CurrentCentenePolicy CP PMN.221

Pitolisant (Wakix) — Coverage Criteria for Narcolepsy (cataplexy & EDS)

Covers medical necessity and prior authorization criteria for pitolisant (Wakix) for treatment of narcolepsy (cataplexy and/or excessive daytime sleepiness) for Centene-affiliated health plans and lines of business including Commercial, HIM, and Medicaid.

Policy Summary

PayerCentene

PolicyPitolisant (Wakix) — Coverage Criteria for Narcolepsy (cataplexy & EDS)

Policy CodePolicy CP PMN.221

Change TypeNo material changes

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit prior authorization with documentation showing criteria are met, including specialist consultation, diagnostic test results, and required step-therapy trials.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

2FDA-indications

12Approval duration (mos)

17.8–35.6Dose range (mg)

2Contraindications

2Tablet strengths

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Coverage Criteria for Pitolisant (Wakix)

Initial Therapy — Cataplexy

Covered when ALL of the following are met for cataplexy:

Cataplexy Initial Criteria: 1) Prescribed for the treatment of cataplexy in narcolepsy;

Cataplexy Initial Criteria: 2) Prescribed by or in consultation with a neurologist or sleep medicine specialist;

Cataplexy Initial Criteria: 3) Age ≥ 18 years;

Cataplexy Initial Criteria: 4) Documentation of ONE of the following diagnostic confirmations: a) EDS associated with narcolepsy confirmed by MSLT with either: (i) mean sleep latency < 8 minutes with ≥2 SOREMPs; OR (ii) at least one SOREMP on MSLT and a SOREMP (<15 minutes) on the preceding overnight PSG; OR b) CSF hypocretin-1 < 110 pg/mL;

Use MSLT/PSG or CSF results as documented in the medical record.

Cataplexy Initial Criteria: 5) Failure of 2 of the following agents, each used ≥1 month unless age ≥65 years, clinically significant adverse effects occur, or agents are contraindicated: venlafaxine, fluoxetine, atomoxetine, clomipramine, protriptyline;

For members age ≥65 years, tricyclic antidepressants are not required for trial; state-specific exemptions (e.g., Illinois HIM) may apply.

Cataplexy Initial Criteria: 6) Dose does not exceed both of the following: a) 35.6 mg per day; AND b) 2 tablets per day;

Provider must submit documentation to support dosing and step therapy exceptions where applicable.

Initial Therapy — Narcolepsy with EDS

Covered when ALL of the following are met for narcolepsy with EDS:

EDS Initial Criteria: 1) Diagnosis of narcolepsy with excessive daytime sleepiness (EDS);

EDS Initial Criteria: 2) Prescribed by or in consultation with a neurologist or sleep medicine specialist;

EDS Initial Criteria: 3) Age ≥ 6 years;

EDS Initial Criteria: 4) Evidence of EDS associated with narcolepsy confirmed by MSLT with either: (i) mean sleep latency < 8 minutes with ≥2 SOREMPs; OR (ii) at least one SOREMP on MSLT and a SOREMP (<15 minutes) on the preceding overnight PSG;

Continuation Therapy

Covered for continuation when ALL of the following are met:

Continuation Therapy: 1) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria; or member is enrolled in continuity of care provisions per state/product rules;

Refer to state-specific addenda for continuity of care details.

Continuation Therapy: 2) Member is responding positively to therapy as evidenced by improvement (e.g., reduction in frequency of cataplexy attacks, reported daytime improvements in wakefulness);

Document clinical response in the medical record (office notes, patient report).

Continuation Therapy: 3) If request is for a dose increase, the new dose does not exceed the specified maxima: a) Adults and pediatric members ≥40 kg: 35.6 mg/day; b) Pediatric members <40 kg: 17.8 mg/day; AND c) Maximum 2 tablets per day;

Approval durations are typically 12 months (Medicaid/HIM and Commercial per policy).

Non‑FDA approved indications that are not specifically addressed by this policy are excluded from coverage unless the provider supplies sufficient documentation of efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for Commercial, HIM.PA.154 for Marketplace, or CP PMN.53 for Medicaid) or other applicable evidence of coverage documents.

For Medicaid members, state Medicaid coverage provisions take precedence when they conflict with the coverage provisions in this clinical policy. Providers should consult the applicable state Medicaid manual for specific coverage requirements.

Requests for indications that are not FDA‑approved and are not supported by sufficient evidence per the payer’s off‑label use policies will not be authorized. Providers must submit the necessary evidence per the referenced off‑label policies for consideration.

Product Coding and Dosing

Neutral — codes not specified in document portionmixed

NDC / HCPCS / CPT not specified

No explicit billing codes listed in this portion of the policy.

Product strengthsmixed

4.45 mg	Pitolisant tablet strength
17.8 mg	Pitolisant tablet strength

inv-09: Maximum daily dose — Dosing thresholds

Adults and pediatric patients ≥40 kgMaximum daily dose: 35.6 mg/day (may be titrated to this dose as described in dosing regimen)

Pediatric patients <40 kgMaximum daily dose: 17.8 mg/day

Maximum tablets/dayLimit: 2 tablets per day as specified in dosing limits

Provider Actions, Prior Authorization, and Documentation

Prior Authorization

Prior Authorization Required and Approval Durations

Prior authorization is required. Approvals must document that the applicable initial or continuation criteria are met, including specialist involvement and required diagnostic testing. Approval durations vary by line of business and historical edits have increased initial approval durations to 12 months for Medicaid/HIM and modified commercial approvals to 12 months or the duration of request, whichever is less.

