HIGHMARK COMMERCIAL MEDICAL POLICY - PENNSYLVANIA

 
 
Medical Policy:
I-7-042
Topic:
Erythropoiesis Stimulating Agents
Section:
Injections
Effective Date:
May 1, 2026
Issued Date:
May 1, 2026
Last Revision Date:
April 2026
Annual Review:
April 2026
 
 

An erythropoiesis-stimulating agent (ESA), is a medicine similar to erythropoietin, which stimulates red blood cell production (erythropoeisis).

Policy Position

Epoetin alfa (Epogen®, Procrit®) and epoetin alfa-epbx (Retacrit™) may be considered medically necessary for the treatment of anemia associated with ANY of the following conditions when reversible causes of anemia are identified and managed: 

  • Chronic kidney disease, whether or not on dialysis, to decrease the need for red blood cell transfusion; or
  • Treatment of individuals eight (8) months of age and older with HIV infection or AIDS - related complex (ARC) and anemia receiving Zidovudine (AZT) therapy when ALL of the following apply:
    • AZT doses of 4200 mg or less/week; and
    • Endogenous levels of erythropoietin of 500 MU/ml or less; and
    • Treatment lasting no longer than three (3) months following the discontinuation of the AZT; or
  • Anemia of prematurity; or
  • Reduction of allogeneic red blood cell transfusions in individuals when ALL of the following apply:
    • Individual is undergoing elective noncardiac/nonvascular surgery; and
    • Individual is not a candidate for autologous blood transfusion preoperatively; and
    • Individual is expected to lose two or more units of blood during surgery; and
    • Individual presents with perioperative hemoglobin levels of greater than 10 g/dL up to 13 g/dL; and
    • Antithrombotic prophylaxis should be strongly considered for concurrent use; or
  • Individuals who will not or cannot receive blood products for treatment of acute hemorrhage or blood loss; or
  • Individuals 18 years and older with anemia secondary to combination of ribavirin and interferon-alfa therapy in patients with hepatitis C; or
  • For the treatment of neonates with hypoxic-ischemic encephalopathy (HIE);

AND

Erythropoiesis stimulating agents (ESAs) may be initiated when ONE of the following criteria is met:

  • The hematocrit (HCT) is less than or equal to 30%; or
  • The hemoglobin (Hgb) is less than or equal to 10g/dL plus adequate iron.

Treatment should be stopped when the hematocrit is greater than or equal to 34% or the hemoglobin is greater than or equal to 11.5g/dL. Erythropoiesis stimulating agents will be considered not medically necessary when the hematocrit or hemoglobin are greater than or equal to these stated levels.

Epoetin alfa (Epogen, Procrit) and epoetin alfa-epbx (Retacrit) not meeting the criteria as indicated in this policy is considered not medically necessary.

J0885

Q4081

Q5105

Q5106

 

 

 


Darbepoetin Alfa (Aranesp®) may be considered medically necessary for the treatment of anemia associated with ANY of the following conditions when reversible causes of anemia are identified and managed:

  • Chronic kidney disease, whether or not on dialysis, to decrease the need for red blood cell transfusion; or
  • Treatment of individuals 18 years of age and older with HIV infection or ARC and anemia receiving Zidovudine (AZT) therapy when ALL of the following apply:
    • AZT doses of 4200 mg or less/week; and
    • Endogenous levels of erythropoietin of 500 MU/ml or less; and
    • Treatment lasting no longer than three months following the discontinuation of the AZT; or
  • Anemia of prematurity; or
  • Reduction of allogeneic red blood cell transfusions in individuals 18 years of age and older when ALL of the following apply:
    • Individual is undergoing elective non-cardiac/nonvascular surgery; and
    • Individual is not a candidate for autologous blood transfusion preoperatively; and
    • Individual is expected to lose two or more units of blood during surgery; and
    • Individual presents with perioperative hemoglobin levels of greater than 10 g/dL up to 13 g/dL; and
    • Antithrombotic prophylaxis should be strongly considered for concurrent use; or
  • Individuals 18 years of age and older who will not or cannot receive blood products for treatment of acute hemorrhage or blood loss; or
  • Individuals 18 years of age and older with anemia secondary to combination of ribavirin and interferon-alfa therapy in patients with hepatitis C; or
  • For the treatment of neonates with hypoxic-ischemic encephalopathy (HIE);

AND

Erythropoiesis stimulating agents (ESAs) may be initiated when ONE of the following criteria is met:

  • The hematocrit (HCT) is less than or equal to 30%; or
  • The hemoglobin (Hgb) is less than or equal to 10g/dL plus adequate iron.

