and diltiazem,
and diltiazem,
10 mg 10 daily;
mg with
daily;concomi-
with concomi-
pation,pation,
diabetes
diabetes
mellitus,
mellitus,
dizziness,
dizziness,
eczema,eczema,
tant amiodarone
tant amiodarone
or amlodipine,
or amlodipine,
20 mg 20 daily;
mg contrain-
daily; contrain-
dicateddicated
with erythromycin,
with erythromycin,
clarithromycin,
clarithromycin,
ketocona-
ketocona- edema, edema,
elevated
elevated
CK andCKserum
and serum
transaminase
transaminase
zole, HIV
zole,
protease
HIV protease
inhibitors,
inhibitors,
and gemfibrozil.
and gemfibrozil. level, level,
flatulence,
flatulence,
gastritis,
gastritis,
headache,
headache,insom-insom-
nia, myalgia,
nia, myalgia,
nausea,nausea,
upperupper
respiratory
respiratory
infec- infec-
'RVH$GMXVWPHQWV
'RVH$GMXVWPHQWV tion, urinary
tion, urinary
tract infection,
tract infection,
vertigo,
vertigo,
vomiting.
vomiting.
Elderly:
Elderly: Less Common:
Less Common: Mild GIMild
symptoms.
GI symptoms.
Use with
Usecaution,
with caution,
and start
andat
start
lowatdose.
low dose. Anaphylaxis,
Rare:Rare: Anaphylaxis,
anemia,anemia,
angioedema,
angioedema,
gyneco-gyneco-
mastia,mastia,
hepatitis,
hepatitis,
hypersensitivity,
hypersensitivity,
impotence,
impotence,
72 72
interstitiallung
interstitial lungdisease,
disease,jaundice,
jaundice, liver
liver failure,
failure, tricular
tricularnode;
node;increased
increased angina
angina
or MI
or MIcancan
de- de-
myopathy,
myopathy, pancreatitis,
pancreatitis,peripheral
peripheral neuropathy,
neuropathy, velop
velopafter
afterstarting
startingor orincreasing
increasingthe the
dose,
dose,
pruritus,
pruritus,rash,
rash,renal
renal failure,
failure, rhabdomyolysis,
rhabdomyolysis, particularly
particularlyininpatients
patients with
withsevere
severeobstructive
obstructive
toxic
toxic
epidermal
epidermalnecrolysis.
necrolysis. coronary
coronaryartery
artery
disease.
disease.

Hepatic
Hepaticimpairment
impairment(half-life
(half-life
prolonged);
prolonged); porphyria
porphyria
'UXJ,QWHUDFWLRQV
'UXJ,QWHUDFWLRQV (acute);
(acute);increased
increased intracranial
intracranialpressure;
pressure;glau-
glau-
Monitor
Monitor closely
closely with:
with: coma.
coma.
Carbamazepine
Carbamazepine– –this thisincreases
increases the the metabolism
metabolism of of Pregnancy
Pregnancy(limited
(limitedinformation
information on on
useuse
in humans;
in humans;
simvastatin,
simvastatin,decreasing
decreasingits its concentration
concentration and and risk
risktotofetus
fetusshould
should bebe balanced
balancedagainst
against
the the
effect.
effect. risk
risk ofofuncontrolled
uncontrolledmaternal
maternal hypertension);
hypertension);
Avoid
Avoid concomitant
concomitantuse usewith:
with: breastfeeding
breastfeeding(presence
(presence in in
milk
milk
is possible;
is possible;
Bile
Bile
acidacid
binding
bindingresins
resins––these
these reduce
reduce GI GI absorp-
absorp- monitor
monitorinfant).
infant).
tion
tion
of of
simvastatin
simvastatin(give(givestatin
statin atat least
least 1 hour
hour
before,
before,oror
4 4hours
hoursafter,
after,the
theresin).
resin). $GYHUVH'UXJ5HDFWLRQV
Clotrimazole
Clotrimazole – increased
– increasedrisk riskofofmyopathy.
myopathy. Common: Abdominal
Common: Abdominal pain, pain,dizziness,
dizziness,fatigue,
fatigue,
CYP3A4
CYP3A4 Inhibitors
Inhibitors(e.g.,
(e.g.,clarithromycin,
clarithromycin, erythromy-
erythromy- flushing,
flushing,gingival
gingivalhyperplasia,
hyperplasia, headache,
headache, nau-nau-
cin,
cin,
ketoconazole,
ketoconazole,diltiazem
diltiazem––see see Appendix)
Appendix) –– sea,
sea,palpitation,
palpitation, peripheral
peripheraledema,
edema,pulmonary
pulmonary
increased
increasedconcentration
concentrationofof the the HMG-CoA
HMG-CoA re- re- edema,
edema,rash,rash,
sleep
sleepdisturbances.
disturbances.
ductase
ductaseinhibitor,
inhibitor,increasing
increasing the the risk
risk of rhab-
rhab- Less Common:Arthralgia,
LessCommon: Arthralgia, dryness
drynessof mouth,
of mouth,chest
chest
domyolysis
domyolysis and
andmyopathy.
myopathy. pain,
pain, constipation,
constipation,dyspepsia,
dyspepsia, dyspnea,
dyspnea, GI GI
disturbances,
disturbances,gynecomastia,
gynecomastia, hypotension,
hypotension, im- im-
$GPLQLVWUDWLRQMay
$GPLQLVWUDWLRQMaybe betaken
takenwith
with or
or without
without food;
food;
potence,
potence,mood moodchanges,
changes, myalgia,
myalgia, paresthe-
paresthe-
avoidexcessive
avoid excessiveconsumption
consumption (>1(>1 L/day)
L/day) of
of sia,
sia, polyuria,
polyuria, pruritus,
pruritus,pulmonary
pulmonary edema,
edema,
grapefruit
grapefruit
juice.
juice. sweating,
sweating,syncope,
syncope, tachycardia,
tachycardia, taste
taste
disturb-
disturb-
3UHJQDQF\&DWHJRU\
3UHJQDQF\&DWHJRU\XX ances,
ances,tinnitus,
tinnitus,tremor,
tremor,urinary
urinarydisturbances,
disturbances,
weight
weightchanges.
changes.
Rare: Agitation,
Rare: Agitation,alopecia,
alopecia,amnesia,
amnesia, angioedema,
angioedema,
$17,+<3(57(16,9(6
$17,+<3(57(16,9(6 arrhythmias,
arrhythmias,ataxia,
ataxia,cardiac
cardiac failure,
failure,
choles-
choles-
tasis,
tasis, coughing,
coughing,dermatitis,
dermatitis,erythema
erythema multi-
multi-
forme,
forme, gastritis,
gastritis, hepatitis,
hepatitis,hyperglycemia,
hyperglycemia,
AMLODIPINE
AMLODIPINE jaundice,
jaundice,myocardial
myocardialinfarction,
infarction,pancreatitis,
pancreatitis,
Parkinsonism,
Parkinsonism,parosmia,
parosmia, peripheral
peripheralneuropa-
neuropa-
thy,
thy, purpura,
purpura, thrombocytopenia,
thrombocytopenia,twitching,
twitching,
2UDO5
2UDO5
mgmg
and
and
1010mg
mgtablet
tablet(as
(asbesylate)
besylate)
vasculitis,
vasculitis, abnormal
abnormalvisual visualaccommodation
accommodation
A Along-acting
long-acting dihydropyridine,
dihydropyridine, calcium-channel
calcium-channel and
andxerophthalmia.
xerophthalmia.
blocker,
blocker,which
whichisisuseful
usefulfor
for hypertension
hypertension and
and
'UXJ,QWHUDFWLRQV
'UXJ,QWHUDFWLRQV
coronary
coronaryartery
arterydisease.
disease.
Monitor
Monitorclosely
closelywith:
with:
,QGLFDWLRQVHypertension;
,QGLFDWLRQVHypertension;prophylaxis
prophylaxis of
of angina.
angina. Drugs
Drugswhich
whichreduce
reducebloodbloodpressure
pressure (see(see
Appendix
Appendix
TableD)D)– –amlodipine
––Table amlodipine cancan
cause
cause hypoten-
hypoten-
&RQWUDLQGLFDWLRQV
&RQWUDLQGLFDWLRQV Known
hypersensitivity to to sion
sionand,
and,if ifgiven
givenwith
with
these,
these,may mayhavehave
en- en-
amlodipine
amlodipineororany
anycomponent
component of of the
the formula-
formula- hanced
hancedhypotensive
hypotensive effects.
effects.
tion;
tion;
unstable
unstableangina;
angina;cardiogenic
cardiogenic shock;
shock; hy-
hy- Avoid
Avoidconcomitant
concomitant use
usewith:
with:
potension;
potension;significant
significant aortic
aortic stenosis;
stenosis; in in-
in- Calcium
CalciumSalts
Salts– –these
thesemay
may diminish
diminishthetheeffect
effect
of of
stances
stancesofofMIMIwith
withheart
heart failure
failure oror poor LV
LV amlodipine.
amlodipine.
function.
function. Simvastatin
Simvastatin– –amlodipine
amlodipinemay mayincrease
increase its its
serum
serum
'RVH
'RVH concentration;
concentration;potential
potential
forfor
myopathy
myopathy maymayin- in-
Hypertension,
Hypertension,bybymouth, mouth, $'8/7,
$'8/7, initially
initially 2.5 mg
mg crease
crease(limit
(limitsimvastatin
simvastatindose
doseto 20
to 20
mg/day
mg/dayif if
onceonce daily,
daily,increased
increasedififnecessary
necessary (maximum,
(maximum, used
usedconcurrently).
concurrently).
1010 mgmg once daily);&+,/',
oncedaily); &+,/', refer
refer to
to aa special-
special- $GPLQLVWUDWLRQ
$GPLQLVWUDWLRQMay
Maybebe
taken
taken
with
with
or without
or without
food.
food.
ist.ist.
SeeSeeClinical
ClinicalPractice
Practice Guidelines
Guidelines - Hyper-
Hyper-
tension
tensionforfor
further
furtherinformation.
information. 3UHJQDQF\&DWHJRU\
3UHJQDQF\&DWHJRU\ CC
Angina,
Angina, mouth,$'8/7,
bybymouth, $'8/7,initially
initially 2.5-5
2.5-5 mg once
once
daily,
daily,
increasing
increasingover over1-2
1-2 weeks
weeks ifif necessary
necessary
(maximum,
(maximum,1010mg mgonce daily); &+,/',
oncedaily); &+,/', refer to to
a specialist.
a specialist. CAPTOPRIL
CAPTOPRIL
'RVH$GMXVWPHQW
'RVH$GMXVWPHQW 2UDO25
2UDO25mg
mgtablet
tablet
Hepatic
HepaticImpairment:
Impairment:
An
Anoral
oralangiotensin-converting
angiotensin-converting enzyme
enzyme(ACE)
(ACE)
inhib-
inhib-
Hepatic
Hepaticinsufficiency:
insufficiency: consider
consider dose
dose reduction,
reduction,
itor,
itor,which
whichis isuseful
useful
in:in:
treating
treating
hypertension,
hypertension,
initiating
initiating
with
with2.5
2.5mg
mgdaily,
daily,by
bymouth.
mouth.
decreasing
decreasingmorbidity
morbidityand andmortality
mortality
in heart
in heart
Severe
Severehepatic
hepaticimpairment:
impairment:titrate
titrateslowly.
slowly.
failure
failureand
andleft leftventricular
ventriculardysfunction
dysfunction afterafter
3UHFDXWLRQV
3UHFDXWLRQV myocardial
myocardialinfarction,
infarction,andanddelaying
delayingthe the
pro-pro-
Hypotension,
Hypotension,poor
poorcardiac
cardiac function
function ifif given
given with
with gress
gressofofdiabetic
diabetic nephropathy.
nephropathy.
other
other cardiodepressant
cardiodepressant drugs;
drugs; congestive
congestive
,QGLFDWLRQV
,QGLFDWLRQVMild-to-moderate
Mild-to-moderate essential
essential
hyperten-
hyperten-
heart
heartfailure;
failure;aortic
aorticstenosis;
stenosis; pre-existing
pre-existing ab-
ab-
sion
sion(alone,
(alone,ororwith
with
thiazide-diuretic
thiazide-diuretic
therapy)
therapy)
normalities
normalitiesininthethesinoatrial
sinoatrial and/or
and/or atrioven-
atrioven-
and
and severe
severehypertension
hypertension resistant
resistant
to other
to other
73
73
treatment; CHF with left ventricular dysfunc- • With hyponatremia (plasma-sodium concentration
tion following MI; diabetic nephropathy (mi- <130 mmol/L);
croalbuminuria >30 mg/day) in type 1 diabe- • With hypotension (SBP <90 mmHg);
• With unstable heart failure;
tes.
• Receiving high-dose vasodilator therapy;
Contraindications: Known hypersensitivity to • Known vascular disease
captopril and other ACE inhibitors, or any Cough (dry, hacking, non-productive one, which
component of the formulation; significant hy- usually occurs within the first few months of
perkalemia; hypotension; significant bilateral treatment and should generally resolve within
renal artery stenosis; angioedema, including 1-4 weeks after discontinuation of the ACE in-
that related to previous treatment with an ACE hibitor).
inhibitor; pregnancy; concurrent use with Angioedema (may occur rarely and may involve
aliskiren in patients with DM or renal impair- head and neck, or the intestine); potential for
ment. myopathy increased (limit simvastatin dose to
20 mg/day if used concurrently); peripheral
Dose: vascular disease or generalized atherosclero-
NOTE: Titrate dose according to patient's response; use the
sis (risk of renovascular disease); in collagen
lowest effective dose.
vascular disease (increased risk of agranulo-
Heart failure, by mouth, ADULT, Initial dose: 6.25-
cytosis).
12.5 mg 3 times daily in conjunction with car-
Severe or symptomatic aortic stenosis (risk of hypo-
diac glycoside and diuretic therapy (initial
tension) and in hypertrophic cardiomyopathy.
dose depends upon patient's fluid/electrolyte
Renal impairment (increased risk hyperkalemia and
status); increased at 2-week intervals to 25-75
may affect the excretion of ACE inhibitors);
mg twice daily (target dose, 50 mg 3 times
jaundice or marked elevations of hepatic en-
daily).
zymes (discontinue use due to risk of hepatic
Hypertension, by mouth, ADULT, initial dose: 25 mg
necrosis); surgery (excessive hypotension
twice daily, may increase by 12.5-25 mg/dose
may occur during anesthesia and after sur-
at 1- to 2-week intervals up to a total dose of
gery); neutropenia and agranulocytosis; aortic
150-200 mg/day in 2 divided doses. See Clini-
stenosis; renal artery stenosis; obstructive
cal Practice Guidelines – Hypertension for fur-
sleep apnea.
ther information.
Elderly (may be more predisposed to first dose
Hypertensive urgencies, by mouth, ADULT, 25 mg
hypotension, hyperkalemia and renovascular
may repeat as required. See Clinical Practice
disease than younger patients).
Guidelines – Hypertension for further infor-
Pregnancy (use in first trimester may cause major
mation.
LV dysfunction following MI, by mouth, ADULT, congenital malformations; use in second and
third trimester may cause fetal renal dysfunc-
Initial: 6.25 mg; if tolerated, follow with 12.5
tion and oligohydramnios, and subsequently
mg 3 times/day; then increase to 25 mg 3
fetal death); breastfeeding (avoid use in the
times/day during next several days and then
first few weeks after delivery, particularly in
gradually increase over next several weeks to
preterm infants, due to risk of profound neona-
target dose of 50 mg 3 times/day (some dose
tal hypertension).
schedules are more aggressive to achieve an NOTE: Initiation of therapy in patients with ischemic heart
increased goal dose within the first few days disease or cerebrovascular disease warrants close
of initiation). observation due to the potential consequences posed
Diabetic nephropathy, by mouth, ADULT, Initial: 25 by falling blood pressure (e.g., MI, stroke). Fluid re-
mg 3 times/day; may be taken with other anti- placement, if needed, may restore blood pressure;
hypertensive therapy if required to further therapy may then be resumed. Discontinue therapy in
patients whose hypotension recurs.
lower blood pressure. NOTE: Concomitant use of an angiotensin receptor blocker
Dose Adjustments: (ARB) or renin inhibitor (e.g., aliskiren) is associated
with an increased risk of hypotension, hyperkalemia,
Elderly: and renal dysfunction.
Start treatment with lower doses.
Renal Impairment: Adverse Drug Reactions:
For mild-to-moderate renal impairment, dose reduc- Common: Cough, dizziness, dysgeusia, fatigue,
tion is warranted; for severe impairment, the headache, hyperkalemia, hypersensitivity re-
patient should be referred to a specialist. actions, hypertension, malaise, nausea, rash.
Less Common: Abnormal dreams, anaphylactoid
Precautions: reactions, angina pectoris, anorexia, chest
WARNING: Overzealous treatment with ACE inhibitors may pain, congestive heart failure, constipation, di-
lead to sudden hypotension, renal insufficiency or arrhea, dryness of mouth, elevated hepatic
failure, hyperkalemia with the risk of arrhythmia.
Discontinue as soon as possible when pregnancy is detect- aminotransferases, alkaline phosphatase and
ed (may cause fetal injury or death). serum bilirubin; fever, flushing, hoarseness,
itching, muscle cramps, MI, pallor, palpita-
NOTE: ACE inhibitors should be initiated with careful clinical
monitoring in those with severe heart failure or those: tions, Raynaud’s syndrome, sore throat, sto-
• Receiving multiple or high-dose diuretic therapy matitis, tachycardia, taste disturbances, urti-
(e.g., more than 80 mg of furosemide daily or its caria, vomiting.
equivalent); Rare: Acute renal failure, angioedema, bron-
• With hypovolemia; chospasm, cardiac arrest, cerebrovascular in-
74
sufficiency, dyspnea, erythema multiforme,
Indications: Hypertension (may be employed alone
exfoliative dermatitis, gynecomastia, hepatitis,
or used concomitantly with other antihyper-
hemolytic anemia, hyponatremia, impotence,
tensive agents).
myalgia, neuropathy, oliguria, orthostatic hy-
potension, pancreatitis, pancytopenia, polyu- Contraindications: Known hypersensitivity to
ria, proteinuria, psoriasis, renal insufficiency, clonidine or any component of the formulation;
rhythm disturbances, serum sickness-like bradyarrhythmia secondary to second- or
syndrome, Stevens-Johnson syndrome, syn- third-degree AV block or sick sinus syndrome.
cope, toxic epidermal necrolysis, visceral an-
gioedema. Dose:
NOTE: The dose of clonidine should be adjusted according
Drug Interactions: to the patient’s individual BP response.
Monitor closely with: Hypertension, by mouth, ADULT, initially 75 mi-
Angiotensin II Receptor Blockers – these may en- crograms 2-3 times daily, increased by 75 mi-
hance the adverse effects of captopril. crograms daily every 2-3 days (maximum, 1.2
Antihypertensives – captopril may enhance the mg daily); Maintenance, 150-300 micrograms
hypotensive effects of other antihypertensives. twice daily.
Drugs which reduce blood pressure (See Appendix Hypertensive urgencies, orally or sublingually,
– Table D) – captopril reduces BP and, if giv- ADULT, 75 micrograms. See Clinical Practice
en with these drugs, may have additional hy- Guidelines – Hypertension for further infor-
potensive effects. mation.
Loop Diuretics – these increase the risk of severe Dose Adjustment:
hypotension with the first dose of an ACE in-
Renal Impairment:
hibitor, especially in patients on high-dose
Dose should be adjusted according to the degree of
loop diuretic and/or conditions, such as heart
impairment (patients may benefit from a lower
failure; may increase the risk of ACE inhibitor-
initial dose); use drug with caution for mild-to-
induced renal impairment.
moderate renal impairment; for severe im-
Thiazide Diuretics – these may increase the risk of
severe hypotension with the first dose of an
specialist.
ACE inhibitor (lesser risk than with loop diuret-
ics). Precautions:
Avoid concomitant use with: WARNING: Severe withdrawal syndrome (rebound HTN)
Antacids (e.g., aluminum or magnesium hydroxide) may occur after abrupt discontinuation. Sudden ces-
– these may decrease the serum concentra- sation of clonidine treatment has, in some cases, re-
tion of captopril. sulted in symptoms, such as nervousness, agitation,
headache, and tremor accompanied or followed by a
Indomethacin – this decreases the antihypertensive
rapid rise in BP and elevated catecholamine concen-
effect of captopril. tration in the plasma.
NSAIDs (including selective COX-2 inhibitors) – Taper dose over 5-7 days before stopping the drug.
these may reduce antihypertensive effect of
ACE inhibitor and may increase risk of renal An excessive rise in BP following discontinuation of
impairment and hyperkalemia. clonidine therapy can be reversed by admin-
Potassium supplements or drugs which can cause istration of oral clonidine hydrochloride; in pa-
potassium retention (e.g., potassium-sparing tients with mild-to-moderate bradyarrhythmia,
diuretics) – combination with these drugs may constipation or polyneuropathy; avoid use in
lead to hyperkalemia. patients with depression or a history of it;
Salicylates – these may reduce the antihypertensive avoid use in coronary heart disease, severe
effect of ACE inhibitors; may diminish other coronary insufficiency, conduction disturb-
beneficial pharmacodynamic effects desired ances, recent MI, cerebrovascular disease,
for the treatment of congestive heart failure. Raynaud’s phenomenon or other vasospastic
peripheral vascular disease (may be exacer-
Administration: Take on an empty stomach. bated by clonidine); diabetes mellitus
NOTE: The patient may feel dizzy when taking this medicine. (clonidine may cause transient rise in blood
Advise the patient to get up gradually from sitting or glucose concentration).
lying to minimize this effect; and sit or lie down if the
Renal impairment (clonidine may worsen chronic
patient becomes dizzy or light-headed.
renal failure; surgery (stopping clonidine ab-
Pregnancy Category: C in 1st trimester; D in 2nd & ruptly may precipitate a severe withdrawal
3rd trimesters. syndrome; maintain treatment through periop-
erative period using parenteral dosing if nec-
essary).
Children (commonly have GI illnesses which lead to
CLONIDINE vomiting; may be particularly susceptible to
hypertensive episodes resulting from abrupt
Oral: 75 microgram tablet (as hydrochloride) inability to take medication); elderly (can
cause drowsiness).
An imidazoline-derived, centrally-acting agonist at Pregnancy (may lower fetal heart rate, but risk
alpha 2 adrenoceptors and imidazoline recep- should be balanced against the risk of uncon-
tors, which acts by reducing sympathetic tone trolled maternal hypertension; avoid IV injec-
resulting in BP lowering.
75
tion); breastfeeding (avoid use if possible; lim-
ited data available; present in milk and may DILTIAZEM
decrease prolactin secretion).
Presence of a beta-blocker can worsen the with- Oral: 30 mg and 60 mg tablet (as hydrochloride)
drawal syndrome (when used with beta- 60 mg, 90 mg, 120 mg and 180 mg MR cap-
blockers, withdraw clonidine over at least 7 sule (as hydrochloride)
days after stopping the beta-blocker as re- 90 mg, 120 mg and 180 mg MR tablet (as
bound hypertension is worse if clonidine is hydrochloride)
suddenly withdrawn).
NOTE: Clonidine may make the patient feel drowsy and may A nondihydropyridine, calcium-channel blocker,
increase the effects of alcohol. If the patient is affect- which has a negative chronotropic effect, thus
ed, do not drive or operate machinery. decreasing the workload of the heart, and
Adverse Drug Reactions: consequently reducing its oxygen require-
ments.
Common: Constipation, depression, dizziness,
drowsiness, dry mouth, fatigue, headache, Indications: Prophylaxis and treatment of angina;
malaise, nausea, orthostatic hypotension, sal- hypertension.
ivary gland pain, sedation, sexual dysfunction,
sleep disturbances, vomiting. Contraindications: Known hypersensitivity to
Less Common: Bradycardia, confusion, delusion, diltiazem or any component of the formulation;
disturbed mental state, hallucination, itching, marked bradycardia (below 40 beats/minute);
nightmare, paresthesia, pruritus, rash, urticar- sick sinus syndrome (except in the presence
ia. of a pacemaker); severe hypotension (<90
Rare: Alopecia, AV block, colonic pseudo- mmHg systolic); congestive heart failure;
obstruction, decreased lacrimation, dry eyes, acute porphyria; second- or third-degree atrio-
gynecomastia, hepatitis, impaired visual ac- ventricular block (without pacemaker); Wolff-
commodation, nasal dryness, Raynaud’s phe- Parkinson-White syndrome; acute MI and
nomenon, urinary retention. pulmonary congestion; pregnancy.
Drug Interactions: Dose:

Monitor closely with: Hypertension, by mouth, ADULT, 30 mg three times
CNS depressants (e.g., alcohol, barbiturates or a day (maximum dose, 360 mg daily in 3-4 di-
other sedating drugs) – these may enhance vided doses).
clonidine’s therapeutic and adverse effects Hypertension (controlled-release products), by
(sedation, bradycardia and hypotension). mouth, ADULT, initially 180-240 mg once dai-
Drugs which affect sinus node function or AV nodal ly; increase as required up to 360 mg once
conduction (e.g., digitalis and calcium channel daily.
blockers) – enhanced potential for additive ef- See under the section on Anti-Anginal Agents for
fects, such as AV block and bradycardia. more information.
Drugs which can reduce blood pressure (See Ap-
pendix – Table D) and can slow heart rate –
these may increase the risk and extent of hy-
potension and bradycardia. ENALAPRIL
Beta-blockers – combination with clonidine may
Oral: 5 mg and 10 mg tablet (as maleate)
enhance bradycardia and hypotension; may
cause paradoxical increase in BP. An oral angiotensin-converting enzyme inhibitor
Tricyclic Antidepressants – these may reduce the (ACEI), which is converted by hydrolysis to
hypotensive effect of clonidine, leading to in- enalaprilat whose effects are similar with cap-
creased BP. topril.
Administration: If further increments are needed Indications: Hypertension; heart failure.
until the desired response is achieved, taking
the larger portion of the oral daily dose at bed- Contraindications: Known hypersensitivity to
time may minimize transient adjustment ef- enalapril and any ACE inhibitor, or any com-
fects of drowsiness and dry mouth. ponent of the formulation; significant bilateral
NOTE: The patient may feel dizzy when taking this medicine. renal artery stenosis; renovascular disease;
Advise the patient to get up gradually from sitting or pregnancy; significant hyperkalemia; hypoten-
lying to minimize this effect; and sit or lie down if the sion; history of angioedema (ACEI-induced,
patient becomes dizzy or light-headed. hereditary or idiopathic); concurrent use of
Pregnancy Category: C aliskiren in patients with DM or renal impair-
ment.
Dose:
Heart failure (adjunct), asymptomatic left ventricular
dysfunction, by mouth, ADULT, initially 2.5 mg
once daily, increased gradually over 2-4
weeks to 10-20 mg twice daily if tolerated.
76
Hypertension, by mouth, ADULT, initially 5 mg once advised for at least 2 hours after administration or un-
daily (lower dose if used in addition to a diu- til blood pressure is stable.
retic); increased at intervals of 1-2 weeks up Adverse Drug Reactions:
to a total dose of 20 mg/day in 1 or 2 divided Common: Blurred vision, cough, depression, dizzi-
doses. See Clinical Practice Guidelines – Hy- ness, dyspnea, headache, hyperkalemia, hy-
pertension for further information; CHILD, re- pertension.
fer to a specialist. Less Common: Abnormal dreams, alopecia, ana-
Dose Adjustments: phylactoid reactions, angioedema, anorexia,
Renal Impairment: chest pain, confusion, diarrhea, drowsiness,
For mild-to-moderate renal impairment, dose reduc- dry cough, dry mouth, elevated hepatic ami-
tion is warranted; for severe impairment, the notransferases and bilirubin; fatigue, fever,
patient should be referred to a specialist. flushing, hoarseness, hypotension, impotence,
Hepatic Impairment: insomnia, muscle cramps, nausea, nervous-
Same dosage as in patients with normal hepatic ness, palpitations, rash, renal impairment,
function may be used in patients with mild-to- sweating, tinnitus, urticaria, vertigo.
moderate hepatic impairment; for severe im- Rare: Abdominal pain, agranulocytosis, allergic
pairment, the patient should be referred to a alveolitis, aplastic anemia, arrhythmias, bron-
specialist. chospasm, electrolyte disturbances, exfolia-
tive dermatitis, GI angioedema, gynecomastia,
Precautions: hepatitis, hemolytic anemia, hypersensitivity-
WARNING: Overzealous treatment with ACE inhibitors may like reactions, hyponatremia, ileus, liver dam-
lead to sudden hypotension, renal insufficiency or age, neuropathy, neutropenia, pancreatitis,
failure hyperkalemia with the risk of arrhythmia. paresthesia, peptic ulcer, proteinuria, psoria-
NOTE: ACE inhibitors should be initiated with careful clinical sis, pulmonary infiltrates, Raynaud’s syn-
monitoring in those with severe heart failure or those: drome, Stevens-Johnson syndrome, thrombo-
• Receiving multiple or high-dose diuretic therapy cytopenia, toxic epidermal necrolysis, visceral
(e.g., more than 80 mg of furosemide daily or its angioedema, vomiting.
equivalent);
• With hypovolemia; Drug Interactions:
• With hyponatremia (plasma-sodium concentration Monitor closely with:
<130 mmol/L); Angiotensin II Receptor Blockers – these may en-
• With hypotension (SBP <90 mmHg); hance the adverse effects of enalapril.
• With unstable heart failure;
Antihypertensives – enalapril may enhance the
• Receiving high-dose vasodilator therapy;
• Known vascular disease
hypotensive effects of other antihypertensives.
Cough (dry, hacking, non-productive one, which Drugs which reduce blood pressure (See Appendix
usually occurs within the first few months of – Table D) – enalapril reduces BP and, if giv-
treatment and should generally resolve within en with these drugs, may have additional hy-
1-4 weeks after discontinuation of the ACE in- potensive effects.
hibitor); concomitant use of diuretics (see Loop diuretics – these increase the risk of severe
notes below); hypotension with the first dose, hypotension with the first dose of an ACE in-
especially in patients: on diuretics, on a low- hibitor, especially in patients on high-dose
sodium diet, on dialysis, if dehydrated, or with loop diuretic and/or conditions, such as heart
heart failure; peripheral vascular disease or failure; may increase the risk of ACE inhibitor-
generalized atherosclerosis; severe or symp- induced renal impairment.
tomatic aortic stenosis. Metformin – its hypoglycemic effect is possibly
Monitor renal function before, and during, treatment; enhanced by enalapril.
renal impairment (reduce dose); hepatic im- Thiazide Diuretics – these may increase the risk of
pairment; history of idiopathic or hereditary severe hypotension with the first dose of an
angioedema. ACE inhibitor (less than with loop diuretics).
Elderly (may be more predisposed to first dose Avoid concomitant use with:
hypotension, hyperkalemia and renovascular Antacids (e.g., aluminum or magnesium hydroxide)
disease than younger patients). – may decrease the serum concentration of
Pregnancy (first trimester: may cause major con- enalapril.
genital malformations; second and third tri- Contraceptives, Oral – possible antagonism of
mesters: may cause fetal renal dysfunction hypotensive effect by estrogens.
and oligohydramnios, and subsequently fetal Indomethacin – this decreases the antihypertensive
death); breastfeeding (amount probably too effects of enalapril.
small to be harmful). NSAIDs (including selective COX-2 inhibitors) –
USE WITH DIURETICS. Because of the risk of very rapid fall these may reduce antihypertensive effect of
in blood pressure in volume-depleted patients, treat- ACE inhibitor and may increase risk of renal
ment should be initiated with very low doses. High- impairment and hyperkalemia.
dose diuretic therapy (e.g., with furosemide at doses Potassium supplements or drugs which can cause
>80 mg daily) should be discontinued, or the dose potassium retention (e.g., potassium-sparing
significantly reduced, at least 24 hours before starting
enalapril (may not be possible in heart failure due to
diuretics, and spironolactone) – combination
the risk of pulmonary edema). If high-dose diuretic with these drugs may lead to hyperkalemia.
therapy cannot be stopped, medical supervision is Salicylates – these may reduce the antihypertensive
effect of ACE inhibitors; may diminish other
77
beneficial pharmacodynamic effects desired volume may diminish uteroplacental perfu-
for the treatment of congestive heart failure. sion); breastfeeding (may inhibit lactation).
Administration: May be taken with or without food. Adverse Drug Reactions:
NOTE: The patient may feel dizzy when taking this medicine. Common: Dizziness, headache, hyperuricemia,
Advise the patient to get up gradually from sitting or hypochloremic alkalosis, hypokalemia, hypo-
magnesemia, hyponatremia, lethargy, muscle
patient becomes dizzy or light-headed.
cramps, orthostatic hypotension, polyuria,
Pregnancy Category: C in 1st trimester; D in 2nd & weakness.
rd
3 trimesters. Less Common: Blurred vision, dyslipidemia, hy-
percalcemia, hyperglycemia, impotence, rash.
Rare: Agranulocytosis, aplastic anemia, cardiac
arrhythmias, cholecystitis, constipation, der-
HYDROCHLOROTHIAZIDE matitis, diarrhea, hemolytic anemia, hyper-
sensitivity reactions, impotence, intrahepatic
Oral: 12.5 mg, 25 mg and 50 mg tablet cholestatic jaundice, leukopenia, nausea, ne-
crotizing vasculitis, pancreatitis, purpura,
A moderately-potent, thiazide diuretic whose maxi- thrombocytopenia, toxic epidermal necrolysis,
mal antihypertensive effect is usually ob- visual disturbances, vomiting.
served at doses lower than those that produce
maximal diuretic effect. Drug Interactions:
Indications: Mild hypertension (alone), or in mod- Digoxin – hypokalemia caused by hydrochlorothia-
erate or severe hypertension (in combination zide may increase its cardiac toxicity.
with other drugs); edema. Drugs which reduce blood pressure (see Appendix
Contraindications: Severe renal impairment or – Table D) – thiazide diuretics reduce BP and,
anuria; severe hepatic impairment; hypo- if given with these drugs, may have additional
natremia, hypercalcemia, refractory hypoka- hypotensive effects.
lemia, symptomatic hyperuricemia; Addison Loop Diuretics – thiazide diuretics, given with these
disease. drugs, have synergistic effect which may
cause profound diuresis and serious electro-
Dose: lyte disturbance.
Hypertension, by mouth, ADULT, 12.5-25 mg daily, Potassium-lowering drugs – these may increase the
increased to 25-100 mg daily if necessary; possible risk of hypokalemia.
CHILD, refer to a specialist. See Clinical Prac- Salbutamol – increased risk of hypokalemia with
tice Guidelines – Hypertension for further in- high doses of this drug.
formation. Avoid concomitant use with:
Dose Adjustment: ACE inhibitors – thiazide diuretics may increase the
risk of severe hypotension with the first dose
Renal Impairment:
of an ACE inhibitor.
Avoid use if creatinine clearance <10 mL/minute
Angiotensin II receptor blockers – treatment with
Precautions: high-dose thiazide diuretics increases risk of
High doses of hydrochlorothiazide (may cause excessive hypotension after the first dose of
hypokalemia; if there is a history of kidney an ARB (due to volume depletion).
stones, avoid use); hypokalemia (may precipi- Contraceptives, Oral – these may antagonize the
tate coma – potassium-sparing diuretic can hypotensive effect of thiazide diuretics.
prevent this); gout (diuretic-induced rise in se- Hydrocortisone – possible antagonism of diuretic
rum uric acid concentration); heart failure with effect; increased risk of hypokalemia.
significant edema (hyponatremia may occur, Ibuprofen – increased risk of nephrotoxicity; antag-
particularly if higher doses are used with a onism of diuretic effect.
salt-restricted diet and/or potassium – sparing Lidocaine – its effect is antagonized by hydrochloro-
diuretics and excess water intake); thiazide-induced hypokalemia.
Hepatic impairment (avoid in severe liver disease; in Metformin – antagonism of hypoglycemic effect.
cirrhosis, diuretic-induced volume depletion NSAIDs (including selective COX-2 inhibitors) –
and/or electrolyte disturbance – may precipi- these may reduce: renal function, diuretic and
tate hepatic coma or encephalopathy); in al- hypotensive effect; and increase risk of ne-
coholic cirrhosis (increased risk of hypomag- phrotoxicity.
nesemia);
Administration: Usually taken once daily in the
Renal impairment; electrolytes may need to be
morning. If the patient is to take it twice a day,
monitored with high doses or in renal impair-
take the first dose in the morning and the sec-
ment; may aggravate diabetes mellitus, gout
ond dose before 6 in the evening.
and systemic lupus erythematosus; porphyria.
Elderly (more susceptible to electrolyte imbalance Pregnancy Category: B
and orthostatic hypotension).
Pregnancy (avoid use; third trimester: may cause
electrolyte disturbances and thrombocytope-
nia in neonates; reduction in maternal blood
78
creased risk of hyperkalemia); hepatic im-
LOSARTAN pairment.
Pregnancy (avoid use unless essential; may ad-
Oral: 50 mg and 100 mg tablet (as potassium salt) versely affect fetal and neonatal BP control,
and renal function; drugs which act on the ren-
An angiotensin II type 1 (AT 1 ) receptor blocker in-angiotensin system can cause injury and
whose efficacy in hypertension is similar to death to the developing fetus); breastfeeding
that of ACE inhibitors, but is associated with a (information is limited; use better alternative
lower incidence of side-effects, such as dry treatment options).
cough and angioedema. NOTE: Concomitant use of an ACE inhibitor or renin inhibitor
(e.g., aliskiren) is associated with an increased risk of
Indications: Treatment of hypertension; treatment
hypotension, hyperkalemia and renal dysfunction.
of diabetic nephropathy in patients with type 2
diabetes mellitus (noninsulin dependent, Adverse Drug Reactions:
NIDDM) and a history of hypertension; risk re- Common: Dizziness, fatigue, headache, hyper-
duction of stroke in patients with HTN and left kalemia, hypoglycemia, nausea, upper respir-
ventricular hypertrophy (LVH). atory tract infections, urinary tract infections.
Less Common: Abnormal liver function, angina,
back pain, decreased hemoglobin, diarrhea,
losartan or any component of the formulation; dyspepsia, dyspnea, edema, hypotension
pregnancy; concomitant use with aliskiren in (first-dose), insomnia, malaise, muscle
patients with diabetes mellitus. cramps, myalgia, nasal congestion, palpita-
Dose: tion, pharyngitis, pruritus, rash, sleep disor-
Hypertension, by mouth, ADULT, usual starting ders.
dose: 50 mg once daily; can be administered Rare: Anaphylaxis, anemia, angioedema, atrial
once or twice daily with a total daily dose fibrillation, cerebrovascular accidents, cough,
ranging from 25-100 mg (usual initial dose in depression, erectile dysfunction, hepatitis, hy-
patients receiving diuretics, or those with in- ponatremia, pancreatitis, purpura, renal im-
travascular volume depletion: 25 mg once dai- pairment, rhabdomyolysis, syncope, thrombo-
ly). See Clinical Practice Guidelines – Hyper- cytopenia, vasculitis.
tension for further information. Drug Interactions:
Nephropathy in patients with type 2 DM and hyper-
tension, by mouth, ADULT, initial dose: 50 mg
Antifungal agents (e.g., azole derivatives, systemic)
once daily; can be increased to 100 mg once – these may decrease the metabolism of
daily based on BP response. losartan, increasing its concentration and risk
Stroke reduction (HTN with LVH), by mouth,
of toxicity.
ADULT, 50 mg once daily (maximum daily
Antihypertensives – ARBs may enhance their hypo-
dose, 100 mg); may be used in combination
tensive effect.
with a thiazide diuretic.
Loop Diuretics – increased risk of excessive hypo-
Dose Adjustments: tension after the first dose of an ARB because
Elderly: of volume depletion.
No initial dosage adjustment necessary. NSAIDs (including selective COX-2 inhibitors) –
Renal Impairment: these may reduce the antihypertensive effect
Same dosage as in patients with normal renal func- of losartan, and increase the risk of hyper-
tion may be used in patients with mild-to- kalemia or acute renal failure.
moderate renal impairment; for severe im- Phenobarbital – this decreases AUC of losartan.
pairment, the patient should be referred to a Rifampicin – this may increase the metabolism of
specialist. losartan, decreasing its concentration and af-
Hepatic Impairment: fecting BP control.
For mild-to-moderate hepatic impairment, dose Thiazide Diuretics – increased risk of excessive
reduction is warranted; for severe impairment, hypotension after the first dose of an ARB be-
the patient should be referred to a specialist. cause of volume depletion.
Precautions: ACE Inhibitors – angiotensin II receptor blockers
WARNING: Should be discontinued when pregnancy is may enhance the adverse effects of ACE in-
detected. hibitors.
Peripheral vascular disease (patients may be more NOTE: Dual blockade of the Renin-Angiotensin- Aldosterone
system (i.e., ARB and ACEI combination) in patients
likely to have renal artery stenosis); volume or
with established heart failure, atherosclerotic disease,
sodium depletion (may activate the renin- or diabetes with end-organ damage is associated with
angiotensin system leading to excessive hy- higher risk for hypotension, syncope, hyperkalemia,
potension); caution in aortic or mitral valve and disordered renal function, including acute renal
stenosis and in hypertrophic cardiomyopathy; failure.
angioedema (may occur rarely and may in- ACE Inhibitors and beta blockers used concomitant-
volve head and neck or the intestine); hyper- ly – increase heart-failure related morbidity.
kalemia; correct volume depletion prior to ad- Potassium supplements or drugs which can cause
ministration in patients who are salt- or vol- potassium retention (e.g., potassium-sparing
ume-depleted; renal function deterioration (in- diuretics and spironolactone) – combination
79
with these drugs may increase the risk of hy- hypotension, psychosis, rash, sleep disturb-
perkalemia. ance, sore or “black” tongue.
Rare: Arthralgia, bone marrow depression, hepato-
toxicity with acute or chronic active hepatitis or
NOTE: The patient may feel dizzy when taking this medicine.
Advise the patient to get up gradually from sitting or hepatic necrosis; hyperprolactinemia, hyper-
lying to minimize this effect; and sit or lie down if the sensitivity reactions, jaundice, leukopenia,
patient becomes dizzy or light-headed. myocarditis, nausea, pancreatitis, Parkinson-
ism, pericarditis, sialadenitis, stomatitis,
Pregnancy Category: C in 1st trimester; D in 2nd
rd thrombocytopenia, toxic epidermal necrolysis,
and 3 trimesters. urine darkens on standing, vomiting.
Drug Interactions:
METHYLDOPA Chlorpromazine – this enhances the hypotensive
effect of methyldopa; there is an increased
Oral: 125 mg and 250 mg tablet risk of extrapyramidal effects.
Drugs which reduce blood pressure (See Appendix
A centrally-acting, alpha 2 -adrenoceptor agonist that – Table D) – methyldopa reduces BP and, if
is useful in the management of hypertension given with these drugs, may have additional
in pregnancy. hypotensive effects.
Indication: Hypertension in pregnancy. Salbutamol – acute hypotension has been reported
with infusion of salbutamol.
Contraindications: Known hypersensitivity to Avoid concomitant use with:
methyldopa or any component of the formula- Iron preparations (e.g., ferrous sulfate, ferrous
tion; pheochromocytoma; active liver disease; gluconate) – these reduce bioavailability of
depression, porphyria; patients in whom pre- methyldopa, decreasing its activity and inter-
vious methyldopa treatment resulted in liver fering with BP control.
abnormalities, or direct Coombs’ positive he- Contraceptives, Oral – possible antagonism of
molytic anemia. hypotensive effect by estrogens.
Dose: Ibuprofen – possible antagonism of hypotensive
Hypertension in pregnancy, by mouth, ADULT, effect.
initially 250 mg 2-3 times daily (gradually in- Administration: May be taken with or without food.
creased at intervals of 2 or more days, if nec- NOTE: The patient may feel dizzy when taking this medicine.
essary; maximum, 3 g daily). Advise the patient to get up gradually from sitting or
Dose Adjustment: patient becomes dizzy or light-headed.
Renal Impairment:
Start with a small dose or adjust dosage frequency
(the usual initial dose may be all that is re-
quired). For severe impairment, the patient
METOPROLOL
Precautions:
Monitor blood count and liver function before treat- Oral: 50 mg tablet
ment and at intervals during first 6-12 weeks,
or if unexplained fever occurs; history of de- A beta 1 -adrenoceptor (cardioselective) antagonist
pression (may be exacerbated by methyldo- without intrinsic sympathomimetic activity
pa); positive direct Coombs’ test (may affect (ISA), which may be advantageous in treating
blood cross-matching; interference with labor- hypertensive patients who also suffer from
atory tests); renal impairment (increased sen- asthma, diabetes, or peripheral vascular dis-
sitivity to hypotensive and sedative effects); ease.
hepatic impairment (caution in history of liver Indications: Hypertension; angina pectoris; con-
disease; avoid use if possible); breastfeeding gestive heart failure.
(amount too small to be harmful).
Avoid abrupt withdrawal. Contraindications: Known hypersensitivity to
SKILLED TASKS. May impair ability to perform skilled or metoprolol and other beta-blockers, or any
hazardous tasks, e.g., operating machinery or driving. component of the formulation; reversible air-
Adverse Drug Reactions: way diseases; second or third degree heart
block; shock (cardiogenic and hypovolemic);
Common: Diarrhea, dizziness, dryness of mouth,
fatigue, fever, headache, light-headedness, bradycardia (45-50 beats/minute); sick sinus
positive Coombs’ test, sedation, tiredness, syndrome, severe hypotension; uncontrolled
weakness. heart failure.
Less Common: Angina, bradycardia, constipation, Dose:
depression, edema, sodium and water/fluid re- Angina, by mouth, ADULT, initially 25-50 mg twice
tention, hemolytic anemia, impaired concen- daily; usual dosage range is 50-200 mg twice
tration and memory, decreased libido and im- daily (maximum dose, 400 mg/day); increase
potence in men, nasal congestion, orthostatic dose gradually at weekly intervals to achieve
80
desired effect; extended release: initially 100 NOTE: Beta-blocker therapy should not be withdrawn
mg/day (maximum, 400 mg/day). abruptly, but gradually tapered over 1-2 weeks to
avoid acute tachycardia, hypertension, and/or ische-
Heart failure, by mouth, ADULT, extended release:
mia. Severe exacerbations of angina, ventricular ar-
initially 25 mg once daily (reduce to 12.5 mg rhythmias and myocardial infarction have been re-
once daily in NYHA class higher than class II); ported following abrupt withdrawal of beta-blocker
may double dosage every 2 weeks as tolerat- therapy. Temporary but prompt resumption of beta-
ed (target dose, 200 mg daily). blocker therapy may be indicated with worsening of
Hypertension, by mouth, ADULT, immediate re- angina or acute coronary insufficiency.
NOTE: Major surgery: Although perioperative beta-blocker
lease: initially 50 mg once daily for 1 week (ef-
therapy is recommended prior to elective surgery in
fective dosage range: 100-200 mg/day in 1 or selected patients, use of high-dose extended-release
2 divided doses; increase dose at weekly in- metoprolol in patients naive to beta-blocker therapy
tervals to desired effect); CHILD, refer to a undergoing non-cardiac surgery has been associated
specialist. See Clinical Practice Guidelines – with bradycardia, hypotension, stroke, and death.
Hypertension for further information. Chronic beta-blocker therapy should not be routinely
withdrawn prior to major surgery.
Dose Adjustments:
Renal Impairment: Adverse Drug Reactions:
Same dosage as in patients with normal renal func- Common: Alteration of glucose and lipid metabo-
tion may be used in patients with mild-to- lism, bradycardia, bronchospasm, cold ex-
moderate renal impairment; for severe im- tremities, depression, diarrhea, dizziness,
pairment, the patient should be referred to a dyspepsia, dyspnea, exacerbation of Ray-
specialist. naud’s phenomenon, fatigue, hallucinations,
Hepatic Impairment: first degree heart block (P-R interval ≥0.26
For mild-to-moderate hepatic impairment, dose seconds), heart failure, hypotension, nausea,
reduction may be warranted; for severe im- pruritus, second- and third-degree heart block,
pairment, the patient should be referred to a shortness of breath, tiredness, syncope, vom-
specialist. iting, wheezing.
Less Common: Acute urinary retention, anxiety,
Precautions: cardiogenic shock, chest pain, claudication,
WARNING: Abrupt withdrawal may exacerbate angina and, confusion, constipation, flatulence, gastric
in some cases, cause myocardial infarction and ven- pain, headache, heartburn, hyperhidrosis, im-
tricular arrhythmias and rebound hypertension. paired concentration, impotence, insomnia,
Anaphylactic reactions (use caution with history of muscle cramps, nasal congestion, nervous-
severe anaphylaxis to allergens; treatment of ness, nightmares, palpitations, peripheral
anaphylaxis, e.g., epinephrine, in patients tak- edema, Peyronie’s disease, rash, reduced li-
ing beta-blockers may be ineffective or even bido, sleep disturbances, somnolence, taste
promote undesirable effects); atrioventricular disturbance, urticaria, visual disturbances,
block (metoprolol commonly produces mild vertigo, xerostomia.
first-degree heart block); it may also produce Rare: Agranulocytosis, alopecia, arthritis, blurred
severe first- (P-R interval ≥0.26 sec), second, vision, cardiac arrest, catatonia, emotional la-
or third-degree heart block. Patients with bility, exacerbation of psoriasis, gangrene,
acute myocardial infarction have a high risk of hepatitis, hypersensitivity reaction, jaundice,
developing heart block of varying degrees. If laryngospasm, liver function abnormality, res-
severe heart block occurs, metoprolol should piratory distress, retroperitoneal fibrosis,
be discontinued and measures to increase thrombocytopenia, thrombocytopenic purpura,
heart rate should be employed. tinnitus.
Diabetes (beta-blockers may mask important signs
of acute hypoglycemia, such as tachycardia Drug Interactions:
and tremor, and increase incidence and se- Monitor closely with:
verity of hypoglycemia); psoriasis; psychiatric Alpha-/Beta-agonists – their vasopressor effect may
disease; hyperthyroidism (beta-blockers may be enhanced by beta-blockers.
mask clinical signs, e.g., tachycardia); pheo- Alpha 2 -agonists – these may enhance the AV-
chromocytoma (beta-blockers may aggravate blocking effect of beta blockers; sinus node
hypertension; alpha-blockers should be given dysfunction may also be enhanced; Beta-
first); hypotension (symptomatic hypotension Blockers may enhance the rebound hyperten-
may occur with use); heart failure; hepatic im- sive effect of the stated drugs.
pairment; myasthenia gravis; peripheral vas- Antihypertensives – beta-blockers may enhance the
cular disease (PVD) and Raynaud's disease; hypotensive effect of other antihypertensives.
conduction abnormality; vasospastic angina. Beta 2 -agonists – beta 1 -selective blockers may
Bronchospastic disease may be exacerbated- moni- diminish the bronchodilatory effect of beta 2 -
tor closely. agonists.
Elderly (bradycardia may be observed more fre- Calcium channel blockers – these may enhance
quently; dosage reductions may be neces- hypotensive effect of beta-blockers; there may
sary). be an increased risk of heart block or brady-
Pregnancy (may cause pharmacologic effects, such cardia due to negative chronotropic and ino-
as bradycardia, in the fetus and newborn in- tropic effects.
fant). Cardiac glycosides – beta-blockers may increase
their risk of heart block or bradycardia.
81
Digitalis glycosides – their concomitant use with Dose Adjustment:
beta blockers can increase the risk of brady- Renal Impairment:
cardia; slow atrioventricular conduction and For mild-to-moderate renal impairment, dose ad-
decrease heart rate. justments are not necessary; for severe im-
Rifampicin – this increases the metabolism of pairment, the drug is not recommended.
metoprolol, reducing its therapeutic effect. Hepatic Impairment:
Avoid concomitant use with: Avoid in severe liver disease.
CYP2D6 Inhibitors (see Appendix) – these increase
Precautions:
plasma metoprolol concentration, and de-
crease its cardioselectivity; may increase its Increased risk of gastritis and GI bleeding; asthma;
adverse effects, including heart block. urticaria; allergic disease; uncontrolled hyper-
NSAIDs – these may diminish the antihypertensive tension.
effect of beta-blockers. Renal impairment (avoid use; due to sodium and
water retention – deterioration in renal func-
Administration: May be taken with or without food. tion may increase risk of GI bleeding).
Hepatic impairment (avoid in severe impairment –
Pregnancy Category: C there is increased risk of GI bleeding).
Elderly; G6PD-deficiency, dehydration; gout.
Pregnancy (third trimester: impaired platelet func-
ANTITHROMBOTICS tion and risk of hemorrhage; delayed onset
and increased duration of labor with increased
blood loss; avoid analgesic doses, if possible,
in the last few weeks; with high doses, closure
ASPIRIN of fetal ductus arteriosus in utero and possibly
persistent pulmonary hypertension in the
Oral: 80 mg and 100 mg enteric-coated tablet
newborn; kernicterus in jaundiced neonates);
An irreversible, cyclo-oxygenase (COX) inhibitor, regular use of high doses could impair platelet
which inhibits platelet aggregation, and is use- function and produce hypoprothrombinemia in
ful in the long-term management of MI, includ- infant if neonatal vitamin K stores are low;
ing the prevention of further attacks. possible risk of Reye syndrome.
Indications: Primary prevention of acute MI and Adverse Drug Reactions:
stroke in patients with risk factors; secondary Common: Abdominal pain, asymptomatic blood
prevention of thrombotic cardiovascular or loss, back pain, bleeding time increased, diar-
cerebrovascular disease, and following by- rhea, dyspepsia, dyspnea, epistaxis, fatigue,
pass surgery; acute MI; acute ischemic stroke. GI irritation, headache, malaise, melena, nau-
sea, vomiting.
Contraindications: Known hypersensitivity (includ- Less Common: Anorexia, asthenia, confusion,
ing asthma, angioedema, urticaria, and rhini- dizziness, fever, flushing, gastritis, hemor-
tis) to acetylsalicylic acid and any other rhage rectum, hemorrhoids, hyperglycemia,
NSAIDs, or any component of the formulation; hypoglycemia (in children), hypotension, my-
children and adolescents <16 years (risk of algia, palpitations, syncope, tachycardia,
Reye syndrome); active peptic ulceration or thirst, tinnitus, vertigo.
bleeding GI ulcers; hemophilia and other Rare: Arrhythmia, convulsions, deafness, edema,
bleeding disorders; aspirin-sensitive asthma; GI ulcer and perforation, intracranial hemor-
thrombocytopenia; ulcerative colitis; lactating rhage, hypersensitivity reactions, including
mothers; acute hemorrhagic stroke or intrac- Stevens-Johnson syndrome; interstitial nephri-
erebral bleeding. tis, iron-deficiency anemia, myocarditis, pares-
Dose: thesia, renal insufficiency, seizures, thrombo-
Acute ischemic stroke, see under Nervous System cytopenia, toxic epidermal necrolysis.
and Musculoskeletal System. Drug Interactions:
Long-term management, by mouth, ADULT, up to Monitor closely with:
160 mg once daily (low-dose aspirin). Anticoagulant therapy (e.g., heparin, warfarin) –
Prophylaxis of myocardial infarction or cerebrovas- increased risk of bleeding.
cular disease, by mouth, ADULT, 80-100 mg Corticosteroids – these may decrease salicylate
once daily; CHILD 12-18 years, 80 mg once concentration when high-dose aspirin is used;
daily; CHILD <12 years, 1-5 mg/kg once daily increased risk of GI bleeding and ulceration.
(maximum, 80 mg). Oral hypoglycemics – their hypoglycemic effect may
Treatment of acute MI, by mouth, ADULT, 150-300 be increased by aspirin.
mg once daily; CHILD 12-18 years, 80 mg Phenytoin – its effect may be enhanced by aspirin.
once daily; CHILD <12 years, 1-5 mg/kg once Valproic acid – its concentration is increased by
daily (maximum, 80 mg). aspirin, thus increasing its therapeutic and ad-
verse effects; it also increases effects on
blood coagulation and platelet function.
ACE Inhibitors (e.g., enalapril) – the hyponatremic
and hypotensive effect of ACE inhibitors may
82
be diminished by aspirin; there is risk of renal Recent MI, stroke, or established peripheral arterial
impairment when aspirin is given in doses of disease, by mouth, ADULT, 75 mg/day (rec-
>300 mg daily. ommended as alternative to aspirin, or con-
Antacids (e.g., aluminum and magnesium hydrox- comitantly with aspirin if patient is not at in-
ide) – increased excretion of aspirin by alka- creased risk for bleeding but at high risk for
line urine. cardiovascular disease).
Diuretics (e.g., spironolactone) – the effectiveness
Dose Adjustments:
of diuretics in patients with underlying renal or
Renal Impairment:
cardiovascular disease may be diminished
Same dosage as in patients with normal renal func-
due to inhibition of renal prostaglandins.
tion may be used in patients with mild-to-
NSAIDs (e.g., ibuprofen, naproxen) – aspirin, even
moderate renal impairment; for severe im-
at low doses, increases risk of gastric ulcera-
tion with NSAIDs; these drugs can reduce the
specialist.
anti-platelet activity of low-dose aspirin and
Hepatic Impairment:
may reduce, or negate, its cardioprotective ef-
Use with caution; experience limited.
fect.
NOTE: CYP2C19 Inhibition and Poor Metabolizers:
Administration: Take tablets from packaging just Clopidogrel may be less effective in poor metabolizers
(lacking CYP2C19). >50% of Asians have CYP2C19
before use. Should be taken with food, or tak- genetic variants that inhibit clopidogrel metabolism.
en immediately after meals. Use of CYP2C19 inhibitors (Proton Pump Inhibitors)
or use in poor metabolizers may decrease anti-
Pregnancy Category: C; D in 3rd trimester
platelet effect.
Precautions:
WARNING: Effectiveness depends on activation to active
CLOPIDOGREL metabolite by cytochrome P450 system, principally
CYP2C19). Poor metabolizers at recommended dos-
Oral: 75 mg tablet es exhibit higher cardiovascular event rates after
acute coronary syndrome or percutaneous coronary
A thienopyridine-derived, platelet aggregation inhibi- intervention.
tor that has no effect on prostaglandin metab- Patients at risk of increased bleeding from trauma,
olism unlike aspirin, and is used as an alterna- surgery, or other pathological conditions; in
tive for patients who are contraindicated to patients taking medications that increase the
aspirin in the treatment of thrombosis. risk of bleeding; history of bleeding or hemo-
static disorders; bleeding diathesis; ulcers;
Indications: Prevention of atherothrombotic events
may need to discontinue 5-10 days before
in: peripheral arterial disease, or within 35
surgical procedure; patients allergic to aspirin
days of MI, or within 6 months of ischemic
who are undergoing PCI (risk of Thrombotic
stroke; in acute coronary syndrome without
thrombocytopenic purpura); renal impairment
ST-segment elevation (unstable angina or
(avoid use in severe impairment; increased
non-Q wave MI), including patients undergo-
risk of bleeding); hepatic impairment; preg-
ing stent placement following percutaneous
nancy (avoid use if possible).
coronary intervention (in combination with as-
pirin); in acute MI with ST-segment elevation, Adverse Drug Reactions:
and in combination with ASA in medically- Common: Abdominal pain, bleeding, chest pain,
treated patients eligible for thrombolytic thera- depression, diarrhea, dyspepsia, flu-like syn-
py; in patients with atrial fibrillation, and for drome, hemorrhage, rhinitis, upper respiratory
whom oral anticoagulation is unsuitable. tract infection, urinary tract infection, urticaria.
Less Common: Constipation, dizziness, flatulence,
gastritis, GI ulcer, headache, leukopenia, nau-
clopidogrel or any component of the formula-
sea, paresthesia, pruritus, rash, vomiting.
tion; severe liver impairment; intracranial
Rare: Acute liver failure, agranulocytosis, angi-
hemorrhage, peptic ulcer or other pathological
oedema, aplastic anemia, bronchospasm, co-
bleeding; breastfeeding.
litis, confusion, exfoliative dermatitis, halluci-
Dose: nations, hepatitis, hypersensitivity-like reac-
Acute coronary syndrome: unstable angina, non- tions, hypotension, interstitial pneumonitis, li-
ST-segment elevation MI (NSTEMI), by chen, myalgia, neutropenia, pancreatitis, Ste-
mouth, ADULT, 300 mg loading dose; then 75 vens-Johnson syndrome, stomatitis, thrombo-
mg/day in combination with aspirin 75-100 cytopenia, Thrombotic thrombocytopenic pur-
mg/day. pura, vasculitis.
Acute coronary syndrome: ST-segment elevation MI
Drug Interactions:
(STEMI), by mouth, ADULT, 75 mg/day (in
NOTE: CYP2C19 enzyme metabolizes clopidogrel to its
combination with aspirin 162-325 mg/ day, active metabolite. Consequently, combining
and then 81-162 mg/day). clopidogrel with inhibitors of CYP2C19 (see Appen-
Acute ischemic stroke, see under Nervous System dix) may decrease its efficacy.
and Musculoskeletal System. Monitor closely with:
Coronary artery disease, by mouth, ADULT, 75 mg Anticoagulants (e.g., warfarin) – combination use
once daily. increases the risk of bleeding.
83
Aspirin – this may cause unusual bleeding, severe ly for one week followed by appropriate
abdominal pain, weakness and the appear- maintenance dose; Maintenance Dose: 3.4 up
ance of black stools. to 5.1 micrograms/kg/day or 0.125 to 0.5 mg
Atorvastatin – may reduce the efficacy of per day; dose is increased gradually every two
clopidogrel, resulting to blood clots. (2) weeks based on clinical responses and
Carbamazepine – increases level or effects of toxicity, and serum drug levels.
clopidogrel. Heart failure, by mouth, ADULT, 125-250 mi-
Clarithromycin, erythromycin – decrease the level or crograms (0.125-0.25 mg) once a day as
effects of clopidogrel. maintenance; higher doses including 375 up
Drugs which can affect the clotting process (e.g. to 500 micrograms/day are rarely needed. Ad-
anticoagulants, NSAIDs and other anti- just maintenance dose by estimating creati-
platelets) – clopidogrel inhibits platelet aggre- nine clearance and measuring serum levels.
gation; increased risk of bleeding when the Higher doses have no additional benefit and
drug is used with the stated drugs. may increase toxicity.
Isoniazid – decreases effects of clopidogrel.
Dose Adjustments:
Rifampin – increases level and effects of
clopidogrel. Elderly:
Avoid concomitant use with: The tendency to develop impaired renal function
Proton pump inhibitors (e.g., omeprazole, and lean body mass can lead to digoxin toxici-
esomeprazole) – these may reduce the anti- ty; thus, lower doses are used.
platelet activity of clopidogrel by reducing for- Loading: by mouth, 125-250 micrograms every 4-6
mation of its active metabolite; decreasing its hours, to a maximum of 500 micrograms;
effectiveness in reducing the risk of cardio- Maintenance: by mouth, 62.5-125 micrograms once
vascular events. daily.
Renal Impairment:
Administration: May be taken with or without food. For mild-to-moderate renal impairment, dose reduc-
Pregnancy Category: B patient should be referred to a specialist.
Precautions:
CARDIOACTIVE WARNING: Fatal arrhythmia may follow overdose.
In acute myocarditis, such as rheumatic carditis, or
in patients with advanced heart failure; severe
DIGOXIN pulmonary disease; sick sinus syndrome; re-
cent MI; avoid rapid intravenous administra-
Oral: 250 microgram tablet tion (increased risk of arrhythmias); fever and
hyperthyroidism (increase sympathetic tone;
A cardiac glycoside, obtained from the leaves of
digoxin relatively ineffective); reduce dose in
Digitalis lanata, which inhibits the Na+/K+
the presence of hypomagnesemia, hypokale-
ATPase pump, and consequently increases
mia, hypercalcemia, hypoxia, hypothyroidism
the force of cardiac contraction and slows the
(may increase the sensitivity to digoxin); the
heart rate.
elderly; renal impairment (toxicity is increased
Indications: Specifically indicated in supraventricu- by electrolyte disturbances).
lar arrhythmias for rate control (particularly Pregnancy (may need dose adjustment); breast-
chronic atrial fibrillation and flutter); also for feeding (amount too small to be harmful).
cardiac failure. NOTE: Heart rate should generally be maintained above 60
beats/minute and early signs of toxicity should be
Contraindications: Ventricular tachycardia or carefully monitored.
fibrillation; hypertrophic obstructive cardiomy-
opathy (unless there is concomitant atrial fi- Adverse Drug Reactions:
brillation and heart failure); intermittent, com- Common: Abdominal pain, agitation, anorexia,
plete heart block or second degree atrioven- blurred vision, confusion, depression, diar-
tricular block; Wolff-Parkinson-White syn- rhea, dizziness, drowsiness, nausea, night-
drome or other accessory pathway; arrhyth- mares, visual disturbances, vomiting
mias caused by cardiac glycoside intoxication; Less Common: Acute psychosis, amnesia, atrial or
hypersensitivity to digoxin, other digitalis gly- ventricular extrasystoles, delirium, fatigue, gy-
cosides or any component of the formulation. necomastia, hallucinations, headache, heart
block, intestinal ischemia, paroxysmal atrial
Dose: tachycardia and fibrillation; shortened QRS
Atrial fibrillation, by mouth, ADULT, Rapid Oral complex.
Loading: 750-1,500 micrograms (0.75-1.5 mg) Rare: Arrhythmias, rash, seizures, thrombocytope-
as a single-dose. Where there is less urgency nia, xanthopsia (yellow vision).
or greater risk of toxicity, e.g., in the elderly,
Drug Interactions:
the oral loading dose is given in divided doses
6 hours apart, with half of the total dose given Monitor closely with:
as the first dose; assess clinical response be- Acarbose – this may decrease absorption of digox-
fore each additional dose; Slow Oral Loading: in.
250-750 micrograms (0.25 up to 0.75 mg) dai-
84
Amiodarone – this increases digoxin concentration
and risk of toxicity; also has additive effects in
slowing cardiac conduction.
Beta-blockers (e.g., atenolol, propranolol) – slow
atrioventricular conduction; higher risk of AV
block and bradycardia.
Carvedilol – this may increase digoxin concentration
and risk of toxicity, especially in children; also
causes bradycardia.
Chloroquine – possibly increased plasma digoxin
concentration, increasing risk of toxicity.
Corticosteroids (e.g., prednisolone, hydrocortisone,
dexamethasone) – possibly increased risk of
hypokalemia that may increase the cardiac
toxicity of digoxin.
Cotrimoxazole – this possibly increases plasma
digoxin concentration, increasing risk of toxici-
ty.
Diltiazem – this may increase digoxin concentration
and risk of toxicity; may have additive nega-
tive effects on heart rate and cardiac conduc-
tion.
Diuretics (e.g., loop diuretics, thiazide diuretics) –
these cause hypokalemia which may increase
cardiac toxicity of digoxin.
Gentamicin – possibly increased plasma digoxin
Ibuprofen – possible exacerbation of heart failure,
reduced renal function, and increased plasma
digoxin concentration.
Macrolides (e.g., azithromycin, clarithromycin, eryth-
romycin) – these may increase the absorption
of digoxin; may rarely lead to digoxin toxicity
(in renal failure).
Nifedipine – possibly increased digoxin concentra-
tion, which may result in an increase in ad-
verse effects.
Quinine – (particularly in antimalarial doses) this
may increase plasma digoxin concentration,
and risk of toxicity.
– possibly reduced absorption of digoxin.
Bile acid binding resins – these reduce absorption
of digoxin, and may reduce its clinical effects.
Rifampicin – plasma digoxin concentration may
possibly be reduced.
Salbutamol – plasma digoxin concentration may
possibly be reduced.
Verapamil – this increases digoxin concentration
and risk of toxicity; has additive negative ef-
fects on heart rate and cardiac conduction.
Administration: Take tablet one hour before, or
two hours after, eating food.
NOTE: For meals high in fiber, take it two hours before, or
two hours after, eating food.
85
is used topically (topical corticosteroids are
DERMATOLOGY less likely to result in drug interactions than
those for systemic use).
ANTI-ALLERGY Administration: Apply enough to cover affected

area. Apply gently unto skin, preferably after
bathing.
HYDROCORTISONE Pregnancy Category: C
Topical: 1%, ointment or cream, 5 g tube

