Orexin Receptor Antagonist

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

1. Indications
   1. Insomnia
2. 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
3. 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
4. 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)
5. Adverse Effects
   1. Daytime Somnolence (including the next day)
   2. Sleep Paralysis or Leg weakness (transient, rare)
6. 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
7. Disadvantages
   1. Expensive agents ($300/month or $15/dose)
   2. No benefit over Zolpidem (Ambien) which is $10/month at generic pricing
8. References
   1. (2015) Presc Lett 22(2):10
   2. (2022) Presc Lett 29(6): 34