FLUCLOXACILLIN ASSOCIATED CHOLESTATIC HEPATITIS - AN AUSTRALIAN AND SWEDISH EPIDEMIC

The clinico-pathological entity of flucloxacillin-associated cholestat ic hepatitis is described and the recognition and documentation of cho lestasis associated with flucloxacillin and with related isoxazolyl-pe nicillins (cloxacillin, dicloxacillin) is examined on an international basis, with particular reference to Australia. Data were obtained fro m the literature, from the Australian adverse drug reaction monitoring agency and from the Collaborative Centre for International Drug Monit oring (World Health Organisation) in Sweden. Approximately 600 cases o f flucloxacillin-associated cholestatic hepatitis were collected, as w ell as 164 cases associated with other isoxazolyl penicillins. Jaundic e and pruritus may first appear several weeks after adminstration of t he drug has ceased and typically are severe and protracted. Liver test s may be abnormal for months after symptomatic recovery. Death is unco mmon. Liver pathology shows centrizonal bile stasis with portal tract inflammation and variable loss of bile ducts. Approximately I in 15,00 0 users of flucloxacillin will develop the reaction. Increasing age (> 55 years) and prolonged intake (> 14 days) are particular risk factor s. Cholestasis associated with cloxacillin/dicloxacillin appears to be similar in nature but is less well defined. Recognition and reporting of the reaction have been uncommon in the United Kingdom inter alia a nd high in Sweden and Australia, although estimates of risk have been similar. In Australia, the remarkably high rate of reports appears to be the result of sustained publicity for the reaction. There is only a trickle of reports of cholestatic hepatitis in association with the u se of cloxacillin and dicloxacillin from the USA and Canada. The high level of awareness of the reaction and consequential regulatory action so far have not resulted in a diminution of its occurrence in Austral ia.