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Drug Details
TAMIFLU Suspension
- Drug Class Description
Antiviral - Generic Name
Oseltamivir - Presentation
Powder for oral suspension The powder is a granulate or clumped granulate with a white to light yellow colour - Description
g of powder for oral suspension contains oseltamivir phosphate equivalent to 30 mg of oseltamivir. After reconstitution, each ml of suspension contains 12 mg oseltamivir. One bottle of reconstituted suspension (75 ml) contains 900 mg of active substance (oseltamivir). A bottle of 30 g Tamiflu powder for oral suspension contains 25.713 g of sorbitol. One dose of 45 mg oseltamivir administered twice daily delivers 2.6 g of sorbitol. - Indications
Treatment of influenza In patients one year of age and older who present with symptoms typical of influenza, when influenza virus is circulating in the community. Efficacy has been demonstrated when treatment is initiated within two days of first onset of symptoms. This indication is based on clinical studies of naturally occurring influenza in which the predominant infection was influenza A.
Prevention of influenza
- Post-exposure prevention in individuals one year of age or older following contact with a clinically diagnosed influenza case when influenza virus is circulating in the community.
- The appropriate use of Tamiflu for prevention of influenza should be determined on a case by case basis by the circumstances and the population requiring protection. In exceptional situations (e.g., in case of a mismatch between the circulating and vaccine virus strains, and a pandemic situation) seasonal prevention could be considered in individuals one year of age or older.
Tamiflu is not a substitute for influenza vaccination. The use of antivirals for the treatment and prevention of influenza should be determined on the basis of official recommendations. Decisions regarding the use of antivirals for treatment and prophylaxis should take into consideration what is known about the characteristics of the circulating influenza viruses and the impact of the disease in different geographical areas and patient populations.
- Adult Dosage
Tamiflu suspension and Tamiflu capsules are bioequivalent formulations. 75 mg doses can be administered as either
- one 75 mg capsule or
- one 30 mg capsule plus one 45 mg capsule or
- by administering one 30 mg dose plus one 45 mg dose of suspension.
Adults, adolescents or children (> 40 kg) who are able to swallow capsules may receive appropriate doses of Tamiflu capsules.
Tamiflu is not recommended for use in children less than one year of age due to insufficient data on safety and efficacy.
Treatment of influenza
Treatment should be initiated as soon as possible within the first two days of onset of symptoms of influenza.
For adolescents (13 to 17 years of age) and adults: The recommended oral dose is 75 mg oseltamivir twice daily for 5 days.
For infants older than 1 year of age and for children 2 to 12 years of age: The recommended dose of Tamiflu oral suspension is indicated in the table below. Tamiflu 30 mg and 45 mg capsules are available as an alternative to the recommended dose of Tamiflu suspension.
The following weight-adjusted dosing regimens are recommended:
Body Weight Recommended dose for 5 days 
15 kg30 mg twice daily < > 15 kg to 23 kg 45 mg twice daily > 23 kg to 40 kg 60 mg twice daily > 40 kg 75 mg twice daily For dosing, an oral dispenser with 30 mg, 45 mg and 60 mg graduations is provided in the box. For accurate dosing, the oral dispenser supplied should be used exclusively.
Children weighing> 40 kg and who are able to swallow capsules may receive treatment with the adult dosage of 75 mg capsules twice daily for 5 days as an alternative to the recommended dose of Tamiflu suspension.
Prevention of influenza
Post-exposure prevention
For adolescents (13 to 17 years of age) and adults: The recommended dose for prevention of influenza following close contact with an infected individual is 75 mg oseltamivir once daily for 10 days. Therapy should begin as soon as possible within two days of exposure to an infected individual.
For infants older than 1 year of age and for children 2 to 12 years of age: Tamiflu 30 mg and 45 mg capsules are available as an alternative to the recommended dose of Tamiflu suspension.
