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Bulletin of the World Health Organization logoLink to Bulletin of the World Health Organization
. 1985;63(1):51–56.

Current status of amantadine and rimantadine as anti-influenza-A agents: Memorandum from a WHO Meeting*

PMCID: PMC2536349  PMID: 3872736

Abstract

Amantadine (1-adamantanamine hydrochloride), an anti-influenza drug, effectively inhibits the replication of all human subtypes of influenza A virus (H1N1, H2N2 and H3N2) both in laboratory studies and in a variety of clinical situations in young and old persons. So far, it has been used on a relatively limited scale by community and hospital clinicians, partly because of concern over mild side-effects in approximately 6% of persons. The related compound, rimantadine (α-methyl-1-adamantane-methylamine hydrochloride), shows comparable antiviral activity with few or no side-effects. Although the mode of antiviral action is considered to be similar, the two drugs differ in their metabolic and pharmacological properties.

Both amantadine and rimantadine have therapeutic uses and shorten the duration of influenza-A-induced fever, malaise, and virus shedding. A dosage of 200 mg of either drug for a 3-5-day period is effective but treatment has to commence on the first day of symptoms. Prophylaxis, particularly using rimantadine, could be usefully initiated in elderly and other high-risk individuals living in institutions and in the general community.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alling D. W., Blackwelder W. C., Stuart-Harris C. H. A study of excess mortality during influenza epidemics in the United States, 1968-1976. Am J Epidemiol. 1981 Jan;113(1):30–43. doi: 10.1093/oxfordjournals.aje.a113063. [DOI] [PubMed] [Google Scholar]
  2. Bleidner W. E., Harmon J. B., Hewes W. E., Lynes T. E., Hermann E. C. Absorption, distribution and excretion of amantadine hydrochloride. J Pharmacol Exp Ther. 1965 Dec;150(3):484–490. [PubMed] [Google Scholar]
  3. Bukrinskaya A. G., Vorkunova N. K., Narmanbetova R. A. Rimantadine hydrochloride blocks the second step of influenza virus uncoating. Arch Virol. 1980;66(3):275–282. doi: 10.1007/BF01314742. [DOI] [PubMed] [Google Scholar]
  4. Centers for Disease Control (CDC) Influenza vaccine efficacy in nursing home outbreaks reported during 1981-1982. MMWR Morb Mortal Wkly Rep. 1982 Apr 23;31(15):190–195. [PubMed] [Google Scholar]
  5. DAVIES W. L., GRUNERT R. R., HAFF R. F., MCGAHEN J. W., NEUMAYER E. M., PAULSHOCK M., WATTS J. C., WOOD T. R., HERMANN E. C., HOFFMANN C. E. ANTIVIRAL ACTIVITY OF 1-ADAMANTANAMINE (AMANTADINE). Science. 1964 May 15;144(3620):862–863. doi: 10.1126/science.144.3620.862. [DOI] [PubMed] [Google Scholar]
  6. Dolin R., Reichman R. C., Madore H. P., Maynard R., Linton P. N., Webber-Jones J. A controlled trial of amantadine and rimantadine in the prophylaxis of influenza A infection. N Engl J Med. 1982 Sep 2;307(10):580–584. doi: 10.1056/NEJM198209023071002. [DOI] [PubMed] [Google Scholar]
  7. GRUNERT R. R., MCGAHEN J. W., DAVIES W. L. THE IN VIVO ANTIVIRAL ACTIVITY OF 1-ADAMANTANAMINE (AMANTADINE). I. PROPHYLACTIC AND THERAPEUTIC ACTIVITY AGAINST INFLUENZA VIRUSES. Virology. 1965 Jun;26:262–269. doi: 10.1016/0042-6822(65)90273-4. [DOI] [PubMed] [Google Scholar]
