Clinical Overview: Daridorexant for the Treatment of Insomnia

The FDA approved daridorexant in January 2022 to treat insomnia after it showed improvements in changes in latency to persistent sleep and wake after sleep onset.

Daridorexant (Quviviq) is a dual orexin receptor (OX1R and OX2R) antagonist taken to improve sleep onset and maintenance. The FDA approved daridorexant in January 2022 to treat insomnia and it will be available following its scheduling by the DEA.

In 2 clinical trials that evaluated 1854 participants diagnosed with insomnia, researchers randomized patients to receive either daridorexant or a placebo to measure changes in latency to persistent sleep (LPS) and wake after sleep onset (WASO). These measures are markers of sleep onset and maintenance, respectively, therefore a reduction in these times is indicative of clinical improvement.

In the first study, researchers found that participants administered 25 mg of daridorexant had an improvement to their WASO and LPS reductions of 12 and 8 minutes more, respectively, compared to placebo at 3 months. This reduction was also seen in participants receiving the 50 mg dosing, who showed reductions of 18 and 12 minutes, respectively, compared to placebo in the same period.

The second study trialed 25 mg and 10 mg dosing. The researchers found that with the 25 mg dosing, there was a similar reduction in WASO and LPS times at 10 and 9 minutes, respectively, at 3 months. They also found no statistically significant reduction in WASO or LPS times in participants who received 10 mg doses compared to placebo over the same period.1

Mechanism of Action1,2

Daridorexant is a dual antagonist on the OX1R and OX2R receptors, which suppresses the wake drive.

Dosage and Administration2

  • Daridorexant 25 mg and 50 mg: Take 1 tablet by mouth within 30 minutes of going to bed.
  • Daridorexant use should be avoided with strong CYP3A4 inhibitors.
  • Daridorexant use should be limited to 25 mg when used with moderate CYP3A4 inhibitors.
  • Daridorexant use should be avoided with use of strong or moderate CYP3A4 inducers.
  • Daridorexant use should be limited to 25 mg in patients with moderate hepatic impairment and is not recommended for use in patients with severe hepatic impairment.

Contraindications2

Daridorexant is contraindicated in patients with narcolepsy.

Adverse Events (AEs)1,2

The most commonly reported AEs with daridorexant are dizziness, headache, and somnolence. In the 50 mg dosage, nausea was also reported.

Warnings and Precautions2

Daridorexant acts as a central nervous system (CNS) depressant and may lead to daytime impairment. Pharmacists should advise patients about the potential of somnolence and that taking daridorexant without a full night of sleep (7 hours) may increase this risk.

Sleep paralysis and cataplexy-like symptoms in the minutes between sleep-wake transitions have been reported with daridorexant use. Pharmacists should explain the nature of these events to the patient.

Sleep walking, sleep-driving, and other complex sleep behaviors have been reported with use of hypnotics. Patients should discontinue daridorexant if they experience complex sleep behaviors.

Concomitant use of alcohol may lead to increased CNS depression and psychomotor impairment. Pharmacists should counsel patients on the increased risk and advise them to avoid alcohol consumption when taking this medication.

Because of potential increases in somnolence and drowsiness, patients (especially the elderly) are at an increased risk for falls.

Pregnancy and Lactation2

Avoid use if pregnant as there are limited data available assessing whether daridorexant causes fetal harm. Daridorexant and its metabolites are likely present in human breastmilk. Infants potentially exposed to daridorexant through breast milk should be monitored for excessive sedation.

About the Author

Matthew Gall is a 2024 PharmD candidate at the University of Connecticut.

References

  1. Idorsia receives US FDA approval of QUVIVIQ (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. Accessed March 7, 2022.
  2. QUVIVIQ Prescribing Information. Idorsia Pharmaceuticals US Inc. Jan 2022. Accessed March 7, 2022.