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

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.