  8. Galbraith A. W., Oxford J. S., Schild G. C., Watson G. I. Protective effect of 1-adamantanamine hydrochloride on influenza A2 infections in the family environment: a controlled double-blind study. Lancet. 1969 Nov 15;2(7629):1026–1028. doi: 10.1016/s0140-6736(69)90639-4. [DOI] [PubMed] [Google Scholar]
  9. Galbraith A. W., Oxford J. S., Schild G. C., Watson G. I. Study of 1-adamantanamine hydrochloride used prophylactically during the Hong Kong influenza epidemic in the family environment. Bull World Health Organ. 1969;41(3):677–682. [PMC free article] [PubMed] [Google Scholar]
  10. Goodman R. A., Orenstein W. A., Munro T. F., Smith S. C., Sikes R. K. Impact of influenza A in a nursing home. JAMA. 1982 Mar 12;247(10):1451–1453. [PubMed] [Google Scholar]
  11. Hayden F. G., Cote K. M., Douglas R. G., Jr Plaque inhibition assay for drug susceptibility testing of influenza viruses. Antimicrob Agents Chemother. 1980 May;17(5):865–870. doi: 10.1128/aac.17.5.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayden F. G., Hoffman H. E., Spyker D. A. Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics. Antimicrob Agents Chemother. 1983 Mar;23(3):458–464. doi: 10.1128/aac.23.3.458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Heider H., Adamczyk B., Presber H. W., Schroeder C., Feldblum R., Indulen M. K. Occurrence of amantadine- and rimantadine-resistant influenza A virus strains during the 1980 epidemic. Acta Virol. 1981 Nov;25(6):395–400. [PubMed] [Google Scholar]
  14. JACKSON G. G., MULDOON R. L., AKERS L. W. SEROLOGICAL EVIDENCE FOR PREVENTION OF INFLUENZAL INFECTION IN VOLUNTEERS BY AN ANTI-INFLUENZAL DRUG ADAMANTANAMINE HYDROCHLORIDE. Antimicrob Agents Chemother (Bethesda) 1963;161:703–707. [PubMed] [Google Scholar]
  15. Lennette E. H. Viral respiratory diseases: vaccines and antivirals. Bull World Health Organ. 1981;59(3):305–324. [PMC free article] [PubMed] [Google Scholar]
  16. Little J. W., Hall W. J., Douglas R. G., Jr, Mudholkar G. S., Speers D. M., Patel K. Airway hyperreactivity and peripheral airway dysfunction in influenza A infection. Am Rev Respir Dis. 1978 Aug;118(2):295–303. doi: 10.1164/arrd.1978.118.2.295. [DOI] [PubMed] [Google Scholar]
  17. Lubeck M. D., Schulman J. L., Palese P. Susceptibility of influenza A viruses to amantadine is influenced by the gene coding for M protein. J Virol. 1978 Dec;28(3):710–716. doi: 10.1128/jvi.28.3.710-716.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Monto A. S., Gunn R. A., Bandyk M. G., King C. L. Prevention of Russian influenza by amantadine. JAMA. 1979 Mar 9;241(10):1003–1007. [PubMed] [Google Scholar]
  19. O'Donoghue J. M., Ray C. G., Terry D. W., Jr, Beaty H. N. Prevention of nosocomial influenza infection with Amantadine. Am J Epidemiol. 1973 Apr;97(4):276–282. doi: 10.1093/oxfordjournals.aje.a121509. [DOI] [PubMed] [Google Scholar]
  20. Oxford J. S., Galbraith A. Antiviral activity of amantadine: a review of laboratory and clinical data. Pharmacol Ther. 1980;11(1):181–262. doi: 10.1016/0163-7258(80)90072-8. [DOI] [PubMed] [Google Scholar]
  21. Oxford J. S., Logan I. S., Potter C. W. In vivo selection of an influenza A2 strain resistant to amantadine. Nature. 1970 Apr 4;226(5240):82–83. doi: 10.1038/226082a0. [DOI] [PubMed] [Google Scholar]
