Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of netupitant. When a single 300 mg-0.5 mg dose of netupitant-palonosetron was administered following 600 mg once daily administration of the potent CYP450 3A4 inducer rifampin for 17 days, mean netupitant peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 62% and 82%, respectively, while mean Cmax and AUC of palonosetron decreased by 15% and 19%, respectively.

MANAGEMENT: Concomitant use of netupitant or its prodrug, fosnetupitant, should generally be avoided during chronic administration of potent CYP450 3A4 inducers due to the potential for reduced efficacy of netupitant.

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.