Introduction
Quviviq (daridorexant) is a novel dual orexin receptor antagonist approved by the FDA in January 2022 for the treatment of adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance. As the newest addition to the orexin receptor antagonist class, Quviviq offers a targeted mechanism for sleep regulation while maintaining a favorable safety profile compared to traditional sedative-hypnotics.
Mechanism of Action
Quviviq exerts its therapeutic effects through selective antagonism of both orexin receptor types 1 and 2 (OX1R and OX2R). Orexin neuropeptides, produced in the hypothalamus, promote wakefulness and arousal. By blocking the binding of orexin A and orexin B to their receptors, daridorexant reduces wakefulness drive without causing widespread CNS depression. This targeted mechanism preserves natural sleep architecture, including REM and slow-wave sleep stages, while minimizing next-day residual effects.
Indications
Quviviq is indicated for the treatment of insomnia in adults, specifically addressing:
- Sleep onset latency (time to fall asleep)
- Sleep maintenance (reduced nighttime awakenings)
- Total sleep time improvement
Dosage and Administration
Standard dosing: 25-50 mg orally once nightly, taken within 30 minutes before bedtime with at least 7 hours remaining before planned awakening Dosage adjustment:- Initial dose: 25 mg once nightly
- May increase to 50 mg based on clinical response and tolerability
- Maximum recommended dose: 50 mg daily
- Hepatic impairment: Not recommended in severe hepatic impairment (Child-Pugh C)
- Renal impairment: No dosage adjustment necessary for mild to moderate impairment; use with caution in severe impairment
- Geriatric patients: Consider starting with 25 mg dose
- CYP3A4 inhibitors: Avoid concomitant use with strong CYP3A4 inhibitors
Pharmacokinetics
Absorption: Rapid absorption with median Tmax of 1.0-1.5 hours; high fat meal may delay absorption but does not affect overall exposure Distribution: Volume of distribution approximately 31 L; protein binding >99% Metabolism: Primarily metabolized by CYP3A4 with minor contributions from CYP2C19 and CYP3A5; forms inactive metabolites Elimination: Half-life approximately 8 hours; excreted primarily in feces (∼68%) and urine (∼28%) Steady-state: Achieved within 3 days with once-daily dosingContraindications
- Hypersensitivity to daridorexant or any component of the formulation
- Narcolepsy
- Concomitant use with strong CYP3A4 inhibitors
- Severe hepatic impairment
Warnings and Precautions
CNS Depression: May impair mental and/or physical abilities; caution patients about operating hazardous machinery or driving Sleep Paralysis/Hallucinations: May experience sleep paralysis and hypnagogic/hypnopompic hallucinations Complex Sleep Behaviors: Rare reports of sleepwalking, sleep driving, and other complex behaviors Worsening Depression/Suicidal Ideation: Monitor patients with depression carefully Respiratory Depression: Use with caution in patients with compromised respiratory function Drug Abuse and Dependence: Schedule IV controlled substance; potential for abuse and dependence Withdrawal Effects: May produce mild withdrawal effects upon discontinuationDrug Interactions
Strong CYP3A4 Inhibitors: Contraindicated (e.g., ketoconazole, itraconazole, clarithromycin) Moderate CYP3A4 Inhibitors: Reduce Quviviq dose to 25 mg (e.g., fluconazole, diltiazem) CNS Depressants: Additive effects with alcohol, benzodiazepines, opioids, and other sedatives CYP3A4 Inducers: May decrease daridorexant exposure (e.g., rifampin, carbamazepine)Adverse Effects
Common (≥2% and greater than placebo):- Headache (6% vs 5% placebo)
- Fatigue (5% vs 3%)
- Somnolence (4% vs 2%)
- Dizziness (3% vs 2%)
- Nausea (3% vs 2%)
- Complex sleep behaviors
- Anaphylaxis
- Angioedema
- Suicidal ideation
Monitoring Parameters
- Sleep quality and duration assessment
- Daytime alertness and functioning
- Mood changes, especially in patients with depression
- Signs of misuse or abuse
- Cognitive and complex motor function
- Adverse effects at follow-up visits
Patient Education
- Take Quviviq only when you can get a full night's sleep (at least 7 hours)
- Take within 30 minutes of going to bed
- Avoid alcohol and other CNS depressants
- Do not engage in hazardous activities until you know how the medication affects you
- Report any unusual sleep behaviors, sleep paralysis, or hallucinations
- Inform healthcare providers of all medications being taken
- Do not abruptly discontinue without medical supervision
- Store securely to prevent misuse by others
References
1. FDA Prescribing Information: Quviviq (daridorexant). January 2022 2. Mignot E, Mayleben D, Fietze I, et al. Safety and efficacy of daridorexant in patients with insomnia: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022;21(2):125-139 3. Roch C, Bergamini G, Steiner MA, Clozel M. Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia. Psychopharmacology (Berl). 2021;238(10):2693-2708 4. Dauvilliers Y, Zammit G, Fietze I, et al. Daridorexant, a new dual orexin receptor antagonist, in elderly subjects with insomnia: a randomized clinical study. J Clin Psychiatry. 2022;83(2):21m14028 5. ClinicalTrials.gov: Phase 3 studies of daridorexant (NCT03545191, NCT03575104)