MHN azacitidine Coverage & Prior Auth Update

Coverage Criteria

Initial Therapy — Myelodysplastic Syndromes (MDS / JMML)

Covered when ALL of the following are met

MDS initial criteria: 1. Diagnosis of myelodysplastic syndrome (MDS), including juvenile myelomonocytic leukemia (JMML); 2. Request is for generic azacitidine or Vidaza; 3. Prescribed by or in consultation with an oncologist or hematologist; 4. One of: (a) age ≥18 years, or (b) age ≥1 month when request is for JMML; 5. For brand Vidaza requests, member must use generic azacitidine unless contraindicated or clinically significant adverse effects are experienced; 6. Request meets one of the following dosing options: (a) For MDS initial: ≤75 mg/m2/day for 7 days per cycle; (b) For MDS maintenance: ≤100 mg/m2/day for 7 days per 28-day cycle; (c) For JMML (administered daily for 7 days per 28-day cycle, up to 6 cycles): (i) age 1 month to <1 year or weight <10 kg: 2.5 mg/kg; (ii) age ≥1 year and weight ≥10 kg: 75 mg/m2; (d) Dose supported by practice guidelines or peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.see text

All elements required

Initial Therapy — Acute Myeloid Leukemia (AML) / Onureg maintenance

Covered when ALL of the following are met

AML maintenance (Onureg): 1. Diagnosis of acute myeloid leukemia (AML); 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥18 years; 4. For Onureg requests, all of the following: (a) request is for maintenance therapy; (b) prescribed as a single agent; (c) member achieved CR or CRi following intensive induction chemotherapy; (d) one of: (i) medical justification supports inability to use SC/IV azacitidine (e.g., excipient contraindication), or (ii) request is for treatment in a state with regulations against step therapy in certain oncology settings (see appendices); 5. For Vidaza requests in AML, permitted as single agent or in combination with targeted agents per mutation status (e.g., with Venclexta; Nexavar for FLT3-ITD relapsed/refractory disease; Tibsovo for IDH1; Idhifa for IDH2; Xospata for FLT3 in absence of IDH1); 6. For brand product requests, member must use generic azacitidine if available unless contraindicated or clinically significant adverse effects are experienced; 7. Request meets one of the following dosing options: (a) Onureg: ≤300 mg (1 tablet) per day for 14 days per 28-day cycle; (b) Vidaza: ≤100 mg/m2/day for 7 days per 28-day cycle; (c) Dose supported by practice guidelines or peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.see text

All elements required

Initial Therapy — Myeloproliferative Neoplasms (advanced phase)

Covered when ALL of the following are met

Myeloproliferative neoplasms (advanced phase): 1. Diagnosis of advanced-phase myeloproliferative neoplasm (accelerated- or blast-phase); 2. Request is for generic azacitidine or Vidaza; 3. Prescribed by or in consultation with an oncologist or hematologist; 4. Age ≥18 years; 5. Prescribed as bridging therapy prior to transplant unless member is not a candidate for transplant; 6. One of: (a) single agent or in combination with Jakafi, Inrebic, Ojjaara, or Vonjo for palliation of splenomegaly or other disease-related symptoms; (b) in combination with Venclexta; 7. For brand Vidaza requests, member must use generic azacitidine unless contraindicated or clinically significant adverse effects are experienced; 8. Request meets one of the following dosing options: (a) ≤100 mg/m2/day for 7 days per 28-day cycle; (b) Dose supported by practice guidelines or peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.see text

All elements required

Initial Therapy — Peripheral T-cell lymphoma

Covered when ALL of the following are met

Peripheral T-cell lymphoma (relapsed/refractory): 1. Diagnosis of one of: angioimmunoblastic T-cell lymphoma; nodal peripheral T-cell lymphoma with TFH phenotype; follicular T-cell lymphoma; 2. Prescribed by or in consultation with an oncologist or hematologist; 3. Age ≥18 years; 4. Disease is relapsed or refractory; 5. Prescribed as a single agent for either initial palliative therapy or second-line/subsequent therapy; 6. For Onureg requests, one of: (a) medical justification supports inability to use SC/IV azacitidine (e.g., contraindication to excipients), or (b) request is for treatment in a state with regulations against step therapy in certain oncology settings (see appendices); 7. For brand product requests, member must use generic azacitidine unless contraindicated; 8. Request meets one of the following dosing options: (a) Onureg: ≤300 mg (1 tablet) per day for 14 days per 28-day cycle; (b) Vidaza: ≤100 mg/m2/day for 7 days per 28-day cycle; (c) Dose supported by practice guidelines or peer-reviewed literature for relevant off-label use (prescriber must submit supporting evidence). Prescribed regimen must be FDA-approved or recommended by NCCN.see text

