Bicalutamide Induced Hepatotoxicity: A Rare Adverse Effect

Abstract

Purpose: There is a small number of cases reported in literature that highlight the hepatotoxic potential of bicalutamide, a nonsteroidal antiandrogen used extensively during the start of androgen deprivation therapy with a luteinizing hormone-releasing hormone agonist to reduce occurrence of the symptoms of tumor flare in patients with metastatic prostate carcinoma. The most common adverse effects of bicalutamide are induced by its pharmacologic property of competitive androgen receptor blockade and include gynecomastia, hot flashes, fatigue, and decreased libido. Although not as common, increases in liver function test results are also seen with bicalutamide therapy. These elevations are typically transient, and patients remain asymptomatic. We share our experience of a case of symptomatic acute hepatoxicity secondary to the use of Bicalutamide and employ this opportunity to present a brief review of existing literature. An 81-year-old African American male with metastatic prostate cancer presented with nonspecific symptoms of decreased appetite and fatigue for three days and jaundice for one day. He also reported dark colored urine for one week. He was started on a trial of Bicalutamide three weeks prior to presentation. On physical examination, scleral icterus was noted. Work-up revealed acutely elevated liver enzymes (more than 5 times the upper limit of normal), alkaline phosphatase, conjugated hyperbilirubinemia and coagulopathy. Ultrasound of the abdomen was negative for obstruction. Other etiologies including viral, common toxins and drugs, autoimmune and ceruloplasmin induced insult were considered. Bicalutamide was held and patient managed with supportive care. He showed clinical improvement and normalization of the above derangements within days. Conclusion: This case highlights the hepatotoxic potential of Bicalutamide. The largest study to date addressing steroidal and non-steroidal antiandrogen induced hepatoxicity was conducted in Spain in 2005, employing the Spanish pharmacovigilance database. It, however, remained inconclusive for Bicalutamide induced hepatotoxicity due to the scarcity of reported cases by physicians, pharmacists and nurses. Our case reviews literature on the topic, and is a valuable addition to this potentially life threatening adverse effect of Bicalutamide.Table: Laboratory results