ModifiedmhnPolicy CP.PMN.42

Sodium Oxybate (Xyrem, Lumryz) and Xywav — Coverage Criteria

Defines medical necessity, prior authorization requirements, and coverage criteria for sodium oxybate products (Xyrem, Lumryz) and Xywav for treatment of cataplexy, excessive daytime sleepiness in narcolepsy, and idiopathic hypersomnia for commercial, HIM/ICHRA, and Medicaid members.

Policy Summary

Payermhn

PolicySodium Oxybate (Xyrem, Lumryz) and Xywav — Coverage Criteria

Policy CodePolicy CP.PMN.42

Change TypeMultiple material revisions (product additions, REMS/boxed warning updates, step therapy and age clarifications)

Effective DateMay 1, 2011

Next Review DateMay 26, 2024

Key ActionSubmit prior authorization with documentation of indication, required prior therapy trials or redirection (Sunosi, Wakix, generic Xyrem where specified), and dosing consistent with product labeling.

SourceLink

POLICY UPDATE CHANGES

Added Lumryz (extended-release oral suspension) product and pediatric extension to the policy.

Updated boxed warning language to specify 'respiratory depression can occur' and noted REMS program availability for Xywav, Xyrem, and Lumryz.

Added redirection to generic Xyrem for brand Xyrem requests and included generic Xyrem in REMS information.

Updated step-wise redirection and trial requirements for alternative agents (Sunosi, Wakix) and age-specific clarifications for trials.

Updated age requirement in initial criteria to reflect minimum age for Lumryz use per PI.

Added requirement for redirection to Sunosi, Wakix, and Xyrem for Lumryz requests in a step-wise fashion for narcolepsy with cataplexy and narcolepsy with EDS.

Updated criteria to reflect pediatric extension approval for Lumryz.

For idiopathic hypersomnia, removed minimal scoring requirements for ESS or IHSS and removed supplemental Appendix D information.

Added step therapy bypass for Illinois high-risk individuals per IL HB 5395 and added ICHRA line of business.

For continued therapy added requirement that for brand Xyrem requests, member must use sodium oxybate (generic Xyrem).

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Coverage Criteria

Initial Therapy: Narcolepsy with Cataplexy

Covered when ALL of the following are met

Initial - Narcolepsy with Cataplexy: 1. Prescribed for the treatment of cataplexy in narcolepsy; 2. Prescribed by or in consultation with a neurologist or sleep medicine specialist; 3. Age ≥ 7 years; 4. For Lumryz requests, one of the following: member weighs ≥ 45 kg OR member weighs < 45 kg and dose has been titrated to ≥ 4.5 mg per day with an alternative sodium oxybate product; 5. Documentation of EDS associated with narcolepsy confirmed by MSLT (mean sleep latency ≤ 8 minutes with ≥2 SOREMPs OR at least one SOREMP on MSLT and a SOREMP on the preceding overnight PSG) OR CSF hypocretin-1 ≤ 110 pg/mL; 6. Failure of 2 of the following agents, each used for ≥ 1 month unless member age ≥ 65 years, intolerant, or contraindicated: venlafaxine, fluoxetine, atomoxetine, clomipramine, protriptyline; 7. If member is ≥ 18 years, failure of a 1-month trial of Wakix at up to maximally indicated doses unless contraindicated or intolerant; 8. For brand Xyrem requests, member must use sodium oxybate (generic Xyrem) unless contraindicated or intolerant; 9. For Xywav or Lumryz requests: if member has failed Wakix, then failure of sodium oxybate (Xyrem) at up to maximally indicated doses unless contraindicated or intolerant; 10. Dose does not exceed 9 grams per day.dose <=9 g/day

Illinois HIM exceptions to some step therapy requirements per IL HB 5395

Initial Therapy: Narcolepsy with EDS

Covered when ALL of the following are met

Initial - Narcolepsy with Excessive Daytime Sleepiness: 1. Diagnosis of narcolepsy with excessive daytime sleepiness (EDS); 2. Prescribed by or in consultation with a neurologist or sleep medicine specialist; 3. Age ≥ 7 years; 4. For Lumryz requests, one of the following: member weighs ≥ 45 kg OR member weighs < 45 kg and dose has been titrated to ≥ 4.5 mg per day with an alternative sodium oxybate product; 5. Documentation of EDS confirmed by MSLT and one of the following (mean sleep latency ≤ 8 minutes with ≥2 SOREMPs OR at least one SOREMP on MSLT and a SOREMP on the preceding overnight PSG) AND daily irrepressible need to sleep or daytime lapses into sleep occurring for ≥ 3 months; 6. Failure of a 1-month trial of a generic CNS stimulant (amphetamine, dextroamphetamine, or methylphenidate) at up to maximally indicated doses unless intolerant or contraindicated; 7. If member is ≥ 17 years, failure of a 1-month trial of armodafinil or modafinil unless intolerant or contraindicated; 8. If member is ≥ 18 years, failure of a 1-month trial of Sunosi unless intolerant or contraindicated; 9. If Sunosi failed, failure of a 1-month trial of Wakix unless intolerant or contraindicated; 10. For brand Xyrem requests, member must use sodium oxybate (generic Xyrem) unless contraindicated or intolerant; 11. For Xywav and Lumryz requests: if member has failed Sunosi and Wakix, then failure of sodium oxybate (Xyrem) at up to maximally indicated doses unless contraindicated or intolerant; 12. If request is for concomitant therapy with other antinarcoleptic agents in members ≥ 18 years, failure of combination therapy with modafinil/armodafinil plus Sunosi unless intolerant or contraindicated; 13. Dose does not exceed 9 grams per day.dose <=9 g/day

