Drug Interaction Report

GENERALLY AVOID: Coadministration with potent inhibitors of CYP450 1A2 may significantly increase the plasma concentrations of tasimelteon, which is primarily metabolized by the isoenzyme. When tasimelteon was administered after 6 days of treatment with the potent CYP450 1A2 inhibitor fluvoxamine 50 mg/day, tasimelteon peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2- and 7-fold, respectively, compared to tasimelteon administered alone.

MANAGEMENT: Concomitant use of tasimelteon with potent CYP450 1A2 inhibitors such as fluvoxamine, ciprofloxacin, or enoxacin should be avoided.

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 tasimelteon. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

ADJUST DOSING INTERVAL: Food may delay the absorption and onset of action of tasimelteon. According to the product labeling, administration of tasimelteon with a high-fat meal decreased peak plasma concentration (Cmax) by 44% and delayed the median time to reach Cmax by approximately 1.75 hours compared to administration in the fasted state.

MONITOR: Smoking induces CYP450 1A2 and may reduce the plasma concentrations of tasimelteon, which is metabolized by the isoenzyme. According to the product labeling, tasimelteon systemic exposure was approximately 40% lower in smokers than in nonsmokers.

MANAGEMENT: Patients receiving tasimelteon should be advised to avoid or limit consumption of alcohol. Tasimelteon should be taken without food. Patients who smoke may have a reduced therapeutic response to tasimelteon.