Drug Interaction Report

GENERALLY AVOID: Coadministration with potent or moderate inducers of CYP450 3A4 may significantly 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. Loss of anti-tumor activity may result.

MANAGEMENT: Concomitant use of capmatinib with potent or moderate CYP450 3A4 inducers should be avoided.

GENERALLY AVOID: Concurrent use of rifampin in patients who ingest alcohol daily may result in an increased incidence of hepatotoxicity. The increase in hepatotoxicity may be due to an additive risk as both alcohol and rifampin are individually associated with this adverse reaction. However, the exact mechanism has not been established.

ADJUST DOSING INTERVAL: Administration with food may reduce oral rifampin absorption, increasing the risk of therapeutic failure or resistance. In a randomized, four-period crossover phase I study of 14 healthy male and female volunteers, the pharmacokinetics of single dose rifampin 600 mg were evaluated under fasting conditions and with a high-fat meal. Researchers observed that administration of rifampin with a high-fat meal reduced rifampin peak plasma concentration (Cmax) by 36%, nearly doubled the time to reach peak plasma concentration (Tmax) but reduced overall exposure (AUC) by only 6%.

MANAGEMENT: The manufacturer of oral forms of rifampin recommends administration on an empty stomach, 30 minutes before or 2 hours after meals. Patients should be encouraged to avoid alcohol or strictly limit their intake. Patients who use alcohol and rifampin concurrently or have a history of alcohol use disorder may require additional monitoring of their liver function during treatment with rifampin.