Pronounced: dar i doh REX ant / cue VIH vick
Mechanism: Orexin receptor antagonist
FDA-approved for: Insomnia
Daridorexant (Quviviq) is the third orexin receptor antagonist, released after suvorexant (Belsomra) and lemborexant (Dayvigo). All three medications are dual orexin (OX1 & OX2) receptor antagonists (DORAs).
Like the other two DORAs, daridorexant is approved for sleep onset and/or sleep maintenance and is expected to be a Schedule IV controlled substance when it is released in 2022.
The advantage of daridorexant over other DORAs is a shorter duration of action, making daridorexant less likely to impair daytime functioning, e.g., driving. Daridorexant has a half-life of 6–10 hours, compared to 12 hours for suvorexant and 18 hours for lemborexant. Even with daridorexant, driving ability was impaired in some subjects at the 50 mg dose.
Daridorexant is to be taken within 30 minutes of bedtime with at least 7 hours remaining prior to planned awakening. Onset of effect is delayed if taken with food.
The most common side effect was headache (7% vs 5% placebo). Daytime somnolence/fatigue occurred in 6% of subjects at 25 mg and only 5% at 50 mg (vs 4% placebo).
Based on mechanism of action DORAs are contraindicated with narcolepsy and may cause hypnagogic/hypnopompic hallucinations (0.6%) and sleep paralysis (0.4%). Cataplexy-like symptoms such as brief periods of leg weakness were observed in dogs given over 3x the maximum recommended dose.
How does the abuse potential of daridorexant compare to other DORAs? Contrast the label of daridorexant with that of suvorexant (Belsomra) which states “Suvorexant may be habit-forming. Misuse can cause addiction, overdose, or death”. The label for daridorexant only states “Individuals with a history of abuse of or addiction to alcohol or other drugs may be at increased risk for abuse of or addiction to Quviviq”. However, among recreational sedative drug users, daridorexant 100–150 mg (2–3 times maximum recommended dose) showed similar “drug-liking” ratings to suvorexant 150 mg (7.5 times max dose).
As with other classes of sedative/hypnotic medication, DORAs should be stopped immediately if complex sleep behaviors (e.g., sleepwalking) occur, due to risk of injury.
As with the other DORAs, daridorexant does not cause QT prolongation, weight gain, or withdrawal symptoms upon discontinuation.
Daridorexant 50 mg was found not to impair nighttime respiratory function in patients with mild/moderate obstructive sleep apnea (OSA) (Boof et al, 2021). It has not been studied in severe OSA or moderate OSA requiring CPAP.
The label includes a warning of worsening depression or suicidal ideation.
Bottom line: Daridorexant sounds like the DORA of choice because of its shorter half-life, which makes it less likely to impair daytime functioning. The main drawback is cost. The patent for the oldest DORA (suvorexant) does not expire until 2033, so no DORA will be available in generic form any time soon.
Dosing: 25–50 mg HS within 30 minutes before going to bed, without food; 25 mg max with moderate hepatic impairment or with moderate 3A4 inHibitors; Contraindicated with severe hepatic impairment or with strong 3A4 inHibitors.
Read more about orexin and the other DORAs in Cafer's Psychopharmacology: Visualize to Memorize 270 Medication Mascots