Sodium oxybate (Xyrem®); calcium, magnesium, potassium, and sodium oxybates (Xywav™)

SELF ADMINISTERED

Diagnosis considered for coverage:
  • Indicated for the treatment of cataplexy or excessive daytime sleepiness (EDS) in patients 7 years of age and older with narcolepsy
  • Indicated for the treatment of idiopathic hypersomnia (IH) in adults
Coverage Criteria:

For diagnosis of narcolepsy with cataplexy (narcolepsy type 1):

  • Dose does not exceed 9 grams total per night, AND
  • Patient is at least 7 years of age, AND
  • Prescribed by or in consultation with one of the following:
    • Neurologist
    • Psychiatrist
    • Sleep medicine specialist, AND
  • Chart note documentation confirms diagnosis of narcolepsy, AND
  • Symptoms of cataplexy are present, AND
  • Symptoms of excessive daytime sleepiness (e.g., irrepressible need to sleep or daytime lapses into sleep) are present, AND
  • For patients under age 65: Trial and failure, contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to TWO of the following antidepressants: venlafaxine, fluoxetine, atomoxetine, clomipramine, or protriptyline, AND
  • Xyrem or Xywav will not be used in combination with a H3 receptor antagonist/inverse agonist (e.g. Wakix®), AND
  • For Xywav requests: chart notes document a medical reason for intolerance or contraindication to Xyrem

For diagnosis of narcolepsy without cataplexy (narcolepsy type 2):

  • Dose does not exceed 9 grams total per night, AND
  • Patient is at least 7 years of age, AND
  • Prescribed by or in consultation with one of the following:
    • Neurologist
    • Psychiatrist
    • Sleep medicine specialist, AND
  • Chart note documentation confirms diagnosis of narcolepsy, AND
  • Symptoms of cataplexy are absent, AND
  • Symptoms of excessive daytime sleepiness (e.g., irrepressible need to sleep or daytime lapses into sleep) are present, AND
  • BOTH of the following (1 and 2):
    • 1) Trial and failure, contraindication (e.g., safety concerns, not indicated for patient's age/weight) or intolerance to BOTH of the following:
      • Generic modafinil or armodafinil
      • Sunosi
    • 2) One of the following:
      • Trial and failure, contraindication, or intolerance to an amphetamine (e.g., amphetamine, dextroamphetamine) or methylphenidate based stimulant, OR
      • History of or potential for a substance use disorder, AND
  • Xyrem or Xywav will not be used in combination with a H3 receptor antagonist/inverse agonist (e.g. Wakix), AND
  • For Xywav requests: chart notes document a medical reason for intolerance or contraindication to Xyrem

For diagnosis of idiopathic hypersomnia:

  • Dose does not exceed 9 grams total per night if taken twice nightly OR 6 grams per night if taken once nightly, AND
  • The request is for Xywav, AND
  • Patient is at least 18 years of age, AND
  • Prescribed by or in consultation with one of the following:
    • Neurologist
    • Psychiatrist
    • Sleep medicine specialist, AND
  • Chart note documentation confirms diagnosis of idiopathic hypersomnia as confirmed by sleep study (unless the prescriber provides justification confirming that a sleep study would not be feasible), AND
  • Symptoms of excessive daytime sleepiness (e.g., nap duration of longer than 60 minutes) are present, AND 
  • Trial and failure, contraindication, or intolerance to generic modafinil, AND
  • Trial and failure, contraindication, or intolerance to generic methylphenidate agent
Reauthorization Criteria:

For diagnosis of narcolepsy with cataplexy (narcolepsy type 1):

  • Dose does not exceed 9 grams total per night, AND
  • One of the following:
    • Documentation demonstrating a reduction in the frequency of cataplexy attacks associated with therapy, OR
    • Documentation demonstrating a reduction in symptoms of excessive daytime sleepiness associated with therapy, AND
  • Xyrem or Xywav will not be used in combination with a H3 receptor antagonist/inverse agonist (e.g. Wakix)

