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Tamiflu®: Globally Endorsed in

the Treatment and Prevention


of Influenza.

Tamiflu® ( oseltamivir INN) is an orally administered anti-influenza drug of

worldwide proven value in the in the treatment and prevention of Influenza A

and Influenza B. Tamiflu® is a member of a small class of drugs called

neuraminidase inhibitors which have largely superseded the older, less

effective anti- influenza agents, the adamantanes (1,2,3,4).

Both Influenza A and Influenza B remain a major worldwide health concern

with well documented seasonal epidemics and, in particular with Influenza A,

pandemics. Which cause significant morbidity and mortality to hundreds of

thousands, if not millions during pandemics, along with social and economic

hardship and human misery (5, 6, 7). The constantly changing antigenic

nature of the influenza virus has hampered effective vaccine production and

vaccine scientists are often locked into a game of catch up with the virus’s

changing immunological appearance. These factors in the context of our ever

increasingly fluid world population mean Influenza remains a real and present

world health threat (2, 5, 6, 7).


Tamiflu® was the product of a rational drug design project undertaken by C

U Kim and his team at Gilead Sciences® and which was subsequently

marketed by Roche®. Tamiflu is a pro-drug which is de-esterified within the

liver to the free carboxylate. This bio-transformed drug is a competitive

inhibitor of influenza neuraminidase, an enzyme essential for viral release

and cellular dissemination, and so inhibits influenza viral reproduction (1, 7).

Tamiflu® is the only orally administered neuraminidase inhibitor available to

date; and this, along with its established efficacy, simple dosing schedules

and safety profile has ensured it has remained an integral component of both

national and international influenza control strategies and World Health

Organisation public health directives(7, 8, 9, 10).

Reputable, well designed and independent clinical trials of Tamiflu have

clearly established the significant benefit of Tamiflu® in the treatment of

influenza in a wide variety of medical settings and patient groups including

children and the medically vulnerable. Tamiflu® was shown to reduce

symptom severity and duration, shorten recovery and convalescence times,

reduce complication rates and reduce virus secretion in influenza infected

patients (11, 13, 14, 15, 16, 17, 18, 19, 20). Tamiflu® was shown to be an

effective prophylactic agent when administered to individual at risk of

influenza infection in both community and residential settings and was well

tolerated, even in patients where clinical circumstances dictated prolonged

administration (11, 13, 16, 18, 19, 20).


Though Tamiflu® was never intended as a replacement for vaccination,

however in the absence of an effective vaccine, limited vaccine availability

and other instances of population vulnerability to influenza the use of

Tamiflu®, notably in the current H1N1 Swine Flu pandemic and the H5N1

Avian Flu outbreaks, has ensured we have had an effective pharmaceutical

defence in addition to other public health measures with which to combat the

continuing national and world influenza threats. Where indicated, Tamiflu®

can be co-administered with trivalent influenza vaccine without impairing

vaccine response and providing antiviral cover while immunity develops in

influenza at risk individuals (11, 21).

The World Health Organisation, the American Centre for Disease Control and

European Medical agency, largely as a result of the current pandemic flu

threat, have all revised their anti- influenza drug guidelines. And a central

tenet of their policy is ensuring adequate supplies of Tamiflu® are readily

available and the recommendation that adequate drug stocks be held in

reserve worldwide. Additionally, drug safety and clinical trial data were

scrutinised which resulted in the extension Tamiflu’s product licence to

include children aged 1 year or greater along with pregnant and

breastfeeding women (7, 8, 9, 10, 11).

In response to concerns about possible worldwide shortages of Tamiflu®,

Roche®, the international product licence holder, has sublicensed the

manufacture of Tamiflu to a number of pharmaceutical companies


throughout the globe to ensure sustainable, adequate production and supply

of the drug in the event of further world influenza contingencies(22).

