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Included as part of the PRECAUTIONS section.

Serious Skin/Hypersensitivity Reactions

Cases of anaphylaxis and serious skin reactions including toxic epidermal necrolysis, Stevens-Johnson Syndrome, and erythema multiforme have been reported in postmarketing experience with TAMIFLU (oseltamivir phosphate) . TAMIFLU (oseltamivir phosphate) should be stopped and appropriate treatment instituted if an allergic-like reaction occurs or is suspected.

Neuropsychiatric Events

Influenza can be associated with a variety of neurologic and behavioral symptoms that can include events such as hallucinations, delirium, and abnormal behavior, 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.

There have been postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving TAMIFLU (oseltamivir phosphate) . Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made but they appear to be uncommon based on TAMIFLU (oseltamivir phosphate) usage data. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of TAMIFLU (oseltamivir phosphate) to these events has not been established. Closely monitor patients with influenza for signs of abnormal behavior. If neuropsychiatric symptoms occur, evaluate the risks and benefits of continuing treatment for each patient.

Bacterial Infections

Serious bacterial infections may begin with influenza-like symptoms or may coexist with or occur as complications during the course of influenza. TAMIFLU (oseltamivir phosphate) has not been shown to prevent such complications.

Limitations of Populations Studied

Efficacy of TAMIFLU (oseltamivir phosphate) in the treatment of influenza in patients 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. No information is available regarding treatment of influenza in patients with any medical condition sufficiently severe or unstable to be considered at imminent risk of requiring hospitalization.

Efficacy of TAMIFLU (oseltamivir phosphate) for treatment or prophylaxis of influenza has not been established in immunocompromised patients.

Patient Counseling Information

See FDA-approved Patient Labeling.

Information for Patients

Patients and/or caregivers should be advised of the risk of severe allergic reactions (including anaphylaxis) or serious skin reactions and should stop TAMIFLU (oseltamivir phosphate) and seek immediate medical attention if an allergic-like reaction occurs or is suspected.

Patients and/or caregivers should be advised of the risk of neuropsychiatric events in patients with influenza and should contact their physician if they experience signs of abnormal behavior while receiving TAMIFLU (oseltamivir phosphate) . Their physician will determine if TAMIFLU (oseltamivir phosphate) treatment should be continued.

Instruct patients to begin treatment with TAMIFLU (oseltamivir phosphate) as soon as possible from the first appearance of flu symptoms. Similarly, prevention should begin as soon as possible after exposure, at the recommendation of a physician.

Instruct patients to take any missed doses as soon as they remember, except if it is near the next scheduled dose (within 2 hours), and then continue to take TAMIFLU (oseltamivir phosphate) at the usual times.

TAMIFLU (oseltamivir phosphate) is not a substitute for a flu vaccination. Patients should continue receiving an annual flu vaccination according to guidelines on immunization practices.

A bottle of 13 g TAMIFLU (oseltamivir phosphate) for oral suspension contains approximately 11 g sorbitol. One dose of 75 mg TAMIFLU (oseltamivir phosphate) for oral suspension delivers 2 g sorbitol. For patients with hereditary fructose intolerance, this is above the daily maximum limit of sorbitol and may cause dyspepsia and diarrhea.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

In 2-year carcinogenicity studies in mice and rats given daily oral doses of the prodrug oseltamivir phosphate up to 400 mg/kg and 500 mg/kg, respectively, the prodrug and the active form oseltamivir carboxylate induced no statistically significant increases in tumors over controls. The mean maximum daily exposures to the prodrug in mice and rats were approximately 130- and 320-fold, respectively, greater than those in humans at the proposed clinical dose based on AUC comparisons. The respective safety margins of the exposures to the active oseltamivir carboxylate were 15- and 50-fold.

Oseltamivir was found to be non-mutagenic in the Ames test and the human lymphocyte chromosome assay with and without enzymatic activation and negative in the mouse micronucleus test. It was found to be positive in a Syrian Hamster Embryo (SHE) cell transformation test. Oseltamivir carboxylate was non-mutagenic in the Ames test and the L5178Y mouse lymphoma assay with and without enzymatic activation and negative in the SHE cell transformation test.

