CurrentUnitedHealthcarePolicy IEXD0028.09

Erythropoiesis Stimulating Agents Iex

UnitedHealthcare Individual Exchange medical benefit drug policy for erythropoiesis-stimulating agents (Aranesp, Epogen, Mircera, Procrit, Retacrit) governing medical necessity criteria, preferred product requirements, diagnosis-specific coverage (CKD dialysis and non-dialysis, chemotherapy-induced anemia, MDS, myelofibrosis, HIV zidovudine-associated anemia, hepatitis C therapy-associated anemia, perioperative use), claim processing instructions, and applicable HCPCS/J-codes and Q-codes for Individual Exchange plans (excludes Nevada).

Policy Summary

PayerUnitedHealthcare

PolicyErythropoiesis Stimulating Agents Iex

Policy CodePolicy IEXD0028.09

Change TypePreferred product update; state applicability revisions

Effective DateApr 1, 2026

Next Review Date

Key ActionEnsure Retacrit is used as the preferred ESA and require documentation of trial/failure or meeting Preferred Product Criteria to continue Epogen or Procrit; verify state-specific plan mandates (Nevada referral).

SourceLink

POLICY UPDATE CHANGES

Removed language indicating the policy did not apply to Massachusetts and New York and added instruction to refer to UnitedHealthcare Commercial policy for Nevada.

Added language clarifying Retacrit is the preferred ESA product for Medical Necessity Plans and Retacrit, Epogen, or Procrit approval contingent on Diagnosis-Specific Criteria for Non-Medical Necessity Plans.

Added language clarifying patient must meet Preferred Product Criteria for continuation of Epogen or Procrit therapy.

Updated References section to reflect current information and archived previous policy version IEXD0028.08.

Coverage Summary

UnitedHealthcare Individual Exchange medical benefit drug policy IEXD0028.09 addresses erythropoiesis-stimulating agents (ESAs) including Aranesp (darbepoetin alfa), Epogen/Procrit (epoetin alfa), Mircera (MPG-epoetin beta), and the biosimilar Retacrit (epoetin alfa). The policy defines diagnosis-specific medical necessity criteria for multiple indications (CKD — dialysis and non-dialysis, cancer chemotherapy–related anemia, myelodysplastic syndromes, myelofibrosis, zidovudine-associated anemia, hepatitis C–therapy associated anemia, and perioperative use) and lists applicable HCPCS/J- and Q-codes for Individual Exchange plans. Retacrit is designated the preferred ESA for Medical Necessity Plans; continuation of Epogen or Procrit is contingent on meeting the policy's Preferred Product Criteria (trial/ intolerance/physician attestation). The policy applies to Individual Exchange plans in all states except Nevada (refer to UnitedHealthcare Commercial policy for Nevada) and the overall coverage stance is covered_with_criteria.

Key thresholds & quick facts

Policy effective date04/01/2026

Typical initial/reauthorization duration12 months (generally); perioperative up to 3 months

Preferred productRetacrit (preferred ESA for Medical Necessity Plans)

Dialysis — initiation Hct thresholdHct < 30%

Dialysis — continuation Hct thresholdHct < 33%

Non-dialysis — initiation Hct thresholdHct < 30%

Non-dialysis — continuation Hct thresholdHct < 30%

Preferred Product Criteria (Epogen or Procrit)

Treatment with Epogen or Procrit is medically necessary for the indications specified in this policy when ONE of the following nested criteria sets is met. Preserve the nested ANY/ALL logic and operational notes.

ANY of the following

Trial of Retacrit with inadequate response
- History of a trial of adequate dose and duration of Retacrit, resulting in minimal clinical response
  Document dose, duration, and objective measures of response (e.g., hemoglobin/hematocrit levels)
- Physician attests that, in their clinical opinion, the clinical response would be expected to be superior to that experienced with Retacrit
  Attestation must include clinical rationale why Epogen or Procrit is expected to be superior
Retacrit failure/contraindication/intolerance

Chronic Kidney Disease — Dialysis (Initial and Continuation)

Chronic Kidney Disease — Non-Dialysis (Initial and Continuation)

Cancer Chemotherapy–Related Anemia (Initial and Continuation)

Myelodysplastic Syndromes (MDS) and Myeloproliferative Neoplasms

Other Indications (HIV, Hepatitis C, Perioperative)

General Unproven / Not Supported Uses

Provider Actions and Administrative Requirements

Prior Authorization

Authorization duration limits and prior authorization requirement

Initial authorizations are generally limited to 12 months (perioperative up to 3 months). Reauthorizations are limited to no more than 12 months. Continued coverage of Epogen or Procrit requires meeting the Preferred Product Criteria (trial of Retacrit or documented failure/contraindication/intolerance with physician attestation).

