What is Dayvigo (Lemborexant)?
Dayvigo (lemborexant) is a dual orexin receptor antagonist approved by the FDA in December 2019 for treating adult patients with insomnia characterized by difficulties with sleep onset and/or sleep maintenance. 1
Mechanism of Action
- Lemborexant works by blocking both orexin 1 (OX1R) and orexin 2 (OX2R) receptors, with stronger inhibitory effects on OX2R. 2
- The orexin system regulates wakefulness and arousal; by antagonizing these receptors, lemborexant reduces the drive for wakefulness and facilitates physiological sleep without significantly altering sleep architecture. 2, 3
- Unlike traditional sedative-hypnotics, lemborexant binds to and dissociates from orexin receptors rapidly, which may contribute to its favorable safety profile regarding next-morning residual effects. 2
Clinical Efficacy
Lemborexant demonstrates effectiveness for both sleep onset and sleep maintenance insomnia:
- Sleep Onset Latency: Reduces time to fall asleep by approximately 9-13 minutes compared to placebo (5 mg and 10 mg doses respectively). 3
- Sleep Maintenance: Decreases wake after sleep onset by approximately 20-22 minutes for both 5 mg and 10 mg doses. 3
- Sleep Efficiency: Improves overall sleep efficiency by 6-7% compared to placebo. 3
- The medication is effective for patients who experience early morning awakenings and maintains efficacy over long-term use. 4
Dosing and Pharmacokinetics
- Approved doses: 5 mg and 10 mg taken at bedtime. 1
- Time to maximum concentration: 1-3 hours after administration. 5
- Mean effective half-life: 17 hours (5 mg) and 19 hours (10 mg). 5
- Plasma concentration at 9 hours post-dose is only 27% of maximum concentration, contributing to minimal next-morning residual effects. 5
- No dose adjustment needed for advanced age. 6
Safety Profile
Lemborexant is generally well-tolerated with a favorable safety profile:
- Most common adverse effect: Somnolence, occurring in approximately 7% of patients versus 3% with placebo. 7
- Treatment-emergent adverse events occur more frequently than placebo but are generally mild. 3
- Minimal next-morning residual effects: Studies show no clinically relevant effects on morning alertness, driving skills, or next-day function at approved doses through 10 mg. 4, 5
- Patients retain ability to respond to external auditory stimuli during the night. 4
- FDA labeling warns of potential cognitive and behavioral changes including amnesia, anxiety, and hallucinations, though these are uncommon. 6
Clinical Positioning
- The American College of Physicians recommends cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment, with pharmacotherapy like lemborexant considered when CBT-I is unsuccessful. 6
- Lemborexant represents a newer alternative to traditional benzodiazepine receptor agonists and other orexin antagonists like suvorexant. 1
- The 5 mg dose may be preferable for patients at risk of excessive daytime somnolence, while maintaining comparable efficacy to the 10 mg dose. 3