Effective Date:

a)    This policy will apply to all services performed on or after the above Revision date which will become the new effective date.

b)    For all services referred to in this policy that were performed before the revision date, contact customer service for the rules that would apply.

Erythropoietin therapy (e.g., EPO, Epogen [epoetin alfa], epoetin beta, Procrit, Retacrit, r-HuEPO) and darbepoetin (Aranesp) are used to stimulate red blood cell production in the bone marrow. This is intended to correct anemia, minimizing the need for transfusions, and improving the quality of life for patients.

1. Erythropoiesis Stimulating Agent (ESA) therapy (e.g., EPO, Epogen [epoetin alfa], Epoetin Beta, Procrit, Retacrit, r-HuEPO and Darbepoetin (Aranesp)) is considered medically necessary when any of the following are met:

                            1.  Treatment of symptomatic anemia associated with chronic renal failure whether or not on dialysis. First line therapy should be with Ferrlecit, since iron deficiency is common and causes resistance to erythropoietin. If iron deficiency has been corrected (transferrin saturation > 20% and serum ferritin >100 ng/ml), ESA therapy can be initiated with a hemoglobin (Hgb) < 10 g/dl.  A reasonable target is a Hgb of 10 – 11.5 g/dl and (per the FDA boxed warning) the ESA dose should be reduced or discontinued if Hgb >11 g/dl; or

                            2.  Treatment of symptomatic anemia related to zidovudine in HIV-infected members, when Hgb < 10 g/dl and the dose of zidovudine has been reduced to less than 4,200 mg/week; or

                            3.  Treatment of symptomatic anemia in members with non-myeloid malignancies and anemia is caused by the effect of administered chemotherapy, when  Hgb < 10 g/dl; or

                            4.    Treatment of symptomatic anemia in members who have a severe comorbidity such as (severe) angina, pulmonary disease, hypotension, congestive heart failure, or cerebrovascular disease causing transient ischemic attacks, where

• The Hgb < 10 g/dl; and

• The member is significantly symptomatic from the anemia (as opposed to symptoms from the comorbidity), documented by such impairments as moderate to severe exercise intolerance, inability to perform activities of daily living, or tachycardia or shortness of breath with minimal activity; or

                            5.  Treatment of anemic members scheduled to undergo elective, non-cardiac, nonvascular surgery or members at high risk for perioperative transfusions with significant, anticipated blood loss and Hgb < 10 g/dl; or

                            6.  Symptomatic anemia  (Hgb < 10 g/dl, serum erythropoietin level < 500mU/ml and transfusion requirements < 2 units/month) from myelodysplastic syndrome; or

                            7.  Special circumstance members, such as a Jehovah’s Witness, who will not/cannot receive whole blood or components as replacement for traumatic or surgical loss.

1. Sodium Ferric Gluconate complex in Sucrose injection (Ferrlecit) is considered medically necessary when used as a first line treatment of iron deficiency anemia in members with chronic kidney disease who are receiving supplemental erythropoietin therapy.

Codes Used In This BI:

 Q4081           Erythropoietin

 J0881            Darbepoetin non-ESRD

 J0882            Darbepoetin (Aranesp on ESRD)

 J0885            Erythropoietin non-ESRD

 J0886            Epoetin (Epogen on ESRD) (deleted eff 1/1/16)

 J2916            Ferric Gluconate in Sucrose

Q5105            Injection, epoetin alfa-epbx, biosimilar (retacrit) for ESRD

Q5106            Injection, epoetin alfa-epbx, biosimilar, (retacrit) for non-ESRD

Erythropoietin or Darbepoetin therapy is considered experimental and investigational for the following conditions because its use in these situations is not supported by the peer reviewed medical literature (not an all-inclusive list):

1. Treatment of members who require immediate correction of severe anemia;
2. Treatment of anemia in cancer or HIV-infected members caused by other factors such as iron or folate deficiencies, hemolysis or GI bleeding. In these cases the underlying cause of the anemia should be managed appropriately;
3. Treatment of anemia in rheumatoid arthritis;
4. Treatment of pruritis associated with renal failure;
5. Treatment of anemia in Gaucher`s disease;
6. Treatment of anemia in Castleman`s disease;
7. Treatment of anemia in paroxysmal nocturnal hemoglobinuria (PNH);
8. Treatment of sickle cell anemia;
9. Treatment of sepsis-associated anemia;
10. Treatment of cerebral hypoxia/ischemia;
11. Treatment of cognitive decline in persons with schizophrenia;
12. Treatment of anemia of prematurity.

