Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of capmatinib. According to the prescribing information, capmatinib is primarily metabolized by CYP450 3A4 and aldehyde oxidase. When administered with rifampin, a potent CYP450 3A4 inducer, capmatinib peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 56% and 67%, respectively. Coadministration with efavirenz, a moderate CYP450 3A4 inducer, decreased capmatinib Cmax and AUC by 34% and 44%, respectively. Data are not available for other, less potent inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of capmatinib should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

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.