A D V ER S E D R U G R EA C TIO N

(A D R )

Vicky Puspitasari
Dept. of Pharmacy
Saiful Anwar General Hospital

1/18/2012
D efi
nition :
Side effect
WHO : Any unintended effect of a
pharmaceutical product occurring at doses
normally used in humans which is related to the
pharmacological properties of the drug. Such
effects may be either positive or negative.
ASHP : An expected, well-known reaction
resulting in little or no change in patient
management (e.g., drowsiness or dry mouth
due to administration of certain antihistamines
or nausea associated with the use of
antineoplastics).

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 Adverse drug events
WHO : Any untoward medical occurrence
that may present during treatment with
a pharmaceutical product but which
does not necessarily have a causal
relationship with this treatment.
MSH : A harmful response that is caused
by a drug or the inappropriate use of a
drug.

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 Adverse Drug Reaction :
WHO : A response to a drug that is noxious
and unintended and occurs at doses
normally used in man for the prophylaxis,
diagnosis or therapy of disease, or for
modification of physiological function.
Karch and Lasagna : Any response to a drug
that is noxious and unintended, and that
occurs at doses used in humans for
prophylaxis, diagnosis, or therapy, excluding
failure to accomplish the intended purpose.

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 A serious adverse reaction is any
medical occurrence that at any dose
normally used in humans (FDA, for
reporting purposes):
results in death
requires inpatient hospitalization or
prolongation of existing hospitalization
results in persistent or significant disability
or incapacity
is life-threatening.

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 ADRs are a serious problem with increasing
incidence, as mo re medicines become
available and more people become exposed to
them.
In the United States, a review of prospective
studies showed that in 1994 :
hospitalized patients : 2.2 million ADRs (6.7 %
incidence)
and an estimated 106,000 fatalities (Lazarou et al.
1998).
Other studies have shown that ADRs account
for 37% of all hospital admissions.
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Classifi
cation ofAD Rs
Type A reactions
These are an exaggerated but otherwise normal
pharmacological response to the effects of the
medicine given in therapeutic dose. These reactions
cause significant morbidity but are rarely severe.
Examples include :
pharmacodynamic, for example bronchospasm with
beta-blocker administration
toxic, for example absolute or relative overdosing
of aminoglycosides causing deafness
withdrawal syndrome or rebound effect, for
example spontaneous rise in blood pressure with
clonidine discontinuation.
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 Type B reactions
These are bizarre and unpredictable with
no relation to dose and are often allergic in
nature. They are often severe and cause
high mortality. Examples include :
idiosyncratic reactions, for example irreversible
aplastic anaemia caused by chloramphenicol
anaphylactic reactions, for example
anaphylactic shock with penicillin
drug-induced diseases, for example antibiotic-
associated colitis.

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 Adverse events as a result of drug interactions
These may be of all degrees of severity and
type, for example
reduced absorption of tetracycline if administered
with ferrous salts
reduced anticonvulsant effects of phenytoin if
administered with some antimalarials such as
pyrimethamine
serious and severe rise in blood pressure following
concurrent administration of monoamine oxidase
inhibitor antidepressants with tricyclic
antidepressants or some antipsychotics.

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 An ADR is always an ADE, but an
ADE might include the result of an
overdose because of a dispensing
error or some other error occurring
during the medication use process.

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Classif c
iation severity of the reaction

Severe : fatal or life threatening

Moderate : requires antidote, medical
procedure, or hospitalization
Mild : symptoms requiring only the
discontinuation of drug therapy
Incidental : very mild symptoms where
the patient can choose whether to
continue drug therapy or not.

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M onitoring A D R s
An important of monitoring ADRs is to process and
analyze ADR case reports arising from patients and
medical providers.
Objectives :
To detect the nature and frequency of ADRs including
periodic re-evaluation of the benefit-risk ratio of medicinal
products
To identify risk factors that may predispose, induce or
influence the development, severity and incidence of
adverse reactions, examples :
i. Patient factors: genetics, racial differences, diets, diseases,
prescribing practices, culture of drug use and traditions of the
people e.g. high carbohydrate, fat diet etc.
ii.Drug interactions, drug distribution, storage and use including
indications, dose, availability and other underlying conditions.

