CurrentCentenePolicy CP.PMN.193

Clinical Policy: Hydroxyurea (Siklos, Xromi)

Policy governing medical necessity and prior authorization criteria for hydroxyurea products Siklos and Xromi for sickle cell disease and certain off-label oncology indications for Centene-affiliated health plans.

Policy Summary

PayerCentene

PolicyClinical Policy: Hydroxyurea (Siklos, Xromi)

Policy CodePolicy CP.PMN.193

Change TypeNo material change noted

Effective Date02.19.19

Next Review Date

Key ActionSubmit prior authorization with documentation of diagnosis, age, dosing within limits, and prior use or response to therapy.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

35 mg/kg/dayMaximum routine SCD dose

80 mg/kg/dayMaximum oncology dose (Siklos)

12 monthsTypical approval duration

Siklos ≥9 mo; Xromi ≥6 moMinimum ages

Oral solution & tabsProduct availability

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Initial Therapy — Sickle Cell Disease

Covered when ALL of the following are met

SCD Initial Approval: 1. Diagnosis of sickle cell disease (SCD); 2. Age meets product-specific minimum: Siklos ≥ 9 months OR Xromi ≥ 6 months and < 18 years; 3. For members aged ≥ 2 years: use of generic hydroxyurea unless contraindicated or clinically significant adverse effects are experienced (Illinois HIM requests are exempt from this step therapy requirement as of 1/1/2026); 4. Dose does not exceed 35 mg/kg per day based on weight.35 mg/kg/day

Prescriber must submit supporting documentation

Initial Therapy — Oncology Indications (off-label)

Covered when ALL of the following are met

Oncology Initial Approval: 1. Diagnosis of one of the following: acute myeloid leukemia; chronic myeloid leukemia; head and neck cancer; myeloproliferative neoplasms (myelofibrosis, polycythemia vera, essential thrombocythemia); myelodysplastic syndromes; or Langerhans cell histiocytosis; 2. Request is for Siklos; 3. Age ≥ 2 years; 4. Member must use generic hydroxyurea unless contraindicated or clinically significant adverse effects are experienced (Illinois HIM requests are exempt from this step therapy requirement as of 1/1/2026); 5. Request meets one of the following: a) dose does not exceed 80 mg/kg per day based on weight; OR b) dose is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).80 mg/kg/day

Prescribed regimen must be FDA-approved or recommended by NCCN

Continuation Therapy

Covered when ALL of the following are met

Continuation Therapy: 1. Member currently receiving medication via Centene benefit or previously met initial approval criteria, or continuity of care applies; 2. Member is responding positively to therapy; 3. If request is for a dose increase: For SCD, new dose does not exceed 35 mg/kg per day based on weight; For Siklos in oncology indications, new dose either does not exceed 80 mg/kg per day based on weight OR is supported by practice guidelines or peer-reviewed literature for the relevant off-label use (prescriber must submit supporting evidence).See individual indication limits

Prescribed regimen must be FDA-approved or recommended by NCCN

Requests for indications that are non‑FDA approved and are not specifically addressed in this policy will be excluded unless the provider submits sufficient documentation of efficacy and safety in accordance with the Health Plan's off‑label use policies (for example, CP.CPA.09 for commercial, HIM.PA.154 for Health Insurance Marketplace, and CP.PMN.53 for Medicaid) or the member's evidence of coverage documents.

Coverage determinations under this clinical policy are subject to all terms, conditions, exclusions, and limitations of the member's coverage documents (such as evidence of coverage, certificate of coverage, or policy). State and federal requirements and applicable Health Plan administrative policies and procedures take precedence where applicable and may affect eligibility or benefit payment.

Uses of hydroxyurea that are not listed in this policy and for which there is insufficient off‑label evidence are considered not authorized unless the provider supplies adequate supporting evidence per the off‑label use policies noted in this document.

Regimen	Indication / Notes	Coverage status
Siklos up to 80 mg/kg/day (weight‑based)
Off‑label oncology indications: AML; CML; head and neck cancer; myeloproliferative neoplasms (myelofibrosis, polycythemia vera, essential thrombocythemia); myelodysplastic syndromes; Langerhans cell histiocytosis. Coverage when age ≥2 years and member has used generic hydroxyurea unless contraindicated or significant adverse effects; alternative: dose supported by practice guidelines or peer‑reviewed literature (prescriber must submit evidence).
Covered with criteria

Regimen / Product	Requirements	Coverage status
Siklos (brand) — prescribed regimen must be FDA‑approved or NCCN‑recommended
Requests must be for Siklos for the listed off‑label oncology indications; prescriber must confirm the prescribed regimen is FDA‑approved or recommended by NCCN. For pediatric extension, Xromi formulation referenced per updated prescribing information (pediatric use up to 18 years).
Covered when requirements met

Provider Actions and Requirements

Prior Authorization

Provider Actions and Requirements — Prior Authorization & Documentation

Prior authorization is required. Requests must document the diagnosis, applicable age criteria, and that dosing is within the limits specified by this policy. For members age ≥ 2 years, prior to approval providers must document trial and failure, intolerance, or contraindication to generic hydroxyurea unless the request is for an Illinois HIM line of business for which step therapy bypass applies per IL HB 5395 (effective 1/1/2026). For off‑label oncology requests, include documentation that the request is for Siklos and that the prescribed regimen is FDA‑approved or recommended by NCCN, or provide peer‑reviewed supporting evidence when dose exceeds standard limits. Provider must submit documentation (such as office chart notes, laboratory results, and other clinical information) that the member meets all applicable approval criteria. Providers are expected to exercise professional medical judgment and submit documentation consistent with the Health Plan’s medical necessity standards and the applicable off‑label use policies referenced below. Coverage decisions remain subject to the member’s evidence of coverage and all applicable state and federal requirements.

Prior authorization requires: diagnosis, age, dosing within policy limits, and evidence of prior use/continuity or positive response to therapy as applicable.
Off‑label oncology requests: must specify Siklos, age ≥ 2 years, trial of generic hydroxyurea for members ≥ 2 years unless contraindicated (IL HIM bypass noted), and state that the prescribed regimen is FDA‑approved or NCCN‑recommended or include peer‑reviewed evidence when dosing exceeds stated limits.
Generic step therapy: members ≥ 2 years must trial generic hydroxyurea before Siklos/Xromi unless contraindicated or clinically significant adverse effects occur. IL HIM line of business: step therapy bypass applies as of 1/1/2026 per IL HB 5395.
Required documentation: office notes, lab results, dosing calculations (mg/kg/day), prior authorization history or continuity of care documentation, and supporting literature for off‑label dosing when applicable.
Provider expectations: exercise professional medical judgment; submit documentation consistent with medical necessity standards and referenced off‑label use policies.
Non‑covered indications risk: requests for non‑FDA approved indications not addressed in this policy will be denied unless sufficient documentation of efficacy and safety is provided per off‑label use policies CC.PHARM.03A/03B (state addendums) and referenced policies for commercial, HIM, and Medicaid.
Coverage & regulatory compliance: coverage decisions are subject to all terms, conditions, exclusions, and limitations of the member’s coverage documents and applicable state and federal law; the Health Plan may change or withdraw this policy and the effective posting date may differ from the plan’s operative date.

OpenPayer

Clinical Policy: Hydroxyurea (Siklos, Xromi)

Coverage Criteria

Coding and Dose Limits

Provider Actions and Requirements

Definitions

Background

Line of Therapy