On Dec 23, 2019 Eisai Inc. announced the FDA approval of DAYVIGO™ (Lemborexant) for insomnia management.
This post will summarize the important clinically relevant facts regarding this medication, in following sections:
- Insomnia in adults: Sleep onset and/or sleep maintenance.
Mechanism of Action:
Orexin receptor antagonist: orexin receptor 1 (OX1R) and 2 (OX2R).
orexin neuropeptide signaling system plays a role in wakefulness. Hence, blocking the binding of orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive.
Dosages and Administration:
- Available as: 5 mg and 10 mg.
- Initial Dose: 5 mg
- Timing: taken no more than once per night, immediately before going to bed, with at least 7 hours remaining before the planned time of awakening.
- Maximum dose: 10 mg.
- Mild hepatic impairment: no dosage adjustment but can have risk of somnolence.
- Moderate hepatic impairment: maximum dose of 5 mg.
- Severe hepatic impairment: not recommended.
- No dosage adjustment with renal impairment, but
- Severe renal impairment: increased risk of somnolence.
Most Common Adverse Reactions:
defined as reported in 5% of patients treated with DAYVIGO and at least twice the rate of placebo.
- Somnolence: 10 mg (10%), 5 mg (7%) and placebo (1%).
Cautions and Warnings:
- Next day somnolence with risk of driving impairment: risk high with 10 mg dose.
- Avoid prescription with other CNS depressants (benzodiazepines, opioids, tricyclic antidepressants)
- Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, and Cataplexy-Like Symptoms.
- Complex Sleep Behaviors: sleep-walking, sleep-driving.
- Patients with compromised respiratory function.
- Elderly > 65 yr age: maximum dose of 5 mg.
- Worsening of Depression and Suicidal Ideation.
Important Drug Interactions:
- Weak CYP3A Inhibitors: maximum dose of 5 mg.
- Moderate CYP3A inhibitors (fluconazole, verapamil): AVOID
- Strong CYP3A inhibitors (itraconazole, clarithromycin): AVOID
- Moderate CYP3A inducers (efavirenz, modafinil): AVOID
- Strong CYP3A inducers (rifampin, carbamazepine): AVOID
- CYP2B6 Substrates (bupropion): Increasing the doses of CY2B6 substrates may be considered as needed.
Risk of Abuse and Dependence?
- pending review by the U.S. Drug Enforcement Administration.
Clinical Studies Showing Effectiveness:
Study 1: A Long-Term Multicenter, Randomized, Double-Blind, Controlled, Parallel Group Study of the Safety and Efficacy of Lemborexant in Subjects With Insomnia Disorder (SUNRISE 2): NCT02952820.
Study 2: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Active Comparator, Parallel-Group Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1): NCT02783729
- A Long-Term Multicenter, Randomized, Double-Blind, Controlled, Parallel Group Study of the Safety and Efficacy of Lemborexant in Subjects With Insomnia Disorder (SUNRISE 2): NCT02952820 (Clinical Trials)
- A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Active Comparator, Parallel-Group Study of the Efficacy and Safety of Lemborexant in Subjects 55 Years and Older With Insomnia Disorder (SUNRISE 1): NCT02783729 (Clinical Trials)
- DAYVIGOTM (lemborexant) Package insert (PDF)
- Eisai Inc. announcement (link)