For diagnosis of narcolepsy without cataplexy (narcolepsy type 2):

  • Dose does not exceed 9 grams total per night, AND
  • Documentation demonstrating a reduction in symptoms of excessive daytime sleepiness associated with therapy, AND
  • Xyrem or Xywav will not be used in combination with a H3 receptor antagonist/inverse agonist (e.g. Wakix)

For diagnosis of idiopathic hypersomnia:

  • Dose does not exceed 9 grams total per night if taken twice nightly OR 6 grams per night if taken once nightly, AND
  • The request is for Xywav, AND
  • Documentation demonstrating a reduction in symptoms of excessive daytime sleepiness associated with therapy
Coverage Duration:
  • Initial: 6 months
  • Reauthorization: 1 year
Authorization is not covered for the following:

The use of this drug for indications not listed in this policy does not meet the coverage criteria established by the Western Health Advantage (WHA) Pharmacy and Therapeutics (P&T) Committee.

Additional Information:
  • Dosing for Narcolepsy:
    • Recommended starting adult dose: 4.5 grams per night orally, divided into two doses
    • Recommended starting pediatric dosage, titration regimen, and maximum total nightly dosage are based on patient weight
    • Doses higher than 9 g per night have not been studied and ordinarily should not be administered
    • Xyrem and Xywav are administered orally twice per night
  • Dosing for adults with IH:
    • Twice nightly:
      • Starting dose: Less than or equal to 4.5 g per night divided into two doses
      • Maximum dose: 9 g (divided into two doses)
    • Once nightly: 
      • Starting dose: Less than or equal to 3 g per night
      • Maximum dose: 6 g per night
  • Schedule III controlled substance
  • Contraindicated for use in:
    • Combination with sedative-hypnotics
    • Combination with alcohol
    • Patients with succinic semialdehyde dehydrogenase deficiency
  • Black box warnings:
    • Central Nervous System depression
    • Abuse and misuse
    • Xyrem and Xywav are available only through a restricted program called the Xywav and Xyrem REMS
  • Warnings: Respiratory depression and sleep-disordered breathing, depression and suicidality, other behavioral and psychiatric adverse reactions, and parasomnias. Additional warning for high salt content in Xyrem
Policy Updates:
  • 10/17/2017– New policy for Xyrem
  • 9/3/2021 – New policy approved by P&T for Xywav and criteria update for Xyrem
  • 2/15/2022 – New criteria for new indication for idiopathic hypersomnia
References:
  • Xyrem [package insert], Palo Alto, CA: Jazz Pharmaceuticals, Inc.; October 2018.
  • Xywav [package insert], Palo Alto, CA: Jazz Pharmaceuticals, Inc.; August 2021.
  • Morgenthaler TI, Kapur VK, Brown T, et al. Practice parameters for the treatment of narcolepsy and other hypersomnias of central origin: An American Academy of Sleep Medicine report. Sleep. 2007 Dec;30(12):1705-11.
  • Wise MS, Arand DL, Auger RR, et al. Treatment of narcolepsy and other hypersomnias of central origin: An American Academy of Sleep Medicine review. Sleep. 2007 Dec;30(12):1712-27.
  • International classification of sleep disorders. 3rd ed. Darien, IL: American Academy of Sleep Medicine; 2014.
  • Sateia MJ. International classification of sleep disorders - third edition: highlights and modifications. CHEST. 2014 Nov;146(5):1387-1394.
  • Scammell TE. Clinical features and diagnosis of narcolepsy. UpToDate Website. March 2017. www.uptodate.com. Accessed October 24, 2018.
  • Per clinical consult with neurologist/sleep specialist, October 9, 2012 (confirmed on March 20, 2015).
  • Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. JCSM. 2021 Sept; 17(9): 1881-1893.

Last review date: December 1, 2023