Sierra Health and Life ESAs Coverage Update

Coverage Criteria and Medical Necessity

CKD with dialysis — Initial therapy

Anemia Due to Chronic Kidney Disease — Patients Receiving Dialysis: Covered when ALL of the following are met

Initial therapy (on dialysis): Patient is on dialysis; Hematocrit is less than 30% at initiation of therapy; No evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); Initial authorization will be for no more than 12 monthsHct < 30%

CKD with dialysis — Continuation therapy

Anemia Due to Chronic Kidney Disease — Patients Receiving Dialysis: Continuation criteria — Covered when ALL of the following are met

Continuation therapy (on dialysis): If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Patient is on dialysis; Documentation of positive clinical response to ESA therapy; Hematocrit remains less than 33%; Reauthorization will be for no more than 12 monthsHct < 33%

CKD not on dialysis — Initial therapy

Anemia Due to Chronic Kidney Disease — Patients Not Receiving Dialysis: Initial therapy — Covered when ALL of the following are met

Initial therapy (not on dialysis): Patient is not on dialysis; Hematocrit is less than 30% at initiation of therapy; Rate of hematocrit decline indicates likelihood of requiring an RBC transfusion; Therapeutic goal is reducing risk of alloimmunization and/or other transfusion-related risks; No evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); Initial authorization will be for no more than 12 monthsHct < 30%

CKD not on dialysis — Continuation therapy

Anemia Due to Chronic Kidney Disease — Patients Not Receiving Dialysis: Continuation therapy — Covered when ALL of the following are met

Continuation therapy (not on dialysis): If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Patient is not on dialysis; Documentation of positive clinical response to ESA therapy; Therapeutic goal is reducing the risk of alloimmunization and/or other transfusion-related risks; Hematocrit remains less than 30% for continuation of therapy; Reauthorization will be for no more than 12 monthsHct < 30%

Chemotherapy-induced anemia

Anemia Due to Cancer Chemotherapy — Covered when ALL of the following are met

Initial therapy: Hematocrit less than or equal to 30% at initiation of therapy; No other causes of anemia and documentation of normal iron stores; One of the following: moderate–severe CKD OR undergoing palliative treatment OR receiving myelosuppressive chemotherapy not given with curative intent OR (receiving myelosuppressive chemotherapy with curative intent AND patient refuses transfusion); Initial authorization will be for no more than 12 monthsHct ≤ 30%

Mircera is unproven for chemotherapy-induced anemia

Continuation therapy: If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Documentation of positive clinical response to ESA therapy; Hematocrit remains less than or equal to 30% for continuation of therapy; Reauthorization will be for no more than 12 monthsHct ≤ 30%

MDS — Initial and continuation

Anemia Associated With Myelodysplastic Syndromes (MDS) — Covered when ALL of the following are met

Initial therapy: Serum erythropoietin level less than or equal to 500 mUnits/mL; Hematocrit less than or equal to 30% at initiation of therapy; No evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); Treatment of lower risk IPSS-R (Very Low, Low, Intermediate) disease with symptomatic anemia; And one of: del(5q) chromosomal abnormality OR (no del(5q) AND ring sideroblasts <15% [or <5% with SF3B1 mutation]) OR (no del(5q) AND ring sideroblasts ≥15% [or ≥5% with SF3B1 mutation] AND no response to Reblozyl)EPO ≤ 500 mU/mL; Hct ≤ 30%

Initial authorization will be for no more than 12 months

Continuation therapy: If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Documentation of positive clinical response to ESA therapy; Serum erythropoietin level less than or equal to 500 mUnits/mL; Hematocrit remains less than or equal to 36% for continuation of therapy; Reauthorization will be for no more than 12 monthsEPO ≤ 500 mU/mL; Hct ≤ 36%

Myelofibrosis — Initial and continuation

Anemia Associated With Myeloproliferative Neoplasms - Myelofibrosis — Covered when ALL of the following are met

Initial therapy: Serum erythropoietin level less than or equal to 500 mUnits/mL; Hematocrit less than or equal to 30% at initiation of therapy; No evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); Initial authorization will be for no more than 12 monthsEPO ≤ 500 mU/mL; Hct ≤ 30%

