Drug Interaction Report

MONITOR: Coadministration with tecovirimat may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Tecovirimat is a weak inducer of CYP450 3A4. In a drug interaction study involving 24 healthy subjects, a single 2 mg dose of midazolam was coadministered with tecovirimat (600 mg twice daily), and the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 39% and 32%, respectively.

MANAGEMENT: The potential for diminished pharmacologic effects of CYP450 3A4 substrates should be considered during coadministration with tecovirimat.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of ramelteon. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Administration of ramelteon with or immediately after a high-fat/heavy meal may delay the onset of hypnotic effects. In study subjects, administration of a 16 mg dose of ramelteon with a high-fat meal decreased the peak plasma drug concentration (Cmax) by 22% and delayed the median time to reach peak plasma drug concentration (Tmax) by approximately 45 minutes compared to administration in a fasted state.

MANAGEMENT: Patients receiving ramelteon should be advised to avoid the consumption of alcohol. For faster sleep onset, ramelteon should not be administered with or immediately after a high-fat/heavy meal.

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.