Treatment should be stopped when the hematocrit is greater than or equal to 34% or the hemoglobin is greater than or equal to 11.5g/dL. Erythropoiesis stimulating agents will be considered not medically necessary when the hematocrit or hemoglobin are greater than or equal to these stated levels.

Darbepoetin Alfa (Aranesp)  not meeting the criteria as indicated in this policy is considered not medically necessary.

J0881

 J0882

 

 

 

 

 


Epoetin beta-methoxy polyethylene glycol (Mircera) may be considered medically necessary for ANY the following:

  • For the treatment of anemia associated with chronic kidney disease, whether on dialysis or not; or
  • For pediatric individuals age 5 to 17 years on hemodialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA;

AND when ONE of the following criteria is met:

  • The hematocrit (HCT) is less than or equal to 30%; or
  • The hemoglobin (Hgb) is less than or equal to 10g/dL plus adequate iron.

Treatment should be stopped when the hematocrit is greater than or equal to 34% or the hemoglobin is greater than or equal to 11.5g/dL. ESAs will be considered not medically necessary when the hematocrit or hemoglobin are greater than or equal to these stated levels.

The use of epoetin beta-methoxy polyethylene glycol (Mircera) for any other indication listed above is considered not medically necessary. 

J0887

J0888

 

 

 

 

 


ESAs administered on the same day as dialysis are considered an integral part of the dialysis. It is not eligible as a separate and distinct service. If ESAs are reported on the same day as dialysis, and the charges are itemized, combine the charges and pay only the dialysis. Payment for the dialysis performed on the same date of service includes the allowance for the erythropoiesis stimulating agents.  

If the ESAs are given independently, process it under the appropriate code.
Modifier 59 may be reported with ESAs to identify it as a significant, separately identifiable service from the dialysis. When the 59 modifier is reported, the patient's records must clearly document that erythropoiesis stimulating agents were given independently.

References

1. Elliot S, Tomita D, Endre Z. Erythropoiesis stimulating agents and reno-protection: a metaanalysis. BMC Nephrology. 2017;18:14.

2. Kang J, Park J, Lee JM, Park JJ, Choi D. The effects of erythropoiesis stimulating therapy for anemia in chronic heart failure: A meta-analysis of randomized clinical trials. Int J of Cardiol. 2016;12–22.

3. Wilhelm-Leen ER, Winkelmayer WC. Mortality risk of darbepoetin alfa versus epoetin alfa in patients with chronic kidney Disease: systematic review and meta-analysis. Am J Kidney Dis. 2015;69–74.

4. Castelli R, Sciara S, Deliliers GL, and Pantaleo G. Biosimilar epoetin alfa increases hemoglobin levels and brings cognitive and socio-relational benefits to elderly transfusion-dependent multiple myeloma patients: results from a pilot study. Ann Hematol. 2017;96:779-786.

5. Kalantar-Zadeh K. History of erythropoiesis-stimulating agents, the development of biosimilars, and the future of anemia treatment in nephrology. Am J Nephrol. 2017;45:235-247.

6. National Comprehensive Cancer Network (NCCN). NCCN Drugs and Biologics Compendium®. 2026. Epoetin alfa.

7. National Comprehensive Cancer Network (NCCN). NCCN Drugs and Biologics Compendium®. 2026. Darbepoetin alfa.

8. Micromedex DrugDex Compendium®. 2026. Epoetin-alfa.

9. Micromedex DrugDex Compendium®. 2026. Darbepoetin-alfa.

10. Micromedex DrugDex Compendium®. 2026. Epoetin-alfa-epbx.

11. Micromedex DrugDex Compendium®. 2026. Methoxy polyethylene glycol-epoetin beta.

12. Clinical Pharmacology TM Compendia. 2026.Tampa FL: Gold Standard, Inc. Epoetin-alfa.

13. Clinical Pharmacology TM Compendia. 2026.Tampa FL: Gold Standard, Inc. Darbepoetin-alfa.

14. Clinical Pharmacology TM Compendia. 2026.Tampa FL: Gold Standard, Inc. Methoxy polyethylene glycol-epoetin beta.

15. Procrit® (epoietin alfa) injection, for intravenous or subcutaneous use [package insert]. Amgen Inc. Thousand Oaks, CA. Revised 04/2024.

