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 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.