Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of aprepitant, which is primarily metabolized by the isoenzyme. According to the product labeling, administration of a single 375 mg dose of aprepitant on day 9 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg/day for 14 days) resulted in an 11-fold decrease in aprepitant systemic exposure (AUC) and 3-fold decrease in the mean terminal half-life.

MANAGEMENT: The possibility of diminished therapeutic response to aprepitant should be considered during coadministration with CYP450 3A4 inducers, particularly potent ones like carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifampin, and St. John's wort. Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.

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.