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Date Printed: June 26, 2017: 11:43 AM

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09-J0000-31

Original Effective Date: 06/15/00

Reviewed: 04/12/17

Revised: 06/15/17

Subject: Erythropoiesis Stimulating Agents

THIS MEDICAL COVERAGE GUIDELINE IS NOT AN AUTHORIZATION, CERTIFICATION, EXPLANATION OF BENEFITS, OR A GUARANTEE OF PAYMENT, NOR DOES IT SUBSTITUTE FOR OR CONSTITUTE MEDICAL ADVICE. ALL MEDICAL DECISIONS ARE SOLELY THE RESPONSIBILITY OF THE PATIENT AND PHYSICIAN. BENEFITS ARE DETERMINED BY THE GROUP CONTRACT, MEMBER BENEFIT BOOKLET, AND/OR INDIVIDUAL SUBSCRIBER CERTIFICATE IN EFFECT AT THE TIME SERVICES WERE RENDERED. THIS MEDICAL COVERAGE GUIDELINE APPLIES TO ALL LINES OF BUSINESS UNLESS OTHERWISE NOTED IN THE PROGRAM EXCEPTIONS SECTION.

           
Dosage/ Administration Position Statement Billing/Coding Reimbursement Program Exceptions Definitions
           
Related Guidelines Other References Updates  
           

DESCRIPTION:

Erythropoietin is a glycoprotein responsible regulating the production of red blood cells (RBCs) by stimulating the division and differentiation of erythroid progenitor cells in the bone marrow. Erythropoiesis stimulating agents (ESAs) are recombinant forms of erythropoietin and have the same biological activity as endogenous erythropoietin. Currently, there are four commercially available ESAs in the United States: epoetin alfa (Epogen® and Procrit®), darbepoetin alfa (Aranesp®), and methoxy polyethylene glycol-epoetin beta (MPG-epoetin beta)( Mircera®). Epoetin alfa was granted orphan designation by the FDA for the treatment of anemia associated with HIV infection or HIV treatment (1991), myelodysplastic syndrome (1993), and anemia associated with end stage renal disease (1986). While all four ESAs share the same mechanism of action, darbepoetin alfa has two additional carbohydrate chains to give it a longer half-life. In 2007 the FDA approved MPG-epoetin beta (Mircera®) for the treatment of anemia associated with chronic renal failure. MPG-epoetin beta is a pegylated version of recombinant human erythropoietin developed by Hoffman-La Roche. However, due to infringement on an Amgen patent, Hoffman-La Roche was not able to commercially release their product until mid-2014. Additionally, as of March 2015, MPG-epoetin beta is only being distributed to Fresenius Medical Care dialysis centers. An additional ESA, peginesatide (Omontys®) was voluntary withdrawn from the United States market on February 24, 2013, in response to reports of serious and fatal hypersensitivity reactions occurring in some individuals receiving their first dose of peginesatide.

POSITION STATEMENT:

Comparative Effectiveness

The Food and Drug Administration has deemed the drug(s) or biological product(s) in this coverage policy to be appropriate for self-administration or administration by a caregiver (i.e., not a healthcare professional). Therefore, coverage (i.e., administration) in a provider-administered setting such as an outpatient hospital, ambulatory surgical suite, or emergency facility is not considered medically necessary.

 

Certificate of Medical Necessity

Submit a completed Certificate of Medical Necessity (CMN) along with your request to expedite the medical review process.

1. Click the link Erythropoiesis Stimulating Agents - Certificate of Medical Necessity (MS Word) to open the form.

2. Complete all fields on the form thoroughly.

3. Print and submit a copy of the form with your request.

Note: Florida Blue regularly updates CMNs. Ensure you are using the most current copy of a CMN before submitting to Florida Blue. For a complete list of available CMNs, visit the Certificates of Medical Necessity page.

NOTE: Procrit is the preferred erythropoiesis stimulating agent for all indications except anemia due to chronic kidney disease in members on dialysis.

Initiation of an erythropoiesis stimulating agent (ESA) (e.g., epoetin alfa [Procrit, Epogen], darbepoetin alfa [Aranesp]) meets the definition of medical necessity when ALL of the following are met:

1. Within the last 4 weeks, evaluation of the member’s iron status includes BOTH of the following (unless member is receiving concurrent intravenous iron):

a. Transferrin saturation is 20% or more

b. Ferritin is 100 ng/mL or more

2. Member’s hemoglobin is less than 10 g/dL or hematocrit is less than 30% (unless otherwise specified in Table 1 [e.g., peri-surgery]).

3. Other causes of anemia (e.g., hemolysis, bleeding) have been ruled out.

4. ESA is administered for treatment of the indications listed in table 1 and ALL of the indication-specific criteria.

Table 1:

Indications and Specific Criteria for ESA Therapy Initiation

Indication

Specific Criteria

Maximum Allowable Dose

Epoetin alfa (i.e., Procrit and Epogen)

Anemia due to CKD

EITHER of the following:

1. Member is on dialysis

2. Member is not on dialysis and BOTH of the following apply:

a. The rate of hematocrit decline indicates the likelihood of requiring a blood transfusion

b. Reducing the risk of alloimmunization and/or other blood transfusion-related risk is a goal

60,000 units weekly

Zidovudine-induced anemia

BOTH of the following:

1. The member’s endogenous serum erythropoietin level is 500 mUnits/ mL or less

2. The dose of zidovudine does not exceed 4200 mg weekly

60,000 units weekly

Chemotherapy-induced anemia

ALL of the following:

