CurrentCentenePolicy CP PMN.116

Clinical Policy: L-glutamine (Endari)

Policy governing medical necessity and prior authorization criteria for Endari and generic L-glutamine to reduce acute complications of sickle cell disease for Centene-affiliated health plans, affecting commercial, HIM, and Medicaid lines of business.

Policy Summary

PayerCentene

PolicyClinical Policy: L-glutamine (Endari)

Policy CodePolicy CP PMN.116

Change TypeRevisions include generic inclusion and approval duration update

Effective Date08.22.17

Next Review Date

Key ActionSubmit prior authorization with supporting documentation showing diagnosis, age ≥5 years, and prior hydroxyurea use or contraindication.

SourceLink

POLICY UPDATE CHANGES

Revised policy/criteria section to also include generic L-glutamine and added redirection to L-glutamine.

Revised approval duration for Commercial line of business to 12 months or duration of request, whichever is less.

Added HIM line of business to the policy.

>=5minimum patient age for FDA indication

30 g/daymaximum daily dose

12 monthsapproval duration

CP PMN.116policy identifier

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Coverage and Medical Necessity Criteria

Initial Therapy — Medical Necessity Criteria

Covered when ALL of the following are met for initial approval:

Initial Approval Criteria: 1) Diagnosis of sickle cell disease; 2) Age >= 5 years; 3) Failure of hydroxyurea at up to maximally tolerated doses unless contraindicated or clinically significant adverse effects are experienced; 4) For Endari requests, member must use L-glutamine unless contraindicated or clinically significant adverse effects are experienced; 5) Dose does not exceed 30 grams per day based on weight.<= 30 g/day

Provider must submit supporting documentation (e.g., office chart notes, lab results).

Continuation Therapy — Medical Necessity Criteria

Covered when ALL of the following are met for continued therapy:

Continued Therapy Criteria: 1) Member is currently receiving medication via Centene benefit or has previously met initial approval criteria (or is covered under applicable continuity of care regulations); 2) Member is responding positively to therapy; 3) For Endari requests, member must use L-glutamine unless contraindicated or clinically significant adverse effects are experienced; 4) If request is for a dose increase, the new dose does not exceed 30 grams per day based on weight.<= 30 g/day

Prior authorization may be required for continued therapy.

Non–FDA approved indications that are not addressed in this policy require supporting documentation consistent with Centene off‑label use policies to be considered for authorization. Providers should reference the applicable off‑label use policy or evidence‑of‑coverage documents when submitting requests for indications outside the FDA‑approved labeling.

Requests for use of L‑glutamine for non‑FDA approved indications may be denied unless there is sufficient documentation of efficacy and safety per the referenced off‑label policies (CP.CPA.09 for Commercial, HIM.PA.154 for Health Insurance Marketplace, and CP PMN.53 for Medicaid) or other evidence‑of‑coverage documentation. Lack of such documentation is a basis for authorization denial.

Coding and Dosing Information

Codes referencedmixed

N/A	No explicit CPT/HCPCS/ICD-10 codes listed in policy document; references prescribing information and literature.

Maximum daily dose

Maximum daily dose30 g/day

BasisMaximum dose based on weight per Dosage and Administration

ContextApplies to sickle cell disease dosing of L-glutamine (Endari)

Weight-based dosing

>65 kg15 g PO twice daily (3 packets per dose)

30–65 kg10 g PO twice daily (2 packets per dose)

Maximum

Provider Requirements and Authorization Workflow

Prior Authorization

Prior Authorization Required

Prior Authorization may be required for L-glutamine (Endari). Approval is contingent on meeting the policys clinical criteria and submission of required documentation; prior authorization decisions will consider step therapy requirements (see Hydroxyurea step therapy) and contraindications.

Prior authorization applies to L-glutamine (Endari) requests.
Approvals contingent on meeting all listed clinical criteria in Initial and Continued Therapy sections.
Prior authorization determinations will follow applicable state-specific continuity of care rules.

Step Therapy

Step Therapy with Hydroxyurea

Hydroxyurea is the preferred first-line therapy. Members must have failure or intolerance to hydroxyurea at maximally tolerated doses before approval of L-glutamine, unless hydroxyurea is contraindicated or causes clinically significant adverse effects.

Background and Indication

L‑glutamine (Endari) is indicated to reduce acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. It is supplied as an oral powder and dosed by weight; dosing guidance and efficacy are described in the prescribing information and supporting clinical trial evidence.

Policy Revision History

2017-08-22effective_date

Policy effective date established.

2020-08-15annual_review

4Q 2020 annual review: added HIM line of business and updated references; P&T Approval Date 11/20/2020.

2021-10-18approval_duration_change

Revised approval duration for Commercial line of business from length of benefit to a fixed 12 months or duration of request, whichever is less.

Policy Summary

PayerCentene

PolicyClinical Policy: L-glutamine (Endari)

Policy CodePolicy CP PMN.116

Change TypeRevisions include generic inclusion and approval duration update

Effective Date08.22.17

Next Review Date

Key ActionSubmit prior authorization with supporting documentation showing diagnosis, age ≥5 years, and prior hydroxyurea use or contraindication.

SourceLink

On This Page

Do not exceed 30 g/day based on weight

Step therapy requires documented trial of hydroxyurea at up to maximally tolerated dose with inadequate response or intolerance.

If hydroxyurea is contraindicated or causes clinically significant adverse effects, document reasons for intolerance/contraindication.

Therapeutic alternatives table (Appendix B) may list hydroxyurea brand/generic; some alternatives may require prior authorization.

Documentation Required

Required Documentation

Provider must submit documentation supporting that the member has met all approval criteria. Documentation should include office chart notes, relevant laboratory results, medication history (including hydroxyurea dosing and response), and any records of adverse effects or contraindications.

Office notes documenting diagnosis of sickle cell disease and clinical course.
Labs and objective data showing treatment response or failure.
Medication history confirming trial and dosing of hydroxyurea (or documentation of contraindication/intolerance).
Documentation of current dosing if requesting dose increase (dose must not exceed 30 g/day based on weight).

Denial Risk

Denial Triggers

Coverage is not authorized for non-FDA approved indications unless sufficient documentation supports off-label use per applicable off-label policies; requests lacking such evidence may be denied.

Denial likely for non-FDA indications without adequate off-label evidence or absence of applicable off-label policy adherence (see CP CPA.09, HIM.PA.154, CP PMN.53).
Denial may occur if required documentation (e.g., hydroxyurea trial evidence, labs, office notes) is not submitted.
Denial may occur if step therapy requirements (trial of hydroxyurea) are not met and no documented contraindication/intolerance is provided.

2022-08-02annual_review

4Q 2022 annual review: no significant clinical changes; references reviewed and template changes applied to continued therapy section (P&T Approval Date 11/22).

2023-07-11annual_review

4Q 2023 annual review: no significant clinical changes; references reviewed and updated (P&T Approval Date 11/23).

2024-07-19material_revisionLatest

4Q 2024 annual review: revised policy/criteria to include generic L-glutamine and added redirection to L-glutamine; references reviewed and updated (P&T Approval Date 11/24).