Drug Interactions between daridorexant and zolpidem

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of zolpidem. 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 zolpidem with food may delay the onset of hypnotic effects. In 30 healthy subjects, administration of zolpidem 20 minutes after a meal resulted in decreased mean peak plasma drug concentration (Cmax) and area under the concentration-time curve (AUC) by 25% and 15%, respectively, compared to fasting. The time to reach peak plasma drug concentration (Tmax) was prolonged by 60%, from 1.4 to 2.2 hours.

MANAGEMENT: Patients receiving zolpidem should be advised to avoid the consumption of alcohol. For faster sleep onset, zolpidem should not be administered with or immediately after a meal.

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of daridorexant, which is primarily metabolized by CYP450 3A4. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice but has been reported for other CYP450 3A4 inhibitors. Per physiologically based pharmacokinetic (PBPK) analysis, concomitant use of itraconazole, a potent CYP450 3A4 inhibitor, increased daridorexant systemic exposure (AUC) by more than 400%. When a 25 mg daridorexant dose was coadministered with multiple 240 mg doses of diltiazem, a moderate CYP450 3A4 inhibitor, daridorexant peak plasma concentration (Cmax) and AUC increased by 1.4- and 2.4-fold, respectively. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased exposure to daridorexant may increase the risk of adverse reactions such as central nervous system (CNS) depression, sleep paralysis, hallucinations, complex sleep behaviors, worsening of depression or suicidal ideation, or headache.

After administration of a high-fat, high-calorie meal, daridorexant Cmax decreased by 16% (no effect on AUC) and the time to maximum concentration (Tmax) was delayed by 1.3 hours.

GENERALLY AVOID: Alcohol may potentiate the pharmacologic effects of daridorexant. Coadministration of daridorexant (50 mg) with alcohol led to additive effects on psychomotor performance. Use in combination may result in an increased risk of complex sleep-related behaviors (e.g., "sleep driving"), additive central nervous system (CNS) depression, and/or impairment of psychomotor performance.

MANAGEMENT: Consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with daridorexant should generally be avoided. Some authorities suggest avoiding grapefruit or grapefruit juice consumption specifically in the evening. Patients should avoid the consumption of alcohol during treatment with daridorexant. The manufacturer makes no recommendation regarding administration with food; however, the time to sleep onset may be delayed if taken with or soon after a meal.

The recommended maximum number of medicines in the 'hypnotics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'hypnotics' category:

• daridorexant
• zolpidem

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.