All elements required

Continuation Therapy

Covered when ALL of the following are met

Continuation therapy: 1. Member is currently receiving Vidaza or Onureg via the Centene benefit, or documentation supports that member has been receiving Vidaza or Onureg for at least 30 days; 2. Member is responding positively to therapy; 3. For brand product requests, member must use generic azacitidine if available unless contraindicated or clinically significant adverse effects are experienced; 4. If request is for a dose increase, new dose must meet one of the following: (a) Onureg: new dose ≤300 mg (1 tablet) per day for 14 days per 28-day cycle; (b) Vidaza for MDS: new dose ≤100 mg/m2/day for 7 days per 28-day cycle; (c) Vidaza for JMML: new dose meets the pediatric JMML dosing limits (age 1 month to <1 year or weight <10 kg: 2.5 mg/kg; age ≥1 year and weight ≥10 kg: 75 mg/m2, daily for 7 days per 28-day cycle, up to 6 cycles); (d) New dose 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.see text

All elements required

Label-indication coverage (Onureg, Vidaza)

Covered indications and dosing as specified in product labeling and NCCN-aligned criteria

Onureg (azacitidine tablets) AML coverage: Onureg (azacitidine tablets) indicated for AML maintenance: 300 mg PO once daily on days 1–14 of each 28-day cycle; maximum dose 300 mg/day for 14 days per cycle. Prescribed regimen must be FDA-approved or recommended by NCCN. Prior authorization criteria require single-agent use for Onureg per policy updates and generic substitution rules apply.dosing per label

See policy criteria section for patient eligibility and NCCN alignment

Vidaza (azacitidine injection) MDS and JMML coverage: Vidaza (azacitidine injection) indicated for MDS: 75 mg/m2 SC or IV once daily for 7 days every 4 weeks (may increase to 100 mg/m2 after 2 cycles); treat a minimum of 4–6 cycles; doses may be adjusted for labs, renal function, or electrolytes. For JMML: age 1 month to <1 year or weight <10 kg: 2.5 mg/kg IV daily for 7 days; age ≥1 year and weight ≥10 kg: 75 mg/m2 IV daily for 7 days in a 28-day cycle; minimum 3 cycles and maximum 6 cycles. Continue treatment while patient benefits; doses adjusted per label recommendations.dosing per label

Pediatric JMML indication recently added/updated.

Coverage for non-FDA approved (off-label) indications that are not specifically addressed in this policy is not authorized unless the provider submits sufficient documentation demonstrating efficacy and safety in accordance with the applicable off‑label use policies (e.g., CP.CPA.09 for commercial, HIM.PA.154 for Marketplace, or CP.PMN.53 for Medicaid) or the member’s evidence of coverage documents.

Azacitidine products have specific contraindications: advanced malignant hepatic tumors is a contraindication for Vidaza only. Additionally, hypersensitivity to azacitidine is a contraindication for all azacitidine products; for Vidaza this includes hypersensitivity to mannitol (an excipient in the formulation).

HCPCS and other billing codes are provided for informational purposes only; inclusion or exclusion of any code does not guarantee coverage. Providers must follow current professional coding guidance and the policy’s coverage criteria when submitting claims to avoid potential denials.

Coding and Product Details

HCPCS Codes referencedHCPCS

J9025

Injection, azacitidine, 1 mg

Onureg and Vidaza — product strengths and key dosing limits

Onureg tablet strengthsTablets available in 200 mg and 300 mg strengths; maximum Onureg dose 300 mg once daily on days 1–14 of each 28‑day cycle (300 mg/day max)

Vidaza vial strengthLyophilized powder supplied in single‑dose 100 mg vials for reconstitution (azacitidine injection)

Vidaza dosing summaryStandard dosing for MDS: 75 mg/m2 SC or IV daily x7 days every 4 weeks (may increase to 100 mg/m2 after 2 cycles); maximum 100 mg/m2/day

Provider Actions and Authorization Requirements

Billing Rule

Coding inclusion not a guarantee of coverage

Codes referenced in this clinical policy are for informational purposes only. Inclusion or exclusion of any codes does not guarantee coverage. Providers should reference the most up-to-date sources of professional coding guidance prior to claim submission. Billing using listed codes does not ensure payment and may still be subject to medical necessity review and denial.