16. Aranesp® (darbepoietin alfa) injection, for intravenous or subcutaneous use [package insert]. Amgen Inc. Thousand Oaks, CA, Revised 12/2024.

17. Retacrit™ (epoietin alfa-epbx) injection, for intravenous or subcutaneous use [package insert]. Pfizer. New York, NY. Revised 06/2024.

18. Mircera® (methoxy polyethylene glycol-epoetin beta) injection, for intravenous or subcutaneous use [package insert]. Hoffmann-La Roche Inc. San Francisco, CA. Revised 04/2024.

19. Epogen® (epoietin alfa) injection, for intravenous or subcutaneous use [package insert]. Amgen Inc. Thousand Oaks, CA. Revised 12/2024.

20. Migdady Y, Barnard J, Al Ali N, et al. Clinical outcomes with ring sideroblasts and SF3B1 mutations in myelodysplastic syndromes: MDS clinical research consortium analysis. 2018;18(8):528-532.

21. Epogen alfa In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated November 27, 2023.

22. Methoxy polyethylene glycol-epoetin beta In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated September 26, 2023.

23. Darbepoetin alfa In: AHFS Drug Information Online Electronic Medical Library. Bethesda, MD: American Society of Health-System Pharmacists. Updated April 25, 2023.

Related Policies

Refer to Medical Policy G-16 Chemotherapy Services for additional information.

Refer to Evolent Policy ECG 3076 Erythropoiesis Stimulating Agents for additional information.


 

Covered Diagnosis Codes for Procedure Codes J0882, J0887, Q4081, and Q5105

N18.6

 

 

 

 

 

 

 

 

 

The Above Diagnosis Code Should be Reported with the Following Diagnosis Code

D63.1

 

 

 

 

 

 

 

 

The Above Diagnosis Codes Should Also be Reported with One of the Following Diagnosis Code

Z99.2

 

 

 

 

 

 

 

 

Covered Diagnosis Codes for Procedure Codes J0885, and Q5106

P61.2

P91.62

P91.63

Z52.010

Z53.1

 

 

 

 

Covered Diagnosis Codes for Procedure Codes J0881

P61.2

P91.62

P91.63

 

 

 

 

 

 

Covered Diagnosis Codes for Procedure Codes J0881, J0885, and Q5106

B17.10

B17.11

B18.2

B19.20

B19.21

 

 

 

 

One of the Above Diagnosis Codes Must be Reported with One of the Following Diagnosis Codes

D63.8

D64.9

 

 

 

 

 

 

 

The Above Codes Also Should be Reported with One of the Following Diagnosis Codes

T37.5X5A

T37.5X5D

T37.5X5S

 

 

 

 

 

 

Covered Diagnosis Codes for Procedure Codes J0881, J0885, and Q5106

B20

B97.35

 

 

 

 

 

 

 

One of the Above Diagnosis Codes Must be Reported with One of the Following Diagnosis Codes

D61.1

D61.2

D61.3

D61.89

D64.9

 

 

 

 

The Above Codes Also Should be Reported with One of the Following Diagnosis Codes

T37.5X5A

T37.5X5D

T37.5X5S

 

 

 

 

 

 

Covered Diagnosis Codes for Procedure Codes J0881, J0885, J0888 and Q5106

N18.30

N18.31

N18.32

N18.4

N18.5

N18.9

 

 

 

One of the Above Diagnosis Codes Should be Reported with One of the Following Diagnosis Codes

D63.1

 

 

 

 

 

 

 

Covered Diagnosis Codes for Procedure Codes J0885, and Q5106

Z41.8

 

 

 

 

 

 

 

 

One of the Above Diagnosis Codes Should be Reported with One of the Following Diagnosis Codes

D60.0

D60.1

D60.8

D60.9

D61.1

D61.2

D61.3

D61.89

D61.9

D64.89

D64.9

Z52.010

 

 


Place of Service: Inpatient/Outpatient

The administration of ESAs (Darbepoetin alfa [Aranesp], Epoetin alfa [Epogen, Procrit]), Epoetin beta-methoxy polyethylene glycol (Mircera), and Epoetin alfa-epbx (Retacrit) is typically an outpatient procedure which is only eligible for coverage as an inpatient procedure in special circumstances, including, but not limited to, the presence of a co-morbid condition that would require monitoring in a more controlled environment such as the inpatient setting.

