Rimantadine: a clinical perspective.
OBJECTIVE
To provide a review of rimantadine, including its antiviral activity, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration. Information on influenza A virus and clinical features of influenza disease are presented. Comparative data on rimantadine and amantadine are described.


METHODS
A MEDLINE search restricted to English-language literature published from 1966 through 1994 and an extensive review of journals was conducted.


METHODS
The data on antiviral activity, pharmacokinetics, adverse effects, and drug interactions were obtained from various articles on rimantadine in open and controlled studies. Controlled double-blind studies were evaluated to assess the efficacy of rimantadine in prophylaxis and treatment of influenza A infection.


RESULTS
Over 90% of a rimantadine dose was absorbed in 3-6 hours in healthy adults. Steady-state plasma concentrations have ranged from 0.10 to 2.60 micrograms/mL at doses of 3 mg/kg/d in infants to 100 mg twice daily in the elderly. Nasal fluid concentrations of rimantadine at steady-state were 1.5 times higher than plasma concentrations, which may explain the effectiveness of rimantadine despite a low plasma concentration. Over 75% of a rimantadine dose was metabolized in the liver, and the parent compound and metabolites were almost completely eliminated by the kidneys. The elimination half-life ranged from 24.8 to 36.5 hours, which allows once-daily dosing. Dosage adjustment is recommended for patients with severe renal impairment (creatinine clearance < or = 0.17 mL/s), severe hepatic dysfunction, or elderly nursing home patients. Drug-resistant strains of influenza A virus to rimantadine occurred in several studies with children and/or adults. Clinical significance of drug-resistant strains has not been established. Rimantadine appeared to be effective in 85-90% of individuals for prevention of influenza A illness and in 50-65% for prevention of influenza A infection. Rimantadine reduced the time to a 50% reduction in symptoms by 1-3 days versus placebo. Differences in symptom reduction between rimantadine and placebo after the first 3 days of treatment was not generally clinically significant. The most common adverse effects of rimantadine administration were associated with the central nervous system (CNS) and the gastrointestinal (GI) tract. CNS-related adverse effects occurred in 3.2% of children younger than 10 years of age and 8.4% of adults. In elderly patients, the incidence of CNS-related adverse effects ranged from 4.9% at 100 mg/d to 12.5% at 200 mg/d. GI adverse effects occurred in 8.4% of children younger than 10 years of age, 3.1% of adults, and 2.9% at 100 mg/d and 17.0% at 200 mg/d in the elderly.


CONCLUSIONS
Rimantadine offers some desirable features for the treatment and prophylaxis of influenza A infection. It appears to be an attractive choice in elderly patients with a history of CNS adverse effects from amantadine and in patients with mild or moderate renal impairment. Although approved for twice-daily dosing, rimantadine has a pharmacokinetic profile that would allow once-daily dosing. It is effective for prophylaxis (not postexposure prophylaxis) and treatment of influenza A virus. It also has a low incidence of adverse effects.
Wintermeyer
S M
SM
Ohio State University, Columbus 43210, USA.
Nahata
M C
MC
D000042:Absorption; D000547:Amantadine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D018849:Controlled Clinical Trials as Topic; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D009980:Influenza A virus / Q000302:isolation & purification; D007251:Influenza, Human / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D007676:Kidney Failure, Chronic / Q000150:complications / Q000378:metabolism; D008107:Liver Diseases / Q000150:complications / Q000378:metabolism; D012299:Rimantadine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology
D012299:Rimantadine; D000547:Amantadine