DOCSLIB.ORG

Clinical Use of Esas in Low-Risk Myelodysplastic Syndromes

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Clinical Use of Esas in Low-Risk Myelodysplastic Syndromes A. Di Veroli, Bellis ED, Rossi V, Biagi A, Rapisarda V, Maurillo L, Principe MID, Voso MT, Journal of Venditti A, Buccisano F. J Rare Dis Res Treat. (2017) 2(6): 41-44 Rare Diseases Research www.rarediseasesjournal.com & Treatment Mini Review Open Access Clinical use of ESAs in Low-Risk Myelodysplastic Syndromes Ambra Di Veroli1, Eleonora De Bellis1, Valentina Rossi1, Annalisa Biagi1, Vito Rapisarda1, Luca Maurillo1, Maria Ilaria Del Principe1, Maria Teresa Voso1, Adriano Venditti1 and Francesco Buccisano1 1Hematology, Department of Biomedicine and Prevention, Tor Vergata University, Rome, Italy Article Info Introduction Article Notes Myelodysplastic syndromes (MDS) are a heterogeneous group Received: July 27, 2017 of clonal hematological diseases characterized by ineffective Accepted: October 21, 2017 maturation of blood cells progenitors. The incidence of MDS is *Correspondence: Dr. Ambra Di Veroli, MD Ematologia, Dipartimento di Biomedicina e Prevenzione the years and the lack of an systematic registration of patients. Università di Roma Tor Vergata Adifficult recent to publication assess because based of onthe thechange SEER of databasediagnostic suggests criteria overthat Via Montpellier 1 –00133 Rome, Italy the incidence of MDS is as high as 75 per 100,000 persons aged Tel: +39 06 20903228 Fax:+390620903221; Email: [email protected] predominantly a disease of the elderly and have a higher incidence ≥65 years. Available data consistently suggest that MDS are © 2017 A. Di Veroli. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License. among white male people; approximately 86% of patients1. The impairment with MDS ofwere hematopoietic aged ≥60 years bone at marrow diagnosis function (median determines age, 76 years), variable and grades only of6% peripheral of cases were cytopenias diagnosed and in patientsa propensity ≤50 years to evolve into acute myeloid leukemia (AML). Prognosis is poor for patients with MDS, with 3-year survival rates estimated at less than 50%. Anemia duringis observed clinical in course.approximately In low-risk 70% MDS, of MDSanemia patients is the majorat diagnosis, clinical leading to a relevant transfusion dependence in >80% of patients more than other cytopenias, is associated with an increase risk of transfusion–relatedproblem and may give complications, rise to significant alloimmunization, morbidity. This iron condition, overload, For these reasons one of the major goal of MDS treatment is the improvementcardiac failure of and anemia a significant with the impairment aim of avoiding of quality or delaying of life chronic (QoL). transfusional support. Erythropoiesis stimulating factors (ESAs), alone or in combination with other grow factors, are indicated to treat anemia in low risk MDS and widely used in this setting with results of ESAs therapy in treating anemia in low risk MDS patients andencouraging their impact results. on the In naturalthis paper course we ofwill the briefly disease. review the main Pathogenesis of Anemia in Mds Pathogenesis of MDS is a multistep process occurring at level of totipotent hemopoietic stem cells (HSC). Several factors may contribute to ineffective hematopoiesis in MDS: 1) an abnormal activation of proapoptotic signals in progenitor cells; 2) a disregulation of signal transduction causing an excess of cells; 3) a limited responsiveness to erythroid-stimulating growth factorsproinflammatory2-67,8. Different cytokines studies andhave an beenaltered conducted immune responseson erythroid in T progenitors (Erythroid colony forming units-CFU-E and Erythroid Page 41 of 44 A. Di Veroli, Bellis ED, Rossi V, Biagi A, Rapisarda V, Maurillo L, Principe MID, Voso MT, Journal of Rare Diseases Research & Treatment Venditti A, Buccisano F. J Rare Dis Res Treat. (2017) 2(6): 41-44 burst-forming units-BFU-E) to explain the pathogenesis Table 1. of anemia. It is well known that erythroid progenitors of Study Most significant ESAs studiesN°pts in low risk MDS.ORR MDS patients show an altered formation of CFU-E and Rossi Ferrini, P.R (1998) 87 36% 9 BFU-E in response to endogenous EPO , and a profound Terpos, E.