Coverage for erythropoiesis stimulating agents is determined according to individual or group customer benefits.

DARBEPOETIN ALFA (Aranesp®), EPOETIN ALFA (Epogen®, Procrit®)

Erythropoiesis stimulating agents may be considered reasonable and necessary for the treatment of anemia when reversible causes of anemia are identified and managed. Erythropoiesis stimulating agents may be initiated when the hematocrit (HCT) is less than 36% or the hemoglobin (Hgb) is less than 12g/dL, and when the anemia is associated with any of the following conditions:

1. End stage renal disease (ESRD) on dialysis/Chronic Kidney Disease (CKD) Stage V on dialysis.

   Erythropoiesis stimulating agents 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 erythropoiesis stimulating agents 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. A participating, preferred, or network provider cannot bill the member separately for erythropoiesis stimulating agents in this case.

   If the erythropoiesis stimulating agents are given independently, process it under the appropriate code.
   
   Modifier 59 may be reported with erythropoiesis stimulating agents 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.
   
   

2. Chronic renal failure not on dialysis/CKD Stage II-V not on dialysis.
   
   
3. Renal tubular damage secondary to cisplatin chemotherapy.
   
   
4. Treatment of anemia associated with documented multiple myeloma.
   • Patient may or may not be receiving chemotherapy
     
     
5. Antineoplastic Therapy. The following patient indications should apply:
   • Currently receiving a course of antineoplastic therapy or within the last three months
     
     
6. Acquired Immunodeficiency Syndrome (AIDS) or AIDS-Related Complex (ARC) receiving Zidovudine (AZT) therapy. All of the following patient indications should apply:
   • AZT doses of 4200 mg or less/week
   • Endogenous levels of erythropoietin of 500 MU/ml or less
   • Treatment lasting no longer than three months following the discontinuation of the AZT
     
     
7. Myelodysplastic Syndrome.
   • Endogenous erythropoietin level should be less than 500 MU/ml
     
     
8. Anemia of prematurity.
   
   
9. Anemia associated with chronic illness.
   • Anemia of chronic illness is a secondary manifestation of an underlying disorder. Epoetin alfa administration may not be the appropriate treatment choice in anemia of chronic disease, because it typically is not severe.
     
     
10. Preoperative Use for Anemia Related to Chronic Disease. All of the following patient indications must apply:
    • Patient is undergoing noncardiac/nonvascular surgery
    • Patient is not a candidate for autologous blood transfusion
    • Patient is expected to lose more than two units of blood during surgery
    • Preoperative workup has revealed that anemia is related to chronic disease
    • Antithrombotic prophylaxis should be strongly considered for concurrent use
      
      
11. Individuals who will not or cannot receive blood products for treatment of acute hemorrhage or blood loss.

The use of erythropoiesis stimulating agents for any indication not listed on this policy is considered not medically necessary, and therefore, not covered. A participating, preferred or network provider cannot bill the member for the denied service unless the provider has given advance written notice, informing the member that the service may be deemed not medically necessary and providing an estimate of the cost. The member must agree in writing to assume financial responsibility, in advance of receiving the service. The signed agreement should be maintained in the provider's records.

The FDA and Amgen notified healthcare professionals and patients that all ESAs must be used under a REMS risk management program. As part of the risk management program, a Medication Guide explaining the risks and benefits of ESAs must be provided to all patients receiving an ESA. Under the ESA APPRISE Oncology program, Amgen will ensure that only those hospitals and healthcare professionals who have enrolled and completed training in the program will prescribe and dispense ESAs to patients with cancer. Amgen is also required to oversee and monitor the program to ensure that hospitals and healthcare professionals are fully compliant with all aspects of the program. FDA is requiring a REMS because studies show that ESAs can increase the risk of tumor growth and shorten survival in patients with cancer who use these products. Studies also show that ESAs can increase the risk of heart attack, heart failure, stroke or blood clots in patients who use these drugs for other conditions.

NOTE:

Use code J0881 for darbepoetin alfa for non-ESRD use.

Use code J0882 for darbepoetin alfa for ESRD on dialysis.

Use code J0885 for epoetin alfa for non-ESRD use.

Use code J0886 or Q4081 for epoetin alfa for ESRD on dialysis.

NOTE:

See Medical Policy Bulletin G-16 on Chemotherapy for Malignant Disease.

Description

Epoetin alfa
Epoetin alfa is a glycoprotein which stimulates red blood cell production. It is produced by the kidney and stimulates the division and differentiation of committed erythroid progenitors in the bone marrow. Epoetin alfa is formulated as a sterile, colorless, preservative-free liquid for intravenous or subcutaneous administration. Epoetin alfa is indicated to elevate or maintain the red blood cell level and to decrease the need for transfusions in selected patients.

