What is the recommended dose and contraindications for Lemborexant (Dayvigo) in adults with insomnia?

Lemborexant Dosing and Contraindications

Lemborexant should be initiated at 5 mg taken once nightly, no more than once per night, within 30 minutes of going to bed with at least 7 hours remaining before planned awakening, and can be increased to a maximum of 10 mg if clinically indicated, though the 5 mg dose appears equally effective with fewer side effects. 1, 2

Recommended Dosing

Standard Adult Dosing

• Starting dose: 5 mg once nightly 1
• Maximum dose: 10 mg once nightly if needed for additional benefit 1
• Timing: Take at least 7 hours before planned awakening to minimize residual morning effects 1
• The medication should be taken within 30 minutes of going to bed, no more than once per night 1

Dose Selection Considerations

• Both 5 mg and 10 mg doses demonstrate significant efficacy for sleep onset latency (5 mg: -9.23 min; 10 mg: -12.56 min vs placebo), wake after sleep onset (5 mg: -19.9 min; 10 mg: -22.24 min vs placebo), and sleep efficiency (5 mg: +6.08%; 10 mg: +7.46% vs placebo) 2
• The 5 mg dose is preferable for most patients as adverse events, particularly somnolence (~10%), are higher at the 10 mg dose 1, 2
• In older adults (≥65 years), both doses showed sustained efficacy through 12 months with good tolerability 3

Special Populations

• Elderly patients (≥65 years): Start with 5 mg; both doses were well-tolerated in clinical trials with sustained benefits through 12 months 3
• No dose adjustments required based on age, sex, or weight as lemborexant pharmacokinetics are not significantly affected by these factors 1

Contraindications and Precautions

Absolute Contraindications

• Narcolepsy (orexin receptor antagonists can worsen cataplexy and other narcolepsy symptoms) 1

Drug Interactions

• Strong CYP3A4 inhibitors: Lemborexant is metabolized by CYP3A4/5, requiring caution or dose adjustment with strong CYP3A4 inhibitors 1
• Moderate CYP3A4 inhibitors: May require dose reduction or monitoring 1

Important Safety Warnings

• Complex sleep behaviors: Can occur, including sleep-walking, sleep-driving, and other activities while not fully awake 1
• Sleep paralysis and hypnagogic/hypnopompic hallucinations: Reported adverse effects that patients should be counseled about 1
• Cataplexy-like symptoms: May occur, particularly relevant in patients with underlying sleep disorders 1
• Emergence of depression or suicidal ideation: Monitor for new or worsening psychiatric symptoms 1
• Daytime somnolence: Most common adverse event (~10% at 10 mg dose), typically mild to moderate and rarely causes discontinuation 4, 1

Clinical Efficacy and Safety Profile

Long-term Use

• Sustained efficacy demonstrated through 12 months of continuous treatment without evidence of tolerance 5
• No rebound insomnia or withdrawal effects observed upon discontinuation after 12 months of treatment 5
• Benefits observed as early as the first week of treatment and maintained throughout the treatment period 3, 5

Next-Day Functioning

• No significant impairment in postural stability, cognitive performance, or driving ability compared to placebo in multiple studies 4
• Significantly greater morning alertness reported compared to placebo through 6 months, sustained to 12 months 3
• Unlike zolpidem (which impaired multiple cognitive measures) and zopiclone (which impaired driving), lemborexant showed minimal residual effects 4

Common Adverse Events

• Somnolence: Most common (10% at 10 mg, lower at 5 mg), typically mild-moderate 4, 1, 2
• Headache: 2-5% of patients 1
• Nightmares: 2-5% of patients 1
• Nasopharyngitis: Common but generally mild 5
• Most treatment-emergent adverse events were mild to moderate in severity 5

Clinical Pearls

• The 5 mg dose should be the default starting and maintenance dose for most patients, as it provides comparable efficacy to 10 mg with a better safety profile 2
• Lemborexant has not been studied in major psychiatric disorders, so close monitoring is essential when used in this population 1
• The 17-19 hour half-life (longer than suvorexant's 12 hours) necessitates ensuring adequate time in bed (≥7 hours) to avoid morning residual effects 1