Summary
Diclofenac is a frequently prescribed nonsteroidal antiinflammatory drug (NSAID). Significant hepatotoxicity related to diclofenac may be more common than previously recognized, as three patients with diclofenac-associated hepatitis were seen by one clinician in a single year. All patients were ANA positive during the hepatitis and had histologic features of chronic active hepatitis. Two had been inappropriately treated with corticosteroids. The third patient presented more acutely with jaundice and symptoms of hepatitis. Two of the patients developed the same hepatic reaction when rechallenged with diclofenac. The third patient was changed to tiaprofenic acid, a NSAID of the same family, and redeveloped evidence of hepatotoxicity. All three were subsequently able to take naproxen without liver dysfunction. Diclofenac-induced liver disease may be misdiagnosed. Twenty-six cases of significant hepatic reactions to diclofenac have been previously reported in the literature and are reviewed. Such hepatic reactions to diclofenac and related NSAIDs may be commoner than realized. Introduction of a NSAID of another class appears to be safe.
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References
Package insert. Voltaren (diclofenac sodium): Ardsley, New York, Geigy Pharmaceuticals Division of Ciba-Geigy Corp, October 1988
Catalano MA: Worldwide safety experience with diclofenac. Am J Med Suppl 4B:81–87, 1980
Iveson TJ, Ryley NG, Kelly PMA, Trowell JM, McGee JOD, Chapman RWG: Diclofenac associated hepatitis. J Hepatol 10:85–89, 1990
Breen EG, McNicholl J, Cosgrove E, McCabe J, Stevens FM: Fatal hepatitis associated with diclofenac. Gut 27:1390–1393, 1986
Schapira D, Bassan L, Nahir AM, Scharf Y: Diclofenac-induced hepatotoxicity. Postgrad Med J 62:63–65, 1986
Dunk AA, Walt RP, Jenkins WJ, Sherlock SS: Diclofenac hepatitis. Br Med J 284:1605–1606, 1982
Babany G, Bernuau J, Danan G, Rueff B, Benhamou J-P: Hépatite fulminante chez une femme prenant de la glafémine et du diclofénac. Gastroenterol Clin Biol 9:185, 1985
Babany G, Pessayre D, Benhamou J-P: Hépatite au diclofénac. Gastroenterol Clin Biol 7:316, 1983
Deshayes P, Leloet X, Bercoff E, Fouin-Fortunet H: Hépatite au diclofénac. Une observation. Presse Med 13:1847, 1984
Lascar G, Grippon P, Levy V-G: Hépatite aiguë mortelle au cours d'un traitement par le diclofénac (Voltarène). Gastroenterol Clin Biol 8:881–882, 1984
Llorca G, Larbre JP, Collett Ph, Ravault A: Changing the class of NSAID in cases of hepatotoxicity. Ann Rheum Dis 47:791, 1988
Ouellette GS, Slitzky BE, Gates JA, Lagarde S, West AB: Reversible hepatitis associated with diclofenac. J Clin Gastroenterol 131:205–210, 1991
Helfgott SM, Sandberg-Cook J, Zakim D, Nestler J: Diclofenac-associated hepatotoxicity. JAMA 264:2660–2663, 1990
Mazeika PK, Ford MJ: Chronic active hepatitis associated with diclofenac sodium therapy. Br J Clin Proc 43:125–126, 1989
Sallie RW, Reed WD, Quinlan MF, McKenzie T, Shilkin KB: Diclofenac hepatotoxicity and chronic active hepatitis. Aust NZ J Med 18:413, 1988
Sallie R: Diclofenac hepatitis. J Hepatol 11:281, 1990 (letter)
Zimmerman HJ, Maddrey WC: Toxic and drug-induced hepatitis.In Diseases of the Liver, 6th ed. L Schiff, ER Schiff (eds). Philadelphia, JB Lippincott, 1987, pp 591–668
Taggart HM, Alderice JM: Fatal cholestatic jaundice in elderly patients taking benoxaprofen. BMJ 1284:1372–1373, 1982
Ciccolunghi SN, Chaudri HA, Schubiger BI, Reddrop R: Report on a long-term tolerability study of up to two years with diclofenac sodium (Voltaren). Scand J Rheumatol 22 (suppl):86–89, 1978
Rodman JS, Deutsch DJ, Gutman SI: Methyldopa hepatitis: A report of six cases and review of the literature. Am J Med 60:941–948, 1976
Black M, Mitchell JR, Zimmerman HJ, Ishak KG, Epler GR: Isoniazid-associated hepatitis in 114 patients. Gastroenterology 69:289–302, 1975
Homberg JC, Abuaf N, Helmy-Khalil S, Biour M, Poupon R, Islam S, Darnis F, Levy VG, Opolon P, Beaugrand M, Toulet J, Danan G, Benhamou JP: Drug-induced hepatitis associated with anticytoplasmic organelle autoantibodies. Hepatology 5:722–727, 1985
Maddrey WC, Boitnott JK: Drug-induced chronic liver disease. Hepatology 72:1348–1353, 1977
Mackay IR: Induction by drugs of hepatitis and autoantibodies to cell organelles: Significance and interpretation. Hepatology 5:904–906, 1985
Andrejak M, Davion T, Gineston JL, Capron JP: Cross hepatoxicity between non-steroidal anti-inflammatory drugs. BMJ 295:180, 1987
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Dr. L.J. Scully was supported by the Ottawa Civic Hospital Research Fund.
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Scully, L.J., Clarke, D. & Barr, R.J. Diclofenac induced hepatitis. Digest Dis Sci 38, 744–751 (1993). https://doi.org/10.1007/BF01316809
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DOI: https://doi.org/10.1007/BF01316809