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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
  • Preparations
  1. Quviviq (Daridorexant) 25 to 50 mg orally at bedtime
  2. Belsomra (Suvorexant) 10 to 20 mg orally at bedtime
    1. Onset: 30 minutes
    2. Half-Life: 12 hours
  3. Dayvigo (Lemborexant) 5 to 10 mg orally at bedtime
    1. Onset: 15 to 20 minutes
    2. Half-Life: 17 to 19 hours
  • 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
  • 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)
  • Adverse Effects
  1. Daytime Somnolence (including the next day)
  2. Sleep Paralysis or Leg weakness (transient, rare)
  • 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
  • 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