Illinois HIM exceptions to step therapy per IL HB 5395

Initial Therapy: Idiopathic Hypersomnia

Covered when ALL of the following are met

Initial - Idiopathic Hypersomnia: 1. Diagnosis of idiopathic hypersomnia (IH); 2. Request is for Xywav; 3. Prescribed by or in consultation with a neurologist or sleep medicine specialist; 4. Age ≥ 18 years; 5. Exclusion of narcolepsy with cataplexy, narcolepsy with EDS, and insufficient sleep syndrome; 6. MSLT documents fewer than two SOREMPs OR no SOREMPs if REM sleep latency on the preceding PSG ≤ 15 minutes; AND presence of at least one of: MSLT mean sleep latency ≤ 8 minutes OR total 24-hour sleep time ≥ 660 minutes on 24-hour PSG or wrist actigraphy with sleep log; 7. Failure of a 1-month trial of armodafinil or modafinil at up to maximally indicated doses unless intolerant or contraindicated; 8. Failure of a 1-month trial of a generic CNS stimulant (amphetamine, dextroamphetamine, methylphenidate) at up to maximally indicated doses unless intolerant or contraindicated; 9. Dose limits: once-nightly dosing maximum 6 grams per day (12 mL) or twice-nightly dosing maximum 9 grams per day (18 mL).IH dosing: once-nightly <=6 g/day (12 mL); twice-nightly <=9 g/day (18 mL)

Illinois HIM exceptions to step therapy per IL HB 5395

Continued Therapy

Covered for continuation when ALL of the following are met

Continued Therapy: 1. Member currently receiving medication via Centene benefit or member previously met initial approval criteria OR member is currently receiving medication and eligible for continuity of care; 2. Member is responding positively to therapy as evidenced by improvement in parameters such as frequency of cataplexy attacks or reported daytime wakefulness; 3. For brand Xyrem requests, member must use sodium oxybate (generic Xyrem) unless contraindicated or intolerant; 4. If request is for a dose increase, new dose does not exceed 9 grams per day.dose <=9 g/day

Approval durations specified per line of business

Initial therapy coverage criteria

Covered when ALL of the following are met for the specified indication per product labeling and policy redirection rules

General coverage prerequisites: Indication is narcolepsy with cataplexy, narcolepsy with EDS, or idiopathic hypersomnia as supported by documentation; prior authorization has been submitted; adherence to REMS program requirements for Xyrem, Xywav, and Lumryz where applicable.

See Appendix C for contraindications and REMS information

Dosing consistent with labeling: Requested product dosing regimen matches product-specific dosing and maximums: e.g., Xyrem/Xywav start 4.5 g/night in two divided doses and titrate by 1.5 g/week to 6–9 g/night; Lumryz start 4.5 g once-nightly titrate to 6–9 g once-nightly; pediatric weight-based dosing applies per policy and product labeling.max 9 g/night (adults)

Pediatric dosing weight bands specified in policy

Step therapy / redirection: For certain product requests (Xywav or Lumryz), member must have trialed or been redirected to specified alternatives (Sunosi, Wakix, and/or sodium oxybate/generic Xyrem) as defined by age-specific exceptions; trials and failures must be documented.

Coverage criteria groups (summary)

Coverage is permitted when specific step-wise redirection, age, and prior therapy requirements are met as detailed below.

Narcolepsy with Cataplexy — redirection and age exceptions: For Lumryz requests, require step-wise redirection to Sunosi, Wakix, and sodium oxybate (Xyrem or generic Xyrem). Trials of tricyclic antidepressants (clomipramine, protriptyline) are required except when member age > 65 years, in which case these specific tricyclic trials are not required; Wakix trial applies only if member is ≥ 18 years.age-based conditions apply

Atomoxetine removed from 'antidepressant' classification for redirection.

Narcolepsy with EDS — redirection and age constraints: For Lumryz requests, require step-wise redirection to Sunosi, Wakix, and sodium oxybate (Xyrem or generic Xyrem). Trial of Sunosi is required if member is ≥ 18 years.age ≥18 for certain redirect trials

Idiopathic Hypersomnia (IH): Removed minimal scoring requirements for ESS or IHSS; coverage aligns with updated criteria without minimal ESS/IHSS thresholds.

