Drug Interaction Report

MONITOR: Coadministration with inhibitors of CYP450 1A2 and/or 3A4 may increase the plasma concentrations of tasimelteon, which is primarily metabolized by these isoenzymes. 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. When administered after 5 days of treatment with the potent CYP450 3A4 inhibitor ketoconazole 400 mg/day, tasimelteon AUC increased by approximately 50%.

MANAGEMENT: Caution is advised if tasimelteon is prescribed in combination with inhibitors of CYP450 1A2 and/or 3A4. Patients should be monitored for excessive sedation and other side effects.

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.