Drug Interactions between enzalutamide and ivacaftor / lumacaftor

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of ivacaftor, which is primarily metabolized by the isoenzyme. In study subjects, administration of a single 150 mg dose of ivacaftor with the potent CYP450 3A4 inducer rifampin (600 mg once daily) decreased ivacaftor peak plasma concentration (Cmax) and systemic exposure (AUC) by 80% and 89%, respectively, compared to administration of ivacaftor alone. When lumacaftor/ivacaftor was coadministered with rifampin, lumacaftor pharmacokinetics were minimally affected, but ivacaftor Cmax and AUC decreased by an average of 50% and 57%, respectively. No pharmacokinetic data are available for elexacaftor or tezacaftor, but decreased exposures are expected according to prescribing information.

MANAGEMENT: Concomitant use of ivacaftor-containing medications with potent CYP450 3A4 inducers is not recommended.

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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.

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