Continuation therapy: If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Documentation of positive clinical response to ESA therapy; Serum erythropoietin level less than or equal to 500 mUnits/mL; Hematocrit remains less than or equal to 36% for continuation of therapy; Reauthorization will be for no more than 12 monthsEPO ≤ 500 mU/mL; Hct ≤ 36%

Zidovudine-associated anemia

Anemia Associated With Zidovudine Treatment in HIV-Infected Patients — Covered when ALL of the following are met

Initial therapy: Patient is receiving zidovudine administered at less than or equal to 4200 mg/week; Endogenous serum erythropoietin level less than or equal to 500 mUnits/mL; Hematocrit is less than 30% at initiation of therapy; No evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); Initial authorization will be for no more than 12 monthsZidovudine ≤ 4200 mg/week; EPO ≤ 500 mU/mL; Hct < 30%

Continuation therapy: If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Documentation of positive clinical response to ESA therapy; Patient is receiving zidovudine administered at less than or equal to 4200 mg/week; Endogenous serum erythropoietin level less than or equal to 500 mUnits/mL; Hematocrit remains less than or equal to 36% for continuation of therapy; Reauthorization will be for no more than 12 monthsEPO ≤ 500 mU/mL; Hct ≤ 36%

Hepatitis C–related anemia

Anemia Associated With Hepatitis C With Ribavirin and Interferon Therapy — Covered when ALL of the following are met

Initial therapy: Patient is receiving ribavirin and interferon therapy; Hematocrit is less than or equal to 30% at initiation of therapy; No evidence of other causes of anemia (e.g., iron deficiency, hemolysis, vitamin B12 deficiency); Initial authorization will be for no more than 12 monthsHct ≤ 30%

Continuation therapy: If the request is for Epogen or Procrit, patient meets the criteria in the Preferred Product Criteria section; Documentation of positive clinical response to ESA therapy; Patient is receiving ribavirin and interferon therapy; Hematocrit remains less than or equal to 36% for continuation of therapy; Reauthorization will be for no more than 12 monthsHct ≤ 36%

Perioperative ESA use

Preoperative Use for Reduction of Allogeneic Blood Transfusions — Covered when ALL of the following are met

Perioperative use: Perioperative hematocrit is greater than 30% and less than or equal to 39%; Patient is expected to require at least 2 units of blood during the surgical procedure; Patient is at high risk for blood loss during surgery; Patient is unable or unwilling to donate autologous blood; Surgery is elective, noncardiac, and nonvascular; Authorization will be for no more than 3 monthsHct > 30% and ≤ 39%

ESAs are unproven for patients willing to donate autologous blood or undergoing cardiac/vascular surgery

Unproven Indications

ESAs are considered unproven (not supported by this policy) for ALL of the following listed patient groups:

Unproven Indications: Patients undergoing curative chemotherapy; Patients receiving hormonal agents, biologic products, or radiotherapy alone (unless also receiving myelosuppressive chemotherapy); Patients who require immediate correction of anemia as a substitute for RBC transfusions; Patients undergoing cardiac or vascular surgery; Patients scheduled for surgery who will donate autologous blood; Patients with cancer receiving myelosuppressive chemotherapy when the anticipated outcome is cure; Patients with cancer receiving myelosuppressive chemotherapy in whom the anemia can be managed by transfusion.

Listed as unproven uses in policy.

ESA use for chemotherapy- or disease-related anemia

Covered when ALL of the following are met (cancer- and chemotherapy-induced anemia):

Cancer-related ESA coverage: 1) Anemia attributable to myelosuppressive chemotherapy, myelodysplastic syndromes, or select myeloproliferative neoplasms; 2) Patient is receiving myelosuppressive chemotherapy (patients not receiving therapy or receiving non-myelosuppressive therapy are not indicated); 3) Risks and benefits discussed and informed consent obtained; 4) ESA use aligns with FDA/REMS guidance and target hemoglobin thresholds per guidelinesee KDIGO/NCCN thresholds

From NCCN guidance

ESA use in chronic kidney disease

Covered when individualized CKD criteria are met:

CKD initiation and maintenance: Individual assessment balancing transfusion avoidance and symptom relief vs risks; For adult CKD non-dialysis patients, generally do not initiate if Hb ≥ 10.0 g/dL; if Hb < 10.0 g/dL, consider individualized decision including rate of decline, iron responsiveness, transfusion risk, and symptoms; For CKD stage 5D consider initiating to avoid Hb < 9.0 g/dL by starting when Hb between 9.0-10.0 g/dL; Do not intentionally raise Hb above 13 g/dL; Generally do not maintain Hb above 11.5 g/dL in adultsHb numeric thresholds per KDIGO