1. Member is diagnosed with a non-myeloid, non-erythroid malignancy (e.g., solid tumors, myeloma, lymphoma)

2. The intent of chemotherapy is treatment of an incurable disease (i.e., intent of chemotherapy is palliative)

3. Member is on chemotherapy or has received chemotherapy in the past 2 months

60,000 units weekly

Peri-surgery

ALL of the following:

1. Member is scheduled to undergo elective, non-cardiac, non-vascular surgery

2. Member’s hemoglobin is greater than 10 g/dL but less than 13 g/dL

3. Member is expected to require more than 2 units of blood during surgery

4. Member is unwilling or unable to provide autologous blood donation

Either of the following:

• 300 units/kg/ day x 15 days

• 600 units/kg/ week x 3 weeks

Anemia of Prematurity

Either of the following:

1. Member’s birth weight is less than 1500 grams

2. Member’s gestational age at the time of birth is less than 33 weeks

1200 units/kg weekly

Anemia associated with MDS

The member’s endogenous serum erythropoietin level is 500 mUnits/ mL or less

60,000 units twice weekly

Anemia associated with Myeloproliferative neoplasms (Primary MF, Post-PV MF, Post-ET MF)

The member’s endogenous serum erythropoietin level is less than 500 mUnits/ mL

60,000 units weekly

Anemia associated with Hepatitis C management

Member is receiving concomitant therapy with ribavirin and EITHER of the following

1. Interferon-alfa

2. Peg-interferon alfa

60,000 units weekly

Anemia associated with RA treatment

Member is prescribed concomitant therapy for the treatment of RA that is known to cause anemia (e.g., methotrexate)

60,000 units weekly

Darbepoetin alfa (Aranesp)

Anemia due to CKD

EITHER of the following:

1. Member is on dialysis

2. Member is not on dialysis and BOTH of the following apply:

a. The rate of hematocrit decline indicates the likelihood of requiring a blood transfusion

b. Reducing the risk of alloimmunization and/or other blood transfusion-related risk is a goal

Any of the following:

• 500 mcg every 21 days

• 300 mcg every 14 days

• 200 mcg every 7 days

Chemotherapy-induced anemia

ALL of the following:

1. Member is diagnosed with a non-myeloid, non-erythroid malignancy

2. The intent of chemotherapy is treatment of chemotherapy for an incurable disease (i.e., intent of chemotherapy is palliative)

3. Member is on chemotherapy or has received chemotherapy in the past 2 months

Anemia associated with MDS

The member’s endogenous serum erythropoietin level is 500 mUnits/ mL or less

Anemia associated with Myeloproliferative neoplasms (Primary MF, Post-PV MF, Post-ET MF)

The member’s endogenous serum erythropoietin level is less than 500 mUnits/ mL

Anemia associated with RA treatment

Member is prescribed concomitant therapy for the treatment of RA that is known to cause anemia (e.g., methotrexate)

Anemia associated with Hepatitis C management

Member is receiving concomitant therapy with ribavirin and EITHER of the following

1. Interferon-alfa

2. Peg-interferon alfa

Methoxy polyethylene glycol-epoetin beta (Mircera)

Anemia due to CKD

BOTH of the following:

1. Member has an inadequate response to or has a contraindication to epoetin alfa

2. EITHER of the following:

a. Member is on dialysis

b. Member is not on dialysis and BOTH of the following apply:

• The rate of hematocrit decline indicates the likelihood of requiring a blood transfusion

• Reducing the risk of alloimmunization and/or other blood transfusion-related risk is a goal

Either of the following:

• 640 mcg every 4 weeks

• 320 mcg every 2 weeks

ESA, erythropoiesis stimulating agent; CKD, chronic kidney disease; MDS, myelodysplastic syndrome; MF, myelofibrosis: Post-PV MF, post polycythemia vera myelofibrosis; Post-ET MF, post essential thrombocythemia myelofibrosis; RA, rheumatoid arthritis

Duration of Approval for Peri-surgery: 21 days

Duration of Approval all other indications: 8 weeks

Continuation of an erythropoiesis stimulating agent (e.g., epoetin alfa, darbepoetin alfa, methoxy polyethylene glycol-epoetin beta) meets the definition of medical necessity when ALL of the following criteria are met:

1. The member has a beneficial clinical response to therapy (defined as a rise in hemoglobin of 1 g/dL or more compared to pre-treatment baseline within 12 weeks of therapy initiation for anemia of chronic kidney disease or within 8 weeks of therapy initiation for all other indications) and EITHER of the following

a. Member has been approved by Florida Blue or another healthplan in the past 6 months

b. Member has previously met Florida Blue’s initial criteria for coverage in the past 6 months

2. Within the past 6 months, evaluation of the member’s iron status includes BOTH of the following

a. Transferrin saturation is 20% or more

b. Ferritin is 100 ng/mL or more

3. ESA is administered for treatment of the indications listed in table 2 and ALL of the indication-specific criteria are met

TABLE 2:

Indications and Specific Criteria for ESA Therapy Continuation

Indication

Specific Criteria†

Epoetin alfa (i.e., Procrit and Epogen)

