Flutamide-induced hepatotoxicity: A case report

Submitted: January 20, 2022
Accepted: May 12, 2022
Published: June 10, 2022
Abstract Views: 1437
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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.

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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