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

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 anemia in individuals five (5) years of age and older with nonmyeloid malignancies where:
  • Anemia is due to the effect of concomitant myelosuppressive chemotherapy; and
  • Upon initiation, there is a minimum of two (2) additional months of planned chemotherapy; and
    • Myelosuppressive therapy is not for curative intent; or
    • Individual is undergoing palliative treatment; or
• Treatment of anemia in individuals with cancer who have ANY of the following:
  • Have moderate to severe chronic kidney disease; or
  • Are undergoing palliative treatment; or
  • Individuals five (5) years of age and older and are receiving myelosuppressive chemotherapy with at least two additional months of planned chemotherapy and have no other identifiable cause of anemia; or
  • Refuse blood transfusions in select cases; 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
• Myelodysplastic Syndrome in individuals 18 years and older when ANY of the following:
  • Treatment of lower risk* disease associated with symptomatic anemia with ring sideroblasts less than 15% (or ring sideroblasts less than 5% with an SF3B1 mutation), with serum erythropoietin less than or equal to 500 mU/mL:
    • As a single agent; or
    • With either lenalidomide or G-CSF following no response to an erythropoiesis-stimulating agent (ESA) alone; or
  • Treatment of lower risk* disease associated with symptomatic anemia with ring sideroblasts greater than or equal to 15% (or ring sideroblasts greater than or equal to 5% with an SF3B1 mutation), with serum erythropoietin less than or equal to 500 mU/mL in combination with a G-CSF; or
  • Treatment of lower risk* disease associated with symptomatic anemia, no del(5q) with or without other cytogenetic abnormalities or ring sideroblasts greater than or equal to 15% (or ring sideroblasts greater than or equal to 5% with an SF3B1 mutation), with serum erythropoietin levels less than or equal to 500 mU/mL:
    • As a single agent; or
    • In combination with a G-CSF; or
    • In combination with or without lenalidomide or G-CSF following no response to an ESA alone or in combination with G-CSF (target hemoglobin range 10 to 12 g/dL; not to exceed 12 g/dL); or
  • Alternative to lenalidomide as treatment of lower risk* disease associated with symptomatic anemia, del(5q) with or without one other cytogenetic abnormality (except those involving chromosome 7), and serum erythropoietin levels less than or equal to 500 mU/mL; or
• Management of myelofibrosis-associated anemia in individuals 18 years and older with serum EPO less than 500 mU/mL; 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.

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 anemia in individuals 18 years of age and older with non-myeloid malignancies where;
  • Anemia is due to the effect of concomitant myelosuppressive chemotherapy; and
  • Upon initiation, there is a minimum of two additional months of planned chemotherapy; and
    • Myelosuppressive therapy is not for curative intent; or
    • Individual is are undergoing palliative treatment; or
• Treatment of anemia in individuals 18 years of age and older with cancer who have ANY of the following:
  • Have moderate to severe chronic kidney disease; or
  • Are undergoing palliative treatment; or
  • Are receiving myelosuppressive chemotherapy with at least two additional months of planned chemotherapy and have no other identifiable cause of anemia; or
  • Refuse blood transfusions in select cases; 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
• Individuals 18 years of age and older with Myelodysplastic Syndrome with ANY of the following:
  • Treatment of lower risk* disease associated with symptomatic anemia with ring sideroblasts less than 15% (or ring sideroblasts less than 5% with an SF3B1 mutation), with serum erythropoietin less than or equal to 500 mU/mL:
    • As a single agent; or
    • With either lenalidomide or G-CSF following no response to an erythropoiesis-stimulating agent (ESA) alone; or
  • Treatment of lower risk* disease associated with symptomatic anemia with ring sideroblasts greater than or equal to 15% (or ring sideroblasts greater than or equal to 5% with an SF3B1 mutation), with serum erythropoietin less than or equal to 500 mU/mL in combination with a G-CSF; or
  • Treatment of lower risk* disease associated with symptomatic anemia, no del(5q) with or without other cytogenetic abnormalities or ring sideroblasts greater than or equal to 15% (or ring sideroblasts greater than or equal to 5% with an SF3B1 mutation), with serum erythropoietin levels less than or equal to 500 mU/mL:
    • As a single agent; or
    • In combination with a G-CSF; or
    • In combination with or without lenalidomide or G-CSF following no response to an ESA alone or in combination with G-CSF (target hemoglobin range 10 to 12 g/dL; not to exceed 12 g/dL); or
  • Alternative to lenalidomide as treatment of lower risk* disease associated with symptomatic anemia, del(5q) with or without one other cytogenetic abnormality (except those involving chromosome 7), and serum erythropoietin levels less than or equal to 500 mU/mL; or
• Management of individuals 18 years and older with myelofibrosis-associated anemia with serum EPO less than 500 mU/mL; 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.

Epoetin beta-methoxy polyethylene glycol (Mircera) not meeting the criteria as indicated in this policy is considered not medically necessary.

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. 

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.

ESAs are not recommended when myelosuppressive chemotherapy is given with curative intent, for patients with cancer who are not receiving therapy, or for patients receiving non-myelosuppressive therapy.

*Note: Lower risk defined as IPSS-R (Very Low, Low, Intermediate), IPSS (Low/Intermediate-1), WPSS (Very Low, Low, Intermediate).