The clinico-pathological entity of flucloxacillin-associated cholestatic hepatitis is described and the recognition and documentation of cholestasis associated with flucloxacillin and with related isoxazolylpenicillins (cloxacillin, dicloxacillin) is examined on an international basis, with particular reference to Australia. Data were obtained from the literature, from the Australian adverse drug reaction monitoring agency and from the Collaborative Centre for International Drug Monitoring (World Health Organisation) in Sweden. Approximately 600 cases of flucloxacillin-associated cholestatic hepatitis were collected, as well as 164 cases associated with other isoxazolyl penicillins.
Jaundice and pruritus may first appear several weeks after adminstration of the drug has ceased and typically are severe and protracted. Liver tests may be abnormal for months after symptomatic recovery. Death is uncommon. Liver pathology shows centrizonal bile stasis with portal tract inflammation and variable loss of bile ducts. Approximately 1 in 15,000 users of ftucloxacillin will develop the reaction. Increasing age (> 55 years)and prolonged intake (> 14 days) are particular risk factors. Cholestasis associated with cloxacillin/dicloxacillin appears to be similar in nature but is less well defined.