Epogen®, Procrit®, Retacrit® (Non-ESRD) — Coverage Criteria
Defines prior authorization, coverage criteria, dosing, and renewal rules for Epogen®, Procrit®, and Retacrit® when used for non-end-stage renal disease indications for Viva Health members.
No material clinical or coverage changes in this revision.
Coverage Criteria
Initial Therapy
Covered when ALL of the following universal criteria are met AND indication-specific criteria are met
From Universal Criteria
From Initial Approval Criteria
From Initial Approval Criteria
Anemia Due to Myelodysplastic Syndromes (MDS)
MDS coverage requires all of the following
From MDS section
Document del(5q) status
No response defined as lack of ≥1.5 g/dL Hb rise or lack of decreased RBC transfusion within 6–8 weeks (ESA) or 3–6 months (luspatercept).
Anemia Due to Myeloproliferative Neoplasms (Myelofibrosis)
MPN/myelofibrosis coverage requires all of the following
From MPN section
From MPN section
Anemia Due to Chemotherapy Treatment
Chemotherapy-induced anemia covered when ALL of the following are met
From Chemotherapy section
From Chemotherapy section
Patients not undergoing palliative treatment who refuse transfusion may be reviewed case‑by‑case.
Anemia Due to Chronic Kidney Disease (Non-ESRD)
Chronic kidney disease (non-dialysis) coverage criteria
From CKD section
Anemia Due to Zidovudine in Patients with HIV-Infection
Zidovudine-associated anemia coverage requires ALL of the following
From Zidovudine section
From Zidovudine section
From Zidovudine section
Reduction of Allogeneic Blood Transfusions in Elective, Non-Cardiac, Non-Vascular Surgery
Covered when ALL of the following are met
From Preoperative/Surgery section
From Preoperative/Surgery section
From Preoperative/Surgery section
Indication-specific dosing and response criteria
Covered when dosing and response-evaluation follow indication-specific regimens and response thresholds
Dosing details in Dosage/Administration
From CKD dosing guidance
From MDS response guidance
From MPN response guidance
From Cancer Chemotherapy guidance
From Zidovudine guidance
Prior authorization is required for all indications listed in this policy. Initial authorizations are valid for 45 days and may be renewed in successive 45-day intervals unless the policy states otherwise. Note: prior authorization validity may NOT be renewed for the indication "Reduction of Allogeneic Blood Transfusions in Elective, Non-Cardiac, Non-Vascular Surgery."
Continuation of therapy is contingent on meeting the indication-specific response thresholds and evaluation timelines specified in the policy. If the documented hemoglobin response or reduction in RBC transfusion requirements does not meet the stated criteria within the defined timeframes (for example, CKD escalation failure after a 12-week dose-escalation, MDS no ≥1.5 g/dL Hb rise by 8 weeks, MPN no ≥2 g/dL Hb rise by 3 months, or chemotherapy-related anemia with no response by 8 weeks), clinicians should consider changing the regimen or discontinuing therapy.
Medicare-specific coverage determinations can affect coverage for Medicare members. Where applicable, compliance with CMS guidance — including the Medicare Benefit Policy Manual and any relevant National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), or Local Coverage Articles (LCAs) — is required and may alter coverage or claims processing for outpatient (Part B) drugs.
Therapy continuation is not supported when patients fail to meet response criteria after the defined dose-escalation or evaluation periods. Examples include lack of a ≥1 g/dL Hb increase after 4 weeks in CKD prompting dose escalation and, if no response after a 12-week escalation, considering discontinuation; MDS with no ≥1.5 g/dL Hb increase by 8 weeks; MPN with no ≥2 g/dL Hb increase by 3 months; and chemotherapy-associated anemia with no response by 8 weeks or at completion of chemotherapy.
