Once the hemoglobin has been stabilized, MIRCERA, If the hemoglobin level exceeds 10 g/dL, reduce or interrupt the dose of MIRCERA. Packaging Type: Injection. The aims of the Aranesp Efficiency Relative to Mircera (AFFIRM) study were primarily to estimate the maintenance dose conversion ratio (DCR) of PEG-Epo to DA in a population of European hemodialysis patients switched from DA to PEG-Epo and with comparable mean hemoglobin (Hb) in the pre- and post-switch periods, and secondarily to investigate Do not pool unused portions from the prefilled syringes. Methoxy polyethylene glycol-epoetin beta, the active substance of MIRCERA, is a continuous erythropoietin receptor activator that shows a different activity at the receptor level characterized by a slower association to and faster dissociation from the receptor, a reduced specific activity in vitro with an increased activity in vivo, as well as an increased half-life, in contrast to . The long-acting r-HuEPO methoxy polyethylene glycol-epoetin beta (Mircera) has been associated with a risk of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) following a. Following administration, remove the needle from the injection site and then release the plunger to allow the needle guard to move up until the entire needle is covered. Donck J, Gonzalez-Tabares L, Chanliau J, Martin H, Stamatelou K, Manamley N, Farouk M, Addison J. Adv Ther. PubMedGoogle Scholar. Kidney Int. PMC The primary outcome measure, the geometric mean maintenance DCR, was calculated to be 1.17 (95% CI 1.05, 1.29). Treatment: Treat to anemia in people with chronic kidney disease. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Box 1557, 6301, Zug, Switzerland, Amgen (UK) Limited, 240 Cambridge Science Park, Milton Road, Cambridge, UK, You can also search for this author in Would you like email updates of new search results? Google Scholar. By definition, the DCR could not be calculated for patients ineligible for the DCR analysis as these did not have the necessary parameters recorded in both EPs. Action Stimulates erythropoesis (production of red blood cells). AFFIRM may therefore help to guide expectations around potential differences in ESA dose requirements when switching hemodialysis patients from DA to PEG-Epo, although the reported mean maintenance DCR is not intended to predict the dose conversion ratio at the individual patient level. Epoetin alfa was the first rhEPO produced and approved for pharmaceutical use, followed by several related products and by newer ESAs with the same mechanism but more prolonged action. See Instructions for Use for complete instructions on the preparation and administration of Mircera. Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Pediatric Patients with CKD Treated with Hemodialysis Administer Mircera intravenously once every 4 weeks to pediatric patients (ages 5 to 17 years) whose hemoglobin level has been stabilized by treatment with an ESA. Following initiation of therapy and after each dose adjustment, monitor hemoglobin weekly until the hemoglobin level is stable and sufficient to minimize the need for RBC transfusion. Conversion Dosing Guide: From epoetin alfa to Aranesp in patients with anemia due to CKD on dialysis. Conversion from Another ESA: dosed once every 4 weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion (2.2). The dose of Mircera, given as a single intravenous or subcutaneous injection, should be based on the Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. MIRCERA is available, for all strengths, in pack sizes of 1 and also pack size of 3 for the strengths 30, 50, 75 micrograms/0.3ml. Data on clinical and laboratory parameters relating to CKD management were abstracted from patient records and entered into an anonymized study-specific central database by study center staff. Choi, P., Farouk, M., Manamley, N. et al. Generic name: Methoxy polyethylene glycol-epoetin beta 30ug in 0.3mL MIRCERA is an erythropoiesis-stimulating agent (ESA) indicated for the treatment of anemia associated with chronic kidney disease (CKD) in: MIRCERA is not indicated and is not recommended for use: MIRCERA has not been shown to improve quality of life, fatigue, or patient well-being. For patients who do not respond adequately over a 12-week escalation period, increasing the MIRCERA, Evaluate other causes of anemia. %PDF-1.7 A brochure to help you understand how to dose and administer Aranesp, and to convert from epoetin alfa to Aranesp in patients with anemia due to CKD. Please see full Prescribing Information including Boxed WARNING, and Medication Guide for MIRCERA (methoxy polyethylene glycol-epoetin beta) Injection, for Intravenous or Subcutaneous Use. The dose of MIRCERA , given as a single intravenous or subcutaneous injection, should be based on the total weekly ESA dose at the time of conversion. Recombinant human erythropoietin is effective in There is limited information published on switching erythropoiesis-stimulating