Risk of cholestatic liver disease associated with flucloxacillin and flucloxacillin prescribing habits in the UK: Cohort study using data from the UK General Practice Research Database

Aims To provide additional quantification of the risk of flucloxacillin-related liver disease and to describe time trends in flucloxacillin prescribing in the UK. Methods This was a cohort study using data from the UK General Practice Research Database. We identified patients with a first-time prescription for flucloxacillin or, for comparison, oxytetracycline from 1992 to 2002 and cases who developed clinically documented cholestatic liver disease of uncertain origin after first-time use of these drugs. We also determined the annual frequency of first-time use of flucloxacillin from 1991 to 2000. results We identified 283 097 and 131 189 first-time users of flucloxacillin and oxytetracycline, respectively. The risk of cholestatic liver disease per 100 000 first-time users was 8.5 (95% CI 5.4, 12.6) in the 1-45 days and 1.8 (95% CI 0.6, 4.1) in the 46-90 days after starting flucloxacillin, and 0.8 (95% CI 0.02, 4.3) in the 1-45 days after starting oxytetracycline. The frequency of first-time use of flucloxacillin remained stable between 1991 and 2000. Conclusions Flucloxacillin is now established as an important cause of cholestatic liver disease. Warnings about the risk have not had an impact on prescribing practices in the UK, where it remains the predominantly prescribed antistaphylococcal oral antibiotic. This situation in the UK is in sharp contrast to regulatory actions and changes in prescribing habits in Australia after identification of the risk of cholestasis associated with flucloxacillin, and to the predominant use of the alternative drug dicloxacillin in the USA.