The recommended post-exposure prevention dose of Tamiflu is:
Body Weight Recommended dose for 10 days 15 kg30 mg once daily > 15 kg to 23 kg 45 mg once daily > 23 kg to 40 kg 60 mg once daily > 40 kg 75 mg once daily For dosing, an oral dispenser with 30 mg, 45 mg and 60 mg graduations is provided in the box. For accurate dosing, the oral dispenser supplied should be used exclusively.
It is recommended that Tamiflu powder for oral suspension be constituted by a pharmacist prior to dispensing to the patient.
Children weighing> 40 kg and who are able to swallow capsules may receive prophylaxis with a 75 mg capsule once daily for 10 days as an alternative to the recommended dose of Tamiflu suspension.
Prevention during an influenza epidemic in the community
The recommended dose for prevention of influenza during a community outbreak is 75 mg oseltamivir once daily for up to 6 weeks.
Special populations
Hepatic impairment
No dose adjustment is required either for treatment or for prevention in patients with hepatic dysfunction. No studies have been carried out in paediatric patients with hepatic disorder.
Renal impairment
Treatment of influenza: Dose adjustment is recommended for adults with severe renal impairment. Recommended doses are detailed in the table below.
Creatinine clearance Recommended dose for treatment > 30 (ml/min) 75 mg twice daily > 10 to 30 (ml/min)75 mg once daily, or 30 mg suspension twice daily, or 30 mg capsules twice daily 10 (ml/min)Not recommended dialysis patients Not recommended Prevention of influenza: Dose adjustment is recommended for adults with severe renal impairment as detailed in the table below.
Creatinine clearance Recommended dose for prevention > 30 (ml/min) 75 mg once daily > 10 to 30 (ml/min)75 mg every second day, or 30 mg suspension once daily, or 30 mg capsules once daily 10 (ml/min)Not recommended dialysis patients Not recommended - Child Dosage
There is insufficient clinical data available in children with renal impairment to be able to make any dosing recommendation.
- Elderly Dosage
No dose adjustment is required, unless there is evidence of severe renal impairment. - Contra Indications
Hypersensitivity to the active substance or to any of the excipients.
- Special Precautions
Oseltamivir is effective only against illness caused by influenza viruses. There is no evidence for efficacy of oseltamivir in any illness caused by agents other than influenza viruses.
The safety and efficacy of oseltamivir for the treatment and prevention of influenza in children of less than one year of age have not been established.
No information is available regarding the safety and efficacy of oseltamivir in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalisation.
The safety and efficacy of oseltamivir in either treatment or prevention of influenza in immunocompromised patients have not been established.
Efficacy of oseltamivir in the treatment of subjects with chronic cardiac disease and/or respiratory disease has not been established. No difference in the incidence of complications was observed between the treatment and placebo groups in this population.
Tamiflu is not a substitute for influenza vaccination. Use of Tamiflu must not affect the evaluation of individuals for annual influenza vaccination. The protection against influenza lasts only as long as Tamiflu is administered. Tamiflu should be used for the treatment and prevention of influenza only when reliable epidemiological data indicate that influenza virus is circulating in the community.
Severe renal impairment
Dose adjustment is recommended for both treatment and prevention in adults with severe renal insufficiency. There is insufficient clinical data available in children with renal impairment to be able to make any dosing recommendation.
This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
- Interactions
Pharmacokinetic properties of oseltamivir, such as low protein binding and metabolism independent of the CYP450 and glucuronidase systems, suggest that clinically significant drug interactions via these mechanisms are unlikely.
No dose adjustment is required when co-administering with probenecid in patients with normal renal function. Co-administration of probenecid, a potent inhibitor of the anionic pathway of renal tubular secretion, results in an approximate 2-fold increase in exposure to the active metabolite of oseltamivir.
Oseltamivir has no kinetic interaction with amoxicillin, which is eliminated via the same pathway, suggesting that oseltamivir interaction with this pathway is weak.
Clinically important drug interactions involving competition for renal tubular secretion are unlikely, due to the known safety margin for most of these substances, the elimination characteristics of the active metabolite (glomerular filtration and anionic tubular secretion) and the excretion capacity of these pathways. However, care should be taken when prescribing oseltamivir in subjects when taking co-excreted agents with a narrow therapeutic margin (e.g., chlorpropamide, methotrexate, phenylbutazone).
