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.

GENERALLY AVOID: Concurrent acute use of barbiturates and ethanol may result in additive CNS effects, including impaired coordination, sedation, and death. Tolerance of these agents may occur with chronic use. The mechanism is related to inhibition of microsomal enzymes acutely and induction of hepatic microsomal enzymes chronically.

MANAGEMENT: The combination of ethanol and barbiturates should be avoided.

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.