DAYVIGO™ (Lemborexant): FDA Approved for Insomnia.

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:

Indication:

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.

Hepatic Impairment:

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.

Renal Impairment:

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.

Contraindication:

Narcolepsy

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

References:

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)