(2002) 281 45·1% alteration of other functional parameters such as EPO- Park, S. (2008) 403 50% dependent DNA synthesis and induction of GATA-1 binding Golshayan AR (2007) 1587 39·5% activity10. Moreover a correlation was observed between Jädersten, M (2008) 121 39% a STAT5defective activation after EPO stimulation (with conserved STAT5 phosphorylation upon stimulation Table 1 summarizes the most important ESAs studies in with IL3) and a block in the EPO signal transduction pathway at an early stage of erythroid development9. Furthermore, dyserythropoiesis has been directly linked MDS. There is general agreement that ESAs have a 40%– to greater expression of proapoptotic molecules as the low50% riskresponse MDS rate,with ina termsmedian of durationerythroid of hematological response of transmembrane mediator of apoptotic cell death Fas/CD95 approximatelyimprovement as2 yearsdefined21. There by IWG is no response difference criteria, between in in the glycophorin A subpopulation11. In the last decades different ESAs formulations. Current guidelines developed the application of sophisticated genetic and molecular by the National Comprehensive Cancer Network22, tools at diagnosis and at progression have allowed European LeukemiaNet (ELN)23, and European Society for to better understanding the pathogenesis of anemia. Medical Oncology (ESMO)23 are generally consistent with Cytogenetic and molecular analyses have demonstrated that both normal and malignant precursor erythroid cells MDS. Pre-emptive treatment of asymptomatic patients are stimulated by cytokine therapy. More recently the role isthe not management recommended of patients and treatment with lower-risk should benon-del(5q) reserved of Ten-Eleven-Translocation 2 and 3 (TET2 and TET3) genes for those with symptomatic anemia. In addition there is in human erythropoiesis has been demonstrated, opening a limited role for addition of G-CSF based on data from a a new scenario in understanding this phenomenon in randomized phase 3 study that evaluated the role of G-CSF MDS. TET2 encodes a member of TET family enzymes and found no difference between EPO versus EPO plus that alters the epigenetic status of DNA by oxidizing G-CSF25 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). as which patients are the ideal candidates to treatment and . However, many issues still need to be clarified, such TET3 encodes a dioxygenase that catalyzes the conversion which is the best schedule available. Predictive Models of ESAs Response into 5-hydroxymethylcytosine (5hmC) and plays a key role It has become increasingly evident that treatment with of the modified genomic base 5-methylcytosine12 (5mC) in reprogramming epigenetic chromatin . Knockdown r-Hu-EPO should become “patient oriented” and different experiments have demonstrated that suppression of types, schedules, and duration of treatment have to be TET3 in CD34+ cells markedly impaired terminal eythroid likely predict, for each individual patient, the best chance effect on erytrhoid progenitors. TET2 knockdown led designed according to the specific criteria which most differentiation as reflected by increased apoptosis without to hyperproliferation and impaired differentiation of Hellström-Lindberg and al.13, included 94 patients across 12 erythroid progenitors . threeof response. ESA studies The firstto determine predictive predictors model, developed of response by Clinical Use of ESAs to a combination of ESAs and G-CSF. The model was able Given the normal presence of EPO receptors on to discriminate 3 classes of patients with a probability progenitor cells in MDS patients, erythropoiesis stimulating agents (ESAs) may represent an useful tool to overcome Patients with low transfusion needs (< 2 units packed the maturation arrest and restore a normal red blood redof response blood cell to