CurrentCentenePolicy CP.PHAR.442

Fedratinib (Inrebic)

Defines medical necessity criteria, approval durations, and coverage rules for fedratinib (Inrebic) for FDA-approved myelofibrosis indications and a specified off-label NCCN-supported indication across Centene lines of business (Commercial, HIM, Medicaid).

Policy Summary

PayerCentene

PolicyFedratinib (Inrebic)

Policy CodePolicy CP.PHAR.442

Change TypePractice-guideline aligned updates and administrative clarifications

Effective DateDec 1, 2019

Next Review Date

Key ActionProvider must submit documentation supporting that member meets all approval criteria, including recent thiamine and platelet lab results and evidence of prior ruxolitinib use or contraindication.

SourceLink

POLICY UPDATE CHANGES

Added off-label criteria for myeloid or lymphoid neoplasm with eosinophilia and Janus kinase 2 arrangement per NCCN category 2A recommendation.

For brand name requests added requirement for generic alternative if available.

Consolidated approval durations: initial auth 6 months for Medicaid/HIM and 12 months for Commercial (or duration of request, whichever is less); continued therapy approvals standardized to 12 months for Medicaid/HIM and Commercial.

Removed prior requirement for failure of hematopoietic cell transplant, hydroxyurea, and concurrent treatment with Jakafi within 14 days.

4Q2024 annual review: no significant changes; references reviewed and updated.

2FDA-approved indications (MF subtypes)

1NCCN-supported off-label indication

400 mg

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>=70 nmol/LRequired thiamine

Coverage Summary

Coverage stance: covered with criteria for fedratinib (Inrebic) per policy CP.PHAR.442 (Effective: 12.01.19; Last review: 11.24). Indications covered include FDA-approved myelofibrosis subtypes: intermediate-2 or high-risk primary MF, post-PV MF, and post-ET MF, and the NCCN 2A off-label indication for myeloid/lymphoid neoplasm with eosinophilia and JAK2 arrangement. Applicable lines of business: Commercial, HIM, Medicaid. Approval durations consolidated in the policy: initial authorization Medicaid/HIM 6 months; Commercial 12 months (or duration of request, whichever is less); continued therapy approvals standardized to 12 months (Medicaid/HIM and Commercial per continuation rules).

Key thresholds and durations

Thiamine level>= 70 nmol/L (3 mcg/dL)

Platelet count>= 50,000/mcL

Maximum daily dose400 mg/day

Maximum capsules/day4 capsules/day

Age requirement>= 18 years

Initial approval duration (Medicaid/HIM)6 months

Initial approval duration (Commercial)12 months or duration of request, whichever is less

Continued therapy approval duration (Medicaid/HIM)12 months

Continued therapy approval duration (Commercial)12 months or duration of request, whichever is less

Boxed warningSerious and fatal encephalopathy including Wernicke encephalopathy (boxed warning present)

Initial Therapy Criteria — FDA-approved indication (myelofibrosis)

Initial Therapy Criteria — Off‑label: Myeloid/Lymphoid Neoplasms with Eosinophilia and JAK2 arrangement

Continuation Therapy Criteria

Other / Not Authorized Indications

Diagnoses/Indications NOT authorized

Coverage is NOT authorized for:

Non–FDA approved indications that are not addressed in this policy, unless sufficient documentation of efficacy and safety is provided per off-label use policies or evidence of coverage documents

Applicable Codes & Product Availability

Product availabilitymixed

100 mg capsule

Inrebic capsule strength (product availability)

Provider Actions / Authorization Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for fedratinib (Inrebic). Providers must submit a prior authorization request and include all required supporting documentation as described below to allow clinical review.

Request must be submitted prior to dispensing/administration.
Include clinical rationale and relevant prescribing information.

