Blue Cross Blue Shield MA ESAs Prior Auth Policy

Coverage and Medical Necessity Criteria

Retacrit — Covered indications and thresholds

Retacrit (epoetin alfa-epbx) may be considered MEDICALLY NECESSARY when ALL of the following are met for the specific indication:

Chronic renal failure indication: Anemia of chronic renal failure defined as GFR < 60 mL/min/1.73 m2 for >= 3 months or patients on dialysisInitiation: Hb < 11.0 g/dL; Continuation: Hb < 12.0 g/dL

Approve x 6 months for initiation or continuation as specified

AZT-associated anemia: Anemia due to AZT treatment in AIDSContinuation: Hb < 12.0 g/dL

Approve x 6 months for continuation

Ribavirin-associated anemia: Anemia due to ribavirin therapy in the treatment of hepatitis CInitiation: Hb < 10.0 g/dL; Continuation: Hb < 12.0 g/dL

Approve x 6 months

Myelodysplastic syndromes confirmed by bone marrow biopsy and/or aspirateInitiation and continuation thresholds as listed (Initiation: Hb < 12.0 g/dL; Continuation: Hb < 12.0 g/dL)

Approve x 6 months

Chemotherapy-associated anemia: Anemia due to the effects of concurrently administered chemotherapy in patients with nonmyeloid malignancies (or anticipated Hb decrease / comorbidities requiring higher Hb)Initiation: some scenarios Hb < 10.0 g/dL; Continuation: Hb < 12.0 g/dL

Approve x 6 months

Post-allogeneic bone marrow transplant anemia: Anemia following allogeneic bone marrow transplantInitiation: Hb < 10.0 g/dL; Continuation: Hb < 12.0 g/dL

Approve x 6 months

Anemic surgical patients (select perioperative use): Elective, non-cardiac, non-vascular surgery; hemoglobin between 10 and 13 g/dL; patient not willing to donate bloodApprove for 1 month of therapy

Approve x 1 month

Non-preferred agents — coverage after Retacrit failure

Other agents (Aranesp, Epogen/Procrit, Jesduvroq, Vafseo) are covered only after treatment failure of Retacrit and when the corresponding criteria are met:

Aranesp after Retacrit failure: Anemia associated with chronic renal failure defined as GFR < 60 mL/min/1.73 m2 for >= 3 months or patients on dialysis; or anemia due to concurrently administered chemotherapy in nonmyeloid malignanciesInitiation: Hb < 11.0 g/dL (or Hb < 10.0 g/dL for some chemotherapy-related indications); Continuation: Hb < 12.0 g/dL

Coverage only after documented treatment failure of Retacrit; approve x 6 months when criteria met

Jesduvroq or Vafseo after Retacrit failure: Anemia associated with chronic renal failure in patients on dialysisInitiation and continuation: Hb < 11.0 g/dL as specified

Coverage only after documented treatment failure of Retacrit; approve x 6 months when criteria met

Epogen/Procrit after Retacrit failure:

Coverage prerequisites and ESRD claim criteria

Coverage is contingent on meeting medical necessity criteria and appropriate coding/documentation for the listed HCPCS and ICD-10 codes.

General coverage prerequisites: Provider must submit up-to-date procedure (HCPCS) and diagnosis (ICD-10) codes and meet the medical necessity criteria in this policy for Commercial Members (HMO, POS, PPO, Indemnity)

Inclusion or exclusion of a code does not by itself guarantee coverage; medical necessity must be met

Modifier and program applicability: One of the specified modifier codes (e.g., EE) must accompany the drug HCPCS code on claims for hematocrit/hemoglobin threshold adjudication; these modifier requirements do not apply to FEP, BlueCard, or plans where Medicare is primary

Modifiers referenced in policy may be program-limited

ESRD-specific documentation for initial claim: Initial ESRD claims must include: patient's diagnosis; most recent creatinine prior to starting ESA; most recent transferrin saturation; most recent hematocrit prior to starting ESA; dosage in units/kg; number of units of erythropoietin administered; and patient weight in kg

Required for adjudication of initial ESRD claims; subsequent claims must include hematocrit, diagnosis, and number of units administered

Epoetin alfa and darbepoetin alfa are not covered for treatment of anemias where published evidence does not demonstrate improved health outcomes. Examples include anemia due to hemolysis, nutritional deficiencies, gastrointestinal bleeding or other GI disorders, iron deficiency anemia with transferrin saturation <20%, and anemia related to cancer in patients who are not receiving chemotherapy.

