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Orexin Receptor Antagonist

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Orexin Receptor Antagonist, Orexin Antagonist, Suvorexant, Belsomra, Dayvigo, Lemborexant, Quviviq, Daridorexant

  • Indications
  1. Insomnia
    1. Suvorexant (Belsomra) is also FDA approved in Sleep Disorders in Alzheimer's Disease
  • Mechanism
  1. FDA Schedule IV Agent (as with other Nonbenzodiazepine Sedative-Hypnotic agents)
  2. Orexin (hypocretin) is a Neurotransmitter that promotes wakefulness (deficiency in Narcolepsy)
  3. Blocking orexin transiently allows for sleep
  • Medications
  1. Daridorexant (Quviviq)
    1. Dose: 25 to 50 mg orally at bedtime
  2. Suvorexant (Belsomra)
    1. FDA approved for Sleep Disorders in Alzheimer's Disease (may decrease neurofibrillary tangles)
    2. Start at 10 mg orally nightly, 30 minutes before bedtime
    3. May increase to 20 mg orally nightly (maximum dose)
    4. Dose: 10 to 20 mg orally at bedtime
    5. Onset: 30 minutes
    6. Half-Life: 12 hours
  3. Lemborexant (Dayvigo)
    1. Dose: 5 to 10 mg orally at bedtime
    2. Onset: 15 to 20 minutes
    3. Half-Life: 17 to 19 hours
  • Adverse Effects
  1. Daytime Somnolence (including the next day)
  2. Sleep Paralysis or Leg weakness (transient, rare)
  3. Abnormal dreams
  4. Hallucinations
  5. Sleepwalking
  • Drug Interactions
  1. Metabolized by CYP3A4
  2. Moderate CYP3A4 Inhibitors (e.g. Verapamil)
    1. Start Belsomra at low dose (e.g. 5 mg)
  3. Strong CYP3A4 Inhibitors (e.g. Clarithromycin, Itraconazole)
    1. Avoid Belsomra with strong CYP3A4 Inhibitors
  • Efficacy
  1. Similar effectiveness to other standard agents used for Insomnia (e.g. Zolpidem)
  2. Compared with Placebo
    1. Reduce time to sleep onset by 5 to 10 minutes
    2. Increase sleep duration by 15 to 20 minutes (22 minutes for Belsomra)
  3. Disadvantages
    1. Expensive agents ($300/month or $15/dose)
    2. No benefit over Zolpidem (Ambien) which is $10/month at generic pricing
  • References
  1. (2015) Presc Lett 22(2):10
  2. (2022) Presc Lett 29(6): 34