Ketoconazole appears not to interact with exemestane,whereasrifampicin reduces exemestane levels.
Clinical evidence,mechanism, importance and management
The manufacturers say that in vitro evidence shows that while exemestane is metabolised by both cytochrome P450 isoenzyme CYP3A4 and aldoketoreductases, a clinical study found that ketoconazole (a specific inhibitor of CYP3A4) had no significant effects on pharmacokinetics of exemestane. The manufacturers therefore suggest that interactions with CYP3A4 enzyme inhibitors are unlikely (See reference number 1,2).
However, in an interaction study potent enzyme inducer rifampicin reduced AUC and maximum plasma levels of exemestane by 54 % and 41%, respectively.
The manufacturers therefore caution use of exemestane with CYP3A4 inducers such as carbamazepine, phenobarbital, phenytoin and St John’s wort (See reference number 1,2). The clinical relevance of these potential interactions is unknown, but it would seem prudent to monitor outcome of concurrent use to ensure exemestane efficacy.
Aromasin (Exemestane). Pharmacia Ltd. UK Summary of product characteristics,August2005.
Aromasin (Exemestane). Pharmacia & Upjohn Company. US Prescribing information,February 2007.