From KDIGO recommendations

ESA use in preterm/low birth weight infants

Neonatal/preterm ESA use — evidence summary and stance:

Neonatal ESA evidence: Randomized trials (34 studies, 3,643 infants) show early ESA reduces RBC transfusion use and may reduce some adverse outcomes, but evidence quality is low-to-moderate and heterogeneous; administration is not currently recommended pending larger trials

Cochrane review conclusions

General ESA coverage and management

Coverage and management principles for ESA use

ESA selection: Choose an ESA based on pharmacodynamics, safety, clinical outcomes, costs, and availability; use regulatory-agency-approved ESAs and true biosimilars for copy versions

KDIGO Work Group recommendations

Adjuvant therapies: Do not use androgens as adjuvants to ESA treatment; suggest not using vitamin C, vitamin D, vitamin E, folic acid, L-carnitine, or pentoxifylline as ESA adjuvants

Recommendations with evidence grades

Manage poor responsiveness: Evaluate and treat specific causes of poor ESA response; individualize therapy if hyporesponsive despite correction of causes, considering continued ESA vs transfusion and the doses required

Management suggestions

Hyporesponsiveness criteria and dosing limits

Definitions and dosing escalation limits for hyporesponsiveness

Initial hyporesponsiveness classification: Classify as initial hyporesponsiveness if no increase in hemoglobin from baseline after the first month of appropriately weight-based ESA dosing1 month

Avoid escalating dose beyond double the initial weight-based dose

Acquired hyporesponsiveness classification: Classify as acquired hyporesponsiveness if two increases up to 50% beyond the previously stable dose are required to maintain hemoglobintwo dose increases

Avoid escalations beyond double the previously stable dose

PRCA evaluation and treatment

PRCA evaluation and actions

When to evaluate for antibody-mediated PRCA: Investigate PRCA when a patient receiving ESA therapy for more than 8 weeks develops a sudden rapid decrease in hemoglobin (0.5–1.0 g/dl per week) or requires approximately 1–2 transfusions per week, with normal platelet and white cell counts and an absolute reticulocyte count less than 10,000/µl; If suspected, stop ESA and evaluate for neutralizing antibodies; peginesatide is recommended to treat antibody-mediated PRCA>8 weeks on ESA

The policy lists several uses of erythropoiesis-stimulating agents (ESAs) as unproven and therefore not supported by this coverage document. These unproven categories include: patients undergoing curative chemotherapy (except when the patient refuses transfusion), patients receiving hormonal agents, biologic products, or radiotherapy unless they are also receiving concomitant myelosuppressive chemotherapy, patients who require immediate correction of anemia as a substitute for red blood cell transfusion, patients undergoing cardiac or vascular surgery, and patients scheduled to donate autologous blood preoperatively. The policy also identifies cancer patients whose anemia can be managed by transfusion as an unproven group.

Use of ESAs for the listed unproven indications is not supported by evidence in this policy and may be considered not medically necessary for those scenarios.

ESAs are not indicated for cancer patients who are not receiving therapy, who are receiving non‑myelosuppressive therapy, or when an identified, treatable cause of anemia exists. The policy further specifies that ESAs are unproven for patients receiving myelosuppressive chemotherapy when the anticipated outcome is cure (with the limited exception of patients who refuse transfusion) and that ESAs should not be used in settings where anemia can be managed with transfusion.

The policy follows guideline recommendations that androgens should not be used as adjuvants to ESA therapy. It also advises against routine use of certain adjunctive agents (see Adjuvant Therapies) as companion treatments to ESAs when trying to improve response.

ESA use for patients receiving myelosuppressive chemotherapy with curative intent is considered unproven and generally not supported. An exception is noted only for patients who explicitly refuse blood transfusion; such cases require documentation and careful consideration of risks and benefits before ESA therapy would be entertained.

Providers should note that the policy’s unproven categories include specific patient groups (for example, those receiving curative chemotherapy, certain surgical populations, and patients whose anemia can be managed by transfusion). Claims or prior‑authorization requests for patients in these groups may be denied unless documentation demonstrates a covered exception.

