suvorexant
Brand: Belsomra
Prototype Drug
Drug Class: orexin receptor antagonist
Drug Family: sedative/hypnotic
Subclass: dual orexin receptor antagonist (DORA)
Organ Systems: cns
Mechanism of Action
Blocks orexin (hypocretin) 1 and 2 receptors in the hypothalamus. Orexin normally promotes wakefulness; antagonism reduces arousal and promotes sleep. Novel mechanism completely distinct from GABA-A modulators, without significant dependence potential and preserving natural sleep architecture.
orexin OX1R and OX2R receptors (hypocretin receptors)
Indications
- insomnia (sleep onset and sleep maintenance)
Contraindications
- narcolepsy
- severe hepatic impairment
Adverse Effects
Common
- next-day somnolence
- headache
- dizziness
Serious
- next-day impaired driving and cognitive function
- complex sleep behaviors (rare)
- suicidal ideation (class effect)
- narcolepsy-like symptoms (sleep paralysis, hypnagogic hallucinations)
Pharmacokinetics (ADME)
| Absorption | oral; bioavailability ~82%; high-fat meal delays absorption |
| Distribution | 96% protein bound |
| Metabolism | hepatic via CYP3A4 (major) and CYP2C19 (minor) |
| Excretion | fecal (66%) and renal (23%) |
| Half-life | 12 hours |
| Onset | 30 minutes |
| Peak | 2 hours |
| Duration | 6–8 hours |
| Protein Binding | 96% |
| Vd | 49 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors | significantly increase suvorexant exposure; reduce to 5 mg with strong inhibitors | major |
| CNS depressants | additive sedation and next-day impairment | major |
Nursing Considerations
- Administer within 30 minutes of bedtime; take only when at least 7 hours available for sleep.
- Significant next-day drowsiness may impair driving; counsel patients.
- Unlike GABA-A modulators, suvorexant targets wakefulness pathways, making it a mechanistically distinct option for patients with prior dependence on benzodiazepines or Z-drugs.
- Dose reduction is mandatory with strong CYP3A4 inhibitors (maximum 5 mg).
Clinical Pearls
- Suvorexant's orexin antagonism mechanism provides sleep by 'turning off wakefulness' rather than by inducing sedation — a conceptual advantage that may translate to more preserved sleep architecture and lower dependence potential.
- Lemborexant (a newer dual orexin antagonist) has a shorter half-life than suvorexant, potentially reducing next-day impairment; both work via the same mechanism.
Safety Profile
Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.