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Chlorzoxazone Hepatotoxic Reactions: An Analysis of 21 Identified or Presumed Cases

Chlorzoxazone Hepatotoxic Reactions: An Analysis of 21 Identified or Presumed Cases Abstract • A drug rechallenge proved chlorzoxazone to be hepatotoxic in a patient who had been treated with a combination of it and acetaminophen (Parafon Forte) for several months. Failure to demonstrate a toxic response to acetaminophen coupled with a dramatic response to a single dose of chlorzoxazone implicated chlorzoxazone as the hepatotoxic agent. A review of US Food and Drug Administration records and cases reported in the medical literature disclosed 23 cases of chlorzoxazone-associated hepatotoxic reactions occurring since 1970. These cases were examined in terms of age, duration of therapy, other confounding etiologic factors, and ultimate outcome. There were two deaths involving hepatic failure. Reports of adverse reactions among six commonly used analgesic—muscle relaxants in Sweden have indicated a low, but comparatively greater, incidence of hepatotoxic reactions associated with a chlorzoxazone-containing compound. (Arch Intern Med 1986;146:1183-1186) References 1. Lindholm L: Fever, skin and liver reactions in a patient treated with Paraflex compound. Lakartidningen 1979;76:2795-2796. 2. Liver injury associated with analgesics containing dextropropoxyphene and/or chlorzoxazone, editorial. Lakartidningen 1982;79:3823. 3. Scheiner JJ: Evaluation of a combined muscle relaxant—analgesic as an effective therapy for painful skeletal muscle spasm. Curr Ther Res 1972;14: 168-177. 4. Walker JM: Value of an acetaminophen-chlorzoxazone combination (Parafon Forte tablets) in the treatment of acute musculoskeletal disorders. Curr Ther Res 1973;15:248-252. 5. Vernon WG: A double-blind evaluation of Parafon Forte tablets in the treatment of musculoskeletal back conditions. Curr Ther Res 1972;14: 800-806. 6. Azoury FJ: Double-blind comparison of Parafon Forte and Flexeril in the treatment of acute musculoskeletal disorders. Curr Ther Res 1982;26: 189-197. 7. Scheiner JJ: Muscle relaxants: Chlorzoxazone compared with diazepam (a double-blind study). Curr Ther Res 1975;19:51-57. 8. Gready DM: Parafon Forte versus Robaxisal in skeletal muscle disorders: A double-blind study. Curr Ther Res 1976;20:666-673. 9. Cranston JP: Double-blind comparison of Parafon Forte tablets vs Norgesic Forte for the relief of pain and spasm of musculoskeletal disorders. Curr Ther Res 1977;21:809-814. 10. Berman HH, Noe O, Goodfield F: Relief of severe spasticity with chlorzoxazone. Dis Nerv Syst 1964;25:430-433. 11. Mayle FC, Sullivan PD, Auth TL: Chlorzoxazone in the treatment of spasticity. Med Ann DC 1959;28:499-536. 12. Brunner G: Gezielte myotonolytische Therapie mit Paraflex (Chlorzoxazon) in der Unfallheilkunde. Med Welt 1964;46:2493-2494. 13. Peak WP, Smith RT: Clinical comparison of chlorzoxazone and zoxazolamine. Penn Med J 1960;63:833-837. 14. American Medical Association Council on Drugs: New Drugs . Chicago, American Medical Association, 1967, p 156. 15. Conney AH, Burns JJ: Biochemical pharmacological considerations of zoxazolamine and chlorzoxazone metabolism. Ann NY Acad Sci 1960;86: 167-177.Crossref 16. Hoffbauer FW, Nelson OLN, Wagner DJ, et al: Fatal liver necrosis in two patients receiving zoxazolamine. Gastroenterology 1958;34:1048. 17. Carr HJ, Knauer QF: Death due to hepatic necrosis in a patient receiving zoxazolamine. N Engl J Med 1961;264:977-980.Crossref 18. Lubell DL: Fatal hepatic necrosis associated with zoxazolamine therapy. NY State J Med 1962;62:3807-3810. 19. Mintz M: The Therapeutic Nightmare . Boston, Houghton Mifflin Co, 1965, p 24. 20. Council on Drugs: New and nonofficial drugs. JAMA 1959;170:194-197.Crossref 21. Popper H, Schaffner F: Drug-induced hepatic injury. Ann Intern Med 1959;51:1230-1252.Crossref 22. Zimmerman HJ: Hepatotoxicity . East Norwalk, Conn, Appleton-Century-Crofts, 1978, p 430. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Chlorzoxazone Hepatotoxic Reactions: An Analysis of 21 Identified or Presumed Cases

