Daridorexant (Quviviq hcp) is a dual orexin receptor antagonist (DORA) o prescribed for adults with insomnia involving difficulty with sleep onset or maintenance.
Inhibits orexin binding to receptors to reduce wake signaling and promote sleep.
Its mechanism is presumed to be antagonism of the orexin receptors OX1R and OX2R blocking the wake-promoting neuropeptides orexin A and orexin B to suppress wake drive rather than producing broad GABAergic sedation.
Dosage and Administration • Dose & Timing: 25 mg to 50 mg orally once nightly within 30 minutes of bed, with at least 7 hours before planned waking.
Onset may be delayed with food.
Limit to 25 mg for moderate hepatic impairment; avoid in severe impairment.
Contraindications & Risks: Not used in narcolepsy or with hypersensitivity.
Risks include next-day CNS depression, complex sleep behaviors (e.g., sleep-driving), worsening depression, and sleep paralysis.
Classification: Schedule IV controlled substance.
Dosing and administration
25–50 mg once per night, taken orally within 30 minutes before bedtime, and only when at least 7 hours remain before planned awakening.
Avoid concomitant use with strong or moderate CYP3A4 inducers; daridorexant is a CYP3A4 substrate, so caution also applies with strong CYP3A4 inhibitors.
Hepatic impairment Moderate impairment (Child-Pugh 7–9): maximum 25 mg once nightly, as exposure is increased.
Severe impairment (Child-Pugh ≥10): not recommended.
CNS-depressant effects and next-day impairment: driving ability was impaired in some subjects at the 50 mg dose; risk increases with less than a full night of sleep or higher-than-recommended doses.
Additive effects occur with alcohol and other CNS depressants (benzodiazepines, opioids, TCAs), and use with other insomnia drugs is not recommended.
Worsening depression/suicidal ideation, particularly in patients with pre-existing psychiatric disorders.
Sleep paralysis, hypnagogic/hypnopompic hallucinations, and mild cataplexy-like symptoms.
Complex sleep behaviors (sleepwalking, sleep-driving, eating, phone calls, or sex while not fully awake) drug to be discontinue immediately if these occur.
Compromised respiratory function — potential depressant effects on respiration should be considered.
Falls, especially in the elderly, due to drowsiness.
Geriatric: no dose adjustment needed for age >65, but somnolence, fatigue, and fall risk increase with age.
Pediatric: safety and effectiveness not established.
The most common adverse reactions (≥5% and greater than placebo) were headache and somnolence or fatigue.
Because endogenous orexin deficiency causes narcolepsy, orexin antagonists are contraindicated/avoided in narcolepsy.
Across meta-analyses, daridorexant 50 mg reduced wake after sleep onset (MD ≈ −13 min) and latency to persistent sleep (MD ≈ −7 min) and increased total sleep time versus placebo, with 25 mg and 50 mg the most effective doses.
Lemborexant 10 mg showed the strongest effect on sleep-onset latency, while daridorexant 50 mg showed the greatest benefit on subjective total sleep time.
Daridorexant is distinguished within the DORA class by a half-life designed to cover the night while minimizing next-morning residual effects, and nonclinical data suggest no tolerance development or physical dependence, though it remains a scheduled hypnotic requiring caution.