Darbepoetin alfa
Darbepoetin alfa is an erythropoiesis stimulating protein, closely related to erythropoietin, that is produced in Chinese hamster ovary cells by recombinant DNA technology. Darbepoetin alfa stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. A primary growth factor for erythroid development, erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia. In responding to hypoxia, erythropoietin interacts with progenitor stem cells to increase red blood cell production. Darbepoetin alfa is formulated as a sterile, colorless, preservative-free protein solution from intravenous or subcutaneous administration.

NOTE:

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 circumstances may warrant individual consideration, based on review of applicable medical records.

Under the Federal Employee Program, all services that utilize FDA-approved drugs, devices, or biological products are eligible when intended for the treatment of a serious or life-threatening condition and when medically necessary and appropriate for the patient's condition.

USPDI-Vol. 1, Edition 26, 2006 Micromedex, Inc.

Aranesp® (darbepoetin alfa)[package insert]. Thousand Oaks, CA: Amgen, Inc., 2007

Epogen® (epoetin alfa)[package insert]. Thousand Oaks, CA, Amgen, Inc., 2007

Procrit® (epoetin alfa)[package insert]. Thousand Oaks, CA, Amgen, Inc., 2007

NCCN Updates Cancer and Treatment Related Anemia Guidelines. National Comprehensive Cancer Network (NCCN), March 5, 2007

U.S. Food and Drug Administration (FDA). FDA Strengthens Safety Information for Erythropoiesis-Stimulating Agents (ESAs), FDA News, P07-40, Rockville, MD: FDA; March 9, 2007

U.S. Food and Drug Administration (FDA). FDA Public Health Advisory, Epoetin alfa; darbepoetin alfa, Rockville, MD: FDA; November 16, 2006, updated March 9, 2007

U.S. Food and Drug Administration (FDA). FDA Receives New Data on Risks of Anemia Drugs, FDA News, Rockville, MD: January 3, 2008

U.S. Food and Drug Administration (FDA). FDA Strengthens Boxed Warnings, Approves Other Safety Labeling Changes for Erythropoiesis Stimulating Agents (ESAs), FDA News, Rockville, MD; November 8, 2007

Correction of Anemia with Epoetin Alfa in Chronic Kidney Disease, The New England Journal of Medicine, Vol 355, No. 20, 11/2006

Correction of Anemia-Payoffs and Problems, The New England Journal of Medicine, Vol 355, No. 20, 11/2006

The New FDA Label for Erythropoietin Treatment: How Does it Affect Hemoglobin Target? Kidney Int. 2007; Vol. 72, No. 7

Venous Thromboembolism and Mortality Associated with Recombinant Erythropoietin and Darbepoetin Administration for the Treatment of Cancer-Associated Anemia, JAMA, Vol. 299, No. 8, 02/2008

New Limits Advised for Anemia Drugs, JAMA, Vol. 297, No. 2, 06/2007

Use of Epoetin in Chronic Renal Failure, JAMA, Vol. 297, No. 15, 04/2007

Givens M, Lapointe M. Is there a place for epoetin alfa in managing anemia during critical illness? Clin Ther. 2004;26(6):819-29.

Remmers PA, Speer AJ. Clinical strategies in the medical care of Jehovah's Witnesses. Am J Med. 2006;119:1013-1018.

Shander A, Goodnough LT. Objectives and limitations of bloodless medical care. Curr Opin Hematol. 2006;13(6):462-70.

Gyamfi C, Berkowitz RL. Management of pregnancy in a Jehovah's Witness. Obstet Gynecol Clin N Am. 2007;34:357-365.

Jaspan D. Erythropoietic therapy: cost efficiency and reimbursement. Am J Health Syst Pharm. 2007;64(16 Suppl 11):519-29.

Thomas J, Martinez A. Blood conservation in the critically ill. Am J Health Syst Pharm. 2007;64(16 Suppl 11):511-8.

Perioperative blood transfusion and blood conservation in cardiac surgery; the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007;83(5 Suppl):527-86.

Ball AM, Winstead PS. Recombinant human erythropoietin therapy in critically ill Jehovah's Witnesses. Pharmacotherapy. 2008;28(19):1383-90.

Shermock KM, Horn E, Rice TL. Erythropoietic agents for anemia of critical illness. Am J Health Syst Pharm. 2008;65(6):540-6.

FDA receives new data on risks of anemia drugs. US Food and Drug Administration. FDA News. January 3, 2008.

New study probes safety of erythropoiesis-stimulating agents. American Society of Clinical Oncology (ASCO) 44th Annual Meeting: Abstract 11007. Presented June 2, 2008. Abstract.

Unger EF, Thompson AM, Blank MJ, et al. Erythropoiesis-stimulating agents - time for a reevaluation. N Engl J Med. 2010;362(3):189-192.

FDA adopts additional strategies to promote safe use of erythropoiesis-stimulating agents. US Food and Drug Administration. FDA News. February 16, 2010.