Group 1 Codes:
J0881INJECTION, DARBEPOETIN ALFA, 1 MICROGRAM (NON-ESRD USE)
J0882INJECTION, DARBEPOETIN ALFA, 1 MICROGRAM (FOR ESRD ON DIALYSIS)
J0885INJECTION, EPOETIN ALFA, (FOR NON-ESRD USE), 1000 UNITS
Q4081INJECTION, EPOETIN ALFA, 100 UNITS (FOR ESRD ON DIALYSIS)
Coverage Indications, Limitations, and/or Medical Necessity
An erythropoietin stimulating agent (ESA) is an analog of erythropoietin. ESAs are biologically engineered hormones produced by recombinant DNA technology. Erythropoietin analogs contain the identical amino acid sequence as naturally occurring erythropoietin, and have the same biological effect. Primarily, the kidneys produce erythropoietin in response to hypoxia. Both erythropoietin and ESAs stimulate the bone marrow to form new red blood cells. They are used to treat anemia by elevating or maintaining the red blood cell level (as demonstrated by the hematocrit and/or hemoglobin levels), therefore decreasing anemia and the need for transfusions. Darbepoetin alfa (brand name Aranesp ®), an erythropoietin analog, differs from recombinant human erythropoietin alfa (brand name Epogen ® or Procrit ®) in having two additional N-glycosylation sites, which slows its clearance and makes its half-life two-three times longer, allowing less frequent injections. This policy will apply to new ESAs as they are approved.
Since darbepoetin alfa and epoetin alfa have a similar mode of action and their structures differ only by the number of N-linked oligosaccharides on the protein, this policy does not distinguish differences for on or off-label indications and contraindications, except for pre treatment of selective surgery where blood loss is anticipated. Several off-label uses are well-accepted clinically, as indicated by inclusion in various compendia. However, a contraindication for either ESA is binding on both. In March 2007, the FDA issued new warnings against target Hgb levels above 12 gm/dl (36% Hct) “for all patients.” The FDA also issued specific warnings against off-label use in cancer patients whose anemia is not directly linked to chemotherapy. The FDA also reminded physicians that the main endpoint in studies for on-label indications has been avoidance or reduction in transfusions. The LCD contains descriptions of specific coverage guidelines and documentation that supports medical necessity for individual patients.
CMS has a national coverage decision on both renal and non-renal uses of ESAs. This local decision elaborates on the NCD and covers some additional indications.
Erythropoietin analogs are covered for the following indications:
Treatment of anemia associated with chronic renal failure, including patients on dialysis and patients not on dialysis;
Treatment of significant anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitantly administered chemotherapy;
Treatment of anemia induced by AZT and/or other Nucleoside Reverse Transcriptase Inhibitors (NRTI) used in treatment of HIV/AIDS;
Treatment of selected patients with anemia related to myelodysplastic syndrome;
Preoperative adjuvant therapy (epoetin alfa only);
The following causes of anemia should be considered, documented, and corrected (when possible) before starting erythropoietin analog therapy for any of the covered indications:
•Underlying infection or inflammatory process
•Underlying hematological disease
•Vitamin deficiencies (e.g. folic acid or B12)
The ESA treatment is not reasonable and necessary for beneficiaries with certain clinical conditions, either because of a deleterious effect of the ESA on their underlying disease or because the underlying disease increases their risk of adverse effects related to ESA use. These conditions include:
any anemia in cancer or cancer treatment patients due to folate deficiency, B-12 deficiency, iron deficiency, hemolysis, bleeding, or bone marrow fibrosis;
the anemia associated with the treatment of acute and chronic myelogenous leukemias (CML, AML), or erythroid cancers;
the anemia of cancer not related to cancer treatment;
any anemia associated only with radiotherapy;
prophylactic use to prevent chemotherapy-induced anemia;
prophylactic use to reduce tumor hypoxia;
patients with erythropoietin-type resistance due to neutralizing antibodies; and
anemia due to cancer treatment if patients have uncontrolled hypertension.
There are rare patients whose cardiac, pulmonary or other medical diseases warrant the use of ESAs to maintain a hemoglobin/hematocrit (Hgb/Hct) higher than the target level discussed in this LCD. Documentation to support this practice must be available upon request. This does not apply to ESA therapy for anemia related to cancer chemotherapy, which follows the rules mandated by the National Coverage Decision.
