Prevention and control of influenza by chemoprophylaxis and chemotherapy. Prospects from examination of recent experience

Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in 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.…”

“…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).…”

Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics

“…At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms (33% of amantadine versus 9% of rimantadine recipients; P < 0.001) and sleep disturbance (39 versus 13%; P < 0.001), but not gastrointestinal symptoms (19.5 versus 16.0o). However, no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations.…”

“…However, no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations. Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations.Clinical trials have documented that amantadine hydrochloride (8,12,16,20,28) and its analog rimantadine hydrochloride (6,12,23,28,29) are effective drugs for the prophylaxis and treatment of influenza A virus infection. However, widespread use of amantadine has been limited in part by concern about its side effects.…”

“…Most studies of amantadine prophylaxis have documented minimal toxicity at a dosage of 200 mg/day (16,20,22 484,1978), but the frequency and severity of side effects increase with increasing dosage (15,16,25). Rimantadine has been considered to be better tolerated in humans than amantadine (12), although conflicting results have been reported from studies of their relative toxicities (22; Noble et al, ICAAC 1978, abstr.…”