Documentation Required

Hematocrit/hemoglobin documentation with claim

ESA claims submitted on a 1500 form and/or 837P electronic claim form must include the hematocrit (Hct) value; the Hct should be obtained within 30 days of the injection.

Applicable Codes

Applicable J-codes and Q-codes (reference list)mixed

J0881	Injection, darbepoetin alfa, 1 mcg (non-ESRD use)
J0882	Injection, darbepoetin alfa, 1 mcg (for ESRD on dialysis)
J0885	Injection, epoetin alfa, (for non-ESRD use), 1000 units
J0887	Injection, epoetin beta, 1 microgram, (for ESRD on dialysis)
J0888	Injection, epoetin beta, 1 microgram, (for non-ESRD use)
Q4081	Injection, epoetin alfa, 100 units (for ESRD on dialysis)
Q5105	Injection, epoetin alfa-epbx, biosimilar, (Retacrit) (for ESRD on dialysis), 100 units
Q5106	Injection, epoetin alfa-epbx, biosimilar, (Retacrit) (for non-ESRD use), 1000 units

Referenced Products (brand/generic examples in text)mixed

Epogen	epoetin alfa (Amgen) - prescribing information referenced
Procrit	epoetin alfa (Janssen) - prescribing information referenced
Retacrit	epoetin alfa biosimilar (Pfizer) - preferred product per policy update
Aranesp	darbepoetin alfa - prescribing information referenced
Mircera	methoxy polyethylene glycol-epoetin beta - prescribing information referenced
Retacrit™	biosimilar epoetin alfa (Pfizer) listed June 2024 PI

Clinical Evidence and Guideline Considerations

0.65Cochrane RR transfusion reduction in cancer patients (ESAs vs control)

1.52Cochrane RR increased thromboembolism in cancer trials (ESAs vs control)

1.17Cochrane HR increased on-study mortality in cancer trials (ESAs)

5.0% vs 2.6%TREAT: stroke rate with darbepoetin alfa vs placebo (CKD, diabetes)

Evidence across systematic reviews, randomized trials, and guideline statements shows that ESAs: (a) reduce the need for red blood cell transfusions (Cochrane and AHRQ findings; examples: RR 0.65 for transfusion reduction in cancer trials and fewer transfusions in TREAT), and (b) are associated with increased thromboembolic events and, in some oncology trials and meta-analyses, an increase in mortality or decreased survival (Cochrane, Cochrane meta-analyses and AHRQ summaries report increased thromboembolism RR ~1.5 and hazard ratios for mortality >1.0 in some analyses).

KDIGO recommendations (graded) emphasize balancing benefits (reduced transfusions, symptom improvement) against harms (stroke, vascular access loss, hypertension, thromboembolism) and provide specific Hb/Hct thresholds and management guidance: do not initiate ESA in adult CKD ND patients with Hb ≥ 10.0 g/dL (2D); individualize initiation for Hb < 10.0 g/dL (2C); for CKD 5D suggest starting when Hb is between 9.0–10.0 g/dL to avoid falling below 9.0 g/dL (2B); generally avoid maintaining Hb > 11.5 g/dL and do not intentionally increase Hb above 13 g/dL (1A). KDIGO also provides guidance on initial dosing, monitoring frequency (monthly during initiation; maintenance: CKD ND at least every 3 months, CKD 5D monthly), hyporesponsiveness definitions and dose-escalation limits, and PRCA evaluation and management (investigate when rapid Hb drop 0.5–1.0 g/dL/week with absolute reticulocyte < 10,000/µl; stop ESA if antibody-mediated PRCA confirmed).

Background and Definitions

Anemia reflects reduced red blood cell mass from blood loss, decreased marrow production, increased destruction, or combinations of these causes. Erythropoietin is an endogenous kidney-derived glycoprotein that stimulates erythroid progenitor differentiation; recombinant epoetin alfa and related erythropoiesis-stimulating proteins (darbepoetin alfa, MPG-epoetin beta) mimic this action. Pharmacologic differences include half-life extensions for darbepoetin alfa (additional carbohydrate chains) and for MPG-epoetin beta (pegylation), producing longer receptor activity and less frequent dosing compared with short-acting epoetin alfa.

The net benefit–harm profile from randomized trials and systematic reviews is consistent: ESAs reduce transfusion requirements and may modestly improve patient-reported fatigue, but they are associated with an increased risk of thromboembolic events and, in some oncology and CKD trials, signals for increased mortality or cardiovascular events (e.g., higher stroke rates in TREAT and mortality differences in trials targeting higher hemoglobin). Evidence quality and effect sizes vary by population and dosing strategy.

Term	Definition
Acquired ESA hyporesponsiveness
Requirement for two increases in ESA dose up to 50% beyond the stable dose to maintain hemoglobin (i.e., needing two dose escalations to sustain Hb)

KDIGO / Guideline-derived Coverage Considerations

Revision History

2026-04-01material_changeLatest

Policy revision effective 04/01/2026: Removed language excluding Massachusetts and New York and added instruction to refer to UnitedHealthcare Commercial policy for Nevada (verify member-specific plan/state mandates).

