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 Pharmacologic response to aprepitant should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the dosage adjusted as necessary.

ADJUST DOSING INTERVAL: Food may increase the extent of tecovirimat absorption following oral administration. When the recommended oral dose of tecovirimat (600 mg every 12 hours) was administered with a meal (approximately 600 calories and 25 g of fat) in healthy adults weighing less than 120 kg, tecovirimat absorption increased by 39% relative to fasting.

MANAGEMENT: Oral tecovirimat should be taken within 30 minutes after a full meal containing moderate or high fat (approximately 600 calories and 25 g of fat) with 6 to 8 ounces of water.