Skip to main content
PMC home page
British Medical Journal (Clinical Research Ed.) logoLink to British Medical Journal (Clinical Research Ed.)
. 1987 Feb 14;294(6569):419–422. doi: 10.1136/bmj.294.6569.419

Hepatic reactions associated with ketoconazole in the United Kingdom.

G Lake-Bakaar, P J Scheuer, S Sherlock
PMCID: PMC1245420  PMID: 3101906

Abstract

Ketoconazole was introduced in the United Kingdom in 1981. By November 1984 the Committee on Safety of Medicines had received 82 reports of possible hepatotoxicity associated with the drug, including five deaths. An analysis of the 75 cases that had been adequately followed up suggested that 16, including three deaths, were probably related to treatment with the drug. Of the remainder, 48 were possibly related to treatment, five were unlikely to be so, and six were unclassifiable. The mean age of patients in the 16 probable cases was 57.9, with hepatotoxicity being more common in women. The average duration of treatment before the onset of jaundice was 61 days. None of these well validated cases occurred within the first 10 days after treatment. The results of serum liver function tests suggested hepatocellular injury in 10 (63%); the rest showed a mixed pattern. In contrast, the results of histological examination of the liver often showed evidence of cholestasis. The characteristics of the 48 patients in the possible cases were similar. Allergic manifestations such as rash and eosinophilia were rare. Hepatitis was usually reversible when treatment was stopped, with the results of liver function tests returning to normal after an average of 3.1 months. In two of the three deaths probably associated with ketoconazole treatment the drug had been continued after the onset of jaundice and other symptoms of hepatitis. Clinical and biochemical monitoring at regular intervals for evidence of hepatitis is advised during long term treatment with ketoconazole to prevent possible serious hepatic injury.

Full text

PDF
419

Images in this article

420FIG 1
on p.420
421FIG 2
on p.421

Selected References

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

  1. Bercoff E., Bernuau J., Degott C., Kalis B., Lemaire A., Tilly H., Rueff B., Benhamou J. P. Ketoconazole-induced fulminant hepatitis. Gut. 1985 Jun;26(6):636–638. doi: 10.1136/gut.26.6.636. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buttke T. M., Chapman S. W. Inhibition by ketoconazole of mitogen-induced DNA synthesis and cholesterol biosynthesis in lymphocytes. Antimicrob Agents Chemother. 1983 Oct;24(4):478–485. doi: 10.1128/aac.24.4.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Duarte P. A., Chow C. C., Simmons F., Ruskin J. Fatal hepatitis associated with ketoconazole therapy. Arch Intern Med. 1984 May;144(5):1069–1070. [PubMed] [Google Scholar]
  4. Eggleston S. M., Belandres M. M. Jaundice associated with cephalosporin therapy. Drug Intell Clin Pharm. 1985 Jul-Aug;19(7-8):553–555. doi: 10.1177/106002808501900710. [DOI] [PubMed] [Google Scholar]
  5. Fung-Herrera C. G., Mulvaney W. P. Cephalexin nephrotoxicity. Reversible nonoliguric acute renal failure and hepatotoxicity associated with cephalexin therapy. JAMA. 1974 Jul 15;229(3):318–319. doi: 10.1001/jama.229.3.318. [DOI] [PubMed] [Google Scholar]
  6. Heiberg J. K., Svejgaard E. Toxic hepatis during ketoconazole treatment. Br Med J (Clin Res Ed) 1981 Sep 26;283(6295):825–826. doi: 10.1136/bmj.283.6295.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hepatitis and ketoconazole therapy. Br Med J (Clin Res Ed) 1981 Oct 17;283(6298):1058–1059. [PMC free article] [PubMed] [Google Scholar]
  8. Lefkowitch J. H. Bile ductular cholestasis: an ominous histopathologic sign related to sepsis and "cholangitis lenta". Hum Pathol. 1982 Jan;13(1):19–24. doi: 10.1016/s0046-8177(82)80134-2. [DOI] [PubMed] [Google Scholar]
  9. Lewis J. H., Zimmerman H. J., Benson G. D., Ishak K. G. Hepatic injury associated with ketoconazole therapy. Analysis of 33 cases. Gastroenterology. 1984 Mar;86(3):503–513. [PubMed] [Google Scholar]
  11. Petersen E. A., Alling D. W., Kirkpatrick C. H. Treatment of chronic mucocutaneous candidiasis with ketoconazole: a controlled clinical trial. Ann Intern Med. 1980 Dec;93(6):791–795. doi: 10.7326/0003-4819-93-6-791. [DOI] [PubMed] [Google Scholar]
  12. Rollman O., Löf L. Hepatic toxicity of ketoconazole. Br J Dermatol. 1983 Mar;108(3):376–378. doi: 10.1111/j.1365-2133.1983.tb03981.x. [DOI] [PubMed] [Google Scholar]
  13. Strauss J. S. Ketoconazole and the liver. J Am Acad Dermatol. 1982 Apr;6(4 Pt 1):546–547. doi: 10.1016/s0190-9622(82)80375-7. [DOI] [PubMed] [Google Scholar]
  14. Svejgaard E., Ranek L. Hepatic dysfunction and ketoconazole therapy. Ann Intern Med. 1982 Jun;96(6 Pt 1):788–789. doi: 10.7326/0003-4819-96-6-788_2. [DOI] [PubMed] [Google Scholar]
  15. Tkach J. R., Rinaldi M. G. Severe hepatitis associated with ketoconazole therapy for chronic mucocutaneous candidiasis. Cutis. 1982 May;29(5):482–484. [PubMed] [Google Scholar]

Articles from British Medical Journal (Clinical research ed.) are provided here courtesy of BMJ Publishing Group

RESOURCES