  22. Payler D. K., Purdham P. A. Influenza A prophylaxis with amantadine in a boarding school. Lancet. 1984 Mar 3;1(8375):502–504. doi: 10.1016/s0140-6736(84)92861-7. [DOI] [PubMed] [Google Scholar]
  23. Rabinovich S. Rimantadine therapy of influenza A infection in mice. Antimicrob Agents Chemother. 1972 May;1(5):408–411. doi: 10.1128/aac.1.5.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saunders M. Would community health councils be missed? Nurs Focus. 1980 Mar;1(7):278–280. [PubMed] [Google Scholar]
  25. Schild G. C., Sutton R. N. Inhibition of influenza viruses in vitro and in vivo by 1-adamantanamine hydrochloride. Br J Exp Pathol. 1965 Jun;46(3):263–273. [PMC free article] [PubMed] [Google Scholar]
  26. Scholtissek C., Faulkner G. P. Amantadine-resistant and -sensitive influenza A strains and recombinants. J Gen Virol. 1979 Sep;44(3):807–815. doi: 10.1099/0022-1317-44-3-807. [DOI] [PubMed] [Google Scholar]
  27. Schwab R. S., Poskanzer D. C., England A. C., Jr, Young R. R. Amantadine in Parkinson's disease. Review of more than two years' experience. JAMA. 1972 Nov 13;222(7):792–795. doi: 10.1001/jama.222.7.792. [DOI] [PubMed] [Google Scholar]
  28. Stuart-Harris C. The epidemiology and prevention of influenza. Am Sci. 1981 Mar-Apr;69(2):166–172. [PubMed] [Google Scholar]
  29. Tillett H. E., Smith J. W., Clifford R. E. Excess morbidity and mortality associated with influenza in England and Wales. Lancet. 1980 Apr 12;1(8172):793–795. doi: 10.1016/s0140-6736(80)91293-3. [DOI] [PubMed] [Google Scholar]
  30. Timberlake W. H., Vance M. A. Four-year treatment of patients with parkinsonism using amantadine alone or with levodopa. Ann Neurol. 1978 Feb;3(2):119–128. doi: 10.1002/ana.410030206. [DOI] [PubMed] [Google Scholar]
  31. Togo Y., Hornick R. B., Dawkins A. T., Jr Studies on induced influenza in man. I. Double-blind studies designed to assess prophylactic efficacy of amantadine hydrochloride against a2/Rockville/1/65 strain. JAMA. 1968 Mar 25;203(13):1089–1094. doi: 10.1001/jama.203.13.1089. [DOI] [PubMed] [Google Scholar]
  32. Togo Y., Hornick R. B., Felitti V. J., Kaufman M. L., Dawkins A. T., Jr, Kilpe V. E., Claghorn J. L. Evaluation of therapeutic efficacy of amantadine in patients with naturally occurring A2 influenza. JAMA. 1970 Feb 16;211(7):1149–1156. [PubMed] [Google Scholar]
  33. Tyrrell D. A., Bynoe M. L., Hoorn B. Studies on the antiviral activity of 1-adamantanamine. Br J Exp Pathol. 1965 Aug;46(4):370–375. [PMC free article] [PubMed] [Google Scholar]
  34. Van Voris L. P., Betts R. F., Hayden F. G., Christmas W. A., Douglas R. G., Jr Successful treatment of naturally occurring influenza A/USSR/77 H1N1. JAMA. 1981 Mar 20;245(11):1128–1131. doi: 10.1001/jama.245.11.1128. [DOI] [PubMed] [Google Scholar]
  35. Younkin S. W., Betts R. F., Roth F. K., Douglas R. G., Jr Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine. Antimicrob Agents Chemother. 1983 Apr;23(4):577–582. doi: 10.1128/aac.23.4.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zlydnikov D. M., Kubar O. I., Kovaleva T. P., Kamforin L. E. Study of rimantadine in the USSR: a review of the literature. Rev Infect Dis. 1981 May-Jun;3(3):408–421. doi: 10.1093/clinids/3.3.408. [DOI] [PubMed] [Google Scholar]

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