Anemia due to CKD

EITHER of the following

1. On dialysis: hemoglobin is 11 g/dL or less

2. Not on dialysis: hemoglobin is 10 g/dL or less

Zidovudine-induced anemia

BOTH of the following

1. Hemoglobin is 12 g/dL or less

2. Zidovudine dose is 4200 mg/week or less

Chemotherapy-induced anemia

ALL of the following

1. Hemoglobin is 10 g/dL or less

2. Member is on chemotherapy or has received chemotherapy in the past 2 months

Anemia of Prematurity

Hemoglobin is 11 g/dL or less

Anemia associated with MDS

Hemoglobin is 12 g/dL or less

Anemia associated with Myeloproliferative neoplasms (Primary MF, Post-PV MF, Post-ET MF)

Hemoglobin is 11 g/dL or less

Anemia associated with RA treatment

BOTH of the following:

1. Hemoglobin is 11 g/dL or less

2. Member is prescribed concomitant therapy for the treatment of RA that is known to cause anemia (e.g., methotrexate)

Anemia associated with Hepatitis C management

BOTH of the following

1. Hemoglobin is 11 g/dL or less

2. Member is receiving concomitant therapy with ribavirin and EITHER of the following:

a. Interferon-alfa

b. Peg-interferon alfa

Darbepoetin alfa (Aranesp)

Anemia due to CKD

EITHER of the following:

1. On dialysis: hemoglobin is 11 g/dL or less

2. Not on dialysis: hemoglobin is 10 g/dL or less

Chemotherapy-induced anemia

ALL of the following

1. Hemoglobin is 10 g/dL or less

2. Member is on chemotherapy or has received chemotherapy in the past 2 months

Anemia associated with MDS

Hemoglobin is 12 g/dL or less

Anemia associated with Myeloproliferative neoplasms (Primary MF, Post-PV MF, Post-ET MF)

Hemoglobin is 11 g/dL or less

Anemia associated with RA treatment

BOTH of the following:

1. Hemoglobin is 11 g/dL or less

2. Member is prescribed concomitant therapy for the treatment of RA that is known to cause anemia (e.g., methotrexate)

Anemia associated with Hepatitis C management

BOTH of the following:

1. Hemoglobin is 11 g/dL or less

2. Member is receiving concomitant therapy with ribavirin and EITHER of the following

a. Interferon-alfa

b. Peg-interferon alfa

Methoxy polyethylene glycol-epoetin beta (Mircera)

Anemia due to CKD

EITHER of the following:

1. On dialysis: hemoglobin is 11 g/dL or less

2. Not on dialysis: hemoglobin is 10 g/dL or less

Hemoglobin level should be current (i.e., within last 30 days)

ESA, erythropoiesis stimulating agent; CKD, chronic kidney disease; MDS, myelodysplastic syndrome; MF, myelofibrosis: Post-PV MF, post polycythemia vera myelofibrosis; Post-ET MF, post essential thrombocythemia myelofibrosis; RA, rheumatoid arthritis

Approval duration for continuation

• Anemia of CKD: 180 days

• All other indications: 90 days

Erythropoietin, darbepoetin, and methoxy polyethylene glycol-epoetin beta are considered experimental or investigational for the following indications because these conditions are not supported by the peer reviewed medical literature (not an all-inclusive list):

1. Anemia in Gaucher’s disease

2. Anemia in Castleman’s disease

3. Sickle cell anemia

4. Sepsis-associated anemia

5. Anemia of cancer not related to cancer treatment

6. Any anemia associated only with radiotherapy.

DOSAGE/ADMINISTRATION:

THIS INFORMATION IS PROVIDED FOR INFORMATIONAL PURPOSES ONLY AND SHOULD NOT BE USED AS A SOURCE FOR MAKING PRESCRIBING OR OTHER MEDICAL DETERMINATIONS. PROVIDERS SHOULD REFER TO THE MANUFACTURER’S FULL PRESCRIBING INFORMATION FOR DOSAGE GUIDELINES AND OTHER INFORMATION RELATED TO THIS MEDICATION BEFORE MAKING ANY CLINICAL DECISIONS REGARDING ITS USAGE.

Iron status should be evaluated in all persons before and during ESA treatment and iron repletion should be maintained. Prior to therapy initiation, other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) should be corrected. Additionally, ESAs should not be initiated in persons with a hemoglobin of 10 g/dL or greater.

The FDA-approved indications and initial recommended doses for erythropoiesis stimulating agents (ESAs) are listed in Table 3. When initiating therapy for persons with CKD, hemoglobin levels should be monitored at least weekly until stable and then monthly thereafter. Both epoetin alfa products and darbepoetin alfa are indicated for treatment of anemia due to the effects of concomitant myelosuppressive therapy. Initiation should only occur in persons with hemoglobin less than 10 g/dL and if there is a minimum of two additional months of planned chemotherapy.

TABLE 3:

FDA-approved Indications and Recommended Dosing

Indication

Recommended Dosing

Epoetin alfa (i.e., Procrit and Epogen)

Anemia due to CKD†

• Initial: 50-100 Units/kg 3 times weekly (adults) and 50 Units/kg 3 times weekly (children on dialysis)

• Maintenance: individualize dose

Anemia due to Zidovudine in HIV-Infected persons

100 Units/kg 3 times weekly

Anemia due to effects of concomitant myelosuppressive chemotherapy‡

• Adults: 40,000 Units weekly or 150 Units/kg 3 times weekly

• Children (5 years or older): 600 Unit/kg weekly

To reduce allogeneic RBC transfusions in persons undergoing elective, non-cardiac, non-vascular surgery

EITHER of the following

• 300 Units/kg/day for 15 days total (10 days before surgery, day of surgery, and for 4 days after surgery

• 600 Units/kg weekly (administered as 4 doses on 21, 14, and 7 days before surgery and on the day of surgery.

