FATAL AND NONFATAL HEPATOTOXICITY ASSOCIATED WITH FLUTAMIDE

Objective: To identify and describe patients with hepatotoxicity possi bly caused by flutamide, an antiandrogen drug. Design: Case series of reports, submitted to the Adverse Drug Event Reporting System of the F ood and Drug Administration. Setting. Outpatient clinics and physician s' offices in the United States. Patients: Nineteen patients treated w ith flutamide for prostate cancer or benign prostatic hypertrophy (for Investigation of a New Drug or off-label use). Measurements: Evidence of increased liver enzyme levels, hyperbilirubinemia, associated clin ical symptoms, and diagnoses of cholestatic hepatitis. Autopsy reports were used when available. Results: From the time of marketing of flut amide in February 1989 through March 1991, the Food and Drug Administr ation received reports of 19 patients in the United States who develop ed serious hepatotoxicity while using flutamide. Fourteen patients had resolution of abnormal liver function test results after discontinuin g or decreasing the dose of flutamide, but five patients died of progr essive liver disease. Autopsy reports from three patients and abnormal pathologic results from three other patients (reported to the Food an d Drug Administration or in the medical literature) showed hepatocellu lar necrosis and possibly cholestasis. Thorough work-ups excluded othe r possible causes than flutamide. Conclusions: Flutamide appears to ca use hepatotoxic effects in certain patients. Physicians should tell pa tients to immediately report to physicians nausea, vomiting, fatigue, jaundice, and other signs and symptoms of liver injury.