Flutamide-induced hepatotoxicity: A case report

Submitted: January 20, 2022
Accepted: May 12, 2022
Published: June 10, 2022
Abstract Views: 1432
PDF: 157
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

Flutamide is a non-steroidal anti-androgen drug effective in the management of prostatic carcinoma. The drug appears to be well tolerated with mild gastrointestinal adverse events and gynecomastia. Flutamide-induced hepatotoxicity may range from minor elevation in liver enzymes to hepatic failure. Here, we tried to discuss the possibility of hepatotoxicity induced by flutamide as antiandrogen therapy in a patient with prostatic adenocarcinoma. Here we present a 75-year-old man who commenced flutamide as a postoperative anti-androgen for prostatic adenocarcinoma for two months. He had markedly elevated levels of liver enzymes due to acute liver failure and subsequent multi-organ failure. The patient died after the failure of the resuscitation measures. The temporal relationship between the flutamide initiation and the emergence of hepatotoxicity is not clear, with a possible latency of 12-16 weeks. Careful monitoring of liver function test during flutamide therapy is essential to prevent serious hepatotoxicity.

Dimensions

Altmetric

PlumX Metrics

Downloads

Download data is not yet available.

Citations

Ferubko EV, Nikolaev SM, Dargaeva TD, Rendyuk TD. Correction of toxic liver damage with a multicomponent herbal extract in an animal experiment. Pharmacogn J 2020;12:168-72. DOI: https://doi.org/10.5530/pj.2020.12.25
Albassam AA, Ahad A, Alsultan A, Al-Jenoobi FI. Inhibition of cytochrome P450 enzymes by thymoquinone in human liver microsomes. Saudi Pharm J 2018;26:673-7. DOI: https://doi.org/10.1016/j.jsps.2018.02.024
Yahaya A, Wa Kammal WS, Abd Shukor N, Osman SS. Oesophageal hepatoid carcinoma with liver metastasis, a diagnostic dilemma. Malays J Pathol 2019;41:59-63.
Ghamsari A, Dadpour B, Najari F. Pathological findings of tramadol on liver tissue in the cadaver referred to legal medicine organization of Tehran 2008-2013. Int J Med Toxicol Forensic Med 2016;6:59-64.
Giorgetti R, di Muzio M, Giorgetti A, et al. Flutamide-induced hepatotoxicity: ethical and scientific issues. Eur Rev Med Pharmacol Sci 2017;21:69-77.
Rojas PA, Iglesias TG, Barrera F, et al. Acute liver failure and liver transplantation secondary to flutamide treatment in a prostate cancer patient. Urol Case Rep 2020;33:101370. DOI: https://doi.org/10.1016/j.eucr.2020.101370
Miquel M, Soler A, Vaqué A, et al. Suspected cross-hepatotoxicity of flutamide and cyproterone acetate. Liver Int 2007;27:1144-7. DOI: https://doi.org/10.1111/j.1478-3231.2007.01549.x
Brahm J, Brahm M, Segovia R, et al. Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature. Ann Hepatol 2011;10:93-8. DOI: https://doi.org/10.1016/S1665-2681(19)31595-9
Cetin M, Demirci D, Unal A, et al. Frequency of flutamide induced hepatotoxicity in patients with prostate carcinoma. Hum Exp Toxicol 1999;18:137-40. DOI: https://doi.org/10.1177/096032719901800301
Wysowski DK, Freiman JP, Tourtelot JB, Horton ML. Fatal and nonfatal hepatotoxicity associated with flutamide. Ann Int Med 1993;118:860-4. DOI: https://doi.org/10.7326/0003-4819-118-11-199306010-00006
Schulz M, Schmoldt A, Donn F, Becker H. The pharmacokinetics of flutamide and its major metabolites after a single oral dose and during chronic treatment. Eur J Clin Pharmacol 1988;34:633-6. DOI: https://doi.org/10.1007/BF00615229
Labrie F. Mechanism of action and pure antiandrogenic properties of flutamide. Cancer 1993;72:3816-27. DOI: https://doi.org/10.1002/1097-0142(19931215)72:12+<3816::AID-CNCR2820721711>3.0.CO;2-3
Thole Z, Manso G, Salgueiro E, et al. Hepatotoxicity induced by antiandrogens: a review of the literature. Urol Int 2004;73:289-95. DOI: https://doi.org/10.1159/000081585
Manso G, Thole Z, Salgueiro E, et al. Spontaneous reporting of hepatotoxicity associated with antiandrogens: Data from the Spanish pharmacovigilance system. Pharmacoepidemiol Drug Saf 2006;15:253-9. DOI: https://doi.org/10.1002/pds.1168
Ohbuchi M, Miyata M, Nagai D, et al. Role of enzymatic N-hydroxylation and reduction in flutamide metabolite-induced liver toxicity. Drug Metab Dispos 2009;37:97-105. DOI: https://doi.org/10.1124/dmd.108.021964
Kashimshetty R, Desai VG, Kale VM, et al. Underlying mitochondrial dysfunction triggers flutamide-induced oxidative liver injury in a mouse model of idiosyncratic drug toxicity. Toxicol Appl Pharmacol 2009;238:150-9. DOI: https://doi.org/10.1016/j.taap.2009.05.007
Teppner M, Böss F, Ernst B, Pähler A. Application of lipid peroxidation products as biomarkers for flutamide-induced oxidative stress in vitro. Toxicol Lett 2015;238:53-9. DOI: https://doi.org/10.1016/j.toxlet.2015.08.005
Zhang L, Guo J, Zhang Q, et al. Flutamide induces hepatic cell death and mitochondrial dysfunction via inhibition of Nrf2-mediated heme oxygenase-1. Oxid Med Cell Longev 2018;2018:8017073. DOI: https://doi.org/10.1155/2018/8017073
Schmitt B, Bennett C, Seidenfeld J, et al. Maximal androgen blockade for advanced prostate cancer. Cochrane Database Syst Rev 2000;2:CD001526. DOI: https://doi.org/10.1002/14651858.CD001526

How to Cite

Kassid, O. M., Odhaib, S. A., & Altemimi, M. T. . (2022). Flutamide-induced hepatotoxicity: A case report. Journal of Biological Research - Bollettino Della Società Italiana Di Biologia Sperimentale, 95(2). https://doi.org/10.4081/jbr.2022.10371