Darbepoetin alfa (Aranesp)

CKD on dialysis

• 0.45 mcg/kg IV* or SQ weekly OR

• 0.75 mcg/kg IV* or SQ every 2 weeks

CKD not on dialysis

• 0.45 mcg/kg IV or SQ every 4 weeks

Anemia due to effects of concomitant myelosuppressive chemotherapy‡

• 2.25 mcg/kg SQ weekly

• 500 mcg SQ every 3 weeks

Methoxy polyethylene glycol-epoetin beta (Mircera)

CKD on dialysis

• 0.6 mcg/kg IV* or SQ every 2 weeks.

• Once Hgb is stabilized, the dose may be administered once monthly at a dose twice that of the every-two-week dose

CKD not on dialysis

• 0.6 mcg/kg IV or SQ every 2 weeks.

• Once Hgb is stabilized, the dose may be administered once monthly at a dose twice that of the every-two-week dose

† On dialysis and not on dialysis; ‡ a minimum of two additional months of chemotherapy should be planned; * IV recommended in persons on hemodialysis; CKD, chronic kidney disease; HIV, human immunodeficiency virus; RBC, red blood cell; IV, intravenous; SQ, subcutaneous

Dose Adjustments

A. Anemia due to CKD

*****All ESAs: Continued administration should be based on the individual’s response to therapy (e.g., hemoglobin levels). The dose should not be increased more frequently than once every 4 weeks for persons with CKD. Avoid frequent dose adjustments

1. Rapid hemoglobin rise: if hemoglobin rises more than 1 g/dL in a 2-week period, reduce the dose by 25% or more as needed to reduce rapid responses.

2. Inadequate responses: if hemoglobin does not rise by more than 1 g/dL after 4 weeks of therapy, increase the dose by 25%. Of note, for persons who do not respond adequately over a 12 week period, further dose escalation is unlikely to improve response and may increase risks.

3. Dose interruption: If hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose.

B. Anemia due to concomitant myelosuppressive chemotherapy

1. Epoetin alfa (Procrit and Epogen)

a. Dose Reduction: reduce by 25% if EITHER of the following:

- Hemoglobin rises more than 1 g/dL in any 2 week period

- Hemoglobin rises to a level need to avoid RBC transfusion

b. Dose Interruption: withhold dose if hemoglobin exceeds a level needed to avoid RBC transfusion. Reinitiate at a dose of 25% below the previous dose when hemoglobin approaches a level where RBC transfusions may be required.

c. Dose Increase: after initial 4 weeks of therapy, if hemoglobin increases by less than 1 g/dL AND remains below 10 g/dL, increase dose to:

- 300 Units/kg three times per week OR 60,000 Units weekly in adults

- 900 Units/kg (max 60,000 units) weekly in children

- If no response as measure by hemoglobin levels or if RBC transfusions are still required after 8 weeks, discontinue epoetin alfa.

2. Darbepoetin alfa (Aranesp): Table 3 provides the recommended dose adjustments

Table 4:

Darbepoetin alfa Recommended Dose Adjustments for Treatment of Anemia Due to Concomitant Myelosuppressive Chemotherapy

Dose Adjustment

Weekly Schedule

Every 3 Week Schedule

Either of the following:

• If hemoglobin increases greater than 1 g/dL in any 2-week period

• If hemoglobin reaches a level needed to avoid RBC transfusion

Reduce dose by 40%

Reduce dose by 40%

If hemoglobin exceeds a level needed to avoid RBC transfusion

• Withhold dose until hemoglobin approaches a level where RBC transfusions may be required

• Reinitiate at a dose 40% below the previous dose

• Withhold dose until hemoglobin approaches a level where RBC transfusions may be required

• Reinitiate at a dose 40% below the previous dose

If hemoglobin increases by less than 1 g/dL and remains below 10 g/dL after 6 weeks of therapy

Increase dose to 4.5 mcg/kg/week

No dose adjustment

• If there is no response as measured by hemoglobin levels or if RBC transfusions are still required after 8 weeks of therapy

• Following completion of a chemotherapy course

Discontinue

Discontinue

Anemia due to zidovudine treatment in HIV infected persons: Epoetin alfa ONLY

Dose increase: if hemoglobin does not increase after 8 weeks of therapy, increase dose by approximately 50-100 Units/kg at 4- to 8-week intervals until hemoglobin reaches a level needed to avoid RBC transfusions or 300 Units/kg

Dose interruption: hold therapy if hemoglobin exceeds 12 g/dL. Resume at a dose 25% below the previous dose when hemoglobin declines to less than 11 g/dL.

Discontinuation: discontinue if an increase in hemoglobin is not achieved at a dose of 300 Units/kg for 3 weeks.