A topical corticosteroid having relatively mild anti-
ANTIBACTERIAL TOPICAL
inflammatory potency that is applied in short PREPARATIONS
courses of 1-2 weeks to manage mild areas of
contact and atopic dermatitis.
FUSIDIC ACID
Indications: Contact dermatitis, atopic dermatitis
(eczema), lichen planus; pityriasis rosea; in- Cream: 2%, 5 g tube
tractable pruritus and phototoxic reactions, in- Ointment: 2%, 5 g and 15 g tube
cluding polymorphic light eruptions and actinic Medicated surgical dressing: 2% (sterile gauze
prurigo; short-term treatment of psoriasis of impregnated with 1.5 g of 2% ointment in sin-
the face and flexures. gle unit foil sachet) (as sodium)
A topical, narrow-spectrum antibiotic isolated from
hydrocortisone or any component of the for-
Fusidium coccineus, which is active against
mulation; rosacea; acne vulgaris; perioral
staphylococci (including methicillin-resistant
dermatitis; untreated skin infections (bacterial,
bacterial strains) and streptococci, and can be
fungal or viral skin lesions); areas with im-
used to treat bacterial infections of the skin,
paired circulation; broken skin. such as impetigo and folliculitis.
Dose:
Indications: Treatment of primary and secondary
Inflammatory skin conditions, by topical use,
skin infections caused by susceptible organ-
ADULT and CHILD, apply sparingly to the af-
isms (e.g., staphylococcal skin infections); 1st
fected area, 1 to 2 times daily until improve-
line therapy for topical treatment of localized
ment occurs, then less frequently.
impetigo.
Dose Adjustment: No information found. Contraindications: Hypersensitivity to fusidic acid
Precautions: or any component of the formulation; infec-
WARNING: Topical steroids may be systematically absorbed tions caused by non-susceptible organisms.
to some degree and chronic use may cause some of
Dose:
the problems associated with systemic steroid.
Superficial dermatologic infections, by topical use,
Diabetes (avoid extensive use as systemic absorp- apply to affected area 3-4 times daily until fa-
tion can increase blood glucose concentra- vorable results are achieved; if a gauze dress-
tion); immunocompromised patients (can lead ing would be used, frequency of application
to further immunosuppression when used ex- may be reduced to 1-2 times daily.
tensively); concomitant use with occlusive
dressings (may increase penetration into ke- Dose Adjustment:
ratinized lesions). Hepatic Impairment:
Children (avoid prolonged use; increased systemic Impaired biliary excretion; possibly increased risk of
absorption due to higher surface area–weight hepatotoxicity; avoid use or reduce dose;
ratio); secondary infection requires treatment monitor liver function.
with an appropriate antimicrobial agent. Precautions:
Pregnancy (use the lowest appropriate potency for Do not use topical cream or ointment near the eye
the shortest time necessary); breastfeeding (irritation of the conjunctiva may occur).
(ensure that the breast area is free from corti- Should not be used for more than 10 days (pro-
costeroid before breastfeeding). longed use may result in superinfection, in-
Adverse Drug Reactions: cluding fungal infections; discontinue treat-
Common: Acneiform, burning, delayed wound ment if superinfection occurs; evaluate and
healing, depigmentation, folliculitis, perioral treat appropriately); avoid extended or recur-
dermatitis, purpura, skin atrophy, steroid rent use (increased risk of developing antibi-
rosacea, striae, telangiectasia. otic resistance and contact sensitization).
Less Common: Allergic contact dermatitis. Pregnancy (may cause kernicterus during the first of
Rare: Hyperesthesia, hypertrichosis, miliaria, sec- month of life); breastfeeding (avoid applying
ondary infections, subcutaneous tissue atro- on breast).
phy. Adverse Drug Reactions:
Drug Interactions: No generally recognized drug Less Common: Contact dermatitis, irritation at the
interactions attributable to hydrocortisone that application site (including pain, stinging, burn-
86
ing and erythema), malaise, pruritus, rash (in- Pregnancy (avoid use unless potential benefit out-
cluding maculopapular, erythematous and weighs risk).
pustular reactions), thrombophlebitis.
Rare: Angioedema, blister, conjunctivitis, hypersen-
sitivity reactions, urticaria. Common: Localized skin reactions, such as itch,
burning, erythema, stinging; dryness, pain,
Drug Interactions: and swelling, nausea.
Monitor closely with: Less Common: Contact dermatitis, increased
Penicillins – possibly diminished therapeutic effect exudate.
of penicillins
Drug Interaction:
HMG-CoA reductase inhibitors – enhanced toxic Monitor closely with:
effect of statins, specifically the risk of muscle Chloramphenicol – in vitro studies indicate that this
toxicities (e.g., rhabdomyolysis). interferes with the antibacterial action of mupi-
rocin on RNA synthesis.
Administration: For cutaneous use only.
Administration: Avoid its contact with the eyes and
Pregnancy Category: C mouth. Children with impetigo should be kept
at home until appropriate treatment is started.
Sores on exposed surfaces should be covered
with a watertight dressing when the child re-
MUPIROCIN turns to school and during child care.
Cream: 2%, 5 g sachet and 15 g tube
Ointment: 2%, 5 g and 15 g tube
A topical, natural product synthesized by Pseudo-
monas fluorescens that is active against SILVER SULFADIAZINE
gram-positive cocci (including methicillin-
susceptible and resistant strains of S. aureus), Cream: 1%, 5 g, 10 g, 15 g, 20 g, 30 g and 50 g
and can be used to treat bacterial infections of tube; 400 g, 450 g and 500 g jar (mi-
the skin, such as impetigo and folliculitis. cronized)
Indications: Skin infections, such as impetigo A topical, bactericidal, sulfonamide preparation,
caused by S. aureus and methicillin-resistant which slowly releases silver, and is used to
strains (MRSA); Group A beta-hemolytic suppress bacterial growth in infected burn and
streptococcus, including S. pyogenes. burn wounds; less toxic topical sulfonamide
than mafenide acetate because it is not ab-
Contraindication: Known hypersensitivity to mupi-
sorbed from burn sites, and does not produce
rocin or any component of the formulation systemic levels.
(e.g., polyethylene glycols).
NOTE: Mupirocin cream is not recommended for use in Indications: For the prophylaxis and treatment of
children <1 year. infections in second- and third-degree burns;
Dose: treatment of infections in leg ulcers and pres-
Superficial dermatologic infections, by topical use, sure sores.
ADULT and CHILD ≥1 year, apply up to 3 Contraindications: Known hypersensitivity to
times daily for up to 10 days. sulfonamides or any component of the formu-
Dose Adjustment: lation; pregnancy (third trimester: risk of neo-
Renal Impairment: natal hemolysis and methemoglobinemia);
Caution is advised when used in moderate or se- porphyria; premature infants or neonates dur-
vere impairment due to the presence of mac- ing the first 2 months of life.
rogols (polyethylene glycols) in the formula- Dose:
tion. Infection in burns, leg ulcers or pressure sores, by
Precautions: topical use, ADULT and CHILD, apply using
Not for ophthalmic and intranasal use. aseptic technique once daily (more frequently
Should not be used for more than 10 days (to pre- if volume of exudate is large) while there is a
vent induction of sensitivity and emergence of possibility of infection or until healing is com-
resistant microorganisms; possible re- plete.
NOTE: Prolonged use of silver sulfadiazine delays healing of
sistance). superficial or partial thickness burns; limit use for the
Its topical application over large infected areas prevention of infection to the first 3 days after the
(decubitus ulcers or open surgical wounds) is burn.
not recommended (identified as a factor for
the emergence of mupirocin-resistant strains). Dose Adjustment:
Wounds and extensive burns (systemic absorption Renal Impairment:
is possible). Use drug with caution for mild-to-moderate renal
Renal impairment (theoretical risk of polyethylene impairment; avoid use in severe impairment.
glycol toxicity with ointments particularly in
children, or in patients with renal impairment).
87
Precautions:
Dose: Apply lotion twice daily for 4 weeks.
In patients with extensive burns, monitor serum
sulfa- concentration and renal function; (ex- Dose Adjustments: None known.
amine urine for sulfonamide crystals).
Impaired renal function (particularly those receiving Precautions:
prolonged treatment for extensive burns, as Avoid contact with the eyes.
systemic absorption may occur); fungal super- Adverse Drug Reactions: Local irritation.
infection may occur; G6PD deficiency (in-
creased risk of hemolysis); avoid contact with Drug Interactions: None known.
the eyes. Administration: For external use only.
Breastfeeding (monitor infant for jaundice – there is
small risk of kernicterus in jaundiced infants Pregnancy Category: No information found.
particularly with long-acting sulfonamides and
of hemolysis in G6PD-deficient infants).
Common: Burning, itch, leukopenia.
CLOTRIMAZOLE
Less Common: Argyria (gray to gray-black stain-
Cream: 1-2%, 3.5 g, 15 g and 450 g tube
ing of the skin), erythema multiforme, intersti-
Lotion: 10 mL
tial nephritis, rash, skin necrosis.
Solution: 10 mg/mL, 15 mL and 25 mL bottle
Rare: Hypersensitivity reactions, sulfonamide-
Vaginal: 100 mg, 300 mg and 500 mg ovule
induced systemic toxicity (including blood dis-
orders and cutaneous reactions). A broad-spectrum imidazole active against fungi,
Drug Interactions: (both dermatophytes and yeasts), and gram-
NOTE: Silver sulfadiazine may prevent the enzymes colla- positive cocci (Staphylococcus and Strepto-
genase, papain or sutilains from working properly. coccus spp.).
Monitor closely with: Indications: Anogenital and vulvovaginal candidia-
Folate antagonists (e.g., pyrimethamine) – possibly sis; ringworm; skin infections, including pityri-
enhanced antifolate effect. asis versicolor and dermatophytosis (e.g., tin-
Methotrexate – increased risk of methotrexate ea corporis, tinea pedis, tinea cruris); protozo-
toxicity. al infections (e.g., trichomoniasis).
Phenytoin – its concentration may be increased by
sulfadiazine. Contraindications: Known hypersensitivity to
Sulfonylureas (e.g., glibenclamide) – sulfadiazine clotrimazole or any component of the formula-
may enhance antidiabetic effect of the sul- tion; severe liver impairment.
fonylureas.
Dose:
Thiopental – its effects may be enhanced by sul-
fadiazine. Anogenital candidiasis, by topical use, ADULT,
Warfarin – enhanced anticoagulant effect. apply 1% cream to anogenital area 2-3 times
Avoid concomitant use with: daily.
Nephrotoxic drugs – sulfadiazine causes nephrotox- Skin infections, including pityriasis versicolor and
icity; additional renal adverse effects may re- dermatophytosis, by topical use, apply cream
sult when given concomitantly with these 2-3 times daily for 1-2 weeks.
drugs. Vulvovaginal candidiasis, vaginal administration
(10% vaginal cream), ADULT, 5 g of a single
Administration: For external use only: apply 2-5 dose at night, repeated once if necessary (1%
mm thick onto the affected area. is to 6 doses; 2% is to 3 doses).
Vulvovaginal candidiasis, vaginal administration
Pregnancy Category: B (pessary), ADULT, insert 100 mg at night for 6
nights or 200 mg at night for 3 nights, or 500
mg at night as a single dose.
ANTIFUNGAL, ANTI-LICE and
ANTI-SCABIES Dose Adjustment:
Vulvovaginal candidiasis in Pregnancy:
Requires a longer duration of treatment, about 7
AKAPULKO [Senna alata L. (Fam. days, to clear the infection (oral antifungal
treatment should be avoided).
Fabaceae)]
Precautions:
Lotion: 60 mL bottle
Should be discontinued if irritation or sensitivity
A natural, liquid preparation containing 50% occurs; should not come in contact with the
akapulko decoction from the leaves of Senna eyes; this damages latex condoms and dia-
alata Linn. (Fam. Fabaceae) that is known for phragms (advise contraceptive precautions).
its antifungal activity due to the fungicide Pregnancy (safety in the first trimester has not yet
chrysophanic acid. been established).
Indication: Pityriasis versicolor. Adverse Drug Reactions:
Common: Local pain or discomfort.
Contraindications: None known.
88
Less Common: Blistering, burning, edema, ery- nape of the neck. Leave on hair for 10
thema, general skin irritation, itch, peeling, minutes and rinse with warm water.
pruritus, stinging.
Rare: Allergic reactions
Drug Interaction:
Monitor closely with: ANTIPRURITIC
Simvastatin – increased risk of myopathy.
Administration: For the topical solution, gently
massage sufficient amount into the affected CALAMINE
and surrounding skin areas twice a day, in the
morning and evening. If the feet are infected, Lotion: 8%, 60 mL and 120 mL bottle
they should be washed and dried, especially A topical antipruritic substance, which contains
between the toes, before applying the cream. basic zinc oxide with about 0.5% colored ferric
Pregnancy Category: B oxide.
Indication: Symptomatic treatment of mild pruritus
and insect stings.
Contraindications: Known hypersensitivity to any
PERMETHRIN component of the formulation; avoid applica-
tion prior to x-ray (since zinc oxide may affect
Lotion: 1%, 125 mL bottle outcomes).
5%, 30 mL and 60 mL bottle
Shampoo: 1%, 30 mL and 60 mL bottle Dose:
Mild pruritus, ADULT and CHILD, apply liberally to
A pyrethroid having similar chemical properties with the entire affected area 3-4 times daily, or as
the natural insecticide pyrethrin, but remains often as needed.
as an effective scabicide for longer periods of
time. Precautions:
Not to be used on open wounds or burns; care
Indications: Head lice (Pediculus humanus capitis) should be taken to avoid contact with the eyes
and body lice (Pediculus humanus corporis); and the mucous membranes of the mouth,
scabies. nose and anogenital area; if condition wors-
Contraindications: Known hypersensitivity to ens or if rash develops, stop the medication
immediately.
permethrin or any component of the formula-
tion; hypersensitivity to plants from Asterace- Adverse Drug Reactions:
ae Family (ragweed); pregnancy. Rare: Irritation, rash.
Dose: Drug Interactions: No information found.
Body lice, ADULT and CHILD, apply lotion over
whole body and wash off after 8-12 hours; if Administration: Shake well prior to use. Apply
hands are washed with soap within 8 hours of gently with a pad of cotton wool to the affected
application, treat the hands again; repeat ap- parts as required.
plication after 7 days. Pregnancy Category: No information found.
Head lice, ADULT and CHILD, apply 1% shampoo
undiluted to affected areas for 10 minutes and
then rinse off with warm water.
Scabies, ADULT and CHILD, apply 5% lotion once
from the neck down the affected area. Leave
on the area for 8-12 hours then wash off.
Precautions:
Should not be used on inflamed or broken skin;
avoid contact with the eyes; not for use in in-
fants <2 years old; breastfeeding (withhold
during treatment).
Common: Local irritation, mild burning, pruritus.
Less Common: Erythema, numbness, stinging,
tingling.
Rare: Cross-sensitization to pyrethrins or chrysan-
themum, edema, rash.
Administration: Apply the lotion or shampoo to
towel-dried hair until hair and scalp are satu-
rated, especially behind the ears and on the
89
flap over the opening of the ear canal) may
EARS, NOSE and THROAT aid penetration of the drops.
ANTIBACTERIAL OTIC PREPARATION
NEOMYCIN + POLYMYXIN B +
FLUOCINOLONE ACETONIDE
Ear Drops Solution: 3.5 mg neomycin (as sulfate)
+ 10,000 units polymyxin B (as sulfate) +
0.025% fluocinolone acetonide/mL, 5 mL bot-
tle
A combination of a corticosteroid and anti-infectives
(aminoglycoside and basic peptides) used in
treating ear diseases.
Indications: Otitis externa, with or without associ-
ated otitis media; adjunct therapy to acute or
chronic dermatoses of the external ear chronic
suppurative otitis media; draining mastoidec-
tomy cavities; otorrhea from ventilation tubes.
neomycin, polymyxin B, or any component of
the formulation; patients with primary infection
of the skin caused by bacteria, fungi, acne
rosacea, perioral dermatitis; patients with her-
pes simplex, vaccinia and varicella; patients
with untreated fungal or viral infections; and
pregnancy (first trimester).
Dose:
Ear infections, instill 3-4 drops 2-4 times daily.
NOTE: Limit treatment to 5-7 days; refer to ENT specialist if
discharge continues.
Precautions:
Patients with perforated eardrum or long standing
chronic otitis media; pregnancy; prolonged
use.
Common: Allergic dermatitis.
Less Common: Acneiform eruptions, burning,
decreased hearing, dryness, ear pain, folliculi-
tis, fungal overgrowth inside ear canal, hyper-
trichosis, hypopigmentation, irritation, itching,
miliaria, perioral dermatitis, secondary infec-
tions, tinnitus.
Rare: Inner ear damage.
Administration: The ears should be clean and dry,
and the patient should lie with the affected ear
uppermost.
Method of drug application depends on degree of
swelling in ear canal:
• For minimal swelling, instill drops directly into
the ear canal then remain in position for a few
minutes.
• For swelling that narrows the ear canal, satu-
rate a sponge wick or ribbon gauze with drops
and insert into the ear canal; review daily until
swelling settles.
When using drops, warm container in cup of warm
water if necessary to reduce viscosity. Gentle
massage or pressure on the tragus (cartilage
90
the product labeling due to the risk of cross-
ENDOCRINE SYSTEM and STEROIDS reaction that exists in patients with allergy to
any of these compounds, especially when the
previous reaction has been severe); surgery
ANTIDIABETIC AGENTS (substitute insulin treatment before surgery).
NOTE: Secondary failure: Loss of efficacy may be ob-
ORAL HYPOGLYCEMIC AGENTS served following prolonged use as a result of the pro-
gression of type 2 diabetes mellitus which results in
continued beta cell destruction. In patients who were
previously responding to sulfonylurea therapy, con-
GLICLAZIDE sider additional factors that may be contributing to de-
creased efficacy (e.g., inappropriate dose, non-
Oral: 30 mg tablet (modified-release) adherence to diet and exercise regimen). If no con-
tributing factors can be identified, consider discontinu-
80 mg tablet (immediate-release)
ing use of the sulfonylurea due to secondary failure of
A second-generation sulfonylurea, which acts by treatment. Additional antidiabetic therapy (e.g., insu-
lin) will be required.
increasing the pancreatic insulin secretion,
and is useful in the treatment of type 2 diabe- Adverse Drug Reactions:
tes mellitus. Common: Dizziness, hypoglycemia, weight gain.
Indication: For the management of type 2 diabetes Less Common: Abdominal pain, angina pectoris,
arthralgia, arthrosis, back pain, bronchitis,
mellitus.
constipation, cough, diarrhea, dyspepsia,
Contraindications: Known hypersensitivity to headache, hypertension, metallic taste, nau-
gliclazide, and other sulfonamides or sulfonyl- sea, rash, rhinitis, upper respiratory infection,
ureas, or any component of the formulation; urinary tract infection, viral infection, vomiting.
type 1 diabetes mellitus (insulin dependent, Rare: Allergic reactions, blood disorders, elevations
IDDM); diabetic ketoacidosis; diabetic pre- of: serum bilirubin, creatinine, blood urea ni-
coma and coma; severe renal or hepatic im- trogen, and hepatic enzymes; erythema multi-
pairment; stress conditions (e.g., serious in- forme, exfoliative dermatitis, fever, hepatic
fection, trauma, surgery); porphyria; pregnan- failure, hepatitis, jaundice, malaise, photosen-
cy; breastfeeding. sitivity, Stevens-Johnson syndrome.
Dose: Drug Interactions:
NOTE: There is no fixed-dosage regimen for the manage- Monitor closely with:
ment of diabetes mellitus with gliclazide. Dose should Alcohol – this decreases blood glucose concentra-
be individualized based on frequent monitoring of
tion by inhibiting the hepatic glucose output
blood glucose during dose titration and throughout
maintenance. and increasing the risk of hypoglycemia; can
Type 2 diabetes, by mouth, ADULT, modified- also mask warning symptoms; gliclazide may
release tablet: initially 30 mg once daily; ti- enhance the adverse effect of alcohol (a flush-
trate in 30 mg increments every 2 weeks ing reaction may occur).
based on blood glucose levels (maximum, 120 Beta-blockers – these may mask some hypoglyce-
mg once daily); immediate-release tablet: mic warning symptoms and increase inci-
initially 80 mg twice daily; titrate based on dence and severity of hypoglycemia.
blood glucose levels. Usual dosage range: 80- Corticosteroids, systemic – these may diminish
320 mg/day (maximum, 320 mg/day); dosage hypoglycemic effect of antidiabetic agents.
of ≥160 mg should be divided into 2 equal Loop Diuretics – these diminish hypoglycemic effect
parts for twice-daily administration. See Clini- of hypoglycemic agents.
cal Practice Guidelines – DM for further infor- Ranitidine – this may increase the serum concentra-
mation. tion of sulfonylureas.
Rifampicin – this may increase metabolism of
Dose Adjustments: gliclazide, decreasing its hypoglycemic effect.
Renal Impairment: Salicylates – these may enhance the hypoglycemic
In severe renal impairment, gliclazide is avoided effect of hypoglycemic agents.
(because of increased risk of hypoglycemia). Sulfonamide Derivatives – these may enhance the
Hepatic Impairment: hypoglycemic effect of sulfonylureas.
Avoid in severe hepatic disease (since jaundice Thiazide Diuretics – these may diminish the thera-
may occur). peutic effect of antidiabetic agents.
Precautions:
CYP2C9 inhibitors (see Appendix) – sulfonylureas
Hypoglycemia (intermediate risk); stress-related
are metabolized by CYP2C9; when given with
states (it may be necessary to discontinue
inhibitors of this enzyme, their concentration
therapy and administer insulin if patient is ex-
may increase, increasing the risk of hypogly-
posed to stressful conditions); cardiovascular
cemia.
mortality; acute illness, including MI, coma,
St. John’s wort – this may decrease the concentra-
trauma, infection (monitor blood glucose and
tion of gliclazide, thus decreasing its hypogly-
urine ketones; substitute insulin treatment if
cemic effect.
glycemic control is inadequate); G6PD defi-
ciency; sulfonamide allergy (use in patients
with sulfonamide allergy is contraindicated in
91
Administration: Take tablet (MR) with food to has recovered); substitute insulin during se-
minimize the risk of hypoglycemia. Immediate- vere infection, trauma or surgery.
release tablets are best given before meals. Discontinue temporarily prior to intravascular use of
radiocontrast.
Pregnancy Category: C Pregnancy (all trimesters: avoid use – but may be
given for pregnant women previously diag-
nosed with PCOS as prescribed by the physi-
cian); breastfeeding (present in milk, but safe
METFORMIN in usual doses; monitor infant).
Oral: 500 mg and 850 mg tablet (as HCl) Adverse Drug Reactions:
Common: Abdominal pain, anorexia, asthenia,
A biguanide that exerts its effects by inhibiting he- diarrhea, disturbance in taste, dyspepsia,
patic gluconeogenesis and increasing periph- headache, indigestion, flatulence, metallic
eral glucose utilization, and is useful in over- taste, nausea, upper respiratory tract infec-
weight and obese patients since it does not tion, vitamin B12 malabsorption, vomiting.
increase weight nor provoke hypoglycemia Less Common: Erythema, pruritus, rash, urticaria.
when used. Rare: Acute hepatitis, lactic acidosis.
Indication: Type 2 Diabetes mellitus. Drug Interactions:
Contraindications: Ketoacidosis; severe infection Monitor closely with:
or trauma; dehydration; alcohol misuse; mod- Alcohol – this decreases blood glucose concentra-
erate to severe heart failure; risk of tissue hy- tion by inhibiting the hepatic glucose output,
poxia caused by sepsis, respiratory failure, re- and increasing the risk of hypoglycemia; can
cent MI, or hepatic impairment (withdraw also mask warning symptoms; increased risk
treatment if tissue hypoxia is likely to occur); of lactic acidosis.
use of iodine-containing X-ray contrast media Beta-blockers – these may mask some hypoglyce-
(do not restart metformin until renal function mic warning symptoms and increase inci-
returns to normal); use of general anesthesia dence and severity of hypoglycemia.
(suspend metformin on the morning of surgery Drugs increasing blood glucose concentration (e.g.,
and restart when renal function returns to glucocorticoids, antipsychotics, calcineurin in-
normal). hibitors and high-dose thiazide diuretics) –
these may increase blood glucose, and may
Dose: alter the control of diabetes by metformin.
Diabetes mellitus, by mouth, ADULT and CHILD Enalapril – possibly enhanced hypoglycemic effect.
>10 years, initially 500 mg with breakfast for Avoid concomitant use with:
at least 1 week, then 500 mg with breakfast Contraceptives, Oral – these antagonize the hypo-
and evening meal for at least 1 week, then glycemic effect of metformin.
500 mg with breakfast, lunch, and evening Furosemide – this antagonizes the hypoglycemic
meal, or 850 mg every 12 hours with or after effect of metformin.
food (usual maximum, 2.5 g daily in divided Hydrocortisone – this antagonizes the hypoglycemic
doses). See Clinical Practice Guidelines – DM effect of metformin.
for further information.
Administration: Take it with meals to reduce stom-
Dose Adjustments: ach upset.
Elderly:
Use cautiously; monitor renal function and for ad- Pregnancy Category: B
verse effects; reduce dose (or stop treatment),
if necessary.
Renal and Hepatic Impairment: INSULINS
For mild-to-moderate impairment, dose reduction is
warranted; for severe impairment, the patient General Information:
Insulin, a polypeptide hormone of complex structure
Precautions: produced by the pancreas, plays a key role in
WARNING: May cause lactic acidosis rarely but with poten- the metabolism of carbohydrate, fat, and pro-
tially severe consequences. tein. The amino-acid sequence of animal insu-
Severe renal and hepatic impairment (increased risk lins, human insulins, and the human insulin
of lactic acidosis); monitor renal function be- analogues differ. Insulin is extracted from por-
fore treatment and once or twice annually cine pancreas and purified through crystalliza-
(more frequently in the elderly, or if deterioration. Beef insulins are rarely utilized now. Hu-
tion suspected). man sequence insulin may be produced sem-
Moderate-to-severe heart failure (may increase risk isynthetically by enzymatic modification of
of lactic acidosis). porcine insulin or biosynthetically by recombi-
Surgery (stop metformin before surgery; monitor nant DNA technology using bacteria or yeast.
plasma glucose concentration; restart when Mode of Action: Increase or restore ability to
patient is no longer fasting and renal function metabolize glucose by enhancing cellular glu-
92
cose uptake; inhibit endogenous glucose out- toacidosis (occurs when adjustments to insulin
put and lipolysis. dosage fail to compensate for increases in the
requirements of insulin, e.g., during severe in-
Types of Insulin: The various formulations of insu-
fection or a major intercurrent illness); sur-
lin are classified according to their duration of gery; renal impairment (if severe; insulin re-
action after subcutaneous injection, as: short quirements fall; compensatory response to
and rapid-acting insulins; intermediate-acting hypoglycemia is impaired).
insulins; and long-acting insulins. The inter- Pregnancy (strict blood glucose control, especially
mediate- and long-acting insulins are given for at the time of conception and early pregnancy
the basal requirements, while the short and to reduce risk of spontaneous abortion and
rapid acting are given before meals to control congenital malformations; assess insulin re-
post-prandial hyperglycemia. quirements frequently).
Indications: Type 1 diabetes mellitus. Exercise (may lower the body’s need for insulin
during and for some time after the activity; it
Type 2 diabetes mellitus inadequately controlled may also speed up the effect of an insulin
with diet, exercise and oral antidiabetic medi- dose especially if the exercise involves the ar-
cations, and where oral therapy cannot be ea of injection site); hot baths, sauna (may al-
used (e.g., during surgery, or in pregnant so accelerate absorption after SC injection by
women with type 2 DM when diet alone fails to increasing skin blood flow).
control the diabetes). See under Clinical Prac- MONITORING: The facility should have monitoring at the
tice Guidelines for Diabetes Mellitus. point of care. Blood glucose concentration varies
Children with diabetes (especially those presumed throughout the day; diabetics should aim to maintain
to have Type 1 diabetes mellitus). their blood glucose concentration between 4-9
mmol/L for most of the time (ideally, 4-7 mmol/L be-
Diabetic emergencies, including diabetic ketoacido-
fore meals, and <9 mmol/L after meals); blood glu-
sis and hyperosmolar hyperglycemic states cose concentration should be prevented from falling
where IV short-acting insulins are frequently below 4 mmol/L because of the risk of hypoglycemia.
used. Post-prandial glucose should be between 6-10
mmol/L. Glycated hemoglobin concentration (HbA1c)
Contraindications: Known hypersensitivity to should be <7% (53 mmol/mol).
insulin, or any of its excipients; episodes of STABILITY and STORAGE: Insulin preparations should
hypoglycemia. be stored in a refrigerator at 2-8°C, protected from
light and not allowed to freeze. It has been recog-
Dose: nized that patients may not follow stringent storage
Dosage of insulin and regimen depend on the indi- guidelines, and most manufacturers consider that
vidual treatment endpoints, and are adjusted storage at a temperature of up to 25°C would be ac-
according to (capillary) blood glucose monitor- ceptable for up to 1 month. Patients should still be
advised not to expose their vials or cartridges to ex-
ing. cessive heat or sunlight.
Dosage of human insulin is always expressed in
units. The word “unit” should not be abbrevi- Adverse Drug Reactions:
ated. One unit of human insulin which is con- Common: Hypoglycemia (see under Clinical Prac-
tained in 0.03846 mg of the first International tice Guidelines in Diabetes Mellitus).
Standard (1986) is equivalent to the amount of Less Common: Edema, lipodystrophy (either as
insulin required to reduce the concentration of lipoatrophy appearing as a depression in the
blood glucose to 45 mg/dL in a fasting rabbit. skin, or as lipohypertrophy which is an en-
largement or thickening of tissue) at the site of
Dose Adjustments: injection, weight gain.
Renal Impairment: Insulin requirements may in- Rare: Localized reactions (or local allergy which
crease in the presence of renal impairment can consist of redness, swelling and itching),
and therefore dose reduction may be neces- generalized hypersensitivity reactions (includ-
sary. The compensatory response to hypogly- ing rash over the whole body, shortness of
cemia is impaired in renal impairment. breath, wheezing, hypotension, tachycardia,
For mild to moderate impairment, reduce the dose. or sweating, or very rarely, anaphylactic reac-
In severe impairment, insulin requirements tions).
fall; refer to the internist or diabetes specialist.
Hepatic Impairment: Insulin requirements may be Drug Interactions:
decreased in patients with hepatic impairment. Monitor closely with:
ACE inhibitors (e.g., enalapril) – these may enhance
Precautions: the hypoglycemic effect.
Dosage requirements are altered by many factors. Alcohol – this decreases blood glucose concentra-
Acute illness or conditions, e.g., trauma, MI, infection by inhibiting the hepatic glucose output
tions, stroke, coma (can worsen diabetes con- and increasing the risk of hypoglycemia; can
trol; insulin-treated diabetics may have in- also mask warning symptoms.
creased insulin requirements); infections are Beta blockers (e.g., atenolol and propranolol) –
more likely to develop in patients with poorly these may enhance hypoglycemic effect; may
controlled diabetes mellitus; driving (hazard- mask warning signs of hypoglycemia, such as
ous when hypoglycemic since awareness is tremor.
impaired; check blood glucose concentration Drugs increasing blood glucose concentration (e.g.,
before driving and, on long journeys, at inter- glucocorticoids, antipsychotics, calcineurin in-
vals of approximately two hours); diabetic ke-
93
hibitors, and high-dose thiazide diuretics) – Precautions: See general information on Insulins
these may increase blood glucose concentra- noted above.
tion, and may alter the control of diabetes by
Adverse Drug Reactions: See general information
insulin.
Nifedipine – occasionally impaired glucose toler- on Insulins noted above.
ance. Drug Interactions: See general information on
Thiazolidinediones (TZDs) – in combination with Insulins noted above.
insulin are associated with an increased risk
of edema and heart failure, especially in pa- Administration: See general information on Insu-
tients with underlying cardiac disease. lins noted above. Shake the suspension gen-
Avoid concomitant use with: tly before a dose is withdrawn. Follow manu-
Contraceptives, Oral (e.g., levonorgestrel and facturer’s instructions.
medroxyprogesterone) – these antagonize the Pregnancy Category: B
hypoglycemic effect of insulin.
Corticosteroids (e.g., dexamethasone, hydrocorti-
sone, prednisolone) – antagonism of hypogly-
cemic effect. NPH HUMAN INSULIN / ISO-
Diuretics (e.g., furosemide and hydrochlorothiazide) PHANE INSULIN HUMAN (Re-
– antagonism of hypoglycemic effect. combinant DNA origin)
Administration: Insulin is given by injection be- Inj.: 100 IU/ml, 10 mL vial as suspension (SC)
cause it is inactivated by the gastrointestinal 100 IU/ml, 3 mL cartridge (SC)
enzymes. The SC route is ideal in most situa-
tions. It is usually injected in the upper arms, Neutral Protamine Hagedorn (NPH Insulin) or iso-
thighs, buttocks, or abdomen. The rate of ab- phane insulin is a crystalline suspension of
sorption from different sites may vary depend- human insulin with protamine and zinc provid-
ing on local blood flow (absorption in the arm ing an intermediate-acting insulin with a slow-
is faster than in the buttock or thigh). er onset of action (within about 2 hours), with
peak activity at about 10-12 hours and a long-
er duration of activity (up to about 24 hours)
than that of regular insulin. It is of particular
REGULAR INSULIN (Recombinant value for the initiation of twice-daily insulin
DNA, Human) regimens. NPH insulin is often combined with
regular insulin to achieve a more rapid onset
Inj.: 100 IU/mL, 3 mL pre-filled syringe (IM, IV, SC)
of action compared to NPH insulin alone.
100 IU/mL, 10 mL vial (IM, IV, SC)
Indication: Diabetes mellitus.
A short-acting, sterile, clear aqueous solution of
regular crystalline zinc insulin, which contains Contraindications: See general information on
a polypeptide hormone structurally identical to Insulins noted above.
the human insulin synthesized through rDNA
Dose: For SC injection only. See general infor-
technology for treatment of diabetes.
Regular or soluble insulin is the most appropriate mation on Insulins noted above.
form of insulin for use in diabetic emergencies Dosage Adjustments: See general information on
and during surgery, and in these cases is typi- Insulins noted above.
cally given in an intravenous infusion (insulin
drip). When injected SC, it has rapid onset of Precautions: See general information on Insulins
action (30-60 minutes), a peak action between noted above.
2 and 4 hours, and a duration of action of up Adverse Drug Reactions: See general information
to 8 hours. When injected IV, it has a very on Insulins noted above.
short half-life of only about 5 minutes and its
effect disappears within 30 minutes. Drug Interactions: See general information on
Indications: Diabetes mellitus; diabetic ketoacido- Insulins noted above.
sis. Administration: For SC injection only. See general
Contraindications: See general information on information on Insulins noted above. Shake
Insulins noted above. the suspension gently before a dose is with-
drawn. Follow manufacturer’s instructions.
Dose: by SC, IM, or IV injection or IV infusion (IV
route is reserved for urgent treatment, e.g., Pregnancy Category: B
DKA, and for fine control in serious illness and
peri-operatively), according to requirements;
see under Insulins, and under Clinical Practice
Guidelines in Diabetes Mellitus.
Dosage Adjustments: See general information on
Insulins noted above.
94
CORTICOSTEROIDS extensive use as systemic absorption can in-
crease blood glucose concentration); psychi-
atric disorders (may be exacerbated); children
HYDROCORTISONE (possible growth retardation); immunocom-
promised patients (increased risk and severity
Inj.: 50 mg/mL, 2 mL vial (IM, IV) of infection); latent TB (may be reactivated).
(as sodium succinate) Pregnancy (corticosteroid use in early pregnancy
125 mg/mL, 2 mL and 4 mL vial (IV) may slightly increase the risk of orofacial
(as sodium succinate) clefts).
Powder, 100 mg, 250 mg (IV) Adverse Drug Reactions:
(as sodium succinate) Common: Acne, adrenal suppression, amenorrhea,
A glucocorticoid used for replacement therapy in bruising, delayed wound healing, dyslipidem-
adrenal insufficiency, management of auto- ia, dyspepsia, edema, fat redistribution, frac-
immune and inflammatory conditions, and as tures, growth retardation, hirsutism, hypergly-
emergency management of anaphylaxis and cemia, hypertension, hypokalemia, increased
severe systemic allergies. appetite, increased susceptibility to infection,
masking of signs of infection, muscle weak-
Indications: Autoimmune or inflammatory condi- ness and wasting, myopathy, osteoporosis,
tions. psychiatric effects, skin atrophy, sodium and
NOTE: This is also used for acute adrenal insufficiency for water retention, weight gain.
which referral to a specialist is warranted.
Less Common: Glaucoma, ocular hypertension,
Contraindications: Known hypersensitivity to the osteonecrosis, particularly of the femoral and
hydrocortisone or any of the components; sys- humeral heads.
temic fungal infections; in patients with infec- Rare: Anaphylactoid reaction, chorioretinopathy
tive arthritis, skin or soft tissue infections near (central), euphoria, hypersensitivity reactions,
joints or a prosthetic joint; administration of hypomania, peptic ulceration, tendon rupture.
live or live, attenuated vaccines; patients with Drug Interactions:
infective arthritis, skin or soft tissue infections NOTE: Hydrocortisone is a substrate for CYP3A-based
near joint. interactions; its concentration may be affected by the
NOTE: Corticosteroids given IM are contraindicated for presence of enzyme inducers and inhibitors (see Ap-
idiopathic thrombocytopenic purpura; they are also pendix).
contraindicated for intrathecal administration. Monitor closely with:
Dose: Acetylsalicylic acid and other salicylates – increased
Anti-inflammatory, by IV or IM injection, ADULT, risk of GI bleeding and ulceration; corticoster-
100-500 mg 3 or 4 times daily; CHILD, 2-4 oids may also decrease plasma salicylate
mg/kg every 6 hours for 24 hours, then reduce concentration.
over subsequent 24 hours, or change to oral Antifungal Agents (e.g., azole derivatives) – these
prednisone. may reduce metabolism of corticosteroids.
Initial control of autoimmune disease, by IV injec- Contraceptives, Oral – contraceptives which contain
tion, ADULT, 100-500 mg 3 or 4 times daily estrogens increase the plasma concentration
according to severity of condition. of hydrocortisone.
Digoxin – increased risk of hypokalemia, which may
Dose Adjustments: lead to arrhythmias.
Renal and Hepatic Impairment: Drugs reducing potassium concentration (e.g.,
For mild-to-moderate impairment, dose reduction is amphotericin B and diuretics) – systemic cor-
warranted; for severe impairment, the patient ticosteroids reduce potassium concentration,
should be referred to a specialist; use with increasing the risk of hypokalemia; also, if cor-
caution. ticosteroids are given with these drugs, there
Precautions: is enhanced risk of adverse effects.
Injection into the deltoid muscle (avoid due to high Drugs increasing blood glucose concentration (e.g.,
antipsychotics, calcineurin inhibitors, and
incidence of subcutaneous atrophy); the low-
est possible dose of corticosteroid should be high-dose thiazide diuretics) – glucocorticoids
used to control the condition under treatment can increase blood glucose concentration,
(whenever reduction is possible, it should be and may increase risk of hyperglycemia if giv-
gradual); en with these drugs.
Peptic ulcer disease (increase the risk of perfora- Ibuprofen – increased risk of GI bleeding and ulcer-
tion); myasthenia gravis (increased muscle ation.
weakness); large doses of corticosteroids can Macrolide antibiotics (e.g., erythromycin) – this may
cause elevation of BP, salt and water reten- cause significant decrease in clearance of cor-
tion, and increased potassium and calcium ticosteroids.
excretion; osteoporosis (increased risk of frac- Phenytoin – this increases the metabolism of corti-
tures and accelerates bone loss); heart failure, costeroids, possibly reducing their activity.
hypertension (may be worsened); Rifampicin – this increases the metabolism of corti-
Chronic use may result in hypothalamic-pituitary costeroids, possibly reducing their activity.
adrenal axis suppression, Cushing’s syn- Salbutamol – increased risk of hypokalemia.
drome, and hyperglycemia; diabetes (avoid
95
Avoid concomitant use with: • Discontinuing especially of long-term therapy requires
Amlodipine – antagonism of hypotensive effect. gradual withdrawal. Abrupt withdrawal may precipitate
Antihypertensives (e.g., enalapril, isosorbide dini- acute adrenal insufficiency.
• Tapering of the steroid dose should be individualized
trate and methyldopa) – antagonism of hypo- depending on the disease and severity of condition.
tensive effect. For example, the dose may be tapered off by 10-20%
Calcium salts – there is reduced absorption of calci- every 3 to 5 days and once a dose of 10 mg per day
um salts. is reached, a slower weekly tapering is recommend-
Diuretics (e.g., furosemide, hydrochlorothiazide) – ed.
hydrocortisone antagonizes the diuretic effect • Consider alternate day therapy for long-term therapy
of these drugs; possibly increased risk of (to reduce adverse effects).
hypokalemia. Autoimmune or inflammatory disease, by mouth,
Drugs controlling blood glucose concentration – ADULT, initially 5-60 mg once daily depend-
hydrocortisone may increase blood glucose ing on the disease and its severity. Adjust
concentration, and may alter the control of di- dose according to response and to recom-
abetes. mended guidelines; CHILD, initially 1-2 mg/kg
Vaccine, Influenza – corticosteroids impair immune once daily (usual maximum dose, 60 mg) with
response, and may reduce therapeutic effect dose adjustments based on guidelines.
of the vaccine. Croup, by mouth, CHILD, 1 mg/kg; repeat dose
Vaccine, Live – corticosteroids impair immune after 12-24 hours if necessary. NOTE: No defini-
response, and may enhance the adverse ef- tive treatment guidelines exist. Dosing is dependent
on institution protocols and individual response.
fect of the vaccines (live).
Pneumocystis carinii pneumonia, by mouth,
Administration: Give directly, or dilute in normal ADULT, begin within 72 hours of PCP thera-
saline or D 5 W; administer within 24 hours af- py: 40 mg twice daily for 5 days, followed
ter diluting. by 40 mg once daily for 5 days, followed by 20
st mg once daily for 11 days or until antimicrobial
Pregnancy Category: C; D in the 1 trimester. regimen is completed; CHILD, 1 mg/kg twice
daily for 5 days, followed by 0.5-1 mg/kg twice
daily for 5 days, followed by 0.5 mg/kg once
daily for 11-21 days.
PREDNISONE Rheumatoid arthritis, by mouth, ADULT, ≤10 mg
daily. NOTE: Once the condition has stabilized, re-
Oral: 5 mg, 10 mg and 20 mg tablet duce to the minimum required to maintain control of
10 mg/5 mL suspension, 60 mL disorder.
A corticosteroid having glucocorticoid and anti- Dose Adjustment:

inflammatory effects; rapidly converted to the Renal Impairment:
active prednisolone in the body. For mild-to-moderate renal impairment, dose reduc-
Indications: Autoimmune disease; croup; short-
term suppression of inflammation in allergic
disorders; atopic dermatitis; Pneumocystis ca- Precautions:
rinii pneumonia; dermatomyositis or polymyo- GI disease, e.g., diverticulitis, peptic ulcer, and
sitis; nephrotic syndrome (idiopathic or related ulcerative colitis (increased risk of perfora-
to lupus erythematosus); immune-mediated tion); myasthenia gravis (increased muscle
thrombocytopenia; eye inflammation. weakness); large doses can cause elevation
of BP, salt and water retention and increased
Contraindications: Known hypersensitivity to any
potassium and calcium excretion; osteoporo-
component of the formulation; untreated sys- sis; heart failure, hypertension myocardial in-
temic fungal infections; administration of live farction; chronic use may result in hypotha-
or live, attenuated virus vaccines with immu- lamic-pituitary adrenal axis suppression,
nosuppressive doses of prednisone. Cushing’s syndrome, and hyperglycemia; dia-
Dose: betes; posterior subcapsular cataracts, glau-
General dosing range, by mouth, Initial: 5-60 mg coma ocular infections; psychiatric disturb-
daily. ances, such as depression, euphoria, insom-
nia, mood swing, and personality changes;
RECOMMENDATIONS ON APPROPRIATE USE: possibly cause Kaposi’s sarcoma; acute myo-
• Prior to use, the dose and duration of treatment pathy; seizure disorders; thyroid disease; he-
should be based on the risk versus benefit for each
individual patient. Generally, use the smallest effec- patic impairment.
tive dose for the shortest duration of time to minimize Immunocompromised patients (increase the risk
the adverse events. A gradual tapering of dose may and severity of infection); may increase sec-
be required prior to discontinuing therapy. ondary infection, mask acute infection (includ-
• Dosage for infants and children should be based on ing fungal infections), prolong or exacerbate
severity of the disease and response of the patient ra- viral infections, or limit response to vaccines;
ther than on strict adherence to dosage indicated by
age, weight, or body surface area.
should not be used to treat ocular herpes sim-
• A gradual tapering of dose may be required prior to plex or cerebral malaria; exposure to chicken-
discontinuing therapy. pox should be avoided; close observation is
required in patients with latent TB and/or TB
96
reactivity; restrict use in active TB (only in THYROID HORMONES and ANTITHYROID
conjunction with antituberculosis treatment).
Pediatrics (may affect growth velocity; growth
should be routinely monitored); and breast- LEVOTHYROXINE
feeding (take dose immediately after a feed
and wait 4 hours before the next feed). Oral: 25, 50, 100 and 150 micrograms tablet (as
Adverse Drug Reactions: anhydrous sodium)
Common: Acne, adrenal suppression, amenorrhea, A synthetic thyroid hormone which is the prepara-
bruising, delayed wound healing, dyslipidem- tion of choice for replacement therapy in treat-
ia, dyspepsia, edema, fat redistribution, frac- ing primary and secondary hypothyroidism.
tures, growth retardation, hiccups, hirsutism,
hyperglycemia, hypertension, hypokalemia, Indication: Hypothyroidism of any etiology.
increased appetite, increased susceptibility to Contraindications: Hyperthyroidism from any
infections, malaise, masking of signs of infec-
cause; thyrotoxicosis.
tion, muscle weakness and wasting, myopa-
thy, nausea, osteoporosis, psychiatric effects, Dose:
skin atrophy, sodium and water retention, Congenital hypothyroidism, juvenile myxedema, by
weight gain. mouth, NEONATE up to 1 month, initially 5-10
Less Common: Glaucoma, ocular hypertension, micrograms/kg daily, (5 micrograms/kg daily in
osteonecrosis or aseptic necrosis (particularly infants and children >1 month), adjusted in
of the femoral and humeral heads). steps of 25 micrograms every 2-4 weeks, until
Rare: Anaphylactoid reaction, chorioretinopathy mild toxic symptoms appear, then reduce
(central), euphoria, hypersensitivity reactions, dose slightly.
hypomania, peptic ulceration, tendon rupture. Hypothyroidism, by mouth, ADULT, usual dose is
1.6-1.7 micrograms/kg daily; may give full
Drug Interactions:
NOTE: Prednisone is a substrate for CYP3A-based interac-
dose right away if without contraindications.
tions; its concentration may be affected by the pres- For most, initially 50-100 micrograms daily
ence of enzyme inducers and inhibitors (see Appen- (25-50 micrograms for those over 50 years)
dix). before breakfast, increased by 25-50 mi-
Monitor closely with: crograms every 3-4 weeks until normal me-
Acetylsalicylic acid and other salicylates – increased tabolism is maintained (maintenance dose,
risk of GI bleeding and ulceration; corticoster- 100-200 micrograms daily); in cardiac dis-
oids may also decrease plasma salicylate ease, initially 25 micrograms daily or 50 mi-
concentration crograms on alternate days, adjusted in steps
Drugs increasing blood glucose concentration (e.g., of 25 micrograms every 4 weeks).
antipsychotics, calcineurin inhibitors, high-
dose thiazide diuretics, somatropin) – gluco- Dose Adjustment:
corticoids can increase blood glucose concen- Elderly:
tration, and may increase risk of hyperglyce- Introduce gradually to avoid sudden increase in
mia if given with these drugs. metabolic demands; maintenance replace-
NSAIDs – oral corticosteroids increase risk of gas- ment dose in the elderly may be less than in
tric ulceration. younger people.
Phenytoin – this increases the metabolism of corti- The initial dose should not exceed 25-50 mi-
costeroids, possibly reducing their activity. crograms/day, and should be maintained at in-
Rifampicin – this increases the metabolism of corti- tervals of at least 4 weeks.
costeroids, possibly reducing their activity. Precautions:
Avoid concomitant use with: WARNING: Use with caution in patients with underlying
Antacids (e.g., aluminum or magnesium hydroxide) coronary artery disease, previous MI or acute coro-
– these may decrease the bioavailability of nary syndromes and tachyarrhythmias.
oral corticosteroids. Patients with cardiovascular disorders, including
BCG vaccine – immunosuppressants may reduce angina, heart failure, myocardial infarction or
the therapeutic effect of BCG. insufficiency and hypertension (lower initial
Drugs controlling blood glucose concentration – doses, smaller increments and longer inter-
prednisone may increase blood glucose con- vals between increases should be necessary;
centration, and may alter the control of diabe- full replacement dose may not be appropri-
tes (diminish the hypoglycemic effect of anti- ate).
diabetic agents). Hypopituitarism or predisposition to adrenal insuffi-
Administration: Best taken with food; taking it early ciency (should be corrected with a corticoster-
in the morning reduces possible side effects. oid prior to treatment with levothyroxine; oth-
erwise, an acute adrenal crisis, e.g., panhy-
Pregnancy Category: C; D in the 1st trimester. popituitarism, may be precipitated); elderly,
long-standing hypothyroidism (introduce grad-
ually to avoid any sudden increase in metabol-
ic demands).
Diabetes insipidus or diabetes mellitus (there may
be a need to increase dose of insulin or oral
97
antidiabetic drug); may occasionally precipi-
tate or exacerbate a pre-existing myasthenic METHIMAZOLE
syndrome.
Pregnancy (monitor thyroid function each trimester; Oral: 5 mg and 20 mg tablet
reassess thyroxine maintenance dosage 6-8
weeks post-partum; thyroxine may cross the An imidazole-derived thioamide that is used in the
placenta and excessive dosage can be detri- treatment of hyperthyroidism.
mental to fetus); breastfeeding (the amount is Indications: Treatment of hyperthyroidism; for long-
small to affect tests for neonatal hypothyroid- term use (given for 1-2 years) to induce re-
ism). mission in small goiters.
Adverse Drug Reactions: Contraindications: Previous agranulocytosis to
Common: Anginal pain, excitability, flushing, head- methimazole; known hypersensitivity to me-
ache, muscular weakness, restlessness, thimazole or any component of the formula-
sweating, vomiting, weight loss. tion; drug-induced nephritis or polyarteritis no-
Less Common: Cramps, diarrhea, insomnia, nerv- dosa; liver disease; and blood disorders, such
ousness, palpitations, tachycardia. as granulocytopenia and aplastic anemia.
Rare: Arrhythmias, decreased bone density (in
women), papilledema, seizures, tremors. Dose:
Hyperthyroidism, by mouth, ADULT, initially 15 mg
Drug Interactions: daily in 3 divided doses (approximately every
Monitor closely with: 8 hours) for mild hyperthyroidism; 30-40 mg
Anticoagulants (e.g., warfarin) – enhanced antico- daily in moderately severe hyperthyroidism;
agulant effect. 60 mg/day in severe hyperthyroidism; mainte-
Combined Oral Contraceptives – the estrogen nance: 5-15 mg daily (given as a single daily
component of COCs may alter thyroxine, such dose in many cases) – which is continued for
that an increased dose is necessary. 12 to 18 months to induce remission, or for 6
Phenobarbital – this accelerates metabolism of to 12 months to prepare patients for definitive
levothyroxine; may increase its requirements therapy in the form of surgery or radioactive
in hypothyroidism. iodine therapy; CHILD, initially 0.4 mg/kg/day
Phenytoin – this accelerates metabolism of levothy- in 3 divided doses, maintenance: 0.2
roxine; may increase its requirements in hypo- mg/kg/day in 3 divided doses.
thyroidism; plasma concentration of phenytoin
is possibly increased. Dose Adjustment:
Rifampicin – this accelerates metabolism of levothy- Renal Impairment:
roxine; may increase its requirements in hypo- For mild-to-moderate renal impairment, dose reduc-
thyroidism. tion is warranted; for severe impairment, the
Theophylline – hypothyroid people may metabolize patient should be referred to a specialist.
theophylline more slowly than euthyroid peo- Precautions:
ple. Hypoprothrombinemia and bleeding; bone marrow
Avoid concomitant use with: suppression (most severe manifestation is
Calcium salts – these decrease absorption of thy- agranulocytosis); aplastic anemia; thrombocy-
roxine, possibly reducing its activity (separate
topenia; leukopenia (use with caution in pa-
administration by at least 4 hours).
tients >40 years of age, with doses ≥40
Ciprofloxacin – this may interfere with absorption of
mg/day); rash and urticaria (discontinue in the
thyroxine, resulting in hypothyroidism (sepa-
presence of exfoliative dermatitis);
rate drug administration times during a long
Discontinue if there are signs of infections (e.g.,
ciprofloxacin course).
fever, sore throat, mouth ulcer) and clinical ev-
Ferrous salts – these reduce thyroxine absorption,
idence of neutropenia; hepatic necrosis, hepa-
possibly decreasing its therapeutic effect (ad-
titis, encephalopathy (discontinue in the pres-
minister at least 4 hours apart).
ence of hepatitis – transaminase >3 times
Orlistat – this may decrease thyroxine absorption,
upper limit of normal); leukocytoclastic vascu-
possibly resulting in hypothyroidism (separate
litis and positive vasculitis (prompt discontinu-
administration by 4 hours).
ation is warranted in patients who develop
Simethicone – when given regularly, this may de-
vasculitis during therapy); lupus-like syn-
crease thyroxine absorption, possibly leading
drome.
to hypothyroidism.
Pregnancy (first trimester: can cause fetal harm;
Administration: Should be taken on an empty high risk of agranulocytosis if doses >40
stomach; take on an empty stomach ½-1 hour mg/day).
before meals, usually before breakfast.
Pregnancy Category: A Common: Pruritus, rash.
Less Common: Abnormal loss of hair, arthralgia,
edema, epigastric distress, headache, loss of
taste, lymphadenopathy, myalgia, nausea,
neuritis, paresthesia, pigmentation, pruritus,
sialadenopathy, urticaria, vertigo, vomiting.
98
Rare: Agranulocytosis, alopecia, aplastic anemia,
drug fever, granulocytopenia, hepatitis, hypo-
prothrombinemia, jaundice, lupus-like syn-
drome, myopathy, nephritis, periarteritis,
thrombocytopenia.
Drug Interactions:
Anticoagulants (e.g., warfarin) – their activity may
be increased by methimazole (because me-
thimazole may potentially inhibit vitamin K ac-
tivity).
Beta-blockers – hyperthyroidism may cause an
increased clearance of beta blockers; may re-
quire adjustments according to changes in
thyroid status.
Cardiac Glycosides – their plasma concentrations
are increased by methimazole.
Macrolide antibiotics – increased risk of QT prolon-
gation.
Prednisolone – its clearance is increased by methi-
mazole.
Theophylline – hyperthyroidism may cause a de-
creased clearance of theophylline; may re-
quire adjustments according to changes in
thyroid status.
Clozapine – increased risk of agranulocytosis.
Administration: May be taken with food or milk to
reduce stomach upset.
NOTE: Methimazole may actually be given in pregnancy if
benefits outweigh risks
99
EYES TOBRAMYCIN
Eye Drops Solution: 0.3%, 5 mL bottle
OPHTHALMIC ANTIBACTERIAL Eye Ointment: 0.3%, 3.5 g tube
PREPARATION An aminoglycoside used for ocular infections, such
as conjunctivitis, caused by gram-negative or-
ganisms, including P. aeruginosa and S. au-
ERYTHROMYCIN reus.
Indication: Treatment of superficial infections of the
Eye Ointment: 0.5%, 3.5 g tube
eye which are caused by susceptible organ-
A macrolide antibiotic used for superficial ocular isms.
infections caused by susceptible organisms,
Contraindication: Known hypersensitivity to to-
and is highly recommended for the prevention
of ophthalmia neonatorum. bramycin, and other ocular aminoglycosides,
or any component of the formulation.
Indication: Treatment of superficial ocular infec-
Dose:
tions involving the conjunctiva or cornea
caused by organisms susceptible to erythro- Mild to moderate ocular infections, ointment: apply
mycin. ½ inch (1.25 cm) 2-3 times a day; solution:
instill 1 drop every 2-4 hours for 2 days; then if
Contraindications: Known hypersensitivity to there is improvement, 1 drop 4 times daily for
erythromycin, or any component of the formu- 5 days.
lation; minor ocular irritation; prophylaxis of Severe ocular infections (including Pseudomonas
ophthalmia neonatorum from both N. gonor- aeruginosa), ointment: apply ½" (1.25 cm)
rhoeae and C. trachomatis. every 3-4 hours; solution: instill 1 drop every
30-60 minutes; then reduce to less frequent
Dose: intervals.
Conjunctivitis, ADULT, apply ½ inch (1.25 cm) on
the eyes every 3-4 hours, 2-6 times a day de- Dose Adjustment: No information found.
pending on the severity of the infection.
Precautions:
Prophylaxis of ophthalmia neonatorum, apply 1 cm
ribbon of 0.5% ointment into each lower con- Hypersensitivity reactions; contact-lens wearers;
junctival sac immediately after birth, then gen- superinfections.
NOTE: The ophthalmic solution is not for injection, and
tly massage the closed eyelids to spread the should not be injected subconjunctivally or directly in-
ointment. to the anterior chamber of the eye.
NOTE: Prophylaxis should not be delayed by more than 1
hour after delivery since delayed application may re- Adverse Drug Reactions:
duce efficacy. Ideally, a new tube or a single-use con- Common: Eye pain, ocular hyperemia.
tainer of ointment should be used for each neonate. Less Common: Conjunctivitis, eye pruritus, eyelid
Dose Adjustment: No information found. edema, headache, increased lacrimation, ocu-
lar discomfort, superficial punctuate keratitis.
Precautions: Rare: Delayed corneal epithelial wound healing,
Pregnancy and breastfeeding; this may result in hypersensitivity reactions, retinal toxicity.
overgrowth of non-susceptible organisms, in-
cluding fungi; for ophthalmic use only. Drug Interactions: Drug interactions are far less
likely to occur since systemic absorption
Adverse Drug Reactions: through topical administration is usually very
Common: Minor ocular reactions, redness. low.
Rare: Hypersensitivity reactions.
Administration: Place a small amount of ointment
Drug Interactions: No information found. into the pocket made by the lower lid and the
Administration: The ointment should be applied eye. A ½-inch strip of ointment is usually
enough, unless otherwise directed. It is advis-
directly to the infected eye through the pocket
able to apply the ointment at night and the
made by the lower lid and the eye. It is advis-
drops during daytime.
able to apply the ointment at night.
NOTE:
NOTE: Avoid contaminating the applicator tip with the mate-
• In case of concomitant therapy with other topical oph-
rial from the eyes, fingers or other sources.
thalmic medicinal products, an interval of 10 minutes
Pregnancy Category: B should be allowed between successive applications.
• If necessary, drops should precede ointments be-
cause the ointments effectively impede the absorption
of the drops.
100
tinal obstruction, osteomalacia, proximal myo-
GASTROINTESTINAL SYSTEM pathy.
Drug Interactions:
NOTE: Antacids should preferably not be taken at the same
ANTACID time as other oral drugs since they may impair ab-
sorption (interactions may be avoided by having an in-
terval of at least 2 hours between taking an antacid
ALUMINUM HYDROXIDE + and the other drug).
MAGNESIUM HYDROXIDE Monitor closely with:
Acetylsalicylic acid – its excretion is increased by
Oral: 225 mg aluminum hydroxide + 200 mg mag-
alkaline urine (produced by the antacid).
nesium hydroxide, per 5 mL suspension, Azithromycin – reduced azithromycin absorption.
120 mL Chloroquine – reduced chloroquine absorption.
A non-systemic antacid that combines aluminum Digoxin – possibly reduced digoxin absorption.
hydroxide and magnesium hydroxide to re- Enalapril – reduced enalapril absorption.
duce effect on bowel movement, and is used Isoniazid – reduced isoniazid absorption.
for the relief of epigastric pain by peptic ulcer Rifampicin – reduced rifampicin absorption.
through acid neutralization. Avoid concomitant use with:
Bisphosphonates – antacids significantly reduce the
Indications: Antacid for symptoms related to hy- absorption of oral bisphosphonates, and may
peracidity associated with heartburn, hiatal reduce their activity (do not take within 2
hernia, upset stomach, peptic ulcer, peptic hours of taking a bisphosphonate).
esophagitis, or gastritis. Iron – antacids may decrease iron absorption (sepa-
Contraindications: Severe renal impairment; hy- rate administration times as long as possible).
pophosphatemia; undiagnosed GI and rectal Ketoconazole – antacids reduce the absorption of
bleeding; porphyria; appendicitis. ketoconazole by increasing gastric pH, possi-
bly decreasing antifungal effect (give at least 2
Dose: hours apart).
Hyperacidity, by mouth, ADULT, 10-20 mL 4 times Quinolones – antacids bind to quinolones in the
daily (maximum, 80 mL daily). GIT, reducing their absorption and activity
Dose Adjustment: (give quinolone at least 2 hours before, or 4-6
hours after, the antacid).
Renal Impairment:
Rosuvastatin – antacids may decrease concentra-
Use with caution due to risk of accumulation and
tion of rosuvastatin (give the antacid 2 hours
toxicity. For mild-to-moderate renal impair-
after it).
ment, dose reduction is warranted. For severe
Tetracyclines (e.g. doxycycline) – antacids form
impairment, its use is avoided and the patient
poorly-soluble chelates with tetracyclines, re-
ducing their absorption and anti-infective ac-
Precautions: tivity.
WARNING: Aluminum and magnesium salts may be haz- Administration: Shake well before use; best given
ardous in patients with renal insufficiency. If intensive
from 1-3 hours after the last principal meal to
antacid therapy is to be used, only non-systemic (non-
absorbable) antacids should be considered because neutralize the acid produced in response to
of the potential danger of alkalosis with systemic ther- the meal, and provide buffering when the food
apy. has already left the stomach.
Acute porphyria; prolonged antacid therapy may Pregnancy Category: B
result in hypophosphatemia (Al in antacid may
form insoluble complexes with phosphate
leading to decreased phosphate absorption in ANTI-EMETICS
the GI tract); dehydration; fluid restriction;
constipation (may be exacerbated by antacids
containing Al); diarrhea (may be exacerbated METOCLOPRAMIDE
by antacids containing Mg); hepatic impair-
ment; renal impairment especially in elderly Oral: 10 mg tablet (as HCl)
and children (severe: aluminum is absorbed 5 mg/5 mL syrup, 60 mL (as base and as HCl)
and may accumulate); elderly (may be predis- Inj.: 5 mg/mL, 2 mL and 3 mL ampul (IM, IV) (as
posed to diarrhea or constipation); GI disor- base and as HCl)
ders associated with decreased bowel motility
or obstruction; some products may contain A dopamine (D 2 ) antagonist that blocks receptors in
phenylalanine. the chemoreceptor trigger zone of the medul-
la, resulting in potent anti-nausea and antie-
Adverse Drug Reactions: metic action; also blocks receptors in the GI
Common: Constipation, diarrhea, GI irritation. tract, stimulating gastric emptying and small
Less Common: Chalky taste, fecal discoloration, intestinal transit.
hypophosphatemia, nausea, vomiting.
Rare: Anemia, encephalopathy, fecal impaction, Indications: Nausea and vomiting in GI disorders,
hypermagnesemia, hypophosphatemia, intes- in migraine, and treatment with cytotoxics or
101
radiotherapy; Gastroesophageal Reflux Dis- Less Common: Bronchospasm, constipation,
ease (GERD). depression, diarrhea, edema, EPS, hyperpro-
NOTE: In children (and in some countries, patients under 20 lactinemia leading to galactorrhea, hyperten-
years), use is restricted to treatment of severe intrac- sion, hypotension, pruritus, rash, restlessness,
table vomiting of known etiology, management of ra-
urticaria.
dio- and chemotherapy-induced nausea and vomiting,
as an aid to GI intubation, and as premedication. Rare: Abnormalities in cardiac conduction (IV form),
acute CHF, agranulocytosis, bradycardia, fluid
Contraindications: Pheochromocytoma; GI ob- retention, hyperaldosteronism, leukopenia,
struction; 3 to 4 days after GI surgery; perfora- methemoglobinemia, neuroleptic malignant
tion or hemorrhage; convulsive disorders. syndrome, neutropenia, porphyria, supra-
Dose: ventricular tachycardia.
Nausea and vomiting, GERD, gastroparesis, by Drug Interactions:
mouth, by IM injection, or by slow IV injection Monitor closely with:
(over 1-2 min), ADULT, 10 mg 3 times daily; Alcohol – metoclopramide may increase the CNS
YOUNG ADULT 15-19 years (under 60 kg), 5 depressant effects of alcohol (may also accel-
mg 3 times daily; CHILD 9-14 years (30 kg erate gastric emptying of alcohol, possibly in-
and over), 5 mg 3 times daily; CHILD 5-9 creasing its rate and extent of absorption).
years (20-29 kg), 2.5 mg 3 times daily; CHILD Analgesics (e.g., aspirin and paracetamol) – their
3-5 years (15-19 kg), 2 mg 2-3 times daily; effect is enhanced by metoclopramide due to
CHILD 1-3 years (10-14 kg), 1 mg 2-3 times increased absorption.
daily; CHILD <1 year (or up to 10 kg), 1 mg Digoxin – its absorption may be decreased by
twice daily; (usual maximum 500 mi- metoclopramide from the stomach.
crograms/kg daily, particularly for children and Avoid concomitant use with:
young adults). Extrapyramidal reactions-causing drugs (e.g., chlor-
NOTE: High-dose metoclopramide with cytotoxic chemo- promazine, fluphenazine and haloperidol) –
therapy ⎼ for patients at a high risk of emesis or when these may increase the frequency and severi-
other therapies are ineffective.
ty of extrapyramidal symptoms.
Dose Adjustment: Opioid-containing medications – antagonism of
Renal Impairment: metoclopramide effect on GI activity.
Administration: Give IV injection over 1-2 minutes
to lessen transient agitation and restlessness.
Precautions:
WARNING: Treatment with metoclopramide can cause
tardive dyskinesia (TD), which is a serious movement ANTI-PEPTIC ULCER
disorder that is often irreversible. Treatment with it for
longer than 12 weeks should be avoided in all but rare
cases where therapeutic benefit is thought to out-
weigh the risk of developing TD.
PROTON PUMP INHIBITOR
Edematous conditions (use in caution in patients
who are at risk of fluid overload; may cause a OMEPRAZOLE
transient increase in serum aldosterone); De-
pression; Parkinson’s disease (avoid its use if Oral: 10 mg, 20 mg and 40 mg capsule
possible as symptoms may worsen; may have
increased risk of EPS); epilepsy; hyperten- A benzimidazole-derived, proton pump
sion; porphyria; severe renal impairment; the (H+/K+ ⎼ATPase) inhibitor, which is used for
elderly (more sensitive to adverse effects; the treatment of acid-peptic disorders.
avoid high doses and prolonged use); young
Indications: Duodenal ulcer, gastric ulcer, and
adults and children (avoid high doses; in-
NSAID-associated gastric and duodenal ul-
creased risk of EPS, particularly acute dysto-
cers and erosions; H. pylori eradication in
nia); may mask underlying disorders, such as
peptic ulcer disease; symptomatic GERD; re-
cerebral irritation; avoid for 3–4 days after GI
flux esophagitis; acid-related dyspepsia;
surgery; short-term use only (<12 weeks) (in-
prophylaxis of acid aspiration before surgery,
creased risk of tardive dyskinesia with cumu-
or aspiration of gastric contents during general
lative dose and length of treatment).
anesthesia.
(present in milk; adverse effects possible, thus Contraindications: Known hypersensitivity to
monitor infants for adverse effects). omeprazole and other proton pump inhibitors,
NOTE: May impair the mental and/or physical abilities or any component of the formulation.
required for performance of hazardous tasks, such as
operating machinery or driving a motor vehicle. Dose:
Duodenal ulcer, by mouth, ADULT, 20-40 mg daily
for at least 4 weeks; CHILD >20 kg, 20 mg
Common: Akathisia, dizziness, drowsiness, fatigue,
daily; CHILD 10-20 kg, 10 mg daily; CHILD 5-
headache, somnolence.
10 kg, 5 mg daily.
102
Erosive esophagitis, by mouth, ADULT, 20-40 mg therapeutic and adverse effects of drugs that are pri-
for at least 4 weeks. Maintenance: 20 mg daily marily metabolized by CYP enzymes (see Appendix).
for up to one year; CHILD >20 kg, 20 mg dai- Monitor closely with:
ly; CHILD 10-20 kg, 10 mg daily; CHILD, 5-10 Anticoagulants (e.g., warfarin) – enhanced effect.
kg, 5 mg daily. Anti-epileptic Agents – enhanced effect.
Helicobacter pylori infection, by mouth, ADULT, 40 Azoles (e.g., ketoconazole) – their absorption is
mg every 12 hours for 10 days, WITH amoxi- reduced by omeprazole, thus decreasing the
cillin at 1 g every 12 hours, AND clarithromy- antifungal effect.
cin at 500 mg every 12 hours for 10-14 days; Benzodiazepines (e.g., diazepam and midazolam) –
CHILD >20 kg, 20 mg daily; CHILD 10-20 kg, their concentration may be increased by
10 mg daily; CHILD 5-10 kg, 5 mg daily. omeprazole, possibly enhancing the effect.
Gastric ulcer, by mouth, ADULT, 40 mg once or Clopidogrel – its antiplatelet activity may be reduced
twice a day for at least 8 weeks; CHILD >20 by omeprazole by reducing the formation of its
kg, 20 mg daily; CHILD 10-20 kg, 10 mg daily; active metabolite.
CHILD, 5-10 kg, 5 mg daily. Clozapine – its concentration may be decreased by
GERD, by mouth, ADULT, 20-40 mg daily for 4-8 omeprazole, possibly affecting its effect.
weeks; CHILD, 5-10 kg, 5 mg daily; CHILD Digoxin – enhanced effect.
10-20 kg, 10 mg daily; CHILD more than 20 Fluconazole – this approximately doubles concen-
kg, 20 mg daily. tration of omeprazole.
Hypersecretory condition (e.g., Zollinger-Ellison Iron Salts – their absorption may be reduced by
Syndrome), by mouth, ADULT, 60 mg daily omeprazole.
(initial) up to 360 mg/day divided every 8 Mycophenolate – omeprazole may decrease its
hours. If dose >80 mg, divide it. absorption (due to increased gastric pH) with
possible loss of efficacy.
Dose Adjustment: Saquinavir – its concentration may be increased by
Hepatic Impairment: omeprazole, possibly increasing risk of toxici-
For mild-to-moderate hepatic impairment, dose ty.
reduction is warranted; for severe impairment, St. John’s wort – this may increase metabolism of
the patient should be referred to a specialist. omeprazole, possibly decreasing its concen-
tration and clinical effect.
Precautions:
Gastric malignancy (relief of symptoms does not Administration: To be taken 30 minutes before
preclude presence of a gastric malignancy); meal; preferably at breakfast if to be taken
GI infection (use of PPI may increase risk of once a day.
infections); fractures (increased incidence of NOTE: For patients with swallowing difficulties, capsules can
osteoporosis-related bone fractures of the hip, be opened, and the contents swallowed or suspended
spine or wrist may occur); hypomagnesemia in a slightly acidic fluid, e.g., fruit juice or in non-
carbonated water. The suspension must be drunk
(rarely reported); gastric carcinoma (exclude within 30 minutes. Alternatively, these patients can
before starting treatment for gastric ulcers; suck the capsule and swallow the contents. The con-
PPI may mask symptoms and delay diagno- tents of the capsule should neither be chewed nor
sis); hepatic impairment (risk of accumulation crushed.
when higher doses are used; monitor for ad-
verse effects); severe liver disease; surgery
(treatment should be continued peri- For more information on the treatment of H. pylori
operatively). infection in peptic-ulcer disease, please see
Pregnancy (use only if really warranted); breast- under Antimicrobial Section.
feeding (omeprazole is excreted in breast
milk, but is not likely to influence the child
when therapeutic doses are used). ANTISPASMODICS
Common: Abdominal pain, constipation, diarrhea,
flatulence, headache, nausea, vomiting. DICYCLOVERINE
Less Common: Decreased absorption of vitamin
B 12 , dizziness, drowsiness, dry mouth, fa- Oral: 10 mg tablet (as hydrochloride)
tigue, insomnia, malaise, paresthesia, pruri- 10 mg/5 mL syrup, 30 mL, 60 mL and 120 mL
tus, rash, somnolence, urticaria, vertigo. (as hydrochloride)
Rare: Alopecia, arthralgia, blurred vision, confusion, An antimuscarinic agent used primarily as anti-
dermatitis, gynecomastia, hemolytic anemia, spasmodic. It has a much less marked anti-
hepatitis, hypersensitivity reactions, hypo- muscarinic action than atropine and may also
magnesemia, interstitial nephritis, jaundice, have some direct action on smooth muscle.
leukopenia, microscopic colitis, myalgia, myo- Indication: Treatment of patients with functional
pathy, pancreatitis, peripheral edema, raised bowel/irritable bowel syndrome; adjunct in GI
liver enzymes, skin reactions, taste disturb- disorders characterized as functional disturb-
ance, thrombocytopenia. ances of gastrointestinal motility.
Drug Interactions: Contraindications: Obstructive diseases of the GI
NOTE: CYP-based interactions: omeprazole (a CYP1A2
inducer and a CYP2C19 inhibitor) may alter both the
tract; severe ulcerative colitis; reflux esopha-
103
gitis; unstable cardiovascular status in acute Drug Interactions:
hemorrhage; obstructive uropathy; glaucoma; Monitor closely with:
myasthenia gravis; breastfeeding; infants <6 Analgesics (Opioid) – their adverse effects may be
months of age; hypersensitivity to dicyclover- enhanced by dicycloverine, specifically the
ine or any component of the formulation. risk for constipation and urinary retention.
Anticholinergic Agents – dicycloverine may enhance
Dose: adverse effect of other anticholinergics.
Gastrointestinal motility disorders/irritable bowel, by Thiazide Diuretics – their serum concentration may
mouth, ADULT, 20 mg 4 times daily for 7
be increased by dicycloverine.
days; after 1 week, may increase to 40 mg 4 Avoid concomitant use with:
times daily; CHILD 6-24 months, 5 mg per
Ipratropium (Oral Inhalation) – this may enhance the
dose 3-4 times daily; CHILD 2-12 years, 10
anticholinergic effect of anticholinergic
mg per dose 3-4 times daily. agents.
NOTE: In adults, if efficacy not achieved in 2 weeks or if
adverse effects require a dose <80 mg/day, therapy Administration: Maybe taken before or after
should be discontinued. Safety data are not available
meals.
for doses >80 mg daily for a duration that exceeds 2
weeks. Pregnancy Category: B
Dose Adjustments:
Geriatric:
Refer to adult dosing. Use with caution; lower dos-
ages may be warranted. HYOSCINE
Renal Impairment:
No dosage adjustment provided in the manufactur- Oral: 10 mg tablet (as N-butyl bromide)
er’s labeling (has not been studied); use with 5 mg/5 mL syrup, 60 mL (as N-butylbromide)
caution. Inj.: 20 mg/mL, 1 mL ampul (IM, IV, SC)
Hepatic Impairment: (as N-butyl bromide)
No dosage adjustment provided in the manufactur- 200 micrograms/mL, 1 mL ampul (IM, IV)
er’s labeling (has not been studied); use with (as hydrobromide)
caution. 500 micrograms/mL, 1 mL ampul (IM, IV)
(as hydrobromide)
Precautions:
WARNING: Should not be given to children below 6 months A poorly-absorbed, quaternary amine, anticholiner-
of age. gic agent that is used to relax smooth mus-
cles, and reduce GI motility and spasm.
Avoid performing tasks which require mental alert-
ness (e.g., operating machinery or driving Indications: Smooth muscle spasm of the genito-
since dicycloverine may cause drowsiness urinary or GI tract (e.g., renal and biliary
and/or blurred vision); discontinue if diarrhea spasm).
occurs since this may be a sign of incomplete
intestinal obstruction; during hot weather Contraindications: Hypersensitivity to hyoscine or
and/or exercise (due to the possible occur- any component of the formulation; glaucoma;
rence of heat prostration). megacolon, myasthenia gravis; stenotic le-
Psychosis and delirium has been reported in pa- sions of the GI tract; paralytic ileus; acute
tients with an extreme sensitivity to anticholin- hemorrhage; tachycardia, angina or heart fail-
ergic effects or at excessive dosages, such as ure; obstructive prostatic hypertrophy; IM ad-
the elderly or patients with mental illness. ministration in patients with anticoagulant
Elderly (avoid long term use due to intolerable therapy.
anticholinergic effects and uncertain effective- Dose:
ness – the potential risk for a toxic reaction is Acute therapy of smooth muscle spasm, by mouth,
greater than the potential benefit). ADULT, 10-20 mg daily; prolonged therapy,
Infants (serious respiratory reactions, central nerv- by mouth, ADULT, 10 mg 3-5 times daily
ous system symptoms, and deaths have been (maximum, 60 mg daily); by IM, IV or SC in-
reported). jection, 10-20 mg (maximum, 100 mg/day);
Adverse Drug Reactions: CHILD >6 years, 10 mg 3 times daily.
NOTE: Doses can be repeated after 30 minutes if needed
Common: Dizziness, xerostomia, nausea, blurred
(may need to be repeated more frequently in endos-
vision, somnolence, nervousness, weakness. copy).
Rare: Abdominal distension, abdominal pain, ana-
phylactic shock, angioedema, confusional Dose Adjustment:
state, constipation, cycloplegia, delirium, der- Renal Impairment:
matitis (allergic), hypersensitivity, dyspepsia, For mild-to-moderate renal impairment, dose reduc-
dyspnea, erythema, facial edema, fatigue, hal- tion is warranted; for severe impairment, the
lucinations, headache, insomnia, lactation patient should be referred to a specialist. This
suppressed, malaise, mydriasis, nasal con- is not recommended in patients with renal fail-
gestion, palpitation, rash, syncope, tach- ure.
yarrhythmias, vomiting.
104
Precautions:
WARNING: Patients who experience blurred vision or
drowsiness must not drive or operate machinery.
CNS effects (may cause drowsiness and blurred
vision, caution in performing tasks which re-
quire mental alertness); idiosyncratic reactions
(though these are rare, patients may experi-
ence acute toxic psychosis, agitation, confu-
sion, delusions, hallucinations, paranoid be-
havior, and rambling speech); visual disturb-
ances (discontinue if patient reports unusual
visual disturbances or pain within the eye);
withdrawal (adverse events, including dizzi-
ness, headache, nausea, vomiting, may occur
following abrupt discontinuation of large doses
or in patients with Parkinson’s disease); de-
mentia (anticholinergics may worsen symp-
toms and antagonize therapeutic effects of an-
ticholinesterases);
Fever, high ambient temperature (risk of hyperther-
mia);
Cardiovascular disease; GI obstruction or atony;
genitourinary disease and obstruction; glau-
coma; hiatal hernia; hyperthyroidism; psycho-
sis; seizure disorders; ulcerative colitis; renal
and hepatic impairment;
Elderly (avoid use due to potent anticholinergic
adverse effects and uncertain effectiveness);
and children (increased risk of adverse ef-
fects);
Anaphylaxis.
Less Common: Diarrhea, dry mouth, nose, throat
or skin, dyshidrosis, headache, increased eye
pressure, itching, mydriasis, nausea, skin re-
actions (e.g., urticaria, pruritus, erythema,
rash), tachycardia, vomiting.
Rare: Acute toxic psychosis, angioedema, de-
creased blood pressure, blurred vision, coma,
confusion, constipation, dizziness, drowsi-
ness, dysuria, fixed drug eruptions, flushing,
hypersensitivity reactions including anaphylax-
is; orthostatic hypotension, palpitations, rapid
and irregular pulse, swallowing difficulties,
tremor, urinary retention.
Drug Interactions:
Alcohol – enhanced CNS depressant effect.
Topiramate and zonisamide – anticholinergics may
decrease sweating, and cause hyperthermia;
risk is increased when given with these drugs.

Anticholinergic drugs (see Appendix – Table A) –
additive anticholinergic effects; may increase
the therapeutic and adverse effects.
Anticholinesterases – these can antagonize the
anticholinergic effect of hyoscine.
Administration: Swallow tablets whole with full
glass of water.
105
Edema, by mouth, ADULT, 40 mg orally daily in
GENITO-URINARY SYSTEM divided doses; may be increased gradually to
120 mg in resistant edema; CHILD, 1-3 mg/kg
daily (maximum, 40 mg daily); INFANT, 1-6
ANTI-UROLITHIASIS mg/kg/day given in divided doses every 6-12
hours; NEONATES/PREMATURE INFANTS,
SAMBONG [Blumea balsamifera by mouth, 1-4 mg/kg/dose once a day to twice
L. DC (Fam. Asteraceae)] a day (poor bioavailability) or by IV injection,
1-2 mg/kg/dose every 12-24 hours, or as con-
Oral: 250 mg and 500 mg tablet tinuous IV infusion, 0.05 mg/kg/hour (maxi-
mum, 0.4 mg/kg/hour).
A natural, medicinal preparation from the leaves of
Oliguria (glomerular filtration rate <20 mL/minute),
Blumea balsamifera Linn. DC (Family Aster-
by slow IV infusion at a rate not exceeding 4
aceae), which is utilized in the treatment of mg/minute, ADULT, initially 250 mg over 1
urological disorders.
hour; if urine output is not satisfactory during
Indications: For urinary tract pain and burning the hour after the first dose, infuse 500 mg
sensation; to increase urinary output in condi- over 2 hours then, if there is no satisfactory
tions characterized by fluid retention or ede- response during the hour after the second
ma; for kidney stones dose, infuse 1 g over 4 hours; if there still is
no response after the third dose, dialysis is
Contraindications: No information found. probably necessary; the effective dose (up to
Dose: 1 g) can be repeated every 24 hours.
NOTE: Dose should be diluted in a suitable amount of
Anti-urolithiasis, by mouth, ADULT, 1 g three times
infusion fluid, according to the hydration of the patient.
a day; CHILD 7-12 years, 250 mg 3-4 times a
day. Dose Adjustment:
Renal Impairment:
Dose Adjustments: No information found.
May require high doses to initiate desired response;
Precautions:
Precautions:
Patients with excretory urogram showing signs of
WARNING: Cases of tinnitus and reversible or irreversible
renal obstruction; pregnancy and lactation.
hearing impairment and deafness have been report-
Adverse Drug Reactions: ed. Ototoxicity is related to rapid injection, severe re-
Elevation in ALT, epigastric pain, constipation. nal impairment, use of higher than recommended
doses, hyponatremia or concomitant therapy with
Drug Interactions: None known. aminoglycoside antibiotics, or other ototoxic drugs. If
high doses are necessary, parenteral therapy with
Administration: May be taken with or without food. controlled IV infusion is advisable.
Pregnancy Category: No information found. Prostatic obstruction (loop diuretics may precipitate
acute urinary retention); prostatic enlarge-
ment; gout (may be aggravated by diuretic-
DIURETICS induced hyperuricemia);
Monitor electrolytes, particularly potassium and
sodium; hypotension;
Elderly (reduce the dose; more susceptible to elec-
FUROSEMIDE trolyte imbalance and orthostatic hypoten-
sion);
Oral: 40 mg tablet
In oliguria, correct hypovolemia before administra-
Inj.: 10 mg/mL, 2 mL ampul (IM, IV)
tion; renal impairment (deafness may follow
A potent, high-ceiling, sulfonamide loop diuretic rapid IV injection; monitor electrolytes and
which produces dose-dependent diuresis of creatinine);
relatively short duration. Hepatic impairment (hypokalemia may precipitate
coma, use potassium-sparing diuretic to pre-
Indications: Edema, pulmonary edema, hepatic vent this; increased risk of hypomagnesemia
cirrhosis, nephrotic syndrome; oliguria due to in alcoholic cirrhosis); diabetes (may see
renal failure. changes in glucose control); SLE (may cause
Contraindications: Known hypersensitivity to SLE exacerbation or activation).
furosemide or any component of the formula- In patients with symptoms of severe urinary reten-
tion; severe fluid and sodium depletion. tion, it may cause an acute urinary retention
(due to increased production and retention of
Dose: urine especially upon initiation of therapy).
Acute pulmonary edema, by slow IV injection, In patients at high risk for radiocontrast nephropa-
ADULT, 40 mg initially, dose may be doubled thy, furosemide can lead to higher incidence
every hour until a ceiling dose of 160 mg; Al- of deterioration in renal function after radio-
ternatively, furosemide may be given by slow contrast is received.
IV drip or infusion at a dose of 40 mg/hour; Pregnancy (avoid use; may cause electrolyte dis-
CHILD, 0.5-1.5 mg/kg daily (maximum, 20 mg turbance in fetus; possible neonatal thrombo-
daily). cytopenia; monitor fetal growth because of po-
106
tential for higher fetal birth weights); breast-
feeding (enters breast milk; use with caution). HYDROCHLOROTHIAZIDE
Oral: 12.5 mg, 25 mg and 50 mg tablet
Common: Dehydration, dizziness, gout, hyperu-
ricemia, hypokalemia, hypomagnesemia, hy- A moderately-potent, thiazide diuretic whose maxi-
ponatremia, orthostatic hypotension, syncope. mal antihypertensive effect is usually ob-
Less Common: Dyslipidemia, hyperglycemia, served at doses lower than those that produce
hypocalcemia, increased creatinine concen- maximal diuretic effect.
tration, rash.
Rare: Acute pancreatitis, agranulocytosis, bone Indication: Edema.
marrow depression, bullous eruptions, exfolia- Contraindications: See under Antihypertensive.
tive dermatitis, hemolytic anemia, interstitial
nephritis, jaundice, photosensitivity, Stevens- Dose:
Johnson syndrome, thrombocytopenia, tinni- Edema, by mouth, ADULT, 25-100 mg daily, or
tus, vertigo. intermittently on 3-5 days each week.
Drug Interactions: See under Antihypertensives for other information.
Alcohol – enhanced hypotensive effect.
ACE inhibitors (e.g., enalapril) – loop diuretics in- FOR BENIGN PROSTATIC HYPERTROPHY
crease risk of severe hypotension with the first
dose of an ACE inhibitor; possibly increased
risk of ACE inhibitor-induced renal impair- TAMSULOSIN
ment.
Drugs causing hypotension (e.g. amlodipine, diaze- Oral: 200 microgram capsule (as HCl)
pam, hydrochlorothiazide and methyldopa) –
furosemide can cause hypotension, and may An alpha 1 -selective adrenoceptor antagonist that is
cause an additional drop in blood pressure used in mediating smooth muscle tone in the
when given with the stated drugs. prostate to relieve symptoms of urinary ob-
Digoxin – hypokalemia caused by furosemide instruction, which is caused by benign prostatic
creases its cardiac toxicity. hypertrophy (BPH).
NSAIDs (including COX-2 inhibitors) – these may Indication: Treatment of sign and symptoms of
reduce renal function and diuretic effect, and benign prostatic hypertrophy.
increase the risk of nephrotoxicity.
Ototoxic drugs (e.g., gentamicin and streptomycin) Contraindications: Known hypersensitivity to
– increased risk of ototoxicity. tamsulosin or any component of the formula-
Salbutamol – increased risk of hypokalemia. tion; in patients with a history of micturition
ARBs – increased risk of excessive hypotension syncope and postural hypotension.
after the first dose of an ARB (because of vol- Dose:
ume depletion). Benign prostatic hypertrophy, by mouth, ADULT,
Thiazide diuretics (e.g., hydrochlorothiazide) – 400 micrograms daily.
results to a synergistic effect, which may NOTE: The dose may be increased after 2-4 weeks to 800
cause profound diuresis and serious electro- micrograms once daily in patients who fail to respond.
lyte disturbance. If therapy is interrupted for several days, restart with
Avoid concomitant use with: 400 micrograms once daily.
Contraceptives, Oral – antagonism of diuretic effect Dose Adjustments:
by estrogens. Renal and Hepatic Impairment:
Hydrocortisone – antagonism of diuretic effect;
Use drug with caution for mild-to-moderate impair-
increased risk of hypokalemia.
ment; for severe impairment, the patient
Ibuprofen – antagonism of diuretic effect; also in-
crease the risk of nephrotoxicity of ibuprofen.
Lidocaine – action of lidocaine is antagonized by Precautions:
hypokalemia caused by furosemide. Do not use as an antihypertensive.
Metformin – antagonism of hypoglycemic effect. Patients who are receiving an antihypertensive
treatment may require dose reduction, and
Administration: The tablet is usually taken once
supervision (alpha 1 -blockers tend to reduce
daily in the morning. If it is taken twice a day,
BP; possibly resulting in additive hypoten-
take the first dose in the morning and the sec-
sion); volume depletion (risk of exacerbation
ond dose at lunchtime. The patient may feel
of orthostatic hypotension); the elderly and in
dizzy on standing when taking the medicine;
patients undergoing cataract surgery (risk of
the patient should get up gradually from sitting
intraoperative floppy iris syndrome); renal im-
or lying to minimize this effect. The patient pairment; hepatic impairment; monitor for an
should sit or lie down if dizziness occurs. To improved urine flow; monitor for “first dose” or-
avoid ototoxicity, IV doses must be given no thostatic hypotension, headache, or GI dis-
faster than 4 mg/minute.
turbances (e.g., nausea and vomiting) at the
Pregnancy Category: C beginning of therapy and on a regular basis.
107
NOTE: Dizziness on standing may occur especially when
starting treatment or when the dose is increased.

