Oral enzalutamide is approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). As mCRPC most commonly occurs in older men, and polypharmacy is prevalent among elderly patients, drug interactions are an important consideration for clinical use of enzalutamide.

This article describes two phase I drug interaction studies: one investigating the effects of coadministered drugs on the pharmacokinetics of enzalutamide, and one investigating the effects of enzalutamide on the pharmacokinetics of coadministered drugs.

The results showed that strong cytochrome P450 (CYP) 2C8 inhibitors can increase the composite area under the plasma concentration–time curve from time zero to infinity (AUC∞) of enzalutamide plus its active metabolite by 2.2-fold, and enzalutamide is a moderate inducer of CYP2C9 and CYP2C19 and a strong inducer of CYP3A4. Precautionary measures for mitigating the risks of clinical drug interactions are described within the article.