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 Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.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: 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.