Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 2C8 may increase the plasma concentrations and effects of tovorafenib, which has been found in vitro to be primarily metabolized by CYP450 2C8 and aldehyde oxidase, and to a lesser extent, by the isoenzymes CYP450 3A, 2C9, and 2C19. Increased plasma concentrations may increase the risk for adverse drug reactions including but not limited to, hemorrhage, skin toxicity, photosensitivity, hepatotoxicity, and reduced growth velocity in patients 18 years of age or younger. However, data from formal clinical drug interaction studies are not available.

MANAGEMENT: Caution is advised if tovorafenib is prescribed in combination with CYP450 2C8 inhibitors. Patients should be monitored for the development of hemorrhage, skin toxicity, photosensitivity, hepatotoxicity, and, in patients 18 years of age or younger, reduced growth velocity. Alternative therapy may need to be considered if a drug interaction is suspected.

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.