Drug Availability:

Epoetin alfa (Epogen and Procrit): supplied as single-dose and multi-dose vials

1. Single-dose vials: 2000-, 3000-, 4000-, 10,000, and 40,000 Units/mL

2. Multi-dose vials (contain benzyl alcohol): 20,000 Units/2 mL and 20,000 Units/mL

Darbepoetin alfa (Aranesp): supplied as single-dose vials and single-dose pre-filled syringes

1. Single-dose vials: 25-, 40-, 60-, 100-, 200-, 300-, and 500 mcg/mL; 150 mcg/0.75 mL

2. Single-dose pre-filled syringes: 10 mcg/0.4 mL, 25 mcg/0.42 mL, 40 mcg/0.4 mL, 60 mcg/0.3 mL, 100 mcg/0.5 mL, 150 mcg/0.3 mL, 200 mcg/0.4 mL, 300 mcg/0.6 mL, and 500 mcg/1 mL

Methoxy polyethylene glycol-epoetin beta (Mircera): supplied as single-use prefilled syringes.

o 30 mcg/0.3 mL, 50 mcg/0.3 mL, 75 mcg/0.3 mL, 100 mcg/0.3 mL, 120 mcg/0.3 mL 150 mcg/0.3 mL, 200 mcg/0.3 mL, 250 mcg/0.3 mL, and 360 mcg/0.6 mL.

PRECAUTIONS:

Boxed Warning (all ESAs)

ESAs increase the risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access and tumor progression or recurrence.

• Chronic Kidney Disease

o In controlled trials, subjects experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a hemoglobin level of greater than 11 g/dL.

o No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks.

o Use the lowest ESA dose sufficient to reduce the need for RBC transfusions

• Cancer

o ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies of subjects with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers.

o Use the lowest dose to avoid RBC transfusions.

o Use ESAs only for anemia from myelosuppressive chemotherapy.

o ESAs are not indicated for persons receiving myelosuppressive chemotherapy when the anticipated outcome is cure.

o Discontinue ESA therapy following the completion of a chemotherapy course.

• Peri-surgery

o Due to increased risk of deep venous thrombosis (DVT), DVT prophylaxis is recommended

Contraindications

• All ESAs

o Uncontrolled hypertension

o Pure red cell aplasia (PRCA) that begins after treatment with epoetin or other erythropoietin protein drugs

o Serious allergic reactions to the specified ESA

• Epoetin alfa (Epogen and Procrit)

o Use of the multi-dose vials in neonates, infants, pregnant women, and nursing mothers

Precautions/Warnings

All ESAs

o Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism: Using ESAs to target a hemoglobin level of greater than 11 g/dL increases the risk of serious adverse cardiovascular reactions and has not been shown to provide additional benefit. Use caution in persons with coexistent cardiovascular disease and stroke.

o Increased mortality and/or increased risk of tumor progression or recurrence in persons with cancer.

o Hypertension: Control hypertension prior to initiating and during treatment with erythropoietin.

o Seizures: erythropoietin increases the risk for seizures in persons with CKD. Increase monitoring of these individuals for changes in seizure frequency or premonitory symptoms

o PRCA: If severe anemia and low reticulocyte count develop during erythropoiesis treatment, withhold erythropoiesis and evaluate for PRCA

BILLING/CODING INFORMATION:

HCPCS Coding:

J0881

Injection, darbepoetin alfa, 1 microgram (Non-ESRD use)

J0882

Injection, darbepoetin alfa, 1 microgram (for ESRD on dialysis)

J0885

Injection, epoetin alfa, (for non-ESRD use), 1000 units

J0887

Injection, epoetin beta, 1 microgram, (for ESRD on dialysis)

J0888

Injection, epoetin beta, 1 microgram, (for non-ESRD use)

Q4081

Injection, epoetin alfa, 100 Units (for ESRD on dialysis)

ICD-10 Diagnoses Codes That Support Medical Necessity:

B18.2

Chronic viral hepatitis C

B19.20

Unspecified viral hepatitis C without hepatic coma

B20

Human immunodeficiency virus [HIV] disease

C00.0 – C00.9

Malignant neoplasm of lip

C01

Malignant neoplasm of base of tongue

C02.0 – C02.9

Malignant neoplasm of other and unspecified parts of tongue

C03.0 – C03.9

Malignant neoplasm of gum

C04.0 – C04.9

Malignant neoplasm of floor of mouth

C05.0 – C05.9

Malignant neoplasm of palate

C06.0 – C06.9

Malignant neoplasm of other and unspecified parts of mouth

C07

Malignant neoplasm of parotid gland

C08.0 – C08.9

Malignant neoplasm of other and unspecified major salivary glands

C09.0 – C09.9

Malignant neoplasm of tonsil

C10.0 – C10.9

Malignant neoplasm of oropharynx

C11.0 – C11.9

Malignant neoplasm of nasopharynx

C12

Malignant neoplasm of pyriform sinus

C13.0 – C13.9

Malignant neoplasm of hypopharynx

C14.0 – C14.8

Malignant neoplasm of other and ill-defined sites in the lip, oral cavity and pharynx

C15.3 – C15.9

Malignant neoplasm of esophagus

C16.0 – C16.9

Malignant neoplasm of stomach

C17.0 – C17.9

Malignant neoplasm of small intestine

C18.0 – C18.9

Malignant neoplasm of colon

C19

Malignant neoplasm of rectosigmoid junction

C20

Malignant neoplasm of rectum

C21.0 – C21.8

Malignant neoplasm of anus and anal canal

C22.0 – C22.9

Malignant neoplasm of liver and intrahepatic bile ducts

C23

Malignant neoplasm of gallbladder

C24.0 – C24.9

Malignant neoplasm of other and unspecified parts of biliary tract

C25.0 – C25.9

Malignant neoplasm of pancreas

C26.0 – C26.9

Malignant neoplasm of other and ill-defined digestive organs

C30.0 – C30.1

Malignant neoplasm of nasal cavity and middle ear

C31.0 – C31.9

Malignant neoplasm of accessory sinuses

C32.0 – C32.9

Malignant neoplasm of larynx

C33

Malignant neoplasm of trachea

C34.00 – C34.92

Malignant neoplasm of bronchus and lung

C37

Malignant neoplasm of thymus

C38.0 – C38.8

Malignant neoplasm of heart, mediastinum and pleura

C39.0 – C39.9

Malignant neoplasm of other and ill-defined sites in the respiratory system and intrathoracic organs