Common: Abnormal ejaculation, chest pain, dizzi-
ness, drowsiness, fatigue, headache, insom-
nia, nasal congestion, rhinitis, urinary urgency,
weakness.
Less Common: Blurred vision, dryness of mouth,
edema, first-dose hypotension, orthostatic hy-
potension, increased sweating, nausea, palpi-
tations, syncope, tachycardia, urinary inconti-
nence, vomiting.
Rare: Angioedema, depression, dyspnea, hyper-
sensitivity reactions, itch, mood changes, par-
esthesia, rash, urticaria, vertigo.
Drug Interactions:
Alpha-/Beta-agonists – their vasoconstricting effect
may be reduced by tamsulosin due to vasodi-
lation.
Beta-blockers – these may enhance the orthostatic
hypotensive effect of tamsulosin.
Calcium channel blockers – their hypotensive effect
may be enhanced by tamsulosin.
CYP3A4 inhibitors – these may increase the con-
centration of tamsulosin; further risk of ad-
verse effects.
MAO inhibitors – these may enhance the orthostatic
hypotensive effect of tamsulosin.
Phosphodiesterase inhibitors – these may enhance
the hypotensive effect of Alpha 1 -blockers.
Alpha 1 -blockers – tamsulosin may enhance their
antihypertensive effect.
Fusidic acid (systemic) – this may increase the
concentration of tamsulosin; further risk of ad-
verse effects.
Administration: Administer it 30 minutes after the
same meal each day. Capsules should be
swallowed whole; do not crush, chew or open.
NOTE: The extent and rate of absorption are reduced in the
presence of food.
108
Myasthenia gravis (since Mg interferes with neuro-
GYNECOLOGY AND OBSTETRICS muscular transmission; possible marked in-
crease in weakness, particularly of respiratory
musculature); hepatic impairment (avoid in
FOR ECLAMPSIA hepatic coma if there is risk of renal failure);
renal impairment (increased risk of toxicity,
e.g., hypermagnesemia).
MAGNESIUM SULFATE Pregnancy (third trimester: not known to be harmful
for short-term IV administration in eclampsia,
Inj.: 250 mg/mL, 2 mL and 10 mL ampul and 20 but excessive doses may cause neonatal res-
mL vial (IM, IV) piratory depression).
500 mg/mL, 2 mL and 10 mL ampul (IM, IV)
A sterile preparation that contains magnesium as Common: Flushing, nausea, vomiting.
heptahydrate. Less Common: Dizziness, drowsiness, headache,
Indications: The drug of choice for the prevention thirst.
Rare: Arrhythmias, cardiac arrest, coma, confusion,
of seizures in women with severe pre-
eclampsia, and for controlling seizures or pre- loss of tendon reflexes, muscle weakness,
venting their recurrence among eclamptic pa- respiratory depression.
tients. Drug Interactions:
Contraindications: Known hypersensitivity to Monitor closely with:
Aminoglycosides – there is additive neuromuscular
magnesium and its salts; heart block; myocar-
blocking effect.
dial infarction; hypermagnesemia; deranged
CNS depressants (e.g., barbiturates, opiates or
renal function; myasthenia gravis.
general anesthetics) – additive central de-
Dose: pressant effects.
Prevention of recurrent seizures, IV loading dose of Neuromuscular blockers (e.g., tubocurarine, vecu-
4 g over 5-15 minutes followed by mainte- ronium and succinylcholine) – potentiation of
nance IV infusion of 1 g/hour for at least 24 neuromuscular blockade.
hours after the last seizure or delivery (which- Nifedipine – this increases effects of parenteral
ever occurs later), or by deep IM injection magnesium sulfate and risk of hypotension.
(used for special situations; when IV lines are
Administration: For IV administration, the rate of
not available), 5 g into each buttock, then 5 g
every 4 hours into alternate buttocks for at injection should not exceed 150 mg/minute.
least 24 hours after the last seizure or delivery Pregnancy Category: D
(recurrent seizure should be treated by further
IV bolus of 2 g; 4 g if body weight is over 70
kg). HORMONES
DILUTION AND ADMINISTRATION. According to manufac-
turer’s directions. The concentration of magnesium
sulfate should not exceed 20% (dilute 1 part of mag-
nesium sulfate injection, 50%, with at least 1.5 parts ETHINYLESTRADIOL +
of water for injection); for IM injection, mix magnesium LEVONORGESTREL
sulfate injection, 50%, with 1 mL lidocaine injection,
2%. Oral: 30 micrograms ethinylestradiol + 150 microg-
rams levonorgestrel per tablet as 21 active
Dose Adjustment:
tablets or 28 day tablet with 21 active and 7
Renal Impairment:
inactive pills
Dose should not exceed 20 g/48 hours (use with
caution). A combined, oral contraceptive, which contains
estrogen as ethinylestradiol, and progesterone
Precautions:
as levonorgestrel; it inhibits ovulation, reduces
WARNING: Magnesium toxicity causes loss of deep tendon receptivity of endometrium to implantation and
reflexes, followed by respiratory depression and ulti-
mately respiratory arrest. In most cases, therapy can
thickens cervical mucus to form a barrier to
be monitored safely by hourly measurement of the pa- sperm.
tellar reflex and respiratory rate (or oxygen satura-
tion). If deep tendon reflexes are absent, further dos-
Indication: Contraception.
es of magnesium sulfate should be withheld until re- Contraindications: Breast cancer (current or re-
flexes return. Magnesium can be reversed with calci-
um gluconate. Calcium is administered as a 10-20 mL
cent); risk factors for venous thromboembo-
IV of 10% solution, and can be given as an antidote lism and arterial disease; heart disease asso-
for problematic signs associated with hy- ciated with pulmonary hypertension or risk of
permagnesemia. Magnesium is excreted by the kid- embolism; migraine; history of subacute bac-
ney and regular monitoring of serum levels should be terial endocarditis; ischemic cerebrovascular
considered in women with oliguria (urine output <100 disease; liver disease, including disorders of
mL/4 hours). If repeated seizures occur despite mag-
nesium, other pre-hospital options include administer-
hepatic secretion; porphyria; systemic lupus
ing diazepam. erythematosus; liver adenoma; history of he-
molytic uremic syndrome; gallstones; estro-
gen-dependent neoplasm; neoplasm of genital
109
tract; undiagnosed vaginal bleeding; history creased risk of thromboembolism and cardio-
during pregnancy of pruritus, chorea, deterio- vascular events); BMI >30 (risk of thrombo-
rating otosclerosis, cholestatic jaundice, or embolism increases with increasing BMI);
pemphigoid gestationis; after evacuation of malabsorption syndromes (efficacy may be
hydatidiform mole (unless urine and plasma reduce due to poor absorption); surgery (con-
gonadotropin values are restored to normal). traceptives may increase the risk of VTE);
SLE (may be exacerbated).
Dose:
Pregnancy (epidemiological evidence suggests no
Contraception, by mouth, 1 tablet daily for 21 days
harmful effects on fetus); use within 3 weeks
starting D1 of menstrual cycle; subsequent
of birth; breastfeeding (combined oral contra-
courses repeated after a 7-day interval (during
ceptives may inhibit lactation — use alterna-
which withdrawal bleeding occurs); or 28 tab-
tive method of contraception until weaning or
lets, by mouth, [everyday (ED) preparations],
for 6 months after birth).
1 active tablet daily started on D1 of the cycle MIGRAINE. Patients should report any increase in headache
up to D21; subsequent courses repeated frequency or onset of focal symptoms (discontinue
without interval (withdrawal bleeding occurs immediately and refer urgently to a neurologist if focal
when inactive tablets are being taken). neurological symptoms not typical of aura persist for
ADMINISTRATION. Each tablet (“pill”) should be taken at more than 1 hour).
approximately the same time each day; if one or more TRAVEL. Women taking oral contraceptives may be at
tablets are forgotten for more than 12 hours, contra- increased risk of deep-vein thrombosis during travel
ceptive protection will be reduced. involving long periods of immobility (over 5 hours).
MISSED PILL. The critical time for loss of contraception The risk may be reduced by appropriate exercise dur-
protection is when a pill is omitted either at the begin- ing the journey, and possibly by wearing elastic hosi-
ning or at the end of a cycle (as this lengthens the pill ery.
free interval). If a woman forgets to take a pill, she
should take it as soon as she remembers, and take Adverse Drug Reactions:
the next one at the normal time. If the delay with any Common: Acne, breakthrough bleeding, breast
pill is 24 hours or longer (but especially with the first enlargement and tenderness, changes in libi-
one in the packet), the pill may not work. She should do, chloasma, fluid retention, headache, in-
still continue taking the pill normally but be aware that creased BP, mood changes (e.g., depres-
she will not be protected for the next 7 days and must
sion), nausea, thrush, vomiting.
therefore either not have sex or use another method
of contraception, such as a condom. If these 7 days Less Common: Alopecia, altered lipid profiles,
run beyond the end of the packet, the next packet amenorrhea, contact lens intolerance, hir-
should be started at once, omitting the pill-free inter- sutism, hyperinsulinemia, insulin resistance,
val (or, in the case of ED pills, omitting the 7 inactive rash.
tablets). Emergency contraception is recommended if Rare: Allergy, breast cancer, cervical cancer, hyper-
more than 2 combined oral contraceptive tablets are
tension, jaundice, liver cancer, pancreatitis,
missed from the first 7 tablets in a packet.
DIARRHEA AND VOMITING. Vomiting within 2 hours of photosensitivity, stroke, VTE.
taking an oral contraceptive or very severe diarrhea
Drug Interactions:
can interfere with the absorption of the pill. Additional
NOTE: CYP-based interactions: combined oral contracep-
precautions should be used during, and for 7 days af-
tives are metabolized by CYP3A4; administration with
ter, recovery. If vomiting and diarrhea occur during
drugs which affect this enzyme may alter the activity
the last 7 pills, the next pill-free period should be omit-
and toxicity of the contraceptives (see Appendix).
ted (or in the case of ED tablets, the inactive ones
should be omitted). Monitor closely with:
Cephalosporins (e.g., ceftriaxone) – these may
Dose Adjustments: reduce the contraceptive effect of estrogens.
Renal Impairment: Hydrocortisone – its plasma concentration is in-
Use drug with caution for mild-to-moderate renal creased by contraceptives containing estro-
impairment; for severe impairment, the patient gens.
should be referred to a specialist. Macrolide antibiotics (e.g., azithromycin and eryth-
Hepatic Impairment: romycin) – these may reduce the contracep-
Do not administer treatment. tive effect of estrogens.
Precautions: Metronidazole – this may reduce the contraceptive
Unexplained vaginal bleeding (investigate cause effect of estrogens.
before starting contraceptive); risk factors for Penicillins (e.g., ampicillin, benzylpenicillin, amoxi-
venous thromboembolism and arterial dis- cillin and phenoxymethylpenicillin) – these
ease; migraine without focal aura or controlled may reduce the contraceptive effect of estro-
with 5HT 1 agonist (see note below); hyperpro- gens.
lactinemia (seek specialist advice); gallbladder Quinolones (e.g., ciprofloxacin, levofloxacin) – these
disease (contraceptives increase the secretion may reduce the contraceptive effect of estro-
of cholic acid in bile and may worsen existing gens.
gall bladder disease); some types of hyper- Tetracyclines (e.g., doxycycline) – these may re-
lipidemia; history of severe depression espe- duce the contraceptive effect of estrogens.
cially if induced by hormonal contraception; Avoid concomitant use with:
long-term immobilization (see travel below); Amlodipine – antagonism of hypotensive effect by
sickle-cell disease; inflammatory bowel dis- estrogens.
ease including Crohn’s disease); diabetes Carbamazepine – this may increase metabolism of
(additional risk of thrombosis); smoking (in- contraceptive pills, and increased risk of con-
traceptive failure.
110
Enalapril – antagonism of hypotensive effect. menstrual irregularities and the potential for a delay in
Furosemide – antagonism of diuretic effect. return to full fertility with long-term use.
Hydrochlorothiazide – antagonism of diuretic effect. Dose Adjustment:
Isosorbide dinitrate – antagonism of hypotensive Hepatic Impairment:
effect. Use with caution; avoid in active or severe liver
Metformin – antagonism of hypoglycemic effect. disease.
Methyldopa – antagonism of hypotensive effect.
Phenobarbital – this may increase the metabolism Precautions:
of estrogen, thus increasing the risk of contra- Unexplained vaginal bleeding (investigate cause
ceptive failure. before starting treatment); history of endome-
Phenytoin – this may increase the metabolism of triosis (potential risk of recurrence or malig-
estrogens, thus increasing the risk of contra- nancy); uterine fibroids (fibroids may increase
ceptive failure. in size); migraine (may be exacerbated).
Rifampicin – this accelerates the metabolism of Liver disease (avoid use in active liver disease and
estrogens and progestogens, thus reducing if there is a history of pruritus during pregnan-
their contraceptive effect. cy); thromboembolic or coronary vascular dis-
ease; diabetes mellitus (treatment may im-
Administration: Each pill should be taken at ap- prove glycemic control; monitor and adjust
proximately the same time each day; if de- dose of antidiabetic drug if necessary); epilep-
layed by longer than 24 hours, contraceptive sy (may increase seizure frequency); smoking
protection may be lost. (increases risk of thromboembolism); SLE
Pregnancy Category: X (risk of flares may be increased).
Hypertension; renal disease; cholestasis may recur
in women with a history of cholestasis during
pregnancy; gall bladder disease (may be ex-
MEDROXYPROGESTERONE acerbated).
Age >60 years (increased risk of coronary heart
Inj.: 50 mg/mL, 3 mL vial + syringe (IM) disease, stroke, VTE and breast cancer);
(as acetate) breastfeeding (present in milk; no adverse ef-
fects reported; preferably start injectable con-
N.B. use one (1) inch long needle traceptive 6 weeks after birth or later).
A long-acting, progestin injectable contraceptive Adverse Drug Reactions:
indicated for the prevention of pregnancy. Common: Abnormal mammogram, breast en-
Indications: Parenteral progestogen-only contra- largement and tenderness, change in libido,
ception (short- or long-term); menstrual symp- depression, endometrial hyperplasia, head-
toms and endometriosis. ache, irregular/breakthrough bleeding, leg
cramps, spotting.
Contraindications: Pregnancy (genital malfor- Less Common: Acne, benign proliferative breast
mations and cardiac defects reported in male disease, breast cancer, cardiovascular events,
and female fetuses; inadvertent use of the de- dementia, edema, exacerbation or recurrence
pot medroxyprogesterone contraceptive injec- of endometriosis, fluid retention, gall stones,
tion in pregnancy unlikely to harm fetus); his- increased BP, increased triglycerides, itch,
tory of breast cancer (may be used after 5 migraine, nausea, premenstrual-like syn-
years if no evidence of current disease); undi- drome.
agnosed vaginal bleeding; history of pruritus Rare: Chloasma, cholestatic jaundice, endometrial
during pregnancy; active liver disease (avoid cancer, enlargement of hepatic hemangiomas,
use in active liver disease and if history of pru- enlargement of uterine fibroids, galactorrhea,
ritus during pregnancy); severe arterial dis- glucose intolerance, hypersensitivity reac-
ease (multiple risk factors for venous throm- tions, ovarian cancer, pancreatitis, visual
boembolism and arterial disease); porphyria. changes.
Dose: Drug Interaction:
Contraception (short-term), by deep IM injection, Avoid concomitant use with:
ADULT (female), 150 mg within the first 7 Metformin – antagonism of hypoglycemic effect.
days of cycle or within the first 5 days after
parturition (delay until 6 weeks after parturition Administration: If the interval between injections is
if breastfeeding). > 3 months and 14 days, exclude pregnancy
Contraception (long-term), by deep IM injection, before administering the next injection and
ADULT (female), as for short-term, repeated advise patient to use additional contraceptive
every 3 months. measures (e.g., a condom) for 7 days after the
NOTE: If the interval between injections is >3 months and injection.
14 days, exclude pregnancy before administering the
Pregnancy Category: X
next injection and advise patient to use additional
contraceptive measures (e.g., a condom) for 7 days
after the injection.
PATIENT ADVICE. It is recommended that before treatment,
women receive full counseling about the likelihood of
111
OXYTOCIC Previous uterine surgery, multiple pregnancy or >4
previous births (increased risk of uterine rup-
ture); induction or enhancement of labor in the
OXYTOCIN presence of borderline cephalopelvic dispro-
portion (avoid use if significant);
Inj.: 5 IU/mL and 10 IU/mL, 1 mL ampul (IM, IV) Mild-to-moderate pregnancy-associated hyperten-
sion or cardiovascular disease; age >35
A synthetic nonapeptide identical with oxytocin ⎼ a years; history of low-uterine segment caesar-
peptide hormone secreted by the posterior pi- ean section; caudal block anesthesia (risk of
tuitary which participates in labor or delivery severe hypertension due to enhanced vaso-
and stimulates uterine contraction. pressor effect of sympathomimetics); avoid
Indications: Prevention and treatment of post- tumultuous labor if fetal death or meconium-
partum and post-abortion hemorrhage; induc- stained amniotic fluid (risk of amniotic fluid
tion and augmentation of labor. embolism) occurs; water intoxication and hy-
ponatremia (avoid large volume infusions and
Contraindications: Allergy to oxytocin or any com- restrict fluid intake).
ponent of the formulation; hypertonic uterine
contractions, mechanical obstruction to deliv-
ery, or fetal distress; any condition where Less Common: Nausea, vomiting
spontaneous labor or vaginal delivery inadvis- Rare: Anaphylactoid reaction, arrhythmias, ECG
able; major cephalopelvic disproportion. changes, flushing, prolonged QT interval,
rash, reflex tachycardia, severe (tetanic) uter-
Dose: ine spasm and contraction leading to uterine
Induction of labor, by IV infusion, ADULT and AD- rupture or fetal distress, hypoxia and death;
OLESCENT, initially 0.001-0.002 IU/minute seizures, transient hypotension, water intoxi-
increased in 0.001-0.002 IU/minute incre- cation.
ments at intervals of 30 minutes until up to 3-4
contractions occur every 10 minutes (maxi- Drug Interactions:
mum rate, 0.02 IU/minute). Monitor closely with:
NOTE: The dose shown above is suitable for use in hospital Ephedrine and epinephrine – these may increase
where equipment to control the infusion rate is availa- the risk of hypertension due to their enhanced
ble. vasopressor effect.
IMPORTANT: Careful monitoring of fetal heart rate and
uterine motility is essential for dose titration (avoid bo- Administration: Administer IV bolus injection slow-
lus IV injection during labor); discontinue immediately ly (avoid rapid injection due to risk of cardio-
in uterine hyperactivity or fetal distress. vascular effects). When using infusion, moni-
Prevention of postpartum hemorrhage, by IM injec- tor fluid balance to prevent water intoxication.
tion, ADULT and ADOLESCENT, 10 IU when
the anterior shoulder is delivered or immedi- Pregnancy Category: X
ately after birth.
Prevention of postpartum hemorrhage, by slow IM
injection, ADULT and ADOLESCENT, 5 IU
when the anterior shoulder is delivered or im-
mediately after birth.
Treatment of postpartum hemorrhage, by slow IV
injection, ADULT and ADOLESCENT, 5-10 IU
or by IM injection, ADULT and ADOLES-
CENT, 10 IU, followed in severe cases by a
total of 40 IU, by intravenous infusion, at a
rate of 0.02-0.04 IU/minute; this should be
started after the placenta is delivered.
DILUTION AND ADMINISTRATION. According to manufac-
turer’s directions. Prolonged IV administration at high
doses with large volume of fluid (e.g., in inevitable or
missed abortion, or in postpartum hemorrhage) may
cause water intoxication with hyponatremia. To avoid
this, use electrolyte-containing diluent (not glucose),
increase oxytocin concentration to reduce fluid, and
restrict fluid intake by mouth; monitor fluid, and elec-
trolytes.
Dose Adjustment:
Renal Impairment:
Use with caution (increased risk of water retention
and oxytocin accumulation).
Precautions:
Avoid prolonged administration in oxytocin-resistant
uterine inertia, in severe pre-eclamptic toxe-
mia, or in severe cardiovascular disease;
112
Dose:
HEMATOLOGIC SYSTEM Menorrhagia/Menometrorrhagia, by mouth, ADULT,
1-1.5 g every 6 to 8 hours for 3 to 4 days
(maximum, 4 g daily).
ANTIANEMIC Dental surgery, by mouth, ADULT, 25 mg/kg 2
hours before surgery, then 25 mg/kg 3 or 4
times daily for 6-8 days.
FERROUS SALT Epistaxis, by mouth, ADULT, 1.5 g every 8 hours
for 4 to 10 days.
Oral: Tablet, equiv. to 60 mg elemental iron Gastrointestinal hemorrhage, ADULT, following a
Solution, (equivalent to 15 mg elemental maximum of 3 days of intravenous dose of 1 g
iron/0.6 mL) drops, 15 mL and 30 mL every 4 hours, tranexamic acid is given by
Solution, (equivalent to 30 mg elemental mouth, 1.5 g every 6 hours for a maximum of
iron/5 mL) syrup, 60 mL 4 days
N.B. The elemental iron content of ferrous salts. Hematuria, by mouth, ADULT, 1 to 1.5 g orally
every 8 to 12 hours daily until macroscopic
Ferrous fumarate - 33% hematuria is no longer present.
Ferrous gluconate - 12%
Ferrous lactate - 19% Dose Adjustments:
Ferrous sulfate, hydrated - 20% Children:
Ferrous sulfate, desiccated - 32% Tranexamic acid has had limited use in children,
principally in tooth extraction. Limited data
An essential trace element required for the for- suggest that dosing instructions for adults can
mation of hemoglobin and for the efficient ox- be used for children needing tranexamic acid
ygen transport in the blood. therapy.
Indications: Treatment of iron-deficiency anemia Elderly:
No dosage reduction is necessary, unless there is
and in people on hemodialysis who are receiv-
evidence of renal failure.
ing erythropoietin (supplement and prophylax-
Renal Impairment:
is).
Reduce dose in patients with renal insufficiency
See under Vitamins and Minerals for other in- (because of risk of drug accumulation).
formation.
Precautions:
For patients on prolonged treatment with tranexamic
acid, perform an ophthalmological examina-
ANTIFIBRINOLYTIC tion (including visual acuity, color vision, eye-
ground, and visual fields) before and at regu-
lar intervals during treatment; discontinue if
TRANEXAMIC ACID changes are found; focal areas of retinal de-
generation have developed in animal studies
Oral: 250 mg and 500 mg capsules at doses 3-40 times the recommended human
An anti-fibrinolytic agent, which is a competitive dose.
inhibitor of plasminogen activity. Treatment with tranexamic is not indicated in hema-
turia caused by diseases of the renal paren-
Indications: For the treatment and control of ex- chyma; (intravascular precipitation of fibrin
cessive bleeding in various surgical and medi- frequently occurs, and may aggravate the dis-
cal, obstetric and gynecologic, and dental ease. Furthermore, antifibrinolytic treatment
conditions. carries the risk of clot retention in the renal
NOTE: Medical conditions include: epistaxis, hemoptysis, pelvis in cases of massive renal hemorrhage
hematuria, peptic ulcer disease with hemorrhage,
of any cause).
blood dyscrasias with hemorrhage. Obstetric and gy-
necologic conditions include: menorrhagia, menome- Patients with a high risk for thrombosis (previous
trorrhagia, postpartum hemorrhage and bleeding fol- thromboembolic event and family history of
lowing abortion. Dental conditions include: bleeding thromboembolic disease) should use tranex-
following tooth extraction and dental surgery. amic acid only if there is a strong medical in-
Contraindications: Hypersensitivity to tranexamic dication and under strict medical supervision
(there are reports of venous and arterial
acid or any component of the formulation; pa-
thrombosis or thromboembolism in patients
tients with a history or risk of thrombosis, un-
given tranexamic acid and cases of central
less concomitant treatment with anticoagu-
retinal artery and central retinal vein obstruc-
lants; active thromboembolic disease, such as
tion; patients taking tranexamic acid devel-
deep vein thrombosis, pulmonary embolism
oped intracranial thrombosis; however, further
and cerebral thrombosis; patients with ac-
observation is needed).
quired disturbances of color vision (if disturb-
Urinary tract obstruction due to clot formations in
ances of color vision arise during the course
patients with severe bleeding from the upper
of treatment, discontinue the drug); patients
urinary tract.
with subarachnoid hemorrhage since cerebral
edema and cerebral infarction may be caused Patients with irregular menstrual bleeding should
in such cases. not use tranexamic acid until the cause of ir-
113
regular bleeding has been established. Con- Contraindications: Known hypersensitivity to
sider an alternative treatment if menstrual phytomenadione or any component of the
bleeding is not adequately reduced by tranex- formulation; avoid IM if bleeding; pregnancy
amic acid. (3rd trimester); it is not effective in hereditary
Indissoluble clots may develop in body cavities, hypoprothrombinemia and that caused by liver
such as pleural space, joint spaces and uri- disease.
nary tract (e.g., renal pelvis, bladder) due to
Dose:
extravascular clots, which may be resistant to
physiologic fibrinolysis. Warfarin-induced hypoprothrombinemia; minor
Pregnancy (there are no adequate and well- bleeding or no bleeding, by slow IV injection,
ADULT, 500 micrograms; moderate hemor-
controlled studies; however, tranexamic acid
rhage, by IM injection, ADULT, 10-20 mg; se-
crosses the placenta and appears in cord
vere hemorrhage, ADULT, by slow IV injec-
blood; use only if clearly needed); lactation
(present in breast milk at 1% of the corre- tion, 5-10 mg.
sponding serum levels; exercise caution when Prophylaxis of hemorrhagic disease of the newborn,
by IM injection, NEONATE, 0.5-1 mg as single
administering to breastfeeding women); use in
children (has had limited use in children, prin- dose or by mouth, 2 mg, followed by a second
cipally in tooth extraction). dose after 4-7 days and for breastfed babies a
third dose after 1 month.
Adverse Drug Reactions: Treatment of hemorrhagic disease of the newborn,
Common: Abdominal pain, anemia, arthralgia, back by slow IV or IM injection, NEONATE, 1 mg
pain, diarrhea, fatigue, headache, muscle (with further doses, if necessary, at 8-hour in-
cramps and spasms, nausea, nasal and sinus tervals).
symptoms, vomiting,
Infrequent or Rare: Allergic skin reactions, diar- Dose Adjustments:
rhea, hypersensitivity reactions, hypotension, Elderly:
thrombosis, thromboembolic events (e.g., Due to greater response to the drug, dosage should
deep vein thrombosis, pulmonary embolism); be at the lower end of the recommended
transient disturbance of color vision. range.
Hepatic Impairment:
Drug Interactions: Use drug with caution for mild-to-moderate hepatic
Monitor closely with: impairment; for severe impairment, the patient
Fibrinolytic preparations – tranexamic acid may should be referred to a specialist.
counteract their thrombolytic effect.
Precautions:
Elderly (lower dose); hepatic impairment; not an
Contraceptives (estrogens and progestins) – may
enhance the thrombogenic effect of tranexam- antidote to heparin; pregnancy (no specific in-
ic acid; increased risk of thromboembolic formation available; use only if potential bene-
events. fit outweighs risk).
NOTE: Phytomenadione is fat-soluble: patients with fat
Administration: May be taken with or without food. malabsorption, especially in biliary obstruction or he-
patic disease, may become deficient in it.
Capsules must be swallowed whole; do not
chew, break, or crush. Adverse Drug Reactions:
Pregnancy Category: B Common: Erythema, flushing, nausea, pain, ten-
derness, tiredness, vomiting, warmth sensa-
tion.
Less Common: Allergic reactions (including ana-
COAGULANT phylaxis), bradycardia, bronchospasm, dizzi-
ness, dyspnea, hypotension, rebound bleed-
ing.
PHYTOMENADIONE Rare: Anaphylactoid reactions, hemolytic anemia,
hyperbilirubinemia, kernicterus.
Inj.: 10 mg/mL, 1 mL ampul (IM, IV, SC) (as aque-
ous colloidal solution with benzyl alcohol) Drug Interactions:
10 mg/mL, 1 mL ampul (IM, IV, SC) Monitor closely with:
(as mixed micelle) Anticonvulsants (e.g., phenobarbital and phenytoin)
and antituberculosis drugs (e.g., isoniazid and
A fat-soluble vitamin that is an essential cofactor in rifampicin) – these may impair the action of
the synthesis of blood coagulation factors: phytomenadione (may cause vitamin K defi-
prothrombin (II), proconvertin (VII), plasma ciency bleeding on the first day of life in new-
thromboplastin component (IX), Stuart factor borns).
(X), and proteins C and S. Avoid concomitant use with:
Indications: Anticoagulant-induced prothrombin Anticoagulants (e.g., warfarin) – their anticoagulant
deficiency caused by indanedione or coumarin effect is decreased by phytomenadione (in-
derivatives; treatment and prophylaxis against creasing the synthesis of blood clotting fac-
hemorrhagic disease of the newborn. tors; patients should constantly keep their die-
tary vitamin K intake).
114
Administration: IV administration of the drug
should be slow (over 30 sec) (rapid infusion
can cause dyspnea, chest and back pain).
rd
Pregnancy Category: C; X in 3 trimester or
near term.
115
Hepatic Impairment:
NERVOUS SYSTEM and Use with caution and avoid prolonged or repeated
MUSCULOSKELETAL SYSTEM use in any type of liver disease. Contraindi-
cated in severe active liver disease.
Precautions:
ANALGESICS/ANTIPYRETICS
WARNING: Massive overdose may cause hepatic necrosis
and, less frequently, renal damage. Lesser overdoses
can frequently cause reversible jaundice.
PARACETAMOL
Sodium restriction (soluble paracetamol products
Oral: 300 mg and 500 mg tablet may contain large amounts of sodium); phe-
nylketonuria (soluble products of paracetamol
120 mg (125 mg)/5 mL syrup/suspension,
may contain aspartame); alcohol dependence;
60 mL (alcohol-free)
overdosage; G6PD deficiency; hepatic im-
250 mg/5 mL syrup/suspension,
60 mL (alcohol-free) pairment; renal impairment; (dose-related tox-
100 mg/mL drops, 15 mL (alcohol-free) icity; avoid large doses, e.g., >4 g/day).
Rectal: 125 mg and 250 mg suppository Pregnancy (not known to be harmful); breastfeeding
(small amount is present in milk; short courses
A para-aminophenol-derived, weak COX-1 and are safe in usual dosage; monitor infant).
COX-2 inhibitor that has no significant anti-
inflammatory activity, and is particularly useful Adverse Drug Reactions:
for treating mild to moderate pain, for reducing Common: Increased aminotransferases.
fever, and in patients where salicylates and Rare: Acute hepatitis, drug fever, hepatocellular
other NSAIDs are contraindicated. necrosis, hypersensitivity reactions, hypoten-
sion, mucosal lesions, leukopenia, neutro-
Indications: Mild-to-moderate pain, including dys- penia, pancytopenia, renal tubular necrosis,
menorrhea and tension headache; pain relief thrombocytopenia, urticarial or erythematous
in osteoarthritis and soft tissue lesions; acute rash.
migraine attacks; pyrexia.
Drug Interactions:
Contraindications: Known hypersensitivity to Monitor closely with:
paracetamol or any component of the formula- Alcohol – increased risk of hepatotoxicity with ex-
tion; severe active liver disease; prolonged or cessive alcohol use (≥3 drinks/day)
repeated administration in patients with ane- Caffeine – increased analgesic efficacy with con-
mia, or cardiac, pulmonary, hepatic and renal comitant administration of caffeine.
disease. Chloramphenicol – paracetamol increases serum
concentration levels of chloramphenicol.
Dose:
Isoniazid – this enhances adverse effects of parace-
Mild-to-moderate pain, pyrexia, by mouth, ADULT,
tamol.
0.5-1 g every 4-6 hours (maximum, 4 g daily);
Metoclopramide – this increases paracetamol ab-
CHILD 6-12 years, 250-500 mg; CHILD 1-5
sorption.
years, 120-250 mg; CHILD <3 months, see
Sulfonylureas – enhanced hypoglycemic effect of
notes below; CHILD 3 months-1 year, 60-125
sulfonylureas.
mg or 10-15 mg/kg/dose (in children doses
Anticoagulants (e.g., warfarin) – prolonged regular
may be repeated every 4-6 hours if neces-
use of paracetamol may enhance their antico-
sary; maximum, 4 doses in 24 hours).
agulant effect (increased INR and the risk of
Post-immunization pyrexia, by mouth, INFANT 2-3
bleeding).
months, 10-15 mg/kg/dose followed by a sec-
ond dose, if necessary, 4-6 hours later (warn
Activated charcoal, anticholinergics and narcotics –
parents to seek medical advice if pyrexia per-
their absorption is decreased when given con-
sists after the second dose).
comitantly with paracetamol.
Treatment of acute migraine attack, by mouth,
Vaccines – these diminish the therapeutic effect of
ADULT, 0.5-1 g at first sign of attack, repeat-
paracetamol.
ed every 4-6 hours if necessary, (maximum, 4
g daily); CHILD 6-12 years, 250-500 mg at the Administration: May be taken with or without food.
first sign of attack, repeated every 4-6 hours if
necessary (maximum, 4 doses in 24 hours). Pregnancy Category: B
NOTE: Infants <3 months should not be given paracetamol
unless advised by a doctor; a dose of 10 mg/kg (5
mg/kg if jaundiced) is suitable.
Dose Adjustment:
TRAMADOL
Renal Impairment:
Oral: 50 mg capsule (as HCl)
Longer dosing intervals and reduced total dose may
be warranted in renal impairment. Avoid pro- 100 mg, 150 mg and 200 mg MR tablet
longed or repeated use. (as HCl)
A centrally-acting, synthetic opioid analgesic that
binds to mu opioid receptors and inhibits
reuptake of norepinephrine and serotonin.
116
pression, dermatitis, dizziness, drowsiness,
Indications: Treatment of moderate-to-severe,
dry mouth, dyspepsia, dyspnea, headache,
acute or chronic pain. hypesthesia, increased sweating, influenza-
Contraindications: Known hypersensitivity to like illness, itch, lethargy, miosis, nasal con-
tramadol and opioids, or any component of gestion, nausea and vomiting, neck pain,
the formulation; comatose patients; in patients nervousness, orthostatic hypotension, pares-
with history of epilepsy; acute intoxication with thesia, pyrexia, respiratory tract infections,
alcohol, hypnotics, centrally-acting analgesics, restlessness, sinus congestion, sneezing,
opioids, or psychotropic drugs; opioid de- sore throat, urinary retention, urinary tract in-
pendency; extended-release formulation is fection, vasodilation.
contraindicated in severe hepatic and renal Less Common: Agitation, appendicitis, bradycar-
impairment; suicidal patients. dia, bronchospasm, cholecystitis, cholelithia-
sis, confusion, delirium, edema, flushing, gas-
Dose: troenteritis, hallucinations, hypertension, hy-
Acute moderate-to-severe pain, by mouth, ADULT pogonadism, hypothermia, irritability, mi-
and CHILD >16 years old, 50-100 mg every graine, mood changes, muscle rigidity, myal-
4-6 hours PRN, (maximum, 400 mg/day); gia, myocardial infarction, myoclonus, palpita-
Chronic moderate-to-severe pain, by mouth, tions, pancreatitis, paralytic ileus, pneumonia,
ADULT and CHILD >16 years old, initially 25 raised liver enzymes, respiratory depression,
mg every morning, increase by 25-50 mg/day sedation, sleep disorder, syncope, tachycar-
every 3 days as separate doses up to 50-100 dia, tinnitus, tremor, ureteric or biliary spasm,
mg every 4-6 hours PRN; (maximum, 400 urticaria, vertigo, visual disturbances.
mg/day);. Rare: Anaphylaxis, seizures, Syndrome of Inappro-
NOTE: For child <16 years, safety and efficacy are not
priate Antidiuretic Hormone (SIADH).
established. For adults >75 years, see Dose Adjust-
ment. Drug Interactions:
NOTE: CYP-based interactions: tramadol is metabolized by
Dose Adjustments:
CYP2D6; administration with drugs which affect this
Renal Impairment: enzyme may alter tramadol’s activity or toxicity (see
Reduce dose. For severe renal impairment, give Appendix).
immediate-release preparation at 50-100 mg Monitor closely with:
PO every 12 hours. Extended-release prepa- CNS Depressants (e.g., alcohol, sedatives and
ration is contraindicated.. tranquilizers) – these potentiate effects of opi-
Hepatic Impairment: oids, increasing the risk of respiratory depres-
For severe hepatic impairment, give immediate- sion, profound sedation or coma.
release preparation at 50 mg PO every 12 Carbamazepine – this induces the metabolism of
hours (maximum, 100 mg/day). Extended- tramadol and may reduce its activity.
release preparation is contraindicated. Drugs which reduce blood pressure (see Appendix
Elderly >75 years old: – Table D) – tramadol may enhance the hypo-
Maximum dose, 300 mg/day. tensive effect of other drugs.
Drugs that may contribute to serotonin toxicity (see
Precautions:
Appendix – Table F) – tramadol can contribute
Raised intracranial pressure (respiratory depression
to serotonin toxicity; and may increase likeli-
due to opioids may be poorly tolerated and
hood of toxicity when given concomitantly with
may further increase ICP; avoid use); hypo-
these drugs.
tension, shock (reduced blood volume in-
creases hypotensive risk and the risk of res-
Buprenorphine – this blocks opioid receptors; block-
piratory depression); biliary colic or surgery
ing their therapeutic effect (may reduce anal-
(may cause spasm of the sphincter of Oddi);
gesia or precipitate withdrawal symptoms in
Epilepsy or a recognized risk of seizures, e.g., head
opioid-dependent people).
injury, metabolic disorders, alcohol and drug
Naloxone – this antagonizes opioids; reversing their
withdrawal, CNS infections (increased risk of
effects (rapid reversal may precipitate acute
seizure; the risk increases with doses exceed-
withdrawal syndrome).
ing the recommended range); use with other
Naltrexone – this reversibly blocks opioid receptors
respiratory depressants and MAO Inhibitors;
and reduces their effects (may precipitate
Serotonin syndrome (potentially life-
withdrawal symptoms at the start of the treat-
threatening) may develop.
ment).
Use with caution for obstetrical preoperative medi-
Ondansetron – may decrease analgesic effect of
cation or for post-delivery analgesia in nursing
tramadol.
mothers.
May impair ability to perform skilled or hazardous Administration: May be taken with or without food.
tasks. Swallow whole, do not chew or crush tablet.
Elderly (increased risk of adverse effects); children
(more susceptible to respiratory depression). Pregnancy Category: C

Common: Abdominal pain, anxiety, arthralgia, back
pain, blurred vision, chest pain, constipation,
cough, decreased appetite and weight, de-
117
ANESTHETIC Injectable:
Severe bradycardia, heart block or impaired cardiac
LOCAL ANESTHETIC conduction (local anesthetics enhance con-
duction defects); severe shock; respiratory
impairment; renal impairment; hepatic impair-
LIDOCAINE ment; epilepsy; porphyria; neuromuscular dis-
eases (e.g., myasthenia gravis) (increases
Jelly: 2%, 30 g (as HCl) sensitivity to local anesthetics; may increase
Inj.: 1%, 5 mL ampul and 50 mL vial (local infiltra- muscle weakness and depress respiration
tion) (as HCl) with central neural blockade); neurological
2%, 5 mL, 10 mL and 50 mL vial (local infiltra- disease (administration of local anesthetics
tion) (as HCl) may worsen condition); the elderly (increased
2%, 1.8 mL carpule (with epinephrine) (local sensitivity); children <6 months (more sensi-
infiltration) tive to toxic effects).
A moderately long-acting, local anesthetic, which Solutions containing epinephrine should be used
blocks initiation and transmission of nerve im- with caution for ring block of digits or append-
pulses at the site of application by stabilizing ages to prevent risk of ischemic necrosis.
neuronal membrane. The elderly or debilitated patients (should be given
reduced doses commensurate with their age
Indications: Injection: surface anesthesia of mu- and physical status).
cous membranes; infiltration anesthesia; pe- Pregnancy (large doses should be avoided during
ripheral and sympathetic nerve block; third trimester to diminish risk of neonatal res-
Topical: local anesthetic for oral mucous mem- piratory depression, hypotonia and bradycar-
brane. dia after paracervical block); breastfeeding.
Contraindications: Known or suspected hypersen- Adverse Drug Reactions:
sitivity to lidocaine or any component of the INJECTABLE
formulation; adjacent skin infection or inflamed Common: Blurred vision, chest pain, confusion,
skin to the proposed site of injection; concomi- disturbances in vision, dizziness, drowsiness,
tant therapy with anticoagulants or an abnor- dyspnea, flushing, headache, light-
mal bleeding tendency; severe anemia or headedness, nausea, paresthesia, tinnitus,
heart disease; spinal/epidural anesthesia in tremors.
dehydrated or hypovolemic patients; hyper- Less Common: Arrhythmias, bradycardia, cardiac
sensitivity to another local anesthetic of the arrest, coma, heart block, hypotension, mus-
amide type (topical). cle twitching, recurrence of SVT, respiratory
depression, restlessness, seizures.
Dose:
Rare: Bronchospasm, convulsions, hypersensitivity
Local anesthetic for oral mucous membrane, topi-
reactions, paraplegia, unconsciousness.
cal, ADULT, apply to affected area ≤4 times
TOPICAL
daily as needed (maximum dose, 3 mg/kg, not Frequency Not Defined:
to exceed 300 mg); CHILD and ADOLES-
Application site reactions: abnormal sensation,
CENT, dose varies with age and weight (max-
altered temperature sensation, burning sensa-
imum dose, 3 mg/kg) tion, edema, erythema, itching, pallor or
Local or percutaneous infiltration and peripheral blanching when application time is prolonged
nerve block, ADULT, 5-300 mg.
(>2 hours), rash, redness.
Peripheral nerve block, CHILD, 505 micrograms/kg.
Systemic reactions (unlikely due to small dose
NOTE: Maximum safe doses of lidocaine for ADULT and
CHILD are: 4 mg/kg for the 1% lidocaine. absorbed; may occur with repeated doses or
NOTE: Use lower doses for debilitated or elderly patients or application to large surface areas): angioede-
in epilepsy or acute illness. ma, bronchospasm, cardiovascular manifesta-
tions (e.g., bradycardia, hypotension), CNS
Dose Adjustments: excitation and/or depression, confusion, dizzi-
Renal Impairment:
ness, double or blurred vision, drowsiness,
Reduce its dose during prolonged infusion (>24 euphoria, nervousness, respiratory depres-
hours) or repeated IV doses. sion, shock, tinnitus, tremors, twitching, un-
Hepatic Impairment: consciousness, vomiting.
Consider halving its dose during prolonged infu-
sions (>24 hours) or repeated IV doses. Drug Interactions:
Precautions: Beta-blockers – these may increase the serum
Topical: concentration of lidocaine (topical), increasing
Application to broken or inflamed skin may lead to the risk of toxicity.
increased systemic absorption; do not leave Avoid concomitant use with:
on large body areas for >2 hours. Bupivacaine – lidocaine increases toxicity of bupi-
Pregnancy (the amount of lidocaine absorbed topi- vacaine, never use combination.
cally varies by dose administered, duration of
exposure, and site of application; cumulative
exposure from all routes of administration
should be considered).
118
Antiarrhythmics (e.g., amiodarone, sotalol and (risk of paralytic ileus); dementia (anticholin-
disopyramide) – lidocaine has proarrhythmic ergics are best avoided; they may worsen
effect; combination with these drugs may symptoms and antagonize therapeutic effects
cause antagonistic effect. of anticholinesterases); fever or high ambient
Diuretics (e.g., furosemide, hydrochlorothiazide) – temperature (risk of hyperthermia); GERD
action of lidocaine is antagonized by hypoka- (may be aggravated); the elderly (more sensi-
lemia caused by these drugs. tive to anticholinergic adverse effects; confu-
Drugs which depresses cardiac contractility and sion may be precipitated or worsened); chil-
conduction – possibly increased risk of heart dren (more susceptible to anticholinergic side-
failure and significant bradyarrhythmia. effects); hepatic impairment.
Pregnancy and breastfeeding (use with caution).
Administration: For topical use, apply a moderate- SKILLED TASKS. May impair ability to perform skilled
ly thick layer to affected area (~1/8 inch thick), tasks, e.g., machinery or driving.
and allow time for numbness to develop (20-
60 minutes for application). Adverse Drug Reactions:
Common: Blurred vision, confusion, constipation,
Pregnancy Category: B decreased sweating, disorientation, dizziness,
drowsiness, dryness of mouth, flushing, light-
headedness, mydriasis, nausea, nervousness,
ANTICHOLINERGICS reduced bronchial secretions, thirst, urinary
hesitancy and retention, vomiting.
Less Common or Rare: Agitation, angle-closure
BIPERIDEN glaucoma, arrhythmias, delirium, delusions,
diplopia, epigastric distress, excitement, hallu-
Oral: 2 mg tablet (as HCl) cinations, hypotension, memory impairment,
muscular cramping and weakness, palpita-
A tertiary-amine, centrally-acting anticholinergic tions, paralytic ileus, paresthesia, psychiatric
drug, used in the management of Parkinson- disturbances, rash, bradycardia followed by
ism and is effective for the treatment of acute tachycardia, urticaria.
EPS.
Drug Interactions:
Indications: Drug-induced extrapyramidal symp- NOTE: Concomitant use of two or more drugs having anti-
toms (except tardive dyskinesia) by phenothi- muscarinic effects can increase side-effects, such as
azines, butyrophenones or reserpine; adjunc- constipation, urine retention and dryness of mouth,
tive treatment of post-encephalitic, idiopathic and can also lead to confusion especially in the elder-
ly.
or arteriosclerotic Parkinson’s disease.
Contraindications: Hypersensitivity to biperiden or Antipsychotic drugs (e.g., phenothiazines, haloperi-
any component of the formulation; angle- dol) – possible masking of extrapyramidal
closure glaucoma; untreated urinary retention; symptoms, tardive dyskinesia, in long-term
prostatic hypertrophy; myasthenia gravis; and therapy with these drugs.
GI obstruction or atony; toxic megacolon. Fluphenazine – increased antimuscarinic effects
(but reduced plasma concentration of
Dose:
fluphenazine).
Parkinsonism, by mouth, ADULT, 2 mg every 8 or 6
Isosorbide Dinitrate – possibly reduced effect of the
hours, with initial dose of 0.5-1mg/day, gradu- sublingual ISDN (failure to dissolve under the
ally increase by 0.5 mg every 5-6 days until tongue owing to dry mouth).
optimum dose. Avoid concomitant use with:
Drug-induced extrapyramidal disorders, by mouth, Alcohol – potentiates CNS depression.
ADULT, 1-4 mg/day, in single or 2 divided
Anticholinergic drugs or other drugs with anticholin-
doses; CHILD > 3 years, 0.02-0.05 ergic effects (see Appendix – Table A) – these
mg/kg/dose every 8-12 hours. increase the risk of adverse effects (including
central anticholinergic delirium, which is often
Dose Adjustments:
missed); avoid these combinations if possible
Elderly: (if a combination is required, monitor the pa-
Start with low dose and increase slowly to the low- tient, and reduce its dose if necessary).
est effective dose.
Anticholinesterases (e.g., neostigmine and pyri-
Hepatic Impairment:
dostigmine) and cisapride – combining anti-
For mild-to-moderate hepatic impairment, dose
cholinergics with these drugs, which increase
reduction is warranted; for severe impairment,
concentration of acetylcholine, will antagonize
the patient should be referred to a specialist.
the anticholinergic effect.
Precautions: Haloperidol – its therapeutic effects may be reduced
Avoid abrupt withdrawal in Parkinson’s disease (to by biperiden (due to central antagonism).
prevent acute exacerbation); may exacerbate Levodopa – its absorption is possibly reduced by
tardive dyskinesia caused by antipsychotic biperiden.
drugs; heart diseases, including arrhythmias, Metoclopramide – its effects on GI activity is antag-
coronary heart disease, and heart failure (may onized by biperiden.
be exacerbated); inflammatory bowel disease
119
Administration: The tablet should be taken with not effective in absence seizures (petit mal)
food. and myoclonic seizures (see Precautions);
idiopathic trigeminal neuralgia and painful dia-
betic neuropathy; acute mania and mainte-
nance therapy of bipolar affective disorders
(see under Antipsychosis).
DIPHENHYDRAMINE Contraindications: Hypersensitivity to carbamaz-
epine or related drugs (e.g. tricyclic antide-
Oral: 25 mg and 50 mg capsule (as HCl) pressants), or any component of the formula-
Inj.: 50 mg/mL, 1 mL ampul (IM, IV) (as HCl) tion; atrioventricular block; bone marrow de-
pression; acute intermittent porphyria; combi-
A monoethanolamine-derived, first-generation H 1 nation with monoamine-oxidase inhibitors
receptor antagonist, which exhibits antimusca- (MAOIs) – before administering carbamaze-
rinic and pronounced sedative property, with pine, MAOIs should be discontinued for 2
low incidence of GI side effects. weeks or longer (see Drug Interactions).
Indication: Drug-induced dystonic reaction (Extrap- Dose:
yramidal Syndrome). NOTE: As a result of slow, controlled release of the active
substance from the CR tablets, these are designed to
Contraindications: See under Allergy and Immune be taken in a twice-daily dosage regimen.
System. Acute mania and maintenance therapy of bipolar
Dose: affective disorders, see under Antipsychosis.
Drug-induced dystonic reaction (extrapyramidal Epilepsy, by mouth, ADULT, initially 100-200 mg
syndrome), by IM or IV injection, ADULT, 25- once or twice daily; slowly raise until an opti-
50 mg in a single dose, may repeat in 20-30 mal response is obtained (generally at 400 mg
minutes if necessary; CHILD, 0.5-1 twice or thrice daily). CHILD, < 5 years, initial
mg/kg/dose. 5 mg/kg/day in 2-4 divided doses, increase
every 5-7 days by 5 mg/kg based on re-
See under Allergy and Immune System for other sponse; 6-12 years, initial 10 mg/kg/day in 2-4
information. divided doses, increase by 5 mg/kg/day week-
ly until therapeutic levels; > 12 years, 5-10
mg/kg/day divided every 12 hours then in-
ANTICONVULSANTS crease gradually to maintenance of 10-30
mg/kg/day divided every 8 or 6 hours (maxi-
mum, 1 g/day for 12-15 years old and 1.2
NOTE: Treatment of epilepsy should start with monotherapy.
g/day if > 16 years old).
The choice of the medicine will depend on the efficacy
of the medicine and the patient’s characteristics. If a Idiopathic trigeminal neuralgia, by mouth, ADULT,
drug fails to control the seizures after it has been slowly raise the dosage of 100 mg 2 times dai-
used in full therapeutic dosage for an adequate peri- ly until freedom from pain is achieved (normal-
od, or if it is not tolerated, it should be gradually sub- ly at 200 mg 3-4 times daily); then, gradually
stituted with another, with the first drug being with- reduce the dose to the lowest possible
drawn only when the new regimen is firmly estab-
maintenance level.
lished. If monotherapy is not effective, two agents are
given in combination. The dose of the second agent Painful diabetic neuropathy, by mouth, ADULT,
is increased gradually until effective response is start with 100 mg 1 to 2 times a day, gradually
obtained. The dosage of the existing agent is increase depending on response; average
maintained or adapted to the second drug. All dose is 200 mg 2-4 times daily.
patients should be under medical supervision
throughout treatment and monitored closely for Dose Adjustment:
adverse effects to help in accurate dose titration. Hepatic Impairment:
Metabolism is impaired in advanced liver disease.
(drug is primarily metabolized in the liver).
Renal Impairment:
CARBAMAZEPINE Use with caution; dose reduction in moderate to
severe impairment.
Oral: 200 mg tablet; Elderly:
200, and 400 mg CR (modified-release) tablet Dosage should be selected with caution. Generally,
100 mg in 5 mL syrup, 120 ml lower dosages are started.
It is an iminostilbene that limits the firing of action Precautions:
potentials evoked by a sustained depolariza-
WARNING:
tion in cortical neurons by slowing the rate of Hematologic: Agranulocytosis and aplastic anemia have
recovery of voltage-activated Na+ channels been reported (see below).
from inactivation. Neurologic: Must be used with caution in patients with
mixed seizures, including absences, which can be
Indications: Epilepsy: complex or simple partial exacerbated by carbamazepine. In case of exacerba-
seizures with or without secondary generaliza- tion, the drug must be discontinued.
tion; generalized tonic-clonic seizures; mixed Transient or persistent decreased platelet or white
forms of seizures. Carbamazepine is usually blood cell count can occur. Agranulocytosis
120
and aplastic anemia have been associated but thy, folic acid deficiency, delayed multiorgan
the overall risk estimate is low. Obtain pre- hypersensitivity, hypertension or hypotension,
treatment Complete Blood Counts with plate- disturbance in cardiac conduction.
let counts at baseline and periodically thereaf- Very Rare (<0.01%): Agranulocytosis, aplastic
ter. Discontinue if there is significant bone anemia, pure red cell aplasia, megaloblastic
marrow depression. anemia, pancreatitis, anaphylactic reactions,
If signs and symptoms of severe skin reaction ap- arrhythmias, renal or urinary dysfunction.
pear, carbamazepine should be discontinued.
Drug Interactions:
Baseline and periodic evaluations of hepatic func-
tion must be performed particularly in those Monitor closely with:
with a history of liver disease and the elderly. Coadministration of inhibitors or inducers of CYP
The drug must be withdrawn immediately in 3A4, the main enzyme catalyzing conversion
cases of aggravated liver dysfunction or active of carbamazepine into the 10,11-epoxide
liver disease. (which is as pharmacologically active as the
The possibility of activation of latent psychosis and, parent compound) may result in altered plas-
in the elderly, confusion and agitation should ma concentrations of carbamazepine and ei-
be kept in mind. ther induce adverse reactions or decrease
Breakthrough bleeding may be seen in women carbamazepine plasma levels.
taking oral contraceptives. The reliability of Agents that raise carbamazepine plasma levels:
oral contraceptives may be adversely affected isoniazid, diltiazem, fluoxetine, macrolide anti-
by carbamazepine. Thus, women of biotics (e.g., erythromycin, clarithromycin),
childbearing age must be advised to use al- azoles (e.g., fluconazole), loratadine, vera-
ternative forms of birth control. pamil.
Pregnancy: the possibility that carbamazepine, like Agents that decrease carbamazepine plasma lev-
all major antiepileptic drugs, increases risk for els: phenobarbitone, phenytoin, theophylline,
developmental disorders has been reported, rifampicin, and possibly, also clonazepam and
with rare reports of developmental disorders, valproic acid.
including spina bifida, with carbamazepine. Clonazepam, valproic acid, alprazolam, corticoster-
Antiepileptic drugs can aggravate folic acid oids, digoxin, doxycycline, felodipine,
deficiency so that supplementation is recom- haloperidol, theophylline, oral anticoagulants
mended before and during pregnancy. Vita- (warfarin), tricyclic anti-depressants- plasma
min K1, to be given to the mother during the levels can be lowered by carbamazepine.
last weeks of pregnancy as well as to the Phenytoin- plasma levels of phenytoin can both be
newborn to prevent bleeding disorders in the raised or lowered by carbamazepine.
offspring has been recommended. Paracetamol- combination with carbamazepine may
Lactation: carbamazepine passes into breast milk reduce bioavailability of paraceta-
so that infants must be closely observed for mol/acetaminophen.
adverse reactions. Isoniazid- combination with carbamazepine in-
SKILLED TASKS. Ability to react may be impaired by creases isoniazid-induced hepatotoxicity.
dizziness and drowsiness especially at the start of Neuroleptics (e.g., haloperidol) – combination with
therapy or during dose adjustments; patients must carbamazepine can increase neurological ad-
exercise caution when driving or operating machinery. verse reactions even in the presence of plas-
Adverse Drug Reactions: ma therapeutic level.
NOTE: Particularly at the start of treatment, or if the initial Diuretics (e.g., hydrochlorothiazide, furosemide) –
dose is too high, or in the elderly, certain adverse re- these may cause symptomatic hyponatremia.
actions (e.g., central nervous system and gastrointes- Valproic acid may, on the other hand, increase
tinal symptoms, and allergy) commonly occur. levels of the active 10,11-epoxide metabolite
Common: Neurologic: ataxia, dizziness, drowsi- so dose adjustments have to be made.
ness, fatigue, headache diplopia, blurred vi- Avoid concomitant use with:
sion; Skin: allergic reactions, urticarial (may Monoamine-oxidase inhibitors (MAOIs) – because
be severe); Blood: leucopenia, thrombocyto- they are structurally related to tricyclic antide-
penia, eosinophilia; Liver: elevated gamma- pressants, carbamazepine is not recommend-
GT (usually not clinically relevant); elevated ed in combination with MAOIs.
alkaline phosphatase; Gastrointestinal: nau- Oral contraceptives – their plasma levels can be
sea, vomiting, mouth dryness; Endo- lowered, or their activity diminished by car-
crine/metabolism: edema, weight increase, bamazepine (alternate contraceptive methods
hyponatremia and reduced plasma osmolality. must be considered).
Less Common: Abnormal involuntary movements,
exfoliative dermatitis, erythroderma, elevated Administration: The tablets and the syrup (to be
transaminases, diarrhea, constipation. shaken before use) may be taken during, af-
Rare: Orofacial dyskinesia, oculomotor disorders, ter, or between meals. Tablets should be tak-
slurred speech, peripheral neuritis, paresthe- en with little liquid. The CR tablets should be
sia, muscle weakness, hallucinations, depres- swallowed unchewed with a little liquid.
sion, loss of appetite, restlessness, agitation, Pregnancy Category: D
confusion, lupus-erythematosus like syn-
drome, pruritus, Stevens-Johnson syndrome,
acne, purpura, leukocytosis, lymphadenopa-
121
Hepatic impairment and renal impairment (can
DIAZEPAM precipitate coma in cases of severe hepatic
and renal impairment); avoid prolonged use
Inj.: 5 mg/mL, 2 mL ampul (IV) and abrupt withdrawal.
Respiratory disease (compromised respiratory drive
Intravenous diazepam is a benzodiazepine used in in respiratory disease or sleep apnea may
the management of seizure activity and for lead to hypoventilation and hypoxemia); mus-
anxiolysis with close neurovital signs monitor- cle weakness may worsen; history of alcohol
ing in severely agitated patients. or drug abuse, marked personality disorder;
Indications: Initial and immediate suppression of use only if the indication is clear, such as sei-
convulsive and non-convulsive status epilepti- zure control; porphyria.
cus prior to transfer to hospital; recurrent or Pregnancy (high doses during late pregnancy or
prolonged febrile convulsions; recurrent gen- labor may cause neonatal hypothermia, hypo-
eralized or grand mal seizures associated with tonia, and respiratory depression); breastfeed-
poisoning and drug and acute alcohol with- ing (adverse effects are possible; monitor in-
drawal. fant for drowsiness);
Contraindications: Known hypersensitivity to Adverse Drug Reactions:

diazepam or any of the excipients; respiratory Common: Intravenous: Coma or sensorial depres-
depression; marked neuromuscular respirato- sion, hypotension, respiratory depression.
ry weakness, including unstable myasthenia Rare: Allergic reactions, including anaphylaxis;
gravis; acute pulmonary insufficiency; sleep jaundice, transient elevated liver function
apnea syndrome; phobic or obsessional tests.
states; hyperkinesis; severe hepatic impair- Drug Interactions:
ment; NOTE: Oral diazepam is not recommended Monitor closely with:
for chronic psychosis, this should not be used alone
Amlodipine – enhanced hypotensive effect.
in depression or in anxiety with depression.
Azole derivatives (e.g., fluconazole) – these may
Dose: (See Precautions prior to administration). inhibit diazepam’s metabolism, increasing the
Status epilepticus (convulsive and non-convulsive), risk of adverse effects.
by slow IV injection, ADULT and CHILD >12 Chlorphenamine – enhanced sedative effect.
years, 5-10 mg at a rate not exceeding 2 Chlorpromazine – enhanced sedative effect.
mg/minute, repeated as necessary every 5-10 CNS depressants (e.g., alcohol, sedatives and
minutes until seizures stop or up to a maxi- tranquilizers) – possibly enhanced CNS de-
mum total dose of 20 mg; INFANT >1 month pression and sedative effect.
and CHILD up to 12 years, 300-400 mi- Enalapril – enhanced hypotensive effect.
crograms/kg at a rate not exceeding 1 Furosemide – enhanced hypotensive effect.
mg/minute every 15-30 minutes up to a maxi- Hydrochlorothiazide – enhanced hypotensive effect.
mum total dose of 5 mg in infants, and 10 mg Methyldopa – enhanced hypotensive effect.
for older children. Nitrates (e.g., isosorbide dinitrate) – enhanced
Prolonged or recurrent febrile convulsions, by hypotensive effect.
slow IV injection, INFANT and CHILD, use Phenytoin – diazepam may possibly increase or
same dose for status epilepticus. decrease the concentration of this drug.
Seizures associated with poisoning, by slow IV Seizure-inducing drugs (see Appendix – Table C for
injection (at a rate not exceeding 2 other drugs which may also cause seizures) –
mg/minute), ADULT, 100-150 micrograms/kg. these may lower seizure threshold when given
concomitantly with benzodiazepines.
Dose Adjustments: Theophylline – these may reduce sedative effects of
Elderly or Debilitated Patients: benzodiazepines.
Reduce dose. Avoid concomitant use with:
Renal Impairment: Isoniazid – metabolism of diazepam inhibited.
No dose adjustment recommended unless used for Rifampicin – this may substantially accelerate me-
prolonged periods; reduce dose in prolonged tabolism of diazepam, thus reducing its con-
periods. centration and clinical effect.
Hepatic Impairment:
Reduce maintenance dose. Contraindicated in Administration: Give IV at a slow rate not faster
severe liver disease. than 2 mg/minute.
NOTE: Avoid extravasation, intra-arterial and IM injection.
Precautions: Avoid dilution and infusion of injection, as diazepam
WARNING: Overdose may produce coma and respiratory has a low solubility and adsorbs to PVC-giving sets.
depression.
When given intravenously, agents for correcting
hypotension and facilities for supporting venti-
lation (e.g., AMBU bag, oxygen) in cases of
respiratory depression should be available. In
such cases, the patient should be referred to
the nearest hospital immediately.
122
specific symptoms such as malaise, weakness, leth-
argy, facial edema, anorexia, and vomiting that may
VALPROATE precede the hepatotoxicity. Loss of seizure control
may also be seen. The drug must be discontinued
Oral: 250 mg/5 ml syrup valproic acid, 120 mL immediately in the presence of suspected or apparent
250 mg divalproex sodium tablet (sodium significant hepatic dysfunction.
valproate and valproic acid compound in a Pancreatitis, which may be life-threatening, has been
1:1 molar relationship) reported. Some were hemorrhagic and progressed
rapidly from initial symptoms to death. Patients and
Valproate inhibits sustained repetitive firing of corti- caregivers must be instructed to monitor for and im-
cal neurons by prolonging recovery of voltage- mediately report symptoms of abdominal pain, nau-
sea, vomiting, and/or anorexia. The drug should im-
activated Na+ channels from inactivation.
mediately be discontinued.
Indications: all forms of seizures, e.g., complex Teratogenicity: may cause neural tube defects. Do not use
in women of child-bearing age unless the drug is es-
partial seizures, simple and complex absence
sential.
seizures, multiple seizures types, generalized
seizures (atonic, tonic-clonic, myoclonic and Hepatotoxicity: see Contraindications and Warning;
secondarily generalized seizures), specific Liver function tests (e.g., SGPT/ALT, pro-
syndromes (West, Lennox Gastaut). thrombin time) must be done pre-treatment
Manic episodes associated with bipolar disor- and periodically especially within the first six
der (see under Antipsychosis). months and in patients most at risk.
Pancreatitis: see Warning; measure plasma amyl-
ase immediately if with abdominal pain.
valproic acid or any component of the formula- Urea cycle disorders: see Contraindications. Hyper-
tion; hepatic disease or significant hepatic ammonemic encephalopathy, sometimes fa-
dysfunction; urea cycle disorders; hereditary tal, has been reported in patients with these
neurometabolic syndromes caused by DNA disorders.
mutations of the mitochondrial DNA polymer- Thrombocytopenia: Platelet counts and coagulation
ase-gamma (POLG) gene (e.g., Alpers Hut- tests, should be done before treatment and
tenlocher Syndrome); active pancreatitis. periodically thereafter particularly during the
Dose: first six months of therapy, and prior to sur-
Epilepsy, by mouth, initiate at 10-15 mg/kg/day, gery or anticoagulant therapy. Thrombocyto-
gradually increase by 5-10 mg/kg/week to penia may be dose-related. Evidence of hem-
achieve optimal clinical response (usual orrhage, bruising, or disordered coagulation
maintenance dose is 20-30 mg/kg/day). Dose are indications for discontinuation.
above 60 mg/kg/day is not recommended. For An increase in the risk of suicidal thoughts and
ADULT and CHILD >12 years, maximum behavior in patients taking antiepileptic drugs
dose is 2.5 grams daily in divided doses; (AEDs) has been reported. Epilepsy and other
CHILD <12 years and >20 kg, maximum illnesses for which AEDs are prescribed can
dose of 35 mg/kg daily. carry the same risk. Patients and their care-
In patients previously receiving valproic acid thera- givers must be instructed to monitor for and
py, divalproex sodium is initiated at the same immediately report any unusual change in
daily dose and dosing schedule. mood or behavior.
Mania: see under Anti-Psychosis medicines. Pediatric Use: Children less than 2 years of age are
at increased risk for fatal hepatotoxicity (see
Dose Adjustments: Warning). When used in this age group, it
Renal Impairment: should be done with extreme caution and as a
No adjustment necessary; protein-binding is re- sole agent.
duced. Pregnancy: Valproic acid may cause teratogenic
Hepatic Impairment: effects, such as neural tube defects (e.g.,
Avoid if possible, hepatotoxicity and hepatic failure spina bifida). It must be considered in women
may occasionally occur, usually in the first six of child-bearing age only after the risks have
months; avoid in active liver disease. been carefully weighed against the benefits.
Elderly: Pregnant women on valproic acid must be
Lower initial dose and slower increase in dosage, immediately referred to the specialist.
regularly monitor fluid and nutritional intake SKILLED TASKS: ability to react may be impaired
and increased somnolence and other side ef- by dizziness and drowsiness especially at the
fects. start of therapy or during dose adjustments;
Precautions: patients must exercise caution when driving or
operating machinery.
WARNING:
Hepatic failure resulting in fatalities has occurred, usually Adverse Drug Reactions:
during the first six months of treatment. Increased risk NOTE: The frequency of adverse effects, particularly elevat-
for fatal hepatotoxicity is seen in: children <2 years ed liver enzymes and thrombocytopenia, can be
old, patients on multiple anticonvulsants, congenital dose-related.
metabolic disorders, severe seizure disorders accom- Common:
panied by mental retardation, or organic brain dis- Gastrointestinal: Nausea, vomiting, abdominal pain,
ease, hereditary neurometabolic syndromes (see
Contraindications). Patients and caregivers must be diarrhea, anorexia, dyspepsia, elevated
instructed to monitor for and immediately report non-
123
AST/ALT (usually minor and appear to be
dose-related). ANTI-INFLAMMATORY AGENTS
Neurologic: Somnolence, tremor, dizziness, insom-
nia, nervousness, anxiety, depression, amne-
sia, mood changes, hallucinations, nystag- CELECOXIB
mus, blurred vision, amblyopia, ataxia, vertigo.
Hematologic: Thrombocytopenia, increased bleed- Oral: 100 mg, 200 mg and 400 mg capsule
ing time, petechiae/ecchymosis.
Respiratory: Flu syndrome, infection, bronchitis, A diaryl-substituted, pyrazole-derived, selective
rhinitis, pharyngitis. cyclo-oxygenase-2 (COX-2) inhibitor, which is
Others: Asthenia, headache, transient alopecia, skin associated with less GI side effects and sus-
rash, increased appetite, weight gain, tinnitus. ceptibility to bruising and bleeding than nonse-
Less Common: Irregular menses, secondary lective NSAIDs.
amenorrhea. Indications: Relief of the signs and symptoms of
Rare: Hepatic failure (may be fatal), pancreatitis,
osteoarthritis, ankylosing spondylitis and
hyperammonemia, Stevens-Johnson syn-
rheumatoid arthritis; and short-term (≤7 days)
drome, toxic epidermal necrolysis (see Warn-
management of moderate to severe acute in-
ing and Precautions).
jury (post-operative, musculoskeletal or soft
Drug Interactions: tissue), or following dental extraction.
Contraindications: Known hypersensitivity to other
Aspirin – this increase valproate free fraction levels
NSAIDs, aspirin, sulfonamides or any compo-
by plasma protein binding competition.
nent of the formulation; active GI disease or
Amitriptyline/Nortriptyline – its plasma clearance is
bleeding; heart failure, angina, peripheral arte-
decreased with co-administration of valproate.
rial disease or cerebrovascular disease; the
Consider lowering dose of amitripty-
perioperative setting of Coronary Artery By-
line/nortriptyline.
pass Graft Surgery; the third trimester of
Carbamazepine – valproate may increase or de-
pregnancy (risk of premature closure of the
crease carbamazepine levels.
ductus arteriosus and prolonged parturition);
Diazepam – valproate displaces diazepam from
breastfeeding (due to potential for serious ad-
binding sites and inhibits its metabolism, in-
verse reactions in nursing infants); severe liv-
creasing free fraction of diazepam.
er impairment or active liver disease; severe
Phenobarbital – valproate inhibits its metabolism;
renal impairment; inflammatory bowel dis-
closely monitor for neurologic toxicity, includ-
ease; known hyperkalemia.
ing CNS depression.
Phenytoin – valproate displaces phenytoin from Dose:
binding sites and inhibits its metabolism, in- NOTE: Risk of cardiovascular adverse events is dose-
creasing free fraction of phenytoin. related; do not use >200 mg daily long-term; use
Rifampin – increases oral clearance of valproate; the lowest effective dose for the shortest duration of
time, consistent with patient treatment goals.
with need to adjust valproate dosage.
Acute dental pain, by mouth, ADULT, 400 mg,
Warfarin – in an in vitro study, valproate increased
followed by an additional 200 mg if needed on
unbound fraction of warfarin. Its therapeutic
Day 1; maintenance dose: 200 mg twice daily
relevance is unknown; however, coagulation
as needed, not to exceed 7 days.
tests should be monitored.
Ankylosing spondylitis, by mouth, ADULT, up to 200
mg daily, in one or two divided doses twice
Carbapenem antibiotics (e.g., meropenem,
daily.
imipenem, ertapenem) – these decrease
Osteoarthritis, by mouth, ADULT, 200 mg daily as a
valproate levels; can result in loss of seizure
single dose or as two divided doses.
control (alternative antibacterial or anticonvul-
Pain, acute (post-operative, musculoskeletal or soft
sant therapy should be considered).
tissue), by mouth, ADULT, 400 mg as a single
Administration: dose on the 1st day, then 200 mg once or
Swallow tablets whole, do not chew or crush. Taken twice daily if needed (maximum: 7 days treat-
preferably after food intake. If dose is skipped, ment).
do not double the next dose. Rheumatoid arthritis, by mouth, ADULT, 100 mg
twice daily; may be increased to 200 mg twice
Pregnancy Category: D daily (short-term use only).
Dose Adjustment:
Elderly:
Initiate at the lowest recommended dose of the
medicine in patients weighing <50 kg (the
AUC in elderly patients may be increased by
50%).
Renal Impairment:
For mild-to-moderate renal impairment, adjustment
may not be necessary (but pre-existing renal
impairment increases the risk of NSAID-
124
induced impairment); for severe impairment, nitis, sinusitis, upper respiratory tract infection,
celecoxib is contraindicated; nephrotoxic. vomiting.
Hepatic Impairment: Less Common: Alopecia, anemia, angina, anorex-
For mild-to-moderate hepatic impairment, dose ia, anxiety, arthrosis, bradycardia, bron-
reduction by 50% is warranted; for severe im- chospasm, cellulitis, chest pain, constipation,
pairment, it is contraindicated; hepatotoxic. cystitis, depression, dermatitis, dryness of
skin, dysphagia, dyspnea, facial edema, fa-
Precautions:
tigue, gastroesophageal reflux, GI ulcer, hy-
WARNING: percholesterolemia, hyperglycemia, hyperten-
Cardiovascular risk – NSAIDs are associated with an
sion, hypokalemia, MI, migraine, myalgia,
increased risk of serious (and potentially fatal) ad-
verse cardiovascular events, including MI, stroke, is- nervousness, pain palpitations, paresthesia,
chemic heart disease, cerebrovascular disease and photosensitivity, pruritus, sinus tachycardia,
congestive heart failure. All NSAIDs may have a simi- somnolence, tinnitus, urinary frequency, urti-
lar risk. This risk may increase with duration of use. caria, ventricular hypertrophy, vertigo, xero-
Patients with cardiovascular disease or risk factors for stomia.
cardiovascular disease may be at greater risk.
Rare: Acute renal failure, agranulocytosis, anaphy-
Gastrointestinal risk – NSAIDs cause an increased risk of
serious GI adverse events, including bleeding, ulcera- lactoid reactions, angioedema, aplastic ane-
tion, and perforation of the stomach or intestines, mia, cerebrovascular accidents, CHF, choleli-
which can be fatal. These events can occur at any thiasis, colitis, DVT, erythema multiforme,
time during their use and without warning symptoms. esophageal perforation, exfoliative dermatitis,
Elderly patients are at greater risk for serious GI gangrene, GI bleeding, hepatic failure and ne-
events.
crosis, hepatitis, hypoglycemia, hyponatremia,
Pre-existing renal impairment increases the risk of NSAID-
induced impairment. intestinal obstruction and perforation, intracra-
nial hemorrhage, jaundice, leukopenia, pan-
In patients with hypertension, congestive heart creatitis, pancytopenia, pulmonary embolism,
failure or cardiovascular disease (NSAIDs can renal papillary necrosis, sepsis, Stevens-
promote sodium and fluid retention in a dose- Johnson syndrome, suicide, syncope, taste
dependent manner, through reduction in glo- disturbance, thrombocytopenia, thrombophle-
merular filtration rate and renal blood flow, bitis, toxic epidermal necrolysis, vasculitis,
which can result in increased BP and/or exac- ventricular fibrillation.
erbation of CHF); Use with caution among pa-
tients with history of GI diseases or bleeding, Drug Interactions:
vitamin K deficiency, or hypoprothrombinemia; Monitor closely with:
may exacerbate existing hepatic or renal in- ACE inhibitors – these may enhance the adverse
sufficiency. effect of NSAIDs, specifically a significant de-
NSAIDs which inhibit prostaglandin biosynthesis crease in renal function. NSAIDs may also re-
interfere with platelet function to varying de- duce their antihypertensive effect.
grees (patients who may be adversely affect- Agents with antiplatelet properties (e.g., NSAIDs,
ed are those on anticoagulants, or suffering SSRIs) – an increased risk of bleeding may
from hemophilia or platelet disorders). occur (NSAIDs may enhance the adverse ef-
Anaphylactoid reactions may be observed; asthma, fect of these drugs).
especially with rhinitis or nasal polyps Aminoglycosides – NSAIDs may decrease the
(NSAIDs may increase the risk of bron- excretion of these drugs.
chospasm); some NSAIDs are associated with Angiotensin II receptor blockers – these may en-
persistent urinary symptoms, hematuria, or hance the adverse effect of NSAIDs, specifi-
cystitis; monitor stool for blood and kidney cally a significant decrease in renal function.
function if NSAIDs are used chronically; the NSAIDs may also reduce their antihyperten-
elderly (increased risk of adverse effects, in sive effect.
particular heart failure, GI ulceration and renal Anticoagulants – their anticoagulant effect may be
impairment). enhanced by NSAIDs; at an increased risk of
Pregnancy (there may be an increased risk for serious bleeding.
miscarriage; risk appears highest when the Benzodiazepines and antidepressants – their ef-
NSAIDs are taken around the time of concep- fects may be altered by NSAIDs.
tion; this is contraindicated in the third tri- Beta-blockers – NSAIDs may diminish the antihy-
mester); women (reconsider NSAID use if pertensive effect of these drugs.
planning for pregnancy, as NSAIDs may im- Digoxin – NSAIDs may increase the serum concen-
pair fertility by preventing or delaying ovulation tration of this drug.
– reversible). Diuretics (e.g., thiazide diuretics, and potassium-
Patient response to NSAIDs is variable. Switch to sparing diuretics) – their therapeutic effect
another preparation if response is inadequate. may be diminished by NSAIDs.
Haloperidol – NSAIDs may enhance the adverse
Adverse Drug Reactions: effect of this drug.
Common: Abdominal pain, back pain, cough, diar- Quinolone antibiotics – NSAIDs may enhance the
rhea, dizziness, dyspepsia, fever, flatulence, neuroexcitatory and/or seizure-potentiating ef-
headache, insomnia, nasopharyngitis, nau- fect of these drugs.
sea, peripheral edema, pharyngitis, rash, rhi-
125
Avoid concomitant use with: Precautions:
Aspirin – concomitant administration with this drug WARNING:
results in an increased rate of GI ulceration or Cardiovascular risks – NSAIDs are associated with an
other complications. increased risk of adverse cardiovascular thrombotic
Loop diuretics – their prostaglandin-mediated effect events, including fatal MI and stroke.
may be antagonized by NSAIDs. Gastrointestinal events – NSAIDs may increase risk of GI
irritation, inflammation, ulceration, bleeding and perfo-
Other NSAIDs – the use of celecoxib in addition to
ration.
any other NSAID is not recommended be-
cause of the absence of any evidence Renal impairment (monitor renal function; may
demonstrating synergistic benefits and the po- cause sodium and water retention; deteriora-
tential for additive adverse reactions. tion in renal function possibly leading to renal
Vitamin K antagonists (e.g., warfarin) – anticoagu- failure); hepatic impairment (increased risk of
lant effect may be enhanced by NSAIDs; in- GI bleeding and can cause fluid retention;
creased risk of serious bleeding. avoid use in severe liver disease); elderly, in
allergic disorders; cardiac disease; coagula-
Administration: May be administered without
tion defects.
regard to meals. Pregnancy (avoid use unless the potential benefit
NOTE: GI absorption is delayed by food and milk.
outweighs risk; third trimester: with regular
Pregnancy Category: C; D in the 3rd trimester or use, there is increased risk of closure of fetal
near delivery. ductus arteriosus in utero, and possible per-
sistent pulmonary hypertension in new-born;
may result in delayed onset and an increase
in duration of labor); breastfeeding (amount is
IBUPROFEN too small to be harmful; short courses safe in
usual doses).
Oral: 200 mg and 400 mg tablet Adverse Drug Reactions:
800 mg MR tablet Common: Diarrhea, dizziness, dyspepsia, GI ulcer-
100 mg/5 mL suspension, 60 mL ation or bleeding, headache, hemorrhage, hy-
A propionic acid-derived, nonselective, nonsteroidal pertension, nausea, raised liver enzymes, salt
anti-inflammatory medicine, which is useful for and fluid retention, vomiting.
the management of pain due to inflammation. Less Common: Bronchospasm, confusion, esoph-
ageal ulceration, heart failure, hyperkalemia,
Indications: Acute pain and inflammation in rheu- rash, renal impairment.
matic diseases and other musculoskeletal Rare: Acute renal failure, aseptic meningitis, blood
disorders; mild to moderate pain, including dyscrasias, blurred vision, colitis, cystitis, fluid
dysmenorrhea and headache; pain in children; retention, hepatitis, anaphylactic and anaphy-
acute migraine attack. lactoid reactions, interstitial nephritis, MI, ne-
Contraindications: Known hypersensitivity to phrotic syndrome, photosensitivity reaction,
ibuprofen and other NSAIDs, or any the com- Stevens-Johnson syndrome, stroke, tinnitus,
ponents of the formulation; should not be giv- toxic epidermal necrolysis, vertigo.
en to patients with active peptic ulceration; Drug Interactions:
should preferably not be used in those with a Monitor closely with:
history of the disease. ACE inhibitors – NSAIDs may reduce antihyperten-
Dose: sive effect of ACE inhibitors, and may in-
Mild to moderate pain, pyrexia and inflammatory crease the risk of renal impairment and hyper-
musculoskeletal disorders, by mouth, ADULT, kalemia.
1.2-1.8 g daily in 3-4 divided doses, increased Angiotensin II receptor blockers – these may en-
if necessary to maximum 2.4 g daily (3.2 g hance the adverse effect of NSAIDs; may re-
daily in inflammatory disease); maintenance sult in significant decrease in renal function;
dose of 0.6-1.2 g daily may be sufficient. NSAIDs may also diminish the antihyperten-
Pain in CHILD (not recommended for children <7 sive effect of these drugs.
kg), by mouth, 20-40 mg/kg daily in divided Aspirin – ibuprofen can reduce the antiplatelet
doses; or CHILD 8-12 years, 200 mg 3-4 activity of low-dose aspirin and may reduce or
times daily; CHILD 3-7 years, 100 mg 3-4 negate its cardioprotective effect.
times daily; CHILD 1-2 years, 50 mg 3-4 times Atenolol, ciprofloxacin and levofloxacin – possibly
daily. increased risk of convulsions.
Corticosteroids, Oral (e.g., hydrocortisone) – these
Dose Adjustments: increase the risk of gastric ulceration with
Renal and Hepatic Impairment: NSAIDs.
The dose should be kept as low as possible; ne- Digoxin – possible exacerbation of heart failure,
phrotoxic and hepatotoxic (see Precautions). reduced renal function and increased plasma
digoxin concentration.
Diuretics (e.g., loop diuretics and thiazide diuretics)
– NSAIDs reduce renal function and may di-
126
minish diuretic effect; risk of nephrotoxicity is associated symptoms and continued accord-
increased. ing to the clinical judgment of the physician.
Other NSAIDs – enhanced adverse effects. Mild to moderate pain, by mouth, ADULT, 500 mg 3
Avoid concomitant use with: times daily, in adults and adolescents >14
Alendronate – this may increase the risk of gastric years.
ulceration with NSAIDs. Premenstrual syndrome, by mouth, ADULT, 500 mg
Antihypertensives (e.g., beta blockers, ARBs, and 3 times daily, starting with the onset of symp-
nitrates) – NSAIDs may increase BP; possible toms and continued until the anticipated ces-
reduction of hypotensive effect. sation of symptoms according to the judgment
Drugs affecting clotting process (e.g., ketorolac) – of the physician.
NSAIDs can cause GI bleeding and affect
platelet function; possibly increased risk of Dose Adjustments:
bleeding. Renal and Hepatic Impairment:
Drugs which are renally excreted (e.g., calcineurin Use drug with caution for mild to moderate impair-
inhibitors) – NSAIDs can impair renal function; ment; contraindicated for severe impairment.
possibly increased risk of adverse effects of Precautions:
these drugs.
WARNING:
Drugs which increase potassium concentration
Cardiovascular risks – NSAIDs are associated with an
(e.g., amiloride and triamterene) – NSAIDs increased risk of adverse cardiovascular thrombotic
can cause hyperkalemia; combination with events, including fatal MI and stroke.
these drugs may increase this risk. Gastrointestinal events – NSAIDs may increase risk of GI
Vitamin K antagonists (e.g., warfarin) – anticoagu- irritation, inflammation, ulceration, bleeding and perfo-
lant effect may be enhanced by NSAIDs; in- ration.
creased risk of serious bleeding. Undesirable effects may be minimized by using the
Administration: Should be taken with food. lowest effective dose for the shortest duration
necessary to control symptoms; anemia,
Pregnancy Category: C, prior to 30 weeks gesta- agranulocytosis, and Coombs’-positive (hemo-
tion; D, ≥30 weeks gestation. lytic anemia are seen with prolonged use;
should not be given for longer than 7 days).
May have nephrotoxicity and hepatotoxicity.
MEFENAMIC ACID Use with caution among patients with history of GI
diseases or bleeding; hepatic and renal dis-
Oral: 250 mg and 500 mg tablet/capsule ease, hypoprothrombinemia or vitamin K defi-
50 mg/5 mL suspension, 60 mL ciency; use with caution in patients with hyper-
tension, CHF and cardiovascular disease;
A fenamate-derived (anthranilic acid), nonsteroidal
may adversely affect BP control; anaphylac-
anti-inflammatory medicine, which possesses
toid reactions may be seen; caution is re-
greater anti-inflammatory and analgesic prop-
quired for patients suffering, or with a previous
erties than ibuprofen or aspirin.
history of, bronchial asthma (may precipitate
Indications: Symptomatic relief of acute pain and bronchospasm).
inflammation; for muscular, traumatic and Patient’s response to NSAIDs is variable, switch to
dental pain; headache of most etiology and another preparation if the response is inade-
postoperative and postpartum pain; the symp- quate; monitor stool for blood and kidney func-
tomatic relief of dysmenorrhea; menorrhagia tion if NSAIDs are to be used chronically (pa-
due to dysfunctional causes or the presence tients on prolonged therapy should be kept
of an IUD when organic pelvic pathology has under surveillance with particular attention to
been excluded; premenstrual syndrome. liver dysfunction, rash, blood dyscrasias or
development of diarrhea).
Contraindications: Hypersensitivity or ASA allergy; Elderly (increased frequency of adverse reactions to
history of aspirin triad; patients with inflamma- NSAIDs, such as GI bleeding and perforation).
tory bowel disease, GI ulcers and history of GI Pregnancy (avoid during last trimester).
bleeding or perforation, related to NSAID
therapy; active or history of recurrent peptic Adverse Drug Reactions:
ulcer or hemorrhage; severe heart failure, he- Common: Diarrhea, dizziness, dyspepsia, GI ulcer-
patic failure and renal failure; pain treatment ation or bleeding, headache, hemorrhage, hy-
after coronary artery bypass surgery; during pertension, nausea, raised liver enzymes, salt
the last trimester of pregnancy. and fluid retention, vomiting.
Less Common: Bronchospasm, confusion, esoph-
Dose: ageal ulceration, heart failure, hyperkalemia,
Dysmenorrhea, by mouth, ADULT, 500 mg 3 times rash, renal impairment.
daily, to be administered on the onset of men- Rare: Similar to Ibuprofen; see under Ibuprofen.
strual pain and continue while symptoms per-
sist according to the clinical judgment of the Drug Interactions:
physician. Monitor closely with:
Menorrhagia, by mouth, ADULT, 500 mg 3 times ACE inhibitors – NSAIDs may reduce antihyperten-
daily, starting with the onset of bleeding and sive effect of ACE inhibitors, and may in-
127
crease risk of renal impairment and hyper-
Dose:
kalemia.
Acute gout, by mouth, ADULT, initial 750 mg, fol-
Angiotensin II receptor blockers – these may en-
lowed by 250 mg every 8 hours until the at-
hance the adverse effect of NSAIDs; may re-
sult in significant decrease in renal function; tack subsides.
NSAIDs may also diminish the antihyperten- Acute musculoskeletal disorders, by mouth,
ADULT, 500 mg initially, then 250 mg 2-3
sive effect of these drugs.
times a day.
Corticosteroids, Oral – these increase the risk of
Ankylosing spondylitis, osteoarthritis, rheumatoid
gastric ulceration with NSAIDs.
arthritis, by mouth, ADULT, 500 mg-1 g daily
Diuretics (e.g., loop diuretics and thiazide diuretics)
– NSAIDs reduce renal function and may di- in 2 divided dose; may increase to 1.5 g daily
of naproxen base if tolerating well and clinical-
minish diuretic effect; risk of nephrotoxicity is
increased. ly indicated (for a limited time period, <6
Other NSAIDs – enhanced adverse effects. months). For extended-release tablets, initial
Avoid concomitant use with: 750 mg-1 g once daily; may temporarily in-
Alendronate – this may increase the risk of gastric crease to 1.5 g of naproxen base if tolerating
ulceration with NSAIDs. well and clinically indicated.
Antihypertensives (e.g., beta blockers, ARBs and Dysmenorrhea, by mouth, ADULT, 500 mg initially,
nitrates) – NSAIDs may increase BP; possible followed by 250 mg every 6-8 hours as re-
reduction of hypotensive effect. quired.
Inflammatory joint pain, by mouth, ADULT, 500 mg
Drugs affecting clotting process (e.g., ketorolac) –
NSAIDs can cause GI bleeding and affect twice daily.
platelet function; possibly increased risk of Juvenile idiopathic arthritis, by mouth, CHILD >2
bleeding. years, 10 mg/kg/day in 2 divided doses (up to
Drugs which are renally excreted (e.g., calcineurin 15 mg/kg/day has been tolerated).
inhibitors) – NSAIDs can impair renal function; Pain (mild to moderate), acute tendonitis, bursitis,
possibly increased risk of adverse effects of by mouth, ADULT, initial 500 mg, followed by
these drugs. 500 mg every 12 hours or 250 mg every 6-8
Drugs which increase potassium concentration hours (maximum daily dose: Day 1: 1.25 g
(e.g., amiloride and triamterene) – NSAIDs naproxen base; subsequent daily doses
can cause hyperkalemia; combination with should not exceed 1 g naproxen base).
NOTE: For relief of acute pain, naproxen sodium may be
these drugs may increase this risk. preferred due to more rapid absorption and onset.
Vitamin K antagonists (e.g., warfarin) – anticoagu-
lant effect may be enhanced by NSAIDs; in- Dose Adjustments:
creased risk of serious bleeding. Elderly:
Dose adjustments may be necessary.
Administration: Should be taken with food, or Renal Impairment:
taken immediately after meals. Dose reduction in mild impairment; nephrotoxicity;
Pregnancy Category: C; D if used for prolonged Avoid use in moderate to severe impairment.
periods, or near term. Hepatic Impairment:
Use drug with caution for mild to moderate impair-
ment; for severe impairment, avoid use;
hepatotoxicity.
NAPROXEN Precautions:
WARNING:
Oral: 250 mg base (275 mg) and 500 mg base (550 Cardiovascular risks – NSAIDs are associated with an
mg) tablet (as sodium salt) increased risk of adverse cardiovascular thrombotic
events, including fatal MI and stroke.
A naphthylpropionic acid-derived, nonsteroidal anti- Gastrointestinal events – NSAIDs may increase risk of GI
inflammatory medicine that inhibits prosta- irritation, inflammation, ulceration, bleeding and perfo-
glandin synthesis; it is pharmacologically re- ration.
lated to ibuprofen but has a longer half-life al- Anaphylactoid reactions may occur (do not use in
lowing for twice daily dosing. patients who experience bronchospasm,
Indications: Rheumatoid arthritis; osteoarthritis; asthma, rhinitis, or urticaria with aspirin or
ankylosing spondylitis; juvenile idiopathic ar- NSAID therapy); Cardiovascular events (risks
thritis; for the relief of signs and symptoms of may be increased with the duration of use or
tendonitis and bursitis; acute gout; manage- pre-existing cardiovascular risk factors or dis-
ment of pain due to inflammation (e.g., period ease; use the lowest effective dose for the
pain, migraine); management of primary dys- shortest duration of time, consistent with indi-
menorrhea; inflammatory joint pain. vidual patient goals); CNS effects (it may
cause drowsiness, dizziness, blurred vision
Contraindications: Known hypersensitivity to and other neurologic effects which may impair
naproxen, aspirin, other NSAIDs, or any com- physical or mental ability); in patients with his-
ponent of the formulation; treatment of periop- tory of GI diseases (bleeding or ulcers), or
erative pain in the setting of Coronary Artery concurrent therapy with aspirin, anticoagu-
Bypass Graft surgery; active peptic ulcers; ac- lants and/or corticosteroids, smoking, use of
tive GI inflammatory disease. alcohol, the elderly or debilitated patients;
128
hematologic effects (platelet adhesion and Antihypertensives (e.g., beta blockers, ARBs and
aggregation may be decreased; thus prolong- nitrates) – NSAIDs may increase BP; possible
ing bleeding time); hyperkalemia (use of reduction of hypotensive effect.
NSAID may increase the risk of hyperkalemia, Digoxin – its serum concentration may be increased
particularly in the elderly, diabetics, or renal by NSAIDs.
disease); skin reactions (NSAID use may Drugs affecting clotting process (e.g., ketorolac) –
cause serious skin reactions; discontinue use NSAIDs can cause GI bleeding and affect
at first sign of skin rash or hypersensitivity); platelet function; possibly increased risk of
aseptic meningitis; hepatic impairment; renal bleeding.
impairment; hypertension; asthma (severe Drugs which are renally excreted (e.g., calcineurin
bronchospasm may occur); elderly (may be at inhibitors) – NSAIDs can impair renal function;
higher risk for adverse effects from NSAIDs). possibly increased risk of adverse effects of
Pregnancy (naproxen crosses the placenta, and can these drugs.
be detected in fetal tissue and the serum of Drugs which increase potassium concentration
newborn infants following in utero exposure; (e.g., amiloride and triamterene) – NSAIDs
NSAID exposure may result to various can cause hyperkalemia; combination with
anomalies and deformities); the chronic use of these drugs may increase this risk.
NSAIDs in women of reproductive age may be Vitamin K antagonists (e.g., warfarin) – anticoagu-
associated with infertility, which is reversible lant effect may be enhanced by NSAIDs; in-
upon discontinuation); breastfeeding (small creased risk of serious bleeding.
amounts are excreted into breast milk).
SKILLED TASKS. May impair ability to perform skilled Administration: For conventional tablets, adminis-
tasks, for example operating machinery or driving. ter with food, milk or antacids to decrease GI
adverse effects (drug may cause GI upset,
Adverse Drug Reactions: bleeding, ulceration and perforation).
Common: Abdominal pain, bleeding time in-
creased, constipation, diaphoresis, diarrhea, Pregnancy Category: C
dizziness, drowsiness, dyspepsia, dyspnea,
edema, flatulence, fluid retention, gross bleed-
ing or perforation; headache, heartburn, he-
molysis, indigestion, lightheadedness, nau- PREDNISONE
sea, palpitation, pruritus, pseudoporphyria,
rash, skin eruption, stomatitis, tinnitus, ulcers, Oral: 5 mg, 10 mg and 20 mg tablet
vertigo, visual disturbance, vomiting. 10 mg/5 mL suspension, 60 mL
Rare: Allergic pneumonitis, aplastic anemia, aseptic
meningitis, cognitive dysfunction, erythema A corticosteroid having glucocorticoid and anti-
multiforme, hemolytic anemia, hepatic im- inflammatory effects, which is rapidly convert-
pairment, non-peptic GI ulceration, Stevens- ed to prednisolone – the active product – in
Johnson syndrome, toxic epidermal necroly- the body.
sis, ulcerative stomatitis, vasculitis. Indications: Rheumatoid and juvenile idiopathic
Drug Interactions: arthritis; other inflammatory and autoimmune
conditions.
ACE inhibitors – NSAIDs may reduce antihyperten- Contraindications: See under Corticosteroids.
sive effect of ACE inhibitors, and may in-
crease risk of renal impairment and hyper- Dose:
kalemia. Autoimmune or inflammatory disease, by mouth,
Aminoglycosides – NSAIDs may decrease the ADULT, initially 5-60 mg once daily (prefera-
excretion of these drugs. bly in the morning) depending on the disease
Angiotensin II receptor blockers – these may en- and its severity (may need to be given in 2 di-
hance the adverse effect of NSAIDs; may re- vided doses initially for severe diseases); ta-
sult in significant decrease in renal function; per the dose according to response. Usual
NSAIDs may also diminish the antihyperten- maintenance dose: 2.5-15 mg once daily
sive effect of these drugs. (higher doses may be needed); CHILD, initial-
Corticosteroids, Oral – these increase the risk of ly 1-2 mg/ kg once daily (usual maximum, 60
gastric ulceration with NSAIDs. mg), reducing dose after a few days if appro-
Diuretics (e.g., loop diuretics and thiazide diuretics) priate.
– NSAIDs reduce renal function and may di- Juvenile idiopathic arthritis, by mouth, CHILD, 0.05-
minish diuretic effect; risk of nephrotoxicity is 2 mg/kg divided two times a day or four times
increased. a day, then taper over 2 weeks as symptoms
Other NSAIDs – enhanced adverse effects. resolve and other antirheumatic drugs take ef-
Quinolone antibiotics – NSAIDs may enhance the fect.
neuroexcitatory and/or seizure-potentiating ef- Rheumatoid arthritis, by mouth, ≤10 mg/day added
fect of these drugs. to disease-modifying antirheumatic drugs.
Avoid concomitant use with: See under Corticosteroids for other information.
Alendronate – this may increase the risk of gastric
ulceration with NSAIDs.
129
ANTITHROMBOTICS ANTI-VERTIGO and ANTI-MOTION
SICKNESS
ASPIRIN
MECLIZINE (MECLOZINE)
Oral: 80 mg and 100 mg enteric-coated tablet
Oral: 12.5 mg chewable tablet (as HCl)
An irreversible, cyclo-oxygenase (COX) inhibitor
25 mg tablet (as HCl)
which inhibits platelet aggregation, and is use-
ful in the long-term management of MI and A piperazine-derived, first-generation, H 1 antihista-
stroke, including the prevention of further at- minic agent, which has minimal anticholinergic
tacks. properties, and is used for the prevention of
Indications: Neurologic indications; transient is- motion sickness and in treating vertigo due to
labyrinth dysfunction.
chemic attack and acute ischemic cerebral in-
farction (for early specific treatment or sec- Indications: Prevention and treatment of symptoms
ondary prevention of ischemic stroke). of motion sickness; management of vertigo
Contraindications: Known hypersensitivity (includ- with diseases affecting the vestibular system.
ing asthma, angioedema, urticaria, and rhini- Contraindications: Known hypersensitivity to
tis) to acetylsalicylic acid and any other meclozine or any component of the formula-
NSAIDs, or any component of the formulation; tion; pregnancy.
children and adolescents <16 years (risk of
Reye syndrome); active peptic ulceration; he- Dose:
mophilia and other bleeding disorders; aspirin- Motion sickness, by mouth, ADULT and CHILD
sensitive asthma. >12 years, 25-50 mg 1 hour before travel, re-
peat dose every 24 hours if needed.
Dose: Vertigo, by mouth, ADULT, 25-100 mg daily in
Acute ischemic infarction, by mouth, ADULT, 80- divided doses.
100 mg once daily. NOTE: Lack of response: If vertigo does not respond in 1-2
Transient ischemic attack (early specific treatment), weeks, it is advised to discontinue use.
by mouth, ADULT, 80-100 mg once daily.
Dose Adjustments:
See under Cardiovascular System for other in- Renal and Hepatic Impairment:
formation. Use drug with caution for mild to moderate impair-
ment; for severe impairment, the patient
Precautions:
CLOPIDOGREL Use with caution in patients with asthma, glaucoma,
prostatic hyperplasia; urinary stricture; pyloric
Oral: 75 mg tablet or duodenal obstruction; CNS depression
A thienopyridine-derived, platelet aggregation inhibi- (may possibly cause CNS depression that
tor that has no effect on prostaglandin metab- may impair physical or mental abilities; pa-
olism unlike aspirin, and is used as an alterna- tients should be cautioned about performing
tive for patients who are unable to take aspirin tasks that require mental alertness, such as
or have contraindications to the use of aspirin operating machinery or driving); elderly (may
in the treatment of thrombosis. be inappropriate in older adults depending on
comorbidities, such as dementia, delirium due
Indications: Neurologic indications; transient is- to its potent anticholinergic effects; elderly
chemic attack and acute ischemic cerebral in- may be more sensitive to adverse effects).
farction (for early specific treatment or sec- Pregnancy (adverse events have been observed in
ondary prevention of ischemic stroke). animal reproduction studies; however, an in-
Contraindications: Known hypersensitivity to creased risk of fetal abnormalities has not
clopidogrel or any component of the formula- been observed following maternal use of
meclizine during pregnancy).
tion; severe liver impairment; intracranial
hemorrhage, peptic ulcer or other pathological Adverse Drug Reactions:
bleeding; breastfeeding. Common: Abdominal distress, drowsiness, confu-
Dose: sion, constipation, fatigue, headache, seda-
tion, motor function impairment, thickened
Acute ischemic infarction and secondary prevention
of acute ischemic stroke, by mouth, ADULT, bronchial secretions, urinary retention, vomit-
75 mg once daily. ing.
Transient ischemic attack (early specific treatment), Rare: Anaphylactoid reactions, blurred vision, dry-
by mouth, ADULT, 75 mg once daily. ness of mouth, palpitations, tachycardia, xero-
stomia.
See under Cardiovascular System for other infor-
mation.
130
Drug Interactions: Hepatic Impairment:
Monitor closely with: For mild-to-moderate hepatic impairment, use lower
CNS depressants (e.g., alcohol, sedatives, and or less frequent dose; for severe impairment,
tranquilizers) – these possibly enhance CNS the patient should be referred to a specialist.
depression.
Avoid concomitant use with: Precautions:
Anticholinergics (see Appendix – Table A) – their WARNING: Antidepressants increase the risk of suicidal
toxic effect may be enhanced by meclizine. thinking and behavior in children, adolescents, and
young adults (18-24 years of age) with major depres-
Administration: Tablet may be taken with or with- sive disorder (MDD) and other psychiatric disorders.
out food; it should be taken 1 hour prior to
SSRIs should be used in caution in patients with
embarkation for the protection against motion
epilepsy (reduced seizure threshold; avoid if
sickness.
poorly controlled, discontinue use if convul-
Pregnancy Category: B sions develop).
Cardiac disease, may cause QT prolongation, dia-
betes mellitus, susceptibility to angle-closure
PSYCHOPHARMACOLOGIC AGENTS glaucoma, a history of mania or bleeding dis-
orders (e.g., GI bleeding), and if used with
other drugs that increase the risk of bleeding;
ANTIDEPRESSANTS people at high risk of bleeding (age >80, or
with previous upper GI bleeding) or taking
drugs known to increase risk of GI bleeding,
such as regular aspirin or NSAIDs (likelihood
FLUOXETINE of serious bleeding may be increased; avoid
combinations or monitor clinical course care-
Oral: 20 mg capsule
fully); renal and hepatic impairment.
A selective serotonin reuptake inhibitor (SSRI) that Bipolar disorder (all antidepressants may provoke a
is less sedating, and has fewer anticholinergic manic episode when used in patients with bi-
and cardiotoxic effects than tricyclic antide- polar disorder).
pressants; it also has longer half-life than the Children and adolescents (increased risk of sui-
other SSRIs. cide).
Avoid abrupt withdrawal (the dose should be ta-
Indications: Moderate to severe depression; anxie- pered over at least a few weeks).
ty disorders (e.g., panic disorder and obses- Hyponatremia, mydriasis, hypoglycemia reported.
sive-compulsive disorder). Pregnancy (this should not be used unless the
Contraindications: Known hypersensitivity to potential benefit outweighs the risk; increased
fluoxetine or any of its components; manic risk of congenital heart defects and neonatal
phase; patients receiving MAO inhibitors cur- withdrawal symptoms); breastfeeding (present
rently or in the past two (2) weeks (due to ser- in milk; avoid use).
otonin toxicity).
tasks, for example operating machinery or driving.
Dose:
Depression, by mouth, ADULT, initially 20 mg once
Common: Agitation, anxiety, diarrhea, dizziness,
daily, increased as necessary after 3-4 weeks
drowsiness, dry mouth, headache, insomnia,
to maximum of 60 mg daily (40 mg daily in the
myalgia, nausea, rash, rhinitis, sexual dys-
elderly, but 60 mg can be used); usual
function, sweating, tremor, weakness, weight
maintenance dose in the range, 20-60 mg
gain or loss.
once daily (20-40 mg once daily in the elder-
Less Common: Abnormal platelet aggregation or
ly); CHILD, refer to a specialist for manage-
hemorrhaging complication (e.g., bruising,
ment.
epistaxis, GI and vaginal bleeding), extrapy-
Obsessive-compulsive disorder, by mouth, ADULT,
ramidal symptoms (including tardive dyskine-
>18 years, 20 mg daily; increased gradually if sia, tachycardia, hyponatremia (as part of SI-
necessary to a maximum of 60 mg daily; EL-
ADH), hypotension, mydriasis.
DERLY, usually maximum of 40 mg daily, but
Rare: Akathisia, blood dyscrasias, elevated liver
60 mg can be used (review treatment if re- enzymes, galactorrhea, hepatic failure, hepati-
sponse is inadequate after 10 weeks). tis, paresthesia, seizures, taste disturbance.
Panic disorder, by mouth, ADULT, 10 mg once
daily; do not exceed 20 mg daily. Drug Interactions:
NOTE: Consider the long duration of action of fluoxetine Monitor closely with:
when adjusting dosage. Analgesics (Opioids) – these may enhance the
Dose Adjustments: serotonergic effect of SSRIs (may cause sero-
Renal Impairment: tonin syndrome).
Use drug with caution for mild-to-moderate renal Agents with antiplatelet properties (NSAIDs) –
impairment; for severe impairment, the patient SSRIs may enhance the antiplatelet effect of
should be referred to a specialist. these drugs.
CNS depressants (e.g., alcohol) – these may en-
hance the adverse effect of SSRIs (specifical-
131
ly, the risk of psychomotor impairment may be steps of 25 to 50 mg at intervals of at least 1
enhanced). week (maximum, 200 mg daily).
Salicylates (e.g., aspirin) – their toxic effect may be
Dose Adjustments:
enhanced by the SSRIs; increased risk of
bleeding may result. Renal Impairment:
Vitamin K antagonists (e.g., warfarin) – their antico- Use with caution.
agulant effect may be enhanced by the Hepatic Impairment:
SSRIs. Reduce dose or increase dose interval in mild or
Avoid concomitant use with: moderate impairment;
Amiodarone – increased QTc interval. Precautions:
Drugs which may contribute to serotonin toxicity WARNING: Antidepressants increase the risk of suicidal
(e.g., MAO inhibitors) – may increase likeli- thinking and behavior in children, adolescents, and
hood of the said toxicity (occasionally, the use young adults (18-24 years of age) with major depres-
of opioids which do not usually affect seroto- sive disorder (MDD) and other psychiatric disorders.
nin metabolism may result in serotonin toxici- Possibility of a suicide attempt is inherent in major
ty). depression and may persist until remission
Seizure-inducing drugs (see Appendix – Table C) – occurs (prescriptions should be written for
SSRIs can lower the seizure threshold; admin- the smallest quantity consistent with good
istration with the said drugs may decrease it patient healthcare; observe for clinical wors-
further. ening and suicidal ideation).
Tramadol – SSRIs may enhance the neuroexcitato- QTc prolongation; SSRIs should be used in caution
ry and/or seizure-potentiating effect of this in patients with epilepsy (reduced seizure
drug. threshold; avoid use if poorly controlled or dis-
Administration: Take this in the morning. continue use if convulsions develop); cardiac
NOTE: Food reduces the incidence of the common symp- disease, diabetes mellitus, susceptibility to
toms of nausea and diarrhea associated with SSRI angle-closure glaucoma and a history of ma-
use. nia.
Pregnancy Category: C Bipolar disorder (all antidepressants may provoke a
manic episode when used in patients with bi-
polar disorder); CNS depression.
People at high risk of bleeding (age >80 or previous
upper GI bleeding), or taking drugs known to
SERTRALINE increase risk of GI bleeding, such as regular
aspirin or NSAIDs (likelihood of serious bleed-
Oral: 50 mg tablet (as HCl)
ing may be increased); avoid combinations or
A selective serotonin reuptake inhibitor (SSRI) that monitor clinical course carefully).
has pharmacokinetic parameters similar to Children and adolescence (increased risk of sui-
those of TCAs, and has short half-life. cide).
Uric acid nephropathy.
Indications: Treatment of major depression, dys- Avoid abrupt withdrawal (the dose should be ta-
thymia and post-traumatic stress disorder; ob- pered over at least a few weeks).
sessive-compulsive disorder; panic disorder. Hyponatremia and mydriasis reported.
Contraindications: Known hypersensitivity to Pregnancy, refer to a specialist (should not be
sertraline or any component of the formula- used unless potential benefit outweighs the
tion; should not be used if the patient enters a risk; increased risk of congenital heart defects
manic phase; use of MAO inhibitors to treat and neonatal withdrawal symptoms); breast-
psychiatric disorders (concurrently or within 14 feeding (present in milk; avoid use if possible).
days of stopping sertraline or a MAO inhibi-
tasks, for example operating machinery or driving.
tor).
Dose: Adverse Drug Reactions:
Depressive illness, by mouth, ADULT, initially 50 Common: Agitation, anxiety, chest pain, constipa-
mg daily, increased if necessary by incre- tion, diaphoresis, diarrhea, dizziness, drowsi-
ments of 25 to 50 mg at intervals of at least 1 ness, dryness of mouth, dyspepsia, fatigue,
week to maximum of 200 mg daily; (usual headache, hypesthesia, impotence, insomnia,
maintenance dose, 50 mg daily). malaise, myalgia, nausea, nervousness, palpi-
Obsessive-compulsive disorder, by mouth, ADULT, tation, rash, rhinitis, sexual dysfunction, som-
initially 50 mg daily, increased if necessary in nolence, sweating, tremor, weakness, weight
steps of 25 to 50 mg at intervals of at least 1 gain or loss, xerostomia.
week (maximum, 200 mg daily); CHILD, refer Less Common: Abdominal pain, abnormal platelet
to a specialist. aggregation or hemorrhaging complications
Panic disorder, post-traumatic stress disorder, or (e.g., bruising, epistaxis, GI and vaginal bleed-
social anxiety disorder, by mouth, ADULT ing), EPS (including tardive dyskinesia, tachy-
>18 years, initially 25 mg daily, increased af- cardia, hyponatremia, hypotension, mydria-
ter 1 week to 50 mg daily; if response is partial sis).
and if drug is tolerated, increase the dose in Rare: Akathisia, allergic reaction including Stevens-
Johnson syndrome, anaphylactoid reaction,
132
angioedema, atrial arrhythmia, AV block, ANTIPSYCHOSIS
blood dyscrasias, bradycardia, diabetes melli-
tus, elevated liver enzymes, hepatic failure,
hepatitis, hyperprolactinemia, hypothyroidism, CHLORPROMAZINE
lupus-like syndrome, neuroleptic malignant
syndrome, optic neuritis, pancreatitis, pares- Oral: 50 mg, 100 mg and 200 mg tablet
thesia, photosensitivity, QT prolongation, renal Inj.: 25 mg/mL, 1 mL ampul (IM, IV) (as HCl)
failure, seizure, serotonin syndrome, SIADH,
ventricular tachycardia. An aliphatic-derived, phenothiazine that is used for
treating schizophrenia, and is effective for
Drug Interactions: other psychoses and agitated states.
Agents with antiplatelet properties (NSAIDs) – Indications: Schizophrenia and some other psy-
SSRIs may enhance the antiplatelet effect of chotic disorders, mania, psychomotor agita-
these drugs. tion and violent behavior; adjunct in severe
Analgesics (Opioids) – these may enhance the anxiety.
serotonergic effect of SSRIs (may cause sero- Contraindications: Known hypersensitivity to
tonin syndrome). chlorpromazine or any component of the for-
CNS depressants (e.g., alcohol) – these may en- mulation; impaired consciousness due to CNS
hance the adverse effect of SSRIs (specifical- depression; bone marrow depression; severe
ly, the risk of psychomotor impairment may be hypotension and cardiovascular disease;
enhanced). subcortical brain damage; concomitant use of
Hypoglycemic agents – SSRIs may enhance their CNS depressants; pheochromocytoma; lac-
hypoglycemic effect (due to their possibly in- tation.
creased concentration). Dose:
Salicylates (e.g., aspirin) – their toxic effect may be Schizophrenia and other psychoses, mania, psy-
enhanced by the SSRIs; increased risk of chomotor agitation, violent behavior, severe
bleeding may result. anxiety (adjunct), by mouth, ADULT, initially
Serotonin agonists and sympathomimetics – in- 10 to 25 mg 3 times daily or 75 mg at night,
creased risk of serotonin syndrome when adjusted according to response to usual
used with these drugs. maintenance dose of 75-300 mg daily (but up
Thiazide diuretics – SSRIs may enhance their hy- to 1 g daily may be required in psychoses);
ponatremic effect. ELDERLY (or debilitated patients) one-third to
Thyroid products – their therapeutic effect may be half of the adult dose; CHILD 6-12 years, one-
diminished by SSRIs. third to half of the adult dose (maximum, 75
Vitamin K antagonists (e.g., warfarin) – their antico- mg daily); CHILD (childhood schizophrenia
agulant effect may be enhanced by the and autism) 1-5 years, 500 micrograms/kg
SSRIs. every 4-6 hours (maximum, 40 mg daily).
Avoid concomitant use with: For relief of acute symptoms, by deep IM injection,
Drugs which may contribute to serotonin toxicity ADULT, 25-50 mg, may repeat in 1 hour;
(e.g., MAO inhibitors) – may increase likeli- CHILD, refer to a specialist.
hood of the said toxicity (occasionally, the use Dose Adjustment:
of opioids which do not usually affect seroto- Hepatic Impairment:
nin metabolism may result in serotonin toxici- Consider dose reduction in mild impairment. Avoid
ty). use in moderate to severe impairment.
Seizure-inducing drugs (see Appendix – Table C) –
Precautions:
SSRIs can lower the seizure threshold; admin-
istration with the said drugs may decrease it WARNING: Patients with dementia-related psychosis who
are treated with antipsychotic drugs are at increased
further. risk for death due to cardiovascular cause (e.g., heart
Tramadol – SSRIs may enhance the neuroexcitato- failure or sudden death) or infections (e.g., pneumo-
ry and/or seizure-potentiating effect of this nia). Not for dementia-related psychosis.
drug. Patients >70 years of age (may cause hypother-
Tricyclic antidepressants – sertraline may enhance mia); Parkinsonism; respiratory disease; epi-
the adverse effect of these drugs (due to their lepsy; acute infections; history of jaundice;
possibly increased serum concentration). hypothyroidism, myasthenia gravis; prostatic
Administration: Administer once daily either in the hypertrophy; angle-closure glaucoma; cardiac
morning or evening; if somnolence is noted, arrhythmia, cardiovascular and cerebrovas-
administer at bedtime. cular disorders; renal impairment (avoid use
NOTE: Food often reduces the incidence of the common if severe; start with small doses; increased
symptoms of nausea and diarrhea associated with cerebral sensitivity); hepatic impairment (avoid
SSRI use. if severe; can precipitate coma, hepatotoxic);
Pregnancy Category: C the elderly (particularly in very hot and very
cold weather; reduce dose); avoid abrupt with-
drawal.
The patient should remain in supine position, and BP
monitored for 30 minutes after IM injection (due
to risk of hypotension).
133
Pregnancy (third trimester: extrapyramidal effects in Epinephrine – antagonism of hypertensive effect.
neonate have been occasionally reported). Seizure-inducing drugs (see Appendix – Table C for
SKILLED TASKS. May impair ability to perform skilled other drugs which may also cause seizures) –
tasks, e.g., operating machinery or driving. chlorpromazine may cause seizures; admin-
NOTE: Owing to the risk of contact sensitization, pharma-
istration with these drugs may increase this
cists, nurses, and other health workers should avoid
direct contact with chlorpromazine; tablets should not risk.
be crushed and solutions should be handled with
Administration: May be taken with or without food;
care.
may be administered with meals to reduce GI
Adverse Drug Reactions: discomfort.
Common: Agitation, anxiety, blurred vision, consti- NOTE: Avoid skin contact with injection solution as there is a
pation, dry mouth, extrapyramidal side effects risk of contact dermatitis. Avoid using crushed tablets
for this reason and to reduce risk of direct irritation to
(e.g., Parkinsonian symptoms, dystonia, aka-
oral mucosa. In cases where there is no alternative,
thisia, tardive dyskinesia), hyperprolactinemia inject deeply into a large muscle mass. Give IV doses
(e.g., galactorrhea, gynecomastia, amenor- well diluted and by infusion.
rhea or infertility), mydriasis, nausea, orthos-
tatic hypotension, sedation, sexual adverse ef- Pregnancy Category: C
fects, tachycardia, urinary retention, weight
gain.
Less Common to Rare: Agranulocytosis, allergic
reactions, anemia, arrhythmias, cardiac arrest, HALOPERIDOL
changes in ECG, cholestatic jaundice, corneal
and lens opacities, dysarthria, dysphagia, he- Oral: 500 microgram, 1.5 mg, 2 mg, 5 mg, 10 mg,
patic fibrosis, hyperthermia, hypothermia, in- and 20 mg tablet
creased blood glucose, neuroleptic malignant Inj.: 5 mg/mL, 1 mL ampul (IM)
syndrome, neutropenia, photosensitivity reac- 50 mg/mL, 1 mL (oily) ampul (IM)
tions (phototoxicity, and hyperpigmentation), (as decanoate)
priapism, SIADH, SLE, sudden death, throm- A butyrophenone-derived, first-generation (typical)
bocytopenia, venous thromboembolism (VTE). antipsychotic drug having potent dopamine
Drug Interactions: receptor antagonist activity, and is character-
Monitor closely with: ized by fewer autonomic (sedative and anti-
Atropine – increased antimuscarinic adverse effects muscarinic) effects; but has greater extrapy-
(but reduced plasma concentration of chlor- ramidal side-effects.
promazine). Indications: Schizophrenia, acute and chronic
CNS depressants (e.g., alcohol, sedatives and psychoses; mania; short-term adjunctive
tranquilizers) – possibly enhanced CNS de- management of psychomotor agitation, violent
pression. behavior and severe anxiety; Tourette’s syn-
Diazepam – enhanced sedative effect. drome.
Drugs causing hypotension (e.g. amlodipine,
atenolol, enalapril, furosemide, hydrochloro- Contraindications: Comatose states; impaired
thiazide and ISDN) – antipsychotics can consciousness due to CNS depression; Par-
cause orthostatic hypotension and may result kinson’s syndrome or preexisting Parkinson-
in additional hypotension when given with like symptoms; bone marrow depression; por-
these drugs. phyria; pheochromocytoma; basal ganglia
Drugs increasing blood glucose concentration (e.g., disease; poorly controlled seizures.
glucocorticoids, calcineurin inhibitors, high- Dose:
dose thiazide diuretics and somatropin) – Acute psychotic conditions, by IM injection, ADULT,
chlorpromazine can increase blood glucose
initially 2-10 mg (half of the adult dose in el-
concentration, and may increase risk of hy-
derly or debilitated patients; up to 18 mg in
perglycemia if given with these drugs.
severely affected patients); subsequent doses
Drugs with anticholinergic effects (see Appendix –
every 4-8 hours according to response (up to
Table A) – chlorpromazine has anticholinergic every hour if necessary) up to a maximum of
effects; administration with these drugs in- 18 mg daily; CHILD, use is not recommend-
creases the risk of adverse effects. ed.
Methyldopa – enhanced hypotensive effect; in- Chronic psychoses, by mouth, ADULT, 1-5 mg 2 or
creased risk of extrapyramidal effects.
3 times daily (maximum, 30 mg daily); long-
Metoclopramide – increased risk of extrapyramidal
acting IM, 50-300 mg every 4 weeks; by
effects.
mouth, CHILD >5 years, initially 0.25-0.5 mg
Propranolol – this may increase chlorpromazine
once daily, increase to 0.15 mg/kg daily (max-
imum, 5 mg).
Schizophrenia and other psychoses, mania, short-
term adjunctive management of psychomotor
– these reduce absorption of chlorpromazine.
agitation, violent behavior and severe anxiety,
Artemether + lumefantrine – these may result to
by mouth, ADULT, 1.5-3 mg 2-3 times daily
potentially hazardous interactions when given
(half of the adult dose in elderly or debilitated
concomitantly with chlorpromazine.
patients; 3-5 mg 2-3 times daily in severely af-
134
fected or resistant patients; up to 30 mg daily akathisia; increased weight, injection site re-
in resistant schizophrenia); CHILD, 25-50 mi- actions, masked facies, muscle rigidity, Par-
crograms/kg daily in 2 divided doses (maxi- kinsonism, salivary hypersecretion, sedation,
mum, 10 mg daily). sexual dysfunction, somnolence, tremor.
Tourette’s syndrome, by mouth, CHILD >5 years, Less Common: Dyspnea, edema, nausea, vomit-
initially 0.25-0.5 mg once daily, increase to ing.
0.05 mg/kg daily (maximum, 5 mg). Rare: Agranulocytosis, anaphylaxis, bronchospasm,
NOTE: May be given in 2 or 3 divided doses. convulsions, gynecomastia, headache, hepati-
tis, hypersensitivity reactions, hypertension,
Dose Adjustments:
hyperthermia, hypoglycemia, hypothermia, in-
Elderly:
appropriate antidiuretic hormone secretion,
Halve the adult dose.
neuroleptic malignant syndrome, photosensi-
Renal Impairment:
tivity reactions and pigmentation, priapism,
For mild to moderate renal impairment, dose reduc-
psychotic disorders, QT prolongation, Ste-
tion is warranted due to increased cerebral
vens-Johnson syndrome, sweating, toxic epi-
sensitivity (start with small dose); for severe
dermal necrolysis, weight loss.
impairment, the patient should be referred to a
specialist. Drug Interactions:
NOTE: Haloperidol is a substrate for CYP enzymes (see
Precautions: Appendix); its plasma concentration may be affected
WARNING: Patients with dementia-related psychosis who by various drugs, which act as enzyme inducers or
are treated with antipsychotic drugs are at increased inhibitors.
risk for death due to cardiovascular cause (e.g., heart Monitor closely with:
failure or sudden death) or infections (e.g., pneumo- Amitriptyline – increased plasma amitriptyline con-
nia). Not for dementia-related psychosis.
centration; may increase the risk of ventricular
Avoid abrupt withdrawal of treatment (should always arrhythmias
be gradual, and closely monitored to avoid Carbamazepine – antagonism of anticonvulsant
risk of acute withdrawal syndromes or rapid effect (convulsive threshold lowered); acceler-
relapse); in patients with Parkinson’s disease ated metabolism of haloperidol, reducing its
(may be exacerbated), epilepsy (and condi- plasma concentration.
tions predisposing to seizure disorders), de- Clomipramine – its plasma concentration is in-
pression, myasthenia gravis, prostatic hyper- creased, possibly increased risk of ventricular
trophy, hypothyroidism, or a susceptibility to arrhythmias.
angle-closure glaucoma; dose adjustment CNS depressants (e.g., alcohol, sedatives, and
may be necessary if the patient started or tranquilizers) – haloperidol causes CNS de-
stopped smoking during treatment; thyrotoxi- pression; administration with these drugs may
cosis; arteriosclerosis, and cardiovascular lead to enhanced adverse effects (e.g., seda-
disorders (an ECG may be required), includ- tion).
ing risk for prolonged QT interval; metabolic Codeine – enhanced sedative and hypotensive
disturbances (hypokalemia, hypocalcemia or effect.
hypomagnesemia); cerebrovascular disorders, Drugs increasing blood glucose concentration (e.g.,
respiratory disease, acute infections. glucocorticoids, other antipsychotics, calcineu-
Hepatic impairment (avoid use; antipsychotic drugs rin inhibitors, high-dose thiazide diuretics and
can precipitate coma if used in hepatic im- somatropin) – haloperidol can increase blood
pairment); leukopenia (blood count is required glucose concentration, and may increase risk
if with unexplained fever or infection); photo- of hyperglycemia if given with these drugs.
sensitization may occur with higher doses (pa- Drugs which reduce blood pressure (see Appendix
tients should avoid direct sunlight); history of – Table D) – antipsychotics can cause hypo-
jaundice; hypotension (when administered tension and, if given with these drugs, may
IM). have enhanced hypotensive effects.
Elderly, particularly in very hot or very cold weather Fluoxetine – increased plasma haloperidol concen-
(associated with a small increased risk of mor- tration.
tality, and an increased risk of stroke or tran- Lithium – increased risk of extrapyramidal effects.
sient ischemic attack; risk of postural hypo- Metoclopramide – increased risk of extrapyramidal
tension, and to hyper- and hypothermia); chil- effects.
dren and adolescents. Morphine – enhanced hypotensive and sedative
Pregnancy (third trimester: depresses neonatal effects.
respiration; extrapyramidal effects and with- Procainamide – increased risk of ventricular ar-
drawal syndrome have been reported); breast- rhythmias.
feeding (possible risk of adverse effects; Quinidine – increased risk of ventricular arrhythmi-
monitor infant for drowsiness). as.
SKILLED TASKS. May impair ability to perform skilled Reserpine – increased risk of extrapyramidal ef-
tasks, such as operating machinery or driving.
fects.
Adverse Drug Reactions: Ritonavir – possibly increased haloperidol concen-
NOTE: Haloperidol has less sedative effects, and fewer tration.
hypotensive and anticholinergic symptoms. Avoid concomitant use with:
Common: Constipation, depression, dryness of Anticholinergic drugs or other drugs with anticholin-
mouth, EPS, specifically acute dystonia and ergic effects (see Appendix – Table A) –
135
PNF new 161 new.pdf 1 1/6/15 6:55 PM
haloperidol has anticholinergic effects; admin- tion; myeloproliferative disorders; severe CNS
haloperidol
istration withhas these anticholinergic
drugs increases effects;theadmin-
risk of tion; myeloproliferative
depression; disorders;
comatose states; severeforCNS
lactation; IM,
istration with
adverse effects these drugs increases
(including the risk of
central anticholiner- depression;
heart surgery. comatose states; lactation; for IM,
adverse
gic effects
delirium that(including central anticholiner-
is often missed); avoid these heart surgery.
gic delirium that is often missed); avoid these 'RVH
combinations if possible (if a combination is 'RVH I disorder (manic or mixed episodes), by
combinations
required, monitor if possible
the patient (if aandcombination
reduce dose is Bipolar
Bipolar I disorder
$'8/7, (manic
start or mixed
at 10 mg or episodes),
15 mg once by
ifrequired,
necessary).monitor the patient and reduce dose mouth,
mouth,$'8/7$'8/7,(instart at 10 mg or 15lithium
mg once
if necessary). daily; combination with or
Artemether + lumefantrine – these may result to daily; $'8/7 (inatcombination with lithium or
Artemether + lumefantrine – these may result to valproate), start 10 mg once daily; $'2
potentially hazardous interactions when given valproate), start $'2
potentially hazardous interactions when given /(6&(17, start at
at 10 mgmg
2.5-5 onceoncedaily;
daily ad-
concomitantly with haloperidol. /(6&(17, startonce
at 2.5-5
concomitantly with haloperidol. justed to 10 mg daily. mg once daily ad-
Atropine – this may reduce effects of haloperidol. justed episodes
to 10 mg once daily. with bipolar I dis-
Atropine ––this Depressive associated
Biperiden thismaymayreducereduceeffectseffectsofofhaloperidol.
haloperidol. Depressive
Biperiden ––this may reduce effects of haloperidol. order episodes associated
(in combination withwith bipolar I dis-
fluoxetine), by
Dopamine antagonism of hypertensive effect. order (in combination
Dopamine –agonists
antagonism of hypertensive $'8/7, start atwith
5 mg fluoxetine), by
once daily;
cabergoline,effect.
mouth,
Dopamine (e.g., pergolide $'8/7, start at 5 mg
Dopamine agonists –(e.g., cabergoline, pergolide
mouth, and
&+,/' $'2/(6&(17, start once
at 2.5daily;
mg
and levodopa) antagonism; haloperidol can &+,/' and $'2/(6&(17, start at 2.5 mg
and levodopa) – antagonism; once daily.
reduce their therapeutic effect. haloperidol can once daily.
Monotherapy for mania, by mouth, $'8/7 and
Drugsreduce
which their
prolongtherapeutic
QT interval effect.
(see Appendix –
DrugsTable
whichB)prolong QT Antimalarials
interval (see –Appendix –
Monotherapy
&+,/' 12-18 for mania,
years, by mg daily$'8/7
15 mouth, adjustedandto
and other the QT in- &+,/'range 12-18ofyears, 15 daily
mg daily adjusted to
Table may
terval B) and other Antimalarials
increase if haloperidol – is the
given QTwith
in- usual 5-20 mg (doses >15 mg
terval may increase if haloperidol is arrhythmi-
given with usual
is givenrange onlyofafter
5-20reassessment;
mg daily (doses >15 mg
maximum,
these drugs; increasing the risk of is given only after reassessment; maximum,
these drugs; increasing the risk of arrhythmi-
as. 20 mg daily).
as. – antagonism of hypertensive effect. 127(20 mg daily).monotherapy is not indicated for the
Olanzapine
Ephedrine 127(treatment
Olanzapine monotherapy
of depressive is notassociated
episodes indicated with
for the
bi-
Ephedrine – –antagonism
Epinephrine antagonismofofhypertensivehypertensiveeffect. effect. treatment of depressive episodes associated with bi-
polar I disorder and resistant depression (treatment).
Epinephrine – –antagonism
Ethosuximide antagonism of of
hypertensive
anticonvulsant effect.
effect polar I disorder and resistant depression (treatment).
Resistant depression (treatment), by mouth, $'8/7
Ethosuximide – antagonism of anticonvulsant effect Resistant depression (treatment), by mouth, $'8/7
(convulsive threshold lowered). (in combination with fluoxetine), start at 5 mg
(convulsive
Levodopa threshold
– haloperidol lowered). the effects of
antagonizes (in combination
once daily. with fluoxetine), start at 5 mg
Levodopa – haloperidol antagonizes the effects of
levodopa. once daily.
Schizophrenia, by mouth, $'8/7 >18 years, start
levodopa.– antagonism of anticonvulsant effect
Phenobarbital Schizophrenia,
at 5-10 mgbyonce daily$'8/7
mouth, >18
adjusted years,range
to usual start
Phenobarbital – antagonism
threshold of anticonvulsant effect at 5-20
5-10 mg
mg daily
once (doses
daily adjusted
(convulsive lowered); accelerated of >10 mgtodaily
usual
is range
given
(convulsive ofthreshold
metabolism haloperidol, reducingaccelerated
lowered); its plasma of 5-20
only mg reassessment;
after daily (doses >10 mg daily is20given
maximum, mg
metabolism of haloperidol, reducing its plasma
concentration. only after reassessment; maximum, 20 mg
daily); &+,/', refer to a specialist.
concentration.
Phenytoin – antagonism of anticonvulsant effect daily); &+,/', refer to a specialist.
Phenytoin – antagonism
(convulsive threshold of anticonvulsant effect
lowered). 'RVH$GMXVWPHQWV
(convulsive threshold lowered). of haloperidol, 'RVH$GMXVWPHQWV
Rifampicin – accelerated metabolism Elderly:
Rifampicin
reducing– accelerated
its plasma metabolism
concentration. of haloperidol, Elderly:
If olanzapine is necessary, use low dose.
reducing its drugsplasma concentration. If olanzapine is necessary, use low dose.
Seizure-inducing (see Appendix – Table C) – Renal Impairment:
Seizure-inducing
antipsychotics drugs can(seepossibly
Appendixlower – Table C) –
seizure
Renal
For mild Impairment:
to moderate renal impairment, dose reduc-
antipsychotics can possibly For mild
tiontoismoderate renal
dueimpairment, dosecerebral
reduc-
threshold; administration with lower
these seizure
drugs warranted to increased
threshold; administration with these drugs tion is warranted
sensitivity duesmall
(start with to increased
dose). Forcerebral
severe
may increase the risk of seizures.
mayacidincrease the risk ofofseizures. sensitivity (start
impairment, with small
the patient dose).
should For severe
be referred to a
Valproic – antagonism anticonvulsant effect
Valproic acid – antagonism of anticonvulsant effect impairment, the patient should be referred to a
specialist.
(convulsive threshold lowered).
(convulsive threshold lowered). specialist.
$GPLQLVWUDWLRQ May be taken with or without food; 3UHFDXWLRQV
$GPLQLVWUDWLRQ May be meals
taken to with or without food; 3UHFDXWLRQV

may be taken with minimize GI irrita- :$51,1*: Elderly patients with dementia-related psychosis

may be
tion; taken should
patients with meals remainto minimize
supine, GI andirrita-
the :$51,1*: Elderly
treated with patients with dementia-related
antipsychotic drugs (includingpsychosis
olanzap-
tion;monitored,
BP patients should for 30 remain
minutessupine,
after IM and the
injec- treated
ine) are with
at anantipsychotic
increased risk drugs (including
of death due toolanzap-
cardio-
BP monitored, for 30 minutes after IM injec- ine) are at
vascular an increased
(e.g., risk sudden
heart failure, of deathdeath)
due toorcardio-
infec-
tion. For long-acting injection, divided injection vascular
tion. For long-acting injection, divided injection tions (e.g.,(e.g., heart failure, sudden death) or infec-
pneumonia).
volumes >3 mL in half, and give at 2 sites. tions (e.g., pneumonia).
Not for dementia-related psychosis.
volumes >3 mL inChalf, and give at 2 sites.
3UHJQDQF\&DWHJRU\ Not for dementia-related psychosis.
3UHJQDQF\&DWHJRU\ C Withdrawal after therapy should always be gradual
Withdrawal after therapy
and closely monitoredshould alwaysrisk
(to avoid beofgradual
acute
and closely syndromes
withdrawal monitored (toand avoid risk relapse);
rapid of acute
withdrawal syndromes and rapid
dose adjustment may be necessary if smoking relapse);
OLANZAPINE dose started,
adjustment
OLANZAPINE was or may be necessary
stopped, during iftreatment;
smoking
was started, or
cardiovascular stopped,
disorders (anduring
ECG may treatment;
be re-
2UDO5 mg and 10 mg tablet
2UDO5 mg and 10 mg tablet cardiovascular
quired); suicidedisorders (an ECG may
attempt (possibility be re-
of suicide
A dibenzodiazepine-derived, second-generation quired); suicide attempt (possibility of
is inherent; requires close supervision of high- suicide
A dibenzodiazepine-derived, second-generation
(atypical) antipsychotic, which is a D 1 , D 2 , D 4 , is inherent; requires close supervision of high-
risk patients).
(atypical)
5-HT antipsychotic, which is a D 1 , D 2 , D 4 ,
2 , histamine-1-, and muscarinic-receptor risk patients).
Hyperglycemia (may be extreme in some cases;
5-HT 2 , histamine-1-, and muscarinic-receptor Hyperglycemia
antagonist, and is a homologue of clozapine. associated(may with be extreme in hyperosmolar
ketoacidosis, some cases;
antagonist, and is a homologue of clozapine. associated with ketoacidosis,
,QGLFDWLRQV Schizophrenia and related psychoses; coma and death); diabetes (risk hyperosmolar
of ketoacido-
,QGLFDWLRQV Schizophrenia and related psychoses; comaweight
sis); and death); diabetes (risk of
gain, hyperlipidemia; ketoacido-
hyperprolac-
monotherapy or combination therapy for ma- sis); weight gain, hyperlipidemia; hyperprolac-
monotherapy
nia, and preventor combination
recurrence intherapy
bipolarfordisor-
ma- tinemia.
nia, and prevent recurrence in bipolar disor- tinemia. neutropenia, and agranulocytosis
Leukopenia,
der. Leukopenia,
der. (monitor neutropenia,
CBC frequently; and agranulocytosis
discontinuation
&RQWUDLQGLFDWLRQV Known hypersensitivity to (monitorbe CBC
should frequently;
considered discontinuation
at the first sign of de-
&RQWUDLQGLFDWLRQV
olanzapine or any Known hypersensitivity
component of the formula- to should be considered at the
cline in WBC with the absence of otherfirst sign causa-
of de-
olanzapine or any component of the formula- cline in WBC with the absence of other causa-
136
136
tive factors); myeloproliferative disease; bone Drugs increasing blood glucose concentration (e.g.,
marrow depression; blood dyscrasia. glucocorticoids, other antipsychotics, calcineu-
Hepatic impairment (avoid use; antipsychotic drugs rin inhibitors, high-dose thiazide diuretics and
can precipitate coma if used in hepatic im- somatropin) – olanzapine can increase blood
pairment); history of jaundice. glucose concentration, and may increase risk
Neurologic disorders; cerebrovascular disease; of hyperglycemia if given with these drugs.
Parkinson’s disease (may be exacerbated), Drugs which reduce blood pressure (see Appendix
epilepsy (and conditions predisposing to sei- – Table D) – antipsychotics can cause hypo-
zure disorders), depression, myasthenia tension and, if given with these drugs, may
gravis, Alzheimer’s disease; neuroleptic ma- have enhanced hypotensive effects.
lignant syndrome (discontinue immediately Lorazepam – increased somnolence with IM
and monitor closely). olanzapine.
Prostatic hypertrophy; susceptibility to angle-closure Ritonavir – this may increase the metabolism of
glaucoma; severe respiratory disease; breast olanzapine, reducing its concentration and
cancer; paralytic ileus; photosensitization may possibly its activity.
occur with higher doses (patients should avoid Avoid concomitant use with:
direct sunlight). Anticholinergic drugs or other drugs with anticholin-
Elderly, particularly in very hot or very cold weather ergic effects (see Appendix – Table A) –
(associated with a small increased risk of mor- olanzapine has anticholinergic effects; admin-
tality and an increased risk of stroke or transi- istration with these drugs increases the risk of
ent ischemic attack; risk of postural hypoten- adverse effects (including central anticholiner-
sion, and to hyper- and hypothermia); gic delirium that is often missed); avoid these
hypovolemia; dehydration. combinations if possible (if a combination is
Pregnancy (in the third trimester: neonatal lethargy, required, monitor the patient and reduce dose
tremor, hypertonia, extrapyramidal effects and if necessary).
withdrawal syndrome have been reported; use Dopamine agonists (e.g., cabergoline, pergolide
only if potential benefit outweighs risk); breast- and levodopa) – antagonism; olanzapine can
feeding (avoid use). reduce their therapeutic effect.
NOTE: Check glucose tolerance if patient gains weight. Seizure-inducing drugs (see Appendix – Table C) –
SKILLED TASKS. May impair ability to perform skilled antipsychotics can possibly lower seizure
tasks, such as operating machinery or driving.
threshold; administration with these drugs
Adverse Drug Reactions: may increase the risk of seizures.
Common: Abdominal pain, abnormal gait, akathis- Administration: May be taken with or without food.
ia, constipation, dizziness, drowsiness, dry
For long-acting IM, inject deep into the gluteal
mouth, fatigue, hallucinations, headache, hy-
muscle.
perglycemia, increased appetite, mild anti-
muscarinic effects, peripheral edema, person- Pregnancy Category: C
ality disorder, postural hypotension, sedation
and delirium after long-acting injection; som-
nolence, tremor, type 2 diabetes mellitus,
weight gain. RISPERIDONE
Less Common: Bradycardia, elevation of liver
aminotransferases, EPS, QT prolongation, Oral: 1 mg, 2 mg, 3 mg and 4 mg tablet
urinary incontinence. 1 mg/mL oral solution, 100 mL
Rare: Angle-closure glaucoma, hepatitis, hypercho- Inj.: 25 mg and 37.5 mg MR powder for suspen-
lesterolemia, hyperlipidemia, hypothermia, sion, vial + 2 mL diluent in pre-filled syringe
leukopenia, neuroleptic malignant syndrome, (IM)
neutropenia, pancreatitis, priapism, rhabdo- NOTE: (IM) for use only by physicians who have completed
myolysis, seizure, thrombocytopenia, urinary training in the proper administration of risperidone.
retention, VTE.
A benzisoxazole-derived, second-generation (atypi-
Drug Interactions: cal) antipsychotic having less side effects, and
NOTE: Olanzapine is a substrate for CYP enzymes (see is efficacious in treatment-resistant patients
Appendix); its concentration may be affected by vari- and against negative symptoms, such as
ous drugs, which act as enzyme inducers or inhibi- emotional withdrawal, poverty of speech and
tors.
movement, anhedonia and loss of initiative.
Antihypertensive agents – enhanced antihyperten- Indications: Schizophrenia and related psychoses
sive effect. (acute and chronic); short-term treatment of
Carbamazepine – this may increase olanzapine’s acute mania; maintenance treatment of bipo-
metabolism, decreasing its concentration and lar I disorder; persistent aggression; behavior
possibly its activity. disturbance in dementia.
CNS depressants (e.g., alcohol, sedatives and
tranquilizers) – olanzapine causes CNS de- Contraindications: Known hypersensitivity to
pression; administration with these drugs may risperidone and paliperidone, or any compo-
enhance its adverse effects (e.g., sedation). nent of the formulation; marked CNS depres-
sion from any cause.
137
Dose: cerebrovascular events, including stroke, in
Behavior disturbance in dementia, by mouth, the elderly with dementia-related psychosis;
ADULT, 0.25 mg twice daily, increasing by low white cell count or previous blood dyscra-
0.25 mg daily every 2 or more days (usual sias (may increase risk of clinically significant
dose range: 0.5-1 mg twice daily). dyscrasia).
Mania, by mouth, ADULT, initially 2 mg once daily, EPS; neuroleptic malignant syndrome; tardive dys-
increased if necessary in steps of 1 mg daily kinesia; hyperglycemia and diabetes mellitus
(usual dose range 1-6 mg daily); ELDERLY, (antipsychotics may increase blood glucose);
initially 500 micrograms twice daily increased hyperprolactinemia.
in steps of 500 micrograms twice daily to 1-2 Orthostatic hypotension; potential for cognitive and
mg twice daily; CHILD, refer to a specialist. motor impairment; dyslipidemia; esophageal
Mania (maintenance), long-acting IM, ADULT, 25 aspiration; disruption of body temperature
mg every 2 weeks; increase if necessary to regulation; Parkinson’s disease (risk of aggra-
maximum of 37.5-50 mg every 2 weeks. vation and potential for drug interactions); epi-
NOTE: Give supplemental oral antipsychotic for the first 3 lepsy (antipsychotics may alter EEG or lower
weeks. Do not adjust dose more frequently than every seizure threshold; use with caution in people
4 weeks. Effects of a dose increase will not be seen
with, or at risk of, seizures); hyperthyroidism
for 3 weeks.
(increases risk of dystonia); risk factors for
Persistent aggression (in Alzheimer’s dementia) , by
mouth, ADULT, initially 250 micrograms twice prolonged QT interval (increase the risk of ar-
rhythmia and sudden death, particularly when
daily, increased according to response in
steps of 250 micrograms twice daily on alter- given IV); shock (drug-related hypotension
nate days; usual dose, 500 micrograms twice may worsen symptoms); suicidal ideation; se-
daily (up to 1 mg twice daily). dation; weight gain; psychological and physi-
Psychoses (acute/chronic), by mouth, ADULT, 2 mg cal dependence.
Pregnancy, refer to a specialist (avoid antipsychot-
in 1-2 divided doses on first day then 4 mg in
1-2 divided doses on second day (slower titra- ics if possible, or use the lowest effective dos-
tion appropriate in some patients); usual dose es when antipsychotic treatment is neces-
range 4-6 mg daily; doses above 10 mg daily sary); breastfeeding (avoid its use if possible;
only if benefit is considered to outweigh risk should not breastfeed during therapy or for 12
(maximum, 16 mg daily); ELDERLY, initially weeks after the last injection).
500 micrograms twice daily increased in steps Adverse Drug Reactions:
of 500 micrograms twice daily to 1-2 mg twice Common: Abdominal pain, akathisia, anxiety,
daily. cough, dizziness, fatigue, fever, headache, in-
Schizophrenia, by mouth, ADULT, 1 mg twice daily, creased appetite, insomnia, nausea, sedation,
increasing by 1 mg twice daily each day (usu- tremor, vomiting, weight gain.
al range: 4-6 mg daily; daily doses greater Less Common: Allergic reaction, anemia, angi-
than 4 mg increase the risk of EPS); long- oedema, AV block first-degree; bradycardia,
acting IM, ADULT, 25 mg every 2 weeks; in- chest pain, EPS (other than akathisia), hyper-
crease if necessary to maximum of 37.5-50 kinesia, hypertension, hypotension, inconti-
mg every 2 weeks. NOTE: Give supplemental oral nence, palpitation, peripheral edema, QT pro-
antipsychotic for the first 3 weeks. Do not adjust dose longation, rash, rhinitis, sexual adverse ef-
more frequently than every 4 weeks. Effects of a dose
fects, somnolence, tachycardia.
increase will not be seen for 3 weeks.
Rare: Dyslipidemia, exacerbation of type 2 DM;
Dose Adjustments: hepatotoxicity, stroke, TIA, tardive dyskinesia,
Elderly: water intoxication due to SIADH or polydipsia.
Halve the usual starting and incremental doses.
Drug Interactions:
Renal Impairment:
NOTE: Risperidone is a substrate for CYP enzymes (see
For mild to moderate renal impairment, dose reduc- Appendix); its concentration may be affected by vari-
tion is warranted; for severe impairment, the ous drugs, which act as enzyme inducers or inhibi-
patient should be referred to a specialist. tors.
Hepatic Impairment: Monitor closely with:
For mild to moderate hepatic impairment, use half Acetylcholinesterase inhibitors (Central) – these
the usual starting and incremental doses; for may enhance the central neurotoxic effect of
severe impairment, the patient should be re- antipsychotics.
ferred to a specialist. Antacids – there is decreased absorption when
these are given with risperidone within 1 to 2
Precautions:
hours.
WARNING: Elderly patients with dementia-related psychosis Anticholinergics – risperidone may enhance the
treated with antipsychotic drugs are at an increased
adverse effect of other anticholinergics.
risk of death due to either cardiovascular cause (e.g.,
heart failure or sudden death) or infections (e.g., Carbamazepine – this may decrease the serum
pneumonia). Risperidone should not be used in pa- concentration of risperidone.
tients with dementia-related psychosis. CNS depressants (e.g., alcohol, sedatives and
Altered cardiac conduction (life-threatening ar- tranquilizers) – risperidone causes CNS de-
rhythmias have occurred; use caution with his- pression; administration with these drugs may
tory of cardiac abnormalities); this may cause enhance its adverse effects (e.g., sedation).
anticholinergic effects; increased incidence of
138
Drugs increasing blood glucose concentration (e.g., ly, the usual dosage being 400-600 mg daily
glucocorticoids, other antipsychotics, calcineu- given in 2-3 divided doses. In acute mania,
rin inhibitors, high-dose thiazide diuretics and the dosage is increased rather quickly,
somatropin) – risperidone can increase blood whereas small dosage increments are rec-
glucose concentration, and may increase risk ommended for maintenance therapy in order
of hyperglycemia if given with these drugs. to provide for optimal tolerability.
Drugs which prolong QT interval (see Appendix –
Dose Adjustments:
Table B) – the QT interval may increase if
risperidone is given with these drugs; increas- Hepatic Impairment:
ing the risk of arrhythmias. Metabolism is impaired in advanced liver disease.
Drugs which reduce blood pressure (see Appendix Renal Impairment:
– Table D) – antipsychotics can cause orthos- Use with caution.
tatic hypotension and, if given with these Elderly:
drugs, may have enhanced hypotensive ef- Dosage should be selected with caution. Generally,
fects. lower dosages are started.
Loop diuretics – may enhance the adverse effect of See under Anticonvulsant/Antiepileptic Medicines
risperidone. for crucial information about Warnings and
Avoid concomitant use with: Precautions, Drug Interactions and other in-
Dopamine agonists (e.g., cabergoline, pergolide formation.
and levodopa) – antagonism; risperidone can
reduce their therapeutic effect.
Seizure-inducing drugs (see Appendix – Table C) –
antipsychotics can possibly lower seizure VALPROATE
threshold; administration with these drugs
may increase the risk of seizures. Oral: 250 mg/5 mL syrup valproic acid, 120 ml
Administration: Give long-acting IM deep into 250 mg divalproex sodium tablet (sodium
either the deltoid or gluteal muscle; avoid in- valproate and valproic acid compound in a
advertent injection into vasculature. Injection 1:1 molar relationship)
should alternate between the two arms or but- Valproate inhibits sustained repetitive firing of corti-
tocks. Oral dosage forms may be adminis- cal neurons by prolonging recovery of voltage-
tered without regard to meals. activated Na+ channels from inactivation.
Pregnancy Category: C Indications: Manic episodes associated with bipo-
lar disorder. There are no systemically ob-
tained data to support the benefits of divalpro-
MOOD STABILIZERS ex sodium in long-term treatment of bipolar
disorder.
CARBAMAZEPINE Contraindications: Known hypersensitivity to

valproic acid or any component of the formula-
Oral: 100 mg, 200 mg, and 400 mg tablet tion; hepatic disease or significant hepatic
dysfunction; urea cycle disorders; hereditary
200 mg and 400 mg CR (modified-release)
neurometabolic syndromes caused by DNA
tablet
mutations of the mitochondrial DNA polymer-
100 mg in 5 mL syrup, 120 mL
ase-gamma (POLG) gene (e.g., Alpers Hut-
It is an iminostilbene that limits the firing of action tenlocher Syndrome).
potentials evoked by a sustained depolariza-
Dose:
tion in cortical neurons mediated by a slowing
of the rate of recovery of voltage-activated Manic episodes associated with bipolar disorder: by
Na+ channels from inactivation. mouth, the recommended initial dose is 750
mg in divided doses, may be increased as
Indications: Acute mania and maintenance therapy rapidly as possible to achieve the lowest ther-
of bipolar affective disorders. apeutic dose hat produces the desired clinical
effect or the desired plasma concentration
Contraindications: Known hypersensitivity to range (maximum dose, 60 mg/kg/day).
carbamazepine or structurally related drugs There are no systemically obtained data to
(e.g. tricyclic antidepressants), or any compo- support the benefits of divalproex sodium in
nent of the formulation; atrioventricular block; long-term treatment of bipolar disorder.
bone marrow depression; acute intermittent
porphyria; combination with monoamine- Dose Adjustments:
oxidase inhibitors (MAOIs)- before administer- Renal Impairment:
ing carbamazepine, MAOIs should be discon- Reduce dose; adjust according to free serum
tinued for 2 weeks or longer (see Drug Inter- valproic acid concentration.
actions). Hepatic Impairment:
Avoid if possible, hepatotoxicity and hepatic failure
Dose:
may occasionally occur, usually in the first six
Acute mania and maintenance therapy of bipolar months; avoid in active liver disease.
disorders: by mouth, about 400-1,600 mg dai-
139
Elderly:
Lower initial dose and slower increase in dosage,
regularly monitor fluid and nutritional intake
and increased somnolence and other side ef-
fects.
Precautions:
WARNING:
Hepatic failure resulting in fatalities has occurred, usually
during the first six months of treatment. Increased risk
for fatal hepatotoxicity is seen in: children <2 years
old, patients on multiple anticonvulsants, congenital
metabolic disorders, severe seizure disorders accom-
panied by mental retardation, or organic brain dis-
ease, hereditary neurometabolic syndromes (see
Contraindications). Patients and caregivers must be
instructed to monitor for and immediately report non-
specific symptoms, such as malaise, weakness, leth-
argy, facial edema, anorexia, and vomiting that may
precede the hepatotoxicity. Loss of seizure control
may also be seen. The drug should be discontinued
immediately in the presence of suspected or apparent
significant hepatic dysfunction.
Pancreatitis, which may be life-threatening, has been
reported. Some were hemorrhagic and progressed
rapidly from initial symptoms to death. Patients and
caregivers must be instructed to monitor for and im-
mediately report symptoms of abdominal pain, nau-
sea, vomiting, and/or anorexia. The drug should be
discontinued immediately.
Teratogenicity: may cause neural tube defects. Do not use
in women of child-bearing age unless the drug is es-
sential.
See under Anticonvulsant/Antiepileptic Medicines

for crucial information about Precautions,
Drug Interactions and other information.
140
BRONCHODILATORS
RESPIRATORY SYSTEM
ANTITUSSIVE SALBUTAMOL
Oral: 2 mg tablet (as sulfate)

BUTAMIRATE 4 mg MR and 8 mg MR tablet (as sulfate)
2 mg/5 mL syrup, 60 mL (as sulfate)
Oral: 50 mg MR tablet (as citrate) Inhalation:
7.5 mg/5 mL syrup, 60 mL and 120 mL MDI:
(as citrate) 100 micrograms/dose x 200 doses (as sulfate)
(spacer recommended)
A centrally-acting antitussive, which is neither
chemically nor pharmacologically related to Breath-Actuated MDI (autohaler):
the opioids, and is intended as a cough sup- 100 micrograms/dose x 400 doses (as sulfate)
pressant. Resp. Soln. (for nebulization):
1 mg/mL, 2.5 mL unit dose (as sulfate)
Indications: Chronic, non-productive, irritative
5 mg/mL, 10 mL multidose (as sulfate)
cough; symptomatic treatment of cough of 5 mg/mL, 20 mL multidose (as sulfate)
various origins.
A short-acting, beta 2 -adrenergic agonist used in the
treatment, or prevention of bronchospasm.
butamirate or any component of the formula-
tion; diabetes mellitus. Indications: Prophylaxis and treatment of asthma;
bronchospasm in patients with reversible ob-
Dose:
structive airway disease; prevention of exer-
Cough, by mouth, ADULT and CHILD >12 years, cise-induced bronchospasm.
10-20 mg every 4 hours or 30 mg every 6-8
hours; INFANT and CHILD 6-12 years, 1 Contraindications: Known hypersensitivity to
mg/kg/d divide every 6-8 hours; Alternatively, salbutamol or any component of the formula-
ADULT, 1 tablet 2-3 times daily; ADULT and tion; severe pre-eclampsia and eclampsia; in-
CHILD >9 years, 1-2 tablespoon 3 times a trauterine infection, intrauterine fetal death;
day; CHILD 1-9 years, 1-2 teaspoon syrup 2-3 ante-partum hemorrhage, placenta praevia
times daily. and cord compression; threatened miscar-
riage; cardiac disease.
Dose Adjustment:
Renal Impairment: Dose:
Eliminated renally; use with caution. Chronic asthma, by mouth, ADULT, 2-4 mg 3-4
times daily; in some patients, up to a maxi-
Precautions: mum of 8 mg 3-4 times daily; CHILD 6-12
Use in the first trimester of pregnancy is not rec- years, 2 mg 3-4 times daily; CHILD 2-6 years,
ommended (during the rest of pregnancy, use 1-2 mg 3-4 times daily; CHILD <2 years, 100
it only if drug therapy is essential); effects on micrograms/kg 4 times daily;
the ability to drive, or operate machinery (bu- Chronic asthma (as an adjunct in stepped treat-
tamirate may cause somnolence; caution ment), by aerosol inhalation, ADULT, 100-200
while driving or performing other tasks which micrograms (1-2 puffs) up to 3-4 times daily;
require alertness). CHILD, 100 micrograms (1 puff) 3-4 times dai-
Adverse Drug Reactions: ly, increased to 200 micrograms (2 puffs) 3-4
Rare: Diarrhea, dizziness, GI discomfort, nausea, times daily if necessary.
skin rash, somnolence, urticaria. Prophylaxis of exercise-induced bronchospasm, by
aerosol inhalation, ADULT, 200 micrograms
Drug Interactions: (2 puffs); CHILD, 100 micrograms (1 puff) in-
Avoid concomitant use with: creased to 200 micrograms (2 puffs) if re-
Expectorants – may lead to the stagnation of the quired.
mucus in the respiratory tract, increasing the Relief of acute bronchospasm, by aerosol inhala-
risk of bronchospasm and airways infection. tion, ADULT, 100-200 micrograms (1-2 puffs);
Penicillins, phenobarbital, salicylates and tetracy- CHILD, 100 micrograms (1 puff) increased to
clines – butamirate has been reported to be 200 micrograms (2 puffs) if necessary.
incompatible with these drugs. Severe acute asthma, chronic bronchospasm (un-
Administration: May be taken with or without food. responsive to conventional treatment), by in-
halation of nebulized solution, ADULT and
Pregnancy Category: C CHILD >18 months, 2.5 mg repeated up to 4
times daily; may be increased to 5 mg if nec-
essary (consider medical assessment since
alternative therapy may be indicated); CHILD
<18 months, clinical efficacy uncertain (tran-
sient hypoxemia may occur – consider oxygen
supplementation).
141
Dose Adjustments: Sympathomimetic amines (e.g., ephedrine, phe-
Elderly: nylephrine and pseudoephedrine) – possibly
Start with a lower dose than the usual adult dosage; result in excess sympathetic stimulation and
gradually increase if needed. sympathetic adverse effects (e.g., tremor,
Renal and Hepatic Impairment: tachycardia and headache).
Use with caution for high-dose treatments.
Administration: Tablet should be taken on an
Precautions: empty stomach. Take 1 hour before, or 2
WARNING: Excessive use and reliance on Beta 2 -agonists hours after, meals. Multidose solution for neb-
for the treatment of asthma without an anti- ulization may need dilution with 0.9% sodium
inflammatory agent have been associated with an in- chloride to obtain final volume for the nebuliz-
creased incidence of sudden deaths. Beta 2 -agonists er.
inhalation can occasionally cause paradoxical bron-
chospasm and hypoxemia. Pregnancy Category: C
Paradoxical bronchospasm may occur (should be
treated immediately with alternative therapy);
hyperthyroidism; myocardial insufficiency, ar-
rhythmias, susceptibility to QT-interval prolon- FLUTICASONE + SALMETEROL
gation, hypertension (risk of cardiovascular
adverse effects); diabetes mellitus, especially Inhalation:
IV administration (ketoacidosis reported; DPI:
monitor blood glucose); discontinue treatment 100 micrograms fluticasone (as propionate) + 50
if the patient develops signs of pulmonary micrograms salmeterol (as xinafoate) x 28 dos-
edema. es and 60 doses with appropriate accompany-
Pregnancy (high doses should be given through ing dispenser
inhalation only – parenteral use can affect the 250 micrograms fluticasone (as propionate) + 50
myometrium and may cause cardiac prob- micrograms salmeterol (as xinafoate) x 28 dos-
lems); breastfeeding (monitor infant; safe in es and 60 doses with appropriate accompany-
usual dosage). ing dispenser
500 micrograms fluticasone (as propionate) + 50
Adverse Drug Reactions: micrograms salmeterol (as xinafoate) x 28 dos-
Common: Cough, headache, musculoskeletal pain, es and 60 doses with appropriate accompany-
palpitations, throat irritation, tremor, upper ing dispenser
respiratory inflammation, viral respiratory in-
fections. A combination product containing an inhaled corti-
Less Common: Agitation, hyperactivity in children, costeroid, and a long-acting beta 2 -
hyperglycemia (high-dose), insomnia, tachy- adrenoceptor agonist, which is used for con-
cardia. trolling the symptoms of asthma.
Rare: Allergic reactions, hypokalemia, lactic acido- Indications: For asthma in patients aged 4 years
sis, paradoxical bronchospasm. and older; maintenance treatment of airflow
Drug Interactions: obstruction, and reduction of exacerbations in
Monitor closely with: patients with COPD.
NOTE: This is not indicated for the relief of acute bron-
Digoxin – possibly reduced plasma digoxin concen-
chospasm; this should be used only if the asthma is
tration. deemed to be not well-controlled with a long-term
Methyldopa – acute hypotension reported with asthma control medicine (e.g., inhaled corticoster-
salbutamol infusion. oids).
Beta-blockers – these may antagonize the thera- Contraindications: Primary treatment of status
peutic effect of beta 2 agonists and may pre- asthmaticus or acute episodes of asthma re-
quiring intensive measures; hypersensitivity to
cipitate asthma.
milk proteins, or any component of the formu-
Corticosteroids, theophylline and diuretics – serious
lation.
hypokalemia may occur with high doses of be-
ta 2 agonists; possibly increased risk of this Dose:
adverse effect when given with these drugs. Treatment of asthma, by inhalation, ADULT and
Drugs increasing blood glucose concentration (e.g., CHILD ≥12 years, 1 inhalation (100/50 to
glucocorticoids, antipsychotics, calcineurin in- 250/50) twice daily (starting dose is based on
hibitors, high-dose thiazide diuretics and so- asthma severity); CHILD 4 to 11 years, 1 in-
matropin) – beta 2 agonists increase blood halation 100/50 twice daily.
glucose concentration; may increase risk of Maintenance treatment of COPD, 1 inhalation
hyperglycemia when given with these drugs. 250/50 twice daily.
Drugs reducing potassium concentration (e.g.,
amphotericin B, and diuretics) – beta 2 ago- Dose Adjustment:
nists can reduce potassium concentration, in- Renal Impairment:
creasing the risk of hypokalemia; if given with Use with caution, but no adjustments necessary.
these drugs, there is enhanced risk of adverse Precautions:
effects. Deterioration of disease and acute episodes: do not
initiate in acutely deteriorating asthma or to
142
treat acute symptoms; use with additional
LABA (do not combine LABAs because of risk FOR CHRONIC OBSTRUCTIVE
of overdose); localized infections (Candida al- PULMONARY DISEASE
bicans infection of mouth and throat may oc-
cur); immunosuppression (potential worsening
of infections); pneumonia (increased risk in IPRATROPIUM
patients with COPD); cardiovascular and CNS
disorders; hypercorticism and adrenal sup- Inhalation:
pression; decreased bone mineral density; MDI:
growth effects; glaucoma and cataracts; met- 20 micrograms/dose x 200 doses (as bromide)
abolic effects (be alert to eosinophilic condi-
tions, hypokalemia and hyperglycemia); pa- Resp. Soln. (for nebulization):
tients with convulsive disorders, thyrotoxico- 250 micrograms/mL, 1 mL and 2 mL (unit dose) (as
sis, diabetes mellitus and ketoacidosis. bromide)
250 micrograms/mL, 20 mL (multidose) (as bro-
Adverse Drug Reactions: mide)
Common: Dizziness, dysphonia, headache, nau-
sea, palpitations, throat irritation, upper res- A selective, anticholinergic bronchodilator that is a
piratory tract infection and inflammation, trem- quaternary ammonium compound chemically
or, vomiting. related to atropine, and provides local, site-
Less Common: Agitation, hyperactivity in children, specific effect rather than a systemic effect.
hyperglycemia (high-dose), insomnia, tachy- Indications: Chronic asthma; chronic obstructive
cardia.
pulmonary disease, including chronic bronchi-
Rare: Allergic reactions, including urticaria, angi-
tis and emphysema.
oedema and anaphylaxis; hypokalemia, lactic
acidosis, paradoxical bronchospasm. Contraindications: Known hypersensitivity to
ipratropium or any component of the formula-
Drug Interactions: tion, and to atropine or any of its derivatives.
Beta-blockers – these may antagonize the thera- Dose:
peutic effect of beta 2 agonists and may pre- Adjunct in acute bronchospasm, by inhalation of
cipitate asthma and severe bronchospasm. nebulized solution, ADULT, 500 micrograms
Corticosteroids (e.g., hydrocortisone), diuretics repeated as required; CHILD 6-12 years, 250
(e.g., furosemide and hydrochlorothiazide) micrograms; maximum, 1 mg daily; CHILD
and theophylline – serious hypokalemia may <up to 6 years, 125-250 micrograms; maxi-
occur with high doses of beta 2 agonists; pos- mum, 1 mg daily.
sibly increased risk of this adverse effect Chronic asthma, chronic obstructive pulmonary
when given with these drugs. disease, by aerosol inhalation, ADULT, 20-40
CYP450 3A4 inhibitors (e.g., ritonavir) – may cause micrograms, 3-4 times daily; CHILD 6-12
systemic corticosteroid and cardiovascular ef- years, 20-40 micrograms 3 times daily; CHILD
fects (decreased metabolism). <up to 6 years, 20 micrograms 3 times daily.
Drugs increasing blood glucose concentration (e.g., Chronic obstructive pulmonary disease, by inhala-
glucocorticoids, antipsychotics, calcineurin in- tion of nebulized solution, ADULT, 250-500
hibitors, high-dose thiazide diuretics and so- micrograms 3-4 times daily.
matropin) – beta 2 agonists increase blood
glucose concentration; may increase the risk Dose Adjustments:
of hyperglycemia when given with these Renal and Hepatic Impairment:
drugs. Use drug with caution for mild to moderate impair-
Drugs reducing potassium concentration (e.g., ment; for severe impairment, the patient
amphotericin B and diuretics) – beta 2 agonists should be referred to a specialist.
can reduce potassium concentration, increas- Precautions:
ing the risk of hypokalemia; if given with these Although side- or adverse effects are less common
drugs; there is enhanced risk of adverse ef- at usual therapeutic doses, their potential oc-
fects. currence still exists when given beyond rec-
Sympathomimetic amines (e.g., ephedrine, phe- ommended levels.
nylephrine and pseudoephedrine) – possibly Prostatic hypertrophy; glaucoma (symptoms may
result in excess sympathetic stimulation and worsen; care needed to protect the patient's
sympathetic adverse effects (e.g., tremor, eyes from drug powder or nebulized drug);
tachycardia and headache). myasthenia gravis; medical supervision is
Administration: Should be administered twice daily necessary for first dose of nebulized solution
every day by the orally inhaled route only; af- (potential risk of paradoxical bronchospasm);
ter inhalation, the patient should rinse the paradoxical bronchospasm (may occur with
mouth with water without swallowing. use of inhaled bronchodilating agents; this
should be distinguished from inadequate re-
Pregnancy Category: C sponse); elderly (they may find it difficult to
use the MDI; a spacer device may be useful;
monitor urinary function in elderly men with
143
benign prostatic hypertrophy while on this Contraindications: Known hypersensitivity to any
medication). of the ingredients; hypersensitivity to atropine
Pregnancy (inhaled ipratropium may be recom- or any of its derivatives; tachyarrhythmias;
mended for use as additional therapy for and hypertrophic obstructive cardiomyopathy
pregnant women with severe asthma exacer- [See also under individual monographs].
bations); breastfeeding (caution when admin-
istering to nursing women). Dose:
Bronchospasm, by inhalation, ADULT, one inhala-
Adverse Drug Reactions: tion four times a day, should not exceed six
Common: Back pain, bronchitis, COPD exacerba- inhalations in 24 hours.
tion, cough, dry mouth, dyspepsia, dyspnea, Treatment of acute attacks, by inhalation using a
headache, influenza-like symptoms, nausea, suitable nebulizer or an intermittent positive
sinusitis, taste disturbance, throat irritation, pressure ventilator, ADULT, 1 unit-dose vial
urinary tract infections. (2 unit-dose vials may be required for severe
Less Common: Blurred vision, dizziness. cases, which have not been relieved by 1 unit-
Rare: Acute closed-angle glaucoma, allergy (urti- dose vial; patients should consult the physi-
caria, rash, angioedema, anaphylaxis), atrial cian immediately); for maintenance treatment,
fibrillation, constipation, dental caries, dryness 1 unit-dose vial for 3-4 times daily.
of skin, palpitations, tachycardia, urinary re- NOTE: The unit-dose vial should not be taken orally or
tention. administered parenterally. The content does not need
to be diluted for nebulization.
Drug Interactions:
Dose Adjustments:
Analgesics (Opioids) – anticholinergics may en- Renal and Hepatic Impairment:
hance their adverse effect, specifically the risk Use drug with caution for mild to moderate impair-
of constipation and urinary retention. ment; for severe impairment, the patient
Anticholinergic drugs or other drugs with anticholin- should be referred to a specialist.
ergic effects (see Appendix – Table A) – these Precautions:
increase ipratropium’s therapeutic effect and Some preparations contain soya lecithin (do not use
risk of adverse effects (including central anti- in patients allergic to soya lecithin or related
cholinergic delirium that is often missed); food products, such as soybean and peanut).
avoid these combinations if possible (if com- Patients with cardiovascular system disorders (use
bination is required, monitor the patient, and with caution due to beta-adrenergic stimula-
reduce dose). tion); urinary retention (use with caution in pa-
Thiazide diuretics – their serum concentration may tients with prostatic hyperplasia or bladder-
be increased by anticholinergics. neck obstruction); paradoxical bronchospasm
Administration: Dilute solution for nebulization to (discontinue immediately and treat with alter-
native therapy); ocular effects (avoid spraying
2-3 mL with sodium chloride 0.9%. Prior to ini-
into the eyes; contact a physician if blurred vi-
tial use,
NOTE: Do not reduce or stop inhaled corticosteroids even if sion, halos, or other visual disturbances oc-
the patient feels better after starting this drug. Do not cur); carefully monitor patients with narrow-
let the mist from the nebulizer get into the eyes (close angle glaucoma; hypersensitivity reactions
eyes or wear eye protection). (discontinue treatment); in patients with hyper-
Pregnancy Category: B thyroidism, diabetes mellitus or convulsive
disorders.
Pregnancy (restricted to those patients in whom the
benefits clearly outweigh the risk; potential be-
ta-agonist interference with uterine contractili-
IPRATROPIUM + SALBUTAMOL ty); safety and efficacy have not been estab-
lished for children.
Inhalation:
MDI: Adverse Drug Reactions:
21 micrograms ipratropium (as bromide) + 120 Common: Back pain, bronchitis, cough, dryness of
micrograms salbutamol x 200 doses x 10 mL mouth, dyspepsia, dyspnea, headache, influ-
Resp. Soln. (for nebulization): enza-like symptoms, musculoskeletal pain,
500 micrograms ipratropium (as bromide anhy- myalgia, nasopharyngitis, nausea, pharyngitis,
drous) + 2.5 mg salbutamol (as base) x 2.5 mL sinusitis, taste disturbance, throat irritation,
tremor, upper respiratory inflammation and in-
(unit dose)
fection, urinary tract infection.
A combination of a cholinergic antagonist and a Less Common: Agitation, blurred vision, diarrhea,
short-acting, beta 2 -adrenoceptor agonist, dizziness, fatigue, hyperactivity in children,
which is used for the treatment of chronic ob- hyperglycemia (high-dose), hypertension, in-
structive pulmonary diseases; in which mono- somnia, vomiting.
therapy is deemed to be insufficient. Rare: Acute closed-angle glaucoma, arrhythmias,
Indications: Treatment of COPD in patients who asthenia, atrial fibrillation, chest discomfort,
are currently on a regular bronchodilator, who constipation, dental caries, dryness of skin,
continue to have evidence of bronchospasm, eye pain, hypersensitivity reactions (including
and require a second bronchodilator. anaphylaxis, angioedema, bronchospasm,
144
rash, urticaria and oropharyngeal edema);
hypokalemia, palpitations, paradoxical bron- CORTICOSTEROIDS
chospasm, tachycardia, urinary retention,
wheezing.
Drug Interactions: HYDROCORTISONE
Corticosteroids (e.g., hydrocortisone), diuretics Inj.: 50 mg/mL, 2 mL vial (IM, IV)
(e.g., furosemide and hydrochlorothiazide) (as sodium succinate)
and theophylline – serious hypokalemia may 125 mg/mL, 2 mL and 4 mL vial (IV)
occur with high doses of beta 2 agonists; pos- (as sodium succinate)
sibly increased risk of this adverse effect Powder, 100 mg, 250 mg (IV)
when given with these drugs. (as sodium succinate)
Drugs reducing potassium concentration (e.g., A glucocorticoid used for replacement therapy in
amphotericin B and diuretics) – beta 2 agonists adrenal insufficiency, management of auto-
can reduce potassium concentration, increas- immune and inflammatory conditions, and as
ing the risk of hypokalemia; if given with these emergency management of anaphylaxis and
drugs, there is enhanced risk of adverse ef- severe systemic allergies.
fects.
MAO inhibitors and Tricyclic Antidepressants – Indication: Acute severe asthma.
these may potentiate effect of salbutamol on Contraindications: See under Endocrine System
the vascular system.
and Steroids – Corticosteroids.
Anticholinergic drugs or other drugs with anticholin- Dose:
ergic effects (see Appendix – Table A) – these Acute severe asthma, by IV injection, ADULT, 100
increase the combination’s therapeutic effect mg every 6 hours; CHILD, 4 mg/kg every 4-6
and adverse effects (including central anticho- hours.
linergic delirium that is often missed); avoid
these combinations if possible (if the combina- See under Endocrine System and Steroids –
tion is required, monitor the patient, and re- Corticosteroids for other information.
duce their dose if necessary).
Anticholinesterases (e.g., neostigmine and pyri-
dostigmine) – combining anticholinergics with
these drugs, which increase acetylcholine PREDNISONE
concentration, will antagonize the anticholin-
ergic effect. Oral: 5 mg, 10 mg and 20 mg tablet
Beta-blockers – these may antagonize the thera- 10 mg/5 mL suspension, 60 mL
peutic effect of salbutamol in the combination, A corticosteroid having glucocorticoid and anti-
and may precipitate asthma. inflammatory effects; rapidly converted to the
Drugs increasing blood glucose concentration (e.g., active prednisolone in the body.
glucocorticoids, antipsychotics, calcineurin in-
hibitors, high-dose thiazide diuretics and so- Indications: Acute asthmatic attack.
matropin) – beta 2 agonists increase blood Contraindications: See under Endocrine System
glucose concentration; may increase the risk and Steroids – Corticosteroids.
of hyperglycemia when given with these
drugs. Dose:
Sympathomimetic amines (e.g., ephedrine, phe- NOTE: The dose depends upon the condition being treated
nylephrine and pseudoephedrine) – possibly and the response of patient; dosage for infants and
children should be based on severity of the disease
result in excess sympathetic stimulation and
and response of the patient, rather than on strict ad-
sympathetic adverse effects (e.g., tremor, herence to dosage indicated by age, weight and body
tachycardia, and headache). surface area. Consider alternate day therapy for long-
term therapy.
Administration: Metered-dose inhalers require Acute asthma, by mouth, ADULT and CHILD over
good hand-breath coordination (unsuitable for 12 years, 40-60 mg once daily for at least 5
use alone in children <8 years or for people days or until recovery (this may need to be
with poor dexterity). The respiratory solution given in 2 divided doses initially for the treat-
(for nebulization) should be administered via a ment of severe diseases); CHILD <0-11
mouth piece. If this is not available, a nebuliz- years, 1-2 mg/kg (maximum, 60 mg) once dai-
er mask should be used and it should fit per- ly for 3-10 days.
fectly); patients who may be predisposed to
glaucoma should be warned specifically to Discontinuation of long-term therapy requires
protect their eyes. gradual withdrawal by tapering the dose.
Pregnancy Category: C See under Endocrine System and Steroids –
Corticosteroids for other information.
145
PNF new 171 new.pdf 1 1/6/15 6:57 PM
'RVH
'RVH
(;3(&725$17
(;3(&725$17 Prophylaxis
Prophylaxis ofof asthma,
asthma, by mouth, $'8/7
by mouth, $'8/7 and and
&+,/'
&+,/' >15>15 years,
years, 10 10 mg
mg once
once daily
daily in
in the
the
LAGUNDI
LAGUNDI [Vitex
[Vitex negundo
negundo L.
L. evening; &+,/' 6-15 years, 5-mg
evening; &+,/' 6-15 years, 5-mg chewable chewable
(Fam. tablet once daily in the evening; &+,/'
tablet once daily in the evening; &+,/' 2-6 2-6
(Fam. Verbenaceae)]
Verbenaceae)] years,
years, 4-mg
4-mg chewable
chewable tablet
tablet once
once daily
daily in
in the
the
2UDO
2UDO 300
300 mg
mg and
and 600
600 mg
mg tablet
tablet evening; &+,/'
evening; &+,/' 6-23
6-23 months,
months, oneone packet
packet of of
300
300 mg/5
mg/5 mL
mL syrup,
syrup, 60
60 mL
mL and
and 120
120 mL
mL 4-mg oral granules.
4-mg oral granules.
A Seasonal allergic rhinitis, $'8/7 and &+,/'
Seasonal allergic rhinitis, $'8/7 and &+,/' >15 >15
A natural,
natural, medicinal
medicinal preparation
preparation from
from the
the leaves
leaves of
of
years,
years, 10
10 mg/day
mg/day inin the
the evening.
evening.
Vitex negundo Linn.
Vitex negundo Linn. (Fam.
(Fam. Verbenaceae),
Verbenaceae),
which is used for the relief of cough.
which is used for the relief of cough. 'RVH$GMXVWPHQWV
'RVH$GMXVWPHQWV
,QGLFDWLRQV RenalDQGHepatic
RenalDQGHepatic Impairment:
,QGLFDWLRQV For
For the
the relief
relief of
of mild
mild to
to moderate
moderate Impairment:
cough Same
Same dosage
dosage asas in
in patients
patients with
with normal
normal function
function
cough due
due to
to common
common colds
colds and
and flu.
flu. may
may be
be used
used inin patients
patients with
with mild
mild to
to moderate
moderate
&RQWUDLQGLFDWLRQV
&RQWUDLQGLFDWLRQV No
No information
information found.
found. impairment;
impairment; for
for severe
severe impairment,
impairment, the
the patient
patient
should
should be
be referred
referred to
to aa specialist.
specialist.
'RVH
'RVH
Cough,
Cough, byby mouth, Tablet, $'8/7,
mouth, Tablet, $'8/7, 11 tablet
tablet 3-4
3-4 3UHFDXWLRQV
3UHFDXWLRQV
times day; &+,/'
times aa day; &+,/' 7-12
7-12 years,
years, ½ ½ tablet
tablet 3-4