No pharmacokinetic interactions between oseltamivir or its major metabolite have been observed when co-administering oseltamivir with paracetamol, acetyl-salicylic acid, cimetidine or with antacids (magnesium and aluminium hydroxides and calcium carbonates).
- Adverse Drug Reactions
The overall safety profile of Tamiflu is based on data from 2107 adult and 1032 paediatric patients treated for influenza, and on data from 2914 adult and 99 paediatric patients receiving Tamiflu for the prophylaxis of influenza in clinical trials.
In adults, the most commonly reported adverse drug reactions (ADRs) were vomiting and nausea in the treatment studies, and nausea and headache in the prevention studies. The majority of these ADRs were reported on a single occasion on either the first or second treatment day and resolved spontaneously within 1-2 days. In children, the most commonly reported adverse drug reaction was vomiting.
The ADRs listed in the tables below fall into the following categories: Very Common (
1/10), Common (1/100 to < 1/10), Uncommon (1/1,000 to < 1/100), Rare (1/10,000 to < 1/1,000), Very rare (< 1/10,000) and not known (cannot be estimated from the available data). ADRs are added to the appropriate category in the tables according to the pooled analysis from clinical trials. Within each frequency grouping ADRs are presented in the order of decreasing seriousness.Treatment and prevention of influenza in adults and adolescents:
Most Frequent Adverse Drug Reactions (
1 % in the oseltamivir group) in Studies Investigating Tamiflu for Treatment and Prevention of Influenza in Adults and Adolescents or Through Post-Marketing SurveillanceSystem Organ Class (SOC)
Frequency Category
Adverse Drug Reaction
Percentage of Patients Experiencing the ADR
Treatment
Prevention
Oseltamivir
75 mg bid
(n = 1057)
Placebo
(n = 1050)
Oseltamivir
75 mg od
(n = 1480)
Placebo
(n = 1434)
Infections and infestations
Common :
Bronchitis
4 %
5 %
1 %
1 %
Bronchitis acute
1 %
1 %
0 %
< 1 %
Upper respiratory tract infections
0 %
0 %
8 %
8 %
Psychiatric disorders
Uncommon :
Hallucinationa
< 1 %
0 %
< 1 %
0 %
Nervous system disorders
Very Common :
Headache
2 %
2 %
20 %
18 %
Common :
Insomnia
1 %
1 %
1 %
1 %
Uncommon :
Convulsiona
< 1 %
0 %
0 %
0 %
Disorders of the ear and labyrinth
Common :
Vertigo
1 %
1 %
< 1 %
< 1 %
Respiratory, thoracic and mediastinal disorders
Common :
Cough
1 %
1 %
6 %
6 %
Rhinorrhoea
< 1 %
0 %
2 %
1 %
Gastrointestinal disorders
Very Common:
Nauseab,c
11 %
7 %
8 %
4 %
Common:
Vomitingc
8 %
3 %
2 %
1 %
Abdominal pain
2 %
2 %
2 %
2 %
Diarrhoea
6 %
8 %
3 %
3 %
Dyspepsia
1 %
1 %
2 %
2 %
Skin and subcutaneous tissue disorders
Uncommon :
Dermatitisa
< 1 %
< 1 %
1 %
1 %
Rasha
< 1 %
< 1 %
< 1 %
< 1 %
Urticariaa
< 1 %
< 1 %
< 1 %
< 1 %
Eczemaa
< 1 %
0 %
< 1 %
< 1 %
General disorders
Common :
Dizziness
2 %
3 %
2 %
2 %
Fatigue
1 %
1 %
8 %
8 %
Pain
< 1 %
< 1 %
4 %
3 %
a These are events identified during post-marketing surveillance. They were also reported in the pooled clinical studies the incidence presented in the table above.
b .Subjects who experienced nausea alone; excludes subjects who experienced nausea in association with vomiting.
c The difference between the placebo and oseltamivir groups was statistically significant.
