Cholestatic hepatitis associated with flucloxacillin

Objective: To estimate the frequency of cholestatic hepatitis of uncertain origin occurring among persons who had recently received flucloxacillin a drug which has recently been reported as causing cholestatic hepatitis and to compare this frequency with that related to oxytetracycline a drug which has seldom been reported as causing this disorder. Design: A retrospective cohort study using data automatically recorded on general practitioners office computers. Setting: Some 600 general practices in the United Kingdom. Subjects: 132 087 people who received flucloxacillin and 145 844 people who received oxytetracycline. Main outcome measure: Clinically documented cholestatic hepatitis of uncertain origin diagnosed 1-45 days after a prescription for flucloxacillin 46-90 days after a prescription for flucloxacillin and for comparison 1-45 days after a prescription for oxytetracycline. Results: There were 10 cases of cholestatic hepatitis of uncertain origin diagnosed within 45 days of receiving flucloxacillin that were either characteristic of or consistent with a syndrome recently described as being associated with this drug; there was one such case 46-90 days after a prescription for flucloxacillin; there were three such cases 1-45 days after a prescription for oxytetracycline. Conclusion: Flucloxacillin is a likely cause of cholestatic hepatitis. The risk is estimated to be in the range of 7.6 per 100 000 users (95% confidence interval 3.6-13.9).