agent (ESA) treatment for anemia associated with chronic kidney disease (CKD) from darbepoetin alfa (DA) to methoxy polyethylene glycol-epoetin beta (PEG-Epo) outside the protocol of interventional clinical studies. Mircera contains no preservatives. Hemoglobin level and weekly equivalent erythropoiesis-stimulating agent dose during the 14-month observation period. PEG-Epo was approved in 2009 for administration Q2W or once a month (QM) to patients on dialysis [5, 8]. x]r9r}W#k There were 16 transfusions and 34 units transfused in the pre-switch period, versus 48 transfusions and 95 units transfused post-switch. Patients were then switched to fortnightly darbepoetin alfa dosing treatments; the existing weekly dose being doubled and Hb levels fell from 125 to 110 g/L (P < 0.0001), despite an increase in the mean dose from 44.9 to 47.5 . 2010;25:400917. Pharmacokinetic studies have shown that the meanSD terminal half-life of DA is 217.5h when administered intravenously (IV) [7]. Conversion from darbepoetin or erythropoietin to Mircera 1. Roche Registration Ltd., Welwyn Garden City, UK, 19 June 2012. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000739/WC500033672.pdf. In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered erythropoiesis-stimulating agents (ESAs) to target a hemoglobin level of greater than 11 g/dL. Adv Ther 30, 10071017 (2013). Mean Hb was 11.5 g/dL in the pre-switch EP and 11.4 g/dL in the post-switch EP. Amgen's two anemia drugs, Epogen and Aranesp, had sales of $6.6 billion last year, nearly half the company's total revenue. Part of Springer Nature. Values are means (arithmetic for hemoglobin, geometric for dose) with 95% confidence intervals. reverse transcriptase polymerase chain reaction (RT-PCR) Amplification of RNA sequences by conversion to cDNA by nucleic acid hybridization A technique of nucleic acid reverse transcriptase, followed by the polymerase chain reac-analy sis via association of complementary single- stranded tion. If Hb increases by < 1 g/dL and remains < 10 g/dL after 6 weeks of therapy: If dosing QW, then increase dose to 4.5 mcg/kg/week. Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) Galle JC, Claes K, Kiss I, Winearls CG, Herlitz H, Guerin A, Di Giulio S, Suranyi MG, Bridges I, Addison J, Farouk M. Nephrol Dial Transplant. Reasons for low Hb, e.g., acute intercurrent events such as bleeding, were not reported. Of 302 patients enrolled, 206 had data available for DCR analysis. Conversion from Another ESA: dosed once monthly or once every two weeks based on total weekly epoetin alfa or darbepoetin alfa dose at time of conversion (2.2). Dose by Weight Chart - Resourcehub Epogen Dosage Guide - Drugs.com Epogen, Procrit (epoetin alfa) dosing, indications, interactions Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events [see Boxed Warning and Clinical Studies (14)]. ESAs resulted in decreased locoregional control/progression-free survival and/or overall survival. Dr. Peter Choi is the guarantor for this article, and takes responsibility for the integrity of the work as a whole. Nephrol Dial Transplant. 1. DCR geometric mean maintenance dose conversion ratio, EP evaluation period, ESA erythropoiesis-stimulating agent, Hb hemoglobin, PEG-Epo methoxy polyethylene glycol-epoetin beta. -. Mircera is a prescription medicine used to treat the symptoms of Anemia associated with Chronic Renal Failure. When a patient with a darbepoetin (Aranesp) or erythropoietin order switches to . MIRCERA is a registered trademark of F. Hoffmann-La Roche Ltd. All Vifor Pharma Groups intellectual rights, including copyright, are reserved by the Vifor Pharma Group. Low hemoglobin at hemodialysis initiation: an international study of anemia management and mortality in the early dialysis period. DA can be administered once a week (QW) or once every 2weeks (Q2W) to hemodialysis patients. Red blood cell transfusions pre- and post-switch were quantified. Individualize dosing and use the lowest dose of Mircera sufficient to reduce the need for RBC transfusions [see Warnings and Precautions (5.1)]. A primary growth factor for erythroid development, erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia. 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. Data quality and completeness were aided by automatic edit checks built into the database software. Peter Choi, MB BChir, PhD, FRCP (UK), has received lecturing and consulting fees from Amgen, and has participated in advisory boards for Amgen. The geometric mean DCR was 1.17 (95% CI 1.05, 1.29). The number of RBC transfusions and units transfused in the post-switch period was approximately threefold higher compared to the pre-switch period. Dosing patterns, drug costs, and hematologic outcome in anemic patients with chronic kidney disease switching from darbepoetin alfa to epoetin alfa. Patients can also have iron-deficiency anemia and need iron replacement using one of the supplements listed in the previous Electrolytes and Minerals section of this lesson. Examine each prefilled syringe for the expiration date. Learn about Mircera, potential side effects, proper use and dosing, and popular alternatives. Hrl WH. ^D[5j@%e This analysis indicated that the concordance decreased with increasing dose. St. Gallen, Switzerland: Vifor (International) Inc.; June 2018. ferrous sulfate, Aranesp, Procrit, Retacrit. 