THERAPEUTICS

Brands

• Belsomra

Generic?

• No

Class

• Orexin receptor antagonist

Commonly Prescribed for

(FDA approved in bold)

• Insomnia characterized by difficulties with sleep onset and/or sleep maintenance

How the Drug Works

• Blocks wake-promoting orexin A and orexin B binding to orexin receptor type 1 and type 2 to suppress wake drive. The orexin pathway originates within the lateral hypothalamus and projects to brain nuclei expressing orexin peptide receptors

How Long Until It Works

• Peak concentrations occur around 2 hours

If It Works

• Continue to use at lowest required dose with appropriate monitoring

If It Doesn't Work

• Increase dose or combine with other anti-insomnia agents

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Often depends on the comorbidity; may use low dose of antihistamine, TCAs, benzodiazepines, or antipsychotics

Tests

• Not available

ADVERSE EFFECTS (AEs)

How the Drug Causes AEs

• CNS depressant

Notable AEs

• Most common: daytime somnolence, abnormal thinking, behavioral change, sleep paralysis, hypnagogic/hypnopompic hallucination, cataplexy-like symptoms

Life-Threatening or Dangerous AEs

• Complex sleep behavior (e.g., sleep-driving)

• Worsening of depression/suicidal ideation

• Respiratory suppression

Weight Gain

• Unusual

Sedation

• Problematic

What to Do About AEs

• Reduce dose or discontinue

Best Augmenting Agents to Reduce AEs

• Most AEs cannot be reduced by use of augmenting agent

DOSING AND USE

Usual Dosage Range

• Insomnia: 10–20mg/night

Dosage Forms

• Tablets: 5, 10, 15, 20mg

How to Dose

• Start with 10mg within 30 minutes of going to bed, with at least 7 hours remaining before the time of awakening

Dosing Tips

• Adjust dose to clinical response and AEs. Re-evaluate if insomnia persists after 7–10 days of treatment

• Reduced dose (5mg) in subjects receiving moderate CYP3A inhibitors (e.g., ciprofloxacin, aprepitant, diltiazem, grapefruit juice, etc.)