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:

  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 (Clinical Trials)
  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 (Clinical Trials)
  3. DAYVIGOTM (lemborexant) Package insert (PDF)
  4. Eisai Inc. announcement (link)

Dr. Harvinder Singh

Admin, Psychiatry Education Forum

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