Drug Interaction Report

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.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.