In a fertility and early embryonic development study in rats, doses of oseltamivir at 50, 250, and 1500 mg/kg/day were administered to females for 2 weeks before mating, during mating and until day 6 of pregnancy. Males were dosed for 4 weeks before mating, during mating, and for 2 weeks after mating. There were no effects on fertility, mating performance or early embryonic development at any dose level. The highest dose was approximately 100 times the human systemic exposure (AUC_0-24h) of oseltamivir carboxylate.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are insufficient human data upon which to base an evaluation of risk of TAMIFLU (oseltamivir phosphate) to the pregnant woman or developing fetus. Studies for effects on embryo-fetal development were conducted in rats (50, 250, and 1500 mg/kg/day) and rabbits (50, 150, and 500 mg/kg/day) by the oral route. Relative exposures at these doses were, respectively, 2, 13, and 100 times human exposure in the rat and 4, 8, and 50 times human exposure in the rabbit. Pharmacokinetic studies indicated that fetal exposure was seen in both species. In the rat study, minimal maternal toxicity was reported in the 1500 mg/kg/day group. In the rabbit study, slight and marked maternal toxicities were observed, respectively, in the 150 and 500 mg/kg/day groups. There was a dose-dependent increase in the incidence rates of a variety of minor skeletal abnormalities and variants in the exposed offspring in these studies. However, the individual incidence rate of each skeletal abnormality or variant remained within the background rates of occurrence in the species studied.

Because animal reproductive studies may not be predictive of human response and there are no adequate and well-controlled studies in pregnant women, TAMIFLU (oseltamivir phosphate) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

In lactating rats, oseltamivir and oseltamivir carboxylate are excreted in the milk. It is not known whether oseltamivir or oseltamivir carboxylate is excreted in human milk. TAMIFLU (oseltamivir phosphate) should, therefore, be used only if the potential benefit for the lactating mother justifies the potential risk to the breast-fed infant.

Pediatric Use

The safety and efficacy of TAMIFLU (oseltamivir phosphate) in pediatric patients younger than 1 year of age have not been studied. TAMIFLU (oseltamivir phosphate) is not indicated for either treatment or prophylaxis of influenza in pediatric patients younger than 1 year of age because of the unknown clinical significance of nonclinical animal toxicology data for human infants [see Nonclinical Toxicology].

Geriatric Use

Of the total number of subjects in clinical studies of TAMIFLU (oseltamivir phosphate) for the treatment of influenza, 19% were 65 and over, while 7% were 75 and over. Of the total number of patients in clinical studies of TAMIFLU (oseltamivir phosphate) for the prophylaxis of influenza, 25% were 65 and over, while 18% were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects.

The safety of TAMIFLU (oseltamivir phosphate) in geriatric subjects has been established in clinical studies that enrolled 741 subjects (374 received placebo and 362 received TAMIFLU (oseltamivir phosphate) ). Some seasonal variability was noted in the clinical efficacy outcomes [see Clinical Studies].

Safety and efficacy have been demonstrated in elderly residents of nursing homes who took TAMIFLU (oseltamivir phosphate) for up to 42 days for the prevention of influenza. Many of these individuals had cardiac and/or respiratory disease, and most had received vaccine that season [see Clinical Studies].

Renal Impairment

Dose adjustment is recommended for patients with a serum creatinine clearance between 10 and 30mL/min [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY]. No recommended dosing regimens are available for patients with end-stage renal disease undergoing routine hemodialysis or continuous peritoneal dialysis treatment.

Hepatic Impairment

No dosage adjustment is required in patients with mild to moderate hepatic impairment. The safety and pharmacokinetics in patients with severe hepatic impairment have not been evaluated [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 2/7/2011
This monograph has been modified to include the generic and brand name in many instances.