ESAstransfusions of 94%, [pRBC]17%, and monthly) 11%, respectively. and a low cells production. ESAs treatment has been demonstrated baseline serum erythropoietin level (less than 500 IU) in clinical trials to substantially reduce or eliminate with erythropoietin and darbepoetin alfa in low-risk MDS andhad aa high74% serum chance erythropoietin of responding level to (>ESAs, 500 IU)while had those only transfusion need in roughly 60% of the patients. Studies with high transfusion needs (≥ 2 units pRBC per month) asidentified International transfusion Working independence Group criteria: as majorsignificant erythroid for werea 7% reported:chance of lowresponding. IPSS score, Further baseline studies haemoglobin, have tried noto QOL and showed primarily erythroid responses defined excessrefine thisof blasts predictive in bone model. marrow, Other iron predictors status ofat responsebaseline, granulocyteshematological13-19 improvement.Recombinant in 29%-47%Human (HI-E)Erythropoietin and minor subtypes RA (refractory anemia) and RARS (RA with ring (R-Hu-EPO)HI-E in 26%-30% alpha withoutand darbepoetinalpha improvements inare platelets the more or sideroblasts)WHO classification, and ESA karyotype,-naïve at baseline hypoplastic. Abone model marrow, based 20. on IPSS-R score, serum EPO, and serum26,29 ferritin level may frequently used ESAs for the treatment of anemia in MDS Page 42 of 44 A. Di Veroli, Bellis ED, Rossi V, Biagi A, Rapisarda V, Maurillo L, Principe MID, Voso MT, Journal of Rare Diseases Research & Treatment Venditti
Load more

Recommended publications
  • Myelodysplastic Syndromes
    MYELODYSPLASTIC SYNDROMES TREATMENT REGIMENS (Part 1 of 3) Clinical Trials: The National Comprehensive Cancer Network recommends cancer patient participation in clinical trials as the gold standard for treatment. Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. First-Line Treatment1 Note: All recommendations are Category 2A unless otherwise indicated. Relatively Lower-Risk Patientsa,b Symptomatic Anemia With del(5q) ± One Other Cytogenetic Abnormality (except those involving chromosome 7) REGIMEN DOSING Lenalidomide2-5,c Days 1–21: Lenalidomide 10mg orally once daily. Repeat cycle every 28 days (or 28 days monthly). Assess response 2–4 months after initiation of treatment.
    [Show full text]
  • OMONTYS® Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION ---------------------DOSAGE FORMS AND STRENGTHS---------------------- These highlights do not include all the information needed to use Dosage Form Strengths OMONTYS® safely and effectively. See full prescribing information for OMONTYS. Single use vials 2 mg/0.5 mL, 3 mg/0.5 mL, (preservative-free) 4 mg/0.5 mL, 5 mg/0.5 mL, and OMONTYS® (peginesatide) Injection, 6 mg/0.5 mL for intravenous or subcutaneous use Single use pre-filled syringes 1 mg/0.5 mL, 2 mg/0.5 mL, Initial U.S. Approval: 2012 (preservative-free) 3 mg/0.5 mL, 4 mg/0.5 mL, 5 mg/0.5 mL, and 6 mg/0.5 mL WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL Multiple use vials 10 mg/mL and 20 mg/2 mL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, (with preservative) THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE -------------------------------CONTRAINDICATIONS------------------------------ See full prescribing information for complete boxed warning. Uncontrolled hypertension (4). Chronic Kidney Disease: In controlled trials, patients experienced greater risks for -----------------------WARNINGS AND PRECAUTIONS------------------------ death, serious adverse cardiovascular reactions, and stroke Increased Mortality, Myocardial Infarction, Stroke, and when administered erythropoiesis-stimulating agents (ESAs) Thromboembolism: Using ESAs to target a hemoglobin level of to target a hemoglobin level of greater than 11 g/dL (5.1). greater than 11 g/dL increases the risk of serious adverse No trial has identified a hemoglobin target level, ESA dose, or cardiovascular reactions and has not been shown to provide dosing strategy that does not increase these risks (5.1). additional benefits (5.1).
    [Show full text]
  • Final List of R-DNA Based Drugs Approved in the Country.Xlsx
    S. Date of Permission Name of the Name of the firm Indication Dosage Form & Strength No. Permission No. Drug For the treatment of type -I and Type -II diabetes mellitus 40 IU/ml (10 ml vial), 100 IU/ml (10 ml vial), 100 Insulin Glargine 1 Wockhardt Limited 22.02.2007 MF-7206/07 patients who required basal IU/ml (3 ml cartridge), 100 IU/ml (3 ml disposable 100 IU (long acting) insulin for the pens) control of hyperglycemia. Solution for injection in vial or prefilled syringe Strength: 1. Each 1 mL of single dose vial contains Treatment of anaemia 25mcg, 40mcg, 60mcg, 100mcg, 200mcg, 300mcg associated with chronic renal and 500mcg 2. Each 0.75 mL of single dose vial failure, including patients on contains 150mcg 3. Each 0.3 mL of single dose dialysis and patients not on prefilled syringe contains 60mcg and 150mcg 4. Dr. Reddy's 23-Mar-10 MF-246/10 dialysis and for the treatment 2 Darbepoetin alfa Each 0.4 mL of single dose prefilled syringe Laboratories Ltd. 20-Jul-10 BULK-668/10 of anaemia in patients with contains 40mcg and 200mcg 5. Each 0.42 mL of non-myeloid malignancies, single dose prefilled syringe contains 25mcg 6. Each where anaemia is due to the 0.5 mL of single dose prefilled syringe contains effect of concomitantly 100mcg 7. Each 0.6 mL of single dose prefilled administered chemotherapy syringe contains 300mcg 8. Each 1 mL of single dose prefilled syringe contains 500mcg Gennova For prevention of neutropenia Pegfilgrastim Prefilled syringe for injection contains Pegfilgrastim 3 Biopharmaceuticals 29-Jan-10 MF-104/10 in the patient receiving cancer (peg-r-hu-GCSF) 6 mg/0.6 mL Ltd.
    [Show full text]
  • Presentation Title
    The COMMANDS trial: a phase 3 study of the efficacy and safety of luspatercept versus epoetin alfa for the treatment of anemia due to Revised International Prognostic Scoring System Very Low-, Low-, or Intermediate-risk myelodysplastic syndromes in erythropoiesis stimulating agent-naive patients who require red blood cell transfusions Matteo Della Porta,1,2 Uwe Platzbecker,3 Valeria Santini,4 Guillermo Garcia-Manero,5 Rami S. Komrokji,6 Rodrigo Ito,7 Pierre Fenaux8 1Cancer Center IRCCS Humanitas Research Hospital, Milan, Italy; 2Department of Biomedical Sciences, Humanitas University, Milan, Italy; 3Medical Clinic and Policlinic 1, Hematology and Cellular Therapy, University Hospital Leipzig, Leipzig, Germany; 4Azienda Ospedaliero-Universitaria Careggi, University of Florence, Florence, Italy; 5Department of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX; 6Moffitt Cancer Center, Tampa, FL; 7Bristol Myers Squibb, Princeton, NJ; 8Service d'Hématologie Séniors, Hôpital Saint-Louis, Université Paris 7, Paris, France Presentation 2198 Presenting author disclosures M.D.P.: no conflicts of interest to disclose. 2 Introduction and objectives Introduction • Studies of epoetin alfa and darbepoetin alfa have demonstrated efficacy among patients with LR-MDS, but the patient population in which a clinically significant effect is observed may be limited1,2 • Luspatercept, a first-in-class erythroid maturation agent with a mechanism of action distinct from ESAs,3 is approved by the US FDA for the treatment of anemia failing an
    [Show full text]
  • Therapeutic Class Overview Erythropoiesis-Stimulating Agents
    Therapeutic Class Overview Erythropoiesis-Stimulating Agents Therapeutic Class · Overview/Summary: The erythropoiesis-stimulating agents (ESAs) currently available are darbepoetin alfa (Aranesp®), epoetin alfa (Epogen®, Procrit®) and peginesatide (Omontys®).1-4 There is no generic ESA is currently available in the United States. All ESAs are approved by the Food and Drug Administration (FDA) for the treatment of anemia in patients with chronic kidney disease; however, peginesatide is only approved for use in patients on dialysis. Darbepoetin alfa and epoetin alfa are also indicated for the treatment of anemia in cancer patients receiving chemotherapy. Moreover, epoetin alfa products are also FDA-approved for the treatment of anemia due to zidovudine therapy in patients with human immunodeficiency virus infection as well as to reduce the need for allogeneic blood transfusion in anemic patients who are at high risk for perioperative blood loss from elective, noncardiac, nonvascular surgery.1-5 Both epoetin alfa and darbepoetin alfa are manufactured via recombinant deoxyribonucleic acid technology and have similar biological effects as endogenous erythropoietin.6 Although darbepoetin alfa has identical pharmacological actions, the additional carbohydrate chains prolong its elimination half-life by two- to three-fold compared to epoetin alfa. Because of this, darbepoetin alfa is dosed less frequently compared to epoetin alfa. Peginesatide is structurally distinct from epoetin alfa and darbepoetin alfa in that it is a synthetic dimeric peptide
