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. 1981 Feb;19(2):226–233. doi: 10.1128/aac.19.2.226

Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults.

F G Hayden, J M Gwaltney Jr, R L Van de Castle, K F Adams, B Giordani
PMCID: PMC181399  PMID: 7347558

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) for 4.5 days. Both drugs were well tolerated at the lower dosage. At 300 mg/day amantadine recipients had a greater frequency and severity of central nervous system (nervousness, lightheadedness, difficulty concentrating) and sleep (insomnia, fatigue) complaints compared with rimantadine or placebo recipients. Amantadine recipients also performed less well on an objective test measuring sustained attention and problem-solving ability. Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients. Because of better tolerance at higher dosage, rimantadine offers more promise than amantadine for treatment of influenza A virus infections.

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Selected References

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

  1. Aldrich P. E., Hermann E. C., Meier W. E., Paulshock M., Prichard W. W., Snyder J. A., Watts J. C. Antiviral agents. 2. Structure-activity relationships of compounds related to 1-adamantanamine. J Med Chem. 1971 Jun;14(6):535–543. doi: 10.1021/jm00288a019. [DOI] [PubMed] [Google Scholar]
  2. Aoki F. Y., Sitar D. S., Ogilvie R. I. Amantadine kinetics in healthy young subjects after long-term dosing. Clin Pharmacol Ther. 1979 Dec;26(6):729–736. doi: 10.1002/cpt1979266729. [DOI] [PubMed] [Google Scholar]
  3. Bryson Y. J., Monahan C., Pollack M., Shields W. D. A prospective double-blind study of side effects associated with the administration of amantadine for influenza A virus prophylaxis. J Infect Dis. 1980 May;141(5):543–547. doi: 10.1093/infdis/141.5.543. [DOI] [PubMed] [Google Scholar]
  4. Dawkins A. T., Jr, Gallager L. R., Togo Y., Hornick R. B., Harris B. A. Studies on induced influenza in man. II. Double-blind study designed to assess the prophylactic efficacy of an analogue of amantadine hydrochloride. JAMA. 1968 Mar 25;203(13):1095–1099. doi: 10.1001/jama.203.13.1095. [DOI] [PubMed] [Google Scholar]
  5. Greenblatt D. J., DiMascio A., Harmatz J. S., Bernardo D. L., Marder J. E. Pharmacokinetics and clinical effects of amantadine in drug-induced extrapyramidal symptoms. J Clin Pharmacol. 1977 Nov-Dec;17(11-12):704–708. doi: 10.1002/j.1552-4604.1977.tb01545.x. [DOI] [PubMed] [Google Scholar]
  6. Grelak R. P., Clark R., Stump J. M., Vernier V. G. Amantadine-dopamine interaction: possible mode of action in Parkinsonism. Science. 1970 Jul 10;169(3941):203–204. doi: 10.1126/science.169.3941.203. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Hutt S. J., Jackson P. M., Belsham A., Higgins G. Perceptual-motor behaviour in relation to blood phenobarbitone level: a preliminary report. Dev Med Child Neurol. 1968 Oct;10(5):626–632. doi: 10.1111/j.1469-8749.1968.tb02947.x. [DOI] [PubMed] [Google Scholar]
  9. Ing T. S., Rahn A. C., Armbruster K. F., Oyama J. H., Klawans H. L. Letter: Accumulation of amantadine hydrochloride in renal insufficiency. N Engl J Med. 1974 Dec 5;291(23):1257–1257. doi: 10.1056/NEJM197412052912320. [DOI] [PubMed] [Google Scholar]
  10. Jackson G. G., Stanley E. D. Prevention and control of influenza by chemoprophylaxis and chemotherapy. Prospects from examination of recent experience. JAMA. 1976 Jun 21;235(25):2739–2742. [PubMed] [Google Scholar]
  11. Knight V., Fedson D., Baldini J., Douglas R. G., Couch R. B. Amantadine therapy of epidemic influenza a(2) (Hong Kong). Infect Immun. 1970 Feb;1(2):200–204. doi: 10.1128/iai.1.2.200-204.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Little J. W., Hall W. J., Douglas R. G., Jr, Hyde R. W., Speers D. M. Amantadine effect on peripheral airways abnormalities in influenza. A study in 15 students with natural influenza A infection. Ann Intern Med. 1976 Aug;85(2):177–182. doi: 10.7326/0003-4819-85-2-177. [DOI] [PubMed] [Google Scholar]
  13. Matarazzo J. D., Wiens A. N., Matarazzo R. G., Goldstein S. G. Psychometric and clinical test-retest reliability of the Halstead impairment index in a sample of healthy, young, normal men. J Nerv Ment Dis. 1974 Jan;158(1):37–49. doi: 10.1097/00005053-197401000-00006. [DOI] [PubMed] [Google Scholar]
  14. Matthews C. G., Harley J. P. Cognitive and motor-sensory performances in toxic and nontoxic epileptic subjects. Neurology. 1975 Feb;25(2):184–188. doi: 10.1212/wnl.25.2.184. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Parkes J. D., Zilkha K. J., Marsden P., Baxter R. C., Knill-Jones R. P. Amantadine dosage in treatment of Parkinson's disease. Lancet. 1970 May 30;1(7657):1130–1133. doi: 10.1016/s0140-6736(70)91211-0. [DOI] [PubMed] [Google Scholar]
  17. Rabinovich S., Baldini J. T., Bannister R. Treatment of influenza. The therapeutic efficacy of rimantadine HC1 in a naturally occurring influenza A2 outbreak. Am J Med Sci. 1969 May;257(5):328–335. doi: 10.1097/00000441-196905000-00005. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Wingfield W. L., Pollack D., Grunert R. R. Therapeutic efficacy of amantadine HCl and rimantadine HCl in naturally occurring influenza A2 respiratory illness in man. N Engl J Med. 1969 Sep 11;281(11):579–584. doi: 10.1056/NEJM196909112811102. [DOI] [PubMed] [Google Scholar]

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