Tamiflu Adverse Reactions

Clinical Trials: Summary of Safety Profile: The overall safety profile of Tamiflu is based on data from 2646 adult/adolescent and 859 paediatric patients with influenza, and on data from 1943 adult/adolescent and 148 paediatric patients receiving Tamiflu for the prophylaxis of influenza in clinical trials. In adult/adolescent treatment studies, the most frequently reported adverse drug reactions (ADRs) were nausea, vomiting and headache. The majority of these ADRs were reported on a single occasion, occurred on either the first or second treatment day and resolved spontaneously within 1-2 days. In adult/adolescent prophylaxis studies, the most frequently reported ADRs were nausea, vomiting, headache and pain. In children, the most commonly reported ADR was vomiting. In the majority of patients, these events did not lead to discontinuation of Tamiflu.
Tabulated summary of adverse drug reactions from clinical trials: Adverse drug reactions from clinical trials are listed according to the MedDRA system organ class. The corresponding frequency category for each adverse drug reaction (Table 5) is based on the following convention: 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).
Treatment and Prophylaxis of Influenza in Adults and Adolescents: In adult/adolescent treatment and prophylaxis studies, ADRs that occurred the most frequently (≥1%) at the recommended dose (75 mg b.i.d. for 5 days for treatment and 75 mg o.d. for up to 6 weeks for prophylaxis), and whose incidence is at least 1% higher on Tamiflu compared to placebo, are shown in Table 5.
The population included in the influenza treatment studies comprised of otherwise healthy adults/adolescents and patients "at risk" (patients at higher risk of developing complications associated with influenza, e.g. elderly patients and patients with chronic cardiac or respiratory disease). In general, the safety profile in the patients "at risk" was qualitatively similar to that in otherwise healthy adults/adolescents.
The safety profile reported in the subjects that received the recommended dose of Tamiflu for prophylaxis (75 mg once daily for up to 6 weeks) was qualitatively similar to that seen in the treatment studies (Table 5), despite a longer duration of dosing in the prophylaxis studies. (See Table 5.)

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Treatment and Prophylaxis of Influenza in Children ≥1 year of age: A total of 1481 children (including otherwise healthy children aged 1-12 and asthmatic children aged 6-12) participated in clinical studies of oseltamivir given for the treatment of influenza. A total of 859 children received treatment with oseltamivir suspension.
The ADR that occurred in ≥1% of children aged 1 to 12 years receiving oseltamivir in the clinical trials for treatment of naturally acquired influenza (n=859), and whose incidence is at least 1% higher on Tamiflu compared to placebo (n=622), is vomiting (16% on oseltamivir vs. 8% on placebo). Amongst the 148 children who received the recommended dose of Tamiflu once daily in a post-exposure prophylaxis study in households (n=99), and in a separate 6-week paediatric prophylaxis study (n=49), vomiting was the most frequent ADR (8% on oseltamivir vs. 2% in the no prophylaxis group). Tamiflu was well tolerated in these studies and the adverse events noted were consistent with those previously observed in paediatric treatment studies.
Data in Children under 1 Year of Age: In two studies to characterize the pharmacokinetics, pharmacodynamics and safety profile of oseltamivir therapy in 124 influenza infected children less than one year of age, the safety profile was similar among age cohorts with vomiting, diarrhea and diaper rash being the most frequently reported AEs (see Pharmacology: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions). Insufficient data are available for infants who have a post-conceptual age of less than 36 weeks.
Safety information available on Tamiflu administered for treatment of influenza in children less than 1 year of age from prospective and retrospective observational trials (comprising together more than 2400 children of that age class), epidemiological database research and post-marketing reports suggest that the safety profile in children less than 1 year of age is similar to the established safety profile of children aged 1 year and above.
Treatment and Prophylaxis of Influenza in Geriatric patients: There were no clinically relevant differences in the safety profile of the 942 subjects, 65 years of age and older, who received Tamiflu or placebo, compared with the younger population (aged up to 65 years).
Treatment and Prophylaxis of Influenza in Immunocompromised subjects: The treatment of influenza in immunocompromised patients were evaluated in two studies receiving standard dose or high dose regimens (double dose or triple dose) of Tamiflu (see Pharmacology: Pharmacodynamics: Clinical/Efficacy Studies under Actions). The safety profile of Tamiflu observed in these studies was consistent with that observed in previous clinical trials where Tamiflu was administered for treatment of influenza in non-immunocompromised patients across all age groups (otherwise healthy patients or "at risk" patients [i.e., those with respiratory and/or cardiac co-morbidities]). Both doses were well tolerated, with the percentage of patients reporting adverse events being lower in the standard dose group compared to the double dose group (49.0% vs 59.4 %, respectively). The most frequent ADR reported in immunocompromised children was vomiting (28%).
In a 12-week prophylaxis study in 475 immunocompromised subjects, including 18 children 1-12 years of age, the safety profile in the 238 subjects receiving Tamiflu was consistent with that previously observed in Tamiflu prophylaxis clinical trials.
Laboratory Abnormalities: No text.
Postmarketing Experience: The following adverse events have been identified during post-marketing use of Tamiflu. Because these events are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency and/or establish a causal relationship to Tamiflu exposure.
Skin and subcutaneous tissue disorder: Hypersensitivity reactions such as allergic skin reactions including dermatitis, rash, eczema, urticaria, erythema multiforme, allergy, anaphylactic/anaphylactoid reactions, face oedema, Stevens-Johnson-Syndrome and toxic epidermal necrolysis have been reported.
Hepatobiliary disorder: Hepatitis and elevated liver enzymes have been reported in patients with influenza-like illness receiving oseltamivir.
Psychiatric disorders/Nervous System Disorders: Convulsion and delirium (including symptoms such as altered level of consciousness, confusion, abnormal behaviour, delusions, hallucinations, agitation, anxiety, nightmares) have been reported during Tamiflu administration in patients with influenza, predominately in children and adolescents. In rare cases, these events resulted in accidental injury. 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.
Gastro-intestinal disorders: Gastro-intestinal bleedings were observed after the use of Tamiflu. In particular, hemorrhagic colitis was reported that subsided when the course of influenza abated or treatment with Tamiflu was interrupted.
Laboratory Abnormalities: Elevated liver enzymes have been reported in patients with influenza-like illness receiving oseltamivir (see Postmarketing Experience as previously mentioned).