Treatment and prevention of influenza in children:
The table below shows the most frequently reported ADRs from paediatric clinical trials.
Most Frequent Adverse Drug Reactions (
1 % in the oseltamivir group in the treatment studies and 10 % in the oseltamivir group in the prophylaxis study) in ChildrenSystem Organ Class (SOC)
Frequency Category
Adverse Drug Reaction
Percentage of Patients Experiencing the ADR
Treatment
Treatment
Preventiona
Oseltamivir
2 mg/kg bid
(n=515)
Placebo
(n=517)
Oseltamivir
30 to 75 mgb
(n=158)
Oseltamivir
30 to 75 mgb
(n=99)
Infections and infestations
Common :
Pneumonia
2 %
3 %
0 %
0 %
Sinusitis
2 %
3 %
0 %
0 %
Bronchitis
2 %
2 %
2 %
0 %
Otitis media
9 %
11 %
1 %
2 %
Disorders of the blood and lymphatic system
Common :
Lymphadenopathy
1 %
2 %
< 1 %
0 %
Respiratory, thoracic and mediastinal disorders
Common :
Asthma (incl. aggravated)
4 %
4 %
0 %
1 %
Epistaxis
3 %
3 %
1 %
1 %
Gastrointestinal disorder
Very Common :
Vomiting
15 %
9 %
20 %
10 %
Diarrhoea
10 %
11 %
3 %
1 %
Common :
Nausea
3 %
4 %
6 %
4 %
Abdominal pain
5 %
4 %
2 %
1 %
Disorders of the eye
Common:
Conjunctivitis
1 %
< 1 %
0 %
0 %
Disorders of the ear and labyrinth
Common :
Ear disorderc
2 %
1 %
0 %
0 %
Tympanic membrane disorder
1 %
1 %
0 %
0 %
Skin and subcutaneous tissue disorders
Common :
Dermatitis
1 %
2 %
< 1 %
0 %
a The prevention study did not contain a placebo arm, i.e. was an uncontrolled study.
b Unit dose = weight-based dosing.
c Patients experienced ear ache and ear pain.
In general, the adverse event profile in children with pre-existing bronchial asthma was qualitatively similar to that of otherwise healthy children.
Further post marketing surveillance data on selected serious adverse drug reactions:
Immune system disorders
Frequency not known: hypersensitivity reactions, including anaphylactic/anaphylactoid reactions.
Psychiatric disorders and nervous system disorders
Frequency not known: influenza can be associated with a variety of neurologic and behavioural symptoms which can include events such as hallucinations, delirium, and abnormal behaviour, in some cases resulting in fatal outcomes. These events may occur in the setting of encephalitis or encephalopathy but can occur without obvious severe disease.
In patients with influenza who were receiving Tamiflu, there have been postmarketing reports of convulsions and delirium (including symptoms such as altered level of consciousness, confusion, abnormal behaviour, delusions, hallucinations, agitation, anxiety, nightmares), in a very few cases resulting in accidental injury or fatal outcomes. These events were reported primarily among paediatric and adolescent patients and often had an abrupt onset and rapid resolution. The contribution of Tamiflu to those events is unknown. Such neuropsychiatric events have also been reported in patients with influenza who were not taking Tamiflu.
Eye disorders
Frequency not known: visual disturbance.
Cardiac disorders
Frequency not known: cardiac arrhythmia.
Gastrointestinal disorders
Frequency not known: gastrointestinal bleedings and hemorrhagic colitis.
Hepato-biliary disorders
Frequency not known: hepato-biliary system disorders, including hepatitis and elevated liver enzymes in patients with influenza-like illness. These cases include fatal fulminant hepatitis/hepatic failure.
Skin and subcutaneous tissue disorders
Frequency not known: severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme and angioneurotic oedema.
Additional information on special populations:
There were no clinically relevant differences in the safety population of the elderly subjects who received oseltamivir or placebo compared with the adult population aged up to 65 years.
The adverse event profile in adolescents and patients with chronic cardiac and/or respiratory disease was qualitatively similar to those of healthy young adults.