Xyrem (sodium oxybate)

POLICY NUMBER

L.5.01.483

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Narcolepsy is a clinical syndrome of daytime sleepiness which can include hypnagogic hallucinations and sleep paralysis and can occur with or without cataplexy. Cataplexy is intermittent manifestation of rapid eye movement (REM) sleep physiology during wakefulness. The syndrome has a central nervous system origin.

The diagnosis of narcolepsy with cataplexy requires the following:

• Daily periods of irrepressible need to sleep or daytime lapses into

  drowsiness or sleep occurring for at least three months;

• Cataplexy and a mean sleep latency of ≤8 minutes and two or more sleep onset REM periods (SOREMPs) on a multiple sleep latency test (MSLT) performed using standard techniques or a SOREMP (within 15 minutes of sleep onset) on the nocturnal polysomnogram;

• The symptoms and signs are not better explained by chronic insufficient sleep, a circadian rhythm sleep-wake disorder or other current sleep disorder, mental disorder, or medication/substance use or withdrawal.

Xyrem (sodium oxybate) is a central nervous system depressant that is indicated for the treatment of cataplexy or excessive daytime sleepiness in patients 7 years of age and older with narcolepsy.

POLICY

Prior authorization is required.

The use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements.

Initial Criteria

Xyrem (sodium oxybate) may be considered medically necessary when ALL of the following are met:

1. Individual is 7 years of age or older;

2. Individual has a diagnosis of narcolepsy with cataplexy

3. BOTH of the following:

   1. Individual’s diagnosis has been confirmed by appropriately conducted polysomnography and a multiple sleep latency test; AND

   2. Individual has clear historic evidence of cataplexy;

4. ONE of the following:

   1. Individual tried and had inadequate response (see Policy Guidelines) to ALL of the following:

      1. BOTH of the following wake-promoting agents:

         1. Modafinil or armodafinil; AND

         2. Methylphenidate or amphetamine-based stimulant; AND

      2. Antidepressant agent with anti-cataplexy effects (e.g., venlafaxine, fluoxetine, duloxetine, amitriptyline); OR

   2. Individual has a documented intolerance, FDA-labeled contraindication, or hypersensitivity to all of the

      wake-promoting agents and antidepressants listed above;

5. The prescriber is certified, and the individual is enrolled in the Xyrem Risk Evaluation and Mitigation Strategy (REMS) program.

6. The requested dose does not exceed the FDA-labeled maximum dose based on individual's weight; AND

1. The individual does not have an FDA-labeled contraindication to therapy with the requested agent.

Length of Approval: 6 months

Renewal Criteria

Xyrem (sodium oxybate) may be approved for RENEWAL when ALL of the following criteria are met:

1. Individual has been previously approved for therapy with the requested agent through BCBSMS PA process;

2. Individualis evaluated by the prescribing provider at least every 3 months;

3. Individual has documented reduction in the frequency of cataplexy attacks;

4. The prescribed dosage is within the program quantity limits based on FDA-approved labeled dosage; AND

5. The individual does not have any FDA-labeled contraindication(s) to therapy with the requested agent.

Xyrem (sodium oxybate) is considered not medically necessary for the treatment of excessive daytime sleepiness as there are other alternatives covered by the Plan.

Length of Approval: 6 months

POLICY EXCEPTIONS

State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medication failure is defined as inadequate response to therapy despite maximally tolerated dose (≥4 weeks use) as appropriate for disease state being treated. Experience of common side effects of medication will not be considered medication failure for the purpose of this review.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

1. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

2. appropriate with regard to standards of good medical practice; and

3. not solely for the convenience of the Member, his or her Provider; and

4. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.

POLICY HISTORY

01/01/2014: New policy added.

07/22/2015: Code Reference section updated for ICD-10.

08/15/2015: Policy description revised to provide additional clinical information regarding narcolepsy and cataplexy. Policy statement revised to state that prior authorization is required for this drug and that it will be limited to a maximum of a 3-month supply initially, with subsequent authorization required every 3 months. Added medications that the patient must try and fail before Xyrem therapy will be approved. Added coverage guidelines for continuation of Xyrem therapy. Sources section updated.

09/29/2015: Policy statements revised for clarification; intent unchanged.

02/02/2016: Approved by Pharmacy & Therapeutics (P&T) Committee. Investigative definition updated in policy guidelines section.

05/31/2016: Policy number L.5.01.483 added.

05/16/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

09/01/2017: Policy section updated to add the following criteria for initial authorization of Xyrem: The prescriber has followed the AASM Clinical Practice Guidelines for the diagnostic testing and treatment of sleep disorders.

03/27/2018: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee.

02/10/2020: Policy title and Policy Exceptions updated to add "(sodium oxybate)." Policy description updated to remove information regarding the diagnosis of narcolepsy without cataplexy. Policy section updated to add that the use of samples by a Member will not be considered current or stable therapy for purposes of Medical Policy review. Initial authorization policy statement criteria updated to change member age from "16" to "7" years of age or older. Added table regarding the FDA labeled maximum dose based on the member's weight. Approval criteria for continued authorization updated to remove statement regarding excessive daytime sleepiness. Added statement that Xyrem (sodium oxybate) is considered not medically necessary for the treatment of excessive daytime sleepiness as there are other alternatives covered by the plan. Policy Guidelines updated to define medically necessary. Sources updated.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

06/27/2024: Policy updated to extend Length of Approval to 6 months.

07/01/2025: Effective 09/01/2025 - Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding narcolepsy diagnosis and indications for Xyrem (sodium oxybate). Policy statement revised to state that the use of samples by an individual will not be considered current or stable therapy to satisfy Medical Policy requirements. Medically necessary criteria revised regarding confirmation of diagnosis, evidence of cataplexy, trial and inadequate responses to agents, documented intolerance, FDA-labeled contraindication, hypersensitivity to the wake-promoting agents and antidepressants listed, and prescriber certification. Added statement that the individual does not have an FDA-labeled contraindication to therapy with the requested agent. Renewal criteria revised regarding therapy approval, dose requirements, and FDA-labeled contraindications. Policy Exceptions updated to remove statement that Xyrem (sodium oxybate) prior authorization is not required for Federal Employee Program (FEP) members. Policy Guidelines updated to define medication failure and to change "Nervous/Mental Conditions" to "Mental Health Disorders." Sources updated. Policy update effective 09/01/2025.

SOURCE(S)

1. Maski K, Trotti LM, Kotagal S, et al. Treatment of central disorders of hypersomnolence: an American Academy of Sleep Medicine clinical practice guideline. J Clin Sleep Med 2021; 17(9):1881-1893. https://doi.org/10.5664/jcsm.9328.

2. National Institute of Neurological Disorders and Stroke. Narcolepsy Fact Sheet. April 2025. Available at https://www.ninds.nih.gov/health-information/disorders/narcolepsy.

3. Scammell, TE. Clinical features and diagnosis of narcolepsy in adults. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on April 14, 2025. https://www.uptodate.com/contents/clinical-features-and-diagnosis-of-narcolepsy-in-adults.

4. Scammell TE. Treatment of narcolepsy in adults. In: UpToDate, Connor RF (Ed), Wolters Kluwer. Accessed on April 14, 2025. https://www.uptodate.com/contents/treatment-of-narcolepsy-in-adults.

5. Xyrem prescribing information. Jazz Pharmaceuticals, Inc. April 2023. Last accessed April 2025.

CODE REFERENCE

None