Drug Interaction Report

MONITOR: Coadministration with enzalutamide may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or P-glycoprotein (P-gp) efflux transporter. The proposed mechanism involves accelerated clearance via these routes due to enzalutamide-mediated induction. The resulting plasma concentrations will depend on the sensitivity of the affected drugs to these isoenzymes.

MANAGEMENT: Caution is advised when enzalutamide is used concomitantly with drugs that are substrates of CYP450 3A4, 2C9, 2C19, and/or P-gp, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever enzalutamide is added to or withdrawn from therapy.

GENERALLY AVOID: Coadministration with inducers of CYP450 2C8 and/or 3A4 may decrease the plasma concentrations of enzalutamide, which is primarily metabolized by CYP450 2C8 to its pharmacologically active metabolite, N-desmethyl enzalutamide, and to a lesser extent by CYP450 3A4. However, the interaction has not been evaluated in vivo.

MANAGEMENT: Concomitant use of enzalutamide with potent CYP450 2C8 and/or 3A4 inducers such as carbamazepine, lumacaftor, mitotane, phenobarbital, phenytoin, primidone (partially metabolized to phenobarbital), rifamycins, and St. John's wort should generally be avoided. Moderate inducers such as bosentan, efavirenz, etravirine, modafinil, nafcillin, and nevirapine should also be avoided if possible. The extent to which other, less potent CYP450 3A4 inducers may interact with enzalutamide is unknown. Caution is advised if they are used with enzalutamide.