Erythropoiesis-Stimulating Agents

POLICY NUMBER

L.5.01.423

Aranesp (darbepoetin alfa)

Epogen (epoetin alfa)

Procrit (epoetin alfa)

Retacrit (epoetin alfa-epbx)

Please perform a formulary drug search on your patient’s member ID to ensure the prescription drug is covered under their benefit plan. The medication(s) in this medical policy may not be covered under a specific member’s benefit plan.

DESCRIPTION

Erythropoietin is an endogenous glycoprotein hormone that stimulates red blood cell production. It is produced in the kidney and stimulates the division and differentiation of erythroid progenitors in bone marrow. Epoetin alfa and darbepoetin alfa are both manufactured by recombinant DNA technology and are immunologically and biologically indistinguishable from the renal hormone erythropoietin. Darbepoetin alfa, a second-generation stimulating protein, is a hyperglycosylated analog with a half-life two to three times longer than epoetin alfa.

Epogen (epoetin alfa), Procrit (epoetin alfa), and Retacrit (epoetin alfa-epbx) are indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and not on dialysis to decrease the need for red blood cell transfusions, the treatment of anemia due to zidovudine administered at ≤4200 mg/week in patients with HIV infection with endogenous serum erythropoietin levels of ≤500 mUnits/mL, the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy when there is a minimum of two additional months of planned chemotherapy, and to reduce the need for allogeneic RBC transfusions among patients with perioperative hemoglobin >10 to ≤13 g/dL who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.

Aranesp (darbepoetin alfa) is indicated for the treatment of anemia due to CKD, including patients on dialysis and patients not on dialysis and for the treatment of anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant myelosuppressive chemotherapy when there is a minimum of two additional months of planned chemotherapy.

POLICY

Epogen (epoetin alfa), Procrit (epoetin alfa), and Retacrit (epoetin alfa-epbx) are considered medically necessary for the following:

• Treatment of anemia related to therapy with zidovudine in HIV-infected individuals;

• The treatment of anemia in individuals with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy;

• Treatment of anemic individuals scheduled to undergo elective, noncardiac, nonvascular surgery to reduce the need for allogeneic blood transfusions; AND

• Treatment of anemia associated with chronic kidney disease, including individuals on dialysis and individuals not on dialysis.

Aranesp (darbepoetin alfa) is considered medically necessary for the following:

• Treatment of anemia associated with chronic kidney disease, including individuals on dialysis and individuals not on dialysis; AND

• Treatment of anemia in individuals with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy.

Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary.

POLICY EXCEPTIONS

State Health Plan (State and School Employees) Participants

POLICY GUIDELINES

The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.

Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Mental Health Disorders, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:

A.  consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and

B.  appropriate with regard to standards of good medical practice; and

C.  not solely for the convenience of the Member, his or her Provider; and

D.  the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.

For the definition of medical necessity, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.

POLICY HISTORY

7/1997: Date originally issued

4/1999: Approved by Pharmacy & Therapeutics (P & T) Oncology Committee

1/17/2001: HCPCS code range Q9920-Q9940 added covered codes 

2/2/2001: ICD-9 diagnosis code 285.21 added covered codes

1/30/2002: Prior authorization deleted

2/15/2002: Investigational definition added

4/26/2002: Type of Service and Place of Service deleted. Code Reference section updated. CPT codes 85007, 85027 and 99204 deleted covered codes. ICD-9 diagnosis code 238.7, 272.7, 280.0, 282.60-282.69, 283.2, 285.29, 285.8, 285.8, 773.0, 776.6, 785.6 added non-covered codes, ICD-9 diagnosis codes 285.9, V78.1 and V72.6 deleted covered codes,  ICD-9 procedure code 99.28 deleted covered codes

3/25/2003: Policy section revised, Code Reference section updated, ICD-9 diagnosis code 238.7 moved to covered codes, ICD-9 diagnosis code 203.00, 203.01, 285.22, V58.1 added covered codes, HCPCS range Q9920-Q9940 listed separately covered codes.

12/19/2003: Code Reference section reviewed, CPT code 90782, 90784 deleted covered codes, ICD-9 diagnosis code 99.29 deleted covered codes, ICD-9 diagnosis code range 282.60-282.69 listed separately non-covered codes, ICD-9 diagnosis code 282.60, 282.61, 282.62, 282.63, 282.69 description revised non-covered codes, ICD-9 diagnosis code 282.64, 282.68 added non-covered codes.

7/9/2004: Code Reference section updated, ICD-9 diagnosis code 585, 586 added covered codes, ICD-9 diagnosis code 593.9 description revised, HCPCS Q9920-9940 deletion date of 12/31/2003 added, HCPCS Q4055 added covered codes.

8/11/2005: Code Reference section updated, ICD-9 diagnosis code 283.0 description revised, ICD-9 diagnosis code 285.29 added covered codes, HCPCS Q4054 with effective date of 1/1/2004 added covered codes, HCPCS Q4055 effective date of 1/1/2004 added, HCPCS Q9920, Q9921, Q9922, Q9923, Q9924, Q9925, Q9926, Q9927, Q9928, Q9929, Q9930, Q9931, Q9932, Q9933, Q9934, Q9935, Q9936, Q9937, Q9938, Q9939, Q9940 deleted covered codes, Non-covered codes table and ICD-9 diagnosis code 272.7, 280.0, 282.60, 282.61, 282.62, 282.63, 282.64, 282.68, 282.69, 283.2, 285.29, 285.8, 285.8, 773.0, 776.6, 785.6 deleted.

