Flutamide-induced liver toxicity including fatal hepatic necrosis

Abstract

To describe hepatic injuries in three patients who received flutamide prior to and during radiation treatment to make radiation oncologists aware of the need for careful monitoring of liver function during use of this drug. The records of three patients who developed abnormal liver function tests while undergoing total androgen suppression (TAS), as well as the literature concerning flutamide toxicity were reviewed and summarized. Three of 34 patients treated with a TAS regimen incorporating flutamide developed significant hepatic abnormalities: elevated transaminases [2] and fatal hepatic necrosis [1]. Following the discontinuation of flutamide, two patients recovered fully. Unfortunately, the third patient's hepatic function continued to deteriorate, which culminated in his death. Transient elevations in serum transaminases, which do not exceed four times the upper limits of normal, are common and apparently without clinical significance. Unfortunately, idiosyncratic serious and/or fatal liver damage can occur. Significant liver toxicity may be obviated by monitoring of liver function tests (LFT) early in the course of flutamide therapy. The incidence of hepatic toxicity associated with flutamide may be higher than previously suggested. To prevent the development of serious hepatic dysfunction, all patients receiving flutamide should be monitored clinically for signs and symptoms referable to hepatic injury and with serial LFT. We recommend baseline LFT followed by serial LFT at weeks 2, 4, 6, and 8 from the start of treatment with flutamide. Flutamide should be stopped promptly if significant liver abnormalities are detected.