DESCRIPTION
Erythropoietin is a glycoprotein that is produced in the kidneys and is responsible for the stimulation of red blood cell production. Epoetin alfa is a synthetic form of erythropoietin. Epoetin alfa, a 165 amino acid glycoprotein manufactured by recombinant DNA technology, has the same biological effects as endogenous erythropoietin.
Darbepoetin alfa is an erythropoiesis stimulating protein, closely related to erythropoietin, which is produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. It is a hematopoietic agent that principally affects erythropoiesis. The advantage of darbepoetin alfa over epoetin alfa is its reduced clearance, resulting in a longer half-life and less frequent dosing requirements.
Epoetin alfa and darbepoetin alfa have the same amino acid sequence as endogenous erythropoietin, while darbepoetin alfa has two additional oligosaccharide chains; however, the epoetins and darbepoetin all have pharmacologic actions identical to those of the endogenous hormone. They increase the number of red blood cells, and thus the blood concentration of hemoglobin, when given to individuals with functioning erythropoiesis.
The term “ESA” refers to epoetin alfa (Epogen®, Procrit®) and to darbepoetin alfa (Aranesp®). ESA treatment should be administered according to current FDA-approved labeling for each product. For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
Examples of preparations of epoetin alfa are: Epogen® and Procrit®.
An example of a preparation of darbepoetin alfa is Aranesp®.
REFER TO DECISION SUPPORT TREE
POLICY
An erythropoiesis-stimulating agent for the treatment of anemia associated with the following conditions is considered medically necessary if the medical appropriateness criteria are met: (See Medical Appropriateness below.)
Elective, noncardiac, nonvascular surgery
Chronic renal failure (with or without dialysis)
Non-myeloid malignancies
Myelodysplastic syndrome
Hepatitis C virus infection
Chronic disease (e.g., anemia associated with: chronic inflammation, infectious, inflammatory, chronic immune activation)
Zidovudine (AZT) therapy in individuals with human immunodeficiency virus
An erythropoiesis-stimulating agent for the treatment of anemia related to other conditions/diseases is considered investigational.
MEDICAL APPROPRIATENESS
An erythropoiesis-stimulating agent for the treatment of anemia is considered medically appropriate for ANY ONE of the following:
Anemic individual scheduled to undergo elective, noncardiac, nonvascular surgery with ALL of the following:
Agent is used to reduce the need for allogeneic blood transfusions
Hemoglobin greater than 10 grams per dL (g/dL) and less than or equal to 13 g/dL
Risk for perioperative transfusion is high
The individual is not willing to donate autologous blood
Initiation of treatment for ALL of the following:
ALL of the following monitoring has occurred:
Anemia related to other sources has been ruled out (e.g., folate deficiencies, hemolysis, or gastrointestinal bleeding)
Blood values of ALL the following:
Hematocrit level less than 30% or hemoglobin less than 10 g/dL
Minimum transferrin saturation of 20% before and during therapy
Minimum ferritin level 100 ng/ml before and during therapy
Anemia is associated with ANY ONE of the following:
Chronic renal failure dialysis (with or without dialysis)
Non-myeloid malignancies with ALL the following:
Provider registered in the ESA APPRISE Oncology Program
Disease is metastatic
Anemia is due to the effect of concomitantly administered chemotherapy
Serum erythropoietin level is less than or equal to 500 mUnits/mL
Myelodysplastic syndromes with ALL the following:
Disease is lower risk without del(5q) mutation
Serum erythropoietin level is less than or equal to 500mUnits/mL
Treatment is ANY ONE of the following:
Single agent for less than 15% ringed sideroblasts
In combination with filgrastim for greater than or equal to 15% ringed sideroblasts
Hepatitis C virus infection when being treated with a combination of ribavirin and interferon alfa or ribavirin and peginterferon alfa
Chronic disease (e.g., anemia associated with: chronic inflammation, infectious, inflammatory, chronic immune activation) with serum erythropoietin level less than or equal to 500 mUnits/mL
Zidovudine (AZT) therapy in individuals with human immunodeficiency virus with ALL of the following:
Serum erythropoietin level is less than or equal to 500mUnits/mL
