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: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.