Medicaid/HIM approval duration: 12 months
Commercial approval duration: 12 months or duration of request, whichever is less
Historical edits: 2Q 2021 consolidation and approval duration changes; subsequent annual reviews documented

Step Therapy

Step Therapy / Therapeutic Trial Requirements

Step therapy requirements apply for specified indications. For narcolepsy with cataplexy, trials of two listed agents (e.g., venlafaxine, fluoxetine, atomoxetine, clomipramine, protriptyline) each used for ≥1 month are required unless the member is ≥65 years (tricyclic trial exceptions apply) or trials are contraindicated or cause clinically significant adverse effects. For narcolepsy with excessive daytime sleepiness (EDS), failure of a 1-month trial of a preferred generic stimulant (amphetamine, dextroamphetamine, or methylphenidate) at up to maximally indicated doses is required unless contraindicated; if age ≥17 years, a 1-month trial of armodafinil or modafinil is also required unless contraindicated. For requests involving concomitant therapy with other antinarcoleptic agents, failure of combination therapy with modafinil or armodafinil and recommended agents (e.g., Sunosi) is required unless contraindicated or adverse effects occur. Note: Illinois HIM requests — step therapy requirements do not apply as of 01/01/2026 per IL HB.

Background

Pitolisant is a selective histamine‑3 (H3) receptor antagonist/inverse agonist indicated for treatment of excessive daytime sleepiness (EDS) and cataplexy in adults with narcolepsy, and for EDS in pediatric patients aged 6 years and older. Diagnostic confirmation for narcolepsy with EDS may rely on testing such as the multiple sleep latency test (MSLT) and polysomnography (PSG), or cerebrospinal fluid hypocretin‑1 measurement when available.

Definitions and Abbreviations

inv-19: MSLT abbreviation

MSLTMultiple sleep latency test

Use in policyDiagnostic test referenced as confirmation for narcolepsy with EDS (MSLT criteria include mean sleep latency and SOREMPs)

AppendixListed in Appendix A: Abbreviation/Acronym Key

inv-20: PSG abbreviation

PSGPolysomnography

Use in policyOvernight PSG may be used in combination with MSLT to document SOREMPs for diagnostic confirmation

Appendix

Policy Summary

PayerCentene

PolicyPitolisant (Wakix) — Coverage Criteria for Narcolepsy (cataplexy & EDS)

Policy CodePolicy CP PMN.221

Change TypeNo material changes

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit prior authorization with documentation showing criteria are met, including specialist consultation, diagnostic test results, and required step-therapy trials.

SourceLink

On This Page

EDS Initial Criteria:

5) Member has daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for ≥3 months;

EDS Initial Criteria: 6) Failure of a 1-month trial of a generic CNS stimulant (amphetamine, dextroamphetamine, or methylphenidate) at up to maximally indicated doses, unless clinically significant adverse effects or contraindicated;

Prior authorization may be required for CNS stimulants; state-specific exemptions (e.g., Illinois HIM) apply.

EDS Initial Criteria: 7) If age ≥ 17 years: failure of a 1-month trial of armodafinil or modafinil at up to maximally indicated doses, unless clinically significant adverse effects or contraindicated;

Prior authorization may be required for armodafinil/modafinil; state-specific exemptions apply.

EDS Initial Criteria: 8) Dose limits do not exceed both of the following: a) Adults and pediatric members ≥40 kg: 35.6 mg per day; OR pediatric members <40 kg: 17.8 mg per day; AND b) 2 tablets per day;

Required trials must be ≥1 month each unless contraindicated or intolerant
Age-based exceptions: certain tricyclic requirements waived if member ≥65 (clarified for clomipramine and protriptyline)
State-specific exception: Illinois HIM (step therapy exemptions as of 01/01/2026)

Documentation Required

Documentation Requirements and Risk of Denial

Providers must submit supporting documentation with requests. Acceptable documentation includes office chart notes, diagnostic test results (e.g., MSLT, PSG, CSF hypocretin levels), medication trial history, and consultation notes from neurologists or sleep medicine specialists. Requests lacking documentation demonstrating that all applicable criteria are met may be denied. Non‑FDA (off‑label) indications require additional evidence per applicable off‑label policies.

Include objective diagnostic documentation (e.g., mean sleep latency <8 minutes with ≥2 SOREMPs on MSLT, or CSF hypocretin <110 pg/mL when applicable)
Document medication trials (agent, dose, duration, and reason for discontinuation)
Document specialist involvement (prescribing clinician or consultation)

Denial Risk

Provider Responsibility and Coverage Administration

Providers are responsible for clinical judgment and maintaining appropriate documentation. This policy is not medical advice and does not replace provider decision‑making. Providers are accountable for ensuring treatment decisions and documentation comply with applicable contract terms, state and federal requirements, and Health Plan administrative policies.

Providers must ensure records support the medical necessity criteria before submitting requests
Coverage decisions and benefit administration follow the member's coverage documents and applicable laws
Policy availability and effective dates may differ from posting; legal/regulatory requirements govern when discrepancies exist

Listed in Appendix A: Abbreviation/Acronym Key

inv-21: SOREMP abbreviation

SOREMPSleep-onset rapid eye movement period

Use in policySOREMPs are part of MSLT/PSG diagnostic criteria (e.g., ≥2 SOREMPs or combinations of MSLT and PSG findings)

AppendixListed in Appendix A: Abbreviation/Acronym Key