Hydroxyurea (Siklos) Form

Hydroxyurea (Siklos) is an antimetabolite. FDA Approved Indication(s) Siklos is indicated to reduce the frequency of painful crises and to reduce the need for blood transfusions in adult and pediatric patients, 2 years of age and older, with sickle cell anemia with recurrent moderate to severe painful crises. 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 Siklos 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 ≥ 2 years;

3. Member must use generic hydroxyurea, unless contraindicated or clinically significant adverse effects are experienced;

   4. Dose does not exceed 35 mg/kg per day based on weight.
      Approval duration:
      Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less B. Oncology Indications (off-label) (must meet all):
   5. Diagnosis of one of the following (a-f); a. Acute myeloid leukemia; b. Chronic myeloid leukemia; c. Head and neck cancer; d. Myeloproliferative neoplasms (myelofibrosis, polycythemia vera, essential thrombocythemia); e. Myelodysplastic syndromes; f. Langerhans Cell Histiocytosis;
   6. Age ≥ 2 years; Page 1 of 6

   CLINICAL POLICY Hydroxyurea

   3. Member must use generic hydroxyurea, unless contraindicated or clinically significant adverse effects are experienced;
4. Request meets one of the following (a or b): a. Dose does not exceed 80 mg/kg per day based on weight; b. Dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Approval duration:
   Medicaid/HIM – 12 months Commercial – 12 months or duration of request, whichever is less C. 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.
      II. Continued Therapy A. All Indications in Section I (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, request meets one of the following (a, b, or c): a. Sickle cell disease: New dose does not exceed 35 mg/kg per day based on weight; b. Oncology indications: New dose does not exceed 80 mg/kg per day based on weight; c. New dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN Approval duration:
   Medicaid/HIM – 12 months Page 2 of 6

   CLINICAL POLICY Hydroxyurea
   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.
      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.
      Dosing Regimen Drug Name Dose Limit/ Maximum Dose Sickle disease: 35 mg/kg/day Oncology indications: 80 mg/kg/day hydroxyurea (Hydrea, Droxia) Sickle cell disease: 15 mg/kg PO QD
      CML: 40 mg/kg/day Head and neck cancer: 1,000 mg q12h 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. Appendix C: Contraindications/Boxed Warnings • Contraindication(s): hypersensitivity to hydroxyurea or any other component of its formulation Page 3 of 6

   CLINICAL POLICY Hydroxyurea
   • Boxed warning(s): myelosuppression and malignancies
   V. Dosage and Administration
   Indication Sickle cell disease Dosing Regimen Initial dose 15 mg/kg in adults and 20 mg/kg in children PO QD. Dose may be increased by 5 mg/kg/day every 8 weeks or sooner if a severe painful crisis occurs. Maximum Dose 35 mg/kg/day (maximum dose based on weight) VI. Product Availability
   Tablets: 100 mg, 1,000 mg VII.