Zidovudine dosage is less than or equal to 4200 mg per week
Continuation of treatment with ALL of the following:
Hematocrit levels have increased by 3% or the hemoglobin level by 1 g/dL within eight weeks of therapy
ANY ONE of the following:
Chronic renal failure with ANY ONE of the following:
Individual not on dialysis with current hemoglobin level less than 10 g/dL (Note: FDA guidelines specify reduction/interruption of dose for hemoglobin levels approaching or exceeding 10 g/dL)
Individual on dialysis with current hemoglobin level less than 11 g/dL (Note: FDA guidelines specify reduction/interruption of dose for hemoglobin levels approaching or exceeding 11 g/dL)
Anemia with ALL of the following:
ANY ONE of the following:
Non-myeloid malignancies
Myelodysplastic syndrome
Hepatitis C virus infection
Chronic disease (e.g., anemia associated with: chronic inflammation, infectious, inflammatory, chronic immune activation)
Zidovudine (AZT) therapy with human immunodeficiency virus
Current hemoglobin level are less than 12 g/dL
APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS
Tennessee State law requires coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is relative to life-threatening illnesses, such as cancer, AIDS, and coronary heart disease and recognized in one of the standard reference compendia (As defined in the statute: The United States Pharmacopoeia Drug Information, The American Medical Association Drug Evaluations, & The American Hospital Formulary Service Drug Information) or in the medical literature. This law is applicable to all fully insured members. The law is not applicable to self-funded accounts, but coverage for off-label uses may be provided based on the contractual agreement.
IMPORTANT REMINDER
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
ADDITIONAL INFORMATION
For appropriate dosage information, contraindications, precautions, warnings, and monitoring information, please refer to one of the standard reference compendia (e.g., The American Hospital Formulary Service Drug Information).
There is insufficient evidence supporting the use of erythropoiesis-stimulating agents for the treatment of anemia in other conditions/diseases.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (5:2011). Erythropoietin (epoetin alfa) (5.01.04). Retrieved July 21, 2011 from BlueWeb.
Brau, N. (2004, May). Epoetin alfa treatment for acute anaemia during interferon plus ribavirin combination therapy for chronic hepatitis C. Journal of Viral Hepatitis, 11 (Issue 3), 191-197. (Level 5 Evidence).
Lexi-Comp Online. (2011, July). AHFS DI. Darbepoetin alfa. Retrieved July 22, 2011 from Lexi-Comp Online with AHFS.
Lexi-Comp Online. (2011, July). AHFS DI. Epoetin alfa. Retrieved July 22, 2011 from Lexi-Comp Online with AHFS.
MICROMEDEX Health Care Series. Drugdex Drug Evaluation. (2011, July) Darbepoetin alfa. Retrieved July 22, 2011 from MICROMEDEX Healthcare Series.
MICROMEDEX Health Care Series. Drugdex Drug Evaluation. (2011, July) Erythropoietin. Retrieved July 22, 2011 from MICROMEDEX Healthcare Series.
National Comprehensive Cancer Network. (2011). NCCN Drugs & Biologics Compendium™. Darbepoetin alfa. Retrieved August 10, 2011 from the National Comprehensive Cancer Network.
National Comprehensive Cancer Network. (2011). NCCN Drugs & Biologics Compendium™. Epoetin alfa. Retrieved August 10, 2011 from the National Comprehensive Cancer Network.
Rizzo, J. D., Somerfield, M. R., Hagerty, K. L., Seidenfeld, J., Bohlius, J, Bennett, C. L., et al. (2008, January). American Society of Clinical Oncology and the American Society of Hematology 2007 clinical practice guidelines update on the use of epoetin and darbepoetin. Journal of Clinical Oncology, (26) 1, pp 132-149.
U. S. Food and Drug Administration. (2011, June). Center for Drug Evaluation and Research. Aranesp® (darbepoetin alfa) injection, for intravenous or subcutaneous use. Retrieved July 21, 2011 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103951Orig1s5173_103951Orig1s5258lbl.pdf.
U. S. Food and Drug Administration. (2011, June). Center for Drug Evaluation and Research. FDA Labeling Information. Epogen® / Procrit ®. Retrieved July 21, 2011 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2011/103234Orig1s5166_103234Orig1s5266lbl.pdf.
UpToDate, Inc. (2012, May). Anemia of chronic disease (anemia of chronic inflammation). Retrieved July 20, 2012 from http://www.uptodate.com/index.
