Coadministration has not been studied but should be avoided. Enzalutamide is primarily metabolized by CYP2C8 and to a lesser extent by CYP3A4. Enzalutamide concentrations may increase to a limited extent as darunavir/ritonavir inhibits CYP3A4 (minor pathway). However, darunavir/ritonavir is metabolized by CYP3A4 and enzalutamide is a strong inducer of CYP3A4. Coadministration of enzalutamide with midazolam (a CYP3A4 substrate), decreased midazolam AUC by 86%. Enzalutamide is expected to significantly decrease darunavir/ritonavir exposure, leading to loss of therapeutic effect and possible development of resistance.