Flutamide hepatotoxicity.
OBJECTIVE
Observed and expected reporting rates were compared in patients who died or were hospitalized due to hepatotoxicity associated with the use of flutamide.


METHODS
Case series were submitted to the MedWatch Spontaneous Reporting System of the Food and Drug Administration. Reporting rates for serious hepatotoxicity due to flutamide were calculated and compared to rates for hospitalized patients with acute idiopathic hepatitis in the medical literature.


RESULTS
After the marketing of flutamide in the United States, between February 1989 and December 1994 the Food and Drug Administration received reports of 20 patients who died and 26 who were hospitalized for hepatotoxicity due to flutamide. The rate of approximately 3 per 10,000 flutamide users exceeds by 10-fold or more the expected rate of hospitalizations for acute noninfectious liver injury of 2.5 per 100,000 men 65 years and older. Autopsies in 6 cases revealed marked to massive hepatic necrosis as the predominant feature.


CONCLUSIONS
Flutamide is a potent hepatotoxin in certain patients. Serial blood aminotransferase levels should be monitored during the first few months of flutamide treatment. Before beginning use of this drug patients should be instructed to report immediately to physicians any episodes of nausea, vomiting, fatigue and jaundice so that flutamide can be promptly discontinued to avoid progression of possible liver injury.
D016907:Adverse Drug Reaction Reporting Systems; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D005485:Flutamide / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006628:Hirsutism / Q000188:drug therapy; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D014481:United States / Q000453:epidemiology; D014486:United States Food and Drug Administration
D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide