Flutamide is the active substance of the drug and belongs to the group of drugs that have antiandrogenic effect. Flutamide prevents the action of male sex hormones, i.e. suppresses the action of testosterone and dihydrotestosterone. Primarily, the indications for the use of flutamide refer to males and the treatment of advanced prostate cancer. It is also used in the treatment of patients with testicles surgically removed, and in patients who have not responded to another type of therapy or do not tolerate other types of treatment. The efficacy of flutamide has also been proven in the treatment of acne, hirsutism and alopecia in men and women with polycystic ovaries. It is important to emphasize that flutamide can cause severe side effects, above all liver damage, so it is not justified to use it in the treatment of conditions other than prostate cancer. Numerous data on hepatotoxicity (retrospective, prospective studies, case reports, surveillance study) were available in literature, which ranged from asymptomatic to acute, fulminant hepatitis that ended in transplantation, i.e. fatal outcome. In our paper, a review of the literature with case reports of notably hepatotoxicity is presented along with a case from our clinical practice.
Giorgetti R, di Muzio M, Giorgetti A, Girolami D, Borgia L, Tagliabracci A. Flutamide-induced hepatotoxicity: ethical and scientific issues. Eur Rev Med Pharmacol Sci. 2017;21(1 Suppl):69-77.
Reilly DR, Delva NJ, Hudson RW. Protocols for the use of cyproterone, medroxyprogesterone, and leuprolide in the treatment of paraphilia. Can J Psychiatry 2000; 45: 559-563.
POCS Australian Alliance. Evidence-based guideline for the assessment and management of polycystic ovary syndrome. Clayton: The Jean Hailes Foundation for Women’s Health; 2011. Available from: http:// www.med.monash.edu.au/epidemiology/news/ sept2nded/evidence-based-guideline-polycystic-ovary-syndrome.pdf.
Cassero-Branco C, Moyano D, Gómez O, Baasch J. Longterm safety and tolerability of flutamide for the treatment of hirsutism. Fertil Steril 2009; 91: 1183-8.
Manso G, Thole Z, Salgueiro E, Revuelta P, Hidalgo A. Spontaneous reporting of hepatotoxicity associated with antiandrogens: Data from the spanish pharmacovigilance system. Pharmaco Epidemiol Drug Saf 2006; 15: 253-9.
Cetin M, Demirci D, Unal A, Altinbas M, Guven M, Uluhizarci K. Frequency of flutamide induced hepatotoxicity in patients with prostatic carcinoma. Hum Exp Toxicol 1999; 18: 137-40.
Brahm J, Brahm M, Segovia R, Latorre R, Zapata R, Poniachik J, et al. Acute and fulminant hepatitis induced by flutamide: case series report and review of the literature. Ann Hepatol 2011; 10:93–8.
LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Flutamide. [Updated 2017 Jul 5]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK548908/.
Higuchi S, Kobayashi M, Yano A, Tsuneyama K, Fukami T, Nakajima M, Yokoi T. Involvement of Th2 cytokines in the mouse model of flutamide-induced acute liver injury. J Appl Toxicol 2012; 32: 815- 822.
Teppner M, Boss F, Ernst B, Pahler A. Application of lipid peroxidation products as biomarkers for flutamide-induced oxidative stress in vitro. Toxicol Lett 2015; 238: 53-59.
Castelo-Branco C, Hernandez-Angeles C, Alvarez-Olivares L, Balasch J. Long-term satisfaction and tolerability with low-dose flutamide: a 20-year surveillance study on 120 hyperandrogenic women. Gynecol Endocrinol 2016; 32: 723-727.
Wallace C, Lalor EA, Chik CL. Hepatotoxicity complicating flutamide treatment of hirsutism. Ann Intern Med 1993; 119: 1150.
Wysowski DK, Fourcroy JL. Flutamide hepatotoxicity. J Urol 1996; 155: 209-212.
Andrade RJ, Lucena MI, Fernandez MC, Suarez F, Montero JL, Fraga E, Hidalgo F. Fulminant liver failure associated with flutamide therapy for hirsutism. Lancet 1999; 353: 983.
Garcia Cortes M, Andrade RJ, Lucena MI, Sanchez Martinez H, Fernández MC, Ferrer T, Martin-Vivaldi R, Pelaez G, Suarez F, Romero-Gomez M, Montero JL, Fraga E, Camargo R, Alcantara R, Pizarro MA, García-Ruiz E, Rosemary-Gomez M. Flutamide-induced hepatotoxicity: report of a case series. Rev Esp Enferm Dig 2001; 93: 423-432.
De Amorim MFD, de Amorim WPD, Duques P, de Amorim PD, de Vasconcelos JR. Flutamide-induced hepatotoxicity during treatment of acne – A case report. An Bras Dermatol 2005; 80: 381-384.
Osculati A, Castiglioni C. Fatal liver complications with flutamide. Lancet 2006; 367: 1140-1141.
Castelo-Branco C, Del Pino M. Hepatotoxicity during low-dose flutamide treatment for hirsutism. Gynecol Endocrinol 2009; 25: 419-422.
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