11/8/2005: Code Reference section updated, 4th digit added to ICD9 diagnosis codes 585.1-585.9, description revised; 5th digit added to code V58.11, description revised.

3/6/2006: Aranesp information added to policy. Rewording of policy section to align with indications.

03/23/2006: Coding updated. 2006 revisions added to policy.

4/2006: Approved by Pharmacy & Therapeutics (P&T) Committee.

9/13/2006: Coding updated. CPT4/HCPCS and ICD9 2006 revisions added to policy.  

9/22/2008: Annual ICD-9 updates effective 10-1-2008 applied.

4/1/2014: Policy description updated regarding FDA Approved Indications for the treatment of anemia due to Chronic Kidney Disease. Removed deleted HCPCS codes Q0136, Q4054, and Q4055 from the Code Reference section.

09/01/2015: Code Reference section updated for ICD-10. Added ICD-9 diagnosis codes 403.00 - 403.91 and 404.00 – 404.93. Deleted ICD-9 diagnosis code 593.9.

12/31/2015: Policy guidelines updated to add medically necessary and investigative definitions.

05/26/2016: Policy number L.5.01.423 added.

11/01/2016: Approved by Pharmacy & Therapeutics (P&T) Committee.

08/15/2017: Policy reviewed and approved by Pharmacy & Therapeutics (P&T) Committee. Code Reference section updated to remove deleted HCPCS code J0886.

11/01/2018: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Medically necessary policy statements updated to change "renal failure" to "kidney disease."

07/30/2020: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy title changed from "Epoetin Alfa (Procrit®, Epogen®) Darbepoetin Alfa (Aranesp®), Epoetin alfa-epbx (Retacrit®)" to "Erythropoiesis-Stimulating Agents." Added drug names to the top of the policy. Policy description and policy statement updated to include Retacrit. Policy statements revised to list criteria. Sources updated. Code Reference section updated to add HCPCS codes Q5105 and Q5106.

09/30/2020: Code Reference section updated to add new ICD-10 diagnosis codes N18.30, N18.31, and N18.32, effective 10/01/2020.

12/31/2020: Code Reference section updated to add ICD-10 diagnosis code D64.81.

02/01/2023: Policy Exceptions updated to add the following: State Health Plan (State and School Employees): The prescription drug(s) in this medical policy may be covered under a prescription drug benefit plan administered by the State Health Plan’s Pharmacy Benefit Manager. Please perform a formulary drug search at https://www.dfa.ms.gov/cvs-caremark and submit any required Prior Authorization Requests for coverage determination to the Plan’s Pharmacy Benefit Manager. Services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Services related to delivery and/or administration of a self-administered drug are not covered.

07/01/2023: Policy Exceptions updated regarding State Health Plan (State and School Employees) Participants. Policy Guidelines updated to change "Nervous/Mental Conditions" to "Mental Health Disorders" and "Medically Necessary" to "medical necessity."

10/01/2024: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy updated to change "patients" to "individuals." Policy Guidelines updated to remove investigative definition. Sources updated.

10/02/2024: Code Reference section updated to add new ICD-10 diagnosis codes C81.0A, C81.1A, C81.2A, C81.3A, C81.4A, C81.7A, C81.9A, C82.0A, C82.1A, C82.2A, C82.3A, C82.4A, C82.5A, C82.6A, C82.8A, C82.9A, C83.0A, C83.1A, C83.390, C83.398, C83.3A, C83.5A, C83.7A, C83.8A, C83.9A, C84.0A, C84.1A, C84.4A, C84.6A, C84.7B, C84.AA, C84.ZA, C84.9A, C85.1A, C85.2A, C85.8A, C85.9A, C86.11, C86.61, C88.01, C88.21, C88.31, C88.41, C88.80, C88.81, and C88.91. Effective 10/01/2024.

09/09/2025: Policy reviewed and approved by the Pharmacy & Therapeutics (P&T) Committee. Policy description updated regarding indications for Epogen (epoetin alfa), Procrit (epoetin alfa), Retacrit (epoetin alfa-epbx), and Aranesp (darbepoetin alfa). Minor revisions made to medically necessary statements. Added statement that services related to delivery and/or administration of a medication determined to be not medically necessary will also be considered not medically necessary. Sources updated.

SOURCE(S)

1. Aranesp prescribing information. Amgen Inc. May 2024. Last accessed June 2025.

2. Epogen prescribing information. Amgen Inc. April 2025. Last accessed June 2025.

3. Procrit prescribing information. Janssen Products, LP. April 2025. Last accessed June 2025.

4. Retacrit prescribing information. Pfizer Laboratories Div Pfizer Inc. June 2024. Last accessed June 2025.

5. Schoener B, Borger J. Erythropoietin Stimulating Agents. [Updated 2024 Jul 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishin; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK536997/ Accessed June 2025.

CODE REFERENCE

This may not be a comprehensive list of procedure codes applicable to this policy.

The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.

Medically Necessary Codes

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