Non‑FDA approved indications that are not specifically addressed in this policy are not authorized for coverage unless the provider submits sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies referenced by this document (e.g., CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace/ICHRA, CP.PMN.53 for Medicaid) or the procedures described for recently changed labels and formulary status.

Requests for off‑label use will be considered only when the provider supplies supporting clinical evidence per the plan’s off‑label use policies. Absent documentation meeting those off‑label policy standards, such uses are excluded from coverage.

The provided excerpt does not list any additional explicit exclusions beyond the general non‑FDA indication exclusion. Any specific exclusions would be documented elsewhere in the full policy or appendices.

Uses outside the indications expressly listed in this policy (narcolepsy with cataplexy, narcolepsy with excessive daytime sleepiness, and idiopathic hypersomnia for Xywav) are considered not authorized unless the provider documents sufficient supporting evidence per the referenced off‑label use policies or other evidence-of-coverage documents.

Off‑label uses that lack adequate documentation of efficacy and safety in accordance with the referenced off‑label use policies (e.g., CP.CPA.09, HIM.PA.154, CP.PMN.53) will be treated as not medically necessary and will not be approved.

No text provided in the excerpt for this item.

Coding and Product Identifiers

Drug identifiersmixed

NDC	Xyrem, Lumryz, Xywav (product-specific NDCs referenced outside this excerpt)

Product availability / NDCNDC

NDC	Product-specific NDCs per manufacturer prescribing information (see PI references)

Covered NDCs / products mentionedNDC

NDCs not listed

Generic Xyrem and brand Xyrem added to criteria and REMS information (no explicit NDCs provided in this excerpt)

Total 24-hour sleep time — diagnostic threshold for IH by 24-hour PSG or wrist actigraphy

Total 24-hour sleep time (IH diagnostic threshold)>= 660 minutes on 24-hour PSG or by wrist actigraphy with sleep log

ContextUsed as part of idiopathic hypersomnia diagnostic criteria when MSLT has fewer than two SOREMPs or no SOREMPs with REM latency on preceding PSG <= 15 minutes

Source guidancePresence of total 24-hour sleep time >= 660 minutes supports IH diagnosis per PSG or wrist actigraphy with sleep log

MSLT mean sleep latency — diagnostic criterion (<= 8 minutes)

MSLT mean sleep latency (diagnostic criterion)<= 8 minutes

Role in diagnosis

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required. Provider must demonstrate that all applicable prior authorization and redirection (step therapy) criteria are met for the requested product and indication, including documentation of diagnosis, prior therapies, age- and weight-based requirements, and dosing within policy limits.

Prior authorization required for sodium oxybate products (Xyrem, Xywav, Lumryz).
Requests must include evidence of meeting indication-specific criteria (see clinical criteria sections).
Age, weight, and dosing limits per product PI must be documented.

Step Therapy

Step Therapy / Redirection Requirements

Providers must document trials of required redirect or step therapy agents in a step-wise fashion where specified before approval of brand Xyrem, Xywav, or Lumryz. For certain requests, redirection sequence includes trials of Sunosi, Wakix, and sodium oxybate (generic Xyrem) as applicable. Illinois HIM (per IL HB 5395) and ICHRA line of business may have step therapy bypasses — indicate if request is subject to that statutory exception.

Background

Sodium oxybate products (sodium oxybate/Xyrem, the calcium/magnesium/potassium/sodium oxybate formulation Xywav, and extended‑release Lumryz) are central nervous system depressants indicated for treatment of cataplexy and excessive daytime sleepiness in patients with narcolepsy; Xywav is additionally indicated for idiopathic hypersomnia in adults. Diagnosis of narcolepsy and idiopathic hypersomnia commonly relies on objective sleep testing such as polysomnography (PSG) and multiple sleep latency testing (MSLT) or CSF hypocretin‑1 levels to confirm diagnostic criteria prior to therapy.

Definitions and Diagnostic Criteria

MSLT / SOREMP / PSG — diagnostic thresholds and test descriptions

MSLT (Multiple Sleep Latency Test)Series of five daytime nap opportunities to objectively measure daytime sleepiness; reports mean sleep latency and number of SOREMPs

SOREMP (Sleep-Onset REM Period)Sleep-onset REM periods are counted on MSLT; diagnostic rules reference >=2 SOREMPs for narcolepsy or fewer than two for IH context

PSG link to MSLTPolysomnography provides preceding-night REM latency and total 24-hour sleep time data used in conjunction with MSLT for diagnosis

MSLT — description of the multiple sleep latency test

Test formatMSLT consists of five daytime nap opportunities to measure mean sleep latency and number of SOREMPs

Diagnostic thresholds