Roche®, based on its own production figures, estimates around 50 million

people worldwide have been treated with Tamiflu. Influenza virus drug

sensitivity monitoring has confirmed that current pandemic H1N1 and avian

H5N1 strains remain sensitive to Tamiflu. Where practicable, in accordance

with best practice guidelines, the prescription of anti-influenza drugs during

seasonal influenza outbreaks should be guided by current local virus

sensitivity data from the relevant authority (11).

Tamiflu® has been endorsed internationally as an effective and safe (7, 8, 9,

10, 11, 23, 24, 25, 26, 27, 28) anti-influenza agent with significant utility in

both the treatment and prevention of Influenza A and Influenza B infection;

this in the absence of a superior comparator, its ease of administration and

simple dosing schedules have made Tamiflu® the drug of choice in the

management and containment of Influenza throughout the world (11).

Tamiflu® (oseltamivir phosphate ) Prescribing Data

Tamiflu® is presented as capsules containing 30mg (light yellow hard gel

caps), 45mg (grey hard gel caps) or 75mg (grey/light yellow hard gel caps) of

oseltamivir as the phosphate salt for oral administration. Roche and dosage
are printed on each capsule in blue ink. Capsules are available as blister

packages of 10 capsules.

Tamiflu® is also available in bottles as a powder for reconstitution to an oral

suspension, which when reconstituted with water as directed contains

12mg/mL of oseltamivir base.

Not to be stored at ambient temperatures above 30°C.

Indications

Tamiflu® is indicated for the treatment and prevention of infections due to

influenza Viruses of type A and B in adults and children one year of age or

older.

Dosage

Treatment of Influenza in Adults and Adolescents aged 13 years or

older: The recommended dose of Tamiflu® is 75mg twice daily for five days.

Treatment should be commenced within 48hrs of onset of symptoms.

Capsules may be taken with food

Prophylaxis of Influenza in Adults and Adolescents aged 13 years or

older: The recommended dose of Tamiflu® is 75mg once daily for at least
ten days. Treatment should commence within 48hrs of exposure. Safety and

efficacy have been demonstrated for up to 6 weeks. The period of has

protection as been determined to be as long as the dosing is continued.

Capsules may be taken with food.

Treatment of Influenza in Paediatric Patients: The recommended dose

of Tamiflu for children aged 1 yr or older is shown in Table 1. Tamiflu oral

suspension may be used in patients unable to swallow a capsule.

Table 1: Oral Dose of Tamiflu® for the Treatment of Influenza in

Paediatric Patients by Weight

Body Weight Body Weight Recommend No. Of No. Of

(kg) (lbs) ed Dose for Bottles of Tamiflu®

5 Days Tamiflu® Capsules

Susp Required for

Needed for a 5 Day

dose 5 Day Regimen

Regimen
≤15kg ≤33lbs 30mg twice 1 10 Tamiflu®

daily Caps

(30mg)
>15kg to >33lbs to 45mg twice 2 10 Tamiflu®

23kg 51lbs daily Caps

(45mg)
>23kg to >51lbs to 60mg twice 2 20 Tamiflu®
40kg 88lbs daily Caps

(30mg)
>40kg >88lbs 75mg twice 3 10 Tamiflu®

daily Caps

(75mg)

Prophylaxis of Influenza in Paediatric Patients: The recommended dose

of Tamiflu® for children aged 1 year or older is shown in Table 2. Tamiflu®

oral suspension may be used in patients unable to swallow a capsule.

Table 2: Oral Dose of Tamiflu® for Prophylaxis of Influenza in

Paediatric Patients by Weight.