Covered Regimens and Dosing
| Indication / Age Group | Typical Starting Regimen (examples) | Titration / Maximum |
|---|---|---|
| Adults (>18 years) — chemotherapy-related or most commonly initiated dosing | 150 units/kg subcutaneously three times weekly OR 40,000 units subcutaneously once weekly | May titrate up to 300 units/kg SC three times weekly OR 60,000 units SC once weekly |
| Pediatric (8 months–17 years) — chemotherapy, MDS, MPN, or other pediatric indications | Administer 50–400 units/kg IV or SC two to three times weekly (or 600 units/kg IV once weekly for some pediatric regimens) | May titrate up to 900 units/kg IV once weekly (pediatric IV maximum 60,000 units) or up to 300 units/kg per dose for SC regimens |
| Pediatric (5–18 years) — alternate weekly pediatric regimen | 600 units/kg IV once weekly | May titrate up to 900 units/kg (maximum 60,000 units) IV once weekly |
| Reduction of allogeneic transfusions — adult and pediatric perioperative regimens | Administer 300 units/kg/day SC for 10 days before surgery, on day of surgery, and for 4 days after surgery (15 days total) OR 600 units/kg SC on days 21, 14, 7 before surgery and on day of surgery (4 total doses) | May titrate up to 300 units/kg per dose as indicated |
| Anemia due to MDS — adult and pediatric regimens | Administer 40,000–60,000 units SC once to twice weekly (pediatric: 50–400 units/kg IV or SC two to three times weekly) | May titrate up to 300 units/kg per dose |
| Anemia due to MPN (myelofibrosis) — adult dosing examples | 10,000 units SC three times weekly (most commonly initiated dose) | May increase to 20,000 units SC three times weekly; may titrate up to 300 units/kg per dose |
Coding and Units
| HCPCS units | Max units specified per indication (see thresholds) |
| 55513-0126-xx | Epogen NDC (2,000 U/mL) example NDC listed |
| 55513-0267-xx | Epogen NDC (3,000 U/mL) |
| 55513-0148-xx | Epogen NDC (4,000 U/mL) |
| 55513-0144-xx | Epogen NDC (10,000 U/mL) |
| 55513-0283-xx | Epogen NDC (10,000 U/mL, 2 mL MDV) |
| 55513-0478-xx | Epogen NDC (20,000 U/mL, 1 mL MDV) |
| 59676-0302-xx | Procrit NDC (2,000 U/mL) |
| 59676-0303-xx | Procrit NDC (3,000 U/mL) |
| 59676-0304-xx | Procrit NDC (4,000 U/mL) |
| 59676-0310-xx | Procrit NDC (10,000 U/mL) |
| C93.10 | Chronic myelomonocytic leukemia, not having achieved remission |
| C94.40 | Acute panmyelosis with myelofibrosis not having achieved remission |
| C94.41 | Acute panmyelosis with myelofibrosis in remission |
| C94.42 | Acute panmyelosis with myelofibrosis in relapse |
| C94.6 | Myelodysplastic disease, not classified |
| D46.0 | Refractory anemia without ring sideroblasts |
| D46.1 | Refractory anemia with ring sideroblasts |
| D46.20 | Refractory anemia with excess of blasts, unspecified |
| D46.21 | Refractory anemia with excess of blasts 1 |
| D46.4 | Refractory anemia, unspecified |
| C93.10 | Chronic myelomonocytic leukemia, not having achieved remission |
| C94.40 | Acute panmyelosis with myelofibrosis not having achieved remission |
| C94.41 | Acute panmyelosis with myelofibrosis in remission |
| C94.42 | Acute panmyelosis with myelofibrosis in relapse |
| C94.6 | Myelodysplastic disease, not classified |
| D46.0 | Refractory anemia without ring sideroblasts, so stated |
| D46.1 | Refractory anemia with ring sideroblasts |
| D46.20 | Refractory anemia with excess of blasts, unspecified |
| D46.21 | Refractory anemia with excess of blasts 1 |
| D46.4 | Refractory anemia, unspecified |
Provider Actions and Documentation Requirements
CMS references may affect prior authorization
Prior authorization may be affected by Medicare Part B rules and CMS coverage determinations. Where applicable, providers must comply with Medicare Benefit Policy Manual (Pub. 100-02) Chapter 15 §50 and any relevant National Coverage Determinations (NCDs), Local Coverage Determinations (LCDs), or Local Coverage Articles (LCAs). Searchable CMS resources (https://www.cms.gov/medicare-coverage-database/search.aspx) and contractor-specific LCD/LCA documents listed in Appendix 2 may change outpatient drug coverage determinations and prior authorization requirements.