When submitting claims related to hematocrit/hemoglobin thresholds, one of the specified modifier codes (e.g., EE) must accompany the drug HCPCS code on the CMS 1500 to allow adjudication. These modifier reporting rules do not apply to the Federal Employee Program (FEP), the BlueCard Program, or to plans where Medicare is the primary insurer (for example, Medicare Advantage or related products).

Systematic reviews and meta-analyses cited in the policy identify safety signals associated with ESA use in certain populations. Notably, pooled analyses have reported an increased risk of venous thromboembolism with ESAs when used for cancer-associated anemia. These safety findings inform the policy’s restrictions on use outside guideline-recommended indications and reinforce the need to follow labeled indications and guideline criteria when requesting coverage.

Epoetin alfa and darbepoetin alfa are considered not medically necessary for specific anemia types where response is poor or benefit is unproven. This includes iron deficiency anemia with transferrin saturation <20%, hemolytic anemia, GI bleed–related anemia, and anemia in cancer patients who are not receiving chemotherapy.

For modifier-based adjudication, a historical hematocrit/hemoglobin threshold is used: a hematocrit >39% (or hemoglobin >13.0 g/dL) sustained for 3 or more consecutive billing cycles immediately prior to and including the current cycle triggers the related coding pathways and may indicate lack of medical necessity at higher targets.

Meta-analyses and randomized trial reviews cited in the policy raise concerns about thrombotic events and potential mortality differences with ESA use in cancer and other populations. These references provide the safety context for limiting ESA use to indications and hemoglobin targets supported by evidence and professional guidelines.

Codes, Thresholds, and Claim Requirements

HCPCS CodesHCPCS

J0881	Injection,darbepoetin alfa; [Arenesp]
J0882	Injection_darbepoetin alfa, mcg (for ESRD on dialysis) [Arenesp]
J0885	Injection, epoetin alfa, (for non-ESRD use) 1000 units [Epogen, Procrit]
Q4081	[Epogen, Procrit]
Q5105	Injection epoetin alfa, biosimilar (Retacrit) (for ESRD on dialysis) 100 units
Q5106	Injection, epoetin alfa, biosimilar (Retacrit) (for non-ESRD use) 1000 units

HCPCS Codes (informational)HCPCS

J0881	Injection,darbepoetin alfa; [Arenesp]
J0882	Injection_darbepoetin alfa, mcg (for ESRD on dialysis) [Arenesp]
J0885	Injection, epoetin alfa, (for non-ESRD use) 1000 units [Epogen, Procrit]
Q4081	[Epogen, Procrit]
Q5105	Injection epoetin alfa, biosimilar (Retacrit) (for ESRD on dialysis) 100 units
Q5106	Injection, epoetin alfa, biosimilar (Retacrit) (for non-ESRD use) 1000 units

ICD-10 Diagnosis Codes considered medically necessary with the HCPCS codesICD-10Covered

D46.0
D46.1	Refractory anemia with ring sideroblasts
D46.22	Refractory anemia with excess of blasts 2
D46.4	Refractory anemia unspecified
D46.9	Myelodysplastic syndrome unspecified
D46.A	Refractory cytopenia with multilineage dysplasia
D46.B	Refractory cytopenia with multilineage dysplasia and ring sideroblasts
D46.C	Myelodysplastic syndrome with isolated del(5q) chromosomal abnormality
D46.Z	Other myelodysplastic syndromes
D61.1	Drug-induced aplastic anemia

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inv-13: Hemoglobin thresholds

Typical initiation thresholdInitiation: approve x 6 months if hemoglobin (Hb) < 11.0 g/dL (some indications require Hb < 10.0 g/dL)

