Drug Interaction Report

GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of macimorelin, which is primarily metabolized by the isoenzyme. Although the interaction has not been evaluated in pharmacokinetic studies, the potential for false positive test results should be considered.

MANAGEMENT: The prescribing information for macimorelin recommends discontinuing potent CYP450 3A4 inducers (e.g., carbamazepine, enzalutamide, lumacaftor, mitotane, phenobarbital, phenytoin, rifamycins, St. John's wort) as well as some moderate ones (e.g., bosentan, efavirenz, etravirine, modafinil) prior to macimorelin administration. A sufficient washout period following discontinuation of the inducers is also advised before using macimorelin. No recommendations are available for other, less potent CYP450 3A4 inducers; however, it may be appropriate to follow the same precaution.

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.

ADJUST DOSING INTERVAL: Food reduces the oral bioavailability of macimorelin. According to the product labeling, administration with a liquid meal decreased macimorelin peak plasma concentration (Cmax) and systemic exposure (AUC) by 55% and 49%, respectively, compared to administration under fasting conditions (i.e., for at least 8 hours).

MANAGEMENT: Macimorelin should be administered after fasting for at least 8 hours.