2026-04-01material_changeLatest

Coverage Rationale updated to designate Retacrit as the preferred ESA product for Medical Necessity Plans; for Non-Medical Necessity Plans Retacrit, Epogen, or Procrit approval contingent on Diagnosis-Specific Criteria.

NCCN applicability and AHRQ findings

Use consistent with the NCCN - Cancer and Chemotherapy-Induced Anemia Guidance when applicable
When treating anemia due to cancer chemotherapy, ensure indication aligns with NCCN recommendations regarding intent of chemotherapy, transfusion alternatives, and hemoglobin/hematocrit thresholds
Consideration of AHRQ findings (2013) regarding comparative effectiveness and safety of ESAs
Provider should document consideration of AHRQ 2013 evidence syntheses on benefits and harms of ESAs; use this in clinical decision-making and attestation

Operational notes for Epogen/Procrit coverage

Prior authorization and documentation requirements must be met per plan rules
Include clinical notes, prior Retacrit trial documentation (if applicable), laboratory values, and physician attestation
Coverage for Epogen or Procrit in members already receiving these products requires switching to Retacrit unless criteria above are met
Document reason for continued Epogen/Procrit rather than step-down to Retacrit

Documentation Required

Clinical response documentation for continuation

For continuation requests, providers must document a positive clinical response to ESA therapy and meet the hematocrit thresholds specified for the indication (e.g., Hct < 33% for dialysis continuation; Hct < 30% for non-dialysis continuation; Hct ≤ 30% for cancer chemotherapy continuation per indication).

Step Therapy

Step requirement to preferred biosimilar (Retacrit)

Retacrit is the preferred ESA. Members already on Epogen or Procrit will be required to change to Retacrit unless they meet the Preferred Product Criteria (history of an adequate trial of Retacrit with minimal response and physician attestation, or documented failure/contraindication/intolerance to Retacrit with physician attestation).

Prior Authorization

Product preference and continuation criteria (policy history 04/01/2026)

Retacrit is designated the preferred ESA for Medical Necessity Plans. For Non-Medical Necessity Plans, Retacrit, Epogen, or Procrit may be approved contingent on meeting the Diagnosis-Specific Criteria; continuation of Epogen or Procrit requires meeting the Preferred Product Criteria.

Documentation Required

Investigate suspected antibody-mediated PRCA

If a patient on ESA therapy for > 8 weeks develops a sudden rapid hemoglobin decline (0.5–1.0 g/dL per week) with normal platelets/WBC and an absolute reticulocyte count < 10,000/µl, with suspected anti-erythropoietin antibodies, withhold ESAs and contact the manufacturer to arrange assays for binding and neutralizing antibodies. Stop ESA therapy if antibody-mediated PRCA is confirmed.

Billing Rule

Follow FDA-approved indications/dosing/REMS in oncology

For chemotherapy-induced anemia in non-curative settings, follow FDA-approved indications, dosing adjustments, and REMS requirements. Document planned additional chemotherapy duration per FDA labeling (e.g., minimum of two additional months of planned chemotherapy upon initiation where specified).

NCCN guidance for oncology limits ESA use to selected indications (myelosuppressive chemotherapy–associated anemia when not given with curative intent, MDS, and myeloproliferative neoplasms), requires patient counseling/informed consent, and notes possible decreased survival in cancer patients receiving ESAs—particularly when targeting Hgb > 12 g/dL—so risks/benefits must be discussed and FDA/REMS dosing and monitoring followed.

AHRQ and Cochrane syntheses: AHRQ (2013) found ESAs reduced transfusions, increased thromboembolism risk, provided small (sub–clinically important) improvements in fatigue scores, and were accompanied by increased mortality in cancer patient studies; Cochrane reviews similarly show transfusion reduction but increased thromboembolic events and signals for worse survival in some cancer trials. These bodies also highlight uncertainty about how dosing practices and overall ESA exposure influence harms.

2026-04-01material_changeLatest

Diagnosis-Specific Criteria updated to require that, for continuation requests involving Epogen or Procrit, the patient meets the Preferred Product Criteria in addition to the indication-specific continuation requirements (e.g., Hct thresholds and documentation of positive clinical response for dialysis, non-dialysis, chemotherapy, MDS, myelofibrosis, HIV zidovudine, hepatitis C, perioperative uses).

2026-04-01operational_updateLatest

Operational/claim instructions reiterated: ESA claims require Hct submitted with claim (within 30 days); initial/reauthorizations generally limited to no more than 12 months (perioperative up to 3 months); Retacrit step requirement for members on Epogen/Procrit unless Preferred Product Criteria met; applicable J-/Q-codes and product list included.