Introduction
Belsomra (suvorexant) is a first-in-class orexin receptor antagonist approved by the FDA in 2014 for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. Unlike traditional sleep medications that act on GABA receptors, Belsomra represents a novel approach to insomnia management by targeting the orexin neurotransmitter system, which plays a key role in promoting wakefulness.
Mechanism of Action
Belsomra exerts its therapeutic effects through selective dual antagonism of orexin receptors OX1R and OX2R. Orexin neuropeptides (orexin A and orexin B) are produced in the hypothalamus and promote wakefulness. By blocking the binding of orexins to their receptors, suvorexant suppresses wake drive, thereby facilitating sleep initiation and maintenance. This mechanism differs from sedative-hypnotics that enhance GABAergic inhibition.
Indications
FDA-approved for:
- Treatment of insomnia characterized by difficulties with sleep onset
- Treatment of insomnia characterized by difficulties with sleep maintenance
Dosage and Administration
Standard dosing: 10-20 mg once nightly, taken within 30 minutes of bedtime Maximum dose: 20 mg daily Administration: Take with no food or after a light meal; avoid with or immediately after a high-fat meal Special populations:- Hepatic impairment: 5 mg recommended for moderate hepatic impairment; not recommended for severe hepatic impairment
- Concomitant CYP3A inhibitors: 5 mg maximum dose when used with moderate CYP3A inhibitors; contraindicated with strong CYP3A inhibitors
- Elderly: Consider starting dose of 5-10 mg
Pharmacokinetics
Absorption: Median Tmax approximately 2 hours (range 0.5-6 hours); high-fat meal delays absorption by approximately 1.5 hours Distribution: Volume of distribution ~49 L; 99.5% protein bound Metabolism: Primarily metabolized by CYP3A4; minor contribution from CYP2C19 Elimination: Terminal half-life ~12 hours; primarily excreted in feces (66%) with minor renal excretion (23%)Contraindications
- Narcolepsy
- Concomitant use with strong CYP3A inhibitors
- History of hypersensitivity to suvorexant or any component of the formulation
Warnings and Precautions
Sleep-driving and other complex behaviors: May occur without complete awakening; risk increases with dose and concomitant CNS depressants CNS depression effects: Dose-dependent impairment of next-day alertness and motor coordination Worsening depression/suicidal ideation: May emerge during treatment; evaluate patients with comorbid depression appropriately Sleep paralysis/hypnagogic hallucinations: May occur, particularly at higher doses Respiratory depression: Caution in patients with compromised respiratory function Drug abuse and dependence: Schedule IV controlled substance; potential for abuse and dependenceDrug Interactions
Strong CYP3A inhibitors: Contraindicated (e.g., clarithromycin, itraconazole, ketoconazole) Moderate CYP3A inhibitors: Reduce Belsomra dose to 5 mg (e.g., ciprofloxacin, diltiazem, fluconazole) CNS depressants: Additive effects with alcohol, benzodiazepines, opioids, and other sedating medications CYP3A inducers: May decrease suvorexant concentrations (e.g., rifampin, carbamazepine, St. John's wort)Adverse Effects
Common (≥5%):- Somnolence
- Headache
- Dizziness
- Fatigue
- Dry mouth
- Abnormal dreams
- Complex sleep behaviors (sleep-driving, sleep-eating)
- Hypersensitivity reactions
- Sleep paralysis
- Cataplexy-like symptoms
- Worsening depression/suicidal ideation
- Respiratory depression
Monitoring Parameters
- Sleep patterns and quality
- Next-day alertness and functioning
- Signs of complex sleep behaviors
- Mood changes, especially in patients with depression
- Respiratory status in patients with COPD or sleep apnea
- Signs of misuse or abuse
- Concomitant medication use
Patient Education
- Take only when able to get a full night's sleep (7-8 hours)
- Take immediately before bedtime
- Avoid alcohol and other CNS depressants
- Report any sleep behaviors you don't remember performing
- Be cautious with morning activities requiring alertness
- Do not increase dose without medical supervision
- Inform healthcare providers of all medications being taken
- Report worsening depression or suicidal thoughts
- Avoid high-fat meals close to dosing time
References
1. FDA Prescribing Information: Belsomra (suvorexant). Revised 2022. 2. Herring WJ, et al. Orexin receptor antagonism for treatment of insomnia: A randomized clinical trial of suvorexant. Neurology. 2012;79(23):2265-2274. 3. Michelson D, et al. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation: A phase 3 randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2014;13(5):461-471. 4. Kishi T, et al. Suvorexant for primary insomnia: A systematic review and meta-analysis of randomized placebo-controlled trials. PLoS One. 2021;16(4):e0250071. 5. American Academy of Sleep Medicine. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults. J Clin Sleep Med. 2017;13(2):307-349.