The policy position applies to all commercial lines of insured business and, if elected, ASO.



Links





This policy is designed to address medical guidelines that are appropriate for the majority of individuals with a particular disease, illness, or condition. Each person's unique clinical or other circumstances may warrant individual consideration, based on review of applicable medical records, as well as other regulatory, contractual and/or legal requirements.

Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect Highmark's reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Highmark retains the right to review and update its medical policy guidelines at its sole discretion. These guidelines are the proprietary information of Highmark. Any sale, copying or dissemination of the medical policies is prohibited; however, limited copying of medical policies is permitted for individual use.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:

  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
    • Qualified sign language interpreters
    • Written information in other formats (large print, audio, accessible electronic formats, other formats)
  • Provides free language services to people whose primary language is not English, such as:
    • Qualified interpreters
    • Information written in other languages

If you need these services, contact the Civil Rights Coordinator.

If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295, TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

U.S. Department of Health and Human Services
200 Independence Avenue, SW
Room 509F, HHH Building
Washington, D.C. 20201
1-800-368-1019, 800-537-7697 (TDD)

Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.

This information is issued by Highmark Blue Shield on behalf of its affiliated Blue companies, which are independent licensees of the Blue Cross Blue Shield Association.  Highmark Inc. d/b/a Highmark Blue Shield and certain of its affiliated Blue companies serve Blue Shield members in the 21 counties of central Pennsylvania. As a partner in joint operating agreements, Highmark Blue Shield also provides services in conjunction with a separate health plan in southeastern Pennsylvania.  Highmark Inc. or certain of its affiliated Blue companies also serve Blue Cross Blue Shield members in 29 counties in western Pennsylvania, 13 counties in northeastern Pennsylvania, the state of West Virginia plus Washington County, Ohio, the state of Delaware[ and [8] counties in western New York and Blue Shield members in [13] counties in northeastern New York].  All references to Highmark in this document are references to Highmark Inc. d/b/a Highmark Blue Shield and/or to one or more of its affiliated Blue companies.




Medical policies do not constitute medical advice, nor are they intended to govern the practice of medicine. They are intended to reflect reimbursement and coverage guidelines. Coverage for services may vary for individual members, based on the terms of the benefit contract.

Discrimination is Against the Law
The Claims Administrator/Insurer complies with applicable Federal civil rights laws and does not discriminate on the basis of race, color, national origin, age, disability, or sex. The Claims Administrator/Insurer does not exclude people or treat them differently because of race, color, national origin, age, disability, or sex. The Claims Administrator/ Insurer:

  • Provides free aids and services to people with disabilities to communicate effectively with us, such as:
  • Qualified sign language interpreters
  • Written information in other formats (large print, audio, accessible electronic formats, other formats)

  • Provides free language services to people whose primary language is not English, such as:
  • Qualified interpreters
  • Information written in other languages
    • If you need these services, contact the Civil Rights Coordinator.

    If you believe that the Claims Administrator/Insurer has failed to provide these services or discriminated in another way on the basis of race, color, national origin, age, disability, or sex, you can file a grievance with: Civil Rights Coordinator, P.O. Box 22492, Pittsburgh, PA 15222, Phone: 1-866-286-8295 , TTY: 711, Fax: 412-544-2475, email: CivilRightsCoordinator@highmarkhealth.org. You can file a grievance in person or by mail, fax, or email. If you need help filing a grievance, the Civil Rights Coordinator is available to help you.

    You can also file a civil rights complaint with the U.S. Department of Health and Human Services, Office for Civil Rights electronically through the Office for Civil Rights Complaint Portal, available at https://ocrportal.hhs.gov/ocr/portal/lobby.jsf, or by mail or phone at:

    U.S. Department of Health and Human Services
    200 Independence Avenue, SW
    Room 509F, HHH Building
    Washington, D.C. 20201
    1-800-368-1019, 800-537-7697 (TDD)

    Complaint forms are available at http://www.hhs.gov/ocr/office/file/index.html.