During therapy with an erythropoietin analog, many patients will eventually require supplemental iron. For these patients, stores of iron should be regularly monitored to ensure transferrin saturation greater than 20% and/or serum ferritin levels greater than 100 ng/ml, in order to guide appropriate supplementation.
For patients receiving chemotherapy for non-myeloid malignancies, the goal of therapy is to maintain the Hgb/Hct at 10/30%. ESA therapy will not be reimbursed when the Hgb/Hct is greater than 10/30%. For all other indications, the goal of therapy is to maintain a stable Hgb/Hct, with a target of 10-12 gm/dl / 30%-36%. Doses must be titrated according to the patient’s response. Erythropoietin analog therapy need not be stopped completely simply due to the achievement of the target Hgb/Hct. However, judicious, appropriately timed dose adjustments are expected to prevent inappropriate increases in Hgb/Hct levels.
ESAs may be administered by intravenous or subcutaneous routes. The dosage may be dependent on several factors including the availability of iron stores, the baseline Hgb/Hct, and the presence of concurrent medical problems.
Although subcutaneous medications are generally considered to be self-administered and therefore not covered, erythropoietin analogs are covered regardless of route of administration when used within the ESRD benefit or for chronic kidney disease patients not yet on dialysis who meet the conditions below.
A.For End Stage Renal Disease (ESRD) patients on dialysis:
Diagnosis of end stage renal disease;
Anemia of ESRD should be treated to maintain a Hgb level of 10-12 gm/dl or a Hct of 30%-36%.
B.For chronic kidney disease patients NOT on dialysis:
Anemia of chronic kidney disease should be treated to maintain the Hgb level of 10-12 gm/dl or a Hct of 30%-36%.
Serum creatinine equal to or greater than 2.5, creatinine clearance less than 60 ml/min, or glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2.
C. For patients with non-myeloid malignancies where anemia is due to the effect of chemotherapy:
1. Anemia with Hgb/Hct less than 10 / 30% at initiation of therapy.
2. The starting dose for ESA treatment is the recommended FDA label starting dose, no more than 150 U/kg/three times weekly for epoetin and 2.25 mcg/kg/1 time weekly for darbepoetin alpha. Equivalent doses may be given over other approved time periods.
3. Maintenance of ESA therapy is the starting dose if the Hgb level remains below 10 gm/dl (or Hct is < 30%) 4 weeks after initiation of therapy and the rise in Hgb is = 1gm/dl (Hct = 3%).
4.For patients whose Hgb rises
5. Continued administration of the drug is not reasonable and necessary if there is a rapid rise in Hgb > 1 gm/dl (Hct >3%) over 2 weeks of treatment unless the Hgb remains below or subsequently falls to
6. The FDA labeling states that ESAs are indicated for treatment of anemia of malignancy when receiving concomitant chemotherapy, which means during an established course of planned chemotherapy. It will also cover ESAs for eight weeks following the final dose of myelosuppressive chemotherapy in a chemotherapy regimen.
D. For patients with anemia related to AZT and/or other Nucleoside Reverse Transcriptase Inhibitors (NRTI) therapy for HIV/AIDS:
The goal of therapy is to maintain a stable Hgb/Hct, with a Hgb target of 10-12 gm/dl or a Hct of 30%-36%
E. For patients with myelodysplastic syndrome:
Low risk myelodysplasia
Pretreatment *erythropoietin levels of 500 or less
The goal of therapy is to avoid transfusions by maintaining a stable Hgb/Hct, with a target of 10-12 gm/dl / 30%-36%. If after two months of treatment, there is no significant increase in Hgb/Hct and/or a significant decrease in transfusion requirements, erythropoietin analogs therapy should be stopped.
*For ESA therapy initiated on or after 12/1/2007, this A/B MAC requires an EPO level less than or equal to 500 IU/L.