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 ADRs are monitored not just for the sake of reporting
and statistics, but more importantly, to encourage
safer use of medicines by minimizing unsafe use of
all drugs and avoiding the use of unsafe medicines.
ADRs should be assessed and managed in three
steps :
1.Evaluate the nature of the ADR
Obtain a detailed history of the patient using an ADR
reporting form
Checking the description with health workers and looking up
the clinical description and suspected medicine(s) in the
literature.
Assess the likelihood of the suspected medicine being the
cause of the ADR

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2. Establish the cause of the ADRs
Confirm the clinical syndrome constituting the ADR to
be investigated.
Inspect the suspect medicine visually and check its
procurement, storage and expiry date.
Calculate the rate of ADRs occurring in different
departments or clinics.
Check whether there are any other differences
between the departments or clinics showing high and
low rates of ADRs to a particular medicine.

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3. Possible action after ADR evaluation
. reporting to the national drug authority and/or
manufacturer
. implementing new prescribing procedures including
restrictions
. educating prescribers if needed
. educating patients if necessary

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N aranjo A lgorithm for assessing the causality of an
AD R

Naranjo, et al. 1981 1/18/2012

P reventing A D R s
Prevention of ADRs is possible, and indeed
necessary! Studies have shown that over
50% of adverse drug reactions may be
preventable. Most ADRs are related to the
prescribing of an incorrect dose or the
administration of a drug to a patient with a
known allergy.
Many ADRs could be avoided if the
relevant health worker asked specific
questions before prescribing and/or
dispensing a drug
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WHO. 2004

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WHO. 2004

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R eporting of A D R s
1. What To Report
a. Patient inf orm ation
b. Adverse reactions description (include laborator y
results if available)
c. Information related to the suspected dr ug(s)
d. Information on management of the adverse
reactions
e. Information about the reporter
2. Who Should Report
. All health care professionals including
specialists, doctors, dentists, pharmacists ,
nurses, and others health care providers
. Manufacturers or Product registrants
. All government hospitals, private hospitals, health
centres, dispensaries private clinics,1/18/2012
private
3. When To Report
Any suspected ADR should be reported as soon as possible
4. How To Report
a. Send your report in a yellow form for reporting ADRs.
b. Dully fill in the ADRs reporting form when encountering an
ADR t o the patient.
c. Use a separate form for each patient (refer to filling
guides)
d. A completed ADRs case report form should immediately be
sealed and mailed preferably directly to BPOM RI (NA-DFC)
5. Where To Report
Pusat Meso Nasional
Direktorat Pengawasan Distribusi
Produk Terapetik & PKRT
BPOM RI
Jl. Percetakan Negara No. 23. Kotak Pos No. 143 Jakarta 1056 0

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Role ofthe Pharm acist
The pharmacist should facilitate :
1. Analysis of each reported ADR,
2. Identification of drugs and patients at
high risk for being involved in ADRs,
3. he development of policies and
procedures for the ADR-monitoring and
reporting program,
4. A description of the responsibilities and
interactions of pharmacists, physicians,
nurses, risk managers, and other health
professionals in the ADR program,

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5. Use of the ADR program for educational
purposes,
6. Development, maintenance, and evaluation
of ADR records within the organization,
7. The organizational dissemination and use of
information obtained through the ADR
program,
8. Reporting of serious ADRs to the FDA or the
manufacturer (or both), and
9. Publication and presentation of important
ADRs to the medical community.
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Direct patient care roles for pharmacists should
include patient counseling on ADRs,
identification and documentation in the patients
medical record of high-risk patients, monitoring
to ensure that serum drug concentrations remain
within acceptable therapeutic ranges, and
adjusting doses in appropriate patients (e.g.,
patients with impaired renal or hepatic function)

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Thank you for your
attention

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