Reported Adverse Drug Reaction Cases
High dose cyproterone and hepatotoxicity
High dose cyproterone (50mg, 100mg; Androcur, Androcur-100) is used predominantly for advanced prostate carcinoma. For the year ending June 2003, 59,000 prescriptions were dispensed for the 50mg or 100mg tablets and 97% of patients prescribed these tablets were male.
Over the years, ADRAC has received 105 reports implicating high-dose cyproterone. The most common adverse reactions are related to the liver with 32 reports. Other more commonly reported reactions include fatigue, dyspnoea, asthenia, confusion, depression and deep vein thrombosis.
All except one of the hepatic reactions involved male patients being treated for prostate cancer, whose ages ranged from 56 to 92 (median: 77) years. Time to onset of liver dysfunction ranged from 4 days to 4 years (median: 4-5 months); only 4 cases had a time to onset under a month.
Where liver function test results were available, the majority indicated the presence of cholestatic hepatitis, but some showed marked elevation of hepatocellular enzymes (AST, ALT). Most patients were jaundiced. Ten patients died, nine due to hepatic failure. One patient with early stage pro-state carcinoma received a liver transplant. Eleven patients had recovered at the time of reporting.
While cyproterone-induced hepatotoxicity is rare, it can be fatal or life-threatening. Severe hepatic reactions have not been reported to ADRAC with the use of low dose cyproterone (1-2mg) in combination with ethinyloestradiol (Brenda, Diane, Juliet) or oestradiol (Climen).
Although the value of monitoring is not clear, it would be reasonable to monitor liver function tests intermittently in patients taking long-term high-dose cyproterone.