Amantadine and
rimantadine are recommended for the treatment and prophylaxis of
influenza A
infections, and constitute an integral component of
influenza control measures in the
nursing home setting. However, optimal use necessitates a thorough understanding of the toxicity profiles of these agents, as well as strategies to reduce the risk of adverse reactions. Adverse reactions of these compounds predominantly involve the gastrointestinal tract and the central nervous system (CNS), including hyperexcitability, slurred speech,
tremors,
insomnia,
dizziness, mood disturbance,
ataxia,
psychosis and
fatigue. Based on data from comparative trials,
rimantadine appears to exhibit a lesser propensity to cause adverse CNS reactions than
amantadine, but a similar propensity to cause adverse gastrointestinal reactions. Factors enhancing the risk of adverse reactions to these agents include reduced renal function (especially for
amantadine),
drug-drug interactions with cationic drugs, which inhibit
amantadine renal tubular secretion (e.g.
trimethoprim,
triamterene, and possibly
cimetidine and
procainamide), elevated peak and trough plasma concentrations, and a history of
seizures. Careful attention to published dosage adjustment guidelines for these compounds, avoidance of interacting drugs and avoiding these agents in patients with a history of
seizures may be the best means to reduce the risk of toxicity in elderly patients.
Rimantadine may have an advantage over
amantadine in the elderly population in light of its lesser propensity to cause adverse reactions, less complex dosage adjustment in the case of renal impairment and probable lack of
drug-drug interaction potential with cationic drugs.