L-glutamine (Endari) Form

L-glutamine (Endari) is an amino acid. FDA Approved Indication(s) Endari is indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that Endari is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Sickle Cell Disease (must meet all):

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. Dose does not exceed 30 grams per day based on weight.
   Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
   B. Other diagnoses/indications (must meet 1 or 2):

   1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or Page 1 of 5

   CLINICAL POLICY L-glutamine

   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      II. Continued Therapy A. Sickle Cell Disease (must meet all):
   3. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
5. Member is responding positively to therapy;

6. If request is for a dose increase, new dose does not exceed 30 grams per day based on weight. Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less
   B. Other diagnoses/indications (must meet 1 or 2):

   1. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
   2. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
      III. Diagnoses/Indications for which coverage is NOT authorized:
      A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
      Page 2 of 5

   CLINICAL POLICY L-glutamine IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key FDA: Food and Drug Administration Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent for all relevant lines of business and may require prior authorization.
   Drug Name Dosing Regimen hydroxyurea (Hydrea, Droxia) Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. 15 mg/kg PO QD
   Dose Limit/ Maximum Dose 35 mg/kg/day Appendix C: Contraindications/Boxed Warnings None reported
   V. Dosage and Administration
   Indication Dosing Regimen Sickle cell disease • Weight > 65 kg: 15 g (3 packets) PO BID • Weight 30 to 65 kg: 10 g (2 packets) PO BID • Weight < 30 kg: 5 g (1 packet) PO BID Maximum Dose 30 g/day (maximum dose based on weight) VI. Product Availability
   Oral powder: 5 g VII.