Drug Interaction Report

MONITOR: Coadministration with inducers of CYP450 1A2 and/or 3A4 may decrease the plasma concentrations of tasimelteon, which is primarily metabolized by these isoenzymes. When tasimelteon was administered after 11 days of treatment with the potent CYP450 inducer rifampin 600 mg/day, tasimelteon systemic exposure (AUC) decreased by approximately 90% compared to tasimelteon administered alone. No data are available for use with other, less potent inducers.

MANAGEMENT: The potential for diminished therapeutic effects of tasimelteon should be considered during coadministration with inducers of CYP450 1A2 and/or 3A4. Alternative treatments may be required if an interaction is suspected.

MONITOR: Isolated case reports have suggested that the ingestion of alcohol during griseofulvin therapy may rarely cause disulfiram-like reactions, flushing, tachycardia, or increased effects of alcohol. The mechanism is unknown.

MANAGEMENT: Patients should be advised of the possibility of increased adverse effects or a disulfiram-like reaction.

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.