3-4 :$51,1*:
:$51,1*: Montelukast
Montelukast hashas nono role
role in
in the
the treatment
treatment of

of
times
times aa day; Syrup, $'8/7,
day; Syrup, $'8/7, 10 10 mLmL (2(2 tsp)
tsp) 3-
3- status
status asthmaticus.
asthmaticus. ItIt cannot
cannot bebe substituted
substituted for
for in-
in-
44 times
times daily,
daily, dose
dose maymay bebe increased
increased as as haled
haled or
or oral
oral corticosteroids
corticosteroids especially
especially for
for persistent
persistent
asthma.
asthma. ItIt should
should not
not be
be used
used as
as monotherapy
monotherapy for
for ex-
needed; &+,/',
needed; &+,/', 15 15 mg/kg/dose
mg/kg/dose or or (0.25
(0.25 ex-
mL/kg/dose) ercise-induced
ercise-induced bronchospasm.
mL/kg/dose) administered
administered 33 times times daily;
daily; bronchospasm.
&+,/'
&+,/' >40>40 kgkg body
body weight,
weight, 22 tsp
tsp 33 times
times dai-
dai- Eosinophilia
Eosinophilia and
and vasculitis;
vasculitis; neuropsychiatric
neuropsychiatric eventsevents
ly; &+,/'
ly; &+,/' 6-12
6-12 years
years (20-40
(20-40 kg),
kg), 11 ½-2
½-2 tsp
tsp 33 (behavioral
(behavioral changes)
changes) have
have been
been reported
reported inin
times daily; &+,/'
times daily; &+,/' 4-6 4-6 years
years (15.5-20
(15.5-20 kg),
kg), 11 patients
patients using
using this this drug;
drug; phenylketonuria
phenylketonuria
tsp
tsp 33 times daily; &+,/'
times daily; &+,/' 2-42-4 years
years (10-15.5
(10-15.5 (chewable
(chewable tablet tablet contains aspartame); pa-
contains aspartame); pa-
kg),
kg), ½-1
½-1 tsp
tsp times
times daily.
daily. tients
tients are
are instructed
instructed toto have
have appropriate
appropriate res-res-
cue
cue treatment
treatment available
available while
while onon montelukast;
montelukast;
'RVH$GMXVWPHQWVNo
'RVH$GMXVWPHQWVNo information
information found.
found.

when
when this
this is
is being
being given
given with
with systemic
systemic cortico-
cortico-
3UHFDXWLRQV
3UHFDXWLRQV steroids,
steroids, appropriate
appropriate tapering
tapering of of corticoster-
corticoster-
Patients
Patients with
with known
known allergy
allergy to lagundi plants.
to lagundi plants. oids
oids isis needed
needed underunder medical
medical supervision;
supervision;
children
children (possibly
(possibly increased
increased riskrisk of
of neuropsy-
neuropsy-
$GYHUVH'UXJ5HDFWLRQV chiatric adverse effects; limited data).
Mild chiatric adverse effects; limited data).
Mild adverse
adverse effects
effects have
have been
been observed,
observed, such
such as
as Pregnancy
Pregnancy (there is limited evidence in the safe
(there is limited evidence in the safe use
use
itchiness,
itchiness, nausea,
nausea, vomiting
vomiting and
and diarrhea.
diarrhea. of
of montelukast;
montelukast; however,
however, itit can
can be be adminis-
adminis-
'UXJ,QWHUDFWLRQV
'UXJ,QWHUDFWLRQV No
No information
information found.
found. tered at normal dose in women
tered at normal dose in women who have who have
shown
shown aa significant
significant improvement
improvement in in asthma,
asthma,
$GPLQLVWUDWLRQ
$GPLQLVWUDWLRQ Shake
Shake well
well before
before use. which
use. which is is not
not achievable
achievable withwith other
other drugs
drugs be-
be-
3UHJQDQF\ fore
fore becoming pregnant); breastfeeding (avoid
becoming pregnant); breastfeeding (avoid
3UHJQDQF\&DWHJRU\
&DWHJRU\ Safety
Safety among
among pregnant
pregnant and
and
lactating use unless essential).
use unless essential).
lactating women
women has
has not
not been
been studied.
studied. 127(:
127(: Rarely,
Rarely, the
the reduction
reduction of
of aa systemic
systemic corticosteroid
corticosteroid
while
while on
on another
another leukotriene
leukotriene receptor
receptor antagonist
antagonist has
has
been
been reported to manifest with eosinophilia, vasculitic
reported to manifest with eosinophilia, vasculitic
/(8.275,(1(5(&(3725$17$*21,67
/(8.275,(1(5(&(3725$17$*21,67 rash, worsening pulmonary symptoms, cardiac
rash, worsening pulmonary symptoms, cardiac com- com-
plications,
plications, or
or neuropathy
neuropathy sometimes
sometimes presenting
presenting asas
Churg-Strauss
Churg-Strauss syndrome.
syndrome.
MONTELUKAST
MONTELUKAST $GYHUVH'UXJ5HDFWLRQV
Common: Abdominal
Common: Abdominal pain pain and
and discomfort,
discomfort, cough,
cough,
2UDO
2UDO 44 mg
mg granules
granules (as
(as sodium
sodium salt),
salt), sachet
sachet diarrhea,
diarrhea, fatigue,
fatigue, fever,
fever, headache,
headache, hyperkine-
hyperkine-
44 mg
mg and
and 55 mg
mg chewable
chewable tablet
tablet sia,
sia, otitis
otitis media,
media, pharyngitis,
pharyngitis, rash,
rash, sinusitis,
sinusitis,
(as sodium salt)
(as sodium salt) thirst,
thirst, upper
upper respiratory
respiratory infection,
infection, weakness.
weakness.
10
10 mg
mg tablet
tablet (as
(as sodium
sodium salt)
salt) Less Common: Abnormal
Less Common: Abnormal dreams,
dreams, arthralgia,
arthralgia,
bruising,
bruising, dizziness,
dizziness, dry dry mouth,
mouth, dyspepsia,
dyspepsia,
A
A selective,
selective, leukotriene-receptor
leukotriene-receptor inhibitor,
inhibitor, which
which edema,
edema, epistaxis,
epistaxis, hypesthesia,
hypesthesia, malaise,
malaise, my-
my-
antagonizes
antagonizes airway
airway smooth
smooth muscle
muscle contrac-
contrac- algia,
algia, paresthesia,
paresthesia, pruritus,
pruritus, seizures,
seizures, sleep
sleep
tion
tion and
and inflammation
inflammation caused
caused byby leukotrienes.
leukotrienes. disturbances,
disturbances, sleepwalking.
sleepwalking.
,QGLFDWLRQV
,QGLFDWLRQV Prophylaxis
Prophylaxis and and treatment
treatment of of asthma
asthma
(as Rare:Allergy,
Rare: Allergy, including
including urticaria,
urticaria, angioedema,
angioedema, and and
(as an
an adjunctive
adjunctive therapy
therapy inin combination
combination with
with anaphylaxis;
aa corticosteroid); anaphylaxis; bleeding,
bleeding, Churg-Strauss
Churg-Strauss syn- syn-
corticosteroid); symptomatic
symptomatic relief
relief of
of sea-
sea- drome,
sonal drome, disorientation,
disorientation, eosinophilia,
eosinophilia, erythema
erythema
sonal allergic
allergic rhinitis
rhinitis in
in patients
patients with
with asthma.
asthma. multiforme,
127(:
127(: There
There is
is aa place
place for
for montelukast
montelukast in
in children
children aged
aged 2-5
2-5 multiforme, erythema
erythema nodosum,
nodosum, hallucina-
hallucina-
years tions,
tions, hepatic
hepatic disorders,
disorders, mood
mood or or behavioral
behavioral
years with
with intermittent
intermittent viral-induced
viral-induced asthma,
asthma, where
where
leukotrienes
leukotrienes play
play aa minor
minor role.
role. changes,
changes, e.g.,e.g., anxiety,
anxiety, depression
depression and and ag-
ag-
gression;
gression; neuropsychiatric
neuropsychiatric effects,
effects, e.g.,
e.g.,
&RQWUDLQGLFDWLRQ
&RQWUDLQGLFDWLRQ Known
hypersensitivity to
to mon-
mon- nightmares
telukast nightmares and and hallucinations;
hallucinations; palpitations,
palpitations,
telukast or
or any
any component
component of
of the
the formulation.
formulation. suicidal
suicidal thoughts
thoughts andand behavior,
behavior, tremor.
tremor.
146
146
Drug Interactions:
CYP450 enzyme inducers (e.g., phenobarbital and
rifampicin) – these decrease the AUC of mon-
telukast, possibly reducing its clinical thera-
peutic effect.
Administration: Take the drug at only one dose
daily in the evening. Administer the oral gran-
ules (sachet) within 15 minutes after opening
the packet (with or without mixing with food).
NOTE: Do not use this drug to relieve symptoms of an
asthma attack; use a short-acting reliever.
147
Pregnancy (should always be under the direction of
VITAMINS AND MINERALS a physician; animal studies have shown toxic
effects on reproduction at high doses of vita-
min D; long-term hypercalcemia in pregnant
CALCIUM + VITAMIN D women can lead to physical and mental retar-
dation, aortic stenosis and retinopathy in a
Oral: 500 mg/200 IU (elemental Ca + vitamin D) newborn child).
500 mg/400 IU (elemental Ca + vitamin D) NOTE: Allowances should be made for calcium and vitamin
600 mg/200 IU (elemental Ca + vitamin D) D supplements from other sources.
600 mg/400 IU (elemental Ca + vitamin D) Adverse Drug Reactions:
A two-component dietary supplement of calcium Less Common: Hypercalcemia, hypercalciuria.
and fat-soluble vitamin D, which serves to in- Rare: Abdominal pain, acid rebound, anorexia,
crease the calcium pool available for GI ab- arrhythmia, bone or muscle pain, constipation
sorption and assimilation into bones. or diarrhea; headache, hypophosphatemia,
flatulence, loss of appetite, metallic taste,
Indications: An adjunct to specific therapy for milk-alkali syndrome, nausea, pruritus, rash,
osteoporosis; situations requiring its therapeu- urticaria, vomiting, xerostomia.
tic supplementation (e.g., lactose-intolerance
or with milk allergy; established vitamin D de- Drug Interactions:
pendent osteomalacia; post-menopausal Monitor closely with:
women; chronic kidney disease with or without Corticosteroids – concomitant use with these drugs
renal replacement therapy); hyperphos- may reduce calcium absorption.
phatemia. Digoxin – its toxicity may be potentiated by calcium
salts (due to possible hypercalcemia).
Contraindications: Known hypersensitivity to the Quinolone antibiotics (e.g., ciprofloxacin) – their
preparation or any of the excipients (e.g., soya absorption may be reduced by the combina-
oil); hypercalcemia; hyperparathyroidism; re- tion product.
nal calculi; hypophosphatemia; vitamin D tox- Thiazide diuretics – these may decrease urinary
icity; abnormal sensitivity to the effects of vit- excretion of calcium and cause hypercalcemia
amin D; malabsorption syndrome; renal failure (high doses of these drugs with calcium may
or severe renal impairment. cause milk-alkali syndrome).
Dose: Avoid concomitant use with:
Calcium deficiency, by mouth, supplementary intake Bisphosphonate derivatives – their serum concen-
to achieve a total elemental calcium dosage of tration may be decreased by calcium salts.
1 g in two divided doses for male and Calcium channel blockers – their effect may be
premenopausal female patients; 1.2-1.5 g in reduced by the combination product.
three divided doses for post-menopausal Iron salts – their absorption may be decreased by
women; not recommended for children <12 the combination product.
years. Levothyroxine – its absorption may be decreased by
calcium (separate dose by 4 hours).
Dose Adjustments: Tetracyclines – their absorption may be affected
Check Recommended Energy and Nutrient Intakes when used concomitantly with the combina-
(RENI) per day for Calcium and Vitamin D for tion product.
dose of different population groups. Zinc salts – their absorption may be decreased by
Renal Impairment: the combination product.
Use caution in severe renal impairment.
Administration:
Precautions: NOTE: Foods that are rich in oxalic acid (e.g., spinach) and
Should not be used in osteoporosis due to pro- phytic acid (e.g., whole cereals) may reduce calcium
longed immobilization, renal stones, or severe absorption (due to formation of insoluble calcium
salts); calcium products should not be taken within 2
hypercalciuria; mild to moderate renal failure
hours of eating such foods.
or mild hypercalciuria (supervise carefully, in- Administer, preferably with food, 2 hours before, or
cluding periodic checks of plasma calcium after, other medications.
levels and urinary calcium excretion); in pa-
tients with history of renal stones; in patients Pregnancy Category: C
receiving treatment for cardiovascular diseas-
es; patients with rare hereditary problems of
glucose-galactose malabsorption or fructose
intolerance; renal. FERROUS SALT
Its absorption is impaired among patients with
achlorhydria; hypercalcemia and hypercalciu- Oral: Tablet, equivalent to 60 mg elemental iron
ria may occur in hypoparathyroid patients who Solution, (equivalent to 15 mg elemental
receive prolonged calcium and high-dose vit- iron/0.6 mL) drops, 15 mL and 30 mL
amin D replacement. Solution, (equivalent to 30 mg elemental
Administration is followed up within 2 hours by iron/5 mL) syrup, 60 mL
increased serum gastric acid secretion. Ade-
quate fluid intake should be maintained.
148
N.B. The elemental iron content of ferrous salts. Drug Interactions:
Ferrous fumarate - 33% Monitor closely with:
Ferrous gluconate - 12% Chloramphenicol – this increases the serum iron
Ferrous lactate - 19% concentration due to chloramphenicol-induced
Ferrous sulfate, hydrated - 20% bone marrow toxicity.
Ferrous sulfate, desiccated - 32% Methyldopa – ferrous salts reduce bioavailability of
methyldopa; its activity is reduced that leads
An essential trace element required for the for- to interference with BP control.
mation of hemoglobin and for the efficient ox- Avoid concomitant use with:
ygen transport in the blood. Antacids (e.g., aluminum or magnesium hydroxide)
Indications: Treatment of iron-deficiency anemia – possibly decreased iron absorption (sepa-
rate administration times by as long as possi-
and in people on hemodialysis who are receiv-
ble).
ing erythropoietin (supplement and prophylax-
Bisphosphonates – ferrous salts significantly reduce
is).
the absorption of oral bisphosphonates and
Contraindications: Known hypersensitivity to the may reduce their activity.
product or any component of the formulation; Calcium – possibly decreased iron absorption.
anemia not due to iron deficiency; parenteral Doxycycline – this reduces absorption of oral fer-
iron therapy; in patients receiving repeated rous salts; they also, in turn, reduce the ab-
blood transfusions; hemochromatosis; hemo- sorption of doxycycline.
siderosis. Food – iron absorption is inhibited by eggs and milk.
Levothyroxine – ferrous salts reduce absorption of
Dose:
the levothyroxine (give at least 2 hours apart).
Iron-deficiency anemia, by mouth, ADULT, ele-
Quinolones (e.g., ciprofloxacin) – ferrous salts bind
mental iron, 100-200 mg daily in divided dos- to quinolones in the GI tract, reducing their
es. absorption and activity.
Prevention of iron-deficiency anemia (in those at Tetracyclines – ferrous salts form poorly-soluble
particular risk), by mouth, ADULT (woman),
chelates with tetracyclines, reducing their ab-
elemental iron 60 mg daily; CHILD >5 years, sorption and anti-infective activity; also re-
elemental iron, 30 mg daily; CHILD <5 years, duced iron absorption.
elemental iron, 2 mg/kg daily (maximum, 30 Zinc salts – reduced absorption of zinc and of fer-
mg); in women and children >5 years, folic rous salts.
acid may also be given.
Administration: Although iron preparations are
Dose Adjustment: best absorbed on an empty stomach, they
Renal Failure: may be taken after food to reduce GI adverse
Give iron supplementation when patient is anemic effects; they may also discolor stools. Liquid
and iron saturation is low. preparations containing iron salts should be
Precautions: well diluted with water, and if possible swal-
WARNING: Iron salts can exacerbate GI bleeding, thus lowed through a drinking straw to prevent
should be used with caution in patients with GI disor- teeth discoloration.
ders.
They should not be administered for longer than 6
months; avoid in transfusion-dependent ane-
mia (increase the risk of iron overload); peptic
ulcer, regional enteritis, ulcerative colitis, in- FERROUS SALT + FOLIC ACID
testinal strictures and diverticula; close moni-
toring for potential complications, which may Oral: 60 mg elemental Iron + 250 micrograms folic
arise on maintained iron supplementation. acid per tablet/capsule
Pregnancy (avoid use in the first trimester; adminis-
ter only in women with low-normal hemoglo- A two-component, nutritional supplement of iron and
bin). folic acid given during pregnancy.
NOTE: Overdosage: initiate therapy with deferoxamine.
Before administration of deferoxamine, the stomach Indication: For the prevention of iron and folic acid
should be emptied by gastric lavage (with a wide-bore deficiencies, especially in pregnancy.
tube), preferably within one hour of ingesting a signifi- NOTE: Low doses of folic acid in combination preparations
cant quantity of iron or if radiography reveals tablets are inadequate for the treatment of megaloblastic
in the stomach. anemia; overdosage: therapy with deferoxamine.
Adverse Drug Reactions: Contraindications: Known hypersensitivity to iron

Common: Abdominal pain, black discoloration of salts, folic acid, or any of the components;
feces, constipation, diarrhea, nausea, vomit- hemolytic anemia; hemochromatosis; hemo-
ing. siderosis; repeated blood transfusions of par-
Less Common: Black discoloration of teeth. enteral iron therapy; pernicious anemia.
Rare: Anaphylaxis, GI erosion and perforation, Dose:
hemosiderosis. Prevention of iron and folate deficiencies in preg-
nancy, by mouth, ADULT, elemental iron, 100
149
mg + folic acid, 350-400 micrograms daily Doxycycline – this reduces absorption of oral fer-
throughout pregnancy. rous salts; they also reduce the absorption of
Severe anemia, by mouth, ADULT, elemental iron, doxycycline.
120 mg + folic acid 400 micrograms daily for 3 Folic Acid antagonists (e.g., methotrexate, py-
months; CHILD 2-12 years, elemental iron 60 rimethamine, triamterene, sulfonamides and
mg + folic acid, 400 micrograms daily for 3 trimethoprim) – these decrease folic acid lev-
months; CHILD <2 years, elemental iron, 25 els.
mg + folic acid 100-400 micrograms daily for 3 Food – iron absorption is inhibited by eggs and milk.
months. Levothyroxine – its absorption is reduced by oral
ferrous salts (give at least 2 hours apart).
Dose Adjustment: Quinolones (e.g., ciprofloxacin and levofloxacin) –
Renal Failure: oral ferrous salts bind to quinolones in the GI
Give iron supplementation when the patient is ane- tract, reducing their absorption and activity.
mic, and iron saturation is <20%. Tetracyclines – iron forms poorly-soluble chelates
Precautions: with tetracyclines, reducing their absorption
WARNING: Iron salts can exacerbate GI bleeding, thus it and anti-infective activity; these also reduced
should be used with caution in patients with GI disor- iron absorption.
ders. Zinc salts – reduced absorption of zinc and of fer-
rous salts.
Transfusion-dependent anemia (increased risk of
iron overload; avoid supplementation); peptic Administration: Take combination on an empty
ulcer, regional enteritis, ulcerative colitis, in- stomach, at least 1 hour before, or 2 hours, af-
testinal strictures, diverticula; the nature ter meal. Avoid taking antacids or antibiotics
should be established and underlying causes within 2 hours before, or after, taking it.
determined if anemia exists; pernicious ane-
Pregnancy Category: A
mia (doses of folic acid >0.1 mg/ day may ob-
scure pernicious anemia with continuing irre-
versible nerve damage progression); severe
iron toxicity may occur in overdose, particular-
ly when ingested by children; in older patients MICRONUTRIENT POWDER
and those with tendency to lead to vitamin B 12
depletion, serum B 12 levels should be regular- Oral:
ly assessed during treatment. Per 1 g sachet:
Pregnancy (avoid use in the first trimester; adminis- Micronutrient per 1 g sachet
ter only in women with low-normal hemoglo- Vitamin A 400 microgram
bin). RE
Adverse Drug Reactions: Vitamin C 30 mg
Common: Abdominal pain, black discoloration of Vitamin D 5 microgram
feces, constipation, diarrhea, nausea, vomit- Vitamin E 5 mg a-TE
ing. Vitamin B1 0.5 mg
Less Common: Black discoloration of teeth. Vitamin B2 0.5 mg
Rare: Anaphylaxis, bronchospasm, fever, GI ero- Vitamin B6 0.5 mg
sion and perforation, hemosiderosis, irritabil- Vitamin B12 0.9 microgram
ity, rash, sleep disturbance. Folic Acid 150 microgram
Drug Interactions: Niacin 6 mg
Monitor closely with: Iron 10 mg
Chloramphenicol – this increases the serum iron Zinc 4.1 mg
concentration due to chloramphenicol-induced Copper 0.56 mg
bone marrow toxicity. Iodine 90 microgram
Methyldopa – its bioavailability is reduced by ferrous Selenium 17 microgram
salts; reducing its activity, and interferes with
BP control. Single-dose packets of iron, and other vitamins and
Phenobarbital – folic acid may decrease the con- minerals, in powder form, which can be sprin-
centration of phenobarbital and its therapeutic kled onto any ready-to-eat semisolid food.
effect. Indications: Prevent vitamin and mineral deficien-
Phenytoin – folic acid may decrease the concentra- cies; improve iron status and reduce anemia
tion of phenytoin, and its therapeutic effect. among infants and children 6-23 months of
Avoid concomitant use with: age.
Antacids (e.g., aluminum and magnesium hydrox-
ide) – these possibly decreased iron absorp- Contraindications: Known hypersensitivity to any
tion (separate administration times by as long component of the preparation; Not applicable
as possible). to children with specific conditions, such as
Bisphosphonates – iron significantly reduces the HIV infection or TB (as the effects and safety
absorption of bisphosphonates, and may re- of the intervention have not been evaluated).
duce their activity.
Calcium – possibly decreased iron absorption.
150
Dose: For Males: (aged 10 to 18 years old)
Prevention of vitamin and mineral deficiencies, Vitamin A – 400-600 micrograms RE
improving iron status, and reducing anemia Vitamin B1 – 0.9-1.4 mg
among INFANTS and CHILDREN (6-23 Vitamin B2 – 1.0-1.5 mg
months of age), by mouth, 1 sachet daily, add Vitamin B6 – 1.3 mg
a mixture of micronutrients in powder form to Vitamin B12 – 2.4 micrograms
any semisolid food. Vitamin C – 45-75 mg
Vitamin D – 5 micrograms
Dose Adjustments:
Vitamin E – 10-13 mg
Folic acid – 400 micrograms DFE
Use with caution.
Niacin – 12-16 mg NE
Precautions: For Females: (aged 10 to 18 years old)
Programs involving the use of multiple micronutrient Vitamin A – 400-450 micrograms RE
powders for fortification at home of foods Vitamin B1 – 0.9-1.1 mg
should be preceded by an evaluation of the Vitamin B2 – 0.9-1.1 mg
nutritional status among children <5 years of Vitamin B6 – 1.2 mg
age, and existing measures to control anemia Vitamin B12 – 2.4 micrograms
and vitamin A deficiency (e.g., hookworm con- Vitamin C – 45-70 mg
trol programs, provision of supplements, and Vitamin D – 5 micrograms
the use of other products for home fortification Vitamin E – 11-12 mg
of foods and fortified complementary foods), Folic acid – 400 micrograms DFE
to ensure that daily micronutrient needs are Niacin – 12-14 mg NE
met and not exceeded.
For Male Adults: (>18 years of age)
Adverse Drug Reactions: Vitamin A – 550 micrograms RE
Common: Diarrhea. Vitamin B1 – 1.2 mg
Less Common to Rare: Darkening of the stools, Vitamin B2 – 1.3 mg
staining of child’s teeth. Vitamin B6 – 1.3-1.7 mg
Drug Interactions: No information found. Vitamin B12 – 2.4 micrograms
Vitamin C – 75 mg
Administration: At minimum, for a period of 2 Vitamin D – 5-15 micrograms
months that is followed by a period of 3-4 Vitamin E – 12 mg
months off supplementation (so that use of the Folic acid – 400 micrograms DFE
micronutrient powders is started every 6 Niacin – 16 mg NE
months).
For Female Adults: (>18 years of age)
Pregnancy Category: No information found. Vitamin A – 500 micrograms RE
Vitamin B1 – 1.1 mg
Vitamin B2 – 1.1 mg
Vitamin B6 – 1.3-1.5 mg
MULTIVITAMINS for INFANTS, Vitamin B12 – 2.4 micrograms
CHILDREN, and ADULTS Vitamin C – 70 mg
Oral: Vitamin D – 5-15 micrograms
Vitamin E – 12 mg
For Infants: (Birth to <12 months of age) Folic acid – 400 micrograms DFE
Vitamin A – 375 – 400 micrograms RE Niacin – 14 mg NE
Vitamin B2 – 0.3-0.4 mg A dietary supplement containing essential multi-
Vitamin B6 – 0.1-0.3 mg vitamins and minerals that are needed for
Vitamin B12 – 0.3-0.4 micrograms good health, growth and development.
Vitamin C – 30 mg Indications: Dietary supplementation; vitamin
Vitamin D – 5 micrograms deficiencies.
Vitamin E – 3-4 mg
Folic acid – 65-80 micrograms DFE Contraindications: Known hypersensitivity to any
Niacin – 1.5-4 mg NE component of the preparations; pre-existing
hypervitaminosis.
For Children: (aged 1 to 9 years old)
Vitamin A – 400 micrograms RE Dose:
Vitamin B1 – 0.5-0.7 mg Prevention or treatment of vitamin deficiencies, by
Vitamin B2 – 0.5-0.7 mg mouth, ADULT, one tablet or capsule daily.
Dose Adjustments:
Vitamin B12 – 0.9-1.8 micrograms
Vitamin C – 30-35 mg
Use with caution.
Vitamin D – 5 micrograms
Vitamin E – 5-7 mg Precautions: Avoid taking similar vitamin products
Folic acid – 160-300 micrograms DFE (may cause vitamin overdose or serious side
Niacin – 6-9 mg NE effects).
151
NOTE: Not all products can be used in children of all age 50,000 IU on diagnosis, repeated the next day
groups; consult specific product labeling prior to use. and again after 2 weeks.
Do not exceed recommended doses. NOTE: Oral vitamin A preparations are preferred for the
prevention and treatment of vitamin A deficiency.
Adverse Drug Reactions: See individual vitamin
monographs. Dose Adjustment:
Drug Interaction: Pregnant women who are susceptible to vitamin
Food – iron absorption is inhibited by eggs and milk A deficiency during third trimester:
Should be given low dose vitamin A supplements on
Administration: May be taken with or without food. a daily or weekly basis.
NOTE: May be taken with meals for better absorption or if GI
discomfort occurs. Precautions:
WARNING: Severe congenital malformations may occur in
Pregnancy Category: No information found.
infants of mothers consuming large amounts of oral
retinoids for acne treatment.
Patients on prolonged daily administration over
RETINOL (Vitamin A) 25,000 IU should be under close supervision;
chronic intake of vitamin A at levels 10 to 20
Oral: 10,000 IU, 25,000 IU, and 50, 000 IU soft gel times the RDA can lead to hypervitaminosis A.
capsule (as palmitate) Pregnancy (first trimester: excessive doses may be
100,000 IU soft gel capsule with nipple (as teratogenic); breastfeeding (there is theoreti-
palmitate) (only for DOH program) cal risk of toxicity in infants of mothers taking
large doses).
200,000 IU soft gel capsule with nipple (as
NOTE: Dietary reference intakes (DRIs): tolerable upper
palmitate) (only for DOH program) intake level (UL) for adults is set at 3,000 mi-
crogram/day of preformed vitamin A; based on terato-
A fat-soluble vitamin and dietary supplement that is
genicity as the critical adverse effect for women of
required by the eyes for the transduction of childbearing age and liver pathology for all other
light into neural signs necessary for vision. adults.
Indications: For the prevention and treatment of Adverse Drug Reactions:
vitamin A deficiency states (e.g., xerophthal- Less Common: Diplopia, headache, nausea, sym-
mia and night blindness); prevention of com- metric papilledema, vomiting.
plications of measles. Rare: Birth defects (e.g., tense and bulging fonta-
Contraindications: Hypervitaminosis A; Known nelle in infants), dry hair, enlarged liver, in-
hypersensitivity to vitamin A, or any compo- creased intracranial pressure; raised serum
nent of the formulation; dosages exceeding alkaline phosphatase concentration, raised
the Recommended Energy and Nutrient In- serum calcium, rough skin.
take (RENI) – contraindicated in women who Drug Interactions:
are, or may become, pregnant. Monitor closely with:
Dose: Contraceptives, Oral – these may increase the
concentration of vitamin A.
Prevention of vitamin A deficiency (universal or
Warfarin – increased anticoagulant effect.
targeted distribution programs), by mouth,
ADULT, 200,000 IU every 6 months; ADULT Avoid concomitant use with:
(pregnant woman), maximum of 10,000 IU Bile acid binding resins (e.g., cholestyramine and
daily or maximum 25,000 IU weekly; ADULT colestipol) – these may reduce the body’s abil-
(woman of childbearing age), 200,000 IU at ity to absorb vitamin A.
delivery or within 8 weeks of delivery; CHILD Retinoid drugs (e.g., acitretin, all-transretinoic acid,
bexarotene, etretinate and isotretinoin) – in-
>1 year (preschool), 200,000 IU every 4-6
creased risk of hypervitaminosis A.
months; INFANT 6-12 months, 100,000 IU
Tetracyclines – these increase the risk of benign
every 4-6 months, preferably at measles vac-
intracranial hypertension.
cination; INFANT <6 months, 50,000 IU.
NOTE: An additional dose should be given the next day in Administration: This vitamin is absorbed along
hospitalized children with measles infection. with fat in the diet. Take it with food.
Treatment of xerophthalmia, by mouth, ADULT
(except woman of childbearing age) and Pregnancy Category: A; X if used in doses above
CHILD over 1 year, 200,000 IU on diagnosis, RENI.
repeated the next day and again after 2
weeks; ADULT (woman of childbearing age
with severe signs of xerophthalmia) as for
other adults; ADULT woman of childbearing VITAMIN B1 B6 B12
age with less severe symptoms, e.g., night
blindness, either 5,000-10,000 IU daily for at Oral: 100 mg B1 + 5 mg B6 + 50 micrograms B12
least 4 weeks or up to 25,000 IU weekly; IN- per tablet/capsule
FANT 6-12 months, 100,000 IU immediately 250 mg B1 + 250 mg B6 + 1000 micrograms
on diagnosis, repeated the next day and again B12 per tablet/capsule
after 2 weeks; INFANT under 6 months,
152
A dietary supplement, which contains vitamins B 1 , 55 mg/5 mL solution, (equiv. to 20 mg ele-
B 6 and B 12 for nerve cell metabolism, and for mental zinc/5 mL) syrup, 60 mL (as sulfate
vitamin B-complex deficiencies. monohydrate)
Indications: Prevention and treatment of vitamin B- An essential, mineral supplement in the diet, which
complex deficiencies; adjunct in the manage- may be used as an adjunct to oral rehydration
ment of neuromuscular pain responsive to vit- in the treatment of acute and persistent diar-
amin B 1 , B 6 and B 12 , including neuralgia, rhea.
neuritis and neuropathies.
Indication: Adjunct to oral rehydration therapy in
Contraindications: Known hypersensitivity to any acute and persistent diarrhea.
component of the formulation; Leber’s disease
or tobacco amblyopia. Contraindication: Severe renal impairment.
Dose:
Dose:
Oral rehydration therapy in acute and persistent
Prevention and treatment of Vitamin B complex
diarrhea (adjunct), by mouth, CHILD 6
deficiency, by mouth, ADULT, one to two tab-
lets or capsules daily. months-5 years, 20 mg (elemental zinc) daily
for 10-14 days; INFANT < 6 months, 10 mg
Dose Adjustments: (elemental zinc) daily for 10-14 days.
Use with caution. Dose Adjustment: No information found.
Precautions: Precautions:
Malabsorption; anemia (confirm the cause before Acute renal failure (may accumulate).
starting supplementation; vitamin B 12 may Adverse Drug Reactions:
mask clinical and hematological features of fo- Common: Diarrhea, dry mouth, dyspepsia, GI
late deficiency); neuropathy (severe, perma- upset, mouth irritation, nausea, regurgitation
nent peripheral neuropathies have been re- and vomiting (in children), unpleasant taste.
ported); vitamin B 12 >10 micrograms daily Less Common: Gastritis, headache, irritability,
may produce hematological response in pa- lethargy.
tients with folic acid deficiency (avoid indis-
criminate use; monitor blood regular- Drug Interactions:
ly);neurotoxicity is more common with long- Avoid concomitant use with:
term administration of large doses (>2 g/day); Bisphosphonates – reduced bisphosphonate ab-
undiagnosed vitamin B 12 deficiency. sorption.
Calcium salts – these may interfere with the absorp-
Adverse Drug Reactions: tion of zinc salts (separate doses by 2-3
Less Common: Headache, peripheral neuropathy hours).
(high doses). Ethambutol – this may inhibit zinc absorption.
Rare: Hypersensitivity reactions. Ferrous salts – reduced absorption of zinc and of
oral ferrous salts.
Drug Interaction:
Food – absorption of zinc is reduced by milk,
phytates (present in cereals, rice, corn, and
Levodopa – pyridoxine may increase peripheral
legumes).
metabolism of levodopa, reducing its thera-
Quinolones (e.g., ofloxacin and ciprofloxacin) – zinc
peutic effect.
binds to quinolones in the GI tract; reducing
Administration: May be taken with or without food; their absorption and activity (separate doses
may be taken with meals to reduce GI discom- by at least 2 hours).
fort. Tetracyclines – zinc forms poorly-soluble chelates
with tetracyclines, reducing their absorption
Pregnancy Category: A, but C if dose is greater and anti-infective activity (separate admin-
than RENI. istration by at least 2 hours).
Administration: Tablets may be dispersed in
breast milk, in oral rehydration solution, or in
ZINC water on a small spoon; older children may
chew the tablets or swallow them with water.
Oral: Chewable tablet, (equiv. to 10 mg elemental Pregnancy Category: C
zinc) (as gluconate)
132 mg tablet, (equiv. to 30 mg elemental
zinc) (as gluconate trihydrate)
220 mg tablet, (equiv. to 50 mg elemental
zinc) (as gluconate trihydrate)
27.5 mg/mL solution, (equiv. to 10 mg ele-
mental zinc/mL) drops, 15 mL (as sulfate
monohydrate)
153
Adverse Reactions:
MISCELLANEOUS Irritating to the eyes, nose (rhinitis) and respiratory
tract causing coughing, dysphagia, and airway
obstruction (laryngeal spasm and edema),
ANTISEPTICS bronchitis and pneumonia; repeated exposure
has caused asthma; nausea, headache and
contact dermatitis.
ETHYL ALCOHOL
Administration: Immerse materials for disinfection
Solution: 70%, 480 mL bottle for 10 to 20 minutes in 2% glutaral aqueous
solution. For complete sterilization, exposure
A clear, aqueous solution of ethyl alcohol which is of up to 10 h may be necessary.
used as a disinfectant and skin antiseptic.
Indications: Disinfection of skin prior to injection,
venipuncture, or surgical procedures.
HYDROGEN PEROXIDE
Contraindications: Broken skin; patients who have
suffered severe burns when diathermy has Solution: 3%, 120 mL bottle
been preceded by application of alcoholic skin
disinfectants. A clear, colorless solution of hydrogen peroxide,
which is a powerful oxidizing agent, and is
Dose: used as a disinfectant.
Disinfection of skin, ADULT and CHILD, apply an
Indication: As a mild disinfectant for minor cuts,
appropriate volume of solution directly to the
skin area. skin ulcers and wounds.
Dose Adjustment: No information found. Contraindications: Known hypersensitivity to the

compound or any of its components; injection
Precautions: or instillation into closed body cavities for
Avoid heat, sparks and open flame and tempera- which the released oxygen has no free exit.
tures above 30°C (vapors formed from the
Dose:
product may travel by air currents and be ig-
Disinfectant, by topical use, ADULT and CHILD,
nited by pilot lights, sparks, electrical equip-
ment and other ignition sources); may emit dress the wound with cotton wool soaked in
toxic fumes of carbon monoxide and carbon an appropriate volume of hydrogen peroxide.
dioxide, if exposed to fire. Dose Adjustment: No information found.
Adverse Drug Reactions: Skin dryness and irrita- Precautions:
tion with frequent application of the aqueous Use with caution in large or deep wounds; avoid on
solution. health skin; avoid contact with the eyes; avoid
Drug Interactions: No information found. contact with the clothing due to its bleaching
effects.
Administration: Apply locally as needed.
Pregnancy Category: No information found. Rare: Hypersensitivity reactions, irritating burns on
the skin and mucous membranes with a white
eschar (strong solution).
Drug Interactions:
GLUTARALDEHYDE Avoid concomitant use with:
Preparations containing iodine and potassium per-
Solution: 2% (with alkaline activating solution),
manganate – hydrogen peroxide has been re-
120 mL and 1 L ported to be incompatible with these prepara-
An aldehyde, which exerts action by forming linkag- tions.
es with amino groups to form azomethines. In Administration: Apply locally as needed.
higher concentrations, it precipitates microbial
proteins. Pregnancy Category: No information found.
NOTE: Glutaral is a bactericidal disinfectant that is rapidly
effective against gram-positive and gram-negative
bacteria.
Indication: For the sterilization of endoscopic and POVIDONE-IODINE

dental instruments, rubber or plastic equip-
ment and for other equipment which cannot Solution: 10%, 60 mL and 120 mL
be sterilized by heat; for disinfection of respir-
atory tubing. A brown-colored, antiseptic solution, which is used
for the disinfection of minor skin infections.
Precautions:
Indications: Skin disinfection; antiseptic.
Avoid contact with the skin and eyes to prevent
irritation; avoid inhaling the vapor.
154
PNF new 180 new .pdf 1 1/8/15 2:33 PM
&RQWUDLQGLFDWLRQV Hypersensitivity to iodine; of clinical and, whenever possible, electrolyte

postmenstrual age of 32 weeks; regular or monitoring. See under Sodium Chloride.
prolonged use in patients with thyroid disor-
'RVH$GMXVWPHQW
ders, or those taking lithium; regular use in
neonates; in very low-birthweight infants (e.g., Renal Impairment:
<1.5 kg). Care should be taken in dose selection (due to
increased risk of adverse effects).
'RVH
3UHFDXWLRQV
Pre-operative and post-operative skin disinfection,
$'8/7 and &+,/', apply an appropriate vol- :$51,1*: Mix the infusion solutions thoroughly after
ume of solution directly to the skin area. adding concentrated electrolytes to avoid possible
toxicity.
Antiseptic (minor wounds and burns), $'8/7 and
&+,/', apply an appropriate volume of solu- Restrict intake in impaired renal function, cardiac
tion to the affected area, twice daily (see Pre- failure, hypertension, peripheral and pulmo-
cautions below). nary edema, and toxemia during pregnancy
(may cause fluid and salt retention in cardiac,
'RVH$GMXVWPHQWNo information found. cirrhotic or nephrotic patients; may aggravate

3UHFDXWLRQV hypertension); may aggravate or precipitate
May interfere with thyroid function tests (due to congestive heart failure; for single use only
systemic effects); broken skin (see notes be- (contamination may lead to injury, illness or
low); renal impairment (avoid regular applica- death).

tion to inflamed or broken mucosa). $GYHUVH'UXJ5HDFWLRQV
Pregnancy (second and third trimesters: sufficient 127(: Adverse reactions which may occur because of the
iodine may be absorbed to affect the fetal thy- solution, added drugs or the technique of reconstitu-
roid). tion or administration include (but are not limited to):
127(: Large open wounds: the application of povidone- air embolization, febrile response, local tenderness,
iodine to large wounds or severe burns may produce tissue necrosis or infection at the site of injection, ve-
systemic adverse effects, such as metabolic acidosis, nous thrombosis or phlebitis extending from the site of
hypernatremia and renal function impairment. injection, extravasation and hypervolemia.
Rare: Edema, sodium accumulation.
Rare: Hypersensitivity reactions, local irritation of 'UXJ,QWHUDFWLRQV
the skin and mucous membranes. Monitor closely with:

Corticosteroids and corticotropin – these are asso-
'UXJ,QWHUDFWLRQV No information found. ciated with the retention of sodium and water,
$GPLQLVWUDWLRQ Apply locally as needed. with hypertension and edema.
3UHJQDQF\&DWHJRU\ D $GPLQLVWUDWLRQ Fluid administration should be

based on calculated maintenance or replace-
ment fluid requirements for each patient.
127(: Parenteral drug products should be inspected visual-
)/8,'6DQG(/(&752/<7(6 ly for particulate matter and discoloration prior to ad-
ministration, whenever solution and container permit.
0.9% SODIUM CHLORIDE 3UHJQDQF\&DWHJRU\ C
,QM 2 mL, 2.5 mL, 5 mL, 10 mL and 20 mL ampul

50 mL, 100 mL, 200 mL, 250 mL, 500 mL and
5% GLUCOSE (DEXTROSE) IN
1 L bottle/bag (IV infusion)
WATER
Composition:
Na+ --- 154 mmol/L ,QM 250 mL bottle/bag (IV infusion, and as vehicle
Cl- --- 154 mmol/L for IV medications)
A sterile, non-pyrogenic, isotonic solution of sodium A sterile, non-pyrogenic solution of dextrose that is
chloride in water for injection. indicated for use in adults and children as a
source of calories and water of hydration.
,QGLFDWLRQV Fluid and electrolyte replacement
therapy in conditions where water and sodium ,QGLFDWLRQV Replacement therapy in conditions
losses are in isotonic proportion; vehicle for IV mainly due to water losses; in patients with el-
drug administration; priming and rinsing fluid evated serum sodium; IV infusion to keep vein
for hemodialysis; lavage in surgical patients. open for IV drug administration.
&RQWUDLQGLFDWLRQV Where the administration of &RQWUDLQGLFDWLRQ Known hypersensitivity to corn

sodium or chloride could be clinically detri- or corn products.
mental. 'RVH
'RVH For replacement therapy, by IV infusion, depending
Fluid and electrolyte replacement, by IV infusion, on requirement, with average dose: 1,000-
$'8/7 and &+,/' determined on the basis 2,000 mL/day (flow rate up to 120
drops/minute, 360 mL/hour).
155
Dose Adjustment: sodium or chloride could be clinically detri-
Renal Impairment: mental.
Care should be taken in dose selection (increased
Dose: Dose is dependent on age, weight and clini-
risk of adverse effects).
cal condition of patient.
Precautions:
Dose Adjustment:
WARNING: Mix the infusion solutions thoroughly after
Renal Impairment:
adding concentrated electrolytes to avoid possible
toxicity. Care should be taken in dose selection (increased
risk of adverse effects).
The administration of IV solutions can cause fluid
and/or solute overload which can result in dilu- Precautions:
tion of serum electrolyte concentration, over- WARNING: Mix the infusion solutions thoroughly after
hydration, congested states or pulmonary
toxicity.
edema; prolonged infusion of isotonic or hypo-
tonic dextrose in water may increase the vol- May cause salt and fluid retention in patients with
ume of extracellular fluid and cause water in- cardiovascular condition, cirrhotic disease,
toxication; may aggravate hyponatremia; may and nephrotic disease, and in patients re-
cause water retention; solutions containing ceiving corticosteroid therapy; may precipi-
dextrose should be used with caution in pa- tate CHF; may aggravate hypertension; so-
tients with overt or known DM or carbohydrate lutions containing dextrose should be used
intolerance for any reason. with caution in patients with overt or known
NOTE: Dextrose injection contains aluminum which may be diabetes mellitus and carbohydrate intoler-
toxic, particularly in those with impaired kidney func- ance for any reason; clinical evaluation and
tion (e.g., premature neonates). periodic laboratory examinations are nec-
Adverse Drug Reactions: essary.
NOTE: Adverse reactions which may occur because of the
solution or the technique during administration include
febrile response, infection at the site of injection, ve- Rare: Sodium accumulation, water retention.
nous thrombosis or phlebitis extending from the site of
Drug Interactions:
injection, extravasation and hypervolemia.
Drug Interactions: No information found. Corticosteroids and corticotropin – associated with
the retention of sodium and water, with in-
Administration: Rate of administration should be
creased risk of hypertension and edema.
adjusted according to the tolerance (too rapid
infusion of hypertonic solutions may cause lo- Administration: Too rapid infusion of hypertonic
cal pain and venous irritation). Use of the solutions may cause local pain and venous ir-
largest peripheral vein and a small bore nee- ritation. The rate of administration should be
dle is recommended. adjusted according to tolerance.
NOTE: Parenteral drug products should be inspected visual- NOTE: Parenteral drug products should be inspected visual-
ly for particulate matter and discoloration prior to ad- ly for particulate matter and discoloration prior to ad-
ministration, whenever solution and container permit. ministration, whenever solution and container permit.
Pregnancy Category: C Pregnancy Category: C
5% GLUCOSE (DEXTROSE) IN 5% GLUCOSE (DEXTROSE) IN

0.3% SODIUM CHLORIDE 0.9% SODIUM CHLORIDE
Inj.: 250 mL, 500 mL, and 1 L bottle/bag Inj.: 500 mL and 1 L bottle/bag (IV infusion)
(IV infusion) Composition:
Composition: Glucose (Dextrose --- 50 g/L
Glucose (Dextrose) --- 50 g/L Na+ --- 155 mmol/L
Na+ --- 51 mmol/L Cl- --- 154 mmol/L
Cl- --- 51 mmol/L
A sterile, non-pyrogenic, large-volume parenteral
A sterile, non-pyrogenic, large-volume parenteral solution, which contains 0.9% of sodium chlo-
solution, which contains 0.3% of sodium chloride and 5% dextrose in water for injection; a
ride and 5% dextrose in water for injection; a source of electrolytes, water and calories for
source of electrolytes, water and calories for patients.
patients.
Indications: Initial fluid and electrolyte replacement
Indications: Initial fluid replacement therapy for therapy in conditions with combined water and
patients having elevated serum sodium and sodium depletion; as vehicle for IV drug ad-
conditions where fluid loss exceeds electrolyte ministration.
loss.
Contraindications: Known hypersensitivity to corn
Contraindications: Known hypersensitivity to corn
or corn products; where the administration of or corn products; where the administration of
156
PNF new 182 new .pdf 1 1/8/15 2:37 PM
sodium or chloride could be clinically detri- &RQWUDLQGLFDWLRQV Known hypersensitivity to

mental. sodium lactate; allergy to corn or corn prod-
ucts.
'RVH Dose is dependent on age, weight and clini-
cal condition of patient. See Sodium Chloride. 'RVH
The dose is dependent on age, weight and clinical
'RVH$GMXVWPHQW
condition of patient.
Renal Impairment:
Care should be taken in dose selection (increased 'RVH$GMXVWPHQWV
risk of adverse effects). RenalDQGHepatic Impairment:
Care should be taken in dose selection (increased
3UHFDXWLRQV risk of adverse effects, e.g., sodium and po-
:$51,1*: Mix the infusion solutions thoroughly after tassium retention).

toxicity. 3UHFDXWLRQV

May cause salt and fluid retention in patients with :$51,1*: Although Lactated Ringer’s and 5% Dextrose
cardiovascular condition, cirrhotic disease, Injection, USP has a potassium concentration similar
to the concentration in plasma, it is insufficient to pro-
and nephrotic disease, and in patients receiv-
duce a useful effect in case of severe potassium defi-
ing corticosteroid therapy; may precipitate ciency; therefore, it should not be used for this pur-
CHF; may aggravate hypertension; solutions pose.
containing dextrose should be used with cau-
tion in patients with overt or known diabetes Mix the infusion solutions thoroughly after adding
concentrated electrolytes to avoid possible toxicity.
mellitus and carbohydrate intolerance for any
reason. The infusion should be stopped immediately if any
$GYHUVH'UXJ5HDFWLRQV signs or symptoms of a suspected hypersensi-
tivity reaction develop.
Rare: Sodium accumulation, water retention.
Not used for the treatment of lactic acidosis or
'UXJ,QWHUDFWLRQV severe metabolic acidosis.
Monitor closely with: Should not be administered simultaneously with
Corticosteroids and corticotropin – associated with citrate anticoagulated/preserved blood
the retention of sodium and water, with in- through the same administration set (in-
creased risk of hypertension and edema. creased likelihood of coagulation).
Pregnancy (hypersensitivity reactions are reported
$GPLQLVWUDWLRQ Too rapid infusion of hypertonic
more frequently).
solutions may cause local pain and venous ir- Can cause fluid and/or solute overloading resulting
ritation. The rate of administration should be in dilution of serum electrolyte concentrations,
adjusted according to tolerance. overhydration, congested states, pulmonary
127(: Parenteral drug products should be inspected visual-
ly for particulate matter and discoloration prior to ad- edema or acid-base imbalance.
ministration, whenever solution and container permit. Patients with hyperkalemia or conditions predispos-
ing to hyperkalemia (such as severe renal im-
3UHJQDQF\&DWHJRU\ C pairment or adrenocortical insufficiency, acute
dehydration, or extensive tissue injury or
burns) and in patients with cardiac disease.
5% GLUCOSE (DEXTROSE) IN Patients with alkalosis or at risk for alkalosis (lactate
LACTATED RINGER’S is metabolized to bicarbonate, administration
may result in, or worsen, metabolic alkalosis).
,QM 250 mL, 500 mL and 1 L bottle/bag Patients with severe renal impairment, hypervole-
(IV infusion) mia, overhydration, or conditions that may
Composition: cause sodium and/or potassium retention, flu-
Glucose (Dextrose) --- 50 g/L id overload, or edema.
Na+ --- 130 mmol/L In patients with impaired glucose tolerance and
K+ --- 4 mmol/L diabetes mellitus (it may result in hyperglyce-
Ca2+ --- 3 mmol/L mia); hyperglycemia has been implicated in
Cl- --- 109 mmol/L increasing cerebral ischemic brain damage
Lactate --- 28 mmol/L and impairing recovery after acute ischemic
strokes.
A sterile, non-pyrogenic solution, which contains 5% In patients with conditions associated with in-
dextrose and lactated ringer’s solution, in a creased lactate levels or impaired lactate utili-
single-dose container for intravenous admin- zation, such as severe hepatic insufficiency
istration and is capable of producing a meta- (hyperlactatemia can develop; may not pro-
bolic alkalinizing effect. duce an alkalinizing effect due impairment of

lactate metabolism).
,QGLFDWLRQV Source of water, electrolytes and
Administration of substantially hypertonic solutions
calories; or as an alkalinizing effect.
127(: Capable of inducing diuresis depending on the
(may cause venous irritation, including phlebi-
clinical condition of the patient tis); hyperosmolar solutions should be admin-
istered with caution, if at all, to patients with
hyperosmolar states.
157
Solutions containing calcium salts should be used Pressurizing intravenous solutions contained in
with caution in patients with hypercalcemia or flexible plastic containers to increase flow
conditions predisposing to hypercalcemia, rates can result in air embolism if the residual
such as patients with severe renal impairment air in the container is not fully evacuated prior
and granulomatous diseases associated with to administration.
increased calcitriol synthesis such as sar-
coidosis, calcium renal calculi or history of Pregnancy Category: C
such calculi.
Pediatric use in newborns (the risk of hyperglycemia
due to infusion of dextrose-containing solu-
tions appears to be greater with lower birth 50% GLUCOSE SOLUTION
weight; In these patients, hyperglycemia and
increased serum osmolarity have been asso- Inj.: 50%, 50 mL vial (IV)
ciated with an increased risk of intraventricular
cerebral hemorrhage); lactate-containing solu- A sterile, hypertonic solution of glucose, which
tions should be administered with particular provides a source of calories in a minimal vol-
caution to neonates and infants less than 6 ume of water, and is used in restoring blood
months of age. glucose concentrations in the treatment of hy-
Elderly – usually starting at the low end of the dos- poglycemia.
ing range, reflecting the greater frequency of Indications: Fluid replacement without significant
decreased hepatic, renal, or cardiac function, electrolyte deficit; severe hypoglycemia in an
and of concomitant disease or drug therapy. adult who is unable to take oral food or fluids.
Adverse Drug Reactions: Contraindications: Hyperglycemia; use of hyper-
Less Common: Pain and inflammation at the injec- osmotic solutions in patients with anuria; dia-
tion site, phlebitis, tissue necrosis, venous irri- betic coma; glucose-galactose malabsorption
tation, venous thrombosis. syndrome; dehydrated patients with delirium;
Rare: Angioedema, anxiety, blood pressure de- intracranial or intraspinal hemorrhage; should
creased, bronchospasm, chest discomfort and not be used after ischemic attacks.
pain, cough, decreased heart rate, dysgeusia,
dyspnea, edema, erythema, flushing, head- Dose:
ache, hyperkalemia, hypersensitivity reac- Fluid replacement, by IV infusion, ADULT and
tions, including anaphylactic and anaphylac- CHILD, determined on the basis of clinical
toid reactions; hypesthesia, nausea, pares- and, whenever possible, electrolyte monitor-
thesia, pruritus, pyrexia, rash, respiratory dis- ing.
tress, tachycardia, throat irritation, urticaria. Treatment of hypoglycemia, by IV infusion (50%
glucose solution into a large vein), ADULT,
Drug Interactions: 25-50 mL.
Acidic drugs (e.g., salicylates and barbiturates) – Dose Adjustment:
their renal clearance may be increased by lac- Renal Impairment:
tated ringer’s solution. Care should be taken in dose selection.
Basic drugs (e.g., sympathomimetics) – their renal Precautions:
clearance may be decreased by lactated ring- Hypertonic solutions of glucose should be adminis-
er’s solution. tered via a large central vein (to minimize
Corticosteroids – increase the risk of sodium and damage at the site of injection, e.g., thrombo-
fluid retention phlebitis); diabetes mellitus (may require addi-
Drugs which can cause hyperkalemia (e.g., potassi- tional insulin); glucose solutions should be
um-sparing diuretics, angiotensin II receptor used with caution in patients with overt or
antagonists, ACE inhibitors or the immuno- known subclinical DM, carbohydrate intoler-
suppressants) – increased risk of hyperkale- ance for any reason, severe undernutrition,
mia. thiamine deficiency, hemodilution, sepsis,
Lithium – possibly increased renal clearance. trauma, hypophosphatemia, shock, metabolic
Thiazide Diuretics or vitamin D – increase the risk of acidosis or severe dehydration; rapid admin-
hypercalcemia. istration of hypertonic glucose solutions may
Avoid concomitant use with: produce substantial hyperglycemia and hy-
Ceftriaxone – risk of ceftriaxone-calcium salt pre- perosmolar syndrome; patients should be ob-
cipitation in the bloodstream. served for signs of mental confusion and loss
Administration: The solution is administered IV; do of consciousness, especially those patients
not administer unless solution is clear and with chronic uremia or carbohydrate intoler-
container is undamaged. ance; prolonged use in parenteral nutrition
NOTE: Parenteral drug products should be inspected visual- may affect insulin production (blood and urine
ly for particulate matter and discoloration prior to ad- glucose should be monitored); IV administra-
ministration, whenever solution and container permit. tion of glucose may result in hypophos-
Do not connect flexible plastic containers in series phatemia, hypokalemia and hypomagnese-
in order to avoid air embolism due to possible mia.
residual air contained in the primary container.
158
Do not administer glucose solutions through the Precautions:
same infusion equipment as whole blood WARNING: Mix the infusion solutions thoroughly after
since hemolysis and clumping may occur. adding concentrated electrolytes to avoid possible
Pregnancy (may result in fetal insulin production, toxicity.
with an associated risk of rebound hypogly- Sodium metabisulfite may cause allergic type reac-
cemia in the neonate). tions, including anaphylactic symptoms, and
Adverse Drug Reactions: life-threatening or less severe asthmatic epi-
NOTE: The administration of glucose without adequate sodes in susceptible patients; patients with
thiamine levels may precipitate overt deficiency states CHF, renal insufficiency and in clinical states,
e.g., Wernicke's encephalopathy. in which there exists edema with sodium re-
Less Common: Pain at the injection site, phlebitis, tention; administration of the solution can
tissue necrosis, venous irritation, venous cause fluid and/or solute overloading resulting
thrombosis. in dilution of serum electrolyte concentration,
Rare: Dehydration, edema or water intoxication, overhydration, congested states or pulmonary
fluid and electrolyte imbalance, glycosuria, edema.
hyperglycemia, hypokalemia, hypomagnese- NOTE: Clinical evaluation and periodical laboratory determi-
mia, hypophosphatemia. nations are necessary to monitor changes in fluid bal-
ance, electrolyte concentration, and acid-base bal-
Drug Interactions: ance during prolonged therapy or whenever the pa-
Monitor closely with: tient’s condition warrants such evaluation.
Magnesium salts – associated with lower fasting Adverse Drug Reactions:
glucose and insulin. NOTE: Adverse reactions which may occur because of the
solution or the technique during administration include
Administration: Should be administered via a large
febrile response, infection at the site of injection, ve-
vein (e.g., into a secure IV cannula in an ante- nous thrombosis or phlebitis extending from the site of
cubital vein). injection, extravasation and hypervolemia.
ly for particulate matter and discoloration prior to ad- Drug Interactions:
ministration, whenever solution and container permit. Monitor closely with:
Pregnancy Category: C Corticosteroids and corticotropin – associated with
Administration: The solution is administered IV; do
BALANCED MULTIPLE not administer unless the solution is clear and
REPLACEMENT SOLUTION container is undamaged.
Inj.: 500 mL and 1 L bottle/bag (IV infusion) ly for particulate matter and discoloration prior to ad-
ministration, whenever solution and container permit.
Composition:
Na+ --- 140 mmol/L Pregnancy Category: C
K+ --- 5 mmol/L
2+
Mg --- 3 mmol/L
-
Cl --- 98 mmol/L
Acetate --- 50 mmol/L LACTATED RINGER’S SOLUTION
Plus 5% glucose (dextrose) (RINGER’S LACTATE)
A sterile, non-pyrogenic solution consisting of bal- Inj.: 500 mL and 1 L bottle/bag (IV infusion)
anced electrolytes with 5% dextrose in water Composition:
for injection. Na+ --- 130 mmol/L
K+ --- 4 mmol/L
Indication: Acute fluid and electrolyte replacement
Ca2+ --- 1.22-1.50 mmol/L
therapy; fluid replacement in hyperchloremic
Cl- --- 109 mmol/L
acidosis.
Lactate --- 28 mmol/L
Contraindication: Not to be used for fluid and
electrolyte maintenance therapy; hyperkale- A sterile, non-pyrogenic, lactate-containing solution,
mia, hypermagnesemia, metabolic alkalosis. which serves as a source of water and elec-
trolytes, and produces a metabolic alkalinizing
Dose: The dose is dependent on age, weight, and effect.
degree of fluid and electrolyte loss.
Indications: Fluid and electrolyte replacement
Dose Adjustment: therapy in the presence of acidosis; IV infu-
Renal Impairment: sion in the initial management of the injured or
Care should be taken in dose selection (increased wounded; hypovolemic shock.
risk of adverse effects, e.g., sodium and po-
tassium retention). Contraindications: Metabolic and respiratory
alkalosis; hypocalcemia; hypochlorhydria; lac-
tic acidosis; anuria, oliguria; hyperkalemia; in-
creased BUN; cardiac failure.
159
Dose: The dose is dependent on age, weight and ORAL REHYDRATION SALTS
clinical condition of patient.
(ORS 75-replacement)
Dose Adjustment:
Oral:
Composition: (WHO recommended)
Care should be taken in dose selection (increased Reduced osmolarity ORS in g/L
risk of adverse effects, e.g., sodium and po-
tassium retention). Sodium chloride - 2.6 g
Trisodium citrate dehydrate - 2.9 g
Precautions: Potassium chloride - 1.5 g
WARNING: Mix the infusion solutions thoroughly after Glucose, anhydrous - 13.5 g
adding concentrated electrolytes to avoid possible Total Weight - 20.5 g
toxicity.
Reduced osmolarity ORS Equivalent in mmol/L:
Avoid simultaneous administration with blood (likeli-
hood of coagulation); hyperkalemia; hyper- Sodium - 75
natremia; hyperchloremia; cardiac diseases; Chloride - 65
alkalosis; increased blood glucose; hepatic Potassium - 20
impairment (impaired lactate utilization); in Citrate - 10
conditions which may cause sodium or potas- Glucose, anhydrous - 75
sium retention, fluid overload or edema (e.g., Total osmolarity - 245
renal impairment, hypervolemia or overhydra- N.B. Reconstitute with clean potable water. Unused reconsti-
tion). tuted solution shall be discarded after 24 hours.
There is risk for hyponatremia due to lower sodium
content compared to 0.9% NaCl or Balanced An oral rehydration salt formulation containing
Multiple Replacement Solution. reduced osmolar concentration of sodium and
glucose that is widely used in treating children
Adverse Drug Reactions: with acute non-cholera diarrhea, and in adults
Less Common: Pain and inflammation at the injec- and children with cholera.
tion site, phlebitis, tissue necrosis, venous irri-
Indications: Replacement of fluid and electrolyte
tation, venous thrombosis.
Rare: Angioedema, anxiety, blood pressure de- losses in mild to moderate dehydration due to
creased, bronchospasm, chest discomfort and acute diarrhea or vomiting; replacement of
pain, cough, decreased heart rate, dysgeusia, continuing loss from vomiting or diarrhea.
dyspnea, edema, erythema, flushing, head- Contraindications: Severe dehydration; severe
ache, hyperkalemia, hypersensitivity reac- and sustained vomiting; diarrhea; glucose
tions, including anaphylactic and anaphylac- malabsorption; to patients with difficulty in
toid reactions; hypesthesia, nausea, pares- drinking.
thesia, pruritus, pyrexia, rash, respiratory dis-
tress, tachycardia, throat irritation, urticaria. Dose:
Fluid and electrolyte loss in acute diarrhea, by
Drug Interactions: mouth, ADULT, 200-400 mL solution after
Monitor closely with: every loose motion; INFANT and CHILD, ac-
Acidic drugs (e.g., salicylates and barbiturates) – cording to Plans A, B, or C (Refer to Guide-
their renal clearance may be increased by lac- lines in the Management of Diarrhea and
tated ringer’s solution. Dehydration for other important and more com-
Basic drugs (e.g., sympathomimetics) – their renal plete information).
clearance may be decreased by lactated ring-
er’s solution. Plan A: No dehydration (in infants and children).
Drugs which can cause hyperkalemia (e.g., potassi- Nutritional advice, increased fluid intake (in the form
um-sparing diuretics, angiotensin II receptor of soup, rice, water and yogurt, or even just
antagonists, ACE inhibitors or the immuno- water), and zinc supplementation at home are
suppressants) – increased risk of hyperkale- usually sufficient. However, for infants aged
mia. <6 months who have not yet started taking
Lithium – possibly increased renal clearance. solids, oral rehydration solution must be pre-
Thiazide diuretics or vitamin D – increase the risk of sented before offering milk. Mother’s milk or
hypercalcemia. dried cow’s milk must be given without any
Avoid concomitant use with: particular restrictions. In the case of mixed
Ceftriaxone – risk of ceftriaxone-calcium salt pre- breast-milk/formula feeding, the contribution of
cipitation in the bloodstream. breastfeeding should be increased. Parents
should be informed about the circumstances,
Administration: The solution is administered IV; do in which they should seek further advice.
not administer unless solution is clear and
container is undamaged. Plan B: Moderate dehydration (in infants and
NOTE: Parenteral drug products should be inspected visual- children).
ly for particulate matter and discoloration prior to ad- Whatever the child’s age, a 4-hour treatment plan is
ministration, whenever solution and container permit. used to avoid short-term problems. It is rec-
Pregnancy Category: C ommended that parents are shown how to
give approximately 75 mL/kg of oral rehydra-
tion solution (in small amounts and at regular
160
intervals) over a 4-hour period. Parents or
caregivers must be observant to see how the SODIUM CHLORIDE
child copes at the beginning of the treatment.
A larger amount of solution can be given if the Inj.: 2.5 mEq/mL, 20 mL and 50 mL vial
child continues to have frequent stools. In the
event of vomiting, rehydration must be discon- A sterile, non-pyrogenic, concentrated solution of
tinued for 10 minutes and then resumed at a sodium chloride administered IV, only after di-
slower rate. In young children, breastfeeding lution, to replenish electrolytes.
should be continued upon demand; older chil- Indications: Hyponatremia with overt manifesta-
dren should receive milk and nutritious food tions.
as normal after completing the 4 hours of oral
rehydration. The child’s status must be reas- Contraindications: Where the administration of
sessed after 4 hours to decide on the most sodium or chloride could be clinically detri-
appropriate subsequent treatment. Zinc sup- mental (e.g., hypernatremia); fluid retention;
plementation should begin as soon as the hypertension; CHF.
child can eat and has completed 4 hours of Dose:
oral rehydration. Oral rehydration solution
Dose of sodium chloride is dependent on degree of
should continue to be offered once dehydra-
sodium depletion (i.e., moderately severe hy-
tion has been controlled, for as long as the
ponatremia where serum sodium is between
child continues to have diarrhea.
125-129 mmol/L or profound hyponatremia
Plan C: Severe dehydration (in infants and chil- where serum sodium is <125 mmol/L); on se-
dren). verity of symptoms (i.e., moderately or severe-
Hospitalization is necessary, but the most urgent ly symptomatic); and on time of development
priority is to start rehydration. of hyponatremia (acute, where hyponatremia
In the hospital (or elsewhere), if the child can is documented to exist <48hrs).
drink, oral rehydration solution must be given IMPORTANT NOTE: Sodium deficit must be cor-
pending, and even during, IV infusion (give 20 rected gradually in stages. Avoid overtly rapid
mL/kg ORS every hour by mouth before infu- correction to prevent development of Osmotic
sion, then 5 mL/kg every hour by mouth dur- Demyelination Syndrome (previously named
ing IV rehydration). Central Pontine Myelinosis). The rate of cor-
For IV supplementation, it is recommended that rection of hyponatremia should not be more
Lactated Ringer’s solution, preferably D5LR than 10 mmol/L (or 10 mEq/L) in 24 hours,
(or, if this is unavailable, normal saline solu- or 18 mmol/L (or 10 mEq/L) in 48 hours.
tion or 0.9% sodium chloride solution) is ad-
Dose Adjustment:
ministered at a rate adapted to the child’s age
Renal Impairment:
(infant under 12 months: 30 mL/kg over 1 hour
Caution should be taken in dose selection (may
then 70 mL/kg over 5 hours; child over 12
result in sodium retention and increased risk
months: 30 ml/kg over 30 minutes then 70
of adverse effects).
ml/kg over 2.5 hours).
If the IV route is unavailable, a nasogastric tube is Precautions:
also suitable for administering oral rehydration WARNING: The product contains aluminum, which may be
solution at a rate of 20 mL/kg every hour for 6 toxic. Aluminum may reach toxic levels with prolonged
hours. If the child vomits, the rate of admin- parenteral administration, especially if kidney function
istration of the oral solution must be reduced. is impaired. Premature neonates are particularly at
Reassess the child's status after 3 hours (6 risk because their kidneys are immature.
hours for infants) and continue treatment as Monitor fluid balance, electrolyte concentration, and
appropriate with plan A, B, or C. acid-base balance; observe for hyper-
natremia, water retention and pulmonary
Dose Adjustment:
edema; restrict in patients with renal insuffi-
Renal Impairment:
ciency or failure, cardiac failure, hypertension,
Care should be taken in dose selection.
peripheral and pulmonary edema, or toxemia
Precautions: of pregnancy (may cause fluid and salt reten-
Renal impairment (there is increased risk of adverse tion in cardiac, cirrhotic or nephrotic patients;
effects); severe dehydration should be treated possibly aggravate hypertension); presence of
with IV electrolyte solutions. seizures or neurologic deficit requires aggres-
sive therapy; the IV administration of this solu-
Adverse Drug Reactions: tion (after appropriate dilution) can cause fluid
Rare: Hypernatremia, vomiting. and/ or solute overloading resulting in dilution
Drug Interactions: No information found. of other electrolyte concentration, overhydra-
tion, congested states or pulmonary edema;
Administration: Reconstitute it with clean potable excessive administration of potassium-free so-
water. Unused reconstituted solution shall be lutions may result in significant hypokalemia.
discarded after 24 hours. It may be taken with
or without food. Adverse Drug Reactions:
Pregnancy Category: C solution, added drugs or the technique of reconstitu-
tion or administration include (but are not limited to):
161
air embolization, febrile response, local tenderness, nates or very small infants, the volume of fluid
tissue necrosis or infection at the site of injection, ve- may affect fluid and electrolyte imbalance.
nous thrombosis or phlebitis extending from the site of NOTE: Label to indicate that no antimicrobial or other sub-
injection and extravasation. stance has been added, and that it is not suitable for
Rare: Edema, sodium accumulation. IV injection without first having been made approxi-
mately isotonic by the addition of a suitable solute.
Drug Interactions: Preserve in single-dose or plastic containers, of not
Monitor closely with: larger than 1-L size. Type I or Type II glass containers
Corticosteroids and corticotropin – associated with are preferable.
Administration: Sodium chloride injection must be solution, added drugs or the technique reconstitution
diluted before infusion to avoid a sudden in- or administration include: febrile response, local ten-
crease in the plasma-sodium level; too rapid derness, abscess, tissue necrosis or infection at the
administration should be avoided (see under site of injection, venous thrombosis or phlebitis ex-
Dose, particularly Important Note). Administra- tending from the site of injection, and extravasation.
tion should be based on calculated dose re- Drug Interactions:
quirements for each patient. Some drugs for injection may be incompatible in a
given vehicle, or when combined in the same
ly for particulate matter and discoloration prior to ad-
ministration, whenever solution and container permit. vehicle.
Do not use unless the solution is clear and seal is in-
Administration: Inspect the reconstituted (dis-
tact. Discard unused portion.
solved or diluted) drugs for clarity and free-
Pregnancy Category: C dom from unexpected precipitation or discol-
oration prior to administration.
Pregnancy Category: No information found.
STERILE WATER FOR INJECTION
Inj.: 2 mL, 5 mL, 10 mL and 20 mL ampul

