Risk factors for the development of amoxycillin-clavulanic acid associated jaundice.

OBJECTIVES: To identify risk factors for the development of amoxycillin-clavulanic acid associated jaundice.

DESIGN: Retrospective case-control study. Cases were selected from those reported to the Adverse Drug Reactions Advisory Committee from the time of introduction of amoxycillin-clavulanic acid to Australia in 1986 until December 1993.

SUBJECTS: Thirty-four cases, defined as individuals who developed jaundice within eight weeks of starting amoxycillin-clavulanic acid, with a biochemical picture of cholestasis, normal calibre bile ducts and no other recognised causes of jaundice or recent use of other hepatotoxic drugs, were selected. For each case, four controls who had been prescribed amoxycillin-clavulanic acid without developing jaundice were randomly selected from the patient register of the prescribing doctor.

RESULTS: Increasing age was a risk factor for amoxycillin-clavulanic acid associated jaundice; patients over 55 years had an odds ratio of 16.1 (95% confidence interval [CI], 2.9-88.9) compared with patients less than 30 years. Men had an odds ratio of 2.5 (95% CI, 1.1-5.4) compared with women, although the proportion of men in the study group was larger than in the reported cases overall. History of serious medical illness, drug dose, route and duration of therapy, other medications, smoking and previous drug allergies or use of amoxycillin-clavulanic acid were not significantly associated with jaundice.

CONCLUSIONS: Because of the higher risk of jaundice with increasing age, the risk-benefit ratio of amoxycillin-clavulanic acid should be carefully considered in older patients. Further assessment is necessary to clarify the association between jaundice and male sex.