Drug Interaction Report

MONITOR: The concomitant use of donepezil and ramelteon may increase the systemic exposure to ramelteon. The mechanism has not been reported. After administration of donepezil 10 mg/day for 26 days and a single 8 mg dose of ramelteon, the overall exposure (AUC) to ramelteon increased by approximately 100% and the Cmax increased by 87%.

MANAGEMENT: Close monitoring of patients is recommended during coadministration.

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.