- Where Medicare Part B applies, CMS NCDs/LCDs/LCAs override non‑Medicare prior authorization rules when applicable.
- Contractor-specific LCD/LCA documents referenced in Appendix 2 (e.g., A58982, A56462, A56795) may apply to claims processing and PA requirements.
Indication-specific non-response
If a patient fails to demonstrate the indication‑specific response within the timeframes below, discontinuation of therapy should be considered and prior authorization renewal may be denied.
- MDS: No ≥1.5 g/dL hemoglobin increase or reduced RBC transfusions after 8 weeks → consider discontinuation.
- MPN: No ≥2.0 g/dL hemoglobin increase or reduced RBC transfusions after 3 months → consider discontinuation.
- Cancer chemotherapy: No hemoglobin response or continued need for RBC transfusions after 8 weeks or upon completion of the chemotherapy course → discontinue.
- Zidovudine-treated HIV: If no response after 8 weeks, follow dose-escalation guidance (increase by ~50–100 U/kg at 4–8 week intervals up to 300 U/kg) before declaring non-response.
Required diagnosis coding and dual coding
Claims must include supported diagnosis coding. When dual coding is required, submit both codes on the claim to avoid processing errors or denials.
- Include one of the Appendix 1 ICD‑10 diagnosis codes on the claim to support medical necessity.
- Dual coding rules: Preoperative use — bill D63.8 or D64.9 AND Z41.8; Anemia due to CKD (not on dialysis) — bill D63.1 AND one of I12.9, I13.0, I13.10, N18.30, N18.31, N18.32, N18.4 or N18.5.
- Failure to include required dual diagnosis codes may lead to claim denials or processing delays.
Dose escalation before discontinuation
Follow the stepwise dose adjustment and evaluation schedule before determining non-response or discontinuation. Avoid increasing dose more frequently than specified and consider discontinuation if there is no response after the indicated escalation period.
- CKD: If after 4 weeks the hemoglobin has increased <1.0 g/dL and current Hb remains below the indication‑specific target, a 25% dose increase may be considered.
- Do not increase dose more frequently than once every 4 weeks; dose decreases of ≥25% are acceptable if Hb rises >1 g/dL in any 2-week period.
- If there is no response after a 12‑week dose escalation period for CKD patients, further dose increases are unlikely to help and discontinuation should be considered.
- Dose and frequency requested on the PA must be the minimum necessary to avoid RBC transfusions; avoid frequent dose adjustments.
Definitions and Biomarker Requirements
Line of Therapy
palliative
Line of therapy: palliative
salvage
Line of therapy: salvage
Background
Erythropoiesis-stimulating agents (ESAs) are indicated in this policy for treatment of anemia across multiple clinical contexts including myelodysplastic syndromes (MDS), myeloproliferative neoplasms/myelofibrosis (MPN), chemotherapy-induced anemia, chronic kidney disease (non-dialysis), zidovudine-associated anemia in HIV, and to reduce allogeneic transfusions for selected elective, non-cardiac, non-vascular surgeries. Dosing and monitoring requirements, baseline laboratory documentation (including adequate iron stores), and indication-specific response thresholds and timelines are required to establish and continue medical necessity per the policy.
Appendices and External References
Appendix 2 cites Centers for Medicare & Medicaid Services (CMS) resources that may modify coverage for Medicare beneficiaries. The policy notes that Medicare Part B rules, the Medicare Benefit Policy Manual, and any applicable NCD, LCD, or LCA documents should be consulted because they may supersede non‑Medicare determinations and affect claims payment or benefit eligibility.
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