Amantadine and rimantadine for preventing and treating influenza A in adults

BACKGROUND: Amantadine hydrochloride and rimantadine hydrochloride have antiviral properties, but they are not widely used due to a lack of knowledge of their properties and concerns about possible adverse effects. OBJECTIVES: The objective of this review was to assess the effects and safety of amantadine and rimantadine in healthy adults. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles. We also contacted manufacturers, researchers and authors. SELECTION CRITERIA: Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control antivirals or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults. DATA COLLECTION AND ANALYSIS: For prevention trials the numbers of participants with clinically defined influenza, with serologically confirmed clinical influenza A and adverse effects were analysed. Analysis for treatment trials was of the mean duration of fever and adverse effects. MAIN RESULTS: Amantadine prevented 23% of clinical influenza cases (95% confidence interval 11% to 34%), and 63% of serologically confirmed clinical influenza A cases (95% confidence interval 42% to 76%). Amantadine reduced duration of fever by one day (95% confidence interval 0.7 to 1.3). Rimantadine demonstrated comparable effectiveness, but there were fewer trials and the results for prevention were not statistically significant. Both amantadine and rimantadine induced significant gastrointestinal adverse effects. Adverse effects of the central nervous system adverse and study withdrawals were significantly more common with amantadine than rimantadine. REVIEWER'S CONCLUSIONS: Amantadine and rimantadine have comparable effectiveness in the prevention and treatment of influenza A in healthy adults, although rimantadine induces fewer adverse effects than amantadine.