50 mL, 100 mL, 500 mL and 1 L bottle/bag (no
preservative)
A sterile, nonpyrogenic water for injection that does
not contain any antimicrobial agent or other
added substances, such as buffer, and is
supplied in single-dose containers to dilute or
dissolve drugs for injection.
Indication: Used only for dissolving or diluting
medicines that are intended for parenteral in-
jection.
NOTE: Should be in accordance with the instructions set by
the manufacturer of the drug.
Contraindications: Sterile water for injection, USP

should be made isotonic prior to use (not for
direct infusion; do not use for non-automated
admixture preparations).
Dose:
The volume of the preparation to be used for any
drug for injection is based on the vehicle con-
centration, dose and route of administration as
recommended by the drug manufacturer.
Precautions:
WARNING: IV administration without a solute may result in
hemolysis.
Do not use for IV injection unless the osmolar con-
centration results in an isotonic admixture; do
not heat over 66°C (150°F); do not use unless
the solution is clear and intact; mix thoroughly
and use promptly after diluting/dissolving
drugs; do not store reconstituted solutions of
drugs for injection, unless otherwise directed;
do not reuse single-dose containers; in neo-
162
Rare: Anaphylaxis.
VACCINES and IMMUNOLOGICALS
Drug Interaction:
Corticosteroids – these may attenuate the immune
ANTI-RABIES SERUM response to the anti-rabies serum.
Vaccines (Live, attenuated, virus) – immunoglobulin
Inj.: 200 IU/mL, 5 mL vial (IM) administration may interfere with the devel-
400 IU/mL, 5 mL vial (IM) opment of immune response to vaccines.
A sterile, non-pyrogenic preparation which consists Administration: Administer as soon as possible, at

of F(ab’)2 fragments of equine antirabies im- the same time as the rabies vaccine, or up to
munoglobulin of not less than 200 IU/mL. 7 days after vaccine injection; the remaining
serum should be administered via the IM route
Indication: (into the gluteal region) in a single injection
For the seroprophylaxis of rabies in individuals who NOTE: Vaccines should be stored within the safe tempera-
are suspected to have been exposed to the ture range of 2-8°C. Freezing is the most common
rabies virus, when rabies immunoglobulin cause of vaccine damage; do not use a defrosted
vaccine unless freezing is the recommended storage
(human) is unavailable or unaffordable.
condition.
Contraindications: Pregnancy Category: C
Known hypersensitivity to products prepared from
horse serum, or any other component within
the serum; Not for IV administration.
NOTE: The lethal risk associated with rabies overcomes any
potential. ANTI-TETANUS SERUM
Dose: Inj.: 4,000 IU/mL, 2.5 mL vial/ampul (IM)
Prophylaxis of rabies from suspected individuals, by 1,500 IU/mL, 1 mL and 1.5 mL vial/ampul (IM)
infiltration, ADULT and CHILD, 40 IU/kg of
body weight in and around the cleansed A sterile, nonpyrogenic preparation obtained from
wound; if infiltration of whole volume is not the fractionation of serum of horses, which
possible, give the remainder by IM injection have been immunized against tetanus toxin,
slowly (wounds in certain anatomical sites, and contains the specific antitoxin globulins
such as fingertips, should be infiltrated with that may neutralize the toxin formed by Clos-
care so as to prevent a local increase in pres- tridium tetani.
sure in the tissue). Indications: Prophylaxis against tetanus in non-
NOTE: When the volume required to infiltrate the wound(s)
exceeds the recommended dose, some clinicians immune individuals after serious injury or bite
recommend diluting the calculated dose in saline to when tetanus immunoglobulin (human) is un-
yield a two- to threefold increase in solution volume to available or unaffordable; treatment of tetanus
ensure that all wound areas receive adequate infiltra- when tetanus immunoglobulin is unavailable
tion. or unaffordable.
Dose Adjustments: No information found. Contraindications: Known hypersensitivity to
Precautions: tetanus antitoxin or any other component with-
Do not administer intravenously (due to a risk of in the serum, and any product prepared from
shock); ensure that the needle has not pene- horse serum.
trated a blood vessel; do not give repeated Dose:
doses once rabies vaccine is given as this Post-exposure prophylaxis against tetanus, by IM
may reduce the immunologic response to the injection, 3,000-5,000 IU.
vaccine; despite the high degree of purifica- Treatment of tetanus infection, by IM injection,
tion of the serum, it is recommended to per- ADULT and CHILD, 50,000-100,000 IU single
form a skin test before administering rabies dose; NEWBORN, 500 units/kg or 5,000-
antiserum (to determine possible allergic 10,000 IU in tetanus neonatorum.
symptoms to horse proteins); if the recom- NOTE: The above doses could be given ½ IV and the rest
mended dosage is not strictly observed (e.g., IM after appropriate testing for sensitivity and desen-
overdosage), there is a risk of immunosup- sitization, if necessary.
pressive interference with rabies vaccine; In Dose Adjustments: No information found.
patients with a history of bleeding disorders,
including thrombocytopenia, and patients on Precautions:
anticoagulant therapy (bleeding/hematoma WARNING: Increased risk of fatal anaphylaxis in hypersen-
may occur from IM administration). sitive individuals.
NOTE: Immunoglobulins may interfere with the immune
response to live virus vaccines. Informed consent and skin test are required (a
negative skin or eye test is not an absolute
Adverse Drug Reactions: indication of the absence of sensitivity); a sy-
Common: Acute febrile reaction, injection site ringe with 0.3 mL of 1:1000 aqueous soln. of
swelling and pain, serum sickness-like re- epinephrine should be always at hand.
actions.
163
NOTE: Immunoglobulins may interfere with the immune Precautions:
response to live virus vaccines which should normally Pregnancy (first trimester: theoretical risk of con-
be given either at least 3 weeks before or at 3 months
genital malformations; but the need for vac-
after administration of an immunoglobulin.
cination may, sometimes, outweigh the possi-
Adverse Drug Reactions: ble risk to fetus); eczema and scabies (vac-
Common: Acute febrile reaction, injection site cine site should be lesion-free); patients who
swelling and pain, serum sickness-like reac- are known to be at high risk for HIV infection.
tions.
Rare: Anaphylaxis.
Common: Enlargement of regional lymph nodes,
Drug Interaction: ulcer at injection site (2-6 weeks after vaccina-
Avoid concomitant use with: tion).
Vaccines (Live, attenuated, virus) – immunoglobulin Less Common: Fainting, fever, injection site reac-
administration may interfere with the devel- tions (pain, redness, itching, small hard lump
opment of immune response to vaccines. that may persist for some weeks).
Rare: Abscess, allergic reactions including anaphy-
Administration: The serum should be administered laxis, disseminated infection, keloid formation,
via the IM route. If a large volume is required, lymphadenitis, osteitis.
it is recommended to administer the serum in
divided doses at different sites. Drug Interactions:
NOTE: Vaccines should be stored within the safe tempera- NOTE: Response to tuberculin test may be: suppressed, if
ture range of 2-8°C. Freezing is the most common given within 4-6 weeks following vaccination with live
cause of vaccine damage; do not use a defrosted viral vaccines (e.g., measles, MMR, polio); sup-
vaccine unless freezing is the recommended storage pressed, in patients receiving systemic corticosteroids
condition. (e.g. hydrocortisone) or aminocaproic acid; altered, in
malnutrition, age and presence of disseminated TB.
Pregnancy Category: X Other vaccines and immunoglobulins – these can
influence the ability of vaccines to induce an
immune response (give a live vaccine on the
same day or not < 4 weeks apart from anoth-
BCG VACCINE er live vaccine).
Inj.: Freeze-dried powder, 100 microgram/0.1 mL, Anti-infectives – avoid giving live vaccines with anti-
1 mL, 1.5 mL and 2 mL vial (ID) infectives, especially if they are active against
500 microgram/mL vial + 1 mL diluent in the organism in the vaccines, as the effective-
ampul (ID), 20 doses ness of vaccines may be reduced, preventing
A vaccine prepared from bacillus Calmette-Guerin, an immune response.
an attenuated strain of Mycobacterium bovis, Immunosuppressive agents (e.g., therapeutic doses
which reduces the incidence of meningeal and of corticosteroids or antineoplastics) and dur-
miliary TB in early childhood. ing radiation therapy – may decrease antibody
response to inactivated vaccines.
Indication: Active immunization against TB.
Administration: Give by ID injection (stretch skin
Contraindications: Known hypersensitivity to the between thumb and finger) above the inser-
vaccine or any of its components; previous TB tion of the deltoid muscle onto the humerus.
infection, or tuberculin reactions >5 mm; HIV NOTE: Vaccines should be stored within the safe tempera-
infection; significant fever (give at least 1 ture range of 2-8°C. Freezing is the most common
cause of vaccine damage; do not use a defrosted
month after fever subsides); patients receiving
immunosuppressive therapy; primary and condition.
secondary immune deficiency states; general-
ized septic skin conditions; burns; pregnancy. Pregnancy Category: C
Dose:
NOTE: Tuberculin test must be done before vaccination
(except in infants <6 months); give vaccine if indura- DIPHTHERIA-TETANUS TOXOID
tion is <5 mm 48-72 hours after dose of 10 tuberculin
units.
and PERTUSSIS VACCINE
Immunization against tuberculosis, by ID injection, Inj.: 0.5 mL ampul (IM)
ADULT and CHILD >12 months, 0.1 mL; IN- 0.5 mL pre-filled syringe (IM)
FANT up to 12 months, 0.05 mL. 0.5 mL, 5 mL, 7.5 mL and 10 mL vial (IM)
manufacturer’s directions. A three-component preparation of diphtheria, teta-
NOTE: Vaccine is preferably given at birth, or any time after nus and pertussis (whole-cell) vaccines whose
birth; may be given at the same time as other live rates of local and systemic reactions are high-
vaccines, if not given simultaneously, should be given er than acellular pertussis vaccine.
4 weeks apart; when given to infants, no need to de-
lay primary immunizations. Indication: Active immunization against diphtheria,
Dose Adjustments: No information found. tetanus, and pertussis.
Contraindications: Prior systemic hypersensitivity
reaction to the preparation or any ingredient in
164
the formulation (e.g., thimerosal); if there has NOTE: Travellers should receive appropriate vaccines
been a severe acute neurological illness with- regardless of the limitations if time is short.
NOTE: Vaccines should be stored within the safe tempera-
in 7 days of pertussis vaccination; individuals
ture range of 2-8°C. Freezing is the most common
with thrombocytopenia or any coagulation dis- cause of vaccine damage; do not use a defrosted
orders. vaccine unless freezing is the recommended storage
condition.
Dose:
Primary immunization of children against diphtheria, Pregnancy Category: C
tetanus, and pertussis, by IM injection,
ADULT, 0.5 mL; CHILD 1-6 years of age, 2
doses, each of 0.5 mL separated by an inter-
val of 2 months, followed by a third dose after HEPATITIS B VACCINE
6-12 months; INFANT from 6 weeks of age, 3 (Recombinant DNA)
doses, each of 0.5 mL with an interval of not Inj.: 10 micrograms/0.5 mL monodose vial
<4 weeks between each dose. (IM) (pediatric)
Dose Adjustments: No information found. 20 micrograms/mL monodose vial
(IM) (adult) (For more than 10 years)
Precautions: 20 micrograms/mL, 1 mL, 5 mL and 10 mL
Whole cell pertussis component associated with vial (IM)
more frequent minor adverse effects than
N.B.: Formulations of different manufacturers are of equal or
acellular pertussis component; frequency of
similar immunogenicity. Follow the re-commended
adverse effects increases with age and num- dose of each manufacturer strictly
ber of injections (vaccines which contain
whole cell pertussis are not recommended for A vaccine that contains HBsAg produced by the
adolescents and adults); children with proven, yeast S. cerevisiae using recombinant DNA
or suspected, underlying active or progressive technology, which is morphologically similar to
neurologic disorders (child may be vaccinated that contained in the plasma-derived hepatitis
⎼ may defer vaccination if there was a seizure B virus vaccine.
in the previous 3 weeks). Indications: Active immunization against Hepatitis
Pregnancy (adult vaccine may be used if neces- B; routine immunization of infants; infants who
sary). have been born to HBsAg-positive women;
Adverse Drug Reactions: other susceptible groups (e.g., health care
Common: Crying, drowsiness, irritability, limb swell- workers, HIV-positive people).
ing, restlessness. Contraindication: Known hypersensitivity to the
Less Common: Fever, lethargy, malaise, myalgia, preparation or any of its components.
transient injection site reactions (pain, red-
ness, itching, burning, small hard lump that Dose:
may persist for some weeks). Primary immunization of children against hepatitis B
Rare: Allergic reactions including anaphylaxis, (3-dose schedule), by IM injection, CHILD, 1
collapse, encephalopathy, headache, hypo- dose of 0.5 mL given between 6 weeks and
tonic-hyporesponsive episodes, peripheral 15 years of age, followed by 2 doses, each of
neuropathy, seizure, urticaria. 0.5 mL given at intervals of 4 weeks; alterna-
tively, 1 dose of 0.5 mL at birth, followed by 2
Drug Interactions: doses, each of 0.5 mL, given at 6 and 14
Monitor closely with: weeks of age.
Other vaccines and immunoglobulins – these can Primary immunization of children against hepatitis B
influence the ability of vaccines to induce an (4-dose schedule), by IM injection, CHILD, 1
immune response (give a live vaccine on the dose of 0.5 mL at birth, followed by 3 doses,
same day or not < 4 weeks apart from anoth- each of 0.5 mL, at 6, 10, and 14 weeks of age.
er live vaccine). NOTE: Immunization with hepatitis B vaccine can be timed
Avoid concomitant use with: to correlate with the diphtheria-tetanus-pertussis
Immunosuppressive agents (e.g., therapeutic doses schedule (see Immunization Schedules).
of corticosteroids or antineoplastics) and dur- Immunization of unimmunized high-risk persons
ing radiation therapy – these may decrease against hepatitis B, by IM injection, ADULT
antibody response to inactivated vaccines. and CHILD >15 years of age, 3 doses, each
NOTE: Any agent which is active against the bacterial or of 1 mL, with an interval of 1 month between
viral strain present in the vaccine may interfere with the first and second dose and 5-11 months
the development of a protective immune response, between the second and third doses; CHILD
but treatment with antibacterials is not a contraindica-
tion to immunization. <15 years, 0.5 mL (minimum recommended
interval between the doses, 4 weeks).
Administration: Live vaccines should either be NOTE: Different products may contain different concentra-
given simultaneously (at different sites) or at tion of antigen. Consult manufacturer’s literature for
an interval of at least three weeks. Live vac- further information.
cines should normally be given at least three Dose Adjustment:
weeks before, or at least three months after Renal Impairment:
the use of immunoglobulin. Larger doses required in chronic renal failure due to
impaired immune response.
165
Precautions: Dose:
Diabetes mellitus; chronic renal failure; impaired Immunization against influenza (annually for high-
liver (reduced immunogenicity); postpone ad- risk persons), by IM injection, ADULT and
ministration in patients with any febrile illness, CHILD >9 years, 0.5 mL as a single dose;
or active infection; lactation; this should not CHILD 3-9 years, initially 0.5 mL, with a sec-
be administered IV or ID. ond dose of 0.5 mL after at least 4 weeks if
not previously infected or vaccinated; CHILD
6-35 months, 0.25 mL as a single dose.
Common: Swelling.
Less Common: Fainting, fever, transient injection Dose Adjustments: No information found.
site reactions (pain, redness, itching, burning,
small hard lump that may persist for some Precautions:
weeks). Anaphylaxis reactions to eggs (may be able to
Rare: Allergic reactions, including anaphylaxis; receive influenza vaccine if egg ovalbumin <1
arthralgia, lymphadenopathy, malaise, myal- microgram/dose; seek the advice of a special-
gia, peripheral neuropathy. ist); children (adverse effects, such as fever,
myalgia and malaise, may be more severe in
Drug Interactions: children <5 years than in older children and
Monitor closely with: adults); breastfeeding (not known to be harm-
Other vaccines and immunoglobulins – these can ful).
immune response (give a live vaccine on the Adverse Drug Reactions:
same day or not < 4 weeks apart from anoth- Common: Fever, headache, malaise, myalgia.
er live vaccine). Less Common: Fainting, transient injection site
Avoid concomitant use with: reactions (pain, redness, itching, burning,
Immunosuppressive agents (e.g., therapeutic doses small hard lump that may persist for some
of corticosteroids or antineoplastics) and dur- weeks),
ing radiation therapy – these may decrease Rare: Allergic reactions, including asthma, hives,
antibody response to inactivated vaccines. angioedema, anaphylaxis; Guillain-Barré syn-
NOTE: Any agent which is active against the bacterial or drome.
viral strain present in the vaccine may interfere with
the development of a protective immune response,
Drug Interactions:
NOTE: Monitoring for possible enhanced drug effect or
toxicity should be considered for persons taking med-
tion to immunization.
ications metabolized by the cytochrome P450 system,
Administration: Vaccine should be given in the including warfarin, theophylline or anticonvulsant
deltoid region in adults and older children; an- when they receive influenza virus vaccination.
terolateral thigh is the preferred site in infants Monitor closely with:
and young children; it should not be injected Other vaccines and immunoglobulins – these can
into the buttock (due to reduced vaccine effi- influence the ability of vaccines to induce an
cacy). immune response (give a live vaccine on the
NOTE: Vaccines should be stored within the safe tempera- same day or not < 4 weeks apart from anoth-
ture range of 2-8°C. Freezing is the most common er live vaccine).
cause of vaccine damage; do not use a defrosted Phenytoin – enhanced effect of phenytoin.
vaccine unless freezing is the recommended storage Warfarin – occasionally enhanced effect of warfarin.
condition. Avoid concomitant use with:
Pregnancy Category: C Immunosuppressive agents (e.g., therapeutic doses
of corticosteroids or antineoplastics) and dur-
ing radiation therapy – these may decrease
antibody response to inactivated vaccines.
INFLUENZA POLYVALENT NOTE: Any agent which is active against the bacterial or
VACCINE viral strain present in the vaccine may interfere with
Inj.: 0.5 mL vial + pre-filled syringe diluent (IM) but treatment with antibacterials is not a contraindica-
0.5 mL suspension in a pre-filled syringe or tion to immunization.
ampul (IM) (adult) Administration: The trivalent, inactivated influenza
A sterile, aqueous suspension of suitable strains of vaccine should be given into the deltoid mus-
influenza virus types A and B, which are de- cle in adults and children >1 year, and the an-
veloped separately in embryonated hen eggs terolateral aspect of the thigh in infants 6-12
and inactivated. months of age.
Indication: Active immunization against influenza in ture range of 2-8°C. Freezing is the most common
individuals at risk. cause of vaccine damage; do not use a defrosted
Contraindications: Severe anaphylactic reactions condition.
to previous doses of influenza vaccine, chick-
en or egg protein; acute, severe febrile illness. Pregnancy Category: C
166
Drug Interactions:
LIVE ATTENUATED MEASLES Monitor closely with:
VACCINE Other vaccines and immunoglobulins – these can
Inj.: Monodose vial + 0.5 mL diluent (SC) influence the ability of vaccines to induce an
Multidose vial + 5 mL diluent (SC) immune response (give a live vaccine on the
A live, attenuated, single-antigen vaccine prepared er live vaccine).
through chick embryo tissue culture. Avoid concomitant use with:
Indication: Active immunization against measles. Immunosuppressive agents (e.g., therapeutic doses
Contraindications: Known hypersensitivity to the ing radiation therapy – these may decrease
preparation or any of its components (e.g., antibody response to inactivated vaccines.
anaphylaxis after measles immunization); se- NOTE: Any agent which is active against the bacterial or
vere immunodeficiency; administration of viral strain present in the vaccine may interfere with
high-dose steroids <1 month before; preg-
nancy. tion to immunization.
Dose: Administration: Administered subcutaneously,
Immunization of HIV-infected infants (unless se- preferably into the outer aspect of the upper
verely immunocompromised) against mea- arm (special care should be taken to ensure
sles, by IM or SC injection, INFANT, 1 dose of that the injection does not enter a blood ves-
0.5 mL at 6 months of age, followed by a sec- sel).
ond dose of 0.5 mL at 9 months of age.
Primary immunization of children against measles, cause of vaccine damage; do not use a defrosted
by IM or SC injection, INFANT and CHILD, 1 vaccine unless freezing is the recommended storage
dose of 0.5 mL at 9 or 12 months of age; a re- condition.
inforcing dose of 0.5 mL can be given after 4
weeks or up to 6 years of age.
Prophylaxis in susceptible individuals after exposure
to measles, by IM or SC injection within 48
hours of contact, ADULT and CHILD >9 LIVE ATTENUATED MEASLES,
months, 1 dose of 0.5 mL. MUMPS and RUBELLA VACCINE
manufacturer’s direction Inj.: Monodose vial + 0.5 mL diluent (SC)
Multidose vial + 5 mL diluent (SC)
A bacterially sterile, freeze-dried preparation of live,
Precautions:
attenuated strains of measles, mumps and ru-
Children with a history of hypersensitivity (anaphy-
bella virus that may contain antimicrobial
laxis) to egg protein must receive the vaccine
agents.
in a setting where reactions can be managed;
tuberculin and other skin test reactions may Indications: Active immunization against measles,
be temporarily reduced; children with history mumps, and rubella; non-immune women of
of seizures should be immunized after advis- child-bearing age at least 28 days before
ing the parents that the risk of seizure after pregnancy, or immediately post-partum; all
immunization is slightly increased (may re- non-immune adults.
quire treatment in reducing fever 5-12 days af-
ter giving the vaccine). Contraindications: Known hypersensitivity to the
Pregnancy (first trimester: risk of congenital malfor- preparation or any of its component (e.g., ne-
mations, but need for vaccination may, some- omycin); pregnancy (avoid use; pregnancy
times, outweigh possible risk to fetus; avoid should be avoided for 1 month after the im-
MMR); thrombocytopenia. munization); immunosuppression.
Adverse Drug Reactions: Dose:

NOTE: Adverse reactions are considerably less common Primary immunization of children against measles,
after the second dose. mumps, and rubella, by IM or SC injection,
Common: Arthralgia and arthritis (in women), fever, CHILD 12–15 months, 1 dose of 0.5 mL; a re-
headache, lymphadenopathy, rash, sore inforcing dose of 0.5 mL can be given 2–5
throat. years after the primary dose.
Less Common: Arthralgia and arthritis (in children), Prophylaxis in susceptible children after exposure to
fainting, febrile seizures, parotid swelling, measles, by IM or SC injection within 72 hours
transient injection site reactions (pain, red- of contact, CHILD 1 year and above, 1 dose
ness, itching, swelling/burning, small hard of 0.5 mL.
lump that may persist for some weeks).
Rare: Allergic reactions including anaphylaxis,
meningitis, chronic joint symptoms, encephali- Precautions:
tis, purpura, thrombocytopenia. Children with history of seizures (may require treat-
ment to reduce fever 5-12 days after vaccina-
tion); untreated TB (MMR can exacerbate the
167
condition; vaccinate when TB is being treat- Contraindications: Known hypersensitivity to the
ed); treatment with immunoglobulins, whole preparation or any of its components; primary
blood (normal immunoglobulin may interfere immunodeficiency; those who are immuno-
with the immune response to some live virus suppressed or their close contacts; diarrhea
vaccines; do not administer MMR vaccine for and vomiting.
3 months after IM immunoglobulin or whole
blood, or 9 months after IV immunoglobulin). Dose:
Pregnancy (avoid pregnancy for 28 days after vac- Primary immunization of children against poliomyeli-
tis, by mouth, CHILD, 3 drops at birth and at
cination; non-immune pregnant women should
be vaccinated postpartum). 6, 10, and at 14 weeks of age. Reinforcing
the immunization of children against poli-
Adverse Drug Reactions: omyelitis, by mouth, CHILD, 3 drops at least
NOTE: Adverse reactions are considerably less common 3 years after completion of primary course
after second dose. and a further 3 drops at 15-19 years of age.
Common: Arthralgia and arthritis (in women), fever, Primary immunization of unimmunized adult against
headache, lymphadenopathy, rash, sore poliomyelitis, by mouth, ADULT, 3 doses,
throat. each of 3 drops, with an interval of at least 4
Less Common: Arthralgia and arthritis (in children), weeks between each dose. Reinforcing the
fainting, febrile seizures, parotid swelling, immunization of adults against poliomyeli-
transient injection site reactions (pain, red- tis, by mouth, ADULT, 3 drops, 10 years after
ness, itching, swelling, burning, small hard completion of primary course.
Rare: Allergic reactions including anaphylaxis, Dose Adjustments: No information found.
meningitis, chronic joint symptoms, encephali- Precautions:
tis, purpura, thrombocytopenia.
The need for strict personal hygiene should be
Drug Interactions: stressed as the vaccine virus is excreted in
Monitor closely with: the feces (e.g., thorough handwashing be
Other vaccines and immunoglobulins – these can done after changing the baby’s diaper).
influence the ability of vaccines to induce an Pregnancy (first trimester: theoretical risk of con-
immune response (give a live vaccine on the genital malformations; the need for vaccina-
same day or not <4 weeks apart from another tion may, sometimes, outweigh the possible
live vaccine). risk of fetus).
Avoid concomitant use with: Adverse Drug Reactions:
Immunosuppressive agents (e.g., therapeutic doses Common: Swelling.
of corticosteroids or antineoplastics) and dur- Less Common: Fainting, fever, transient injection
ing radiation therapy – these may decrease site reactions (pain, redness, itching, burning,
antibody response to inactivated vaccines. small hard lump that may persist for some
NOTE: Any agent which is active against the bacterial or
viral strain present in the vaccine may interfere with weeks),
the development of a protective immune response, Rare: Allergic reactions, including anaphylaxis;
but treatment with antibacterials is not a contraindica- vaccine-associated paralytic poliomyelitis.
Drug Interactions:
Administration: Administered subcutaneously, Monitor closely with:
preferably into the outer aspect of the upper Other vaccines and immunoglobulins – these can
arm (special care should be taken to ensure influence the ability of vaccines to induce an
that the injection does not enter a blood ves- immune response (give a live vaccine on the
sel). same day or not < 4 weeks apart from anoth-
NOTE: Vaccines should be stored within the safe tempera- er live vaccine).
vaccine unless freezing is the recommended storage Immunosuppressive agents (e.g., therapeutic doses
condition. of corticosteroids or antineoplastics) and dur-
Pregnancy Category: C antibody response to inactivated vaccines.
LIVE ATTENUATED TRIVALENT but treatment with antibacterials is not a contraindica-
ORAL POLIO VACCINE tion to immunization.
Oral: 0.5 mL plastic tube and 0.5 mL vial Administration: For oral use only; it may be admin-
1 mL vial (10) doses and 2 mL vial (20) doses istered directly, or mixed with beverages or
or plastic tube with vaccine vial monitor (for foods such that these do not contain sub-
DOH Mass Immunization Program Only) stances that may inactivate polio-viruses, e.g.,
preservatives.
Indication: Active immunization of infants and NOTE: Suitable vehicles are simply syrup, milk, bread and a
children against poliomyelitis. lump of sugar. Care should be taken not to contami-
nate a multidose dropper with the saliva of the vac-
cine recipient.
168
NOTE: Vaccines should be stored within the safe tempera- Adverse Drug Reactions:
ture range of 2-8°C. Freezing is the most common Less Common: Anorexia, diarrhea, drowsiness,
fainting, fever, headache, malaise, nausea,
condition. transient injection site reactions (pain, red-
ness, itching, swelling, burning), vomiting,
Pregnancy Category: C warmth.
Rare: Allergic reactions including anaphylaxis,
nodule or sterile abscesses may be palpable
at the site of injection.
PENTAVALENT VACCINE
Drug Interactions:
Inj.: 0.4 mL vial suspension for injection (IM) Monitor closely with:
Other vaccines and immunoglobulins – these can
Contains: influence the ability of vaccines to induce an
Diphtheria toxoid ≥20 Lf to ≤30 Lf immune response (give a live vaccine on the
Tetanus toxoid ≥2.5 Lf to ≤10 Lf same day or not < 4 weeks apart from anoth-
B. pertussis ≥4 IU er live vaccine).
HBsAg (rDNA) ≥10 micrograms Avoid concomitant use with:
Purified capsular HiB 10 micrograms Anticoagulant therapy; Immunosuppressive thera-
Polysaccharide pies (e.g., antimetabolites, alkylating agents,
Adsorbed on ≤1.25 mg irradiation, cytotoxic drugs and corticoster-
Aluminum Phosphate, oids) – these may reduce the immune re-
Al
3+ sponse to the vaccine.
Preservative: 0.005% Administration: The liquid vaccine pre-filled sy-
Thiomersal ringe should be shaken before use to homog-
A homogeneous liquid that consists of purified enize the suspension. It should be injected IM.
diphtheria and tetanus toxoids, inactivated The vaccine should be visually inspected for
pertussis (whole cell), non-infectious particles any foreign particulate matter and/or variation
of Hepatitis B surface antigen (HBsAg) and H. of physical aspect prior to an administration.
influenza type b (Hib) capsular polysaccha-
ride. cause of vaccine damage; do not use a defrosted
Indications: Pentavalent vaccine is indicated for
condition.
the active immunization of infants, at or above
the age of 6 weeks against Diphtheria, teta- Pregnancy Category: C
nus, whooping cough, Hepatitis B and H. in-
fluenzae type b infections.
Contraindications: Known hypersensitivity to any RABIES IMMUNOGLOBULIN
component of the vaccine; after an immediate (EQUINE) – ERIG purified
anaphylactic reaction associated with a previ-
ous dose; infants or children with severe, fe- Inj.: Equine Rabies Immunoglobulin 200
brile illness. 200 IU/ml, 5 ml/vial
F(ab’)2 fragments of equine origin
Dose: 200 IU/ml, 5 ml/vial
For active immunization of infants and preschool
children, it is recommended that three IM in- Equine rabies immunoglobulin (ERIG) is of equine
jections of 0.5 mL should be administered with origin and is used as part of the management
an interval of four weeks between doses start- of potential rabies (passive immunity) follow-
ing at six weeks of age. ing exposure of an unimmunized individual to
a suspected animal.
Dose Age at immunization NOTE: ERIG is associated with more significant adverse
1st dose 6 weeks reactions compared to the human rabies immuno-
nd
2 dose 10 weeks globulin (HRIG). Purified ERIG is still used in develop-
ing countries due to its lower cost or availability. Min-
3rd dose 14 weeks imal adverse effects occur if it is in the purified form.
A booster dose of DTP and Hib should be adminis- If unpurified, it may cause serum sickness and ana-
phylaxis.
tered at the age of 15 to 18 months.
Indication:
Passive immunization, either post-exposure or in
Precautions:
suspected exposure, to rabies in unimmun-
The patient should remain under observation for not
ized individuals given in combination with ra-
<30 min for possibility of occurrence of imme-
bies vaccine.
diate or early allergic reactions. Adrenaline in-
jection (1:1000) should be immediately availa-
ble should an acute anaphylactic reaction oc-
cur.
169
NOTE: The Guidelines in the 2012 National Rabies Preven- caria, adenopathy and arthralgia, serum sick-
tion and Control Program recommend that Rabies ness-like reactions.
Immunoglobulin be given, in conjunction with rabies
Rare: Anaphylaxis (with hypotension, dyspnea and
vaccine, to patients with Category III Exposure that
includes: urticaria); nephrotic syndrome.
Treatment of anaphylaxis: give 0.5 mL of 0.1 percent
a. Transdermal bites (puncture wounds, lacerations, solution of Epinephrine/Adrenaline (1 in 1000, 1
avulsions) or scratches/abrasions with spontane- mg/mL) for adults, and 0.01 mL/kg body weight for
ous bleeding; children, injected subcutaneously or IM.
b. Licks on broken skin or mucous membrane;
c. Exposure to a rabies patient through bites, con- Drug Interaction:
tamination of mucous membranes (eyes, Avoid concomitant use with:
oral/nasal mucosa, genital/anal mucous mem- Vaccines (Live, attenuated, virus) – immunoglobulin
brane) or open skin lesions with body fluids
administration may interfere with the devel-
through splattering and mouth-to-mouth resuscita-
tion; opment of immune response to vaccines.
d. Unprotected handling of infected carcass; NOTE: Live virus vaccines should normally be given either at
e. Ingestion of raw infected meat; least 3 weeks before or at least 3 months after admin-
f. Exposure to bats; and istration of an immunoglobulin.
g. All Category II exposures on head and neck areas.
Administration:
Contraindications: Hypersensitivity or known To perform skin test for hypersensitivity to ERIG,
history of allergic symptoms to equine pro- using a gauge 26 needle, infiltrate 0.02 mL of
teins; not for intravenous administration (risk 1:10 dilution solution to raise a bleb 3 mm and
for shock). read after 15 minutes. A positive skin test is
an induration of >6 mm surrounded by a flare
Dose: or erythema. If initial skin test is positive, re-
Passive immunization against rabies (post-exposure peat skin test on the same arm; then infiltrate
or following suspected exposure), by infiltra- distilled water on the opposite arm to serve as
tion, ADULT and CHILD, 40 IU/kg. Refer to control. The skin test is considered positive if
Administration. the ERIG skin is positive and the control is
NOTE: It should be administered in conjunction with rabies
negative.
vaccine regimen.
If anatomically feasible, the full rabies immuno-
Precautions: globulin dose should be infiltrated around and
Perform skin test before administration: into the wound(s), even if the wound has
1. Skin tests may detect the rare case of IgE mediated (type healed. Any remaining amount should be ad-
I) hypersensitivity to equine serum protein. However, ministered deep IM at a site distant from the
majority of reactions to ERIG are due to complement
vaccine administration site (e.g., deltoid mus-
activation which will not be predicted through skin test-
ing. A negative skin test will not assure that an anaphy- cle of the upper arm or lateral thigh muscle).
laxis will not occur. The gluteal area should be avoided to reduce
2. If skin test is positive, HRIG is indicated (see section on the risk of sciatic nerve damage. Do not ad-
HRIG). minister rabies vaccine in the same syringe or
3. During skin testing or administration of ERIG, immediate at the same administration site as RIG.
treatment for anaphylaxis or hypersensitivity reactions, WITH RABIES VACCINE. If schedule requires rabies vac-
including epinephrine 1:1000, should be available. For cine and rabies immunoglobulin to be administered at
treatment of anaphylaxis, see under Adverse Reac- the same time, they should be administered
tions. ing separate syringes and at separate sites. If RIG
and the rabies vaccine cannot be given on the same
In patients with a history of bleeding disorders,
day, the vaccine should be given before RIG because
including thrombocytopenia, and in patients the latter inhibits production of neutralizing antibodies
on anticoagulant therapy, watch out for bleed- induced by vaccination.
ing/hematoma that may occur from IM admin- NOTE: Vaccines should be stored within the safe tempera-
istration; ture range of 2-8°C. Freezing is the most common
A single dose of the Rabies Immunoglobulin is cause of vaccine damage; do not use a defrosted
recommended; repeating the dose may inter-
condition.
fere with maximum active immunity expected
from the vaccine; immunoglobulins may inter- Pregnancy Category: See above under Precau-
fere with the immune response to live virus tions.
vaccines which should normally be given ei-
ther at least 3 weeks before or at least 3
months after administration of an immuno-
globulin.
RABIES IMMUNOGLOBULIN
Pregnancy (however, pre-exposure prophylaxis may (HUMAN) – HRIG
be indicated if the risk for exposure to rabies Inj.: 150 IU/mL, 2 mL and 5 mL vial (IM)
is significant). 150 IU/mL, 2 mL and 5 mL and 10 mL (IM)
Administer RIG in conjunction with rabies vaccine.
Human rabies immunoglobulin is a preparation
containing immunoglobulins derived from the
Adverse Reactions: plasma of adult humans immunized with ra-
Common: Acute febrile reaction, injection site bies vaccine, which is used as part of the
swelling and pain, fever, pruritus, rash or urti- management of potential rabies (passive im-
170
munity) following exposure of an unimmunized laxis with human diploid cell vaccine (HDCV), purified
individual to a suspected animal. chick embryo cell vaccine, or rabies vaccine ad-
sorbed, or previous vaccination with any other rabies
Indication: vaccine and documentation of antibody response.
Passive immunization, either post-exposure or in Adverse Reactions:
suspected exposure, to rabies in unimmun- Common: Acute febrile reaction, injection site
ized individuals (in conjunction with rabies swelling and pain, serum sickness-like reac-
vaccine). tions.
See section on ERIG for more detailed indications. Rare: Anaphylaxis, nephrotic syndrome.
Situations where HRIG is preferred are: history of
Treatment of anaphylaxis: give 0.5 mL of 0.1
hypersensitivity to equine sera; multiple se-
per cent solution (1 in 1000, 1 mg/mL) for
vere exposures especially where the dog is
adults, and 0.01 mL/kg body weight for chil-
sick or suspected of being rabid; and symp-
dren, injected subcutaneously or IM.
tomatic HIV infected patient.
Drug Interaction:
Contraindications: Avoid repeat doses after vac- Avoid concomitant use with:
cine treatment is initiated; not for intravenous Vaccines (Live, attenuated, virus) – immunoglobulin
administration administration may interfere with the devel-
NOTE: Documentation of allergenic cross-reactivity for
immunoglobulins is limited. However, because of opment of immune response to vaccines.
similarities in chemical structure and/or pharmacolog- Live virus vaccines should normally be given
ic actions, the possibility of cross-sensitivity cannot be either at least 3 weeks before or at least 3
ruled out with certainty. months after administration of an immuno-
Dose: globulin.
Passive immunization against rabies (post-exposure Administration: If anatomically feasible, the full
or following suspected exposure), by infiltra- rabies immunoglobulin dose should be infil-
tion, ADULT and CHILD, 20 IU/kg (in a single- trated around and into the wound(s), even if
dose) in and around the cleansed wound; if the wound has healed. Any remaining amount
wound is not visible or has healed, or if infiltra- should be administered deep IM at a site dis-
tion of whole volume is not possible, give re- tant from the vaccine administration site (e.g.,
mainder by IM injection (should always be deltoid muscle of the upper arm or lateral
administered as part of rabies vaccine regi- thigh muscle). The gluteal area should be
men). avoided to reduce the risk of sciatic nerve
NOTE: If rabies vaccine was initiated without rabies immu- damage. Do not administer rabies vaccine in
noglobulin, rabies immunoglobulin may be adminis-
the same syringe or at the same administra-
tered through the seventh day after the administration
of the first dose of the vaccine (day 0). Administration tion site as RIG.
of immunoglobulin is not recommended after the sev- WITH RABIES VACCINE. If schedule requires rabies vac-
enth day post vaccine since an antibody response to cine and rabies immunoglobulin to be administered at
the vaccine is expected during this time period. the same time, they should be administered
ing separate syringes and at separate sites. If RIG
Precautions: and the rabies vaccine cannot be given on the same
Anaphylaxis or hypersensitivity reactions (hyper- day, the vaccine should be given before RIG because
the latter inhibits production of neutralizing antibodies
sensitivity and anaphylactic reactions, alt-
induced by vaccination.
hough rare, can occur; immediate treatment, NOTE: Vaccines should be stored within the safe tempera-
including epinephrine 1:1000, should be avail- ture range of 2-8°C. Freezing is the most common
able); for treatment of anaphylaxis, see Ad- cause of vaccine damage; do not use a defrosted
verse Reactions. vaccine unless freezing is the recommended storage
In patients with isolated immunoglobulin A deficien- condition.
cy or a history of systemic hypersensitivity to Pregnancy Category: C
human immunoglobulins.
In patients with a history of bleeding disorders,
including thrombocytopenia, and patients on
anticoagulant therapy (bleeding/hematoma RABIES VACCINE
may occur from IM administration).
A single dose is recommended; repeating the dose
Inj.: Lyophilized powder, 2.5 IU/dose + diluent
may interfere with maximum active immunity
expected from the vaccine. (1 mL or 0.5 mL) (IM, ID)
Immunoglobulins may interfere with the immune Purified vaccine containing inactivated rabies virus
response to live virus vaccines which should cultivated in chick embryo cells or Vero cells..
See 2012 DOH NRPCP Manual for further details
normally be given either at least 3 weeks be-
fore or at least 3 months after administration Indications: Active immunization against rabies;
of an immunoglobulin. pre-exposure prophylaxis, and post-exposure
Pregnancy (however, pre-exposure prophylaxis may treatment.
NOTE: WHO recommends pre-exposure immunization of
be indicated if the risk for exposure to rabies individuals at increased risk of contracting rabies, in-
is significant). cluding those at risk due to occupational exposure
Administer RIG in conjunction with rabies vaccine. (such as health and laboratory workers, animal han-
NOTE: Not recommended for use in patients with a history dlers, and veterinary surgeons), and people living or
of pre-exposure vaccination or post-exposure prophy-
171
traveling to enzootic areas (in such areas, children they should be given using separate syringes and
aged 5-15 years are at particular risk of exposure). separate sites.
Contraindications: Known hypersensitivity to the Adverse Drug Reactions:
vaccine or any of its components; vaccines of Common: Abdominal pain, allergic reactions, diar-
nerve cell tissue origin should not be used rhea, dizziness, dyspnea, fainting, headache,
(due to being less potent and are frequently lymphadenopathy, malaise, myalgia, nausea,
associated with adverse events). rash, serum sickness-like reactions, transient
Dose: fever, transient injection site reactions (pain,
NOTE: The treatment is dependent upon the individual’s redness, itching, swelling or burning, small
immune status and upon the level of risk of rabies. hard lump that may persist for some weeks),
Doses may vary between products. vomiting, weakness.
Pre-exposure prophylaxis against rabies, by IM Less Common: Angioedema.
injection, ADULT and CHILD, 3 doses on Rare: Neuroparalytic events.
days 0, 7, and 28 (day 28 preferable, but ad- Drug Interactions:
ministration may be advanced towards day 21 Monitor closely with:
if time is limited); alternatively, by ID injection, Other vaccines and immunoglobulins – these can
3 doses, each of 0.1 mL on days 0, 7, 28
(administration may be advanced towards day
immune response (give a live vaccine on the
21 if time is limited).
BOOSTER DOSES. Periodic booster doses are recom-
mended only for individuals whose occupation puts er live vaccine).
them at continuous or frequent risk of rabies expo- Avoid concomitant use with:
sure. In such cases, a booster dose should be given Anti-infectives – avoid giving live vaccines with anti-
at intervals dictated by regular testing for antibodies infectives, especially if they are active against
(a concentration of virus neutralizing antibodies of at the organism in the vaccines, as the effective-
least 0.5 IU/mL indicates protection). Where serologi-
ness of vaccines may be reduced, preventing
cal testing is unavailable, booster vaccination every 5
years may be an acceptable alternative. an immune response.
Post-exposure treatment against rabies in unim- Immunosuppressive agents and during radiation
munized individuals, by IM injection, ADULT therapy – these may interfere with the active
and CHILD, 1 dose given on days 0, 3, 7, 14, antibody response to rabies vaccine, and in-
and 28 (total of 5 doses); or, alternatively 2 crease the risk of the patient developing ra-
doses on day 0 (one in each deltoid or thigh), bies.
followed by 1 dose on days 7 and 21 (total of Administration: The bite wound must be thorough-
4 doses). ly cleansed. When administered by IM injec-
Post-exposure treatment against rabies in unim- tion, the vaccine should be given in the deltoid
munized individuals, by ID injection, ADULT region in adults and children; the anterolateral
and CHILD (8-site regimen), 1 dose of 0.1 mL thigh is the preferred site in children < 2 years
administered at 8 separate sites on day 0 (one of age.
in each upper arm, one in each lateral thigh, NOTE: There may be a suboptimal response if a vaccine is
one on each side of the suprascapular region, injected incorrectly (route or area); local response
and one on each side of the lower quadrant may also be increased; IM injections must be given
region of the abdomen), followed by 1 dose of slowly to reduce pain.
0.1 mL in each upper arm on days 30 and 90; ture range of 2-8°C. Freezing is the most common
or, alternatively, (2-site regimen), 1 dose of cause of vaccine damage; do not use a defrosted
0.1 mL at 2 sites on days 0, 3, 7, and 28 (total vaccine unless freezing is the recommended storage
of 8 doses). condition.
Post-exposure treatment against rabies in fully
immunized individuals, by IM or ID injection,
ADULT and CHILD, 2 doses, separated by 3
days.
NOTE: Check the antibody response to post-exposure
immunization course in immunocompromised people TETANUS IMMUNOGLOBULIN
as further doses may be needed.
Dose Adjustments: No information found. Inj.: 1,000 IU/mL, 1.5 mL vial (IM)
1,500 IU/mL, 1 mL ampul (IM)
Precautions: 250 IU/mL, 1 mL, 2 mL and 4 mL ampul (IM)
Caution in individuals with history of systemic aller- 250 IU/mL, 1 mL pre-filled syringe (IM)
gic reaction to any ingredient in the vaccine; 250 units/mL, 1 mL and 2 mL vial (IM)
acute febrile illness (postpone all vaccinations
until patient is well); once initiated, rabies A sterile preparation of globulins derived from the
prophylaxis should not be interrupted nor dis- plasma of adult human donors who have been
continued because of development of local or immunized with tetanus toxoid, which is used
mild systemic reactions (the risk of acquiring for the management of tetanus-prone wounds.
rabies should be weighed before deciding to Indications: Passive immunization against tetanus
discontinue vaccination). in susceptible people sustaining serious injury,
NOTE: If schedule requires rabies vaccine and rabies
immunoglobulin to be administered at the same time,
punctures, cuts, animal bites and dirty wounds
172
in unimmunized individuals; treatment of teta-
nus. TETANUS TOXOID
Contraindications: Hypersensitivity to human
Inj.: 0.5 mL ampul (IM)
immunoglobulins or any component of the 5 mL and 10 mL vial (IM)
formulation (e.g., thimerosal); selective IgA
deficiencies. A sterile solution of tetanus toxoid in isotonic sodi-
um chloride solution, which is used as a
Dose:
booster injection against tetanus.
Management of tetanus-prone wounds, by IM injec-
tion, ADULT and CHILD, 250 IU, increased to Indications: Active immunization against tetanus;
500 IU if wound is older than 24 hours, or tetanus prophylaxis as part of wound man-
there is possible risk of heavy contamination, agement (e.g., tetanus-prone wounds and
or following burns. clean wounds).
Treatment of tetanus infection, by IM injection,
Contraindication: Known hypersensitivity to the
ADULT and CHILD, 150 units/kg (multiple
preparation or any of its components.
sites).
Dose:
Immunization of unimmunized pregnant women
Precautions: against tetanus, by IM injection, ADULT, 2
In those patients with coagulation disorders or doses, each of 0.5 mL, with an interval of at
thrombocytopenia; should not be used for IV least 4 weeks between each dose (second
administration (because of the potential for dose at least 2 weeks before delivery), fol-
anaphylactic reactions); drug products made lowed by a third dose of 0.5 mL 6 months lat-
from human plasma may contain infectious er; and 2 booster doses, each of 0.5 mL, the
agents, such as viruses, which can cause dis- first at least 1 year after completion of the pri-
eases. mary course, and the second dose at least 1
Pregnancy and lactation (safety has not yet been year later.
established). Management of tetanus-prone wounds and clean
TETANUS VACCINE. If schedule requires tetanus vaccine wounds, by IM injection, ADULT, 0.5 mL as a
and antitetanus immunoglobulin to be administered at single dose (the dose schedule will be de-
the same time, they should be administered using
pendent upon the immune status of the pa-
separate syringes and separate sites.
tient, and the level of contamination of the
Adverse Drug Reactions: wound).
Common: Erythema, injection site swelling and NOTE: For clean wounds, fully immunized individuals and
pain. those whose primary immunization is complete (with
boosters up to date) do not require tetanus vaccine.
Less Common: Drowsiness, low grade fever,
Individuals whose primary immunization is incomplete
malaise, mild pyrexia, urticaria. or whose boosters are not up to date require a rein-
Rare: Anaphylaxis, angioedema, convulsions, forcing dose of tetanus vaccine (followed by further
headache, hives, nausea, vomiting. doses as required to complete the schedule). Non-
immunized individuals (or those whose immunization
Drug Interaction: status is not known, or immunized but are now im-
Monitor closely with: munocompromised) should be given a dose of the
Live, attenuated virus vaccines (e.g., measles and vaccine immediately (followed by completion of the
poliomyelitis) and immunoglobulins – these full course of the vaccine if records confirm the need).
For tetanus-prone wounds, management is as for
can influence the ability of vaccines to induce
clean wounds with the addition of a dose of antiteta-
an immune response (reduce the efficacy of nus immunoglobulin given at a different site; the im-
live vaccines). munoglobulin is needed only if the risk of infection is
especially high (e.g., contamination with manure).
Administration: It should be brought to room tem-
Primary immunization of unimmunized adolescents
perature before use, and given slowly by deep
and adults (including women of child-bearing
IM injection using an appropriate sized nee- age) against tetanus, by IM injection, ADULT
dle; if a large dose (more than 5 mL) is re- and ADOLESCENT, 3 doses, each of 0.5 mL,
quired, it is advisable to give it in divided dos-
with an interval of not < 4 weeks between the
es at different sites; the patient should be ob-
first and second doses and 6 months between
served for at least 20 minutes after admin-
the second and third doses; followed by 2 re-
istration.
inforcing doses, each of 0.5 mL, the first at
ture range of 2-8°C. Freezing is the most common least 1 year after completion of the primary
cause of vaccine damage; do not use a defrosted course and the second dose at least 1 year
vaccine unless freezing is the recommended storage later.
condition. Reinforcing immunization of adults against tetanus,
Pregnancy Category: C by IM injection, ADULT, 2 doses, each of 0.5
mL, the first 10 years after completion of the
primary course, and the second dose 10 years
later.
NOTE: A childhood tetanus immunization schedule of 5
doses is recommended; the primary 3 doses must be
given during the first year of life, as the combined
173
DPT. The 4th booster dose with a tetanus toxoid-
containing vaccine should be given at 4-7 years, and
the 5th dose during adolescence at 12-15 years. A
6th dose can be given in early adulthood for life-long
protection; when tetanus prophylaxis is needed fol-
lowing an injury, combined diphtheria and tetanus
preparations must be used to promote immunity
against diphtheria.

Precautions:
IM injections should be given with caution in pa-
tients with thrombocytopenia or other coagula-
tion disorders; history of Guillain-Barré syn-
drome (GBS) (increased risk of recurrent GBS
after subsequent doses of vaccine).
ANTITETANUS IMMUNOGLOBULIN. If schedule requires
tetanus vaccine and antitetanus immunoglobulin to be
administered at the same time, they should be admin-
istered using separate syringes and separate sites.

Common: Nausea.
Less Common: Fainting, fever, lethargy, myalgia,
rash, transient injection site reactions (pain,
redness, itching, swelling, burning, small hard
Rare: Allergic reactions, including anaphylaxis;
disturbances in EEG, Guillain-Barré syn-
drome, headache, hypotension, malaise, pe-
ripheral neuropathy, urticaria.
Drug Interaction:
Immunosuppressive agents (e.g., therapeutic doses
antibody response to inactivated vaccines.
Administration: Inject IM in the area of the lateral

mid-thigh or deltoid. The vaccine should not
be injected into the gluteal area or areas
where there may be a major nerve trunk.
NOTE: Parenteral products should be inspected visually for
discoloration and/or extraneous particulate matter pri-
or to administration whenever solution and container
permit. It should not be used if particulate matter or
discoloration is found.
condition.
174
175
APPENDICES
176
US FDA PREGNANCY RISK CATEGORIES
The FDA-assigned pregnancy categories as used in the Manual are as follows:
Category Interpretation
A CONTROLLED STUDIES SHOW NO RISK.
Adequate and well-controlled studies in pregnant women have failed
to demonstrate a risk to the fetus in the first trimester of pregnancy
(and there is no evidence of risk in later trimesters).
B NO EVIDENCE OF RISK IN HUMANS.

Animal reproduction studies have failed to demonstrate a risk to the
fetus and there are no adequate and well-controlled studies in preg-
nant women.
C RISK CANNOT BE RULED OUT.

Animal reproduction studies have shown an adverse effect on the
fetus and there are no adequate and well-controlled studies in hu-
mans, but potential benefits may warrant use of the drug in pregnant
women despite potential risks.
D POTENTIAL EVIDENCE OF RISK.

There is positive evidence of human fetal risk based on adverse re-
action data from investigational or marketing experience or studies in
humans, but potential benefits may warrant use of the drug in preg-
nant women despite potential risks.
X CONTRAINDICATED IN PREGNANCY.
Studies in animals or humans have demonstrated fetal abnormalities
and/or there is positive evidence of human fetal risk based on ad-
verse reaction data from investigational or marketing experience, and
the risks involved in the use of the drug in pregnant women clearly
outweigh potential benefits.
177
SYMBOLS and ABBREVIATIONS
ACE – Angiotensin-converting enzyme L – Liter
ADR – Adverse drug reaction lin. – Liniment
AIDS – Acquired immunodeficiency lot. – Lotion
syndrome LVH – Left Ventricular Hypertrophy
a.m. – Morning; before noon MAOI – Monoamine oxidase inhibitor
Amp – Ampul MDI – Metered dose inhaler
ARB – Angiotensin receptor blocker MDR-TB – Multidrug-resistant tuberculosis
AV – Atrioventricular mEq – Milliequivalent
BCG – Bacille Calmette-Guérin (vaccine) mg – Milligram
BP – Blood pressure mL – Milliliter
BPH – Benign prostatic hypertrophy mmol – Millimole
BSA – Body surface area MR – Modified release [includes Con-
cap., caps. – Capsule trolled Release (CR), Extended
CFU – Colony-forming unit Release (ER), Immediate Re-
CNS – Central nervous system lease (IR), Sustained Release
comp. – Compound (SR), Long Acting (LA)]
cr., crm. – Cream nebul. – Spray
CSF – Cerebrospinal fluid NSAID – Non-steroidal anti-inflammatory
D5NS – Glucose (dextrose) 5% in nor- drug
mal saline (0.9%) p.m. – Evening
D5W – Glucose (dextrose) 5% solution prn – As needed (from Latin pro re
dL – Deciliter nata)
DOTS – Directly observed treatment, RE – Retinol equivalent
short-course Resp. Soln. – Respiratory solution
DMARD – Disease-modifying agents in SC / (SC) – Subcutaneous
rheumatoid disorders SL / (SL) – Sublingual; under the tongue
DPI – Dry powder inhaler Soln. – Solution
ECG – Electrocardiogram spp. – Species
emuls. – Emulsion SSRI – Selective serotonin reuptake
EPS – Extrapyramidal syndrome inhibitor
g – Gram supp. – Suppository
GERD – Gastroesophageal reflux dis- susp. – Suspension
ease syr. – Syrup
GFR – Glomerular filtration rate tab. – Tablet
GI – Gastrointestinal top. – Topical
gtt (s) – Drop (s) TB – Tuberculosis
h., hr. – Hour
HbA1c – Glycosylated hemoglobin
HIV – Human immunodeficiency virus
HRT – Hormone replacement therapy
HTN – Hypertension
ICP – Intracranial pressure
ID / (ID) – Intradermal
IM / (IM) – Intramuscular
Inj. – Injection
INR – International normalized ratio
IU – International unit/s
IV / (IV) – Intravenous
178
MEASUREMENTS
Notes on writing measurements:
• Quantities of 1 gram or more are written as 1 g, etc.

• Quantities less than 1 gram are written in milligrams (e.g., 500 mg, not 0.5 g).
• Quantities less than 1 milligram are written in micrograms (e.g., 100 micrograms, not
0.1 mg).
• When decimals are unavoidable, a zero is written before the decimal point where
there is no other figure (e.g., 0.5 mL and not .5 mL).
• The term milliliter (mL) is used and not cubic centimeter or cc.
Household Measures*
1 glassful = 250 mL 1 fluid (f3) = 3.69 mL
1 teacupful = 180 mL 1 fluid ounce (foz) = 29.57 mL
1 pint (pt) = 473 mL
1 tablespoonful (tbsp) = 15 mL
1 teaspoonful (tsp) = 5 mL 1 gallon (gal) = 3,785 mL
½ tsp = 2.5 mL 1 gal = 128 oz
Some Practical Conversions WEIGHT

1g = 15.432 gr
LENGTH 1 kilogram (kg) = 2.2 lb (avoir)
1 meter = 39.37 inches 1 grain (gr) = 64.8 mg
1 inch = 2.54 cm 1 ounce (oz) (avoir) = 28.35 g
1 oz (apoth) = 31.1 g
VOLUME 1 pound (lb) (avoir) = 454 g
1 mL = 16.23 minims 1 lb (apoth) = 373.2 g
1 mL = 20 drops (gtt) 1 oz (avoir) = 437.5 gr
1 minim = 0.06 mL 1 oz (apoth) = 480 gr
*Household measures stated in this Formulary may not be equal to the household utensils.
These utensils are usually LESS in volume as compared with standard measures.
179
DRUGS AND CYP ENZYMES
Many drug interactions have resulted from the ability of one drug to stimulate the me-
tabolism of another, most often by increasing the activity of hepatic enzymes that are involved in
the metabolism of numerous therapeutic agents. The increased activity is probably due to en-
hanced enzyme synthesis, resulting in increased amounts of drug-metabolizing enzymes, an
effect frequently referred to as enzyme induction. Enzyme induction will usually result in an
increased metabolism and excretion, and a reduced pharmacologic action of the agent being
metabolized by hepatic enzymes. Meanwhile, enzyme inhibition will usually result in a de-
creased metabolism and excretion, and an increased activity of the agent being metabolized.
This table serves only as a guide for potential interactions. Other interactions not listed below
may occur.
CYP1A2 inducers CYP2C9 substrates

Omeprazole Amitriptyline
Phenobarbital, Phenytoin Celecoxib
Tobacco smoking Fluoxetine, Fluvastatin
CYP1A2 inhibitors Glibenclamide, Gliclazide, Glimepiride,
Ciprofloxacin (moderate) Glipizide
Verapamil (weak) Ibuprofen
CYP1A2 substrates Phenytoin
Amitriptyline Rosiglitazone, Rosuvastatin
Clozapine Sulfamethoxazole
Haloperidol Tamoxifen
Lidocaine Warfarin
Olanzapine, Ondansetron CYP2C19 inducers
Paracetamol, Propranolol Carbamazepine
Theophylline Rifampicin
Warfarin St. John’s wort
CYP2B6 inducers CYP2C19 inhibitors
Phenobarbital, Phenytoin Clarithromycin
Rifampicin, Ritonavir Fluoxetine
CYP2B6 inhibitors Ketoconazole
Clopidogrel Omeprazole (strong)
CYP2B6 substrates Topiramate
Clopidogrel CYP2C19 substrates
CYP2C8 inducers Amitriptyline
Rifampicin Clomipramine, Clopidogrel
CYP2C8 inhibitors Diazepam
Gemfibrozil (strong) Imipramine
Trimethoprim Lansoprazole
CYP2C8 substrates Omeprazole
Pioglitazone Pantoprazole, Phenobarbital, Phenytoin,
Rosiglitazone Propranolol
CYP2C9 inducers Warfarin
Rifampicin CYP2D6 inhibitors
St. John’s wort Amiodarone (weak)
CYP2C9 inhibitors Celecoxib, Chlorphenamine, Clomipramine
Amiodarone (moderate) Fluoxetine (strong)
Fluconazole (moderate), Fluoxetine Haloperidol
Isoniazid Paroxetine (strong)
Ritonavir Quinidine
180
Ritonavir Quinidine, Quinine
CYP2D6 substrates Risperidone, Ritonavir
Amitriptyline Saquinavir, Sildenafil, Simvastatin
Carvedilol, Chlorpromazine, Clomipramine, Tamoxifen, Tramadol
Clozapine, Codeine Verapamil, Vincristine
Dextromethorphan Warfarin
Fluoxetine Zolpidem
Haloperidol P-glycoprotein inducers
Lidocaine Rifampicin
Metoclopramide, Metoprolol St. John’s wort
Olanzapine, Ondansetron, Oxycodone P-glycoprotein inhibitors
Propranolol Amiodarone, Azithromycin
Risperidone Carvedilol, Clarithromycin
Tamoxifen, Timolol, Tramadol Erythromycin
CYP2E1 inducers Ritonavir
Alcohol Verapamil
Isoniazid P-glycoprotein substrates
CYP2E1 substrates Carvedilol, Clopidogrel, Colchicine
Alcohol Digoxin
Paracetamol Loperamide
CYP3A4/5 inducers Paclitaxel
Carbamazepine, Corticosteroids Saquinavir
Phenobarbital, Phenytoin
Rifampicin, Ritonavir
St. John’s wort
CYP3A4/5 inhibitors
Clarithromycin (strong)
Danazol, Diltiazem (moderate)
Erythromycin (moderate)
Fluconazole (moderate)
Grapefruit juice (moderate)
Ketoconazole (strong)
Ritonavir (strong)
Saquinavir (strong)
Verapamil (moderate)
CYP3A4/5/7 substrates
Alfentanil, Alprazolam, Amiodarone,
Amitriptyline, Amlodipine, Atorvastatin
Buspirone, Budesonide
Carbamazepine, Chlorphenamine,
Clarithromycin, Cocaine, Codeine,
Colchicine
Dexamethasone, Diazepam, Diltiazem
Ergot alkaloids, Erythromycin,
Ethinylestradiol, Etoposide, Etoricoxib
Felodipine, Fentanyl, Fluticasone,
Fluvastatin
Haloperidol, Hydrocortisone
Ketoconazole
Lidocaine
Methylprednisolone, Midazolam,
Mirtazapine
Nifedipine, Nimodipine
Omeprazole, Ondansetron, Oxycodone
Propranolol
181
Table A. Drugs with anticholinergic effects
Drugs with anticholinergic effects
Amantadine, Amitriptyline, Atropine
Belladonna alkaloids, Benztropine, Biperiden, Brompheniramine
Chlorpheniramine, Chlorpromazine
Diphenhydramine
Hyoscine (butylbromide or hydrobromide)
Ipratropium (nebulized)
Table B. Drugs that may prolong QT interval

Class Drug/s
Antiarrhythmics Amiodarone, Disopyramide, Sotalol
Antipsychotics Haloperidol
Anti-infectives Azithromycin, Chloroquine, Clarithromycin, Erythromycin, Fluconazole,
Moxifloxacin, Quinine
Miscellaneous Cocaine, Tricyclic Antidepressants
Table C. Drugs that may cause seizures

Drugs that may cause seizures
Antipsychotics
Chloroquine
Ertapenem
Imipenem, Isoniazid
MAO Inhibitors, Mirtazapine, Moxifloxacin
Neostigmine, Norfloxacin
Pizotifen, Promethazine, Pyridostigmine, Pyrimethamine
Rivastigmine
Selective Serotonin Reuptake Inhibitors
Tricyclic Antidepressants, Theophylline
182
Table D. Drugs which reduce blood pressure
Drugs which reduce blood pressure
Alcohol, Amlodipine, Atenolol
Chlorpromazine, Olanzapine, Risperidone
Diazepam
Captopril, Enalapril
Clonidine
Diltiazem
Furosemide
Hydralazine, Hydrochlorothiazide
Isosorbide dinitrate
Losartan
Methyldopa
Nifedipine
Metoprolol, Propranolol
Sodium Nitroprusside
Spironolactone
Timolol
Verapamil
Table E. Drugs that may add to serotonin toxicity

Class Drugs
Antidepressants St. John’s wort, MAO inhibitors (including moclobemide),
SSRIs, TCAs
Opioids Dextromethorphan, Fentanyl, Pethidine
Stimulants Hallucinogenic Amphetamines, Phentermine
Others Illicit drugs (e.g., ‘ecstasy’, LSD, cocaine), Selegiline,
Linezolid, Lithium
183
CLINICAL
PRACTICE
GUIDELINES
184
CLINICAL PRACTICE GUIDELINES
(CPG) USER GUIDE
The concept algorithm is defined as a step-by-step procedure for solving a prob-
lem which contains conditional logic (‘if’/‘then’) statements. Flow-chart algorithms or clinical
algorithm maps are reported to be uniquely suited for explicitly communicating conditional
logic and have become the main format for representing a clinical algorithm clearly and
succinctly. These algorithms are constructed with a flow of major decisions from top to
bottom and courses of action and alternatives from left to right. Different types of boxes are
used in algorithms:
• Clinical state boxes (rounded rectangle) define a clinical state or problem which is
to be addressed. They always appear at the beginning and may also be used with-
in the body of an algorithm. These boxes may or may not have an entry path but
have only one exit path.
• Decision boxes (hexagon) contain statements that are phrased as questions,

punctuated with question marks (‘?’)
• Action boxes (rectangle) contain a clinical action, which is either diagnostic or

therapeutic. Algorithms usually end in a clinical report. These boxes always have
an entry path, but may not have an exit.
• Link boxes (small oval) are used for continuity purposes for algorithms which can-
not fit in a single page.
These boxes are numbered sequentially from left to right and top to bottom,
with the exception of link boxes.
Aside from the boxes which have been presented in these Clinical Practice
Guidelines, ‘Essential Practice Points’ have been included to contain important details
and information that are essential in treating various diseases – both communicable and
non-communicable. Note that the texts within the practice points have been presented
either in green font color and enclosed in green-colored, round rectangles (for the salient
characteristics of the condition and the medicine, or for recommended good practices), or
in red font color and enclosed in red-colored, round rectangles (for warnings and precau-
tions).
Readers are enjoined to confirm the information contained in the CPGs by

referring to additional sources, particularly with regard to the most recent updates
of the guidelines and new medicines.
185
A
Is ANY of the following present?

4
• RR >30/min
• PR/HR >125/min Is ANY of the following
• Temperature >40°C or <36°C present? 5
• SBP <90 mmHg YES
1. Severe sepsis and YES
• DBP <60 mmHg HIGH-RISK CAP
septic shock or
• Altered mental status (acute)
2. Need for mechani- 6
• Suspected aspiration
cal ventilation
• Unstable co-morbid conditions ICU Admission
• Chest x-ray: multilobar, pleural
NO
effusion or abscess 7
MODERATE-RISK CAP
9 NO
8
LOW-RISK CAP
187
Hospital Ward Admission

10
Outpatient Treatment
Most Common Agents in Low-Risk CAP:
11 ♦ Typical Bacterial Pathogens:
Microbiological Studies: - Streptococcus pneumoniae
• Optional in low-risk CAP - Haemophilus influenzae
- Moraxella catarrhalis
• Done only when there is:
- Failure to respond to previous antibiotics, or ♦ Atypical pathogens:
- Mycoplasma pneumoniae
- Clinical condition where drug resistance may be an issue
- Chlamydophila pneumoniae
12 ♦ Enteric Gram-negative bacillus in
those with co-morbidities
Empiric Antimicrobial Therapy
187
B Prudent and cautious use of fluoroquinolones
14 as an alternative agent in the outpatient setting is
strongly advised.
For typical pathogens,
13 give Amoxicillin
OR For Low Risk CAP patients without comorbidities,
Does the patient have co- NO For suspected atypical Amoxicillin, which is directed against presumed S.
morbid illness OR recent pathogens, give pneumoniae or H. influenzae infection, is consid-
previous antibiotic therapy?* Extended Macrolides ered an adequate regimen.
(Azithromycin dihydrate or
Clarithromycin)
YES Cotrimoxazole is NOT recommended for CAP due

*Gram-negative bacilli
to increasing resistance of S. pneumoniae and H.
15 may co-exist influenzae to this antibiotic.
Oral Beta-Lactam/Beta-Lactamase Inhibitor Combination (BLIC):
(e.g., Amoxicillin-Clavulanic acid )
OR
Oral 2nd-generation Cephalosporin (e.g., Cefuroxime axetil)
(+/–) Extended Macrolides
188
17
16
Refer to higher level of healthcare facility
NO
Is there good therapeutic re- OR
sponse to completed 1st line Do extensive work-up to identify factors for failures
(e.g., sputum G/S, C/S)
YES
18
In patients showing good therapeutic response;

a follow-up x-ray is not necessary. Follow-up
cultures of blood and sputum are also not indi-
cated for patients who respond to therapy.
188
Guidelines for the Management of Community Acquired
Pneumonia (CAP) in Immunocompetent Adults at the
Primary Healthcare Level
I. What is the approach to the diagnosis of CAP?
A. What is the definition of CAP?
1. CAP is an acute infection of the pulmonary parenchyma with symptoms
of acute illness accompanied by abnormal chest findings. This is ac-
quired in the community within 24 hours to less than 2 weeks.
2. Its causative pathogens may be typical or atypical.
a. Typical pathogens: Streptococcus pneumoniae, Haemophilus influ-
enzae and Moraxella catarrhalis present with findings limited to the
lungs.
b. Atypical pathogens: Mycoplasma pneumoniae, Chlamydophila
pneumoniae and Legionella have predilection for certain extrap-
ulmonary organ systems (GI, cutaneous).
B. How is CAP diagnosed?
1. By its clinical presentation:
a. There is no particular clinical symptom or abnormal finding suffi-
cient enough to distinguish CAP from other lower respiratory tract
infections.
b. The accuracy of predicting CAP using its common clinical findings
as bases is only between 60-76%.
c. However, combination of the history and physical examination find-
ings can better predict the existence of CAP. Prediction rules com-
bining these parameters can be utilized to better identify patients
who may have pneumonia and therefore need a chest x-ray.
d. The common presentation of CAP includes:
i. Acute cough
ii. Tachypnea (RR >20 breaths/minute)
iii. Tachycardia (cardiac rate >100/minute)
iv. Fever (temperature >37.8°C)
v. With at least one of the following abnormal chest findings: di-
minished breath sounds, rhonchi, crackles or wheezes.
e. Important Note: There is no clinical feature that can reliably dis-
tinguish typical from atypical pneumonia. The main feature that may
help to differentiate between the two is the presence of extrap-
ulmonary finding in pneumonia due to atypical pathogens.
2. By Chest x-ray:
a. The chest x-ray should be done to confirm the diagnosis of CAP. It
is useful in the assessment of its severity, differentiation of pneu-
monia from other diseases, and prognostication.
b. A new parenchymal infiltrate in the chest x-ray is the reference di-
agnostic standard for pneumonia.
189
c. Recommended specific views: Standing PA and lateral views of
the chest in full inspiration, with the left lateral view being the pre-
ferred position for the lateral view since this will minimize the size of
the heart on the image.
d. In settings with limited resources, a chest x-ray may not be routine-
ly done in suspected CAP patients with the following conditions:
i. Healthy individuals or those with stable co-morbid
tions, AND
ii. Normal vital signs and PE findings, AND
iii. Where reliable follow-up can be ensured.
e. Important Note: There is no characteristic x-ray finding that can
predict the likely etiologic agent.
f. Important Note: An initial “normal” chest x-ray may connote a radi-
ographic lag phase. Chest radiographic findings also usually clear
more slowly than clinical findings and repeated x-rays are generally
not required.
g. In addition to disease progression, possible pulmonary complica-
tions, such as pleural effusion (10.6%), empyema (5.2%), lung ab-
scess, or atelectasis should be assessed.
C. When are microbiologic studies necessary?
1. In low-risk CAP, microbiologic studies are optional.
2. Sputum gram stain and culture in low-risk CAP are generally not done
since the bacterial etiology is predictable with the most common etiolog-
ic agents being the bacteria S. pneumoniae and H. influenzae and the
atypical pathogens being M. pneumoniae and C. pneumoniae. There is
also a low risk for mortality.
3. Sputum gram stain and culture are done in the following situations:
1. Failure of response to previous antibiotics;
2. Clinical conditions where drug resistance may be an issue.
II. What is the approach to the treatment of CAP?
A. Determination of Risk Stratification of CAP:
1. A risk stratification based on the clinical presentation, status of any co-
morbid condition and chest x-ray findings is used to determine the site
of care for the patient (see Table 1).
Sites of care are the: outpatient clinic, hospital/medical ward and ICU.
2. The risk stratification guidelines must be applied together with the phy-
sician’s best clinical judgment and supplemented by objective findings.
The initial decision can change depending on the clinical course.
190
Table 1. Clinical features in CAP according to risk categories
LOW-RISK CAP MODERATE-RISK CAP HIGH-RISK CAP
Presence of: Any of the following: Any of the criteria un-
Stable vital signs: Unstable vital signs: der moderate-risk CAP
RR <30 breaths/minute RR >30 breaths/minute category PLUS severe
PR <125 beats/minute PR >125 beats/minute sepsis and septic shock
Temp. >36ᵒC or <40ᵒC Temp. >40°C or <36°C
SBP >90 mmHg SBP <90 mmHg With need for
DBP >60 mmHg DBP <60 mmHg mechanical ventilation
No altered mental status of Altered mental state of

acute onset acute onset
No suspected aspiration Suspected aspiration
No or stable co-morbid Decompensated co-morbid
conditions condition
Chest X-ray: Chest X-ray:
- Localized infiltrates - Multilobar infiltrates
- No pleural effusion or - Pleural effusion or ab-
abscess scess
3. Patients with low-risk CAP can be managed as an outpatient in the ab-

sence of contraindications. Clinically immunocompetent patients with
CAP who have stable or medically controlled co-morbid conditions (e.g.,
diabetes mellitus, neoplasms, neurologic disease, congestive heart fail-
ure Class I, coronary artery disease, COPD, asthma, chronic liver dis-
ease, renal insufficiency, and chronic alcohol abuse) are also classified
under the low-risk category.
4. Those with moderate to high-risk CAP are hospitalized for closer mon-
itoring and/or parenteral therapy.
5. Important Note: Pneumonia itself can lead to worsening or exacerba-
tion of an underlying medical illness which may require hospital admis-
sion regardless of the severity of the pneumonia.
B. Initiation of Empiric Antimicrobial Therapy for CAP:

1. In previously healthy adult patients with low-risk CAP, S. pneumoniae
and H. influenzae are the predominant etiologic agents. Amoxicillin is
considered the standard regimen for these patients (see Table 2).
2. When atypical organisms are suspected (M. pneumoniae or C. pneu-
moniae), extended macrolides (e.g., azithromycin dihydrate, clarithro-
mycin) or azalides are given.
3. In patients with low-risk CAP and with stable co-morbid illnesses or in
those with recent antibiotic therapy, Gram-negative bacilli may co-
exist with the above pathogens so that β-lactamase inhibitor combina-
tions or BLIC (e.g., amoxicillin-clavulanic acid) or second-generation
oral cephalosporins (e.g., cefuroxime axetil), with or without extend-
ed macrolides or azalides are recommended. For patients who have
completed first-line antibiotics without response, extensive workup sould
be done to identify factors causing failure of response. The CAP guide-
191
lines also include, as an alternative treatment, the use of oral third-
generation cephalosporin with or without extended macrolides.
4. In patients hypersensitive to the β-lactams, the extended macrolides
may cover for S. pneumoniae and H. influenzae while respiratory fluo-
roquinolones have added coverage for Gram-negative bacilli. However,
judicious use of the fluoroquinolones is warranted (see warning below).
Antimicrobial Resistance Alert! Due to the continuing increase in the

rates of resistance of S. pneumoniae and H. influenzae to cotrimoxa-
zole, its use for CAP is not recommended.
Antimicrobial Resistance Alert! Judicious use of fluoroquinolones as

an alternative agent in the outpatient setting is strongly advised. A pre-
sent local study has shown that ciprofloxacin and ofloxacin are be-
coming significantly less effective therapy in tuberculosis.
5. Duration of treatment for low-risk uncomplicated bacterial pneumonia is

5 – 7 days.
Table 2. Empiric antimicrobial therapy for Low-Risk CAP

Risk
Potential Pathogen Empiric Therapy
Stratification
Low-risk CAP Streptococcus Previously healthy:
pneumoniae; Amoxicillin
Haemophilus influenzae; Or
Chlamydophila Extended macrolides
pneumoniae; (suspected atypical pathogen)
Mycoplasma
With stable co-morbid illness:
pneumoniae;
Moraxella catarrhalis; β -lactam/β-lactamase inhibitor
Enteric Gram-negative combination (BLIC)
bacilli Or
(among those with co- Second-generation oral
morbid illness) cephalosporins +/– extended
macrolides
Alternative:
Third generation oral cephalosporin
+/– extended macrolides
192
C. Usual recommended dosages of antibiotics in 50-60 kg adults with
normal liver and renal functions (See Table 3)
Table 3. Usual recommended dosage in 50-60 kg adult with normal liver and renal
functions
Antibiotic Dosage Antibiotic Dosage
Low-risk CAP (All antibiotics are taken orally)
β-lactams: Second-generation
cephalosporin:
Amoxicillin 500 mg thrice a
day
Macrolides: Cefuroxime axetil 500 mg twice a
day
Azithromycin 500 mg once a
dihydrate day
Clarithromycin 500 mg twice a

day
β-lactam with
β-lactamase
inhibitor
combination (BLIC):
Co-amoxiclav (Amox- 625 mg thrice a

icillin-clavulanate) day or
1 g twice a day
D. How is response to initial therapy assessed?

1. The following parameters are regularly monitored: temperature, respira-
tory rate, heart rate, blood pressure, sensorium, and when available, the
oxygen saturation.
2. Response to therapy is expected within 24-72 hours of initiating antibi-
otic treatment.
E. What is done in case of failure to respond?
1. Failure to improve after 72 hours of initiating antibiotic treatment is an
indication to repeat the chest x-ray.
2. Failure to respond to completed initial treatment should prompt a refer-
ral to the higher level of healthcare facility or initiation of extensive work-
up to search for factors causing treatment failure (e.g., sputum G/S and
C/S).
III. What are the recommended preventive measures for CAP?

A. Vaccination
1. Influenza vaccination is recommended for the prevention of CAP. Influ-
enza predisposes individuals to bacterial CAP.
(Grade A Recommendation)
2. Pneumococcal vaccination is recommended for the prevention of inva-
sive pneumococcal disease in adults.
193
B. Smoking Cessation
• Smoking cessation is recommended for all persons with CAP who
smoke.
REFERENCE:
Joint Statement of the Philippine Society for Microbiology and Infectious Diseases, Philippine
College of Chest Physicians, Philippine Academy of Family Physicians and Philippine
College of Radiology, 2010, Philippine Clinical Practice Guidelines on the Diagnosis,
Empiric Management, and Prevention of Community-acquired Pneumonia (CAP) in
Immunocompetent Adults 2010 Update, Makati City, Philippines: Zurbano Publishing
& Printing Corp., PPGG-ID Philippine Society for Microbiology and Infectious Disease.
194
Guidelines for the Management of Pediatric Community
Acquired Pneumonia at the Primary Healthcare Level
I. What is the approach to the diagnosis of pediatric Community Ac-

quired Pneumonia (pCAP)?
A. Who shall be considered as having Community Acquired Pneumo-

nia?
1. The presence of pneumonia may be considered even without a

chest radiograph in a pediatric patient presenting with:
a. cough and/or respiratory difficulty (Recommendation Grade D-
refer to Table 5 for Grades of Recommendation);
b. plus any of the following predictors of radiographic pneumonia:
1.) at the Out-Patient Clinic as the site-of-care:
• tachypnea as defined by the World Health Organiza-
tion (WHO) for a patient aged 3 months to 5 years
(Recommendation Grade B); or
• fever at any age (Recommendation Grade B).
2.) at the Emergency Room as the site-of-care:
• tachypnea as defined by WHO in a patient aged 3
months to 5 years (Recommendation Grade B); or
• fever at any age (Recommendation Grade B); or
• oxygen saturation < 92% at room air at any age (Rec-
ommendation Grade B) in the absence of any co-
existing illness (neurologic, musculoskeletal, or cardiac
condition) that may potentially affect oxygenation
(Recommendation Grade D).
2. The presence of pneumonia should be determined using a chest
radiograph in a patient presenting with:
a. cough and/or respiratory difficulty (Recommendation Grade D)
in the following situations:
1.) presence of dehydration aged 3 months to 5 years; or
2.) presence of severe malnutrition aged < 7 years.
b. high grade fever and leucocytosis in patients aged 3 – 24
months without respiratory symptoms (Recommendation
Grade C);
B. Who will require admission?
1. Consider Revised Risk Classification for pneumonia-related mortali-

a
ty (see Table 4).
2. Patients under 5 years old (Recommendation Grade B) and more
than 5 years old (Recommendation Grade D) who are classified as
pCAP C but whose chest x-ray is without any of the following: ef-
fusion, lung abscess, air leak or multilobar consolidation, and
whose oxygen saturation is > 95% at room air can be managed ini-
tially on an out-patient basis.
195
Table 4. Revised risk classification for pneumonia-related mortalitya (Recommendation
Grade D) for pediatric community acquired pneumonia.
CLASSIFICATION
Philippine Academy of
Pediatric Pulmonologists pCAP A / pCAP B pCAP C pCAP D
World Health NONSEVERE SEVERE VERY

Organization SEVERE
VARIABLESb
a.Clinical Variables
1.Dehydrationc pCAP A – None /
pCAP B – Mild Moderate Severe
2.Malnutritiond None Moderate Severe
3.Pallor None Present Present
4.Respiratory Rate:
a. 3 – 12 monthse >50/min to <60/min >60/min to <70 >70/min
b. 1 – 5 yearse >40/min to <50/min >50/min >50/min
c. > 5 years >30/min to <35/min >35/min >35/min
5.Signs of respiratory
failure:
a. Retraction None Intercostal/ Supraclavi-
Subcostal cular/Inter-
costal/Sub-
costal
b. Head bobbing None Present Present
c. Cyanosis None Present Present
d. Grunting None None Present
e. Apnea None None Present
f. Sensorium Normal Irritable Lethargic/
Stuporous/
Comatose
b.Diagnostic Variables (Diagnostic Aids at Site-of-care)f

1.Chest X-ray findings of
any of the following:
effusion, abscess, air None Present Present
leak or lobar consolida-
tion
2.Oxygen saturation at
room air using pulse 95% <95% <95%
oximetry
ACTION PLAN
1.Site-of-care of treatment Admit to Admit to
Outpatient Hospital Ward Critical Care
Facility
2.Follow-up At end of treatment
a
In order to classify to a higher risk category, at least 2 variables (i.e., clinical and diagnostic aid)
should be present. In the absence of diagnostic aid variables, the clinical variables will suffice.
196
b
Risk factors for mortality based on evidence and/or expert opinion among members of the 2012
PAPP Task Force on pCAP.
c
Weight for Height (WFH) SD score < -2 moderate; SD score < -3 severe, from WHO Manage-
ment of Severe Malnutrition: a Manual for Physicians and other Health Workers, Geneva, WHO,
1999.
d
Grading of Dehydration adapted from Nelson’s Textbook of Pediatrics: MILD (thirsty, normal or
increased pulse rate, decreased urine output and normal physical examination); MODERATE
(tachycardia, little or no urine output, irritable/lethargic, sunken eyes and fontanel, decreased
tears, dry mucous membranes, mild tenting of the skin, delayed capillary refill, cool and pale); SE-
VERE (rapid and weak pulse, decreased blood pressure, no urine output, very sunken eyes and
fontanel, no tears, parched mucous membranes, tenting of the skin, very delayed capillary refill,
cold and mottled).
e
WHO age-specific criteria for tachypnea for children under 5 years old.
f
Chest x-ray and pulse oximetry are desirable variables but not necessary as determinants of ad-
mission at site-of-care.
C. What diagnostic aids are initially requested for a patient classified

as either pCAP A or pCAP B being managed in an ambulatory set-
ting?
1. In pediatric patients, chest x-ray may be requested to rule out

pneumonia-related complications or pulmonary conditions simulat-
ing pneumonia (Recommendation Grade D).
Chest X-ray should not be requested to predict end-of-treatment
outcome.
2. Chest x-ray, complete blood count, C-reactive protein, erythrocyte
sedimentation rate, procalcitonin, or blood culture should not be
routinely requested to determine appropriateness of antibiotic us-
age (Recommendation Grade D).
II. What is the approach to the treatment of pediatric Community Ac-

quired Pneumonia (pCAP)?
A. When is an antibiotic recommended?

