Flutamide-induced acute hepatitis: investigation on the role of immunoallergic mechanisms.
Flutamide is a nonsteroidal antiandrogen drug used in the treatment of prostatic cancer. Hepatotoxic reactions due to flutamide have been reported with an incidence ranging from 1% to 5%. These reactions are usually reversible upon withdrawal of the drug but can occasionally be life-threatening. The mechanism of flutamide-associated hepatotoxicity is not well established. We report a case of a 69-year-old man with prostatic carcinoma in whom flutamide induced an acute hepatitis which resolved completely soon after drug withdrawal. In this patient, we have studied the possible involvement of an immunological mechanism in causing flutamide hepatitis by investigating the presence of circulating antibodies directed against reactive metabolites of flutamide bound to liver proteins with enzyme-linked immunosorbent assay technique. Although, in the present case, we have failed to detect IgG reacting with rat liver microsomes incubated in vitro with flutamide, this does not completely rule out the possibility of an immunological involvement in flutamide hepatotoxicity. The possibility of severe flutamide-related injury, independently of the underlying pathogenic mechanism, strongly suggests the need for careful monitoring of liver enzymes in patients taking this drug.
Institute of Medicine, University of Turin, Novara, Italy.
L
L
Pontiroli
M
M
Sartori
S
S
Pittau
S
S
Morelli
R
R
Boldorini
E
E
Albano
D000208:Acute Disease; D000368:Aged; D000726:Androgen Antagonists / Q000009:adverse effects*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005485:Flutamide / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy; D051381:Rats
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D007074:Immunoglobulin G; D005485:Flutamide