Suvorexant

Dual orexin receptor antagonist (DORA), the first approved

Suvorexant

Belsomra

Suvorexant (brand name Belsomra) is the first FDA-approved dual orexin receptor antagonist (DORA), approved August 2014 for insomnia. Suvorexant established the DORA class as a treatment paradigm, reducing arousal via orexin blockade rather than enhancing GABA-mediated inhibition. Subsequent DORAs (lemborexant 2019, daridorexant 2022) have been positioned as iterative improvements with different pharmacokinetics. Suvorexant has been studied in mild-moderate Alzheimer disease with positive results; trials have suggested potential for reducing sleep-disordered breathing exacerbations and possibly delaying cognitive decline (though the cognitive claim remains controversial).

Experience

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Problems

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Titration strategies

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Effects

Next-day somnolence (more common than with daridorexant due to longer half-life), headache, abnormal dreams, dry mouth, fatigue. Sleep paralysis and hallucinations near sleep onset. Complex sleep behaviors class warning.

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Pharmacodynamics

Competitive antagonist at OX1R (Ki ~0.55 nM) and OX2R (Ki ~0.35 nM). Receptor dissociation slower than lemborexant or daridorexant.

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Pharmacy

Starting dose

10 mg PO 30 min before bedtime (with ≥7 hours of sleep planned)

Preparations

5 mg, 10 mg, 15 mg, 20 mg tablets

US FDA Max

20 mg/d

Common uses

Classification(s)

Classes

Dual orexin receptor antagonist (DORA), the first approved

Pharmacology

Routes

Oral

Onset

~30 min

Duration

~7-8 hours

Half-life

~12 hours

Bioavailability

~82%

Pregnancy

Limited data; avoid

Legal status

Rx, Schedule IV (US)

Purported mechanism

Competitive antagonist at OX1R and OX2R. First-in-class DORA. Receptor dissociation slower than lemborexant or daridorexant.