FDA Approves New Insomnia Therapy: What Pharmacists Need to Know

On January 10, 2022, the FDA approved daridorexant (Quviviq; Idorsia) for the treatment of adults with insomnia who have difficulty with sleep onset and/or maintenance. Daridorexant is expected to be available in May 2022, after scheduling by the Drug Enforcement Administration.¹

What is Daridorexant and How Does It Work?

Daridorexant is an orexin receptor antagonist. It is thought to work by binding to and inhibiting orexin receptors. The orexin neuropeptide signaling system is associated with wakefulness. By blocking the binding of wake-promoting neuropeptides orexin A and B to their receptors, daridorexant is thought to suppress wake drive.² 

What is the Dosage?

Daridorexant is available in 25 mg and 50 mg tablets. Dosing is 25 mg to 50 mg by mouth, no more than once per night. The patient should take daridorexant in the 30 minutes before going to sleep, with at least 7 hours remaining to sleep.² 

Counseling pearl: Daridorexant takes longer to work if it is taken with—or shortly—after a meal.² 

Daridorexant should not be used in combination with strong CYP3A4 inhibitors. When taken with a moderate CYP3A4 inhibitor, the maximum dose is 25 mg once per night.² Additionally, daridorexant should not be used in combination with strong or moderate CYP3A4 inducers.² 

Patients with moderate liver impairment should not exceed a dose of 25 mg once per night, and patients with severe liver impairment should not take daridorexant.²

What Are the Adverse Effects?

The most common adverse effects are headache, fatigue, dizziness, and nausea.²

Are There Any Contraindications?

Daridorexant is contraindicated in patients with narcolepsy.²

What Are the Warnings and Precautions?

• As a central nervous system (CNS) depressant, daridorexant can impair daytime wakefulness, even when used as directed. These effects may last for up to a few days after discontinuation of the drug. Advise patients about the potential for next-day drowsiness and possible driving impairment. Remind patients to take the exact dose prescribed and to ensure that there is a full night of sleep ahead. Patients should not drive or perform other activities the next day that require complete alertness if they exceed the dosage or do not get a full night of sleep.² 
• Taking daridorexant with other CNS depressants increases the risk of CNS depression and daytime impairment. Daridorexant should not be used with other insomnia medications.² 
• Patients should not drink alcohol while taking daridorexant.² 
• Older adults are at higher risk of falls due to the side effects; however, they do not require a dosage adjustment.² 
• Patients with psychiatric conditions, including insomnia, are at an increased risk of suicide. In patients with depression who take hypnotics, there have been cases of worsening depression and suicidal thoughts and behaviors. Daridorexant should be used with caution in patients who have depression; these patients should be carefully monitored for suicide risk.²
• Daridorexant may cause sleep paralysis (the inability to move or speak for up to a few minutes during sleep/wake transitions), leg weakness, and hallucinations.² Prescribers and pharmacists should counsel patients on these possible reactions.²
• Complex sleep behaviors such as walking, driving, eating, and having sex while not fully awake, have been reported with hypnotics, including orexin antagonists. If this occurs, daridorexant should be discontinued right away.²
• Daridorexant has not been studied in patients with respiratory problems.² 
• If insomnia does not improve after 7 to 10 days of treatment, refer the patient to their physician for evaluation. This could indicate another medical or psychiatric condition.² 

Other Counseling Tips:

• Advise patients to read the medication guide and take daridorexant exactly as instructed. Patients should take daridorexant in the 30 minutes before going to bed, and only if they have at least 7 hours to sleep. Daridorexant will take longer to work in the presence of food.
• Remind patients that daridorexant can cause drowsiness the next day, even if taken exactly as instructed, which can increase the risk of falls.
• Counsel patients on the risk of worsening depression and suicidal thoughts and behavior. Patients or their caregivers and/or families should report any mood or behavior changes right away.
• Remind patients to avoid alcohol when taking daridorexant.
• Patients who are pregnant, planning to become pregnant, or are breastfeeding, should consult their healthcare provider. There is no data on the use of daridorexant in pregnancy or breastfeeding. There will be a pregnancy exposure registry. Patients can call Idorsia at 1-833-400-9611 for more information. 

References

1. Idorsia receives US FDA approval of QUVIVIQ (daridorexant) 25 and 50 mg for the treatment of adults with insomnia. News release. Idorsia. January 10, 2022. Accessed January 19, 2022. https://www.idorsia.com/media/news-details?newsId=2665386
2. Quviviq. Prescribing information. Idorsia; 2022. Accessed January 19, 2022. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/214985s000lbl.pdf