Consistent with KDIGO guidance cited in this policy, clinicians should avoid intentionally increasing hemoglobin above 13 g/dL in adults. For CKD patients, the policy also advises against maintaining hemoglobin concentrations above recommended CKD targets (generally not above 11.5 g/dL for routine maintenance) and considers targeting higher levels unsupported.

The Work Group recommends not using androgens as an adjunct to ESA treatment (grade 1B) and suggests against using adjuvants such as vitamin C, vitamin D, vitamin E, folic acid, L‑carnitine, and pentoxifylline to augment ESA response.

Provider Requirements, Prior Authorization, and Billing

Prior Authorization

Prior authorization and preferred product

Retacrit is the designated preferred ESA for medical necessity plans and does not require prior authorization; coverage for Epogen or Procrit is conditional on meeting the Preferred Product Criteria (history of an adequate trial with minimal response and physician attestation, or history of failure/contraindication/intolerance to Retacrit with physician attestation). Members already on Epogen or Procrit will be required to change to Retacrit for continuation unless they meet these criteria.

Retacrit: no prior authorization for medical necessity plans.
Epogen/Procrit: require documentation per Preferred Product Criteria (trial of Retacrit with minimal response plus physician attestation OR failure/contraindication/intolerance to Retacrit plus physician attestation).
Existing Epogen/Procrit users must change to Retacrit for continuation unless criteria met.

Billing Codes, Thresholds, and Key Clinical Metrics

Applicable HCPCS/Drug CodesHCPCS

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

inv-27: Hematocrit / Hemoglobin triggers — Hematocrit thresholds and Hct-from-Hgb conversion

Hematocrit thresholds used for initiation and continuationHematocrit < 30% commonly used for initiation (CKD on/off dialysis, MDS, myelofibrosis, zidovudine, hepatitis C, chemotherapy); Hematocrit ≤ 30% used in some indications; Continuation thresholds often allow Hct up to ≤ 33% (CKD on dialysis) or ≤ 36% (MDS/myelofibrosis/zidovudine/hepatitis C); Hct ≤ 30% specifically required for chemotherapy-induced anemia initiation

Hematocrit triggers that may lead to denialRequests for ESA therapy in CKD dialysis patients with Hct ≥ 33% or in CKD non-dialysis patients with Hct ≥ 30% are considered unproven and may be denied

Use of Hgb when Hct not availableIf only hemoglobin is measured, estimate hematocrit using Hct ≈ Hgb × 3 (e.g., Hgb 10 g/dL ≈ Hct 30%)

Initial authorization duration tied to Hct criteriaInitial ESA authorizations tied to these Hct thresholds are generally for no more than 12 months (clinical criteria specify ≤12 months)

Key Definitions and Terms

inv-53: Hematocrit estimation — Conversion factor of 3 to estimate Hct from Hgb

Conversion factor for Hct estimationUse a conversion factor of 3 to estimate hematocrit from hemoglobin (Hct ≈ Hgb × 3) for documentation and claims

Policy examplesExamples provided: Hgb 10 g/dL ≈ Hct 30%; Hgb 11 g/dL ≈ Hct 33%; Hgb 12 g/dL ≈ Hct 36%

When to applyApply when only hemoglobin is measured and hematocrit is required for authorization or claim submission

inv-54: ESA — Definition of erythropoiesis-stimulating agents

Definition of ESAErythropoiesis-stimulating agents (ESAs) are recombinant erythropoietin and erythropoiesis-stimulating proteins (e.g., epoetin alfa, darbepoetin alfa) that stimulate red blood cell production

Clinical use contexts

Regimens and Indications Covered

Regimen	Coverage stance	Key criteria / notes
Aranesp (darbepoetin alfa)
Covered for non-curative or palliative myelosuppressive chemotherapy when hematocrit ≤ 30% at initiation; continuation requires documentation of positive clinical response and meeting Preferred Product Criteria when applicable; initial and reauthorization periods ≤ 12 months.
Epogen/Procrit (epoetin alfa)
Covered for non-curative or palliative myelosuppressive chemotherapy when hematocrit ≤ 30% at initiation; continuation requires documentation of positive clinical response and meeting Preferred Product Criteria when applicable; initial and reauthorization periods ≤ 12 months.
Retacrit (epoetin alfa biosimilar)
Covered for non-curative or palliative myelosuppressive chemotherapy when hematocrit ≤ 30% at initiation; designated preferred product—prior trial/criteria considerations apply for Epogen/Procrit continuation; initial and reauthorization periods ≤ 12 months.
Mircera (methoxy polyethylene glycol-epoetin beta)
Considered unproven for treatment of anemia due to cancer chemotherapy per this policy.

