Drug Interactions between Hetlioz and mitotane

ADJUST DOSING INTERVAL: Fat-rich food enhances the absorption of mitotane. One study evaluated blood levels of mitotane (o,p'-DDD) after subjects ingested a single dose of 2 g administered using various delivery vehicles (e.g., tablets, granules, milk, chocolate or oil emulsion). Mitotane plasma levels were significantly higher for milk, chocolate, and oil emulsion when compared to those who received tablets or granules alone. In the same study, mitotane levels were evaluated in subjects following long-term treatment (total dose of 200 g over 30 to 60 days) in tablet, oil emulsion, or milk formulations. Significantly higher mean plasma levels were recorded in subjects who received mitotane as an oil emulsion or mixed in milk, when compared to tablets alone. Additionally, the recovery of o,p'-DDD from the feces was about 5 times higher in subjects who received tablets alone, suggesting absorption was reduced when compared to subjects who received mitotane mixed with a fat-rich vehicle (e.g., oil emulsion or milk).

GENERALLY AVOID: Concomitant use of mitotane with central nervous system (CNS) depressants, including alcohol, may potentiate adverse effects such as somnolence and sedation.

MANAGEMENT: According to product labeling, mitotane tablets should be taken during meals containing fat-rich food (e.g., milk, chocolate, or oil) and with a full glass of water. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them.

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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.

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