Vardiman, J. W., Thiele, J. T, Arber, D. A., Brunning, R. D., Borowitz, M. J., Porwit, A. e.t. al. (2009, July). The 2008 revision of the WHO classification of myeloid neoplasms and acute leukemia: Rationale and important changes. Blood, 114 (No. 5). 937-951.
Weiss G, Goodnough LT. (2005, March). Anemia of chronic disease. The New England Journal of Medicine, 352 (10) 1011-23.
ORIGINAL EFFECTIVE DATE: 1/14/2006
MOST RECENT REVIEW DATE: 11/16/2011
ID_BT
Pharmaceutical Decision Support Tree
Erythropoiesis-Stimulating Agents: Epoetin Alfa (Epogen®, Procrit®), Darbepoetin Alfa (Aranesp®)
Is the anemic individual scheduled to undergo elective, noncardiac, nonvascular surgery with ALL of the following?
Agent is used to reduce the need for allogeneic blood transfusions
Hemoglobin greater than 10 grams per dL (g/dL) and less than or equal to 13 g/dL
Risk for perioperative transfusions is high
The individual is not willing to donate autologous blood
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #2
Is the ESA request for initiation of treatment for anemia?
If yes, go to question #3
If no, go to question #10
ALL the following monitoring has occurred?
Anemia related to other sources has been ruled out (e.g., folate deficiencies, hemolysis, or gastrointestinal bleeding)
Blood values of ALL the following:
Hematocrit level less than 30% or hemoglobin less than 10 g/dL
Minimum transferrin saturation of 20% before and during therapy
Minimum ferritin level 100 ng/ml before and during therapy
If yes, go to question #4
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is anemia associated with chronic renal failure (with or without dialysis)?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #5
Is anemia associated with non-myeloid malignancies with ALL the following?
Provider is registered in the ESA APPRISE Oncology Program
Disease is metastatic
Anemia is due to the effect of concomitantly administered chemotherapy
Serum erythropoietin level is less than or equal to 500mUnits/mL
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #6
Is anemia associated with myelodysplastic syndromes with ALL the following?
Disease is lower risk without del(5q) mutation
Serum erythropoietin level is less than or equal to 500mUnits/mL
Treatment is ANY ONE of the following:
Single agent for less than 15% ringed sideroblasts
In combination with filgrastim for greater than or equal to 15% ringed sideroblasts
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #7
Is anemia associated with hepatitis C virus infection when being treated with a combination of ribavirin and interferon alfa or ribavirin and peginterferon alfa?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #8
Is anemia associated with chronic disease (e.g., anemia associated with: chronic inflammation, infectious, inflammatory, chronic immune activation) and are serum erythropoietin levels less than or equal to 500mUnits/mL?
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, go to question #9
Is anemia associated with zidovudine (AZT) therapy with human immunodeficiency virus with ALL of the following?
Serum erythropoietin level is less than or equal to 500mUnits/ml
Zidovudine dosage is less than or equal to 4200 mg per week
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is the ESA request for continuation of treatment for anemia?
If yes, go to question #11
If no, this does not meet medical necessity and/or medical appropriateness criteria
Have the hematocrit levels increased by 3% or hemoglobin level by 1 g/dL within eight weeks of therapy?
If yes, go to question #12
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is anemia associated with chronic renal failure?
If yes, go to #14
If no, go to question #13
Is anemia associated with ALL of the following?
ANY ONE of the following:
Non-myeloid malignancies
Myelodysplastic syndrome
Hepatitis C virus infection
Chronic disease (e.g., anemia associated with: chronic inflammation, infectious, inflammatory, chronic immune activation)
Zidovudine (AZT) therapy with human immunodeficiency virus
Current hemoglobin level are less than 12 g/dL
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
Is anemia associated with chronic renal failure with ANY ONE of the following?
Not on dialysis with current hemoglobin level less than 10 g/dL (Note: FDA guidelines specify reduction/interruption of dose for hemoglobin levels approaching or exceeding 10 g/dL)
On dialysis with current hemoglobin level less than 11 g/dL (Note: FDA guidelines specify reduction/interruption of dose for hemoglobin levels approaching or exceeding 11 g/dL)
If yes, this satisfies medical necessity and medical appropriateness criteria
If no, this does not meet medical necessity and/or medical appropriateness criteria
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