A Controlled Trial of Amantadine and Rimantadine in the Prophylaxis of Influenza a Infection

• Published in: The New England journal of medicine Vol. 307; no. 10; pp. 580 - 584
• Main Authors: Dolin, Raphael, Reichman, Richard C, Madore, H. Paul, Maynard, Raina, Linton, Pamela N, Webber-Jones, Joan
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 02.09.1982
• Subjects: Adamantane - analogs & derivatives; Adolescent; Adult; Amantadine; Amantadine - adverse effects; Amantadine - therapeutic use; Antimicrobial agents; Antiviral drugs; Chemotherapy; Clinical Trials as Topic; Disease prevention; Enzymes; Family medical history; Health surveillance; Humans; Illnesses; Immunoglobulins; Infant, Newborn; Infections; Infectious diseases; Influenza; Influenza A; influenza A virus; Influenza A virus - isolation & purification; Influenza, Human - epidemiology; Influenza, Human - prevention & control; Laboratory animals; Middle Aged; Outbreaks; Patient Compliance; Prophylaxis; Random Allocation; Respiratory diseases; Rimantadine - adverse effects; Rimantadine - therapeutic use; Viruses; Volunteers
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJM198209023071002

Four hundred fifty volunteers participated in a placebo-controlled, double-blind, randomized trial of the prophylactic effects of rimantadine and amantadine during an outbreak of influenza A. The subjects received drugs orally at a dose of 100 mg twice a day for six weeks. Influenza-like illness occurred in 41 per cent of the subjects receiving placebo but in only 14 per cent of those receiving rimantadine and 9 per cent of those receiving amantadine (P<0.001 for either drug vs. placebo). Laboratory-documented influenza occurred in 21 per cent of placebo recipients, 3 per cent of rimantadine recipients, and 2 per cent of amantadine recipients (P<0.001). These findings represent efficacy rates of 85 per cent for rimantadine and 91 per cent for amantadine, as compared with placebo. More recipients of amantadine (13 per cent) than recipients of rimantadine (6 per cent; P<0.05) or placebo (4 per cent; P<0.01) withdrew from the study because of Central-nervous-system side effects. On the basis of this study, rimantadine appears to be the drug of choice for the prophylaxis of influenza A. (N Engl J Med. 1982; 307: 580–4.) AMANTADINE hydrochloride (1-adamantanamine hydrochloride) was licensed in 1966 for the prophylaxis of infections with influenza A viruses of the H2N2 subtype, and it has subsequently been approved for the prophylaxis of infections with all influenza A subtypes. Despite accumulated evidence of the efficacy of amantadine in the prophylaxis of influenza in human beings, 1 2 3 4 5 6 the drug has received relatively little use for this purpose. In part, this has been a result of continued challenges to the evidence of its efficacy by some workers, 7 as well as concern over its reported side effects, which have varied considerably in frequency from study to . . .