Therapeutic Uses

Amantadine and rimantadine are effective for the prevention and treatment of influenza A virus infections. Seasonal prophylaxis with either drug (a total of 200 mg/day in one or two divided doses in young adults) is ~70-90% protective against influenza A illness. Efficacy has been shown during pandemic influenza, in preventing nosocomial influenza, and in curtailing nosocomial outbreaks. Doses of 100 mg/day are better tolerated yet still protective against influenza. Postexposure prophylaxis with either drug provides protection of exposed family contacts if ill young children are not concurrently treated.

Seasonal prophylaxis is an alternative in high-risk patients if the influenza vaccine cannot be administered or may be ineffective due to impaired immunity. Prophylaxis should be started as soon as influenza is identified in a community and continued for the period of risk (usually 4-8 weeks). Alternatively, the drugs can be started in conjunction with immunization and continued for 2 weeks until protective immunity develops.

In uncomplicated influenza A illness of adults, early amantadine or rimantadine treatment (200 mg/day for 5 days) reduces duration of fever and systemic complaints by 1-2 days, speeds functional recovery, and may decrease the duration of virus shedding. In children, rimantadine treatment may be associated with less illness and lower viral titers during the first 2 days of treatment, but treated children have more prolonged virus shedding. The optimal dose and duration of therapy in children are not established.

Resistant variants have been recovered from ~30% of treated outpatient children or adults by the fifth day of therapy. Resistant variants also arise commonly in immunocompromised patients and inpatient children. Illnesses owing to apparent transmission of resistant virus associated with failure of drug prophylaxis have been documented in contacts of drug-treated ill persons in households and in nursing homes. Resistant variants appear to be pathogenic and can cause typically disabling influenza.

Oseltamivir chemistry and antiviral activity Oseltamivir carboxylate [(3R, 4R, 5S)-4-acetylamino-5-amino-3(1-ethylpropoxyl)-1-cyclohexene-1-carboxylic acid] is a sialic acid analog that potently inhibits influenza virus neuraminidases.

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