Documentation Required

Documentation Requirements

Submit clinical documentation with the prior authorization request to demonstrate that the member meets policy criteria. Documentation should include office/clinic notes and relevant laboratory results. Specifically, provide evidence of prior use of ruxolitinib (Jakafi) with documentation of failure, intolerance, or contraindication when required by the clinical criteria, or documentation supporting why ruxolitinib is not appropriate.

Office chart notes documenting diagnosis, prescriber specialty (hematologist/oncologist), and treatment history.

Clinical Evidence & Guidelines

Key evidence and guidance cited in the policy include the randomized clinical trial: Pardanani A, Harrison C, Cortes JE, et al., JAMA Oncol. 2015 (safety and efficacy of fedratinib), and guideline support from NCCN Myeloproliferative Neoplasms Version 1.2024. Safety context includes the prescribing information boxed warning for serious and fatal encephalopathy, including Wernicke encephalopathy.

Background

Background: Fedratinib (Inrebic) is a kinase inhibitor indicated by the FDA for treatment of adult patients with intermediate-2 or high-risk primary or secondary (post-PV or post-ET) myelofibrosis. The policy references the Inrebic prescribing information and NCCN recommendations for MF; the prescribing information includes a boxed warning for serious and fatal encephalopathy, including Wernicke encephalopathy. Dosing guidance in the policy notes a maximum dose of 400 mg/day (capsules available as 100 mg each) and monitoring requirements such as baseline thiamine and platelet thresholds as specified in the policy and referenced sources.

Definitions

MFMyelofibrosis

Post-PVPost-polycythemia vera

Post-ETPost-essential thrombocythemia

Revision History

4Q2022added

Added off-label criteria for myeloid or lymphoid neoplasm with eosinophilia and Janus kinase 2 arrangement per NCCN category 2A recommendation (off‑label section added and NCCN referenced).

4Q2022revised

For brand Inrebic requests added requirement that member must use generic fedratinib if available (brand vs generic requirement added).

2021-2022consolidated

Policy Summary

PayerCentene

PolicyFedratinib (Inrebic)

Policy CodePolicy CP.PHAR.442

Change TypePractice-guideline aligned updates and administrative clarifications

Effective DateDec 1, 2019

Next Review Date

SourceLink

On This Page

Evidence of prior ruxolitinib use, intolerance, contraindication, or justification for skipping ruxolitinib when the policy requires trial and failure.

Documentation Required

Laboratory Monitoring Requirement

Obtain and submit baseline laboratory monitoring results as part of the authorization. Lab values must be recent (within 30 days prior to the request) to assess safety and eligibility for therapy.

Thiamine level: document a result ≥ 70 nmol/L (≥ 3 mcg/dL) obtained within 30 days of the request.
Platelet count: document a result ≥ 50,000/mcL obtained within 30 days of the request.

Billing Rule

Brand vs. Generic Requirement

When a generic version of fedratinib is available, the generic product must be used unless the prescriber documents a contraindication or a clinically significant adverse effect to the generic formulation.

If brand Inrebic is requested, include documentation of medical necessity for brand over generic fedratinib.

Denial Risk

Dose Limit Enforcement

Dose requests above the policy limits may be denied. Requests for dosing in excess of 400 mg per day or more than 4 capsules per day require supporting justification (e.g., guideline or peer-reviewed literature) to be considered and may be denied if unsupported.

Maximum routine dose: 400 mg/day and a maximum of 4 capsules/day.
Requests exceeding these limits should include literature or guideline support; unsupported requests may be denied.

Consolidated approval durations: initial auth standardized to Medicaid/HIM 6 months and Commercial 12 months (or duration of request, whichever is less); continued therapy approvals standardized to 12 months for Medicaid/HIM and Commercial.

4Q2021removed

Removed prior requirement for failure of hematopoietic cell transplant (HCT), hydroxyurea, and concurrent treatment with Jakafi within 14 days.

11.24P&T approval

P&T Approval Date = 11.24 (policy last reviewed and P&T approved).

4Q2024reviewLatest

4Q2024 annual review: no significant changes; references reviewed and updated (latest review marked).