C40.0 – C40.92

Malignant neoplasm of bone and articular cartilage of limbs

C41.0 – C41.9

Malignant neoplasm of bone and articular cartilage of other and unspecified sites

C43.0 – C43.9

Malignant melanoma of skin

C44.0 – C44.9

Other malignant neoplasm of skin

C45.0 – C45.9

Mesothelioma

C46.0 – C46.9

Kaposi’s sarcoma

C47.0 – C47.9

Malignant neoplasm of peripheral nerves and autonomic nervous system

C48.0 – C48.8

Malignant neoplasm of retroperitoneum and peritoneum

C49.0 – C49.9

Malignant neoplasm of other connective and soft tissue

C49.A0 -- C49.A9

Gastrointestinal stromal tumor

C50.0 – C50.929

Malignant neoplasm of breast

C51.0 – C51.9

Malignant neoplasm of vulva

C52

Malignant neoplasm of vagina

C53.0 – C53.9

Malignant neoplasm of cervix uteri

C54.0 – C54.9

Malignant neoplasm of corpus uteri

C55

Malignant neoplasm of uterus, part unspecified

C56.0 – C56.9

Malignant neoplasm of ovary

C57.0 – C57.9

Malignant neoplasm of other and unspecified female genital organs

C58

Malignant neoplasm of placenta

C60.0 – C60.9

Malignant neoplasm of penis

C61

Malignant neoplasm of prostate

C62.00 – C62.92

Malignant neoplasm of testes

C63.0 – C63.9

Malignant neoplasm of other and unspecified male genital organs

C64.0 – C68.9

Malignant neoplasm of urinary tract

C69.0 – C69.92

Malignant neoplasm of eye and adnexa

C70.0 – C70.9

Malignant neoplasm of meninges

C71.0 – C71.9

Malignant neoplasm of brain

C72.0 – C72.9

Malignant neoplasm of spinal cord, cranial nerves and other parts of central nervous system

C73

Malignant neoplasm of thyroid gland

C74.00 – C74.92

Malignant neoplasm of adrenal gland

C75.0 – C75.9

Malignant neoplasm of other endocrine glands and related structures

C76.0 – C76.8

Malignant neoplasm of other and ill-defined sites

C77.0 – C77.9

Secondary and unspecified malignant neoplasm of lymph nodes

C78.00 – C78.89

Secondary malignant neoplasm of respiratory and digestive organs

C79.00 – C79.9

Secondary malignant neoplasm of other and unspecified sites

C80.0 – C80.2

Malignant neoplasm without specification of site

C81.00 – C81.99

Hodgkin lymphoma

C82.00 – C82.99

Follicular lymphoma

C83.00 – C83.99

Non-follicular lymphoma

C84.00 – C84.99

Mature T/NK-cell lymphomas

C85.10 – C85.99

Other specified and unspecified types of non-Hodgkin lymphoma

C86.0 – C86.6

Other specified types of T/NK-cell lymphoma

C88.0 – C88.9

Malignant immunoproliferative diseases and certain other B-cell lymphomas

C90.00 – C90.32

Multiple myeloma and malignant plasma cell neoplasms

C91.00 – C91.92

Lymphoid leukemia

C92.10

Chronic myeloid leukemia, BCR/ABL-positive, not having achieved remission

C94.0 – C94.82

Other leukemias of specified cell type

C96.0 – C96.9

Other and unspecified malignant neoplasms of lymphoid, hematopoietic and related tissue

D00.0 – D00.2

Carcinoma in situ of oral cavity, esophagus and stomach

D01.0 – D01.9

Carcinoma in situ of other and unspecified digestive organs

D02.0 – D02.4

Carcinoma in situ of middle ear and respiratory system

D03.0 – D03.9

Melanoma in situ

D04.0 – D04.9

Carcinoma in situ of skin

D05.0 – D05.99

Carcinoma in situ of breast

D06.0 – D06.9

Carcinoma in situ of cervix uteri

D07.0 – D07.69

Carcinoma in situ of other and unspecified genital organs

D09.0 – D09.9

Carcinoma in situ of other and unspecified sites

D37.0 – D37.9

Neoplasm of uncertain behavior or oral cavity and digestive organs

D38.0 – D38.6

Neoplasm of uncertain behavior of middle ear and respiratory and intrathoracic organs

D39.0 – D39.9

Neoplasm of uncertain behavior of female genital organs

D40.0 – D40.9

Neoplasm of uncertain behavior of male genital organs

D41.0 – D41.9

Neoplasm of uncertain behavior of urinary organs

D42.0 – D42.9

Neoplasm of uncertain behavior of meninges

D43.0 – D43.9

Neoplasm of uncertain behavior of brain and central nervous system

D44.0 – D44.9

Neoplasm of uncertain behavior of endocrine glands

D45

Polycythemia vera

D46.0 – D46.9

Myelodysplastic syndromes

D46.A

Refractory cytopenia with multilineage dysplasia

D46.B

Refractory cytopenia with multilineage dysplasia and ring sideroblasts

D46.C

Myelodysplastic syndrome with isolated del (5q) chromosomal abnormality

D46.Z

Other myelodysplastic syndromes

D47.0 – D47.9

Other neoplasms of uncertain behavior of lymphoid, hematopoietic and related tissue