1. For pCAP A or pCAP B, an antibiotic may be administered if a pa-
tient is:
a. beyond 2 years of age (Recommendation Grade D); or
b. with high grade fever without wheeze (Recommendation Grade
D).
2. For pCAP C, an antibiotic:
a. should be administered if alveolar consolidation on chest x-ray
is present (Recommendation Grade C);
b. may be administered if a patient presents with any of the fol-
lowing:
1) elevated serum C-reactive protein (CRP) (Recommenda-
tion Grade A);
2) elevated serum procalcitonin level (Recommendation
Grade B);
3) elevated white blood cell count (Recommendation Grade
D);
4) high grade fever without wheeze (Recommendation Grade
D);
5) beyond 2 years of age (Recommendation Grade D).
3. For pCAP D, refer urgently to the hospital.
197
B. What empiric treatment should be administered if a bacterial etiol-
ogy is strongly recommended?
1. For a patient who has been classified as having pCAP A or pCAP

B without previous antibiotics:
a. amoxicillin at 40-50 mg/kg/day with maximum dose of 1,500
mg/day in 3 divided doses for at most 7 days is the drug of
choice (Recommendation Grade B).
1) Amoxicillin may be given for a minimum of 3 days (Rec-
ommendation Grade A).
2) Amoxicillin may be given in 2 divided doses for a minimum
of 5 days (Recommendation Grade B).
b. For patients with known hypersensitivity to amoxicillin, the
following can be given (Recommendation Grade D):
1) azithromycin at 10 mg/kg/day once daily for 3 days or 10
mg/kg/day at day 1 then 5 mg/kg/day for days 2 to 5 with
maximum dose of 500 mg/day; or
2) clarithromycin at 15 mg/kg/day with maximum dose of
1,000 mg/day in 2 divided doses for 7 days.
2. For a patient who has been classified as having pCAP C not requir-
ing oxygen support and hospitalization, who can tolerate oral feed-
ing and without previous antibiotic, amoxicillin at 40 – 50 mg/
kg/day with maximum dose of 1,500 mg/day in 3 divided doses for
at most 7 days may be given on an out-patient basis (Recom-
mendation Grade B).
3. For a patient classified as pCAP C who is severely malnourished or
suspected to have methicillin-resistant Staphylococcus aureus, or
classified as pCAP D, urgent referral to a hospital with adequate
facilitites is highly recommended.
4. For a patient established to have Mycobacterium tuberculosis infec-
tion or disease, antituberculosis medicines should be started.
C. What treatment should be initially given if a viral etiology is strong-

ly considered?
1. Oseltamivir (for >1 year old, give 30 mg twice a day for a patient
with <15 kg body weight; 45 mg twice a day for >15-23 kg; 60 mg
twice a day for >23-40 kg; and 75 mg twice a day for >40 kg) re-
mains to be the drug of choice for laboratory confirmed (Recom-
mendation Grade A), or clinically suspected (Recommendation
Grade D) cases of influenza.
2. The use of immunomodulators for the treatment of viral pneumonia
is not recommended (Recommendation Grade D).
D. When can a patient be considered as responding to the current an-

tibiotic?
1. Decrease in respiratory signs and/or defervescense within 72 hours
after initiation of antibiotic are predictors of favorable response
(Recommendation Grade D).
2. If clinically responding, further diagnostic aids to assess response
such as chest x-ray, C-reactive protein, and complete blood count
should not be routinely requested (Recommendation Grade D).
198
PNF new 224 new.pdf 1 1/6/15 6:59 PM
( :KDWVKRXOGEHGRQHLIDSDWLHQWLVQRWUHVSRQGLQJWRFXUUHQWDQWL
ELRWLFWKHUDS\"
1. If an outpatient classified as either pCAP A or pCAP B is not re-
sponding to the current antibiotic within 72 hours, consider any of
the following (Recommendation Grade D):
a. other diagnosis such as:
1) co-existing illness; or
2) conditions simulating pneumonia.
b. other etiologic agents for which chest x-ray, C-reactive protein,
or complete blood count may be used to determine the nature
of the pathogen.
1) May add an oral macrolide if atypical organism is highly
considered.
2) May change to another antibiotic if microbial resistance is
highly considered.
) :KDWDQFLOODU\WUHDWPHQWFDQEHJLYHQ"
1. For pCAP A or pCAP B,
a. a bronchodilator may be administered in the presence of
wheezing (Recommendation Grade D).
b. cough preparation (Recommendation Grade A), elemental zinc
(Recommendation Grade B), vitamins A and D, probiotic, and
chest physiotherapy (Recommendation Grade D for the last 3),
should not be routinely given during the course of illness.

,, :KDWDUHWKHSUHYHQWLYHPHDVXUHVIRUS&$3"

$ 9DFFLQDWLRQ
Vaccine against the following pathogens should be given:
1. Streptococcus pneumoniae (conjugate type) (Recommendation
Grade A)
2. Influenza (Recommendation Grade A);
3. Diphtheria, Pertussis, Rubeola, Varicella, Haemophilus influenzae
type B (Recommendation Grade A).
% 0LFURQXWULHQW
1. Elemental zinc for ages 2 to 59 months should be given for 4-6
months (Recommendation Grade A).
2. Vitamin D3 supplementation may be given (Recommendation
Grade B).
3. Vitamin A should not be given (Recommendation Grade A).
127(: For further guidelines on the management of community acquired pneumo-

nia in children, please refer to the latest ,QWHJUDWHG 0DQDJHPHQW RI &KLOGKRRG
,OOQHVV ,0&, +DQGERRNDQG &KDUW %RRNOHtt published and provided by WHO and
distributed by DOH to the primary healthcare providers. This may also be downloaded
from the internet.
199
Table 5. Grade recommendation with level of evidence.
LEVEL OF
GRADE THERAPY DIAGNOSIS
EVIDENCE
A 1a Systematic review with Systematic review of level 1 diagnostic studies or a
homogeneity of RCT clinical practice guideline validated on a test set
A 1b Individaul RCT with Independent blind comparison of an appropriate spec-
narrow trum of consecutive patients, all of whom have under-
confidence interval gone both the diagnostic test and the reference standard
A 1c All or none SnIN and SnOUT
B 2a Systematic review with Systematic review with homogeneity of level 2 diagnostic
homogeneity of cohort studies
study
B 2b Independent blind comparison but either in non-
consecutive patients or confined to a narrow spectrum of
study individuals (or both), all of whom have undergone
both the diagnostic test and the reference standard, or a
diagnostic clinical practice guideline not validated in a
test set
B 2c “Outcomes” research
B 3a Systematic review with
homogeneity of case
control studies
B 3b Individual case control Independent blind comparison of an appropriate spec-
studies trum but reference standard was not applied to all study
patients
C 4 Case series or poor Reference standard was not applied independently or
quality cohort not applied blindly
D 5 Expert opinion Expert opinion
REFERENCE:
PAPP Task Force on pCAP, Philippine Academy of Pediatric Pulmonologists.2012. PAPP Per-
spective. PAPP Update in the Evaluation and Management of Pediatric Community-
Acquired Pneumonia. Kalayaan Avenue: Quezon City. Philippine Academy of Pediat-
ric Pulmonologists.
200
URINARY TRACT INFECTION
Algorithm 1
1
WOMAN with ≥1 symptom of UTI*
2 3
YES
Pregnant? Refer to Section on UTI in Pregnancy.
NO
4
5
Recurrent YES Refer to a higher level of healthcare facility

>2x/year? for further diagnostic work-up.
NO 7
6
YES Do urinalysis, urine culture to establish diagnosis.
With risk factors Consider initiating empirical treatment.
for complicated UTI? Refer to higher level of healthcare facility.
9
NO
8
Consider Acute Uncomplicated Pyelonephritis.
YES Do urinalysis, urine culture to establish diagnosis.
With flank pain Consider empiric treatment.
or fever?
See Section on Acute Uncomplicated Pyelonephritis.
11
NO
Low to intermediate probability of UTI (~20%).
10
Consider Sexually Transmitted infections.
YES Do pelvic examination (including cervical culture
With vaginal when appropriate), urinalysis, urine culture, urine.
discharge?
Chlamydia to establish diagnosis.
See Section on Acute Uncomplicated Cystitis (AUC)
NO
12
13
With clear history of >1 High probability of AUC (~90%).

YES
symptom of UTI – acute Start empiric treatment without urinalysis, urine
onset of dysuria, frequen- culture.
cy, urgency, hematuria? See Section on Acute Uncomplicated Cystitis.
NO
14
Perform dipstick analysis
15 16
YES High probability of AUC (~80%).

Dipstick result Start empiric treatment without urine culture.
positive?
See Section on Acute Uncomplicated Cystitis.
NO
17
Low to intermediate probability of UTI (~20%).

Consider urine culture or close clinical follow-up and pelvic
examination including cervical cultures and radiologic imaging *dysuria, frequency,
when appropriate. urgency, hematuria,
See Section on Uncomplicated Urinary Tract Infection. discomfort in lower
abdomen
201
Algorithm 2
1
Healthy pre-menopausal, non-pregnant

WOMAN w/ acute uncomplicated cystitis
Treat empirically with recommended oral

antibiotics (Table 7)
Reassess at end of therapy
4 5
YES
Symptoms No further treatment
resolved?
NO
6
Do urinalysis, urine culture and change

antibiotics empirically pending urine c/s results
1 Algorithm 3
Healthy non-pregnant WOM-
AN with acute uncomplicated
pyelonephritis
2
Assess severity of illness and likelihood adherence to treatment.
4
3
1. Admit patient.
Septic, too ill YES
2. Do urinalysis, urine GS, C/S.
or likely to be 3. Do blood C/S 2x if septic.
-
noncompliant? 4. Start empiric IV antibiotics.
NO
5
1. Do urinalysis, urine GS, C/S. 6

2. Treat as outpatient. Reassess patient
3. Start empirical oral antibiotics (Table 9) within 72 hours.
based on gram stain results.
7
8
YES
1. Shift IV antibiotics to oral Symptoms im-
once patient is afebrile and can proved on Day 3?
tolerate oral medications.
2. Continue antibiotics for 10- NO
14 days. 9
3. Antibiotic choice should be 1. Repeat urine C/S.
guided by urine C/S results 2. Consider doing radiologic evaluation.
once available. 3. Consider urologic consultation.
202
Clinical Practice Guidelines on the Diagnosis and
Management of Urinary Tract Infections in Adults at
the Primary Healthcare Level
I. Uncomplicated Urinary Tract Infection
A. Acute Uncomplicated Cystitis (AUC) in Women
1. What is the approach to the diagnosis of AUC?
• Clinically, AUC is suspected in premenopausal non-pregnant
women presenting with acute onset of dysuria, frequency, urgency,
and gross hematuria; and without vaginal discharge.
• Urinalysis is not necessary to confirm the diagnosis of AUC in
women presenting with one or more of the above symptoms of uri-
nary tract infection (UTI) in the absence of vaginal discharge and
complicating conditions enumerated in Table 6.
• Women presenting with urinary symptoms plus vaginal discharge
should undergo further evaluation to rule out or rule in other dis-
ease conditions.
• Conditions that define complicated urinary tract infection (cUTI)
must be absent as obtained in history taking (Table 6).
Table 6. Conditions that define complicated UTI
• Presence of an indwelling urinary catheter or intermittent catheterization
• Incomplete emptying of the bladder with >100 mL retained urine post-voiding
• Impaired voiding due to neurogenic bladder, cystocoele
• Obstructive uropathy due to bladder outlet obstruction, calculus, urethral or
ureteric strictures, and tumors
• Vesicoureteral reflux and other urologic abnormalities including surgically
created abnormalities
• Chemical or radiation injuries of the uroepithelium
• Peri- or post-operative UTI
• Azotemia due to intrinsic renal disease
• Renal transplantation
• Diabetes mellitus
• Immunosuppressive conditions – e.g., febrile neutropenia, HIV AIDS
• UTI caused by unusual pathogens (M. tuberculosis, Candida spp.)
• UTI caused by multi-drug resistant organisms (MDROs)
• UTI in males except in young males presenting exclusively with lower UTI
symptoms
• Urosepsis
2. What is the approach to the treatment of AUC?

a. Are laboratory tests necessary before initiation of antibiotic thera-
py?
• Empiric antibiotic treatment is the most cost-effective approach
in the management of AUC.
• Pre-treatment urine culture and sensitivity is not recommend-
ed.
203
PNF new 229 .pdf 1 1/9/15 11:53 AM
mal resistance, minimal adverse effects, low propensity for col-
lateral damage, and reasonable cost. However, the nitrofu-
rantoin monohydrate/macrocrystal formulation is not locally
available. Thus, the locally available nitrofurantoin macro-
crystal formulation 100 mg is recommended, but it should be
given four times a day for five days.
iv. Antimicrobial Resistance Alert!
Quinolones should not be used as a first line drug for acute
uncomplicated cystitis despite their efficacy due to its high pro-
pensity for collateral damage.
v. Beta-lactam agents, including co-amoxiclav (amoxicillin-
clavulanate), and cefuroxime are appropriate alternative choic-
es for therapy when the primary recommended agents cannot
be used.
vi. The recommended duration of treatment for healthy elderly
women with AUC is the same as the duration for the general
population.
3. What is the course of action for patients who do not respond to
treatment?
a. Patients whose symptoms worsen or do not improve after comple-
tion of treatment should have a urine culture done, and, the antibi-
otic should be empirically changed pending result of sensitivity test-
ing.
b. Patients whose symptoms fail to resolve after treatment should be
managed as complicated UTI.
4. Are post-treatment diagnostic tests needed in patients who re-
spond to treatment?
Routine post-treatment urine culture and urinalysis in patients
whose symptoms have completely resolved are NOT recommended as
it does not provide any added clinical benefit.
B. Acute Uncomplicated Pyelonephritis (AUP)

1. What is the approach to the diagnosis of AUP?
a. Acute uncomplicated pyelonephritis (AUP) is suspected in other-
wise healthy women with no clinical or historical evidence of ana-
tomic or functional urologic abnormalities, who present with the
classic syndrome of fever (T ≥38°C), chills, flank pain, costoverte-
bral angle tenderness, nausea and vomiting, with or without signs
and symptoms of lower urinary tract infection.
b. Laboratory findings include pyuria (≥5 WBC/HPF of centrifuged
urine) on urinalysis and bacteriuria with counts of ≥10,000 CFU of
uropathogen/mL on urine culture.
(Strong recommendation, Moderate quality of evidence)
c. What pre-treatment diagnostic tests are necessary?
i. Urinalysis and Gram-stain are recommended. Urine culture
and sensitivity test should also be performed routinely to facili-
tate cost-effective use of antimicrobial agents and because of
205
b. What are the recommendations with regard to the specific utiliza-
tion of other antibiotics in the treatment of AUP?
The following is a strong recommendation based on high
quality of evidence:
Quinolones are recommended as the first-line treatment only for
acute uncomplicated pyelonephritis not requiring hospital admis-
sion (high quality of evidence).
The following are strong recommendations based on
moderate quality of evidence:
i. Antimicrobial Resistance Alert!

The aminopenicillins (ampicillin or amoxicillin) and first gen-
eration cephalosporins are not recommended for AUP be-
cause of the high prevalence of resistance and increased re-
currence rates in patients given these beta-lactams.
ii. Antimicrobial Resistance Alert!

Because of high resistance rates to cotrimoxazole, this drug
is not recommended for empiric treatment of AUP, but it can
be used when an organism is susceptible on urine culture and
sensitivity.
iii. In patients not requiring hospital admission, an initial single

IV/IM dose of ceftriaxone or aminoglycoside may be consid-
ered followed by any of the oral antibiotics recommended in
Table 9.
[
iv. For suspected enterococcal infection, ampicillin may be com-

bined with an aminoglycoside (weak recommendation based
on low quality of evidence).
4. What is the role of radiologic imaging in the management of AUP?
a. The following are strongly recommended based on moderate quali-
ty of evidence:
• Routine urologic evaluation and routine use of imaging proce-
dures are not recommended.
• Consider early radiologic evaluation if the patient has a history
of urolithiasis, urine pH ≥7.0 or renal insufficiency.
b. The following may also be considered (only weakly recommended
due to low quality of evidence):
• Consider radiologic evaluation if the patient remains febrile
within 72 hours of treatment or if symptoms recur to rule out
the presence of nephrolithiasis, urinary tract obstruction, renal
or perinephric abscesses or other complications of pyelone-
phritis.
• Obtain urologic consultation if radiologic workup shows abnor-
malities.
207
5. What are the follow-up laboratory tests needed?
The following may also be considered (weakly recommended
• In patients who are clinically responding to therapy (usually appar-
ent in <72 hours after initiation of treatment), a follow-up urine cul-
ture is not necessary.
• Routine post-treatment cultures in patients who are clinically im-
proved are also not recommended.
• In women whose symptoms do not improve during therapy and in
those whose symptoms recur after treatment, a repeat urine culture
and sensitivity test should be performed.
6. What is the course of action in patients with recurrence of
symptoms?
The following may also be considered (weakly recommended
• Recurrence of symptoms requires antibiotic treatment based on
urine culture and sensitivity test results in addition to assessing for
underlying genito-urologic abnormality.
• The duration of re-treatment in the absence of a urologic abnormali-
ty is two weeks.
• For patients whose symptoms recur and whose culture shows the
same organism as the initial infecting organism, a four- to six-week
regimen is recommended.
Table 10. Strength of recommendation, and quality of evidence

Category / Definition
Grade
RECOMMENDATION
Strong Clear desirable or undesirable effects
Weak Desirable and undesirable effects closely balanced or uncertain
QUALITY OF EVIDENCE
High Consistent evidence from well-performed RCTs or exceptionally
strong evidence from unbiased observational studies
Moderate Evidence from RCTs with important limitations or moderately
strong evidence from unbiased observational studies
Low Evidence for ≥1 (one) critical outcome from observational stud-
ies, from RCTs with serious flaws or from indirect evidence
Very Low Evidence for ≥1 (one) critical outcome from unsystematic clini-
cal observation or very indirect evidence
II. Asymptomatic Bacteriuria in Adults

1. What is Asymptomatic Bacteriuria (ASB)?
Asymptomatic bacteriuria (ASB) is the presence of ≥100,000 cfu/mL of
one or more uropathogens in two consecutive midstream urine speci-
mens or in one catheterized urine specimen in the absence of symp-
toms attributed to a UTI.
208
2. Who should be screened for ASB?
• Patients who will undergo genitourinary manipulation or instrumen-
tation
• Post-renal transplant patients up to the first 6 months
• Diabetes mellitus patients with poor glycemic control, autonomic
neuropathy or azotemia
• All pregnant women (refer to next section on UTI in Pregnancy)
3. What is the treatment for ASB?
Any of the antibiotics listed in Table 11 can be used to treat ASB in the
above group of patients except pregnant women (refer to next section
for specific treatment of UTI in Pregnancy).
Table 11. Antibiotics that can be used for Asymptomatic Bacteriuria in Adults (except
pregnant females)
Antibiotics Dose and Frequency Duration
Cotrimoxazole 800/160 mg twice a day 7-14 days
(Trimethoprim-Sulfamethoxazole)
Ciprofloxacin 250 mg twice a day 7-14 days
Nitrofurantoin 100 mg four times a day 7-14 days
Cefuroxime 125-250 mg twice a day 7-14 days
Co-amoxiclav 625 mg twice a day 7-14 days
(Amoxicillin-Clavulanate)
III. Urinary Tract Infections in Pregnancy

A. Asymptomatic Bacteriuria in Pregnancy
1. When is asymptomatic bacteriuria in pregnancy diagnosed?
• Asymptomatic bacteriuria in pregnancy is the presence of
>100,000 CFU/mL of the same uropathogen in two consecutive
midstream urine specimens, or >100 CFU/mL of a single uropatho-
gen in one catheterized urine specimen, in the absence of symp-
toms attributable to urinary tract infection.
• In situations or settings where obtaining two consecutive urine cul-
tures are not feasible or difficult, one urine culture is an acceptable
alternative for the diagnosis of ASB in pregnancy (weak recom-
mendation due to low quality of evidence).
2. Do all pregnant women have to be screened for ASB?
• All pregnant women must be screened for ASB on their first prena-
tal visit between the 9th to 17th weeks, preferably on the 16th week
age of gestation.
3. What is the optimal screening test for ASB in pregnancy?
• A standard urine culture of clean-catch midstream urine is the test
of choice in screening for asymptomatic bacteriuria.
• If urine culture is not available, an initial gram stain of uncentrifuged
urine (more than one organism per oil immersion field) is recom-
mended for screening for ASB. Dipslide culture technique may be
209
used as an alternative to urine culture in settings where this is
available.
• Urinalysis is not recommended as the initial screening test. Urine
dipsticks for leucocyte esterase and/or nitrite tests are not recom-
mended for screening also.
4. What is the effective treatment for ASB in pregnancy?
• Antibiotic treatment for asymptomatic bacteriuria is indicated to re-
duce the risk of acute cystitis and pyelonephritis in pregnancy as
well as to reduce the risk of low birth weight neonates and preterm
infants
• It is recommended that antibiotic treatment be initiated upon the
diagnosis of ASB in pregnancy. The choice depends on the sen-
sitivity of the urine isolate. Among the antibiotics that can be used
are cefalexin, cefuroxime, and co-amoxiclav.
Cotrimoxazole should be avoided in the 1st and 3rd trimesters and

nitrofurantoin must be used with caution (not for near term).
• Duration of treatment depends on the antibiotic used, but, short

course (7 days) treatment is preferred over single-dose regimens.
• Do follow-up cultures one week after completing the course of
treatment (Grade C).
Table 12. FDA Pregnancy Risk and Hale’s Lactation Risk Categories for commonly
prescribed antimicrobials in urinary tract infection
Category Ba, L1, L2b Category Ca, L3b Category Da, L3b
Co-amoxiclav Cotrimoxazole (avoid in 1st Aminoglycosides
Cephalosporins and 3rd trimesters)
Nitrofurantoin (must be used
with caution; not for near
term)
ᵃRefer to the US FDA Pregnancy Risk Categories (See Appendix)
ᵇLactation Risk Category:
L1 – safest, controlled study = fails to demonstrate risk
L2 – safer, limited number of women studied without risk
L3 – moderately safe, no controlled study or controlled study shows minimal, non-
life-threatening situation
L4 – hazardous, positive evidence of risk, may be used if maternal life-threatening
situation
L5 – contraindicated, significant, and documented risk
210
Table 13. Recommended antibiotics for Asymptomatic Bacteriuria in Pregnancy at the
Primary Healthcare Facility
RECOMMENDED DOSE FDA PREGNANCY RISK
ANTIBIOTICS
AND DURATION CATEGORY
Cefalexin 500 mg 2x a day for 7 days B
Cefuroxime 500 mg 2x a day for 7 days B

axetil
Co-amoxiclav 625 mg 2x a day for 7 days B
(Amoxicillin-
Clavulanate)
Nitrofurantoin 100 mg 4x a day for 7 days B
macrocrystal • May cause hemolytic anemia,
anophthalmia, hypoplastic left
heart syndrome, ASD, cleft lip
and palate;
• May be given on the 2nd tri-
mester of pregnancy until 32
weeks age of gestation;
• Use in the first trimester of
pregnancy is appropriate
when NO OTHER suitable al-
ternative is available.
B. Acute Uncomplicated Cystitis in Pregnancy

1. When do you suspect acute uncomplicated cystitis in pregnancy?
• In an otherwise healthy pregnant woman, acute cystitis is charac-
terized by urinary frequency and urgency, dysuria and bacteriuria
without fever and costo-vertebral angle tenderness. Gross hematu-
ria may also be present.
2. Is a pre-treatment diagnostic test required in acute cystitis in
[
pregnancy?
• In pregnant women suspected to have acute uncomplicated cystitis,
obtain a pre-treatment urine culture and sensitivity test of a
mid-stream clean-catch urine specimen.
• In the absence of a urine culture, the laboratory diagnosis of acute
cystitis is determined by the presence of significant pyuria on uri-
3
nalysis defined as a) >8 pus cells/mm of uncentrifuged urine OR
b) >5 pus cells/hpf of centrifuged urine, AND c) a positive leukocyte
esterase and nitrite test on dipstick (Strong recommendation with
moderate quality of evidence).
3. What is the treatment for acute cystitis in pregnancy?
• Treatment of acute cystitis in pregnancy should be instituted im-
mediately to prevent the spread of infection to the kidney.
• Since E. coli remains to be the most common organism isolated,
antibiotics to which this organism is most sensitive and which are
safe to give during pregnancy should be used.
• In the absence of urine culture and sensitivity, empiric therapy
should be based on local susceptibility patterns of uropathogens.
211
Cotrimoxazole and fluoroquinolones are relatively contraindicated
during pregnancy because of their potential teratogenicity as well
as the third trimester risk of kernicterus with cotrimoxazole.
• A 7-day treatment with an oral antibiotic safe for use in pregnancy

is recommended.
• For a patient who is clinically responding to the present treatment,
there is no need to change the antibiotic that was empirically start-
ed even if resistance is reported on urine culture and sensitivity.
Adjust antibiotic treatment based on urine C/S only when there is
no improvement in the clinical signs and symptoms or laboratory
results or when there is worsening of the patient’s condition.
Table 14. Recommended antibiotics that can be used for Acute Cystitis in Pregnancy at the
Primary Healthcare Facility
RECOMMENDED PREGNANCY
BIRTH DEFECTS/ COMMENTS/
ANTIBIOTICS DOSE AND RISK
COMPLICATIONS QUALIFIERS
DURATION CATEGORY
Cefalexin 500 mg 4x a B None Safe in any
day for 7 days trimester
Cefuroxime 500 mg 2x a B None Safe in any

axetil day for 7 days trimester
Nitrofurantoin 100 mg 4x a B Hemolytic May be given on

day for 7 days anemia, the 2nd trimester
for anophthalmia, until 32 weeks
macrocrystals hypoplastic left age of gestation.
heart syndrome. Use in the 1st
ASD, cleft lip trimester is
and palate appropriate only
when NO
OTHER suitable
alternative is
available.
Co-amoxiclav 625 mg 2x a B Neonatal Avoid in women
(Amoxicillin- day for 7 days necrotizing at risk of preterm
Clavulanate) enterocolitis labor.
4. What is the clinical utility of a post-treatment urine culture?

• Post-treatment urine culture 1 – 2 weeks after completion of thera-
py should be obtained to confirm eradication of bacteriuria and res-
olution of infection in pregnant women.
• Pregnant patients with pyelonephritis, recurrent UTIs, concurrent
gestational DM, concurrent nephrolithiasis or urolithiasis, and pre-
eclampsia, should be monitored at monthly intervals until delivery to
ensure that urine remains sterile during pregnancy.
212
C. Acute Uncomplicated Pyelonephritis in Pregnancy
1. When is acute uncomplicated pyelonephritis in a pregnant woman
suspected?
• The classic syndrome of acute uncomplicated pyelonephritis in
healthy women also applies to pregnant women. This is character-
ized by shaking chills, fever (T>38 °C), flank pain, nausea and
vomiting, costovertebral angle tenderness, with or without signs
and symptoms of lower urinary tract infections. Urinalysis shows
pyuria of >5 WBC/hpf of centrifuged urine and bacteriuria of
>10,000 CFU of a uropathogen/mL on urine culture.
2. What is the recommended action for acute uncomplicated pyelo-
nephritis in pregnant women?
• Pregnant patients with acute pyelonephritis should be referred to
the hospital and be given immediate antimicrobial therapy.
• Indications for admission are: inability to maintain oral hydration or
take medications; concern about compliance; presence of possible
complicating (co-morbid) conditions; severe illness with high-grade
fever, severe pain, marked debility; signs of preterm labor; and
signs of sepsis (see Table 8).
3. To guide antibiotic choice and to establish an etiologic diagnosis,
what tests are done?
• Urinalysis with gram stain of uncentrifuged urine is recommended
to differentiate gram positive from gram-negative bacteriuria, which
can guide the choice of empiric antibiotic therapy.
• Important Note: Urine culture and sensitivity test should be done
routinely to facilitate cost-effective use of the antibiotic and to avert
potential serious sequelae due to an inappropriate antimicrobial.
Important Note: Blood cultures are not routinely recommended un-
less sepsis is present.
IV. Urinary Tract Infections in Men

A. Uncomplicated Cystitis in Young Men
1. What is the definition of uncomplicated cystitis in young men?
• UTI in men is generally considered complicated.
• However, the first episode of symptomatic lower UTI in young (15 –
40 years old) otherwise healthy sexually active men with no clinical
or historical evidence of a structural or functional urologic abnor-
mality is considered as uncomplicated UTI.
2. How is uncomplicated cystitis in males diagnosed?
3
• Significant pyuria in men is defined as >10 WBC/mm or >5
WBC/hpf in a clean catch midstream urine specimen. This shows
good correlation with bladder bacteriuria and the growth of >1,000
colonies of one predominant species/mL of urine and best differen-
tiates sterile from infected bladder urine (Grade C – see Table 15).
213
3. What is the recommended diagnostic workup for uncomplicated
cystitis in men?
• Recommended diagnostic workup includes: urinalysis and urine
culture.
• A pre-treatment urine culture should be performed routinely in all
men with UTI (Grade C).
• Routine urologic evaluation and use of imaging procedures are not
recommended (Grade C).
4. What is the recommended treatment?
• Seven-day antibiotic regimens are recommended (Grade C).
• Antibiotics to be used depend on the prevailing susceptibility
patterns in the community or institution. Refer to Section on Acute
Uncomplicated Cystitis in Women for antibiotic choices.
Table 15. Categories reflecting the strength of evidence.

Grade Definition
A Good evidence to support a recommendation for use
B Moderate evidence to support a recommendation for use
C Poor evidence to support a recommendation for or against use
D Moderate evidence to support recommendation against use
E Good evidence to support recommendation against use
REFERENCES:
The Task Force on Updates in Urinary Tract Infection in Pregnancy, Philippine Practice Guide-
lines Group in Infectious Diseases, 2013, Philippine Clinical Practice Guidelines on the Di-
agnosis and Management of Urinary Tract Infections in Adults: Urinary Tract Infections in
Pregnancy 2013 Update, PPGG-ID, Philippine Society for Microbiology and Infectious Dis-
eases, Quezon City, Philippines.
The Task Force on Urinary Tract Infections, Philippine Practice Guidelines Group in Infectious
Diseases, 2013, Philippine Clinical Practice Guidelines on the Diagnosis and Management
of Urinary Tract Infections in Adults: Uncomplicated Urinary Tract Infection 2013 Update,
PPGG-ID, Philippine Society for Microbiology and Infectious Disease, Quezon City, Philip-
pines.
The Task Force on Urinary Tract Infections 2003-04, Philippine Practice Guidelines Group in
Infectious Diseases, 2004, Philippine Clinical Guidelines on the Diagnosis and Manage-
ment of Urinary Tract Infections in Adults 2004 Update, PPGG-ID, Philippine Society for
Microbiology and Infectious Diseases, Quezon City, Philippines, vol. 2, no. 1.
214
TUBERCULOSIS
Recommended Treatment Regimen for Tuberculosis
in Adults and Children
(Based on DOH National TB Control Program Manual of Procedures, 2014)
Table 16. Recommended Treatment Regimen for TB for Adults and Children Based on Anatom-
ical Site and Bacteriologic Status (including drug resistance and history of prior
treatment).
Category of Treatment
Classification and Registration Group
Treatment Regimen
Pulmonary TB, new (whether bacteriologically-
confirmed or clinically-diagnosed)
Category I 2HRZE / 4HR
Extra-pulmonary TB, new (whether bacteriological-
ly-confirmed or clinically-diagnosed) except CNS/
bones or joints
Category Ia Extra-pulmonary TB, new (CNS / bones or joints) 2HRZE / 10HR
Category II Pulmonary or extra-pulmonary, Previously treated
drug-susceptible TB (whether bacteriologically-
confirmed or clinically-diagnosed)
2HRZES / 1HRZE /
• Relapse 5HRE
• Treatment After Failure
• Treatment After Lost to Follow-up (TALF)
• Previous Treatment Outcome Unknown
• Others
Category IIa Extra-pulmonary, Previously treated drug- 2HRZES / 1HRZE
susceptible TB (whether bacteriologically- / 9HRE
confirmed or clinically-diagnosed –CNS/ bones or
joints)
Standard Rifampicin-resistant TB or ZKmLfxPtoCs
Regimen Drug- Multidrug-resistant TB • Individualized
resistant once DST result
(SRDR) is available
• Treatment dura-
tion for at least 18
months
XDR-TB Extensively drug-resistant TB Individualized based
Regimen on DST result and
history of previous
treatment
LEGEND: R - Rifampicin, H - Isoniazid, E - Ethambutol, Z - Pyrazinamide, S - Streptomycin, Km - Kanamycin,
Lfx - Levofloxacin, Pto - Prothionamide, Cs - Cycloserine
DST - Drug Susceptibility Test
215
Table 17. Dosages of Drugs for Treatment Category I (2HRZE/4HR).
Intensive Phase Continuation Phase
Body Weight (kilograms) 2 months of (HRZE) daily 4 months a of (HR) daily
No. of tablets/day No. of tablets/day
30 – 37 2 2
38 – 54 3 3
55 – 70 4 4
>70 5 5
a
10 months for Category Ia
NOTE: HRZE – Isoniazid (75 mg) / Rifampicin (150 mg) / Pyrazinamide (400 mg) / Ethambutol (275 mg)
HR – Isoniazid (75 mg) / Rifampicin (150 mg)
Table 18. Dosages of Drugs for Treatment Category II (2HRZES/HRZE/5HRE).

Continuation
Intensive Phase (daily)
Phase (daily)
Body Weight First 2 months Third month 4th to 8th month b
(kilograms) HRZE
HRZE S HRE
No. of
No. of Tablets (1 g/2 mL) No. of Tablets
Tablets
30 – 37 2 2 2
38 – 54 3 1gc 3 3
55 – 70 4 4 4
>70 5 5 5
b
4th to 12th month for Category IIa
c
For patients with body weight <50 kgs and those >60 years old, consider 500-700 mg or 10 mg/kg/day
NOTES: HRZE – Isoniazid (75 mg) / Rifampicin (150 mg) / Pyrazinamide (400 mg) / Ethambutol (275 mg)
HRE - Isoniazid (75 mg) / Rifampicin (150 mg) / Ethambutol (275 mg)
HR – Isoniazid (75 mg) / Rifampicin (150 mg)
S - Streptomycin
Table 19. Drug Dosage per Kg Body Weight (If using Single Dose Formulations).
DRUG ADULTS CHILDREN
Isoniazid (H) 5 (4-6) mg/kg, 10 (10-15) mg/kg,
Not to exceed 400 mg daily Not to exceed 300 mg daily
Rifampicin (R) 10 (8-12) mg/kg, 15 (10-20) mg/kg,
Not to exceed 600 mg daily Not to exceed 600 mg daily
Pyrazinamide (Z) 25 (20-30) mg/kg, 30 (20-40) mg/kg,
Not to exceed 2 g daily Not to exceed 2 g daily
Ethambutol (E) 15 (15-20) mg/kg, 20 (15-25) mg/kg,
Not to exceed 1.2 g daily Not to exceed 1.2 g daily
Streptomycin (S) 15 (12-18) mg/kg, 30 (20-40) mg/kg,
Not to exceed 1 g daily Not to exceed 1 g daily
NOTES: Dosages for children are higher since there are more metabolizing enzymes among children than
adults leading to faster metabolism.
If the child is a newborn (<4 weeks), consider referral to a pediatrician so that Streptomycin can be
used instead of Ethambutol.
216
Table 20. Guide in the Management of Adverse Reactions to Anti-TB Drugs.
Drug(s) Probably
Adverse Reactions Management
Responsible
MINOR
Gastrointestinal intolerance Rifampicin/ Give drugs at bedtime or with
Isoniazid/ meals.
Pyrazinamide
Mild or localized skin reactions Any of the drugs Give anti-histamines.
Orange/red colored urine Rifampicin Reassure the patient.
Pain at injection site Streptomycin Apply warm compress; rotate
sites of injections.
Burning sensation at feet due to Isoniazid Give pyridoxine (Vitamin B6) at
peripheral neuropathy 50–100 mg daily for treatment,
and 10 mg daily for prevention.
Arthralgia due to hyperuricemia Pyrazinamide Give aspirin or NSAID; if symp-
toms persist, consider gout and
request for blood chemistry (se-
rum uric acid) and manage ac-
cordingly.
Flu-like symptoms (fever, mus- Rifampicin Give antipyretics.
cle pains, inflammation of the
respiratory tract)
MAJOR
Severe skin rash due to allergy Any of the drugs (espe- Discontinue anti-TB drugs and
cially streptomycin) refer to specialist.
Jaundice due to hepatitis Any of the drugs (espe- Discontinue anti-TB drugs and
cially isoniazid, rifampic- refer to specialist; if symptoms
in, and pyrazinamide) subside, resume treatment and
monitor closely.
Impaired visual acuity and color Ethambutol Discontinue Ethambutol and refer
vision due to optic neuritis to ophthalmologist immediately.
Hearing impairment, ringing of Streptomycin Discontinue Streptomycin and
the ear, and dizziness due to refer to specialist.
damage of the 8th cranial nerve
Oliguria or albuminuria due to Streptomycin/ Discontinue anti-TB drugs and
renal disorder Rifampicin refer to specialist.
Psychosis and convulsions Isoniazid Discontinue Isoniazid and refer to
specialist.
Thrombocytopenia, anemia, Rifampicin Discontinue anti-TB drugs and
shock refer to specialist.
217
Table 21. Dosing Recommendations for Patients with Reduced Renal Function or Receiving
Hemodialysis.
RECOMMENDED DOSE and FREQUENCY for
Drugs Change in Patients with creatinine clearance <30 mL/minute
Frequency? or undergoing hemodialysis
Isoniazid No change Not to exceed 300 mg once daily, or 900 mg three
times per week
Rifampicin No change Not to exceed 600 mg daily, or 600 mg three times
per week
Pyrazinamide Yes 25-35 mg/kg per dose three times per week (not
daily)
Ethambutol Yes 15-25 mg/kg per dose three times per week (not
daily)
Streptomycin Yes 12-15 mg/kg per dose two or three times per week
NOTE: It is recommended that anti-TB medications be taken after hemodialysis.
Reference:
Department of Health, 2014, National TB Control Program Manual of Procedures, 5th Edition,
Manila, Philippines.
218
NONCOMMUNICABLE DISEASES
HYPERTENSION IN ADULTS
1
♦ Proper BP measurement is essential.
HYPERTENSION
♦ Suspect HTN in certain conditions
(See section I-C of the CPG).
2
>140/90
EVALUATION
CLINICAL HISTORY:
● Identify risk factors (include BP range and factors affecting it)
PHYSICAL EXAMINATION:
● Identify signs indicating secondary causes
LABORATORY EXAMINATIONS:
● Routine examination and special examination
3 ♦ Must be initiated in ALL patients
219
Lifestyle Modifications and maintained throughout treat-
ment.
4
Has the GOAL BP been achieved?
YES NO
5 patients with diabetes or chronic kidney
♦ For patients <60 years old, including
Determine Cardiovascular Disease Risk

disease, GOAL BP is <140/90.
♦ For patients >60 years old, GOAL BP
6
is <150/90.
7
Low Cardiovascu- Middle to – High Cardiovas-
lar Disease Risk cular Disease Risk
A B C
219
Recommended Guidelines for the Management of
Hypertension at the Primary Healthcare Level
I. What is the definition of hypertension (HTN)?
A. Definition
Value is >140 mmHg systolic BP OR >90 mmHg diastolic BP
Table 22. Definition of hypertension
Systolic BP Diastolic BP Conditions
>140 mmHg >90 mmHg Measurements done in at least 2 visits taken at least 1
week apart
>140 mmHg >90 mmHg Seen in the first visit but with evidence of target organ
damage (e.g., cardiac, renal, cerebrovascular, peripheral
vascular, ophthalmologic)
B. Method for Indirect Measurement of Blood Pressure

1. Aneroid, digital or other automated devices must satisfy technical re-
quirements for accuracy and calibrated and tested regularly.
2. The manometer cuff should cover at least 2/3 of the length of the pa-
tient’s arm while the bladder should cover at least 80% of the arm cir-
cumference.
3. The patient should be seated or supine with arms bared, supported, and
at heart level. He should have rested for at least 5 minutes, and should
not have smoked or ingested caffeine within 30 minutes before meas-
urement.
4. The edge of the cuff should be place 1 inch above the elbow crease
with the bladder directly over the brachial artery.
5. The bladder should be inflated to 30 mmHg above the point of radial
pulse extinction as determined by a preliminary palpatory determination.
It should then be deflated at a rate of 2 mmHg/beat with the stethoscope
bell placed directly over the brachial artery.
6. The systolic pressure should be recorded at the appearance of the 1st
clear tapping sound (Korotkoff phase 1). Diastolic BP should be record-
ed at the disappearance of these sounds (Korotkoff phase V) unless
these are still present near 0 mmHg in which case the softening of the
sounds shall be used as diastolic pressure (Korotkoff phase IV).
7. For every visit, the mean of 2 readings, taken at least 2 minutes apart,
should be regarded as the patient’s BP. If the first 2 readings differ by 5
mmHg or more, a 3rd reading should be included in the average.
8. If BP is being taken for the 1st time, the procedure should be repeated
on the other arm. Subsequent determinations should then be performed
on the arm with a higher blood pressure reading.
9. All members of the healthcare facility must be trained to do proper BP
measurement. However, it is strongly advised that only one particular
staff member will be assigned to measure the BP measurement during
all consultations.
221
C. Conditions where HTN is Suspected
1. White coat HTN defined as BP elevation in the clinic setting but which
is repeatedly normal out of the office.
2. Isolated systolic HTN defined as systolic BP of 140 mmHg or more
and a diastolic BP of less than 90 mmHg.
3. Masked HTN defined as a condition where the patient’s office or clinic
BP is <140/90 mm Hg but ambulatory or home BP readings are in the
hypertensive range.
II. What is the approach to the diagnosis of a patient with HTN?
A. Objectives of Evaluation
1. To assess lifestyle and identify other cardiovascular risk factors and
concomitant disorders that can affect prognosis and treatment
2. To reveal identifiable causes of hypertension
3. To assess the presence or absence of target organ damage and cardio-
vascular diseases.
B. Risk Factors for Cardiovascular Disease
Table 23. Risk factors for cardiovascular disease
Modifiable Risk Factors Non-Modifiable Risk Factors
Smoking Age (Older than 55 years for men, 65
Hypertension years for women)
Dyslipidemia Male sex
Diabetes Mellitus Family history of premature cardiovas-
Obesity (BMI >30 kg/m2) cular disease (men <55 years of
Physical Inactivity age, or women <65 years of age)
Estimated GFR <60 mL/min
Microalbuminuria
C. Information included in Medical History

1. Duration of HTN and previous level of BP
2. Secondary Hypertension:
a. Family history of chronic kidney disease or Polycystic Kidney Dis-
ease
b. History of renal disease, UTI, hematuria, and analgesic abuse
c. Drug/substance intake: NSAIDs, steroids, amphetamine vasocon-
strictive nasal drops, oral contraceptives, and cocaine
d. Repetitive sweating, and palpitations (pheochromocytoma), head-
aches, and anxiety
e. Tetany (hyperaldosteronism) and episodic muscle weakness
f. Thyroid disease
3. Risk Factors:
a. Family and personal history of HTN and cardiovascular disease,
dyslipidemia, and diabetes
b. Smoking habits
222
c. Dietary habits
d. Weight changes, obesity
e. Physical exercise
f. Snoring, sleep apnea
g. Low birth weight
4. History and symptoms of organ damage and cardiovascular diseases:
a. Brain and eyes: headache, vertigo, TIA, blurring of vision, and
stroke
b. Heart: chest pains, shortness of breath, ankle edema, MI, syncope,
and palpitations
c. Kidney: thirst, polyuria, nocturia, and hematuria
d. Snoring or chronic lung disease
e. Peripheral arteries: cold extremities, intermittent claudication
5. HTN management:
a. Current medicines
b. Past medicines
c. Compliance
d. Efficacy and adverse effects of the medicines
e. Concurrent medications, herbal medicines and supplements that
may affect BP or response to treatment
6. Substance abuse, and physical, psychosocial, domestic, and occupa-
tional stresses.
D. Information included in Physical Examination
1. Appropriate measurement of BP;
2. Height and weight measurement, waist-hip ratio, and calculation of
Body Mass Index (BMI) computed as:
BMI = [(Weight / 2.205) / (Height / 39.37)²] in kg/m²
3. Head and Neck: carotid bruits, distended veins, and thyroid enlarge-
ment;
4. Chest and Lungs: heart rate, point of maximal impulse, apex beat,
heaves, clicks, murmurs, arrhythmias, gallops, and examination of the
lungs;
5. Abdomen: examination for truncal obesity, purple striae, bruits, enlarged
kidneys, masses and abnormal aortic pulsations;
6. Extremities: diminished or absent peripheral arterial pulsations, bruits
and edema, arm BP discrepancies >10 mmHg or when indicated similar
discrepancies between leg BPs, postural hypotension in the elderly (>10
mmHg drop on assumption of upright from recumbent position);
7. Neurologic assessment for stroke residuals or encephalopathy.
223
E. Laboratory Tests
1. Routine laboratory tests: urinalysis, serum potassium, fasting blood glu-
cose, and creatinine;
2. Special tests are indicated if BP remains poorly controlled or if the histo-
ry, PE and routine laboratory tests indicate other organ involvement.
These tests include: ECG, chest X-ray, lipid profile, uric acid, hemato-
crit, and test for microalbuminuria.
3. Confirmatory tests for secondary HTN will be requested by the HTN
specialist. Clinical clues will suggest the identifiable cause (e.g., chronic
kidney disease, coarctation of the aorta, Cushing’s syndrome and other
glucocorticoid excess states including chronic steroid use, drug-
induced, obstructive uropathy, pheochromocytoma, primary aldosteron-
ism and other mineralocorticoid excess states, renovascular HTN, sleep
apnea, thyroid or parathyroid disorders).
Table 24. Clinical clues to secondary causes of HTN
Clinical Clues Suspected Conditions
Abdominal or flank masses, family history of Polycystic kidney
adult polycystic kidney
Abdominal bruits, especially if diastolic com- Renovascular disease
ponent is present
Truncal obesity with purple striae Cushing’s syndrome
Tachycardia, tremor, orthostatic hypotension, Pheochromocytoma
sweating, flushing, pallor
Anemia, edema, azotemia, casts Chronic kidney disease
Pulse deficit, unequal pulses Takayasu’s arteritis,
coarctation of the aorta
Cramps, body malaise, hypokalemia Hyperaldosteronism
Use of contraceptive pills Contraceptive-induced HTN
Neck mass with bruit, lid lag, tremors with or Thyrotoxicosis
without exophthalmos
Poor BP control with drug therapy Any of the above
Sudden onset of hypertension Any of the above
Sudden deterioration of BP control Any of the above
III. What is the approach to the treatment of HTN?

A. Lifestyle Modification
These are the cornerstones of HTN prevention and are likewise equally
important in treatment, and are thus initiated in all patients and maintained
throughout the duration of management (See Table 25).
B. Pharmacologic Treatment
1. When is pharmacologic treatment initiated, and what are the target
BP goals?
The Goal BP for adults younger than 60 years old, including
those with diabetes and chronic kidney disease, is <140/90 mm Hg
while the target BP for those 60 years old or over is <150/90 (Philippine
Heart Association).
224
Table 25. Lifestyle modification
Approximate SBP
Modification Recommendation
Reduction (Range)
Weight Reductionᵃ Maintain normal body weight 5-20 mmHg/10 kg
(BMI 18.5 – 24.9 kg/m2)ᵇ
Adopt Dietary Consume a diet rich in fruits, 8-14 mmHg
Approaches to Stop vegetables, and low fat dairy
Hypertension (DASH) products with reduced content
Eating Plan of saturated and total fat.
Dietary Sodium Reduce dietary sodium intake 2-8 mmHg
Reduction to no more than 100 mmol per
day (2.3 g Na or 5 g NaCl –
equivalent to approximately 0.9
teaspoon). This is absolutely
necessary in CKD and CHF.
Physical Activity Engage in regular aerobic 4-9 mmHg
physical activity, such as brisk
walking (at least 30 min./day;
most days of the week)
Moderation of Alcohol Limit to 30 mL or 28 g of etha- 2-4mmHg
Consumption nol/day or to no more than 2
drinks (e.g. 720 mL or 2 bottles
of beer, 240 mL or 2 glasses of
wine, or 60 mL or 2 jiggers of
100-proof whiskey) per day to
most men, and to no more than
1 drink in women and lighter
weight men.
Cessation of Smoking It is recommended to give all –
smokers advice to quit smoking
and to offer assistance.
ᵃ Overweight patients (excess of >10% of ideal body weight with a waist-hip ratio of >0.9 in males
and >0.8 in females and an abdominal circumference of >90 cm in males and >80 cm in females)
should attempt a weight reduction at a rate of 1.0 lb or 0.5 kg per week.
ᵇ Weight reduction can be achieved by regular aerobic activities and total caloric reductions for
which prescriptions can be obtained from a nutritionist. In the absence of one, patients can be ad-
vised to decrease their total caloric intake by 15%.
Patients with the following conditions will require pharmacolog-

ic therapy:
a. Systolic BP >180 or Diastolic BP >110;
b. Presence of cardiovascular disease or target organ damage or dia-
betes/chronic kidney disease;
c. Failure to achieve goal BP of <140/90 in all other patients.
2. What are the guidelines for selection of drug therapy?

a. The main objective of hypertension treatment is to attain and main-
tain goal BP and to reduce the increased risk of future cardiovascu-
lar events.
225
b. The initial choice of antihypertensive agent is directed towards
the most probable pathophysiologic abnormalities or presence of
compelling indications. Table 26 lists the priority therapeutic op-
tions based on these underlying circumstances.
c. Monotherapy is recommended as an initial option but if the patient
has co-morbid conditions and/or target organ damage, combina-
tion therapy is started.
d. In some patients on once-daily doses, the antihypertensive effect
may diminish towards the end of the dosing interval. All physicians
should be aware of this TROUGH effect. BP must be measured
just prior to dosing and adjustment in dose and frequency may be
considered.
e. If goal BP is not reached within a month of treatment with the initial
drug, increase the dose of this drug or add a second drug from one
of the classes in Table 26. The clinician should continue to assess
BP and adjust treatment regimen until goal BP is reached.
f. If goal BP is not reached with 2 drugs, add and titrate a third drug
from the list provided.
Do not use an ACEI and ARB together in the same patients since
this can lead to hyperkalemia or renal failure.
3. What is the recommended dose of the medication?

a
Table 26. Recommended doses of antihypertensive agents
Target Dose No. of
Initial Daily
Medication in RCTs b, Dosing per
Dose, mg
mg day
ACE Inhibitors (ACEI):
Captopril 50 150-200 2
Enalapril 5 20 1-2
Angiotensin Receptor Blocker
(ARB): 50 100 1-2
Losartan
Beta Blocker (BB):
Metoprolol 50 100-200 1-2
Calcium Channel Blocker (CCB):
Amlodipine 2.5 10 1
Thiazide-type Diuretic:
Hydrochlorothiazide 12.5 – 25 25-100 1-2
a
Available at the primary healthcare facilities
b
Randomized Controlled Trials
226
4. What are the choices of drug classes for uncomplicated HTN and
HTN with compelling indications?
Table 27. Recommended medicines for treatment of patients with HTN associat-
ed with compelling indications
Compelling Beta-
Diuretic ACEI ARB CCB
Indications blocker
Uncomplicated HTN     
Heart Failure    
Post MI   
High Coronary    
Disease Risk
Diabetes     
Chronic Kidney * * 
Disease
Recurrent Stroke   
Prevention
* Indicates addition of loop diuretics
5. What are the contraindications to the use of the anti-hypertensive

medications?
a. For Thiazide diuretics – Gout
b. For Beta-blockers – Asthma, COPD, AV block (grades 2 and 3),
and peripheral vascular disease
c. For Calcium antagonists (verapamil, diltiazem) – AV block (grades
2 and 3, trifascicular block), severe LV dysfunction, and heart fail-
ure
d. For ACEI – Pregnancy, angioneurotic edema, hyperkalemia, and
bilateral renal artery stenosis
e. For ARB – pregnancy, hyperkalemia, and bilateral renal artery ste-
nosis
IV. What is the management for special conditions?

A. Pregnancy
1. What is the recommendation regarding pharmacologic treatment of
chronic hypertension in pregnancy?
Table 28. Pharmacologic treatment of chronic HTN in pregnancy
Agent Comments
Methyldopa Preferred based on long-term follow-up studies support-
ing safety
!! ACEIs, Angiotensin II Receptor Antagonists are contraindicated in

pregnancy since there are reported fetal toxicity and death.
227
B. Elderly Patients
In elderly hypertensive patients, low-dose thiazide diuretics and calcium
channel blockers are the preferred agents. Beta blockers are alternative
agents. In the very elderly patients up to 85 years old, treatment and control
of HTN are associated with clinical benefits.
C. Hypertensive Crises: Emergencies and Urgencies
1. Emergencies
a. Definition: Severe elevations (>180/120 mm Hg) complicated by
evidence of impending or progressive target organ damage (TOD)
that include the following: hypertensive encephalopathy, intracere-
bral hemorrhage, acute MI, acute left ventricular failure with pulmo-
nary edema, unstable angina pectoris, eclampsia, dissecting aortic
aneurysms, malignant nephrosclerosis, and findings of papilledema
and optic nerve head edema.
!! Patients with hypertensive emergencies must be transferred

immediately to the hospital.
b. Aggressive BP lowering should be achieved immediately (within

minutes to hours) except in patients with ischemic strokes.
Recommended therapy is the use of intravenous parenteral
agents that will allow a more controlled rate of reduction. These in-
clude Nicardipine HCl.
c. Emergency treatment at the RHU or CHO while awaiting transfer or
during transport to the hospital:
i. Initial goal is to reduce mean arterial BP by no more than 25%
within minutes to 1 hour, then, if stable, to 160/100-110 mmHg
within the next 2-6 hours.
ii. Excessive falls in pressure that may precipitate or aggravate
renal, cerebral or coronary ischemia must be avoided.
!! Short-acting nifedipine is no longer considered acceptable

in the initial treatment of hypertensive crisis because it can
cause excessive falls in BP.
iii. Nicardipine HCl, when available in facilities capable of manag-

ing its complications, is administered as intravenous bolus in-
jection using 1 mg dose, with close BP and cardiac rate moni-
toring. Other adverse reactions include: tachycardia, head-
ache, flushing, and local phlebitis.
!! Oral captopril and clonidine will not provide the desired

controlled rate of BP reduction and may lead to severe hypo-
tension that can precipitate unexpected myocardial infarct or
acute ischemic stroke.
iv. Monitor BP and heart rate every 15 to 30 minutes.
228
2. Urgencies
a. Definition: Severe elevations of BP without evidence of target or-
gan damage. The patients present with higher levels of BP that
may be associated with headaches, shortness of breath, epistaxis,
or severe anxiety.
b. These patients may benefit from treatment with short-acting oral
medicines that include captopril and clonidine (see Table 29). The
patients should be observed closely for several hours at the
healthcare facility.
The Council on Hypertension of the Philippine Heart Association
(written communication received August 18, 2014) enumerates the
following conditions for treatment of hypertensive urgencies
with oral captopril and clonidine: BP level of >180 mm Hg systol-
ic or >120 mm Hg diastolic; absence of active target organ damage,
and absence of external causes of sudden BP elevation such as
stress or severe pain.
c. The appropriate oral antihypertensive agents should be maintained
and control of blood pressure achieved within 3 days. Close follow-
up at the center is necessary.
Table 29. Captopril and clonidine use in hypertensive urgencies.
Onset of Action Adverse
Medicine Dose
(minutes) Reactions
Captopril 25 mg, by mouth, 15-30 Hypotension,
repeat as required to renal failure in
reach target BP bilateral renal
artery stenosis
Clonidine 75 micrograms, by 30-60 Hypotension,
mouth (or SL*), repeat drowsiness,
every 30-60 minutes dry mouth
as required to reach
target BP
*Sublingual (SL) Clonidine may be used in fasting patients or in those unable to absorb
drugs through the gastrointestinal route.
V. What are the causes of resistant HTN?

A. Improper BP measurement
B. Volume overload due to:
1. Excess sodium intake
2. Volume retention from kidney disease
3. Inadequate diuretic therapy
C. Drug-induced or other causes:
1. Nonadherence
2. Inadequate doses (including the frequency of intake per day)
3. Inappropriate combinations
4. NSAIDs; cyclo-oxygenase 2 inhibitors
5. Cocaine, amphetamines, other illicit drugs
229
6. Sympathomimetics (decongestants, anorexics)
7. Oral contraceptive hormones
8. Adrenal steroid hormones
9. Cyclosporine and tacrolimus
10. Erythropoietin
11. Selected dietary supplements and medicines (e.g., ephedra, ma huang,
bitter orange)
D. Associated conditions:
1. Obesity
2. Excess alcohol intake
VI. When is referral to the higher level of care warranted?
Referral to the higher level of care or hypertension specialist is indicated:
• When goal BP cannot be attained using the above strategies; or,
• When management of patients with complications need additional clinical
consultation.
VII. How often should the patient follow-up at the clinic?
Regular follow-up must be emphasized. Patients should follow-up at least once a
month. When the goal BP becomes stable, follow-up should be at least once
every 2 to 3 months.
VIII. How can HTN be prevented among normotensives?
Weight reduction among overweight individuals through moderate physical activi-
ty and reduced total caloric intake decrease the incidence of hypertension.
REFERENCES:
Cunningham FE, Baughman VL, Peters J, Laurito CE. “Comparative pharmacokinetics of oral
versus sublingual clonidine,” (Abstract). J Clin Anesth, 1994 Sep-Oct, 6 (5):430-3.
Philippine Heart Association Council on Hypertension, Position Statement on Management of

Hypertension in Adults, August 18, 2014 (through communication).
Multisectoral Task Force Consensus on the Detection and Management of Hypertension in the
Philippines, 2011, Philippine Clinical Practice Guidelines on the Detection and Manage-
ment of Hypertension – 2011 (also known as the 140/90 Report).
National Institutes of Health, U.S. Department of Health and Human Services, August 2004, The
Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure.
Spah F, Grosser KD. “Treatment of hypertensive urgencies and emergencies with nitrendipine,
nifedipine, and clonidine: effect on blood pressure and heart rate,’ (Abstract). Journal of
Cardiovascular Pharmacology, 1988; 12 Suppl 4:S154-6.
The Panel Members Appointed to the Eighth Joint National Committee (JNC 8), February 2014,
‘2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults:
Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC
8)’, The Journal of the American Medical Association, vol. 311, no. 5, pp. 507-520.
230
The Task Force for the Management of Arterial Hypertension of the European Society of Hyper-
tension and of the European Society, June 2013, ‘2013 ESH/ESC Guidelines for the Man-
agement of Arterial Hypertension’, European Heart Journal, vol. 34, issue 28, pp. 2159-
2219.
The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and
Treatment of High Blood Pressure. NIH Publication No. 04-5230. August 2004. National In-
stitute of Health, US Department of Health and Human Services.
231
DIABETES MELLITUS
1
• WITH CLINICAL SYMPTOMS: Weight loss, polyuria, polydipsia, pruritus vulvae, non-healing wound Universal screening using laboratory
tests is not recommended.
IGT* or IFG or GDM, PCOS, overweight or obese, abnormal waist circumference or waist-hip ratio, first-degree rela-
• WITHOUT CLINICAL SYMPTOMS BUT WITH ANY OF THE FOLLOWING RISK FACTORS: Age >40 years old,
tive with Type 2 DM, sedentary lifestyle, hypertension, history of vascular disease (including stroke, peripheral arte-
rial occlusive disease, coronary artery disease), acanthosis nigricans, schizophrenia, low serum HDL, high serum All patients seen at the clinic should be
triglycerides evaluated annually for risk factors for
• ALL PREGNANT WOMEN (see section on GDM; screening is by OGTT) type 2 diabetes and pre-diabetes.
2
SCREENING TESTS Testing should be carried out within the
Any of the following tests may be used: healthcare setting under the supervision
• Plasma glucose of a qualified professional.
(using 75 g OGTT)
The use of the following tests for
• Two-hour plasma glucose
the diagnosis of diabetes mellitus
232
is not recommended: (1) Urine
• Random blood glucose
glucose and (2) Plasma insulin.
3 4 5
NORMAL RESULTS PRE-DIABETES DIABETES MELLITUS
FBS 5.6-6.9 mmol/L or after overnight fast of 8-14 hours

• FBS <5.6 mmol/L (<100 mg/dL) • Impaired Fasting Glucose:
100-125 mg/dL
• FBS >7 mmol/L (>126 mg/dL)
• Random/casual blood glucose
mmol/L (>200 mg/dL)

<7.7 mmol/L (<140 mg/dL)
RBS 7.7-11 mmol/L

• 2-hour plasma glucose >11.1
• Two-hour blood sugar in the • Impaired Glucose Tolerance:
mg/dL) (140-199 mg/dL) in patients with classic symptoms

75 g OGTT <7.7 mmol/L (<140 • RBS >11.1 mmol/L (>200 mg/dL)
6 7
Repeat testing at least annually
Lifestyle modifications and *
monitoring every 3-6 months IGT: Impaired Glucose Tolerance
IFG: Impaired Fasting Glucose
GDM: Gestational Diabetes Mellitus
A PCOS: Polycystic Ovarian Syndrome
232
A
8 9
Asymptomatic Symptomatic
10 11
EVALUATION OF TYPE 2 DIABETES MELLITUS
Repeat FBS after 2-4
weeks; HbA1c after 3
months 12
Search for risk factors for diabetes, cardio-
Medical History: Must include:
vascular risk factors and the complications
1. Age and characteristics of onset of diabetes
of diabetes: cardiovascular, visual, and
2. Nutritional status and weight history
neuropathic.
3. Smoking
4. Diabetes education history
5. Previous treatment and response
6. Current treatment of diabetes
Inquire about awareness regarding diabe-
7. Use of medications that can affect blood sugars
tes and hypoglycemia detection and
8. Hypoglycemic episodes and risk for and causes of hypoglycemia
management to determine extent of
9. DKA history: frequency, severity and causes
patient self-management education.
10. Diabetes-related complications
11. Others: psychosocial problems, dental disease, gestational history.
233
13
Physical Examination: Must include: A diabetic patient’s risk for developing foot
1. Height, weight, BMI, waist circumference ulcer can be as high as 25%. Thus, one
2. BP, including orthostatic measurement needs to identify risk factors which in-
3. Skin examination clude: previous foot ulceration, neuropa-
4. Comprehensive foot examination: inspection, palpation of peripheral pulses, patellar and ankle jerks, thy, foot deformity, and vascular disease.
proprioception, vibration and mono-filament sensation
5. Tests for autonomic dysfunction
6. Heart rate variability
7. Fundoscopic examination ideally Due to the insidious onset of
8. Thyroid palpation diabetes, some patients may
already have retinopathy at the
14 time of diagnosis.
Laboratory Tests:
Routine: Fasting blood glucose, lipid profile, including total, LDL and HDL cholesterol and triglycerides,
HbA1c, liver enzyme/transaminases (AST/ALT)
Optional: ECG (resting) and Treadmill exercise tests; thyroid stimulating hormone in women over 50 years old
B
233
DIABETES MELLITUS
1
• WITH CLINICAL SYMPTOMS: Weight loss, polyuria, polydipsia, pruritus vulvae, non-healing wound Universal screening using laboratory
tests is not recommended.
IGT* or IFG or GDM, PCOS, overweight or obese, abnormal waist circumference or waist-hip ratio, first-degree rela-
• WITHOUT CLINICAL SYMPTOMS BUT WITH ANY OF THE FOLLOWING RISK FACTORS: Age >40 years old,
tive with Type 2 DM, sedentary lifestyle, hypertension, history of vascular disease (including stroke, peripheral arte-
rial occlusive disease, coronary artery disease), acanthosis nigricans, schizophrenia, low serum HDL, high serum All patients seen at the clinic should be
triglycerides evaluated annually for risk factors for
• ALL PREGNANT WOMEN (see section on GDM; screening is by OGTT) type 2 diabetes and pre-diabetes.
2
SCREENING TESTS Testing should be carried out within the
Any of the following tests may be used: healthcare setting under the supervision
• Plasma glucose of a qualified professional.
(using 75 g OGTT)
The use of the following tests for
• Two-hour plasma glucose
the diagnosis of diabetes mellitus
232
is not recommended: (1) Urine
• Random blood glucose
glucose and (2) Plasma insulin.
3 4 5
NORMAL RESULTS PRE-DIABETES DIABETES MELLITUS
FBS 5.6-6.9 mmol/L or after overnight fast of 8-14 hours

• FBS <5.6 mmol/L (<100 mg/dL) • Impaired Fasting Glucose:
100-125 mg/dL
• FBS >7 mmol/L (>126 mg/dL)
• Random/casual blood glucose
mmol/L (>200 mg/dL)

<7.7 mmol/L (<140 mg/dL)
RBS 7.7-11 mmol/L

• 2-hour plasma glucose >11.1
• Two-hour blood sugar in the • Impaired Glucose Tolerance:
mg/dL) (140-199 mg/dL) in patients with classic symptoms

75 g OGTT <7.7 mmol/L (<140 • RBS >11.1 mmol/L (>200 mg/dL)
6 7
Repeat testing at least annually
Lifestyle modifications and *
monitoring every 3-6 months IGT: Impaired Glucose Tolerance
IFG: Impaired Fasting Glucose
GDM: Gestational Diabetes Mellitus
A PCOS: Polycystic Ovarian Syndrome
232
Guidelines for the Management of Type 2 Diabetes Mellitus
I. What are the recommendations for screening for diabetes and pre-
diabetes?
A. Universal screening using laboratory tests is not recommended as it would
identify very few individuals who are at risk.
B. However, all individuals being seen at any physician’s clinic or by any
healthcare provider should be evaluated annually for risk factors for type 2
diabetes and pre-diabetes.
C. Who should undergo screening for diabetes mellitus?
1. All patients with clinical symptoms of diabetes (polyuria, polydipsia, pol-
yphagia, non-healing wound, pruritus);
2. All pregnant women;
3. Asymptomatic individuals with any of the following risk factors for Type
2 diabetes mellitus:
a. Age ≥40 years (NNHES 2004 showed that significant burden of di-
abetes begins at age 40 years, approximating already the national
prevalence). Screening individuals as early as age 40 years in fami-
ly physicians’ offices has proved to be useful in detecting unrecog-
nized diabetes.
b. All adults of any age who are overweight or obese defined as:
2 2
• Overweight: Body Mass Index (BMI) of ≥23 kg/m
2 2
• Obese: BMI of ≥25 kg/m or
• Waist circumference of ≥80 cm (females) and ≥90 cm (males)
or
3
• Waist-hip ratio (WHR) of ≥1 for males and ≥0.85 for females
c. Any individual with at least one of the following risk factors:
• First-degree relative with Type 2 diabetes
• History of IGT or IFG
• History of GDM or delivery of a baby weighing 8 lbs or above
• Hypertension (BP ≥140/90 mmHg)
• Diagnosis or history of any vascular diseases including stroke,
peripheral arterial disease, or coronary artery disease
• HDL cholesterol <35 mg/dL (<0.9 mmol/L) and/or triglycerides
>250 mg/dL (>2.82 mmol/L)
• Polycystic ovarian syndrome (PCOS)
• Acanthosis nigricans
• Physical inactivity
• Schizophrenia
D. Testing should ideally be carried out within the healthcare setting (clinics,
hospitals, local health centers) because of the need for follow-up and dis-
cussion of abnormal results by qualified health care professionals (nurse, di-
abetes educator, and physician).
E. Testing at any setting should be supervised by a qualified health care pro-
fessional.
F. If initial test/s is/are negative for diabetes, then a REPEAT testing should
ideally be done annually.
G. What are the standard recommended screening tests for diabetes?
235
1. Any of the following tests may be done:
a. Fasting Blood Glucose after an overnight fast for at least 8 hours up
to a maximum of 14 hours;
b. Two-hour plasma glucose during a 75 g Oral Glucose Tolerance
Test; or
c. Random plasma glucose
2. A 75 g OGTT is preferred as the first test in the following individuals
who have: (Grade B, Level 3)
a. A previous FBS showing Impaired Fasting Glucose (100 to 125
mg/dL or 5.6 to 6.9 mmol/L)
b. Previous diagnosis of cardiovascular disease (coronary artery dis-
ease, stroke, peripheral arteriovascular disease) or who are at high
risk for cardiovascular disease.
c. A diagnosis of Metabolic Syndrome
3. Currently, the routine use of the following tests for the diagnosis of dia-
betes is not recommended*:
• HbA1c (due to poor access to this test and lack of standardization)
• Capillary Blood Glucose
• Fructosamine
• Urinalysis (urine glucose)
• Plasma insulin
*However, if any of these tests is available upon consulta-
tion due to prior testing, it should be interpreted with caution and
should be confirmed by any of the 3 tests that are considered
standard: fasting plasma glucose, oral glucose tolerance test or
random plasma glucose.
II. When is the diagnosis of Diabetes Mellitus and Pre-diabetes made?

A. Normal blood sugar is defined as:
• An FBS <5.6 mmol/L (<100 mg/dL), or
• Random/casual blood glucose <7.7 mmol/L (<140 mg/dL), or
• 2-hour blood sugar in the 75 g OGTT <7.7 mmol/L (<140 mg/dL)
B. Diabetes Mellitus (DM) is defined as:
• Fasting Plasma glucose ≥7 mmol/L (≥126 mg/dL) after an over-
night fast for at least 8 hours up to a maximum of 14 hours; or,
• Two-hour plasma glucose ≥11.1 mmol/L (≥200 mg/dL) during a 75
g Oral Glucose Tolerance Test; or,
• A random plasma glucose ≥11.1 mmol/L (≥200 mg/dL) in a patient
with classic symptoms of hyperglycemia (weight loss, polyuria, pol-
yphagia, polydipsia) or with signs and symptoms of hyperglycemic
crisis.
C. Pre-diabetes is defined as either:
• Impaired Fasting Glucose (IFG) when there is FBS of 5.6 up to 6.9
mmol/L (100-125 mg/dL);
• Impaired Glucose Tolerance (IGT): casual blood glucose of 7.7 up
to 11.0 mmol/L (140-199 mg/dL) OR 2-hour blood sugar in the 75 g
OGTT equal to 7.7 up to 11.0 mmol/L (140-199 mg/dL)
236
Table 30. Criteria for normal glucose tolerance, pre-diabetes and DM.
Range of Values
Category 2-hr RBS in 75 g Random blood
FBS
OGTT sugar
Normal glucose <5.6 mmol/L <7.7 mmol/L <7.7 mmol/L (<140
tolerance (<100 mg/dL) (<140 mg/dL) mg/dL)
Pre-diabetes: – –
Impaired Fasting 5.6 – 6.9 mmol/L
Glucose: (100-125 mg/dL)
Impaired Glucose – 7.7-11 mmol/L 7.7-11 mmol/L
Tolerance: (140-199 mg/dL) (140-199 mg/dL)
Diabetes Mellitus ≥7.0 mmol/L ≥11.1 mmol/L ≥11.1 mmol/L
(>126 mg/dL) (>200 mg/dL) (>200 mg/dL)
D. Among ASYMPTOMATIC individuals with positive results, any of the three

tests should be REPEATED within two weeks for confirmation.
III. What is the approach to the screening and diagnosis of Gestational Diabe-
tes Mellitus (GDM)?
A. All pregnant women should be screened for gestational diabetes.
B. All pregnant women should be evaluated at the first prenatal visit for the fol-
lowing risk factors for diabetes mellitus:
• Prior history of GDM
• Glucosuria
• Family history of Diabetes
• First-degree relative with type 2-DM
• Prior macrosomic baby
• Age >25 years old
• Diagnosis of polycystic ovary syndrome
• Overweight/obese before pregnancy
• Macrosomia in current pregnancy
• Polyhydramnios in current pregnancy
• Intake of drugs affecting carbohydrate metabolism
C. When should screening be done?
1. High-risk women should be screened at the soonest possible time.
2. Routine testing for gestational diabetes is recommended at 24 to 28
weeks age of gestation for women with no risk factors.
3. Testing for gestational diabetes should still be carried out in women at
risk, even beyond 24 to 28 weeks of gestation.
D. What tests should be done and how should these be interpreted?
1. An oral glucose tolerance test (OGTT), preferably the 75 g OGTT,
should be used to screen for gestational diabetes
2. The criteria of the International Association of Diabetes & Pregnancy
Study Groups (IADPSG) should be used to interpret the 75 g OGTT
where any one value meeting threshold is considered gestational diabe-
tes.
3. The following tests should not be used for the diagnosis of diabetes in
pregnancy: capillary blood glucose, FBS, RBS, HbA1c, fructosamine,
urine glucose
237
4. However, if patients already have FBS or RBS at the time of consulta-
tion, thresholds for DM will be the same as non-pregnant individuals.
Those with glucosuria, elevated CBG or HbA1c should undergo 75 g
OGTT.
Table 31. Interpreting the 75 g OGTT results
Threshold(s) for diagnosing gestational diabetes (mg/dL)
75 g
OGTT IADPSG* ADA** ASGODIP & DIPSI POGs
FBS 92 95 NA 92
1-hour 180 180 NA NA
2-hour 153 155 140 140
3-hour NA 140 NA NA
*Any one value meeting threshold is considered gestational diabetes.
**Two values must meet thresholds to be considered gestational diabetes.
NOTE: The 75 g OGTT (IADPSG) for pregnant women is similar except that 3
tests are done: FBS, 1-hr and 2-hr post-load blood sugar. In the ADA, 4 determi-
nations are done.
IV. What is the approach to treatment of patients with Type 2 diabetes mellitus
in the outpatient setting?
A. Non-Pharmacologic Therapy
All individuals diagnosed to have diabetes mellitus should receive advice
and instruction regarding therapeutic lifestyle change, including medical nu-
trition therapy (dietary modification) and exercise.
1. Diet
a. Advise patients to consume enough calories to maintain ideal body
weight or prevent further weight gain. Monitor carbohydrate intake
using either the plate method or counting carbohydrate exchanges.
Minimize intake of trans-fat and reduce saturated fat to <7% of total
calories. Sugar alcohols and non-nutritive sweeteners are safe
when consumed within the acceptable daily intake levels. Patients
with diabetes who take alcohol should limit intake to one drink per
day or less for women and two drinks per day for men. Routine
supplementation with vitamins E and C or chromium is not advised.
Figure 1. Illustration of the serving sizes of diabetic meals for a 9-inch diameter plate
for lunch/dinner (this provides 1,200-1,500 calories)
238
b. Starch refers to rice, bread, noodles/pasta or corn. Protein refers to
meat, fish or vegetable proteins such as soybean (“tokwa” or tofu).
Preferred vegetables are green (deep green) leafy vegetables. The
large circle represents the typical plate of a diabetic where non-
starchy vegetables comprise half of the meal, while starch sources
and proteins (viand) each comprise a quarter of the plate.
c. Patients are advised to follow the following diet rules:
1.) EAT MOST
Use one or more of these foods as the basis of every
meal: Vegetables, legumes, lentils, noodles, rice, bread,
grains, wholegrain cereals, fresh fruit (non-sweet).
Note that many sauces and preservatives that are added
to these foods are high in salt, sugar or fat, and should be
avoided.
2.) EAT MODERATELY
Have small servings of protein-rich foods e.g., fish, sea-
food, eggs, lean meat, skinless chicken, low-fat cheese, low-fat
yoghurt, low-fat milk, nuts.
3.) EAT LEAST
Minimize fats, sugars, salt and alcohol e.g., butter, oil,
cream, coconut milk and cream, processed meat, fried foods,
preserved or processed foods, pastries, sweets, biscuits, soft
drink.
2. Exercise
Advise regular physical activity at least 150 minutes/week of mod-
erate-intensity aerobic physical activity (50-70% of maximum heart
rate). The physician should assess patients for possible contraindica-
tions to exercise such as uncontrolled hypertension, severe autonomic
or peripheral neuropathy, history of foot lesions and unstable prolifera-
tive retinopathy. In the absence of contraindications, patients are en-
couraged to perform resistance training three times per week.
B. Pharmacologic Therapy
The following is the approach to pharmacologic treatment for Type 2 DM:
1. Among the newly diagnosed diabetics, classify the level of severity of the di-
abetes according to the glycemic levels, presence of symptoms and compli-
cations: Determine how severe the diabetes is.
a. Those who are asymptomatic with relatively lower levels of blood sugar
(HbA1c <8.0%, FBS <140, RBS <200 mg/dL) should be advised to un-
dertake MNT, physical activity and exercise, and weight reduction, (with
an option of starting pharmacologic therapy with Metformin).
b. If glycemic targets are not reached within 3 months, then pharmacologic
treatment will be started or combination therapy considered.
c. Those who have higher blood sugars at the onset or who are sympto-
matic should be started right away on one or more pharmacologic
239
agents as applicable (refer to algorithm) since diet and lifestyle changes
are unlikely to achieve the target values.
2. Who are the patients ideally referred to internists or diabetes specialists (en-
docrinologists or diabetologists)?
a. Individuals with Type 1 DM;
b. Patients with moderate to severe hyperglycemia;
c. Patients with co-morbid conditions e.g., infections, acute cardiovascular
events such as congestive heart failure or acute myocardial infarction;
d. Patients with significant hepatic and renal impairment; and
e. Women with diabetes who are pregnant.
3. What is the initial preferred drug?
Treatment is usually initiated with Metformin unless there are contraindica-
tions or intolerance to its adverse drug effects, such as the development of
diarrhea, severe nausea or abdominal pain.
4. When should combination therapy be considered?
a. When glycemic targets are not achieved with one medication given at
the maximum effective dose (i.e., the optimal dose or half maximum
dose), another drug from another pharmacologic class should be added
rather than increasing the first drug to its maximum dose.
b. Eventually all forms of monotherapy fail since DM type 2 is a progres-
sive disease.
5. What are the principles behind combination therapy?
a. A second agent can be chosen from Table 32 based on the following
considerations: amount of HbA1c lowering, hypoglycemia risk, weight
gain, patient profile such as dosing complexity, renal and hepatic prob-
lems, other contraindications, and age.
b. Combination therapy capitalizes on the complementary actions of differ-
ent drug classes.
6. What agents can be used in combination therapy?
The secretagogues (sulphonylurea and glinides), TZD, alpha-
glucosidase inhibitors, incretin-based therapies (DPP4 inhibitors and incretin
analogues) may be used with metformin in various combinations when
treatment targets are not achieved. They may also be used with insu-
lin/insulin analogues. These agents and the usual doses are found in Table
32.
7. When is insulin therapy initiated?
a. Insulin is started in patients: with severe diabetes; with inadequate con-
trol using oral anti-diabetic agents; or, with medical conditions which ne-
cessitate insulin administration e.g., those needing surgery, presence of
infections or pregnant diabetics.
b. Ideally, all patients who are on insulin or will be started on insulin should
be under the care of diabetes specialists (endocrinologists and dia-
betologists), especially those who are on multiple dose insulin injection
(MDII), or 2 or more injections per day.
240
Suggested beginning dose of Regular Human Insulin is 10 units/day SC
(or 0.1-0.2 units/kg/day) in the evening or divided every 12 hours. Refer to a
specialist for subsequent doses or for shifting to other insulins (see under
Medicine and Therapeutic Information – Insulins).
8. What are the goals and targets of treatment?
a. The glycemic targets should be reached within 6 months but manage-
ment of diabetes should be global, addressing as well the other co-
morbid cardiovascular conditions such as overweight and obesity,
dyslipidemia and hypertension.
b. Ideally, the blood sugar should be monitored using the FBS 2-4 weeks
after initiation of therapy and either HbA1c every 3-4 months or FBS
every 1-2 months to assess long term consistent control.
c. Below are suggested targets for relatively young and newly diagnosed
individuals or individuals who are not at increased risk for hypoglycemia
(see Table 33). These targets should be individualized based on factors
such as age, severity of the co-morbid conditions, the over-all risk for
hypoglycemia, and the attributes of the medications. These attributes
include: risk of inducing hypoglycemia, risk of weight gain, ease of use,
safety impact on hepatic, renal or cardiac disease, and cost of treat-
ment.
241
Table 32. Types of Anti-diabetic Agents and their Glycemic Efficacy
Amount of
Examples (range of
Drug Class Action HbA1c
doses per day)
lowering
Sulfonylureas Stimulate Gliclazide (modified- 1-2%
(SUs) pancreatic β-cells release) 30-120 mg/day;
to release insulin (immediate-release) 80-
into the blood- 320 mg/day
stream Glipizide* 5-20 mg/day
Glimepiride* 1-6 mg/day
Meglitinides Also an insulin Repaglinide* 0.5-4 mg 0.5-1.5%
secretagogue (but per meal (maximum of
short acting) 16 mg/day)
Nateglinide* 60-120 mg
3x/day
Biguanides Decrease the Metformin 500-2,500 1-2%
amount of glucose mg/day
made by the liver
Increase insulin
sensitivity of
muscle and
adipose
Thiazolidinediones Improve insulin Pioglitazone* 15-45 0.5-1.4%
sensitivity by stimu- mg/day
lating PPARγ
receptors
Alpha-Glucosidase Block α- Acarbose* 50-200 mg 0.5-0.8%
Inhibitors (AGIs) glucosidase three times daily
enzymes that break Voglibose* 200-300 mcg
down complex three times daily
carbohydrates into (after the first spoonful
a more absorbable of food)
form (simple
sugars)
Dipeptyl Peptidase- Inhibits the action Sitagliptin* 50-100 mg 0.5-1.0%
IV Inhibitors of the DPP4 Vildagliptin* 50 mg
(DPP4-inhibitors) enzyme which Saxagliptin
breaks down GLP- Linagliptin* 5 mg
1, effectively (per day dosing)
increasing the
levels of GLP-1;
causes glucose-
dependent
increase in insulin
secretion
Adapted from JL Jameson. LJ De Groot. Endocrinology: Adult and Pediatric, 6th edition.
*Not included in the Medicines for Primary Healthcare facility
242
Table 33. Treatment Goals for Patients with Diabetes Mellitus
Components of Global
Treatment Goals
Management
GLYCEMIC CONTROL
FBS 5- 6.1mmol/L (90-110 mg/dL)
HbA1c <7.0%
Pre-prandial capillary blood 5-7.2 mmol/L (90-130 mg/dL)
glucose
Peak post-prandial CBG <10.0 mmol/L (<180 mg/dL)
BLOOD PRESSURE <140/80 mmHg
LIPIDS
LDL <2.6 mmol/L (<100 mg/dL)
Triglycerides <1.7 mmol/L (<150 mg/dL)
V. How is hypoglycemia recognized and treated?

