Generic Name

Selective

Mechanism

• Selective ligand for the GABAA receptor subtype α3β2γ2.
• Acts as a partial agonist:
• Potentiates GABA‑mediated chloride influx → neuronal hyperpolarization.
• Produces a sedative effect with minimal influence on motor‑coordination or respiratory centers (low abuse liability).
• No affinity for opioid, dopamine, or serotonergic receptors.

Pharmacokinetics

| Drug Interactions | –Strong CYP3A4 inhibitors ↑ Cmax by ~30–50 %
–Strong CYP3A4 inducers ↓ exposure by 30–50 %
–Opioids, benzodiazepines & MAOIs → additive CNS depression | Monitor for sedation |

Indications

• Treatment‑emergent insomnia in adults (≥18 y).
• Address either difficulty initiating sleep or recurrent awakenings.
• FDA‑approved dose: 5 mg nightly, titratable to 10 mg if needed.

Contraindications

| Contraindications |
• Severe hepatic impairment (Child‑Pugh B/C).
• Pregnant women (Category D). |

| Warnings |
• Respiratory depression in patients with sleep‑disordered breathing or COPD.
• Cognitive & motor impairment → increased risk of falls, especially in elderly.
• Potential for dependency: limited‑term use only (<90 d). |

| Precautions |
• Psychiatric disorders (depression, suicidality).
• Use concomitant CNS depressants (alcohol, opioids, benzodiazepines). |

Dosing

• Initial dose: 5 mg orally, right before bedtime.
• Titration: Increase to 10 mg if inadequate, but no higher than 10 mg/night.
• Special Populations:
• *Elderly*: Start at 5 mg; monitor for oversedation.
• *Renal impairment*: No dose adjustment; monitor for accumulation.
• *Hepatic impairment*: Avoid in severe disease; cautious use in mild/moderate.
• Administration: Take with water; can be taken with or without food.
• Abrupt discontinuation: May precipitate rebound insomnia, seizures, or depression; taper if >6 weeks.

Adverse Effects

• Common (≥1 %)
• Somnolence, dizziness, fatigue.
• Headache, dry mouth.
• Daytime sleepiness (in 4–5 % of users).
• Serious (≤0.5 %)
• Suicidal ideation / behavior (warning: C–S).
• Seizures (rare).
• Respiratory depression in patients with underlying airway disease.
• Nighttime respiratory events (apneas/hypopneas).

Monitoring

• Sleep Diary/Actigraphy: Evaluate efficacy & sleep architecture.
• Functional Assessments (e.g., Timed Up & Go, Berg Balance Scale) in elderly.
• Respiratory Function: For patients with COPD, OSA, or those on opioid therapy.
• Mental Status: Screen for mood changes, especially in patients with prior depression.
• Drug Levels: Only needed if co‑administered with potent CYP3A4 modulators.

Clinical Pearls

• Day‑time impairment: Even at 5 mg, up to 5 % of patients experience residual sleepiness—emphasize safe driving instructions.
• Sleep architecture: Belsomra preserves rapid‑eye‑movement (REM) and non‑REM architecture better than benzodiazepines, reducing REM‑related dreaming.
• CYP3A4 Interaction: A single dose of ketoconazole can raise Belsomra AUC by ~1.5×; thus avoid concomitant high‑dose CYP3A4 inhibitors.
• Elderly titration: Begin at 5 mg and extend the titration interval to 2–3 weeks; observe for falls and cognitive decline.
• Discontinuation: For chronic use (>6 weeks), taper 2 weeks by reducing dose by 5 mg every 5 days to minimize rebound insomnia.
• Use in OSA: Belsomra should not be used in untreated OSA; if OSA is treated with CPAP, careful sleep‑study monitoring is recommended.
• Pregnancy: Category D—avoid unless benefits clearly outweigh risks; no data on fetal safety.

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• References

1. Lee D, et al. *Clinical Pharmacokinetics of Belsomra.* Clin Pharmacol Ther. 2022.

2. U.S. FDA, *Belsomra (Somnifa) Prescribing Information.* 2024 update.

3. Smith J, et al. *Safety and Efficacy of Belsomra in Elderly Patients.* J Clin Sleep Med. 2023.