Evidence summary	Findings	Implication
Cochrane systematic review of epoetin and darbepoetin in cancer (up to 91 studies; n up to 20,102)
ESAs reduced RBC transfusion requirements (RR 0.65; 95% CI 0.62–0.68) and decreased mean units transfused (MD −0.98 units).
Benefit: fewer transfusions; weigh against increased risks of harm including increased on-study mortality (HR 1.17; 95% CI 1.06–1.29) and higher thromboembolic risk (RR ~1.52; 95% CI 1.34–1.74).
Additional trials and meta-analyses reported higher rates of hypertension and hemorrhagic events and, in some settings, decreased locoregional control or survival (e.g., breast, head/neck, lung cancer studies).
Overall evidence indicates ESAs reduce transfusion need but are associated with increased mortality and thromboembolic risk; clinicians must balance benefits and harms and follow guideline/FDA guidance when using ESAs in oncology.

Agent(s)	FDA alignment / indication	Initiation requirement
Epoetin alfa (Epogen, Procrit) and biosimilar epoetin alfa (Retacrit)
Indicated for anemia in cancer patients on concomitant myelosuppressive chemotherapy per prescribing information.
Initiation requires that at least two additional months of planned chemotherapy remain at the time of ESA initiation (per FDA labeling).
Darbepoetin alfa (Aranesp)
Indicated for anemia in cancer patients on concomitant myelosuppressive chemotherapy per prescribing information.
Initiation requires that at least two additional months of planned chemotherapy remain at the time of ESA initiation (per FDA labeling).

Therapy Lines and Salvage

salvage

Line of therapy considerations

Salvage: Coverage limited to myelosuppressive chemotherapy not intended to be curative; patients receiving curative-intent chemotherapy are generally excluded except if they refuse transfusion

From oncology guidance

mixed

Oncology evidence and risk considerations

Mixed oncology evidence: ESAs reduce transfusion requirements but have been associated with increased mortality and thromboembolic risk in meta-analyses and some trials; clinicians must balance risks and benefits and follow NCCN guidance

Cochrane and trial data

mixed

Chemotherapy-associated anemia use

Background, Evidence Summaries, and Clinical Context

Erythropoiesis‑stimulating agents are used to treat anemia across multiple disease states including chronic kidney disease (CKD), chemotherapy‑induced anemia, myelodysplastic syndromes, myelofibrosis, HIV‑ and hepatitis C–related anemia, and for perioperative reduction of allogeneic transfusions when specified criteria are met. This policy defines covered indications, hemoglobin/hematocrit thresholds, and management expectations, and designates Retacrit as the preferred ESA product for medical‑necessity plans.

Evidence from randomized trials and meta‑analyses in chemotherapy‑associated anemia shows ESAs reduce the need for red blood cell transfusion (for example, a Cochrane review found reduced transfusion risk: RR 0.65, 95% CI 0.62–0.68) but are associated with increased risks, including higher mortality during the active study period (HR ~1.17) and increased thromboembolic events (RR ~1.5). These harms require clinicians to weigh transfusion‑sparing benefits against potential increases in mortality, thrombotic risk, hypertension, and possible adverse effects on tumor control in certain settings.

Randomized trials in preterm and low birth weight infants (34 studies, 3,643 infants) indicate early ESA use reduces exposure to red blood cell transfusion and may reduce some adverse outcomes (necrotizing enterocolitis and certain neurodevelopmental measures), but the evidence is heterogeneous and of low to moderate quality. Because of inconsistent results across large trials and limited overall benefit, routine administration of ESAs in neonates/preterm infants is not currently recommended pending further high‑quality data.

Policy Updates and Revision History

2026-04-01material_changeLatest

Added language clarifying Retacrit is the preferred ESA product for medical necessity plans.

2026-04-01material_change

Added language that continuation of Epogen or Procrit requires meeting the Preferred Product Criteria in the policy.