1.    Stem Cell Growth Factors; Arkansas Blue Cross Blue Shield Coverage Policy at: http://www.arkbluecross.com/members/ex_report.asp?ID=1997190

2.    Use of Epoetin in Patients With Cancer: Evidence-Based Clinical Practice Guidelines; American Society of Clinical Oncology at: http://www.asco.org/ac/1,1003,_12-002032-00_18-0024623-00_19-0024624-00_20-001,00.asp

3.    Agency for Healthcare Research, Quality (AHRQ). Use of epoetin for anemia in chronic renal failure. Rockville, MD: AHRQ; 2001.

4.    Blumenauer B, Cranney A, Clinch J, Tugwell P. Quality of life in patients with rheumatoid arthritis: Which drugs might make a difference? Pharmacoeconomics. 2003;21(13):927-940.

5.    Cvetkovic RS, Goa KL. Darbepoetin alfa: In patients with chemotherapy-related anemia. Drugs. 2003;63(11):1067-1074; discussion 1075-1077.

6.    Pajoumand M, Erstad BL, Camamo JM. Use of epoetin alfa in critically ill patients. Ann Pharmacother. 2004;38(4):641-648.

7.    Henry DH, Bowers P, Romano MT, Provenzano R. Epoetin alfa. Clinical evolution of a pleiotropic cytokine. Arch Intern Med. 2004;164(3):262-276.

8.    Carson JL. Should patients in intensive care units receive erythropoietin? JAMA. 2002; 11;288(22):2884-2886.

9.    Corwin HL, Gettinger A, Pearl RG, et al. and the EPO Critical Care Trials Group. Efficacy of recombinant human erythropoietin in critically ill patients: A randomized controlled trial. JAMA. 2002;288(22):2827-2835.

10. Eckardt KU. Anemia of critical illness-- implications for understanding and treating rHuEPO resistance. Nephrol Dial Transplant. 2002;17 Suppl 5:48-55.

11. Darveau M, Notebaert E, Denault AY, Belisle S. Recombinant human erythropoietin use in intensive care. Ann Pharmacother. 2002;36(6):1068-1074.

12. Corwin HL. Anemia in the critically ill: the role of erythropoietin. Semin Hematol. 2001;38(3 Suppl 7):24-32.

13. van Iperen CE, Gaillard CA, Kraaijenhagen RJ, et al. Response of erythropoiesis and iron metabolism to recombinant human erythropoietin in intensive care unit patients. Crit Care Med. 2000;28(8):2773-2778.

14. Zimmerman JL. Use of blood products in sepsis: An evidence-based review. Crit Care Med. 2004;32(11 Suppl):S542-S547.

15. Ehrenreich H, Timner W, Siren AL. A novel role for an established player: Anemia drug erythropoietin for the treatment of cerebral hypoxia/ischemia. Transfus Apheresis Sci. 2004;31(1):39-44.

16. Ehrenreich H, Aust C, Krampe H, et al. Erythropoietin: Novel approaches to neuroprotection in human brain disease. Metab Brain Dis. 2004;19(3-4):195-206.

17. Ohls RK, Christensen RD, Kamath-Rayne BD, et al. A randomized, masked, placebo-controlled study of darbepoetin alfa in preterm infants. Pediatrics 2013; 132:e119.

18. Ohls RK, Roohi M, Peceny HM, et al. A randomized, masked study of weekly erythropoietin dosing in preterm infants. J Pediatr 2012; 160:790.

19. Schrier SL, Steensma DP, Lorpinzi CL. Role of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancerRole of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancerRole of erythropoiesis-stimulating agents in the treatment of anemia in patients with cancer.  UpToDate. Updated May 22,2018.  Accessed at www.uptodate.com 5/30/2018.

20. Berns JS. Treatment of anemia in hemodialysis patients. UpToDate. Updated Dec 08, 2016. Accessed at www.uptodate.com 5/30/2018.

21. Esyet EH, Schrier SL. Management of the complications of the myelodysplastic syndromes. UpToDate. Updated Jun 07, 2017.  Accessed at www.uptodate.com 5/30/2018.

22. Garcia-Prats JA. Anemia of prematurity. UpToDate. Updated Dec 18, 2017.  Accessed at www.uptodate.com 5/30/2018.