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References (26)

Publisher
American Medical Association
Copyright
Copyright © 1986 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1986.00360180197029
Publisher site
See Article on Publisher Site

Abstract

Abstract • A drug rechallenge proved chlorzoxazone to be hepatotoxic in a patient who had been treated with a combination of it and acetaminophen (Parafon Forte) for several months. Failure to demonstrate a toxic response to acetaminophen coupled with a dramatic response to a single dose of chlorzoxazone implicated chlorzoxazone as the hepatotoxic agent. A review of US Food and Drug Administration records and cases reported in the medical literature disclosed 23 cases of chlorzoxazone-associated hepatotoxic reactions occurring since 1970. These cases were examined in terms of age, duration of therapy, other confounding etiologic factors, and ultimate outcome. There were two deaths involving hepatic failure. Reports of adverse reactions among six commonly used analgesic—muscle relaxants in Sweden have indicated a low, but comparatively greater, incidence of hepatotoxic reactions associated with a chlorzoxazone-containing compound. (Arch Intern Med 1986;146:1183-1186) References 1. Lindholm L: Fever, skin and liver reactions in a patient treated with Paraflex compound. Lakartidningen 1979;76:2795-2796. 2. Liver injury associated with analgesics containing dextropropoxyphene and/or chlorzoxazone, editorial. Lakartidningen 1982;79:3823. 3. Scheiner JJ: Evaluation of a combined muscle relaxant—analgesic as an effective therapy for painful skeletal muscle spasm. Curr Ther Res 1972;14: 168-177. 4. Walker JM: Value of an acetaminophen-chlorzoxazone combination (Parafon Forte tablets) in the treatment of acute musculoskeletal disorders. Curr Ther Res 1973;15:248-252. 5. Vernon WG: A double-blind evaluation of Parafon Forte tablets in the treatment of musculoskeletal back conditions. Curr Ther Res 1972;14: 800-806. 6. Azoury FJ: Double-blind comparison of Parafon Forte and Flexeril in the treatment of acute musculoskeletal disorders. Curr Ther Res 1982;26: 189-197. 7. Scheiner JJ: Muscle relaxants: Chlorzoxazone compared with diazepam (a double-blind study). Curr Ther Res 1975;19:51-57. 8. Gready DM: Parafon Forte versus Robaxisal in skeletal muscle disorders: A double-blind study. Curr Ther Res 1976;20:666-673. 9. Cranston JP: Double-blind comparison of Parafon Forte tablets vs Norgesic Forte for the relief of pain and spasm of musculoskeletal disorders. Curr Ther Res 1977;21:809-814. 10. Berman HH, Noe O, Goodfield F: Relief of severe spasticity with chlorzoxazone. Dis Nerv Syst 1964;25:430-433. 11. Mayle FC, Sullivan PD, Auth TL: Chlorzoxazone in the treatment of spasticity. Med Ann DC 1959;28:499-536. 12. Brunner G: Gezielte myotonolytische Therapie mit Paraflex (Chlorzoxazon) in der Unfallheilkunde. Med Welt 1964;46:2493-2494. 13. Peak WP, Smith RT: Clinical comparison of chlorzoxazone and zoxazolamine. Penn Med J 1960;63:833-837. 14. American Medical Association Council on Drugs: New Drugs . Chicago, American Medical Association, 1967, p 156. 15. Conney AH, Burns JJ: Biochemical pharmacological considerations of zoxazolamine and chlorzoxazone metabolism. Ann NY Acad Sci 1960;86: 167-177.Crossref 16. Hoffbauer FW, Nelson OLN, Wagner DJ, et al: Fatal liver necrosis in two patients receiving zoxazolamine. Gastroenterology 1958;34:1048. 17. Carr HJ, Knauer QF: Death due to hepatic necrosis in a patient receiving zoxazolamine. N Engl J Med 1961;264:977-980.Crossref 18. Lubell DL: Fatal hepatic necrosis associated with zoxazolamine therapy. NY State J Med 1962;62:3807-3810. 19. Mintz M: The Therapeutic Nightmare . Boston, Houghton Mifflin Co, 1965, p 24. 20. Council on Drugs: New and nonofficial drugs. JAMA 1959;170:194-197.Crossref 21. Popper H, Schaffner F: Drug-induced hepatic injury. Ann Intern Med 1959;51:1230-1252.Crossref 22. Zimmerman HJ: Hepatotoxicity . East Norwalk, Conn, Appleton-Century-Crofts, 1978, p 430.

Journal

Archives of Internal Medicine – American Medical Association

Published: Jun 1, 1986

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