Drug Interaction Report

ADJUST DOSE: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of exemestane, which is primarily metabolized by the isoenzyme. In 10 healthy postmenopausal volunteers, administration of exemestane (25 mg single dose) following pretreatment with the potent inducer rifampin (600 mg daily for 14 days) resulted in a 41% decrease in exemestane peak plasma concentration (Cmax) and a 54% decrease in exemestane systemic exposure (AUC).

MANAGEMENT: The manufacturer recommends increasing the dosage of exemestane to 50 mg once daily when used with potent CYP450 3A4 inducers such as carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, primidone (partially metabolized to phenobarbital), rifamycins, and St. John's wort. However, it has also been suggested that suppression of estrogen levels is not affected by the interaction, thus dosage adjustment of exemestane is not required. The extent to which other, less potent CYP450 3A4 inducers may interact with exemestane is unknown. Caution is advised if they are used with exemestane.

ADJUST DOSING INTERVAL: Coadministration with food increases the oral bioavailability of etravirine. The mechanism is unknown. Compared to administration following a meal, the systemic exposure (AUC) to etravirine was decreased by about 50% when the drug was administered under fasting conditions. The types of meal studied (ranging from 345 kilocalories containing 17 grams fat to 1160 kilocalories containing 70 grams fat) did not appear to make a difference with respect to impact on etravirine bioavailability.

MANAGEMENT: Etravirine should always be administered following a meal.