Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults

Abstract

The relative toxicities of amantadine and rimantadine 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) Clinical trials have documented that amantadine hydrochloride (7,11,14,17,18,22 483, 1978) and rimantadine hydrochloride (6,11,26,33) are effective prophylactic and therapeutic drugs in influenza A virus infections. Several in vitro (10, 31) and animal (1, 28, 31) models have suggested that rimantadine has greater antiviral activity than amantadine against influenza A viruses. However, the relative effectiveness of the two compounds in human infections has not been fully defined.Available information regarding the relative toxicities of the two compounds in humans is also inconclusive. Most studies of amantadine prophylaxis with a dose of 200 mg/day have described few side effects (14,22,25 484, 1978). However, recent work found substantial rates of subjective central nervous system (CNS) complaints and possible adverse effects on objective measures of psychomotor performance at this dosage (4). Rimantadine has been considered to be better tolerated in humans (11), but several studies (25; Noble et al., 18th ICAAC, abstr. no. 484) have not confirmed this observation. Optimal antiviral and therapeutic effects in treatment of influenza A virus infections would likely be achieved with administration of higher drug dosages. If lower drug toxicity were confirmed for rimantadine, then it would be an appropriate candidate for future chemotherapy studies in which higher dosages are used.The present study was undertaken to compare the relative toxicities of equivalent doses of amantadine and rimantadine. Both subjective and objective measures of potential drug side effects were studied at conventional (200 mg/ day) and higher (300 mg/day) dosages in healthy adults. Our results indicated that both drugs were well tolerated at the lower dosage, but that rimantadine was significantly better tolerated than amantadine at a dosage of 300 mg/day.

Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine

“…Van Voris and co-workers (16) found that 33% of amantadine recipients experienced minor central nervous system side effects by day 5 of therapy, but less than 5% failed to take all medications. Hayden et al (9) concluded that 200 mg of amantadine daily was very well tolerated by healthy volunteers over a short treatment period, although 300 mg daily lead to unacceptable side effects. Bryson et al (2) also described central nervous system side effects in 33% of a large group of college students treated with 200 mg of amantadine daily for 4 weeks.…”

Zanamivir: from drug design to the clinic

“…Until recently, the adjuncts to vaccination were limited to the use of the M2 inhibitors amantadine or rimantadine. However, their use has not gained wide acceptance due in part to their ine¡ectiveness against in£uenza B, the rapid emergence of drug-resistant variants Hayden et al 1989;Hayden 1994) and their poor adverse event pro¢le (Hayden et al 1981(Hayden et al , 1983. Furthermore, the e¡ectiveness of amantadine or rimantadine in severe in£uenza or in patients at high risk of developing in£uenza-related complications is uncertain.…”

Crystal structure of 5-(adamantan-1-yl)-3-[(4-chloroanilino)methyl]-2,3-dihydro-1,3,4-oxadiazole-2-thione, C19H22ClN3OS

“…Several adamantane derivatives are currently used as e cient therapies against in uenza [3][4][5], herpes simplex [6] and HIV [7][8][9] viruses. In addition, numerous adamantane derivatives were reported to exhibit marked anticancer [10,11], antibacterial [12][13][14][15] and antifungal [16] activities.…”