Body Body Recommend No. Of No. Of

Weight Weight ed Dose for Bottles of Tamiflu®

(kg) (lbs) 10 days Tamiflu® Capsules

Susp Required for

Needed for a 10 Day

a 10 Day Regimen

Regimen
≤15kg ≤33lbs 30mg once 1 10 Tamiflu®

daily Caps

(30mg)
>15kg to >33lbs to 45mg once 2 10 Tamiflu®

23kg 51lbs daily Caps


(45mg)
>23kg to >51lbs to 60 mg once 2 20 Tamiflu®

40kg 88lbs daily Caps

(30mg)
>40kg >88lbs 75 mg once 3 10 Tamiflu®

daily Caps

(75mg)

Special Precautions and Dosage Instructions

Pregnancy and Nursing Mothers: To date research suggests that any risk

associated with the use of Tamiflu® during pregnancy or nursing mothers to

be extremely low. However, the use of Tamiflu® in these clinical instances is

indicated only if the potential benefit justifies any potential risk to the foetus

or breast-fed infant (11, 23).

Hepatic Impairment: No dose adjustment is recommended for patients for

patients with mild to moderate hepatic impairment (11).

Renal Impairment: Dose adjustment is recommended for patients with

creatinine clearance between 10 and 30 mL/min. For the treatment of

influenza the dose should be reduced to 75mg once daily for five days. For

the prophylaxis of influenza the dose of Tamiflu® should be reduced to 75mg


every other day or 30mg of Tamiflu® once daily. No recommended dosing

regimens are available for patients undergoing routine haemodialysis and

continuous peritoneal dialysis with end stage renal disease (11).

Adverse Events

Tamiflu® is well tolerated in the vast majority of patients, opinion which has

been supported by evidence from numerous clinical trials and extensive post

marketing drug surveillance ( 11, 24, 25, 26, 27, 28).

The most commonly reported adverse events to Tamiflu® occurring in

around 1-2% of patients have been gastrointestinal, with diarrhoea and

vomiting being the most prevalent. This is frequently mild in nature and there

is evidence to suggest it can be mitigated by dosing Tamiflu® at mealtimes.

Other more infrequent adverse events associated with the administration of

Tamiflu® have included allergic type reactions including skin rashes and

tissue oedema.

Very rarely, Tamiflu® administration, particularly in young children, may be

associated with adverse neurological reactions ranging from mild mood

disturbances to very atypical behavioural changes. These have been in most

instances self limiting and evidence of causality has not been established(11,

25, 26, 27, 28).


Contraindications

The administration of Tamiflu is contraindicated in patients with a known


hypersensitivity to oseltamivir or any other component of Tamiflu’s
formulation.

References

• Law W, Chen X, Kim CU: Discovery and development of GS 4104

(oseltamivir, Tamiflu®): an orally influenza neuraminidase inhibitor.

Curr Med Chem. 2000 Jun; 7 (6): 663-72.

• Ward Penelope, Small Ian, Smith James, Suter P, Dutkowski R:

Oseltamivir (Tamiflu®) and its potential for use in the event of an

influenza pandemic. Journal of Antimicrobial Chemotherapy (2005) 55,

Suppl. S1, i5-i21.

• Rungrotmongkol T, Intharathep P, Malaisree M, Nunthaboot N,

Kaiyawet N, Sompornpisut P, Payungporn S, Poovorawan Y,

Hannongbua S: Susceptability of antiviral drugs against 2009 influenza

A (H5N1) virus. Biochem Biophys Res Commun. 2009 Jul 31; 385(3):

390-4. Epub 2009 May 20.

• http://www.rocheexchange.com/influenza/productinformation/tamiflu

• Zambon MC: Epidemiology and pathogenesis of influenza. J Antimicrb

Chemother. 1999 Nov; Supp B 3-9.


• Influenza A and Influenza B virus infection. The Merk Manual.

• http://www.telegraph.co.uk/health/swine-flu/5509060/World-flu-

pandemics-a-timeline.html

• http://www.who.int/csr/disease/swineflu/notes/h1n1_use_antivirals_200

90820/en/

• http://www.emea.europa.eu/pdfs/human/vwp/21430106en.pdf

• http://www.cdc.gov/flu/professionals/antivirals/dosage.htm

• http://www.rocheexchange.com/influenza/productinformation/tamiflu

• Tappenden P, Jackson R, Cooper K, Rees A, Simpson E, Read R,

Nicholson K: Amantadine, oseltamivir and zanamivir for the prophylaxis

of influenza (including a review of existing guidance no. 67): a

systematic review and economic evaluation. Health Technol Assess.