D48.0 – D48.9

Neoplasm of uncertain behavior of other and unspecified sites

D49.0 – D49.9

Neoplasms of unspecified behavior

D50.9

Iron deficiency anemia, unspecified

D61.01 – D61.9

Other aplastic anemias and other bone marrow failure syndromes

D63.0

Anemia in neoplastic disease

D63.1

Anemia in chronic kidney disease

D63.8

Anemia in other chronic diseases classified elsewhere

D64.2

Secondary sideroblastic anemia due to drugs and toxins

D64.81

Anemia due to antineoplastic chemotherapy

D64.9

Anemia, unspecified

D75.81

Myelofibrosis

I12.0 – I12.9

Hypertensive chronic kidney disease

I13.0 – I13.2

Hypertensive heart and chronic kidney disease without heart failure

M05.40 – M06.9

Rheumatoid arthritis

N18.1 – N18.9

Chronic kidney disease

P61.2

Anemia of prematurity

Q85.00

Neurofibromatosis, unspecified

Q85.01

Neurofibromatosis, type 1

Q85.02

Neurofibromatosis, type 2

T37.5X5A – T37.5X5S

Adverse effect of antiviral drugs

T39.4X5A – T39.4X5S

Adverse effect of antirheumatics, not elsewhere classified

T45.1X5A – T45.1X5S

Adverse effect of antineoplastic and immunosuppressive drugs

Z21

Asymptomatic human immunodeficiency virus [HIV] infection status

Z41.8

Encounter for other procedures for purposes other than remedying health state

Z51.11

Encounter for antineoplastic chemotherapy

Z51.89

Encounter for other specified aftercare

REIMBURSEMENT INFORMATION:

Refer to section entitled POSITION STATEMENT.

PROGRAM EXCEPTIONS:

Federal Employee Program (FEP): Follow FEP guidelines.

State Account Organization (SAO): Follow SAO guidelines.

Medicare Part D: BCBSF has delegated to Prime Therapeutics authority to make coverage determinations for the Medicare Part D services referenced in this guideline.

Medicare Advantage Products: The following National Coverage Determination (NCD) and Local Coverage Determination (LCD) located at www.fcso.com were reviewed on the last guideline revised date: Erythropoiesis Stimulating Agents in Cancer and Related Neoplastic Conditions, (110.21), Erythropoiesis Stimulating Agents, (L36276)

DEFINITIONS:

AZT: a drug used in the treatment of Human Immunodeficiency Virus (HIV).

Chronic Renal Failure (CRF): the Glomerular Filtration Rate (GFR) is less than 20 to 25% of normal. The kidneys cannot regulate volume and solute composition and patients develop edema, metabolic acidosis and hypocalcemia.

Creatinine: an end product of metabolism, found in muscle and blood, excreted in the urine; increased quantities are found in advanced stages of renal disease.

Erythroid: pertaining to any of the cells in the developmental series ending in erythrocytes.

Erythropoietin: a protein naturally made in the kidneys, which acts on the bone marrow to stimulate the body’s production of red blood cells.

ESRD: end-stage renal disease (kidney failure).

Hematocrit: a method for determining the volume of packed red blood cells in a blood specimen.

Hemoglobin: a method for measuring the oxygen carrying capacity of the red blood cells.

Hepatitis C: a form of viral hepatitis previously referred to as non-B hepatitis. It is the most common form of blood transfusion acquired hepatitis. Risk factors include recent blood transfusion, IV drug abuse, and occupational exposure to blood products. Sexual transmission is considered rare.

Myelodysplasia: The bone marrow is not effective in producing enough red blood cells, as well as other cells, resulting in anemia.

Myelodysplastic syndrome (MDS): a bone marrow disorder that is marked especially by an abnormal reduction in one or more types of circulating blood cells due to defective growth and maturation of blood-forming cells in the bone marrow and that sometimes progresses to acute myelogenous leukemia.

Non-myeloid malignancy: a cancer of the body that is not associated with cancer of the white blood cells in the bone marrow, spleen or blood.

Renal failure: kidney failure, often requiring dialysis.

Zidovudine: AZT.

RELATED GUIDELINES:

None applicable.

OTHER:

None applicable.

REFERENCES:

  1. AASLD/IDSA/IAS–USA. Recommendations for testing, managing, and treating hepatitis C. http://www.hcvguidelines.org. Accessed March 10, 2015.
  2. Aranesp (darbepoetin alfa) [package insert]. Amgen Inc., Thousand Oaks (CA): April 2017.
  3. Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. URL www.clinicalpharmacilogy-ip.com Accessed 3/20/17.
  4. Darbepoetin alfa. In: McEvoy GK, editor. AHFS drug information 2017 [monograph on the Internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2017 [cited2017 Mar 21]. Available from: http://online.statref.com. Subscription required to view.
  5. Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006;355(20):2071-84
  6. Epoetin alfa. In: McEvoy GK, editor. AHFS drug information 2017 [monograph on the Internet]. Bethesda (MD): American Society of Health-System Pharmacists; 2017 [cited 2017 Mar 20]. Available from: http://online.statref.com. Subscription required to view.
  7. Epogen (epoetin alfa) [package insert] Amgen Inc., Thousand Oaks (CA): April 2017.
  8. Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO clinical practice guideline for anemia in chronic kidney disease. Kidney Int Suppl. 2012 Aug;2(4):279-335. [247 references]
  9. Mircera (methoxy polyethylene glycol) [package insert]. Hoffmann-La Roche Inc., San Francisco (CA): May 2016.
  10. Micromedex® Healthcare Series [Internet Database]. Greenwood Village, Colo: Thomson Healthcare. Updated periodically. Accessed 3/20/17.
  11. National Comprehensive Cancer Network (NCCN). Cancer Guidelines and Drugs and Biologics Compendium. Accessed 3/24/17..
  12. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Cancer- and Chemotherapy-induced Anemia 2.2017. Available at http://www.nccn.org/professionals/physician_gls/pdf/anemia.pdf. Accessed 3/27/17.
  13. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Myelodysplastic Syndromes 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/mds.pdf. Accessed 3/27/17.
  14. National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology: Myeloproliferative neoplasms 2.2017. Available at http://www.nccn.org/professionals/physician_gls/PDF/mpn.pdf. Accessed 3/28/17.
  15. Procrit (epoetin alfa) [package insert]. Janssen Products, LP. Horsham (PA): April 2017.
  16. Rizzo JD, Brouwers M, Hurley P, et. al. American Society of Clinical Oncology/American Society of Hematology Clinical Practice Guideline Update on the use of epoetin and darbepoetin in adult patients with cancer. J Clin Oncol 2010;20(33):4996-5010

COMMITTEE APPROVAL:

This Medical Coverage Guideline (MCG) was approved by the BCBSF Pharmacy Policy Committee on 04/12/17.

GUIDELINE UPDATE INFORMATION:

06/15/00

New Medical Coverage Guideline.

08/29/02

Reviewed with no revisions.

01/01/04

Annual HCPCS coding update.

04/01/05

Reviewed and revised: Anemia of CRF on dialysis Hgb 10 g/dl or Hct 30%, Anemia of CRF not on dialysis Hgb 11 g/dl or Hct 33%, and added continuation of coverage statement.

01/01/06

HCPCS update deleted expired code Q4055, added new code J0886.

07/15/06

Reviewed with no revisions.

10/15/06

Revised by updating ICD-9 code.

01/01/07

HCPCS update, added Q4081. MCG revised to include Medicare Part D as program exception.

08/15/07

Reviewed: Reformatted guideline, added note regarding how to proceed once HCT and HGB reach 12 and 36, renamed guideline to include Non-ESRD indications, maintain current coverage and limitations, updated dosing guidelines, added Non-ESRD code J0885, reformatted ICD-9 codes to be consistent with LCD 5984, and updated references.

03/15/08

Review and revision; consisting of renaming guideline to include darbepoetin, updated coverage criteria, updated coding, reformatted, updated references and links.

04/15/08

Revision; consisting of updating a “NOTE” for clarification and updating dosing and administration section to be consistent with coverage criteria.

09/15/08

Revision; consisting of revising boxed warning.

03/15/09

Review and revision; consisting of adding maximum doses and updating references.

06/15/09

Revision consisting of removing coverage for anemia from previous chemo in past 12 months.

10/15/09

Revision; consisting of clarifying dosages and updating coding.

01/15/10

Revision; consisting of updating codes.

04/15/10

Revision; consisting of updating codes.

05/15/10

Review and revision; consisting of clarifying position statement and updating references.

10/01/10

Revision; consisting of updating codes.

11/15/10

Revision; consisting of updating codes.

02/01/11

Revision; consisting of updating codes.

02/15/11

Revision; consisting of adding ICD-10 codes, and adding note regarding age of laboratory values.

05/15/11

Review and revision to guideline; consisting of updating references.

06/15/11

Revision to guideline; consisting of modifying coverage criteria for CRF.

08/15/11

Revision to guideline; consisting of modifying position statement and updating precautions, updates of ICD-10 codes.

01/15/12

Revision to guideline; consisting of updating dosage and administration.

05/15/12

Review and revision to guideline; consisting of updating position statement and references.

07/01/12

Revision to guideline, consisting of adding new agent and update coding.

01/01/13

Annual HCPCS Update: added HCPCS code J0890 and removed code Q2047

02/15/13

Revision to guideline; consisting of updating coding.

06/15/13

Review and revision to guideline; consisting of revising and reformatting the position statement; revising and reformatting dosage/administration and precautions sections; updating references, coding, and program exceptions

10/15/13

Revision to guideline; consisting of clarifying language for treatment of chemotherapy induced anemia.

05/15/14

Review and revision to guideline; consisting of reformatting position statement and updating references.

10/01/14

Revision to guideline; consisting of adding HCPCS codes Q9972 and Q9973.

01/01/15

Revision to guideline; consisting of annual coding update.

05/15/15

Review and revision to guideline; consisting of updating description, position statement and decision tree, dosage/administration, and references.

10/01/15

Revision to guideline consisting of coding updates and update to Program Exceptions section.

11/01/15

Revision: ICD-9 Codes deleted.

12/15/15

Revision to guideline consisting of update to the position statement.

01/01/16

Annual HCPCS coding update: deleted code J0886.

05/15/16

Review and revision to guideline; consisting of updating the position statement, dosing, coding, and references.

10/01/16

Update to ICD-10 codes.

05/15/17

Review and revision to guideline; consisting of updating the position statement, coding, and references.

06/15/17

Review and revision to guideline; consisting of updating the position statement and references.

Date Printed: June 26, 2017: 11:43 AM