Typical continuation thresholdContinuation: approve x 6 months if hemoglobin (Hb) < 12.0 g/dL

Indication-specific initiationFor certain indications (e.g., ribavirin-associated anemia, post–allogeneic bone marrow transplant) initiation threshold may be Hb < 10.0 g/dL

inv-14: Hematocrit / Hemoglobin threshold

Hematocrit/hemoglobin upper thresholdHematocrit > 39% or hemoglobin > 13.0 g/dL for 3 or more consecutive billing cycles

Modifier reporting requirement

Prior Authorization, Documentation, and Billing Actions

Prior Authorization

Prior Authorization Required

Prior authorization is required for erythropoiesis-stimulating agents (ESAs). Providers must submit the Massachusetts Standard Form for Medication Prior Authorization Requests (eForm) or print and fax Form #434 to Pharmacy Operations (Blue Cross Blue Shield of Massachusetts Pharmacy Operations, 25 Technology Place, Hingham, MA 02043; Tel: 1-800-366-7778; Fax: 1-800-583-6289). Individual consideration requests for atypical patients may be submitted when clinical criteria are not met.

Use the Massachusetts eForm link or Form #434 to request prior authorization.
Contact Pharmacy Operations by phone or fax for assistance.

Documentation Required

Proof of Prior Trials and Clinical Rationale

Submit documentation showing prior trials and clinical rationale when a formulary alternative was not used. Documentation must include the name and strength of alternatives tried and failed, dates if available, and specific reasons for treatment failure or clinical contraindication preventing a switch to the formulary agent.

Initiation Criteria and ESRD Start Requirements

Initiation criteria

Initiation criteria vary by indication and agent; many starts occur at specified hemoglobin thresholds. Approvals are typically time-limited.

Initiation thresholds (general): Initiation generally: approve x 6 months if Hb < 11.0 g/dL; certain indications (e.g., ribavirin-associated anemia, post-transplant, some chemotherapy contexts) require initiation when Hb < 10.0 g/dLHb < 11.0 g/dL or Hb < 10.0 g/dL depending on indication

Applies to Retacrit; other agents require prior Retacrit failure

Initiation for dialysis-specific HIF agents: For Jesduvroq or Vafseo in dialysis patients, initiation criteria include Hb < 11.0 g/dLHb < 11.0 g/dL

Coverage only after Retacrit failure; approve x 6 months when criteria met

Initial ESRD therapy

Continuation and Ongoing Claims Requirements

Continuation therapy rules

Continuation approvals are time-limited and linked to hemoglobin thresholds.

Continuation for chronic renal failure and other covered indications: Approve x 6 months if Hb < 12.0 g/dLHb < 12.0 g/dL

Applies to Retacrit and, when covered after Retacrit failure, to other agents as specified

Continuation for dialysis-specific HIF agents: For Jesduvroq or Vafseo in dialysis patients, continuation criteria specify Hb thresholds as listed (e.g., continuation approve x 6 months if Hb < 11.0 g/dL for dialysis indications)Hb thresholds per agent and indication as specified in policy

Time-limited approvals (typically 6 months)

ESRD continuation claims

Step Therapy Sequencing and Prior Failure Requirements

Agent	Step therapy requirement	Coverage condition / notes
Retacrit (epoetin alfa-epbx)
Retacrit is the preferred/formulary epoetin alfa product and must be tried first per policy prior to coverage of other ESAs or HIF inhibitors; prior authorization required for Retacrit.
Covered when medical necessity criteria are met (see Retacrit covered indications and hemoglobin thresholds); retail specialty pharmacy dispensing and current hemoglobin values may be required.

Agent	Prior step required	Policy history / formulary notes
Vafseo (vadadustat)
May be covered only after documented treatment failure with Retacrit for specified indications; prior authorization required.
Added to the policy in 11/2024 per policy history; formulary listing indicates NFNC, PA, QCD where applicable.