HCPCS: J9025 (Injection, azacitidine, 1 mg)

Step Therapy

Step therapy / SC/IV azacitidine

Step therapy/redirection rules apply for subcutaneous (SC) or intravenous (IV) azacitidine (Vidaza) in certain indications. For AML and other oncology indications, members are generally required to use SC/IV azacitidine (Vidaza or generic azacitidine) before brand oral Onureg unless one of the following applies: medical justification supports inability to use SC/IV azacitidine (e.g., contraindication to excipients), or the request is for treatment associated with cancer in a state with regulations that prohibit step therapy/redirection in specified oncology settings (see Appendix E). Note: For Illinois HIM requests, step therapy requirements do not apply as of 1/1/2026 per IL HB 5395.

Background

Azacitidine is a nucleoside metabolic inhibitor available in oral (Onureg) and injectable (Vidaza/generic azacitidine) formulations and is used across several myeloid malignancies. Onureg is indicated as maintenance oral therapy for adults with acute myeloid leukemia (AML) in first complete response (CR) or complete response with incomplete hematologic recovery (CRi) after intensive induction chemotherapy, per labeled dosing. Vidaza (and generic azacitidine) is indicated for various myelodysplastic syndromes (MDS) and, per recent updates, pediatric juvenile myelomonocytic leukemia (JMML) with age/weight‑based dosing. Providers must observe product‑specific contraindications (e.g., Vidaza in advanced malignant hepatic tumors, hypersensitivity to azacitidine or mannitol) and ensure that off‑label uses are supported by appropriate documentation and applicable off‑label use policies.

Definitions

Appendix A abbreviations (CR / CRi)

CR abbreviationCR = complete response

CRi abbreviationCRi = complete response with incomplete hematologic recovery

Appendix referenceAbbreviations listed in Appendix A of the policy (CR, CRi, AML, ANC, etc.)

Complete response (CR) — NCCN definition

CR (definition)Morphologic complete response (CR) per NCCN: marrow blasts <5% with absolute neutrophil count (ANC) >1,000/mcL and platelets ≥100,000/mcL in transfusion‑independent patients

Context — Onureg indicationOnureg indicated for adults with AML who achieved first CR or CRi after intensive induction and are unable to complete intensive curative therapy

Line of Therapy

maintenance — maintenance therapy criteria node

maintenance: Onureg is indicated for maintenance therapy in AML after achievement of CR or CRi following intensive induction chemotherapy; Onureg must be prescribed as single-agent maintenance per policy criteria and dosing limited to 300 mg PO daily on days 1–14 of each 28-day cycle.

second-line | salvage — criteria node

second-line | salvage: Permitted as second-line or salvage therapy when disease is relapsed or refractory and prescriber documents indication and prior therapies; Onureg requests must meet single-agent and dosing criteria or provide medical justification for inability to use SC/IV azacitidine or state-specific step therapy exceptions.

first-line — criteria node

first-line:

Biomarker Requirements

FLT3‑ITD, FLT3‑TKD, IDH1, IDH2 — mutation test considerations

Mutation tests relevantFLT3-ITD, FLT3-TKD, IDH1, and IDH2 mutation status are referenced for selecting Vidaza combination regimens in AML (e.g., Nexavar for FLT3‑ITD, Xospata for FLT3, Tibsovo for IDH1, Idhifa for IDH2)

Required considerationMutation testing should be used to guide combination therapy choices per the policy (Vidaza combined with targeted agents based on mutation status)

Clinical implicationDocumentation of the relevant mutation may be required to justify use of specific Vidaza combinations per prior authorization criteria

Covered Regimens and Dosing

Regimen	Indication	Coverage
Onureg single-agent 300 mg PO once daily on days 1–14 of each 28-day cycle (maximum 300 mg/day)
AML — maintenance after achievement of CR or CRi following intensive induction chemotherapy; member unable to complete intensive curative therapy
Single-agent Onureg maintenance per policy criteria; prior authorization required and step-therapy to SC/IV azacitidine may apply unless medical justification or state exception documented

Regimen	Mutation / Combination	Coverage
Vidaza (azacitidine injection) as single agent or in combination with targeted agents
Examples: with Venclexta; with Nexavar for relapsed/refractory FLT3-ITD; with Tibsovo for IDH1; with Idhifa for IDH2; with Xospata for FLT3 (in absence of IDH1 mutation)
Permitted when mutation status and clinical context support the combination; prior authorization required per policy criteria

Drug	Dosing (adult / pediatric JMML)	Notes
Onureg (azacitidine tablets)
300 mg PO once daily on days 1–14 of each 28‑day cycle (maximum 300 mg/day for 14 days)
Indicated for AML maintenance per labeling; continue while patient benefits; prior authorization required

OpenPayer

Azacitidine (Onureg, Vidaza)

Coverage Criteria

Coding and Product Details

Provider Actions and Authorization Requirements

Background

Definitions

Line of Therapy

Biomarker Requirements

Covered Regimens and Dosing