F. Preoperative adjuvant therapy: epoetin alfa for patients who:
1. Are undergoing hip or knee surgery;
2. Have an anemia with a Hgb between 10 and 13 gm/dl;
3. Are not a candidate for autologous blood transfusion;
4. Are expected to lose more than two units of blood; and
5. Have been evaluated to ensure that their anemia is due to chronic disease.
NOTE: This ESA LCD is for Epoetin and Darbepoetin Alfa only. Other products that may be used for anemia of ESRD will be covered for their FDA approved indications.
Bill Type Codes:
Contractors may specify Bill Types to help providers identify those Bill Types typically used to report this service. Absence of a Bill Type does not guarantee that the policy does not apply to that Bill Type. Complete absence of all Bill Types indicates that coverage is not influenced by Bill Type and the policy should be assumed to apply equally to all claims.
012xHospital Inpatient (Medicare Part B only)
022xSkilled Nursing – Inpatient (Medicare Part B only)
023xSkilled Nursing – Outpatient
071xClinic – Rural Health
072xClinic – Hospital Based or Independent Renal Dialysis Center
077xClinic – Federally Qualified Health Center (FQHC)
085xCritical Access Hospital
Contractors may specify Revenue Codes to help providers identify those Revenue Codes typically used to report this service. In most instances Revenue Codes are purely advisory. Unless specified in the policy, services reported under other Revenue Codes are equally subject to this coverage determination. Complete absence of all Revenue Codes indicates that coverage is not influenced by Revenue Code and the policy should be assumed to apply equally to all Revenue Codes.
*Revenue code 0636 relates to HCPCS code. Indicate HCPCS code J0885 in Form Locator 44 of the UB-04 form. The specified units of service to be reported are to be in thousands (1000s), rounded to the nearest thousand.
Revenue codes only apply to providers who bill these services to Part A.
0634Pharmacy – Erythropoietin (EPO)0635Pharmacy – Erythropoietin (EPO)>=10,000 Units
0636Pharmacy – Drugs Requiring Detailed Coding
ICD-10 Codes that Support Medical Necessity
I12.0Hypertensive chronic kidney disease with stage 5 chronic kidney disease or end stage renal disease
I12.9*Hypertensive chronic kidney disease with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease
I13.0*Hypertensive heart and chronic kidney disease with heart failure and stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease
I13.10*Hypertensive heart and chronic kidney disease without heart failure, with stage 1 through stage 4 chronic kidney disease, or unspecified chronic kidney disease
I13.11Hypertensive heart and chronic kidney disease without heart failure, with stage 5 chronic kidney disease, or end stage renal disease
I13.2Hypertensive heart and chronic kidney disease with heart failure and with stage 5 chronic kidney disease, or end stage renal disease
N18.3Chronic kidney disease, stage 3 (moderate)
N18.4Chronic kidney disease, stage 4 (severe)
N18.5Chronic kidney disease, stage 5
C00.0Malignant neoplasm of external upper lip
C00.1Malignant neoplasm of external lower lip
C00.3Malignant neoplasm of upper lip, inner aspect
C00.4Malignant neoplasm of lower lip, inner aspect
C00.8Malignant neoplasm of overlapping sites of lip
C01Malignant neoplasm of base of tongue
C02.0Malignant neoplasm of dorsal surface of tongue
C02.1Malignant neoplasm of border of tongue
C02.2Malignant neoplasm of ventral surface of tongue
C02.4Malignant neoplasm of lingual tonsil
C02.8Malignant neoplasm of overlapping sites of tongue
C03.0Malignant neoplasm of upper gum
C03.1Malignant neoplasm of lower gum
C04.0Malignant neoplasm of anterior floor of mouth
C04.1Malignant neoplasm of lateral floor of mouth
C04.8Malignant neoplasm of overlapping sites of floor of mouth
C05.0Malignant neoplasm of hard palate
