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Antiandrogens are a class of drugs used in androgen deprivation therapy for the treatment of advanced or metastatic prostate cancer. They are classified into two groups: nonsteroidal antiandrogens ( Flutamide, Bicalutamide and Nilutamide ) and steroidal antiandrogens ( Cyproterone acetate ). Both groups work by competing with circulating androgens for receptor sites within the prostate cell, thus promoting apoptosis and inhibiting prostate cancer growth. Steroidal antiandrogens have the added ability of suppressing the production of testosterone. Depending on the drug, antiandrogens are indicated for use in monotherapy, or in combination with radiotherapy, luteinizing hormone-releasing hormone analogues or orchiectomy for complete androgen blockade.

Health Canada has received 25 case reports of hepatotoxicity in men aged 60-98 years old that were suspected of being associated with antiandrogens, 24 of which were serious. The most common adverse reactions included jaundice, increased liver enzyme levels, nausea, hepatic necrosis, ascites and hepatitis. One report of hepatotoxicity involved a woman using an antiandrogen for hirsutism.

The risk of hepatotoxicity with the use of antiandrogens has also been described in the clinical literature. Although both steroidal and nonsteroidal antiandrogens have been associated with hepatotoxicity, the frequency of these adverse reactions, and their clinical features, appear to differ from one drug to another. For example, the results of an observational study showed a higher occurrence of hepatotoxicity among patients taking Flutamide than among those taking Cyproterone acetate ( 15.3% versus 9.5%, p=0.034 ). Furthermore, this study found that the occurrence of serious hepatotoxicity ( defined as an elevation in liver enzyme levels greater than 6 times the upper limit of normal ) was 4.8% with the use of Flutamide and 3.8% with Cyproterone acetate. Serious hepatotoxicity is reported to be rare with Bicalutamide and Nilutamide.

Data from published clinical studies and case reports from the Canada Vigilance database consistently suggest that the risk of hepatotoxicity has been associated with all antiandrogen products marketed in Canada. Health care professionals should be aware of the risk of hepatotoxicity associated with the use of these products.

Source: Health Canada - CARN, 2012

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