Can clarithromycin cause hepatotoxicity?/nBACKGROUND: A 45-year-old woman with alcohol anamnesis ha

Fråga: Can clarithromycin cause hepatotoxicity?

BACKGROUND: A 45-year-old woman with alcohol anamnesis has been treated with clarithromycin (Klacid) in ordinary dose due to an otitis media while on vacation in Mallorca. Just after the start of treatment nausea, vomiting and icterus started. The drug was discontinued after 2-3 days. Nausea, icterus and steatosis still continued after her arrival back to Sweden (time from stopping the treatment unknown). Other liver values (unspecified) are slowly decreasing but bilirubin has further increased from 169 to 282 (normally <26).

Sammanfattning: Clarithromycin treatment can cause hepatotoxicity both with long and short term use.

Svar: Clarithromycin is a widely used macrolide antibiotic especially among AIDS patients with Mycobacteria avium complex disease (1). Although it is usually a well-tolerated drug, some gastrointestinal (anorexia, nausea, vomiting, dyspepsia), CNS symptoms (confusion, light-headedness, insomnia, euphoria), and alterations in liver enzymes have been reported especially among elderly patients (1-3).

The pattern of hepatotoxicity is primarily cholestatic (4-6) and symptoms usually begin after 10-20 days of treatment (7). A 62-year-old patient with lung infection caused by Mycobacterium chelonae treated with clarithromycin, 1.0 g orally twice a day, developed cholestatic hepatitis. His liver enzyme values including bilirubin increased 2-4 times within two months. One month after discontinuation, all enzyme levels returned to normal. After receiving a challenge dose of clarithromycin (1.0 g), he immediately developed nausea, vomiting, diarrhea and increased bilirubin and gamma-glutamyl transpeptidase.

The patients with clarithromycin induced hepatotoxicity mostly received high doses of the drug and they were mostly elderly patients. This suggests that clarithromycin´s hepatotoxicity may be dose-dependent and not due to a hypersensitivity reaction (8). On the other hand, the case of a patient with recurrence of hepatic dysfunction after a single rechallenge dose of clarithromycin, and some other case reports with onset of clarithromycin hepatotoxicity within a week suggest an idiosyncratic reaction at least in some of the subjects (8, 9).

There are five cases reported to the Swedish Adverse Drug Reactions Advisory Committee (SADRAC) related with hepatic side effects of clarithromycin (10). The present case is also suggested to be reported to SADRAC. 1 Wallace RJ Jr, Brown BA, Griffith DE: Drug intolerance to high-dose clarithromycin among elderly patients. Diagn Microbiol Infect Dis 1993; 16: 215-21

2 Dukes MNG, editor. Meyler´s Side effects of drugs. 13th ed. Amsterdam: Elsevier; 1996
3 Stricker BHCh. Drug-induced hepatic injury. 2nd ed. Elsevier: Amsterdam; 1992
4 Aronson JK, Van Boxtel CJ, editor. Side effects of drugs. Annual 19. Amsterdam: Elsevier; 1996
5 Aronson JK, editor. Side effects of drugs. Annual 20. Amsterdam: Elsevier; 1997

6 Yew WW, Chau CH, Lee J, Leung CW: Cholestatic hepatitis in a patient who received clarithromycin therapy for a Mycobacterium chelonae lung infection. Clin Infect Dis 1994; 18: 1025-6 7 Dukes MNG, editor. Meyler´s Side effects of drugs. 13th ed. Amsterdam: Elsevier; 1996 8 Brown BA, Wallace RJ Jr, Griffith DE, Girard W: Clarithromycin-induced hepatotoxicity. Clin Infect Dis 1995; 20: 1073-4 9 Shaheen N, Grimm IS: Fulminant hepatic failure associated with clarithromycin. Am J Gastroenterol 1996; 91: 394-5 10 Swedis (The Swedish Drug Information System)