A. Causes of Hypoglycemia
1. Administering too much insulin
2. Missing or delaying meals
3. Exercising or working more than usual
4. Infection or illness (especially with diarrhea or vomiting)
5. A change in the body’s need for insulin
6. Disease of the adrenal, thyroid gland or progression of kidney or liver
disease
7. Interactions with other drugs that lower blood glucose (e.g., oral hypo-
glycemics, salicylates, such as aspirin, sulfa antibiotics, and certain an-
tidepressants)
8. Consumption of alcoholic beverages.
B. Symptoms of Hypoglycemia
1. Mild-to-moderate Hypoglycemia
Sweating Drowsiness
Dizziness Sleep disturbances
Palpitation Anxiety
Tremor Blurred vision
Hunger Slurred speech
Restlessness Depressive mood
Tingling in the hands, feet, Irritability
lips, tongue Abnormal behavior
Lightheadedness Unsteady movement
Inability to concentrate Personality changes
Headache
243
2. Severe Hypoglycemia
Disorientation
Unconsciousness
Seizures
Death
Important Note:
The need to recognize these signs and symptoms early and
then to act promptly must be emphasized when educating the patients and
their families or caregivers. Early warning symptoms may be different or less
pronounced under certain conditions, such as long duration of diabetes, dia-
betic neuropathies, diabetes in the elderly, use of medications such as beta-
blockers, change in insulin preparations, or intensified control (3 or more in-
sulin injections per day) of diabetes.
C. Treatment of Hypoglycemia
Mild to moderate hypoglycemia is treated by taking in foods or
drinks containing sugar (e.g. half a glass of juice with sugar or regular soft-
drinks). Patients should always carry a quick source of sugar, such as can-
dies.
More severe hypoglycemia may require the assistance of another
person. Patients who cannot take in food or drinks and unconscious pa-
tients need IV administration of glucose at the nearest medical facility.
244
Table 34. Safety and Tolerability of Anti-diabetic Agents
Class of Anti-diabetic Agents
Alpha-
Safety Issues Sulfonylureas / Thiazolidinediones
Metformin Glucosidase DPP4-inhibitors Insulin
Glinides (TZD’s)
Inhibitor
Hypoglycemia -- * -- -- -- 
Weight gain   -- 
Gastrointestinal  --  --  --
symptoms
Lactic Acidosis ** -- -- -- -- --
Congestive Heart Avoid if with -- --  -- --
245
failure active CHF
*Especially true for first generation sulfonylureas and for glibenclamide/glyburide. Avoid glibenclamide/glyburide whenever possible due to excess
risk of hypoglycemia.
**Although listed as a possible ADR, this is actually rare in practice.
245
Table 35. Types of Insulin- Clinical Use and Pharmacokinetics
Type of Insulin Onset of action Approximate Peak Duration of Action
PRANDIAL INSULIN
Human regular 0.5-1 hour 2-4 hours 6-8 hours
(inject 30 minutes
before meals)
Rapid acting analogues
Lispro* 10-15 minutes (inject 10-15 1 hour 3-4 hours
Aspart* minutes before meals)
Glulisine*
246
BASAL INSULIN
NPH insulin (Human 1-3 hours 6-8 hours 12-16 hours
Intermediate-acting)
Glargine* 1-2 hours Flat (no peak) but max- 24 hours
(inject anytime, imal effect in 16-24 hours
Detemir* preferably in the 5-6 hours
morning)
*Not included in the Medicines for Primary Healthcare facility
246
Figure 2. Sequential Insulin Strategies in T2DM
NOTE: Basal insulin is typically started at a dose of 0.2 units/kg per day (e.g., 50
kg x 0.2 units/kg = 10 units starting dose once a day).
Source: Diabetes Care, Diabetologia. 19 April 2012
How about herbal medication?

At the moment, it is only Ampalaya (Momordica charantia), especially
the leaves of the Makiling variety, that has some evidence for efficacy and
safety. However, this herbal medication is relatively less potent than the
standard anti-diabetic medications. Thus, they can only be used by patients
who have pre-diabetes or relatively near normal blood sugar levels. If used
by those with higher blood sugar levels, it can only be adjunct or add-on to
standard drugs.
REFERENCES:
UNITE FOR Diabetes Philippines, 2013, ‘Philippine Practice Guidelines on the Diagnosis and
Management of Diabetes Mellitus’, Philippine Pharmaceutical Directory (PPD) Compendi-
um of Philippine Medicine (CPM), 16th edition, Medicomm Pacific, Inc., Pasig City, Philip-
pines.
References cited in the 2013 Philippine Practice Guidelines

American Association of Clinical Endocrinologists (AACE), 2007.
American College of Physicians (ACP), 2007.
American Diabetes Association Standards of Medical Care (ACE), 2010 and updates as of
2013.
Canadian Diabetes Association (CDA), 2008.
Diabetes Care, Diabetologia, 19 April 2012.
International Diabetes Federation Global Guideline (IDF), 2005.
Ministry of Health and New Zealand Guidelines Group (NZGG), 2003.
National Collaborating Centre for Chronic Conditions (NCCCC), 2008.
247
COMMON POISONING
CAUSTICS: ACIDS
An acid is a proton donor. It generally causes significant tissue injury at a pH
below 3. Aside from pH, other factors that should be considered when establishing
the degree of injury are: concentration, Molarity, volume, contact time and pre-morbid
condition of the stomach. The acids most commonly encountered in poisoning cases
are:
• Mineral acids (automobile battery acids, toilet bowl cleaners and other clean-
ing agents);
• Inorganic acids (hydrochloric acid, sulfuric acid); and
• Organic acids (acetic acid, formic acid)
Fatalities have been recorded with ingestion of 30 mL of the following: sulfu-
ric acid 95% (18 M), nitric acid 69% (15 M), and hydrochloric acid 36% (12 M). How-
ever, ingestion of less than 5 mL of mineral acids is known to have caused death.
Non-accidental ingestions often present with more severe injuries and complications.
Ingestion of acids, except for hydrofluoric acid, produces coagulation necro-
sis resulting in eschars which tend to self-limit further damage. The stomach, primarily
the antrum, lesser curvature and pylorus, are the common sites of injury. However,
the esophagus may also be affected. Ulceration of necrotic tissues may lead to perfo-
ration, peritonitis, strictures and stenosis of the esophagus, stomach or pylorus.
Table 36. Common acids
Common Acids
Acetic Acid
• Permanent wave neutralizers, photography stop bath, disinfectants, hat-making, printing,
dyeing, rayon manufacturing
Boric Acid
• Roach powders, water softener, germicides
Carbolic Acid
• Disinfectants, pharmaceuticals, dyes, plastics manufacturing, preservatives
Formic Acid
• Airplane glue-making, tanning, deodorizing tablets, plastic menders, fumigants, embalming
fluids
Hydrochloric (muriatic) acid
• Bleaching agents, metal and toilet bowl cleaners, dye and chemical synthesis, metal refin-
ing
Hydrofluoric acid
• Glass etching, brick cleaning, etching chips in semiconductor industry, electroplating, leath-
er tanning, rust removal, cleaning of porcelain
Nitric acid
• Engraving, electroplating, metal refining, fertilizer manufacturing
Oxalic acid
• Tanning, blueprint paper, disinfectants, household bleach, iron cleaner, leather, chemical
synthesis, anti-rust polish
Phosphoric acid
• Metal and toilet bowl cleaner, rust-proofing
Sulfuric acid
• Automobile batteries, drain cleaners, chemical munitions, fertilizer manufacturing
248
A
General Examinations
CBC Prothrombin time
LABORATORY ABG Urinalysis
EXAMINATION RBS Urine hemoglobin
Na+, K+, Cl-, Ca++ Typing (save blood for x-matching)
X-rays: Chest PA upright, abdominal
ABCs of life support. Maintain vital signs.

Use copious amounts of water to decontaminate eyes/skin ex-
posed to acid spills or vomitus.
Put patient on NPO. Give intravenous fluids.
Adult: D5 0.9NaCl or AR 1 L x 8 hours
Pedia: D5 0.3NaCl or AR according to KBW
In the presence of moderate to severe epigastric or chest pain,
GENERAL give opioid analgesics.
MEASURES Pethidine (Meperidine) as needed
Adult: 25-50 mg IM in the first 24 hours
Pedia: 1 mg/kg/dose IM
If with signs of upper GI bleeding, or burns in the oral cavity, start
Famotidine (or other H2 blocker or proton pump inhibitor)
Adult: 20 mg IV every 12 hours
Pedia: 0.8 mg/kg/dose IV every 12 hours
Refer for emergency endoscopy.
SPECIFIC
MEASURES
Grade 1 to 2a Grade 2b Grade 3a to 3b

Observe 48 hours. Admit to ICU. Admit to ICU.
Liquid diet for 48 hours. Maintain on NPO for 2 to 3 Maintain on NPO for 2 to 3 days.
Give H2 blockers oral or IV. days. Give IV hydration or hyperalimen-
Give demulcent or locally Give IV hydration or hyper- tation or jejunostomy feeding.
acting antacids or cytopro- alimentation or jejunos- Give H2 blocker or proton pump
tective agent tomy feeding. inhibitor IV.
(e.g., Sucralfate) Give H2 blocker or proton Continue pethidine (meperidine)
pump inhibitor IV. only after decision to operate is
made in order to avoid mask-
ing signs and symptoms of per-
foration.
Look for signs of intra-

abdominal perforation or
necrotic gastric lesions.
Negative
Positive
Refer for laparotomy: exploration or

debridement of non-viable tissue.
Refer to Psychiatry if non-accidental.

If stable and asymptomatic after observation period, discharge.
Follow-up c/o surgeon or gastroenterologist.
For repeat endoscopy after two weeks.
250
KEROSENE
Kerosene, an aliphatic hydrocarbon, is the leading cause of accidental poi-
soning among children aged six (6) years old and younger. This is because kerosene,
which is commonly used for cooking fuel, is often stored inappropriately in soft drink
bottles or drinking water containers, and placed in areas which are within reach of
children.
The compound is completely absorbed in the gastrointestinal tract because
of its low molecular weight. It can likewise be absorbed through inhalation and mini-
mally through the skin.
The toxicity of kerosene is due to its local irritating effect and its systemic ef-
fects on various organ systems. It has a high aspiration potential because of its low
viscosity. Thus, close monitoring of the lungs is imperative. The compound can also
depress the CNS, particularly the ventilatory drive, and cause seizures because of
hypoxia. Studies have shown that ingestion of >30 mL with vomiting, present a higher
risk for development of pulmonary toxicity. However, such parameters are not 100%
predictive.
Kerosene naturally volatilizes through the esophagus up to the pharynx. The
insertion of a nasogastric tube and the decision to lavage are thus dependent on the
volume ingested and the length of the patient’s esophagus.
Table 40. Specific precautions
Specific Precautions
• Do not induce emesis (mechanical or chemical) unless a more toxic poison is incorporated
or ingested along with kerosene.
• Do not use mineral oil or olive oil. The thickened consistency of the hydrocarbon predis-
poses to the development of lipoid pneumonia and enhances hydrocarbon absorption.
• Activated charcoal lavage would not be of benefit unless other toxic substances (e.g., pes-
ticides) are taken concomitantly.
• It is important to wash the perianal area after a bowel movement since contact with stool
containing kerosene can produce first- to second-degree burns on the skin.
Management
Amount taken
Time of ingestion
Intake of other substances
HISTORY
Symptoms of:
Diarrhea Difficulty of breathing
Nausea CNS effects: initial excitation by CNS
Vomiting depression; seizures
Cough Mucous membrane irritation
Emphasis on lung findings (note signs of respiratory distress):

Tachypnea; Coarse or decreased breath sounds; Rales, wheezes
PHYSICAL Cyanosis
Tachycardia, arrhythmias
EXAMINATION
Abdominal tenderness
Perianal burns
Changes in sensorium
CBC, platelets Urinalysis
LABORATORY ABG Urine hemoglobin
EXAMINATION Creatinine Typing (save blood for x-matching)
Na+, K+, Cl- X-rays: Chest PA upright, abdominal
Prothrombin time
253
A
Remove patient’s clothes and do decontamination procedures,
especially with history of vomiting.
GENERAL
MEASURES Adult: D5 0.9NaCl or AR 1 L x 8 hours
Give oxygen via nasal cannula.
Volume Ingested
SPECIFIC
MEASURES
KNOWN UNKNOWN or
UNCONSCIOUS
Pedia: ≤1 mL/kg Pedia: ≤1 mL/kg Pedia: >1 mL/kg

Adult: ≤60 mL Adult: ≤60 mL plus other Adult: >60 mL
toxic substances
Defer NGT. Protect airway.

Insert NGT. Insert NGT.
Lavage with activated charcoal Careful lavage with water
Adult: 100 g in 200 mL water
Pedia: 1 g/kg to make a slurry
Give sodium sulfate:

Pedia: 250 mg/kg as a 10% solution
Repeat if no bowel movement within 1 hour.
Once with bowel movement, clean peri-anal area at once to prevent chemical burns.
Remove NGT.
Check for the following conditions:
• Unconsciousness
• Seizures
• Pneumonitis by x-ray or clinical parameters (If with
clinical evidence of pneumonia but none on X-ray,
repeat chest x-ray on the 3rd day.
• Ingestion of other toxic substances (e.g., organo-
phosphate pesticides (treat as for toxic substance)
None of the Any of the

above above
Observe for Observe for Observe for at least 3 days.

12 hours. 24 hours. Treat accordingly.
Refer to Psychiatry if non-
accidental.
Refer to Psychiatry if non-accidental. Discharge

if with no signs of pneumonia.
Treatment of Specific Problems
254
Table 41. Commonly encountered n-methyl carbamates
Commonly Encountered N-Methyl Carbamates
Chemical Hazard Category
Aldicarb Ia
Bendiocarb II
Benomyl IV
BMPC II
Carbaryl II
Carbofuran Ib
Fenobucarb II
Formetanate Ib
Isoprocarb II
Methomyl Ib
Oxamyl Ib
Propoxur II
Thiophanate-methyl IV
ORGANOCHLORINE
Organochlorine pesticides are also known as chlorinated hydrocarbons.
There are three different types: cyclodienes, dichlorodiphenylethanes and hexachlo-
rocyclohexanes. Except for Lindane, which is used as an anti-scabicide, organochlo-
rines are either banned or restricted by the Fertilizer and Pesticide Authority.
Organochlorines are potent stimulants of the CNS and the sympathetic sys-
tem. Cyclodienes, such as endosulfan and chlordane antagonize the neurotransmitter
+ +
gaba-aminobutyric acid (GABA) and inhibit Na –K ATPase. Dichlorodiphenylethanes
increase the sensitivity of neurons to small stimuli by reducing the transport of potas-
sium into the cell, interfering with the transport of sodium outside the cell, and by in-
hibiting the actions of ATPase and calmodulin.
Liquid preparations are dissolved in petroleum distillate solvents. Absorption
is through all routes of entry and enterohepatic recirculation occurs during metabo-
lism. Organochlorines are stored in fat depot. The half-lives of these pesticides are
relatively long (weeks to years). In the environment, organochlorines pose potential
problems as persistent organic pollutants.
Table 42. Commonly encountered organochlorines
Commonly Encountered Organochlorines
Chemical Hazard Category
Dichlorophenylethanes
DDT II
Cyclodienes
Aldrin Ia
Chlordane II
Dieldrin Ib
Endrin Ib
Endosulfan II
Heptachlor II
Hexachlorocyclohexanes
Lindane II
256
Table 45. Clinical features
Clinical Features
• Mild – mainly muscarinic
Malaise, vomiting, nausea, diarrhea, sweating, abdominal pain, salivation, miosis
• Moderate – muscarinic and nicotinic
Symptoms of mild poisoning PLUS dyspnea, decreased muscular strength, bronchospasm,
bronchorrhea, speech impairment, muscle fasciculation, tremor, motor incoordination,
bradycardia, involuntary urination / defecation, muscular cramps, hypotension / hyperten-
sion
• Severe – muscarinic, nicotinic and CNS
Symptoms of moderate poisoning PLUS coma, respiratory paralysis, extreme hypersecre-
tion, cyanosis, sustained hypotension, extreme muscle weakness, muscular paralysis, con-
vulsion, behavioral changes
Table 46. Commonly encountered organophosphates*
Commonly Encountered Organophosphates
Category Ia Category Ib Category II Category III Category IV
Ethoprophos Dichlorvos/DDVP Chlorpyrifos Malathion Temephos
Methyl parathion Edifenphos Diazinon Primiphos
Mevinphos Methamidophos Dimethoate methyl
Phorate Methidathion Fenitrothion
Phosphamidon Monocrotophos Fenthion
Terbufos Omethoate Phenthion
Triazophos Phosalone
Pyrazophos
*Categories are based on WHO Classification
• Contraindicated drugs: aminoglycosides, aminophylline, barbiturates, beta-blockers, furo-
semide, morphine, phenothiazines, succinylcholine, sulfonamides, theophylline and other
xanthines, and local anaesthetics especially procaine derivatives
• Do not give IV atropine if patient is cyanotic as this may cause ventricular fibrillation in a
hypoxic patient. Give atropine IM and correct cyanosis before IV administration.
• Aggressive treatment must be instituted if there is a history of concomitant intake of pheno-
thiazine/haloperidol since these drugs aggravate organophosphate poisoning and increase
mortality.
• In case of under atropinization manifested by cholinergic symptoms, re-atropinize.
• In case of atropine toxicity manifested by behavioral changes, high-grade fever, flushing of
the face and tachyarrhythmias, discontinue atropine temporarily or adjust dose/frequency
of administration. Observe and hydrate patient. Never give any anticholinesterase, such as
physostigmine or neostigmine.
• For arrhythmias, never give beta-blockers or lidocaine. Give calcium blockers, phenytoin
or bretylium.
• Although furosemide is contraindicated in organophosphate poisoning, the drug is recom-
mended in cases of pulmonary edema. However, ensure that respiration is normal and po-
tassium is within acceptable limits.
• Defer regular diet (e.g., solid foods) until patient is fully conscious and atropine dose is al-
ready given by oral route. Start with liquid diet.
• Organophosphates may produce organophosphate-induced delayed neuropathy (OPIDN)
weeks or months after exposure.
259
Management
Amount taken
HISTORY Time and mode of exposure
Intake of other substances
Symptoms (see Clinical Features)
See Clinical Features

PHYSICAL Note size of pupils, respiration, heart rate, cyanosis, de-
EXAMINATION pressed sensorium, muscle fasciculations, fine tremors
Toxicologic Examination
Collect 5 mL heparinized blood in vacutainer.
Immerse tube in ice and submit to lab within 24 hours.
LABORATORY General Examinations
EXAMINATION ABG Na+, K+, Cl- LFTs Urinalysis
CBC BUN Protime ECG
RBS Creatinine Amylase
ABCs of life support. Put patient in Trendelenburg position.

Maintain vital signs.
If poison is absorbed through skin, inhaled or ingested then vomited,
give oxygen, remove clothing and sponge bath using alkaline soap.
If poison is ingested:
Insert nasogastric tube (appropriate size for age).
GENERAL Do gastric lavage with activated charcoal.
MEASURES Adult: 100 g in 200 mL water
Give sodium sulfate.
Pedia: 250 mg/kg in water to make a 10% solution
Insert Foley catheter when necessary.
Give phenytoin 10-20 mg/kg IV/PO loading dose, then 5-7 mg/kg in 3
divided doses (not faster than 50 mg/minute if IV) for cases of
malathion, parathion or dichlorvos poisoning, even in the absence
of seizures.
If pralidoxime chloride is available, this should be given within the first

36 hours.
Adult: 1 g in 250 mL 0.9NaCl
Pedia: 50-100 mg/kg in 125 mL 0.3NaCl to run 1 hour
SPECIFIC In severe cases, give the second dose 1 hour later; and subse-
MEASURES quent doses 6 hours apart.
Pralidoxime is effective in poisoning cases secondary to: Diazinon,
Dichlorvos, Disulfoton, EPN, Fenthion, Isoflurophate, Malathion,
Methyl demeton, Methyl parathion, Mevinphos, Parathion, Sarin,
Phosphamidon, and TEPP.
Severity of poisoning
Mild Moderate Severe

20-40% depression of 40-60% depression of >60% depression of
RBC cholinesterase RBC cholinesterase RBC cholinesterase
Give atropine every 10-15 minutes until parameters for initial atropinization are achieved:
• Pupils ≥4 mm
• Heart rate 100-140 per minute
• Dry mouth
• Hypoactive bowel sounds
B C D
260
WATUSI (DANGEROUS FIRECRACKERS)
In 1991, the first documented patient who swallowed an unknown amount of
Watusi died in the emergency room complex of the Philippine General Hospital.
Watusi, dancing firecracker, or “spit devil” is reddish in color, thin like a
matchstick, and measures about ½ to 1 inch long. Chemical analysis reveals that it
has the following components:
Table 48. Chemical components and toxicity rating of watusi
Chemical Components and Toxicity Rating of Watusi
Chemical Toxicity Rating Lethal Dose
Yellow or white phosphorus 6 Super toxic (<5 mg/kg)
Trinitrotoluene (TNT) 4 Very toxic (50-500 mg/kg)
Potassium nitrate 3 Moderately toxic (0.5-5 g/kg)
Potassium chlorate 4 Very toxic (50-500 mg/kg)
Table 49. Summary toxicities from TNT, Potassium chlorate and Potassium nitrate
Summary of Toxicities from Trinitrotoluene (TNT), Potassium Chlorate and Potassium
Nitrate
TNT Potassium Chlorate Potassium Nitrate
Lethal dose 50-500 mg/kg 50-500 mg/kg 0.5 to 5 g/kg
Adult: 12 g Adult: 2-6 kg
Child: 5 g
Infant: 1 g
Clinical Effects
Hypotension + – +
Nausea and vomiting – + +
Methemoglobinemia + + +
Red cell hemolysis – + +
Aplastic anemia + – –
Subacute hepatic necro- + – –
sis
Table 50. Clinical stages of acute yellow phosphorus poisoning

Clinical Stages of Acute Yellow Phosphorus Poisoning
Stage 1
Vomiting with or without hematemesis, severity of symptoms depends on amount ingested
Stage 2
Relatively symptom-free period
Stage 3
Severe gastrointestinal symptoms, acute degeneration of liver with metabolic derangements,
significant ECG changes mimicking MI
• Phosphorus is a protoplasmic poison whose toxicity is enhanced when dissolved in alcohol,
digestible fats and oils like castor oil.
• Skin or mucosal contact with phosphorus produces painful second and third degree burns.
• Yellow phosphorus is insoluble in water but readily soluble in most oils.
• White phosphorus reacts rapidly with oxygen, easily catching fire at temperatures 10-15
degrees above room temperature.
262
Management
Amount ingested
Time and mode of administration
HISTORY Intake of other substances
Characteristic course following ingestion (see clinical stages)
Evidence of cutaneous or mucosal burns

PHYSICAL Garlic odor in the vomitus or feces
EXAMINATION “Smoking stool” and luminescence of vomitus and feces
CBC Reticulocyte count Protime
APTT Ionized Ca++ Amylase
Glucose TP AG ratio LFTs
TB, DB, IB Creatinine BUN
LABORATORY ABG Electrolytes Blood typing
EXAMINATION ECG
Peripheral blood smear
CPK MB (in massive ingestion)
Urinalysis with urobilinogen
Fecalysis with occult blood
Diagnostic endoscopy

Avoid oxygen unless patient is hypoxic.
Give raw egg whites
GENERAL Adult: use 8-12 eggs
MEASURES Pedia: use 6-8 eggs
Do not insert NGT. Do not lavage with NSS solution.
Put patient on NPO initially.
General Antidotes
Glucose, Calcium and H2 blockers
Specific Antidotes
N-Acetylcysteine (NAC) same dosage schedule as in Paracetamol
Poisoning
Vitamin K1 initially at 1 mg/kg not to exceed 10 mg in pediatric pa-
tients. An empiric dose of 10 mg IV may be given to adult patients.
Ascorbic Acid, in the presence of documented methemoglobinemia.
SPECIFIC
Give 500-1,000 mg every 6 hours for adults and 10-20 mg/kg for
MEASURES pediatric patients.
Supportive measures
Give Vitamin B complex by the 72nd hour.
Watch out for development of nosocomial infection.
Limit physical activity.
Watch out for multiple target organ damage.
Refer to psychiatry if non-accidental.
ETHANOL
Ethanol is a CNS depressant with sedative-hypnotic properties. Acute over-
dose of ethanol may lead to respiratory depression, cardiovascular collapse and
death. It is rapidly absorbed from the upper gastrointestinal tract and is distributed in
the tissues according to their water content.
The pleasurable effects of alcohol are thought to be mediated via mu opioid
receptors in the ventral tegmental area, while central effects, such as ataxia, sedation
and anxiolysis, are mediated through the GABA-benzodiazepine receptor complex.
Glutamate receptor changes, such as NMDA withdrawal and together with reduced
GABA-ergic function, result to increased risk of seizure and neurotoxicity.
Alcohol is commonly taken with other drugs, particularly drugs of abuse. The
fatal dose is difficult to ascertain because of individual tolerance (the result of physical
263
dependence and genetic predisposition) but the equivalent of about 400 mL of pure
ethanol consumed in one hour may be lethal.
Patients with blood alcohol levels of 0.05% (50 mg/100 mL) are considered
medically intoxicated. The rate of metabolism is measured in the blood as 13-15
mg/dL/hour for a non-alcoholic, and greater than 30 mg/dL/hour for a chronic alcohol-
ic. In cases of intoxication, alcohol follows zero-order kinetics and metabolism is con-
stant at 100 mg/kg/hour.
Table 52. Ethanol content of common alcohol-containing products
Ethanol Content of Common Alcohol-containing Products
Alcoholic Drinks % Ethanol*
Beer
Lager 2–3
Pilsen 5–6
Strong Beer 9 – 14
Wines 7 – 12
Fortified wines (e.g., champagne) 15 – 20
Distillates 40 – 50
(e.g., whiskey, rye, bourbon, rhum, gin, brandy, scotch)
Local distilled spirits 60 – 80
(e.g.,) tuba, lambanog
Other Products
Aftershaves 15 – 80
Cold/allergy medications 5 – 16
Cough preparations 2 – 25
Glass cleaners 10
Mouth washes 15 – 25
Perfumes and colognes 25 – 95
*Proof is numerically twice the percent value
Table 53. Common local terms for alcohol drinks and their corresponding volumes
Common Local Terms for Alcoholic Drinks and their Corresponding Volumes
Alcoholic Drinks Volume
Lapad 325 mL
Bilog 325 mL
Kwatro kantos 325 mL
Long neck 740 mL
Beer grande 1L
Beer (regular) 320 mL
Table 54. Clinical features

Clinical Features
Blood Ethanol Clinical Description
Concentration (mg/dL)
<50 Talkativeness, subjective feeling of well-being
Mild Intoxication: Decreased inhibition, slurred speech, emotional
instability, incoordination, slight visual impairment, slow reaction
time, and increased confidence
100 – 300 Moderate Intoxication: Ataxia, slurred speech, slight visual impair-
ment, muscular incoordination, decreased attention span, altered
perception, altered equilibrium, and diplopia
300 – 500 Severe Intoxication: Vision impairment and double vision, severe
ataxia, and stupor
>500 Very Severe Intoxication: Coma, respiratory failure
264
Table 55. Formula for calculating blood alcohol level
Formula for Calculating Blood Alcohol Level
(mL ingested) x (% alcohol) x (specific gravity of ethanol)
Plasma Level (in mg/dL) = (VD) x (weight in kg) x 10
Where, VD = Volume of Distribution (0.7 L/kg in children and 0.6 L/kg in adults)
Specific gravity of ethanol = 800 mg/mL

• Ethanol enhances the effects of:
anticoagulants (coumadin), antidepressants, antihistamines, hypnotics, insulin, MAO inhibi-
tors, sedatives and tranquilizers.
• Disulfiram-like intolerance to ethanol is associated with:
acetohexamide, animal charcoal, calcium carbimide, carbon disulfide, carbitamide, furazoli-
done, griseofulvin, imidazoles, metronidazole, quinacrin, sulfonylureas, thiocarbamates,
third-generation cephalosporins, tolazoline.
• Alcohol with aspirin increases the likelihood of gastrointestinal bleeding.
• Gastric lavage, induction of emesis and activated charcoal are not indicated since alcohol is
rapidly absorbed from the gastrointestinal tract. These procedures are indicated only when
multiple drug ingestion is suspected.
Management
Amount taken
Time and mode of administration
Acute or chronic user
HISTORY Intake of other substances (alcohol, barbiturates, drugs of abuse)
Check for the following:
Vomiting Respiratory Depression Seizures
Coughing Aspiration Head trauma
Check vital signs, especially BP, RR and temperature

(using low-reading thermometer).
PHYSICAL
Note changes in sensorium, eye movements, papillary size, evidence
EXAMINATION of head trauma, tremors, breath odor, and size of thyroid gland.
Check for signs of respiratory failure, chronic liver disease.
Toxicologic Examinations
Blood alcohol level: 5 mL oxalated blood, 100 mL urine (first void)
LABORATORY
CBG, ABG Na+, K+, Mg++, Cl- Amylase
EXAMINATION RBS Creatinine CPK (MB and MM)
Chest x-ray BUN Ionized Ca++
Urinalysis Urine ketones Liver function tests
ABCs of life support. Respiratory support if necessary.

Maintain vital signs and keep patient warm.
GENERAL Put patient on NPO. Give intravenous fluids.
265
A
If patient is conscious
Give thiamine 100 mg IV/IM
Then D50-50 100 mL fast drip IV
Observe for 24 hours. Check for:
History of withdrawal
Signs and symptoms of withdrawal
High risk for developing withdrawal
If (+) for any of the above:
Admit. Refer to Neurology/Psychiatry Services
Begin treatment for withdrawal.
If (–) for all of the above:
Refer to Psychiatry.
If no untoward events within 6 hours, discharge with maintenance
thiamine 50 mg thrice a day.
SPECIFIC If patient is unconscious

MEASURES Give thiamine 100 mg IV/IM
Then D50-50 100 mL fast drip IV
Continue thiamine 100 mg IV every 8 hours.
Admit. Refer to Neurology.
Level of consciousness
• Regains consciousness
See box above for treatment of conscious patient.
If no untoward events, discharge with maintenance PO thiamine 50
mg thrice a day, folic acid 1 mg once a day and multivitamins.
• Partially conscious
Determine cause of depressed sensorium.
Treat specific problems.
See treatment of patient who regains consciousness.
• Remains unconscious
Naloxone 2 mg IV push. May be given every 2 minutes for a total of
10 mg
If with good response, treat as per partially conscious / conscious pa-
tient.
If patient remains unconscious, determine cause. Consider hemodi-
alysis. Refer to Neurosurgery. Treat specific problems.
Table 57. Alcohol withdrawal syndrome

Alcohol Withdrawal Syndrome
A. Cessation of (reduction in) alcohol use that has been heavy and prolonged.
B. Two (or more) of the following developing within several hours to a few days after:
1. Autonomic hyperactivity (e.g., sweating or pulse rate greater than 100)
2. Increased hand tremor
3. Insomnia
4. Nausea and vomiting
5. Transient visual, tactile, or auditory hallucinations or illusions
6. Psychomotor agitation
7. Anxiety
8. Grand mal seizures
C. The symptoms in criterion B cause clinically significant distress or impairment in social, oc-
cupational, or other important areas of functioning.
D. The symptoms are not due to a general medical condition and not better accounted for by
any other mental disorder.
Specify if: With perceptual disturbances
266
Table 58. Treatment for alcohol withdrawal syndrome
Treatment for Alcohol Withdrawal Syndrome
Pharmacologic Treatment
• Symptom-Triggered Therapy: Start diazepam 5 to 10 mg every 8 hours, adjusting dose and
frequency based on Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA-
Ar) Score.
• If there is severe liver dysfunction, drugs metabolized by oxidation (such as diazepam) are
eliminated slowly. In these cases, the “CLOT” benzodiazepines (clonazepam, lorazepam,
oxazepam and temazepam) should be used (see Table below).
• Supplementary multivitamins, including thiamine, pyridoxine and folic acid
• Maintain euglycemia.
• Potassium, phosphate and magnesium supplements
Non-pharmacologic Treatment
• Reassurance, reality orientation, personal attention, general nursing care
• Frequent monitoring of signs and symptoms using the CIWA-Ar Scale
Table 59. Drugs for treatment of acute withdrawal syndrome

Drugs for Treatment of Alcohol Withdrawal Syndrome
Diazepam Lorazepam* Chlordiazepoxide Oxazepam*
Route IV, PO IV, IM, PO IV, PO PO
Initial dose 5-20 mg 1-2 mg 2x to 4x a 15-20 mg 3x to 4x a 15-30 mg 3x to 4x
3x to 4x a day day a day
day
Liver Oxidation Glucuronidation Oxidation Glucuronidation
metabolism
Active Yes No Yes No
metabolite
Half-life Long Intermediate Long Intermediate
(in hours)
Range 20-70 5-25 6-30 5-20
Average 33 15 10 8
*Not available in the Philippines
COBRA BITE
Snake venom contains neurotoxins which can cause paralysis by blocking
the nicotinic acetylcholine receptors at the postsynaptic motor endplates and/or af-
fecting the mode of neurotransmitter release at the pre-synaptic motor endplates.
Death is due to respiratory failure as a result of paralysis of the respiratory muscles.
In the Country, there are more than 60 species of snakes, seven of which
are venomous. By far, the most important local snake is the Philippine cobra (Naja
philippinensis).
The Philippine cobra predominantly causes paralysis. Local tissue injury is
uncommon. Neurotoxic signs can appear as late as 24 hours after the bite. Initial
evaluation should focus on the local signs at the bitten area (swelling, blistering and
necrosis), neurologic signs (ptosis, ophthalmoplegia, followed by dysarthria, poor
tongue protrusion, dysphagia, drooling, limb weakness, depressed or absent deep
tendon reflexes), and respiratory distress which is a sign of severe envenomation.
The available antivenom in the country is specific for cobra bites. Therefore, it should
not be used when envenomation is due to a pit viper. WARNING: Using a tourniquet,
cutting and suctioning the wound, or applying chemicals have no value, and in fact
can be detrimental to the patient.
267
• Immobilization of the affected limb using pressure bandaging is a useful technique to re-
duce venom transport, especially when local necrotic injury is not evident.
• Patients may develop extreme anxiety and may hyperventilate with consequent pares-
thesias and numbness. This may be mistaken as envenomation.
• When administering the antivenom, extreme caution should be taken in patients with hy-
persensitivity to horse serum or have a history of atopy.
• Under no circumstances should a skin test be done unless the antivenom must be ad-
ministered.
• When administering anticholinesterases, pre-treatment with atropine should be done to
prevent cholinergic side effects, such as bradycardia and hypersalivation.
Management
Time patient was bitten

Type of snake involved. Ideally snake should be killed and
brought in for identification.
HISTORY Field treatment done, if any
Intake or application of traditional remedies
Concurrent intake of other drugs
Complete physical and neurologic examination.

PHYSICAL Check wound site for edema and/or necrosis.
EXAMINATION Check for signs of envenoming.
CBC Prothrombin time Urinalysis – test for hematuria,
LABORATORY ABG Creatinine myoglobinuria
EXAMINATION LFTs Na+, K+, Cl-, Ca++ Chest x-ray
Platelets CPK (MM)
ABCs of life support

Maintain vital signs.
Intubate if with signs of respiratory depression.
Place patient on Trendelenburg position. Bitten area should be lower
than the heart.
GENERAL Put patient on NPO. Give intravenous fluids.
Administer oxygen when indicated.
Give anti-tetanus prophylaxis.
Local wound care
No signs of envenoming
Observe for 24-48 hours.
If still asymptomatic, discharge.
If with signs of envenoming, see below
SPECIFIC
MEASURES
With signs of envenoming
Administer antivenom.
268
Table 61. Actions taken if cobra antivenom is available
If Cobra Antivenom is Available:
• Perform skin test using 0.2 mL of a 1:100 dilution of the serum with NSS. Inject intra-
dermally on the extremity opposite the bite and read after 15 minutes. Observe patient
constantly after the injection. If no erythema or pseudopodia of the test wheal occurs, the
test is probably negative. Compare with the negative control using NSS 0.2 mL intra-
dermal in the opposite volar area.
• Give 5-10 ampuls (800 IU/amp) IV over 15 minutes (both adult and pedia) after negative
skin test. Repeat every 1-2 hours until a response is observed. Alternatively, dilute 5-10
ampuls in 500 mL isotonic fluid to run for 1-2 hours.
• If with history of allergy, but condition is life-threatening, administer diphenhydramine 50-
100 mg slow IV prior to antivenom therapy, then give slow IV infusion of antivenom. Dis-
continue with the first sign of hypersensitivity reaction and manage the reaction with
1:1000 epinephrine 0.5-1.0 mL subcutaneous.
Table 62. Actions taken if cobra antivenom is not available
If Cobra Antivenom is NOT Available:
• Pre-treat with atropine 0.6 mg IV.
• Follow with test dose edrophonium chloride 10 mg IV over 1-2 minutes.
• If with positive response, start neostigmine 100 micrograms/kg IV infusion over 4 hours
or 25 micrograms/kg IV push hourly until reversal of neurotoxic signs is observed.
• If neostigmine is not available, may give pyridostigmine per NGT, 60 mg 1 tablet two to
four times a day.

• ACUTE RESPIRATORY FAILURE:
Hook to mechanical ventilator; Pulmonary toilet
• INFECTION: Look for focus of infection; Start broad-spectrum antibiotics
• LOCAL TISSUE NECROSIS: Debridement; Local wound care, Antibiotics
• MYOGLOBINURIA: Hydration: 3-4 L per day
PARALYTIC SHELLFISH POISONING

“Red tides” are marine phenomena that usually occur during the rainy sea-
son. They are produced by an overgrowth of dinoflagellates that contain pigments
that are responsible for giving sea water a red-brown appearance. In the country, the
species of dinoflagellates involved are Pyrodinium bahamense var. compressum and
Gymnodinium catanella.
These dinoflagellates contain neurotoxins, particularly saxitoxin, neosaxitox-
in, gonyautoxin, and decarboylsaxitoxin. Generally, these toxins are found in the di-
gestive glands of mollusks which feed on dinoflagellates.
Paralytic shellfish poisoning (PSP) in humans results from the ingestion of
toxin-containing bivalves. Saxitoxin acts on the peripheral and autonomic nervous
system and blocks depolarization at the neuromuscular junction by increasing sodium
permeability in exchange for potassium efflux. The most common manifestations oc-
curring within 30 minutes include numbness or tingling sensation, weakness and mo-
tor incoordination.
Cases have been encountered where shellfish vendors spray their produce
with pesticides in order to keep away flies and other pests. Diarrhea and muscle
weakness also occur with exposure to organophosphates, a class of pesticides used
frequently in the Philippines. Organophosphate poisoning is therefore worth ruling out
in cases of PSP by determining RBC cholinesterase levels.
269
• The toxin is heat-stable. Cooking, frying or baking only partially lower toxicity. In neuro-
toxic shellfish poisoning, cooking will not lower toxicity.
• Do not give laxative or cathartic if diarrhea is present.
• Avoid use of digitalis.
Management
History and intake of shellfish
Time of ingestion
Symptoms:
HISTORY • GI: diarrhea, nausea, vomiting abdominal pain
• Neurologic: paresthesias of the face, muscle paralysis
(weakness, dysphagia, ataxia, respiratory paralysis)
• Others: headache, thirst, myalgia, vertigo
PHYSICAL Emphasis on neurologic examination

EXAMINATION
Toxicologic Examinations
RBC cholinesterase to rule out organophosphate poisoning
LABORATORY Gastric aspirate
EXAMINATION General Examinations
ABG RBS Urine pH CBC Na+, K+, Cl-, Ca++
ECG Fecalysis and stool culture
ABCs of life support. Maintain vital signs. Keep patient in a quiet room.
Do gastric lavage with 1.5% sodium bicarbonate.
1 tablespoon baking soda in 1 L water OR
2 vials of 8.4% sodium bicarbonate in 1 L water
GENERAL After 5 minutes, do gastric lavage with activated charcoal.
MEASURES Adult: 100 g in 200 mL water
After lavage, give sodium sulfate.
Pedia: 250 mg/kg in water to make a 10% solution
May be repeated only once if initial dose does not result in bowel movement
after one hour.
Give 8.4% sodium bicarbonate 1 mEq/kg IV every 6 hours until urine pH ≥7.5.
No respiratory distress
Observe for 24 hours. If still asymptomatic, discharge.
SPECIFIC
MEASURES With respiratory distress
Sodium bicarbonate
1-2 mEq/kg/IV every 6 hours
No respiratory failure Respiratory failure
Observe for 24 hours. Ventilatory support

If still asymptomatic, dis- Admit to ICU.
charge. Test dose of edrophonium 1-2 mg IV
If respiratory failure develops, If with good response, continue treatment with
see box to right. neostigmine 1-3 mg IV and atropine 0.4-
0.6 mg IV.
If with no response, consider other etiologies.
270
• ELECTROLYTE IMBALANCES: Correct potassium and other electrolyte imbal-
ances.
• HYPOVOLEMIC SHOCK: IV fluids, Fluid challenge
• METABOLIC ACIDOSIS: Sodium bicarbonate (1 mEq/kg or based on acid-base
deficit)
• RESPIRATORY DISTRESS: Ventilatory support, Oxygenation
REFERENCE:
Cortes-Maramba NP, Panganiban LCR, Pascual JC, Dioquino CPC, Westergaard MLS. (Eds.).
Algorithms of Common Poisoning, 3rd Editon. National Poison Management and Control
Center, Philippines; 2011.
271
5
Based on the greater efficacy
TREATMENT PLAN A: TREAT DIARRHEA AT HOME of Reduced (Low) Osmolari-
Counsel the mother or caregiver on the 4 RULES of Home Treatment ty ORS Solution, especially
for children with acute, non-
1. GIVE EXTRA FLUID (as much as the child wants), to prevent dehydration: cholera diarrhea, WHO and
a. Tell the mother or caregiver: UNICEF recommend its use
currently. This formulation
• Breastfeed frequently and for longer at each feed;
has reduced the sodium
• If child is exclusively breastfed, give ORS or clean water in addition to breastmilk; concentration to 75 mEq/L,
• If child is not exclusively breastfed, give one or more of the following: the glucose concentration to
75 mmol/L, and the total
ORS solution, food-based fluids (e.g., chicken or vegetable soup with salt, salted rice water or salted yogurt osmolarity to 245 mOsm/L.
drink), clean water.
It is especially important to give ORS at home when:
- Child has been treated with Plan B or C during this visit;
Fluids unsuitable for rehydra-
- Child cannot return to a clinic if diarrhea gets worse. tion must be avoided. These
b. Teach the mother or caregiver how to mix and give ORS. Give the mother 2 packets of ORS to use at include: commercial carbonat-
home. ed drinks, commercial fruit
juices, sweetened tea.
c. Show the mother or caregiver how much fluid to give in addition to the usual fluid intake: Avoid also fluids with stimulant,
- Up to 2 years: 50 – 100 ml (1/4 – 1/2 of a large cup) after each loose stool and between stools diuretic or purgative effects
274
- 2-10 years: 100 – 200 ml (1/2 – 1 large cup) after each loose stool and between stools such as: coffee and some
medicinal teas.
- Older child to Adult: As much fluid as they want.
• Tell the mother or caregiver to:
- Give frequent small sips from a cup.
- If child vomits, wait 10 minutes then continue but more slowly.
- Continue giving extra fluid until diarrhea stops. The child should be brought to
2. GIVE ZINC SUPPLEMENTS the health worker if he shows
a. Tell the mother or caregiver how much zinc to give: any of the following signs of
dehydration or of other prob-
- Up to 6 months: ½ tablet per day for 14 days; lems:
- 6 months and more: 1 tablet per day for 14 days. • Passage of many watery
b. Show the mother or caregiver how to give zinc supplements: stools
• Repeated vomiting
- Infant: dissolve tablet in small amount of expressed breastmilk, ORS or clean water in a small cup or
• Child becomes very
spoon; thirsty
- Older child: tablet can be chewed or dissolved in a small amount of clean water in a cup or spoon. • Fever
c. Remind the mother or caregiver to give the zinc supplement for the full 14 days. • Blood in the stool
• Failure to improve in 3
3. CONTINUE FEEDING, to prevent malnutrition.
days.
4. INSTRUCT MOTHER OR CAREGIVER WHEN TO RETURN
274
6
TREATMENT PLAN B: TREAT SOME DEHYDRATION WITH ORS
Give in the CLINIC the recommended amount of ORS over a 4-hour period.
1. DETERMINE THE AMOUNT OF ORS TO GIVE DURING THE 1st 4 HOURS:

AGE Less than 4 months 4-11 months 12-23 months 2 – 4 years 5 – 14 years 15 years or older
WEIGHT Less than 5 kg 5-7.9 kg 8-10.9 kg 11-15.9 kg 16-29.9 kg 30 kg or more
Amount in mL 200-400 400-600 600-800 800-1,200 1,200-2,200 2,200-4,000

*
Use the child’s age only when you do not know the weight. The approximate amount of ORS required (in ml) can also be
calculated by multiplying the child’s weight (in kg) times 75.
• If the child wants more ORS than shown, give more. When oral rehydra-
tion fails (usually due
• For infants under 6 months who are not breastfed, if using the old WHO ORS solution containing 90 mmol/L of sodium,
to continuing rapid
also give 100 – 200 mL of clean water during this period. This is not necessary if the new reduced (low) osmolarity so- stool loss, e.g., in
lution with 75 mmol/L of sodium is being used. cholera, or due to
insufficient ORS
2. SHOW THE MOTHER OR CAREGIVER HOW TO GIVE ORS SOLUTION: solution intake from
fatigue or lethargy, or
275
• Give frequent small sips from a cup. due to frequent and
• If the child vomits, wait 10 minutes, then continue but more slowly. severe vomiting), the
child must be given
• Continue breastfeeding whenever the child wants. ORS by nasogastric
tube or Lactated
3. AFTER 4 HOURS: Ringer’s solution or
• Reassess the child and classify the child for dehydration. D5LR intravenously.
• Select the appropriate plan to continue treatment.
• Begin feeding the child in the clinic.
4. IF THE MOTHER OR CAREGIVER MUST LEAVE BEFORE COMPLETING THE TREATMENT: Oral Rehydration
• Show her how to prepare ORS solution at home. Therapy should not be
given in patients with
• Show her how much ORS to give to finish 4-hour treatment at home. abdominal distension
• Give her enough ORS packets to complete rehydration. Also give her 2 packets as recommended in Plan A. with paralytic ileus and
• Explain the 4 Rules of Treatment at Home: in patients with glucose
malabsorption.
- GIVE EXTRA FLUID
- GIVE ZINC SUPPLEMENTS See Plan A for recommended fluids and
- CONTINUE FEEDING See COUNSEL THE MOTHER section
7 - WHEN TO RETURN
275
TREATMENT PLAN C: TREAT SEVERE DEHYDRATION QUICKLY
*Follow the arrows

YES
Can you give Intravenously (IV) Start IV fluid immediately. If the child can drink, give ORS by mouth while the drip is set
Fluid immediately? up. Give 100 mL/kg Ringer’s Lactate Solution, or preferably, D5LR (or if unavailable, use
Normal Saline). Divide as follows:
AGE First give 30 mL/kg in: Then give 70 mL/kg in: Plain glucose
Infants 1 hour* 5 hours (dextrose) solution
(under 12 months) should not be used
Children 30 minutes* 2 ½ hours for IV rehydration.
(12 months – 5 years)
*Repeat once if radial pulse is still very weak or not detectable.
NO
• Reassess child every 1-2 hours. If rehydration status not improving, give IV drip more
rapidly.
• Also give ORS (about 5mL/kg/hour) as soon as the child can drink: usually after 3-4
hours (infants) or 1-2 hours (children).
• Reassess infant after 6 hours and a child after 3 hours. Classify dehydration then
choose appropriate plan (A, B or C) to continue treatment.
276
YES • Refer URGENTLY to hospital for IV treatment
Is IV treatment available nearby
(within 30 minutes)? • If the child can drink, provide the mother with ORS solution and show her how to give
frequent sips during the trip.
NO
Are you trained to use a nasogastric • Start rehydration by nasogastric tube or by mouth, if the child can drink, with ORS
tube (NGT) for rehydration? solution; give 20 mL/kg/hour for 6 hours (total of 120 mL/kg).
YES • Reassess the child every 1-2 hours:
- If there is repeated vomiting or increasing abdominal distension, give fluid more
NO slowly.
- If hydration status not improving after 3 hours, send the child for IV therapy.
Can the child drink? • After 6 hours, reassess child. Classify dehydration then choose the appropriate plan (A,
B or C) to continue treatment.
NO
NOTE:
Refer URGENTLY to hospital for IV If possible, observe the child at least 6 hours after rehydration to be sure the mother can
or NG treatment maintain hydration by giving the child ORS solution by mouth.
276
VACCINATION SCHEDULES
IN CHILDHOOD
Route & Site of AGE
Vaccines
Administration At birth 1 ½ Months 2 ½ Months 3 ½ Months 9 Months 12 Months
BCG Intradermal 
(upper arm)
Hep B at birth Intramuscular 
(upper thigh)
DPT-Hep B- Intramuscular   
Hib (upper thigh)
Oral   
OPV (mouth)
IPV Intramuscular 
(upper arm)
PCV Intramuscular   
(upper arm)
Measles Subcutaneous 
(upper arm)
278
MMR Subcutaneous 
(upper arm)
IN PREGNANT WOMEN
2 – 5 doses:
Tetanus Toxoid (TT) • TT1 – At first contact with woman of childbearing age or at first antenatal care visit, as early as possible
for Pregnant women • TT2 – At least 4 weeks after TT1 (at next antenatal care visit)
• TT3 – At least 6 months after TT2
• TT4 – At least 1 year after TT3
• TT5 – At least 1 year after TT4
278
VACCINATION SCHEDULES
IN ADULTHOOD
Recommended Vaccination schedule by the Committee on Adult Immunization, Philippine Society of Microbiology & Infectious
Diseases (PSMID), and the Philippine Foundation for Vaccination.
Precautions/
Vaccine Type/Route Target Individuals Schedule
Contraindications
1. Tetanus, diphtheria,
acellular pertussis ticularly: 1 dose of Tdap in to vaccine component or
Recommended for all susceptible adults par- 3 doses of Td with • Severe allergic reactions
vaccine the series 0, 1, 6- following prior dose

12 months
• Pregnant women
Inactivated vaccine Booster every 10 illnesses

• Health care workers • Moderate to severe
Intramuscular years with Tdap

• New mothers
2. Hepatitis B Recommended for all susceptible adults par- 3 doses 0, 1, 6

• Adults and adolescents
ticularly: months a vaccine component or

• Severe allergic reaction to
279
Inactivated vaccine to a previous dose
Intramuscular Alternate: 4 doses
• Immigrants from areas of high
0, 1, 2, 12 months
• Hemodialysis patients
• IV drug users
• Homosexual males
• Household contacts of HBV carrier
• Recipients of blood products
contacts
• Health care workers with frequent blood
3. Varicella Recommended for all susceptible adults par- 13 years – 2

ticularly: doses to a component (gelatin
• Severe allergic reaction
Live attenuated or neomycin) or to a

vaccine cella infection or vaccination 0, 1 month previous dose
• Persons >13 years without history of vari-
Subcutaneous
illnesses
• All health care workers • Moderate or severe acute
• Teachers of young children
• Non-pregnant women of child-bearing age • Pregnancy
279
• International travellers • Immunosuppression
DIRECTORY
DEPARTMENT OF HEALTH
Website: http://www.doh.gov.ph/
Phone Number: (02) 6517800
DOH – Antimicrobial Resistance Surveillance Program (ARSP)

Antimicrobial Resistance Surveillance Reference Laboratory
DOH Compound, Filinvest Corporate City, Alabang, Muntinlupa
Website: www.ritm.gov.ph
Telefax: (02) 8099763
Email address: arsp_ph@yahoo.com
DOH – National Center for Pharmaceutical Access and Management (NCPAM)

Website: http://www.ncpam.doh.gov.ph/
Phone Number: (02) 6517800 Loc. 2554-2558, (02) 7110570
Telefax: (02) 7112589
PHILIPPINE FOOD AND DRUG ADMINISTRATION

Email Address: info@fda.gov.ph
Website: http://www.fda.gov.ph/about-food-and-drug-administration
Center for Food Regulation and Research

Phone Number: (02) 8571992, (02) 8571993
Center for Cosmetics Regulation and Research

Phone Number: (02) 8571940, (02) 8571984
Center for Drugs Regulation and Research

Center for Device Regulation, Radiation Health and Research

Phone Number: (02) 7499443, (02) 7116824
NATIONAL DRUG INFORMATION CENTER

Telefax: (02) 5264384
Website: http://www.druginfo.ph
Email Address: ndic@druginfo.ph
NATIONAL POISON MANAGEMENT AND CONTROL CENTER

LUZON
Philippine General Hospital
Phone Number: (02) 5241078, (02) 5548400 Loc. 2311, (02) 4040257, (02) 5260062 (F)
Website: http://www.uppoisoncenter.org/network.html
East Avenue Medical Center

282
Rizal Medical Center
Phone Number: (02) 5706273, (02) 6719615, (02) 6719740
Batangas Regional Hospital

VISAYAS
Eastern Visayas Regional Medical Center
Phone Number: (053) 3213131, (053) 3213129 (F)
Western Visayas Medical Center / Iloilo Doctors Hospital

MINDANAO
Zamboanga Medical Center
Phone Number: (062) 9912934, (062) 9910537
PHILIPPINE HEALTH INSURANCE CORPORATION

Trunkline: (02) 4417444
Call center: (02) 4417442
Website: http://www.philhealth.gov.ph
Email Address: actioncenter@philhealth.gov.ph
PHILIPPINE INSTITUTE OF TRADITIONAL AND ALTERNATIVE HEALTH CARE (PITAHC)

Website: http://www.pitahc.piaem.org
Email Address: pitahc@gmail.com
283
REFERENCES
Administrative Order No. 163 s. 2002. “Implementing Guidelines and Procedures in the Pro-
curement and Requisition of Drugs and Medicines by the Department of Health pursuant to
Executive Order No. 49.”
Administrative Order No. 2012-0023. “Revised Implementing Guidelines for the Philippine Na-
tional Formulary System.”
Administrative Order No. 2012-0023-A. “Amendment to Administrative Order No. 2012-0023,

Entitled: “Revised Implementing Guidelines for the Philippine National Formulary System
(PNFS).”
Administrative Order No. 2014-0009. “Implementing Guidelines on the Rational Use of Medicine
(RUM) Pillar of the Philippine Medicines Policy.”
American Association of Clinical Endocrinologists (AACE), 2007.
American College of Physicians (ACP), 2007.
American Diabetes Association Standards of Medical Care (ACE), 2010 and updates as of 2013.
Bravo, LC, Gatchalian, SR, Gonzales, MLM, et. al., 2011, Handbook of Pediatric Infectious Dis-
ease, 5th Edition. UP College of Medicine-Philippine General Hospital.
BMJ Group and the Royal Pharmaceutical Society of Great Britain, September 2013 – March
2014, British National Formulary, 66th edition, London: BMJ Group and Pharmaceutical
Press.
BMJ Group, the Royal Pharmaceutical Society of Great Britain, and RCPCH Publications Ltd.,
July 2013 – July 2014, British National Formulary for Children, London: BMJ Group, Phar-
maceutical Press and RCPCH Publications Ltd.
Canadian Diabetes Association (CDA), 2008.
Carlos, C., et. al. Antimicrobial Resistance Surveillance Program 2012 Data Summary Report.
Antimicrobial Resistance Reference Laboratory, Manila: Department of Health Research
Institute for Tropical Medicine, ARSP, 2012.
Carlos, C., et. al. Antimicrobial Resistance Surveillance Program 2013 Data Summary Report.
Antimicrobial Resistance Reference Laboratory, Manila: Department of Health Research
Institute for Tropical Medicine, ARSP, 2013.
Centers for Disease Control and Prevention. (2013). Methicillin-resistant Staphylococcus aureus
(MRSA) infections. Retrieved from http://cdc.gov/mrsa/.
Collaborative Statement of the Philippine Society for Microbiology and Infectious Diseases, and
Philippine Foundation for Vaccination, 2012, Handbook on Adult Immunization for Filipinos
2012 Update, 2nd edition, Makati City, Philippines: Zurbano Publishing & Printing Corp.
Cortes-Maramba, NP, Panganiban, LCR, Pascual, JC, Dioquino, CPC, and Westergaard, MLS
(Eds)., Algorithms of Common Poisoning, 3rd Edition, 2011. National Poison Management
and Control Center, Manila, Philippines.
Cunningham FE, Baughman VL, Peters J, Laurito CE. “Comparative pharmacokinetics of oral
versus sublingual clonidine,” (Abstract). J Clin Anesth, 1994 Sep-Oct, 6 (5):430-3.
284
Dantes MB, Fariñas IF, Ceria JA, Genuino AJ, Ala MV. “A rapid assessment of the practices
pertaining to the formulary and the rational use of medicine among primary healthcare pro-
viders,” November 2012, NCPAM, Department of Health, Manila.
Department Memorandum No. 2009-0009. “Generics Only Prescribing.”
Department of Child and Adolescent Health and Development, 2005, Handbook IMCI Integrated
Management of Childhood Illness. World Health Organization and UNICEF. Geneva.
Department of Child and Adolescent Health and Development, 2005, The Treatment of Diarrhea:
A Manual for Physicians and other Senior Health Workers. World Health Organization. Ge-
neva.
Department of Health - National Center for Disease Prevention and Control - Degenerative Dis-
ease Office (DOH-NCDPC-DDO), 2009, Prevention and Control of Chronic Lifestyle-
Related Noncommunicable Diseases in the Philippines: Manual of Operations.
Department of Health. National Rabies Prevention and Control Program Manual of Operations
(2012), Manila, Philippines.
Department of Health, 2003, ‘Pregnancy, Childbirth, Postpartum and Newborn Care: A Guide for
Essential Practice in Philippine Setting’, Integrated Management of Pregnancy and Child-
birth, Philippines.
Department of Health - National Center for Pharmaceutical Access and Management, 2011, The
Philippine Medicines Policy: Strategic Directions on Access to Medicines for Filipinos 2011-
2016.
Department of Science and Technology - Research and Development Institute, Food and Nutri-
tion Research Institute, 2002, Recommended Energy and Nutrient Intakes for Filipinos,
Philippines.
Department Order No. 2014-0088. “Guidelines on the Exemption of Medicines for National
Health Programs as provided in Administrative Order No. 2012-0023 or the “Revised Im-
plementing Guidelines for the Philippine National Formulary System (PNFS).”
Executive Order No. 49, s. 1993 “Directing the Mandatory Use of the Philippine National Drug
Formulary (PNDF) Volume I as the Basis for Procurement of Drug Products by the Gov-
ernment.”
Family Health Office, 2014, Expanded Program on Immunization, Manila, Philippines: Depart-
ment of Health.
Gerbino, P and the Editorial Board, 2005, Remington: The Science and Practice of Pharmacy,
21st edition, United States of America: Lippincott Williams & Wilkins.
Integrated Management of Childhood Illness Chart Booklet, March 2014, World Health Organi-
zation, Geneva.
Infectious Diseases Society of America and American Thoracic Society, 2007, ‘Infectious Dis-
eases Society of America/American Thoracic Society Consensus Guidelines on the Man-
agement of Community-Acquired Pneumonia in Adults’, Oxford Journals – Clinical Infec-
tious Diseases, vol. 44, issue supplement 2, pp. S27-S72.
Interagency Committee on Antimicrobial Resistance, June 2014, 1st Interagency Committee

Meeting on Antimicrobial Resistance, Manila: Department of Health.
International Diabetes Federation Global Guideline (IDF), 2005.
285
Joint Statement of the Philippine Society for Microbiology and Infectious Diseases, Philippine
College of Chest Physicians, Philippine Academy of Family Physicians, and Philippine Col-
lege of Radiology, 2010, Philippine Clinical Practice Guidelines on the Diagnosis, Empiric
Management, and Prevention of Community-acquired Pneumonia (CAP) in Immunocompe-
tent Adults 2010 Update, Makati City, Philippines: Zurbano Publishing & Printing Corp.,
PPGG-ID Philippine Society for Microbiology and Infectious Disease.
Katzung, B, 2006, Basic and Clinical Pharmacology, 10th edition, United States of America:
McGrawHll.
Lexicomp, 2013, Lexicomp Online, viewed since October 2013, https://online.lexi.com/lco-

/action/home/switch.
Maramba-Lazarte, CC, Bravo, LC, Gatchalian, SR, et. al., 2010, Rational Antibiotic Use in Pedi-
atrics: A Study Guide and Workbook, Department of Pediatrics, College of Medicine – Phil-
ippine General Hospital, UP Manila.
MIMS, 2013, MIMS Online, viewed since October 2013, https://www.mimsonline.com-

/Search/Search.aspx.
Ministry of Health and New Zealand Guidelines Group (NZGG), 2003.
Multisectoral Task Force Consensus on the Detection and Management of Hypertension in the
Philippines, 2011, Philippine Clinical Practice Guidelines on the Detection and Manage-
ment of Hypertension – 2011 (also known as the 140/90 Report).
National Collaborating Centre for Chronic Conditions (NCCCC), 2008.
National Formulary Committee, National Drug Policy – Pharmaceutical Management Unit 50,
2008, Philippine National Drug Formulary: Essential Medicines List, 7th edition, vol. 1, Ma-
nila, Philippines: Department of Health.
National Formulary Committee, Philippine National Drug Policy Program, 2006, Philippine Na-
tional Formulary: Essential Drug Monographs, 3rd edition, vol. 2, Manila, Philippines: De-
partment of Health.
National Institutes of Health, U.S. Department of Health and Human Services, August 2004, The
Treatment of High Blood Pressure.
National Tuberculosis Control Program Manual of Procedures, 5th Edition, 2014, Department of
Health, Manila.
Philippine Children’s Medical Center Pharmacy and Therapeutics Committee, 2013, Philippine
Children’s Medical Center Formulary, 4th Edition, Quezon City, Philippines.
Panel Members Appointed to the Eighth Joint National Committee (JNC 8), February 2014,
‘2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults:
Report from the Panel Members Appointed to the Eighth Joint National Committee (JNC
8)’, The Journal of the American Medical Association, vol. 311, no. 5, pp. 507-520.
PAPP Task Force on pCAP, 2012, The 2012 PAPP Update in the Management of Pediatric
Community-Acquired Pneumonia, Philippine Academy of Pediatric Pulmonologists, Quezon
City, Philippines.
Philippine Foundation for Vaccination, Immunization Schedule – Child and Adult, Compendium
of Philippine Medicine 2012, 14th edition, Manila, Philippines.
286
Philippine Heart Association Council on Hypertension, Position Statement on Management of
Hypertension in Adults, August 18, 2014 (through communication).
Philippine Practice Guidelines Group-Infectious Diseases. The Philippine Clinical Practice

Guidelines on the Diagnosis, Treatment and Prevention of Leptospirosis in Adults 2010.
Philippine Society for Microbiology and Infectious Diseases, Quezon City, Philippines,
2010.
Pharmaceutical Society of Australia, the Royal Australian College of General Practitioners and
the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists,
2012, Australian Medicines Handbook, Adelaide SA: Australian Medicines Handbook Pty
Ltd.
Republic Act No. 6675. “Generics Act of 1988.”
Republic Act No. 9502. “Universally Accessible Cheaper Quality Medicines Act of 2008.”
Republic Act No 10606. “National Health Insurance Act of 2013”
Treatment of High Blood Pressure. NIH Publication No. 04-5230. August 2004. National In-
stitute of Health, US Department of Health and Human Services.
Stroke Society of the Philippines, 2014, Guidelines for the Prevention, Treatment and Rehabilita-
tion of Stroke, 6th edition, GoldenPages Publishing, Philippines
Spah F, Grosser KD. “Treatment of hypertensive urgencies and emergencies with nitrendipine,
nifedipine, and clonidine: effect on blood pressure and heart rate,’ (Abstract). Journal of
Cardiovascular Pharmacology, 1988; 12 Suppl 4:S154-6.
Task Force for the Management of Arterial Hypertension of the European Society of Hyperten-
sion and of the European Society, June 2013, ‘2013 ESH/ESC Guidelines for the Manage-
ment of Arterial Hypertension’, European Heart Journal, vol. 34, issue 28, pp. 2159-2219.
Task Force on the New Comprehensive Diabetes Algorithm, March/April 2013, ‘American Asso-
ciation of Clinical Endocrinologists’ Comprehensive Diabetes Algorithm 2013’, Endocrine
Practice, vol. 19, no. 2.
Task Force on Updates in Urinary Tract Infection in Pregnancy, Philippine Practice Guidelines
Group in Infectious Diseases, 2013, Updates on Urinary Tract in Pregnancy, PPGG-ID,
Philippine Society for Microbiology and Infectious Diseases, Quezon City, Philippines.
Task Force on Urinary Tract Infections, Philippine Practice Guidelines Group in Infectious Dis-
eases, 2013, Philippine Clinical Practice Guidelines on the Diagnosis and Management of
Urinary Tract Infections in Adults 2013 Update, PPGG-ID, Philippine Society for Microbiol-
ogy and Infectious Disease, Quezon City, Philippines.
Task Force on Urinary Tract Infections 2003-04, Philippine Practice Guidelines Group in Infec-
tious Diseases, 2004, Philippine Clinical Guidelines on the Diagnosis and Management of
Urinary Tract Infections in Adults 2004 Update, PPGG-ID, Philippine Society for Microbiol-
ogy and Infectious Diseases, Quezon City, Philippines, vol. 2, no. 1.
Technical Team on Antimicrobial Resistance (WHO), 2012, Country Situation Analysis on Anti-
microbial Resistance: Final Report, Philippines.
Thomson Healthcare, Inc., 2007, Physicians’ Desk Reference: Guide to Drug Interactions, Side
Effects, and Indications, 61st edition, Montvale, New Jersey: Thomson PDR.
287
Turnidge J. Principles of Appropriate Prescribing of Antimicrobials. Australian Journal of Hospital
Pharmacy, 1994;24:533-536.
UNITE FOR Diabetes Philippines, 2013, ‘Philippine Practice Guidelines on the Diagnosis and
Management of Diabetes Mellitus’, Philippine Pharmaceutical Directory (PPD) Compendi-
um of Philippine Medicine (CPM), 16th edition, Medicomm Pacific, Inc., Pasig City, Philip-
pines.
WebMD Health Corporation, 2012, Medscape, viewed since October 2013,

www.medscape.com.
World Health Organization, 2008, WHO Model Formulary, Geneva, Switzerland, WHO Press,
pages 1-14, 15-218, 262-312, 320-424, 432-451, 454-627.
World Health Organization, 2010, Package of Essential Noncommunicable (PEN) Disease Inter-
ventions for Primary Health Care in Low-Resource Settings, France.
288
INDEX Diazepam 122
Dicycloverine 103
A Diethylcarbamazine 59
Aciclovir / Acyclovir 64 Digoxin 84
Activated Charcoal, USP 26 Diltiazem 69, 76
Akapulko 88 Diphenhydramine 23, 120
Albendazole 58, 59 Diphtheria-Tetanus Toxoid and Pertussis Vaccine
Aluminum Hydroxide + Magnesium Hydroxide 101 164
Amlodipine 73 Dopamine 66
Amoxicillin 29, 50 Doxycycline 44, 63
Ampicillin 30
E
Anti-rabies Serum 163
Enalapril 76
Anti-tetanus Serum 163
Epinephrine 67
Artemether + Lumefantrine 61
Erythromycin 45, 100
Aspirin 82, 130
Ethambutol 53
Atropine 26
Ethinylestradiol + Levonorgestrel 109
Azithromycin 31
Ethyl Alcohol 154
B
F
Balanced Multiple Replacement Solution 159
Fenofibrate 70
BCG Vaccine 164
Ferrous Salt 113, 148
Biperiden 119
Ferrous Salt + Folic Acid 149
Butamirate 141
Fluoxetine 131
C Fluticasone + Salmeterol 142
Calamine 89 Furosemide 106
Calcium + Vitamin D 148 Fusidic Acid 86
Captopril 73
G
Carbamazepine 120, 139
Gentamicin 46
Cefalexin 32
Gliclazide 91
Cefixime 33
Glucose (50%) Solution 158
Ceftriaxone 33
Glucose (Dextrose, 5%) in Lactated Ringer’s 157
Cefuroxime 35
Glucose (Dextrose, 5%) in 0.3% Sodium Chloride
Celecoxib 124
156
Cetirizine 23
Glucose (Dextrose, 5%) in 0.9% Sodium Chloride
Chloramphenicol 36
156
Chloroquine 62
Glucose (Dextrose, 5%) in Water 155
Chlorpromazine 133
Glutaraldehyde 154
Ciprofloxacin 37
Clarithromycin 38, 50 H
Clindamycin 39 Haloperidol 134
Clofazimine 51 Hepatitis B Vaccine (Recombinant DNA) 165
Clonidine 75 Hydrochlorothiazide 78, 107
Clopidogrel 83, 130 Hydrocortisone 25, 86, 95, 145
Clotrimazole 88 Hydrogen Peroxide 154
Cloxacillin 41 Hyoscine 104
Co-Amoxiclav (Amoxicillin + Potassium Clavula- Hypertension in Adults, (CPG) 219
nate) 41
Cobra Antivenin 27 I
Common Poisoning, (CPG) 248 Ibuprofen 126
Cotrimoxazole (Trimethoprim + Sulfamethoxazole) Influenza Polyvalent Vaccine 166
42 Insulin 92
Regular Insulin (Recombinant DNA, Human) 94
D NPH/Isophane Insulin Human 94
Dapsone 52 Ipratropium 143
Dehydration, treatment 161-162, 272-276 Ipratropium + Salbutamol 144
Dextrose (see Glucose) Isoniazid 53
Diabetes Mellitus, (CPG) 232 Isoniazid + Rifampicin 57
Diarrhea, (WHO Guidelines) 272 Isoniazid + Rifampicin + Ethambutol 57
289
Isoniazid + Rifampicin + Pyrazinamide + Ethambu- Pneumonia, Community-Acquired, (CPG)
tol 57 In immunocompetent adults 186
Isosorbide Dinitrate 68 Pediatric CAP 195
Povidone-Iodine 154
L
Praziquantel 60
Lactated Ringer’s Solution (Ringer’s Lactate) 159
Prednisone 25, 96, 129, 145
Lagundi 146
Primaquine 63
Leptospirosis 44
Pyrazinamide 54
Levothyroxine 97
Pyridostigmine 28
Lidocaine, Gel and Inj. 118
Live Attenuated Measles Vaccine 167 R
Live Attenuated Measles, Mumps and Rubella Rabies Immunoglobulin,
Vaccine 167 Equine (ERIG), Purified 169
Live Attenuated Trivalent Oral Polio Vaccine 168 Human (HRIG) 170
Loratadine 24 Rabies Vaccine 171
Losartan 79 Regular Insulin (Recombinant DNA, Human) 94
Retinol (Vitamin A) 152
M
Rifampicin 52, 55
Magnesium Sulfate 109
Risperidone 137
Meclizine (Meclozine) 130
Rosuvastatin, 70
Medroxyprogesterone 111
Mefenamic Acid 127 S
Metformin 92 Salbutamol 141
Methicillin-resistant Staphylococcus aureus (MRSA) Sambong 106
39 Sertraline 132
Methimazole 98 Silver Sulfadiazine 87
Methyldopa 80 Simvastatin 72
Metoclopramide 101 Sodium Chloride (0.9%) 155
Metoprolol 80 Sodium Chloride 161
Metronidazole 47, 51, 61 Sterile Water for Injection 162
Micronutrient Powder 150 Streptomycin 56
Montelukast 146
T
Multivitamins for Infants, Children and Adults 151
Tamsulosin 107
Mupirocin 87
Tetanus Immunoglobulin 172
N Tetanus Toxoid 173
Naproxen 128 Tobramycin 100
Neomycin + Polymyxin B + Fluocinolone Acetonide Tramadol 116
90 Tranexamic Acid 113
Nitrofurantoin 57 Trimethoprim + Sulfamethoxazole
NPH/Isophane Insulin Human 94 (See cotrimoxazole)
Tuberculosis, (NTP MOP) 215
O
Olanzapine 136 U
Omeprazole 102 Urinary Tract Infection, (CPG) 201
Oral Rehydration Salts 160 V
In management of dehydration in infants and
Valproic Acid (See Valproate)
children
Valproate 123, 139
Oseltamivir 65
Vitamin B1 B6 B12 152
Oxytocin 112
Z
P
Zinc 153
Paracetamol 116
Penicillin G Benzathine (Benzathine benzylpenicil-
lin) 48
Penicillin G Crystalline (Benzylpenicillin) 49
Pentavalent Vaccine 169
Permethrin 89
Phenoxymethylpenicillin (Penicillin V) 49
Phytomenadione 114
290
NOTES
291

PN F Manual For Primary Healthcare Final

Hochgeladen von

Dokumentinformationen

Originalbeschreibung:

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

PN F Manual For Primary Healthcare Final

Hochgeladen von

Copyright:

Verfügbare Formate

i

Moreover, the recommendations incorporated into the clinical practice guide-

All rights reserved 2014

The Formulary Executive Council

Madeleine De Rosas-Valera, MD, MScIH (Heidelberg)

NATIONAL CENTER FOR PHARMACEUTICAL

Anna Melissa S. Guerrero, MD, MPH (HTA)

FORMULARY EXECUTIVE COUNCIL

Marita B. Dantes, MD, FPNA

Mac Ardy J. Gloria, RPh

Isidro C. Sia, MD, PhD

Philippine Nutrition Society

Philippine Obstetrical and Gynecological Society

Philippine Psychiatric Association

Philippine Society of Hematology and Blood Transfusion

The existence of a national formulary is very essential in providing

I urge each individual to be one with us in the achievement of univer-

Enrique T. Ona, MD, FPCS, FACS

The Manual provides an adequate list of essential medicines neces-

The PHC Formulary is intended to serve as the primary reference

I commend the NCPAM, the Formulary Executive Council, the edito-

Thank you and mabuhay!

Lilibeth C. David, MD, MPH, MPM, CESO III

To explicitly define these needs, a situational analysis of the practices per-

a. Provision of a comprehensive list of medicines that will allow the pri-

b. Provision of a readily accessible, and updated rapid reference on the

The medicines list, the monographs, and cross-references were integrated

Clinical practice guidelines on the management of hypertension, diabetes

c. Provision of strategies to implement the rational and responsible use

Sections on the Rational Use of Medicines and a review of proper prescrib-

Discussions on the growing global and local problems of antimicrobial re-

A situational analysis of the problems in the use of the National Formulary

The Formulary remains as an integral part of the rational and responsible

It is our turn to challenge the healthcare practitioners to utilize the Na-

Marita B. Dantes, MD, FPNA

Mr. Frederick Pereña who prepared the cover design;

THYROID HORMONES and ANTITHYROID ................................................................................. 97

INTRODUCTION OF THE MEDICINE

DOSAGE FORM/STRENGTH: (for oral or parenteral administration)

ANTIMICROBIAL RESISTANCE ALERT! This section lists precautions and recommendations

ADMINISTRATION: This section lists recommendations on the proper intake or administration

2. BODY WEIGHT AND AGE

x Changes in a drug’s bioavailability may be thought of in

x This indicates that a drug in two or more similar dosage

7. RECOMMENDATIONS TO THE PRESCRIBERS

NOTE: Interactions which modify the effects of a medicine may involve

Recommended empiric treatment for suspected H. influenzae in-

b. In Salmonella gastroenteritis, increasing rates of ciprofloxacin

c. Due to the emerging resistance of Shigellae to the quinolones and

F. DRIVING FORCES BEHIND ANTIMICROBIAL RESISTANCE

As contained in Section 6 of RA 6675 those required to use the generic

• Administrative Order No. 2012-0023 entitled “Revised Implementing Guidelines

• An additional amendment to A.O. 2012-0023, the Department Order No. 2014-

• Administrative Order No. 2014-0009 entitled “Implementing Guidelines of the Phil-

Precautions: Contraindications: Known hypersensitivity to

Inj.: 50 mg/mL, 2 mL vial (IM, IV)

doses, maximum of 1,500 mg/day, for at most 'UXJ,QWHUDFWLRQV

>GD\V, ൑1.2 kg weight: 25 mg/kg/dose eve-

Adverse Drug Reactions:

&+,/' 1-5 years, 125 mg every 6 hours; ANTI-H. PYLORI INFECTION IN

&RQWUDLQGLFDWLRQV Known hypersensitivity to $GYHUVH'UXJ5HDFWLRQV

Precautions: Pregnancy Category: C

doses, maximum of 1,500 mg/day, for at most 'UXJ,QWHUDFWLRQV

>GD\V, ൑1.2 kg weight: 25 mg/kg/dose eve-

&RQWUDLQGLFDWLRQV Known hypersensitivity to $GYHUVH'UXJ5HDFWLRQV

'RVH smaller doses for 2-3 days to avoid potential

&RQWUDLQGLFDWLRQV Hypersensitivity to iodine; of clinical and, whenever possible, electrolyte

3UHJQDQF\&DWHJRU\ D $GPLQLVWUDWLRQ Fluid administration should be

0.9% SODIUM CHLORIDE 3UHJQDQF\&DWHJRU\ C

,QM 2 mL, 2.5 mL, 5 mL, 10 mL and 20 mL ampul

&RQWUDLQGLFDWLRQV Where the administration of &RQWUDLQGLFDWLRQ Known hypersensitivity to corn

sodium or chloride could be clinically detri- &RQWUDLQGLFDWLRQV Known hypersensitivity to