Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults

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Abstract
The relative toxicities of amantadine and rimantadine [used in prophylactic and therapeutic treatment of influenza A virus infections] were compared in a double-blind, placebo-controlled study involving healthy adults. In separate studies, drugs were administered at a dosage of 200 mg/day (52 volunteers) or 300 mg/day (196 volunteers) for 4.5 days. Both drugs were well tolerated at the lower dosage. At 300 mg/day amantadine recipients had a greater frequency and severity of CNS (nervousness, lightheadedness, difficulty concentrating) and sleep (insomnia, fatigue) complaints compared with rimantadine or placebo recipients. Amantadine recipients performed less well on an objective test measuring sustained attention and problem-solving ability. Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients. Because of better tolerance at higher dosage, rimantadine offers more promise than amantadine for treatment of influenza A virus infections.