Suvorexant

• Insomnia
• Sleep Onset Insomnia
• Sleep Maintenance Insomnia
• Chronic Insomnia

Suvorexant is a dual orexin receptor antagonist (DORA) used to treat insomnia characterized by difficulty with sleep onset and/or sleep maintenance. It represents a novel mechanism for treating insomnia by blocking wake-promoting orexin signaling.

Mechanism of Action

Suvorexant works by antagonizing orexin receptors:

• Dual orexin receptor antagonism: Blocks both OX1R and OX2R receptors
• Suppresses wake drive: Orexins A and B promote and maintain wakefulness
• Promotes natural sleep: Reduces orexin-driven arousal without sedation
• Preserves sleep architecture: May maintain more normal sleep stages than GABA-targeting drugs

Orexin neurons are most active during wakefulness and silent during sleep.

Available Formulations

Suvorexant is available as tablets:

• 5 mg, 10 mg, 15 mg, 20 mg tablets

Medical Uses

FDA-Approved Indication:

• Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance

Suvorexant improves both time to fall asleep and total sleep time.

Dosing Guidelines

Adults:

• Starting dose: 10 mg once nightly within 30 minutes of bedtime
• May increase to 20 mg if 10 mg is tolerated but not effective
• Maximum: 20 mg nightly

Time Requirements:

• Take within 30 minutes of going to bed
• Allow at least 7 hours before planned awakening

With CYP3A4 Inhibitors:

• Moderate CYP3A4 inhibitors: Start at 5 mg; max 10 mg
• Strong CYP3A4 inhibitors: Avoid use

Important Safety Information

Controlled Substance:

• Schedule IV controlled substance

Contraindications:

• Narcolepsy

Warnings and Precautions:

• CNS depressant effects: Impaired alertness and motor coordination, including next-day impairment
• Sleep paralysis, hypnagogic/hypnopompic hallucinations: May occur
• Complex sleep behaviors: Sleepwalking, sleep-driving, and other activities while not fully awake (discontinue if occurs)
• Worsening of depression/suicidal ideation: Monitor patients with depression
• Compromised respiratory function: Use with caution in patients with respiratory impairment
• Cataplexy-like symptoms: Possible in susceptible individuals

Drug Interactions

Strong CYP3A4 Inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir):

• Avoid concomitant use

Moderate CYP3A4 Inhibitors (diltiazem, erythromycin, fluconazole):

• Start at 5 mg; max 10 mg

Strong CYP3A4 Inducers (rifampin, carbamazepine, phenytoin):

• May reduce efficacy substantially

Other CNS Depressants (alcohol, opioids, benzodiazepines):

• Additive CNS depression; use with caution

Digoxin:

• Suvorexant may increase digoxin levels; monitor

Special Populations

• Hepatic Impairment:
  • Mild to moderate: No adjustment
  • Severe: Not recommended
• Renal Impairment: No adjustment needed
• Elderly: No specific adjustment; consider 5 mg starting dose
• Pregnancy: Limited data; not recommended
• Lactation: Unknown if excreted in milk
• Pediatric: Safety not established