C05.1Malignant neoplasm of soft palate
C05.2Malignant neoplasm of uvula
C05.8Malignant neoplasm of overlapping sites of palate
C06.0Malignant neoplasm of cheek mucosa
C06.1Malignant neoplasm of vestibule of mouth
C06.2Malignant neoplasm of retromolar area
C06.89Malignant neoplasm of overlapping sites of other parts of mouth
C07Malignant neoplasm of parotid gland
C08.0Malignant neoplasm of submandibular gland
C08.1Malignant neoplasm of sublingual gland
C09.0Malignant neoplasm of tonsillar fossa
C09.1Malignant neoplasm of tonsillar pillar (anterior) (posterior)
C09.8Malignant neoplasm of overlapping sites of tonsil
C10.0Malignant neoplasm of vallecula
C10.1Malignant neoplasm of anterior surface of epiglottis
C10.2Malignant neoplasm of lateral wall of oropharynx
C10.3Malignant neoplasm of posterior wall of oropharynx
C10.4Malignant neoplasm of branchial cleft
C10.8Malignant neoplasm of overlapping sites of oropharynx
C11.0Malignant neoplasm of superior wall of nasopharynx
C11.1Malignant neoplasm of posterior wall of nasopharynx
C11.2Malignant neoplasm of lateral wall of nasopharynx
C11.3Malignant neoplasm of anterior wall of nasopharynx
C11.8Malignant neoplasm of overlapping sites of nasopharynx
C12Malignant neoplasm of pyriform sinus
C13.0Malignant neoplasm of postcricoid region
C13.1Malignant neoplasm of aryepiglottic fold, hypopharyngeal aspect
C13.2Malignant neoplasm of posterior wall of hypopharynx
C13.8Malignant neoplasm of overlapping sites of hypopharynx
C14.2Malignant neoplasm of Waldeyer’s ring
C14.8Malignant neoplasm of overlapping sites of lip, oral cavity and pharynx
C15.3Malignant neoplasm of upper third of esophagus
C15.4Malignant neoplasm of middle third of esophagus
C15.5Malignant neoplasm of lower third of esophagus
C15.8Malignant neoplasm of overlapping sites of esophagus
C16.0Malignant neoplasm of cardia
C16.1Malignant neoplasm of fundus of stomach
C16.2Malignant neoplasm of body of stomach
C16.3Malignant neoplasm of pyloric antrum
C16.4Malignant neoplasm of pylorus
C16.8Malignant neoplasm of overlapping sites of stomach
C17.0Malignant neoplasm of duodenum
C17.1Malignant neoplasm of jejunum
C17.2Malignant neoplasm of ileum
C17.3Meckel’s diverticulum, malignant
C17.8Malignant neoplasm of overlapping sites of small intestine
C18.0Malignant neoplasm of cecum
C18.1Malignant neoplasm of appendix
C18.2Malignant neoplasm of ascending colon
C18.3Malignant neoplasm of hepatic flexure
C18.4Malignant neoplasm of transverse colon
C18.5Malignant neoplasm of splenic flexure
C18.6Malignant neoplasm of descending colon
C18.7Malignant neoplasm of sigmoid colon
C18.8Malignant neoplasm of overlapping sites of colon
C19Malignant neoplasm of rectosigmoid junction
C20Malignant neoplasm of rectum
C21.1Malignant neoplasm of anal canal
C21.2Malignant neoplasm of cloacogenic zone
C21.8Malignant neoplasm of overlapping sites of rectum, anus and anal canal
C22.0Liver cell carcinoma
C22.1Intrahepatic bile duct carcinoma
C22.3Angiosarcoma of liver
C22.4Other sarcomas of liver
C22.7Other specified carcinomas of liver
C22.9Malignant neoplasm of liver, not specified as primary or secondary
C23Malignant neoplasm of gallbladder
C24.0Malignant neoplasm of extrahepatic bile duct
C24.1Malignant neoplasm of ampulla of Vater
C24.8Malignant neoplasm of overlapping sites of biliary tract
C25.0Malignant neoplasm of head of pancreas
C25.1Malignant neoplasm of body of pancreas
C25.2Malignant neoplasm of tail of pancreas
C25.3Malignant neoplasm of pancreatic duct
C25.4Malignant neoplasm of endocrine pancreas
C25.7Malignant neoplasm of other parts of pancreas
C25.8Malignant neoplasm of overlapping sites of pancreas
C26.1Malignant neoplasm of spleen
C26.9Malignant neoplasm of ill-defined sites within the digestive system
C30.0Malignant neoplasm of nasal cavity
C30.1Malignant neoplasm of middle ear
C31.0Malignant neoplasm of maxillary sinus10>10>1>