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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.