BlueCross BlueShield of Tennessee Medical Policy Manual

Erythropoiesis-Stimulating Agents (ESAs)

DESCRIPTION

Erythropoietin is a glycoprotein produced in the kidneys responsible for the stimulation of red blood cell production. Epoetin alfa is a synthetic form of erythropoietin. Epoetin alfa, a 165 amino acid glycoprotein produced through recombinant DNA technology, has the same biological effects as endogenous erythropoietin.

Darbepoetin alfa is closely related to epoetin alfa and is also produced through recombinant DNA technology. With the addition of two additional oligosaccharide chains it remains in systemic circulation approximately three times longer than epoetin alfa.

Both epoetin alfa and darbepoetin alfa have the same amino acid sequence as endogenous erythropoietin.  Like the endogenous hormone, they stimulate increased production of red blood cells in individuals with functioning erythropoiesis and are referred to as erythropoietin-stimulating agents or ESAs.

Both types of ESAs should be administered in accordance with current FDA-approved labeling for each product.  Each product label bears boxed warnings about significant risks and for oncological use require enrollment by providers and hospitals in the FDA REMs (Risk Evaluation Mitigation) program, ESA APPRISE Oncology Program.

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

MEDICAL APPROPRIATENESS

APPLICABLE TENNESSEE STATE MANDATE REQUIREMENTS

BlueCross BlueShield of Tennessee’s Medical Policy complies with Tennessee Code Annotated Section 56-7-2352 regarding coverage of off-label indications of Food and Drug Administration (FDA) approved drugs when the off-label use is recognized in one of the statutorily recognized standard reference compendia or in the published peer-reviewed medical literature.

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).

For individuals with CRF on dialysis, FDA guidelines recommend dose reduction or interruption if hemoglobin approaches or exceeds 11g/dL. 

For those with CRF and not on dialysis, FDA guidelines recommend dose reduction or interruption if hemoglobin exceeds 10g/dL.

No controlled studies were found in the published literature that validate the use of erythropoiesis stimulating agents in the treatment/prevention of any other conditions/diseases.

SOURCES

BlueCross BlueShield Association. Medical Policy Reference Manual. (9:2014). Erythropoietin (epoetin alfa) (5.01.04). Retrieved October 28, 2014 from BlueWeb.

Lexi-Comp Online. (2014). AHFS DI. Darbepoetin alfa. Retrieved October 28, 2014 from Lexi-Comp Online with AHFS.

Lexi-Comp Online. (2014). AHFS DI. Epoetin alfa. Retrieved October 28, 2014 from Lexi-Comp Online with AHFS.

MICROMEDEX Health Care Series. Drugdex Drug Evaluation. (2014, September) Darbepoetin alfa. Retrieved October 28, 2014 from MICROMEDEX Healthcare Series.

MICROMEDEX Health Care Series. Drugdex Drug Evaluation. (2014, September) Erythropoietin. Retrieved October 28, 2014 from MICROMEDEX Healthcare Series.

National Comprehensive Cancer Network. (2014). NCCN Drugs & Biologics Compendium™. Epoetin alfa. Retrieved October 28, 2014 from the National Comprehensive Cancer Network.

National Comprehensive Cancer Network. (2014). NCCN Drugs & Biologics Compendium™. Darbepoetin alfa. Retrieved October 28, 2014 from the National Comprehensive Cancer Network.

Rizzo, J. D., Brouwers, M., Hurley, P., Seidenfeld, J., Arcasoy, M.O., Spivak, J.L., et al. (2010, November). American Society of Clinical Oncology and the American Society of Hematology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Journal of Clinical Oncology, 28(33): 4996-5010.

U. S. Food and Drug Administration. (2013, December). Center for Drug Evaluation and Research. Aranesp® (darbepoetin alfa) injection, for intravenous or subcutaneous use. Retrieved October 28, 2014 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103951s5349lbl.pdf.

U. S. Food and Drug Administration. (2013, December). Center for Drug Evaluation and Research. FDA Labeling Information. Epogen® / Procrit ®. Retrieved October 28, 2014 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/103234s5323lbl.pdf.

ORIGINAL EFFECTIVE DATE: 1/14/2006

MOST RECENT REVIEW DATE:  12/1/2014

ID_BT

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

Pharmaceutical Decision Support Tree

Erythropoiesis-Stimulating Agents: Epoetin Alfa (Epogen®, Procrit®), Darbepoetin Alfa (Aranesp®)

  1. Is the anemic individual scheduled to undergo elective, noncardiac, nonvascular surgery with ALL of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #2

  1. Is the ESA request for initiation of treatment for anemia?

If yes, go to question #3

If no, go to question #10

  1.  Has ALL the following monitoring has occurred?

If yes, go to question #4

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. 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

  1. Is anemia associated with non-myeloid malignancies with ALL the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #6

  1. Is anemia associated with myelodysplastic syndromes with ALL the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, go to question #7

  1. 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

  1. 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

  1. Is anemia associated with zidovudine (AZT) therapy with human immunodeficiency virus with ALL of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. 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

  1. 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

  1. Is anemia associated with chronic renal failure?

If yes, go to #14

If no, go to question #13

  1. Is anemia associated with ALL of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

  1. Is anemia associated with chronic renal failure with ANY ONE of the following?

If yes, this satisfies medical necessity and medical appropriateness criteria

If no, this does not meet medical necessity and/or medical appropriateness criteria

This document has been classified as public information.