Quantity Limits and Dosing Reference

inv-41: Retacrit, Aranesp, Epogen/Procrit, Jesduvroq, Vafseo — refer to Quality Care Dosing (policy #621B)

Quantity limits policy referenceSee Quality Care Dosing (policy #621B) for quantity limits for Retacrit, Aranesp, Epogen/Procrit, Jesduvroq, and Vafseo

Formulary / specialty notesRetacrit covered under pharmacy benefit only (specialty pharmacy); other agents are PA, QCD and many are non-formulary/non-covered unless criteria met

Step therapy requirementAranesp, Epogen/Procrit, Jesduvroq, Vafseo require treatment failure with Retacrit per formulary status notes

Site of Care and Specialty Pharmacy Requirements

Billing Rule

Dispense via BCBSMA retail specialty pharmacy for applicable members

Members (except certain Medicare/Medicare‑linked plans) are required to fill prescriptions for covered ESAs at a BCBSMA retail specialty pharmacy in the network; the policy specifies retail specialty pharmacy dispensing for applicable members.

Does not apply to Medicare Advantage/Medex/Blue MedicareRx members as noted

Biosimilar Preference and Authorization Notes

Billing Rule

Retacrit preferred — other epoetin alfa products require PA and Retacrit failure

Retacrit (epoetin alfa‑epbx) is the preferred epoetin alfa biosimilar/formulary product; other epoetin alfa products (Epogen/Procrit) require prior authorization and generally require documented failure of Retacrit before coverage.

Note

Policy history shows Retacrit preference and prior Procrit/Epogen status changes

Policy history documents that Retacrit was designated preferred at times and that Procrit/Epogen status has changed historically (including moves to non‑covered); review the policy history for prior formulary changes when applying preference rationale.

Background and Scope

This policy governs prior authorization, step therapy, quantity limits, and medical necessity criteria for erythropoiesis‑stimulating agents (ESAs) and hypoxia‑inducible factor (HIF) inhibitors for BCBSMA commercial members. It covers indications such as anemia of chronic renal failure (defined in the policy as chronic kidney disease or dialysis-dependent patients), chemotherapy‑associated anemia in nonmyeloid malignancies, AZT‑ or ribavirin‑associated anemia, myelodysplastic syndromes (with confirmation by bone marrow biopsy/aspirate), post‑allogeneic bone marrow transplant anemia, and select perioperative anemia. The policy requires prior authorization for ESAs and HIF inhibitors, generally prefers the biosimilar Retacrit (epoetin alfa‑epbx) first with other agents covered only after documented Retacrit failure, and ties initiation and continuation approvals to specified hemoglobin thresholds and time‑limited authorizations.

Key Definitions and Code Lists

inv-32: Anemia of chronic renal failure definition

Definition (policy) for anemia of chronic renal failureDefined as GFR < 60 mL/min/1.73 m2 for at least 3 months or patients on dialysis

Typical treatment thresholdsInitiation: approve x 6 months if Hb < 11.0 g/dL; Continuation: approve x 6 months if Hb < 12.0 g/dL

Applies toThis definition is the basis for coverage of Retacrit and for determining applicable initiation/continuation thresholds

inv-33: Codes for ESAs and related diagnoses

Key HCPCS codes (ESAs)J0881, J0882, J0885, Q4081, Q5105, Q5106

Related ICD-10 diagnosis groupsD46.* (myelodysplastic syndromes), D61.* (aplastic anemias), D63.* (anemia in chronic disease), D64.* (other anemias), N18.* (CKD/ESRD)

OpenPayer

Erythropoiesis-stimulating agents (ESAs) and HIF inhibitors prior authorization and quantity limits

Coverage and Medical Necessity Criteria

Codes, Thresholds, and Claim Requirements

Prior Authorization, Documentation, and Billing Actions

Initiation Criteria and ESRD Start Requirements

Continuation and Ongoing Claims Requirements

Step Therapy Sequencing and Prior Failure Requirements

Quantity Limits and Dosing Reference

Site of Care and Specialty Pharmacy Requirements

Biosimilar Preference and Authorization Notes

Background and Scope

Key Definitions and Code Lists