    [Show full text]
  • Conversion Dosing Guide: from Epoetin Alfa to Aranesp® in Patients with Anemia Due to CKD on Dialysis
    Conversion Dosing Guide: From epoetin alfa to Aranesp® in patients with anemia due to CKD on dialysis Indication Aranesp® (darbepoetin alfa) is indicated for the treatment of anemia due to chronic kidney disease (CKD), including patients on dialysis and patients not on dialysis. Limitations of Use • Aranesp® has not been shown to improve quality of life, fatigue, or patient well-being. • Aranesp® is not indicated for use as a substitute for red blood cell transfusions in patients who require immediate correction of anemia. Please see Important Safety Information, including Boxed WARNINGS about INCREASED RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE, on pages 2 and 3. Important Safety Information including Boxed WARNINGS • Aranesp® is contraindicated in patients with: WARNING: ESAs INCREASE THE RISK OF DEATH, – Uncontrolled hypertension MYOCARDIAL INFARCTION, STROKE, VENOUS – Pure red cell aplasia (PRCA) that begins after treatment with Aranesp® or other THROMBOEMBOLISM, THROMBOSIS OF VASCULAR erythropoietin protein drugs ACCESS AND TUMOR PROGRESSION OR RECURRENCE – Serious allergic reactions to Aranesp® Chronic Kidney Disease: • Use caution in patients with coexistent cardiovascular disease and stroke. • Patients with CKD and an insufficient hemoglobin response to ESA therapy may be • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and at even greater risk for cardiovascular reactions and mortality than other patients. stroke when administered erythropoiesis-stimulating agents A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these risks. (ESAs) to target a hemoglobin level of greater than 11 g/dL. • In controlled clinical trials, ESAs increased the risk of death in patients undergoing ® coronary artery bypass graft surgery (CABG) and the risk of deep venous • No trial has identified a hemoglobin target level, Aranesp thrombosis (DVT) in patients undergoing orthopedic procedures.
    [Show full text]
  • Epoetin Alfa-Epbx
    HIGHLIGHTS OF PRESCRIBING INFORMATION maintenance dose. Intravenous route recommended for patients on These highlights do not include all the information needed to use hemodialysis (2.2). RETACRIT safely and effectively. See full prescribing information for • Patients on Zidovudine due to HIV-infection: 100 Units/kg 3 times weekly RETACRIT. (2.3). RETACRIT™ (epoetin alfa-epbx) injection, for intravenous or • Patients with Cancer on Chemotherapy: 40,000 Units weekly or 150 subcutaneous use Units/kg 3 times weekly (adults); 600 Units/kg intravenously weekly (pediatric patients > 5 years) (2.4). Initial U.S. Approval: 2018 • Surgery Patients: 300 Units/kg per day daily for 15 days or 600 Units/kg RETACRIT (epoetin alfa-epbx) is biosimilar* to EPOGEN/PROCRIT weekly (2.5). (epoetin alfa) WARNING: ESAs INCREASE THE RISK OF DEATH, -------------------- DOSAGE FORMS AND STRENGTHS -------------------- MYOCARDIAL INFARCTION, STROKE, VENOUS Injection THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS 2,000 Units/mL, 3,000 Units/mL, 4,000 Units/mL, 10,000 Units/mL, and AND TUMOR PROGRESSION OR RECURRENCE 40,000 Units/mL in single-dose vials (3) See full prescribing information for complete boxed warning. ------------------------------CONTRAINDICATIONS----------------------------- Chronic Kidney Disease: • Uncontrolled hypertension (4) • In controlled trials, patients experienced greater risks for death, • Pure red cell aplasia (PRCA) that begins after treatment with RETACRIT serious adverse cardiovascular reactions, and stroke when or other erythropoietin protein drugs (4) administered erythropoiesis-stimulating agents (ESAs) to target a • Serious allergic reactions to RETACRIT or other epoetin alfa products (4) hemoglobin level of greater than 11 g/dL (5.1). • No trial has identified a hemoglobin target level, ESA dose, or dosing -----------------------WARNINGS AND PRECAUTIONS----------------------- strategy that does not increase these risks.
