CurrentmhnPolicy CP.PMN.221

Pitolisant (Wakix) - Coverage Criteria

Medical necessity and prior authorization criteria for pitolisant (Wakix) for treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy across Commercial, HIM, and Medicaid lines of business.

Policy Summary

Payermhn

PolicyPitolisant (Wakix) - Coverage Criteria

Policy CodePolicy CP.PMN.221

Change TypeNo material change

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit prior authorization with supporting clinical documentation (office notes, labs, sleep study results) demonstrating that the member meets the approval criteria.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

≥6Min age for EDS (peds)

≥18Min age for cataplexy

35.6 mgMax adult daily dose

12 monthsStandard approval duration

2Required failed agents for cataplexy

2024

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Prescribing info year

Coverage Criteria for Pitolisant (Wakix)

Initial: Narcolepsy with Cataplexy

Covered when ALL of the following are met

Cataplexy initial criteria: 1) Prescribed for the treatment of cataplexy in narcolepsy; 2) Prescribed by or in consultation with a neurologist or sleep medicine specialist; 3) Age ≥ 18 years; 4) Documentation of one of the following (a or b): (a) EDS associated with narcolepsy confirmed by documented MSLT and one of the following: (i) mean sleep latency ≤ 8 minutes with evidence of two or more SOREMPs; or (ii) at least one SOREMP on MSLT and a SOREMP (<15 minutes) on the preceding overnight PSG; (b) CSF hypocretin-1 level ≤ 110 pg/mL; 5) Failure of 2 of the following agents, each used for ≥ 1 month, unless member age ≥ 65, clinically significant adverse effects, or contraindicated: venlafaxine, fluoxetine, atomoxetine, clomipramine, protriptyline (note: tricyclic antidepressants may not be required if age ≥ 65); 6) Dose does not exceed both: (a) 35.6 mg per day and (b) 2 tablets per day.see nodes

Per policy; IL HIM carve-out for step therapy effective 1/1/2026 applies

Initial: Narcolepsy with Excessive Daytime Sleepiness

Covered when ALL of the following are met

EDS initial criteria: 1) Diagnosis of narcolepsy with excessive daytime sleepiness (EDS); 2) Prescribed by or in consultation with a neurologist or sleep medicine specialist; 3) Age ≥ 6 years; 4) Documentation of both (a and b): (a) EDS associated with narcolepsy confirmed by documented MSLT and one of the following: (i) mean sleep latency ≤ 8 minutes with evidence of two or more SOREMPs; or (ii) at least one SOREMP on MSLT and a SOREMP (<15 minutes) on the preceding overnight PSG; (b) daily periods of irrepressible need to sleep or daytime lapses into sleep occurring for at least 3 months; 5) 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; 6) If age ≥ 17 years: failure of a 1-month trial of armodafinil or modafinil unless intolerant or contraindicated; 7) If age ≥ 18 years: failure of a 1-month trial of Sunosi unless contraindicated or intolerant (prior authorization may be required for comparators); 8) Dose limits: (a) adults and pediatric members weighing ≥ 40 kg: 35.6 mg/day; (b) pediatric members weighing < 40 kg: 17.8 mg/day; and (c) maximum 2 tablets per day.see nodes

Some prior authorization or step therapy requirements for comparators may apply; IL HIM carve-out per IL HB 5395

Continued Therapy

Covered when ALL of the following are met

Continued therapy criteria: 1) Member meets one of the following: (a) currently receiving medication via Centene benefit or previously met initial approval criteria; or (b) member is currently receiving medication and is enrolled in a state/product with continuity of care regulations; 2) Member is responding positively to therapy as evidenced by, but not limited to, reduction in frequency of cataplexy attacks or reported daytime improvements in wakefulness; 3) If request is for a dose increase, new dose does not exceed: (a) adults and pediatric members weighing ≥ 40 kg: 35.6 mg/day and 2 tablets/day; or (b) pediatric members weighing < 40 kg: 17.8 mg/day and 1 tablet/day.see nodes

Approval durations mirror initial (Medicaid/HIM 12 months; Commercial 12 months or duration of request, whichever is less)

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

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

Uses for diagnoses or indications that are not FDA‑approved and that lack adequate supporting documentation per the referenced off‑label use policies are considered not authorized under this policy.

Diagnostic Criteria and Codes

inv-07: MSLT mean sleep latency / SOREMP criteria

MSLT/SOREMP diagnostic thresholdMean sleep latency ≤ 8 minutes with evidence of ≥2 SOREMPs OR at least one SOREMP on MSLT plus a SOREMP (<15 minutes) on the preceding overnight PSG

Context of useDocumented as part of EDS confirmation for narcolepsy in initial approval criteria for cataplexy and EDS indications

Age applicabilityApplies to adults (cataplexy criteria specify age ≥18 years) and to EDS criteria (age ≥6 years) when used to confirm EDS

inv-08: CSF hypocretin-1 level

CSF hypocretin-1 cutoffCerebrospinal fluid (CSF) hypocretin-1 level ≤ 110 pg/mL

PurposeAccepted alternative diagnostic finding to MSLT/SOREMP for narcolepsy with cataplexy in initial approval criteria

Prior Authorization, Documentation, and Step Therapy

Prior Authorization

Prior Authorization Required

Prior authorization required. Approval durations: Medicaid/HIM — 12 months; Commercial — 12 months or duration of request, whichever is less.

