Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of rolapitant, which is primarily metabolized by the isoenzyme. When the potent CYP450 3A4 inducer rifampin was administered at 600 mg once daily for 7 days before and 7 days after a single 180 mg dose of rolapitant, mean rolapitant peak plasma concentration (Cmax) and systemic exposure decreased by 30% and 85%, respectively, compared to administration of rolapitant alone. Mean half-life of rolapitant decreased from 176 hours to 41 hours with rifampin. Loss of therapeutic efficacy may occur.

MANAGEMENT: Rolapitant should not be used in patients who require chronic treatment with potent CYP450 3A4 inducers.

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.