    [Show full text]
  • Aranesp, INN-Darbepoetin Alfa
    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Aranesp 10 micrograms solution for injection in pre-filled syringe. Aranesp 15 micrograms solution for injection in pre-filled syringe. Aranesp 20 micrograms solution for injection in pre-filled syringe. Aranesp 30 micrograms solution for injection in pre-filled syringe. Aranesp 40 micrograms solution for injection in pre-filled syringe. Aranesp 50 micrograms solution for injection in pre-filled syringe. Aranesp 60 micrograms solution for injection in pre-filled syringe. Aranesp 80 micrograms solution for injection in pre-filled syringe. Aranesp 100 micrograms solution for injection in pre-filled syringe. Aranesp 130 micrograms solution for injection in pre-filled syringe. Aranesp 150 micrograms solution for injection in pre-filled syringe. Aranesp 300 micrograms solution for injection in pre-filled syringe. Aranesp 500 micrograms solution for injection in pre-filled syringe. Aranesp 10 micrograms solution for injection in pre-filled pen. Aranesp 15 micrograms solution for injection in pre-filled pen. Aranesp 20 micrograms solution for injection in pre-filled pen. Aranesp 30 micrograms solution for injection in pre-filled pen. Aranesp 40 micrograms solution for injection in pre-filled pen. Aranesp 50 micrograms solution for injection in pre-filled pen. Aranesp 60 micrograms solution for injection in pre-filled pen. Aranesp 80 micrograms solution for injection in pre-filled pen. Aranesp 100 micrograms solution for injection in pre-filled pen. Aranesp 130 micrograms solution for injection in pre-filled pen. Aranesp 150 micrograms solution for injection in pre-filled pen. Aranesp 300 micrograms solution for injection in pre-filled pen.
    [Show full text]
  • Coding Medical Necessity: Erythropoiesis Stimulating Agents (Esas)
    Coding Medical Necessity: Erythropoiesis Stimulating Agents (ESAs) This article contains instructions for coding medical necessity in accordance with both the national coverage determination (NCD) and local coverage determination (LCD) and other CMS instructions on darbepoetin alfa (Aranesp®, DPA) and epoetin alfa (Epogen®, Procrit®, EPO). These coding guidelines are not intended to replace any found in the ICD-9-CM Official Guidelines for Coding and Reporting, nor are they intended to provide guidance on when a condition should be coded. Rather, this article should be used in conjunction with the UB-04 Data Specifications Manual and the ICD-9-CM Official Guidelines for Coding and Reporting. This article supersedes all previous articles on this subject. Providers should refer to CMS manuals and updates issued in Change Requests for additional claim form-specific billing instructions, including, but not limited to modifiers, necessary for payment. General Information for all claims for ESAs: These coding guidelines specifically address the documentation of medical necessity on the claim, i.e., the coding in this guidance must be used to indicate the conditions that convey medical necessity of the drug treatment. Providers may not code a claim with more than one drug code (J or Q) for DPA or EPO, i.e., only one of the DPA or EPO codes may appear on a claim. The administration of this class of drugs should NOT be billed using any of the chemotherapy administration codes. Providers should use the appropriate therapeutic, prophylactic, and diagnostic injections and infusions code. No payment can be made for drugs when self-administered or administered by a caregiver (except for drugs administered under the auspices of the ESRD program).