Prior authorization required
Approval duration (Medicaid/HIM): 12 months
Approval duration (Commercial): 12 months or duration of request, whichever is less

Documentation Required

Required Documentation

Provider must submit documentation (such as office chart notes, laboratory results, diagnostic testing like MSLT/PSG, lumbar puncture results when performed, prior therapy trial documentation, and other clinical information) supporting that the member has met all applicable approval criteria. Requests that lack sufficient clinical documentation to demonstrate criteria have been met may be denied.

Definitions and Abbreviations

inv-18: Excessive daytime sleepiness (EDS) definition shorthand

Shorthand termEDS = excessive daytime sleepiness

Clinical feature referencedDaily periods of irrepressible need to sleep or daytime lapses into sleep occurring for ≥3 months (per EDS criteria)

Role in policyUsed to define the symptom constellation that must be confirmed (with MSLT or CSF criteria) for narcolepsy coverage determinations

inv-19: Multiple sleep latency test (MSLT) definition

AbbreviationMSLT = multiple sleep latency test

PurposeObjective test used to confirm EDS associated with narcolepsy as required by initial coverage criteria

Background

Pitolisant is a selective histamine H3 receptor antagonist/inverse agonist indicated for the treatment of excessive daytime sleepiness (EDS) and cataplexy in patients with narcolepsy. Prescribing information (Wakix) provides dosing guidance, age indications (including pediatric EDS from age 6 years), and formulation details.

Policy Summary

Payermhn

PolicyPitolisant (Wakix) - Coverage Criteria

Policy CodePolicy CP.PMN.221

Change TypeNo material change

Effective DateMar 1, 2020

Next Review Date

Key ActionSubmit prior authorization with supporting clinical documentation (office notes, labs, sleep study results) demonstrating that the member meets the approval criteria.

SourceLink

On This Page

Test typeLumbar puncture (CSF assay) as specified in policy initial criteria

Laboratory results (e.g., CSF hypocretin-1 when applicable)

Diagnostic testing results (e.g., MSLT, PSG)

Documentation of prior medication trials and durations

Specialist consultation notes (neurologist or sleep medicine)

Step Therapy

Step Therapy Requirements

Step therapy/redirect requirements apply as specified in the clinical criteria. For cataplexy: member must have failed 2 of the following agents, each used for ≥ 1 month, unless member is ≥ 65 years, experiences clinically significant adverse effects, or all are contraindicated: venlafaxine, fluoxetine, atomoxetine, clomipramine, protriptyline. Note: if member is ≥ 65 years, tricyclic antidepressants (clomipramine and protriptyline) are not required. For narcolepsy with EDS: trials of preferred stimulant or wake-promoting agents are required as detailed in the criteria (e.g., 1-month trial of amphetamine/dextroamphetamine/methylphenidate; armodafinil/modafinil when age criteria met; Sunosi and combination therapy requirements when applicable).

Cataplexy: failure of 2 agents (venlafaxine, fluoxetine, atomoxetine, clomipramine, protriptyline), each ≥1 month unless exception applies
If age ≥65, tricyclics (clomipramine, protriptyline) are not required
EDS: trial of one-month of generic CNS stimulant (amphetamine, dextroamphetamine, or methylphenidate) unless contraindicated
EDS age-based additional trials: armodafinil/modafinil (if ≥17) and Sunosi (if ≥18) per criteria
Prior authorization may be required for certain redirected agents (e.g., CNS stimulants, armodafinil/modafinil, Sunosi)

Note

Step Therapy / Redirection Notes and Prior Authorization History

Step therapy and redirection history/notes: brand-name redirection language for Provigil® and Nuvigil® was removed in 2024 to clarify redirection is to the generic products only. Pediatric extension for narcolepsy with EDS was added in 2024. In 2025 clarifications were made that for narcolepsy with cataplexy, the age >65 exception to required trials applies to clomipramine and protriptyline only and that atomoxetine (although an SNRI) is not considered an antidepressant for redirection purposes. Per Illinois legislation (IL HB 5395), step therapy requirements do not apply for Illinois HIM requests effective 1/1/2026; a step therapy bypass for IL HIM was added in 2025.

2021: consolidated legacy Medicaid version and increased initial approval duration from 3 months to 12 months; commercial duration revised to 12 months or duration of request
2024: removed brand names Provigil/Nuvigil to clarify redirection to generics only; added pediatric EDS extension
2025: clarified age >65 tricyclic exception applies to clomipramine/protriptyline; atomoxetine not treated as antidepressant for redirection; added IL HIM step therapy bypass per IL HB 5395

Interpretation guidanceMSLT findings used with SOREMP count and mean sleep latency (e.g., mean sleep latency ≤8 minutes) to support diagnosis

inv-20: Sleep-onset rapid eye movement period (SOREMP) definition

AbbreviationSOREMP = sleep-onset rapid eye movement period

Diagnostic criterionPolicy requires evidence of two or more SOREMPs on MSLT or at least one SOREMP on MSLT plus a SOREMP (<15 minutes) on preceding overnight PSG

Use in testingSOREMP count combined with mean sleep latency on MSLT is used to confirm narcolepsy-related EDS

inv-21: Polysomnography (PSG) definition

AbbreviationPSG = polysomnography

Role in policyAn overnight PSG may be used preceding MSLT; a SOREMP on the preceding PSG plus a SOREMP on MSLT fulfills one diagnostic pathway

Testing contextPSG provides the overnight sleep study referenced when combining PSG and MSLT results for narcolepsy diagnosis

inv-22: Wakix (pitolisant) — brand name reference from prescribing information

Brand nameWakix (pitolisant) — brand name per prescribing information (Harmony Biosciences, LLC)

ReferenceWakix Prescribing Information cited in policy references (June 2024)

Product identityPitolisant referred to by its brand name Wakix throughout clinical references and prescribing information