enzalutamide + gemfibrozil

Enzalutamide + gemfibrozil refers to the coadministration of enzalutamide, an androgen receptor inhibitor used primarily in metastatic castration-resistant prostate cancer, with gemfibrozil, a strong CYP2C8 inhibitor typically used for hyperlipidemia. Enzalutamide acts by preventing androgen receptor nuclear translocation and DNA binding, thereby blocking androgen receptor-mediated cellular proliferation. Gemfibrozil is a lipid-lowering agent that potently inhibits CYP2C8, an enzyme highly relevant to the metabolism of enzalutamide. Coadministration significantly increases plasma exposure to enzalutamide and its active metabolites, resulting in higher risk for dose-related toxicities such as seizures. Clinical guidance recommends reducing enzalutamide dose when used with gemfibrozil and avoiding this combination if possible due to increased toxicity risk.