TAMIFLU*
Indications and Usage
TAMIFLU is indicated for the treatment of uncomplicated acute illness due to influenza infection in adults who have been symptomatic for no more than 2 days. This indication is based on studies of naturally occurring influenza in which the predominant infection was influenza A, and influenza challenge studies in which antiviral activity of TAMIFLU was supported for influenza A and B (see Description of Clinical Studies and PRECAUTIONS ).
Description of Clinical Studies
Naturally Occurring Influenza Trials: Two phase 3 placebo-controlled and double-blind clinical trials were conducted: one in the USA and one outside the USA. Patients were eligible for these trials if they had fever >100°F, accompanied by at least one respiratory symptom (cough, nasal symptoms or sore throat) and at least one systemic symptom (myalgia, chills/sweats, malaise, fatigue or headache) and influenza virus was known to be circulating in the community. In addition, all patients enrolled in the trials were allowed to take fever-reducing medications. Of 1355 patients enrolled in these two trials, 849 (63%) patients were influenza-infected (age range 18 to 65 years; median age 34 years; 52% male; 90% Caucasian; 31% smokers). Of these 849 patients, 95% were infected with influenza A, 3% with influenza B, and 2% with influenza of unknown type. TAMIFLU was started within 40 hours of onset of symptoms. Subjects participating in the trials were required to self-assess the influenza-associated symptoms as "none," "mild," "moderate" or "severe." Time to improvement was calculated from the time of treatment initiation to the time when all symptoms (nasal congestion, sore throat, cough, aches, fatigue, headaches, and chills/sweats) were assessed as "none" or "mild." In both studies, at the recommended dose of TAMIFLU 75 mg twice daily for 5 days, there was a 1.3 day reduction in the median time to improvement in influenza-infected subjects receiving TAMIFLU compared to subjects receiving placebo. Subgroup analyses of these studies by gender showed no differences in the treatment effect of TAMIFLU in men and women. No increased efficacy was demonstrated in subjects receiving treatment of 150-mg TAMIFLU twice daily for 5 days.
Contraindications
TAMIFLU is contraindicated in patients with known hypersensitivity to any of the components of the product.
Precautions
General: There is no evidence for efficacy of TAMIFLU in any illness caused by agents other than influenza viruses Types A and B. Data on treatment of influenza B are limited (see INDICATIONS AND USAGE : Description of Clinical Studies ).
Efficacy of TAMIFLU in patients who begin treatment after 40 hours of symptoms has not been established.
Efficacy of TAMIFLU in 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. 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.
Use of TAMIFLU should not affect the evaluation of individuals for annual influenza vaccination in accordance with guidelines of the Center for Disease Controls and Prevention Advisory Committee on Immunization Practices. Efficacy of TAMIFLU has not been established for prophylactic use to prevent influenza.
Safety and efficacy of repeated treatment courses have not been studied.
Information for Patients
Patients should be instructed to begin treatment with TAMIFLU as soon as possible from the first appearance of flu symptoms.
Patients should be instructed 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 at the usual times.
TAMIFLU is not a substitute for a flu shot. Patients should continue receiving an annual flu shot according to guidelines on immunization practices.
Drug Interactions
Information derived from pharmacology and pharmacokinetic studies of oseltamivir suggests that clinically significant drug interactions are unlikely.
Oseltamivir is extensively converted to oseltamivir carboxylate by esterases, located predominantly in the liver. Drug interactions involving competition for esterases have not been extensively reported in literature. Low protein binding of oseltamivir and oseltamivir carboxylate suggests that the probability of drug displacement interactions is low.
* Available from Dr. Manso’s office.