Drug Interaction Report

CONTRAINDICATED: Coadministration with fluvoxamine may significantly increase the plasma concentrations and pharmacologic effects of ramelteon. The mechanism is fluvoxamine inhibition of the CYP450 1A2-mediated metabolism of ramelteon. According to the product labeling, administration of ramelteon (16 mg single oral dose) following pretreatment with fluvoxamine (100 mg orally twice daily for 3 days) resulted in a 70-fold increase in ramelteon peak plasma concentration (Cmax) and a 190-fold increase in systemic exposure (AUC) compared to administration of ramelteon alone. Fluvoxamine pharmacokinetics were not significantly altered by ramelteon.

MANAGEMENT: The use of ramelteon in combination with fluvoxamine is considered contraindicated. Other SSRIs such as citalopram, escitalopram, fluoxetine, paroxetine, or sertraline may be safer alternatives in ramelteon-treated patients, since they are generally believed to have little, if any, effect on CYP450 1A2.

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

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

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.