    [Show full text]
  • Aranesp, INN-Darbepoetin Alfa
    SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion for the approval of Aranesp. This scientific discussion has been updated until 1 September 2003. For scientific information on procedures after this date please refer to module 8B. 1. Introduction Patients with chronic renal failure (CRF) develop uremic anaemia as one of the most obvious signs of the disease. This symptom is caused by impeded renal production of erythropoietin (EPO). EPO controls red blood cell counts (RBC) production by promoting survival, proliferation and differentiation of erythroid progenitors in the bone marrow. Effective management of anaemia in chronic renal failure (CRF) has a major impact on quality of life and may influence survival. Supplementation with recombinant human erythropoietin (r-HuEPO) is currently the standard treatment for anaemia in those patients. It is regarded as an effective drug, which has an established safety record. Recombinant human erythropoietin is currently available as a treatment for anaemia in end stage renal disease. Administration 2 to 3 times weekly is required in the majority of subjects. The aim of inventing this new molecular entity of darbepoetin alfa was to obtain a therapeutic with a longer biological half-life compared to r-HuEPO, allowing a reduction of the frequency of injections necessary to maintain a desired level of systemic haemoglobin and haematocrit. The chronic nature of CRF (unless a subject receives a kidney transplant) means that treatment may continue for a long part of the subject’s life and multiple weekly injections of r-HuEPO can have a major impact on subjects and care givers. Research has indicated that the sialic acid containing carbohydrate of erythropoietin determines its serum half-live.
    [Show full text]
  • Aranesp® (Darbepoetin Alfa)
    Aranesp® (darbepoetin alfa) Aranesp (darbepoetin alfa) is a man-made protein that helps your body produce red blood cells (RBC’s). This protein may be reduced because of kidney failure or with use of certain medications. When fewer red blood cells are produced, you can develop a condition called anemia. Aranesp is used to treat anemia caused by chemotherapy or chronic kidney disease. How do I take Aranesp? • Aranesp is injected under the skin, it is given most often in clinic by a nurse or doctor. • It is given every 1 to 4 weeks depending on the condition being treated and as prescribed by your doctor. • You may need frequent medical tests to be sure that there are no harmful effects from the use of Aranesp. Your injections may be delayed based on the results of these tests. • If you need to have surgery, make your surgeon aware that you are using Aranesp. You may need to stop using for a period of time. What drugs interact with Aranesp? Other drugs may interact with Aranesp including: • Prescription and over-the-counter medicines • Vitamins • Herbal products Tell each of your health care providers about all medicines you use now and any medicine you start or stop using. Department of Nephrology - 1 - What should I discuss with my healthcare provider before using Aranesp? 1. You should not use this medication is you are allergic to Aranesp; or if allergic to Epogen or Procrit (epoetin alfa) 2. To make sure that Aranesp is safe for you, tell your healthcare provider if you have: • Heart disease, congestive heart failure, high blood pressure
    [Show full text]
  • Aranesp® (Darbepoetin Alfa) for Injection
    Aranesp® (darbepoetin alfa) For Injection WARNINGS: INCREASED MORTALITY, SERIOUS CARDIOVASCULAR EVENTS, THROMBOEMBOLIC EVENTS, STROKE and INCREASED RISK OF TUMOR PROGRESSION OR RECURRENCE Chronic Renal Failure: • In clinical studies, patients experienced greater risks for death, serious cardiovascular events, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target hemoglobin levels of 13 g/dL and above. • Individualize dosing to achieve and maintain hemoglobin levels within the range of 10 to 12 g/dL. Cancer: • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in some clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers (see WARNINGS: Table 1). • To decrease these risks, as well as the risk of serious cardio- and thrombovascular events, use the lowest dose needed to avoid red blood cell transfusion. • Use ESAs only for treatment of anemia due to concomitant myelosuppressive chemotherapy. • ESAs are not indicated for patients receiving myelosuppressive therapy when the anticipated outcome is cure. • Discontinue following the completion of a chemotherapy course. (See WARNINGS: Increased Mortality, Serious Cardiovascular Events, Thromboembolic Events, and Stroke, WARNINGS: Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence, INDICATIONS AND USAGE, and DOSAGE AND ADMINISTRATION.) DESCRIPTION Aranesp® is an erythropoiesis stimulating protein, closely related to erythropoietin, that is produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. Aranesp® is a 165-amino acid protein that differs from recombinant human erythropoietin in containing 5 N-linked oligosaccharide chains, whereas recombinant human erythropoietin contains 3 chains.1 The two additional N-glycosylation sites result from amino acid substitutions in the erythropoietin peptide backbone.
    [Show full text]