2009 Feb; 13(11): iii, ix-xii, 1-246.

• Khazeni N, Bravata DM, Holty JE, Uyeki TM, Stave CD, Gould MK: Safety

and Efficacy of Extended-Duration Antiviral Chemoprophylaxis Against

Pandemic and Seasonal Influenza. Ann Intern Med. 2009 Aug 3. [Epub

ahead of print].
• Piedra PA, Schulman KL, Blumentals WA: Effects of oseltamivir on

influenza related complications in children with chronic medical

conditions. Paediatrics. 2009 Jul; 124(1): 170-8.

• White NJ, Webster RG, Govorkova EA, Uyeki TM: What is the optimal

therapy for patients with H5N1 influenza. PLos med. 2009 Jun 23; 6(6):

e1000091. Epub 2009 Jun 23.

• Schirmer P, Holodniy M: Oseltamivir for treatment and prophylaxis of

influenza infection. Expert Opin Drug Saf. 2009 May; 8(3): 357-71.

• Orzeck EA, Shi N, Blumentals WA: Oseltamivir and the risk of

influenza-related complications and hospitalizations in patients with

diabetes.

• Matheson NJ, Harnden AR, Parera R, Sheikh A, Symmonds-Abrahams

M: Neuraminidase inhibitors for preventing and treating influenza in

children. Cochrane Database Syst Rev. 2007 Jan 24; (1): CD002744.

• Hayden FG, Pavia AT: Antiviral management of seasonal and pandemic

influenza. J Infec Dis, 2006 Nov 1; 194 Suppl 2: S119-26.

• Milrose, SC http://goldpharma.com/search/Tamiflu/lang/ENGLISH/

• Cooper NJ, Sutton AJ, Abrams KR, Wailoo A, Turner D, Nicholson KG:

Effectiveness of neuraminidase inhibitors in treatment and prevention

of influenza A and B: systematic review and meta-analysis of

randomised controlled trials. BMJ. 2003 Jun 7; 326(7401): 1235.


• Antiviral drugs in influenza: an adjunct to vaccination in some

situations. Prescrire Int 2006 Feb; 15(81): 21-30.

• http://articles.latimes.com/2005/dec/13/business/fi-briefs13.

• Tanaka T, Nakajima K, Murashima A, Garcia-Bournissen F, Koren G,

Ito S: Safety of neuraminidase inhibitors against novel influenza A

(H1N1) in pregnant and breastfeeding women. CMAJ. 2009 Jul 7; 181(1-

2): 55-8. Epub 2009 Jun 15.

• Wallensten A, Oliver T, Lewis D, Harrison S: Compliance and side

effects of prophylactic oseltamivir treatment in a school South West

England. Euro Surveill. 2009 Jul 30; 14(30): 19285.

• Casscells SW, Granger E, Kress AM, Linton A: The association between

oseltamivir use and adverse neuropsychiatric outcomes among

TRICARE beneficiaries, ages 1 through 21 years diagnosed with

influenza. Int J Adolesc Med Health. 2009 Jan-Mar; 21(1): 79-89.

• Toovey S, Rayner C, Prinssen E, Chu T, Donner B, Thakrar B, Dutkowski

R, Hoffman G et al: Assessment of neuropsychiatric events in influenza

patients treated with oseltamivir: a comprehensive review.

• Blumentals WA, Song X: The safety of oseltamivir in patients with

influenza: analysis of healthcare claims data from six influenza

seasons. MedGenMed. 2007 Oct 30;9(4):23.


• Dutkowski R, Thakrar B, Froehlich E, Suter P, Ward P: Safety and

Pharmacology of oseltamivir in clinical use. Drug Saf. 2003; 26(11):

7867-801.