8600 Rockville Pike In controlled clinical trials of patients with cancer, ESAs increased the risks for death and serious adverse cardiovascular reactions. 2). 20,000 Units/2 mL (10,000 Units/mL) and 20,000 Units/mL of RETACRIT as a clear and colorless liquid in multiple-dose vials (contains benzyl alcohol). Disclaimer. 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. The MHRA is aware of very rare cases of severe cutaneous adverse reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, in patients treated with erythropoietins; some cases were fatal. Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at even greater risk for cardiovascular reactions and mortality than other patients. It is not known if Mircera is safe and effective in children younger than 5 years of age. NCI CPTC Antibody Characterization Program, Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Adult Patients with CKD Mircera can be administered once every two weeks or once monthly to patients whose hemoglobin has been stabilized by treatment with an ESA (see Table 1). Red blood cell transfusions pre- and post-switch were quantified. Unable to load your collection due to an error, Unable to load your delegates due to an error. Strength: 100 mcg / 0.3ml. Logistic regression was used to estimate an odds ratio comparing the number of patients receiving an RBC transfusion in the post-switch period relative to their dose ratio at switch (<1 vs. 1). This suggests that the decision to transfuse was consistent with respect to Hb over the observation period (Fig. | DOWNLOAD SIZE: Dose Conversion Ratio in Hemodialysis Patients Switched from Darbepoetin Alfa to PEG-Epoetin Beta: AFFIRM Study. Patients were required to fulfill the following criteria for study entry: switched from treatment with DA to treatment with PEG-Epo at least 7months before study enrollment; receipt of hemodialysis for at least 12months prior to switching; receipt of IV DA for at least 7months immediately prior to switching; receipt of at least 1 dose of PEG-Epo after switching; and provision of informed consent, according to local requirements. Data were collected from 7months before until 7months after switching treatment. [citation needed] Google Scholar. Adverse Reactions: Hypertension, diarrhea,. Methoxy polyethylene glycol-epoetin beta, sold under the brand name Mircera, is a long-acting erythropoietin receptor activator (CERA) used for the treatment of anaemia associated with chronic kidney disease. This compares with a 35% decline in Epogen sales during the same period to $1.13bn, as competition from Mircera and biosimilars, like by Sandoz' Binocrit, reach the markets. If severe anemia and low reticulocyte count develop during treatment with Aranesp or EPOGEN, withhold Aranesp or EPOGEN and evaluate patients for neutralizing antibodies to erythropoietin. AFFIRM (Aranesp Efficiency Relative to Mircera) was a retrospective, multi-site, observational study designed to estimate the population mean maintenance dose conversion ratio [DCR; dose ratio achieving comparable hemoglobin level (Hb) between two evaluation periods] in European hemodialysis patients whose treatment was switched from DA to PEG-Epo. 2012;59:444451. For administration using the prefilled syringe, the plunger must be fully depressed during injection in order for the needle guard to activate. When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Anemia of chronic kidney disease (CKD) becomes increasingly prevalent and severe as kidney function declines [1], with over 90% of patients who require renal replacement therapy becoming anemic [2]. This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration. Conversion - Epoetin alfa (Procrit) to Darbepoetin alfa (Aranesp) #Epoetin #Darbepoetin #Erythropoietin #Conversion #Table #ESAs #Procrit #Aranesp #Pharmacology #Hematology #Nephrology. Appropriately control hypertension prior to initiation of and during treatment with MIRCERA, Seizures have occurred in patients participating in MIRCERA, For lack or loss of hemoglobin response to MIRCERA, If typical causes of lack or loss of hemoglobin response are excluded, evaluate for PRCA. and darbepOetin alfa in patieNts Undergoing dialySis [PATRONUS] [9]); however, there is a lack of published literature on switching in patients receiving routine clinical care (i.e., outside interventional clinical trials). Please know that the sponsors of this site are not responsible for content on the site you are about to enter. }"nUEcJumC0ooF Aranesp (darbepoetin alfa) Summary of product characteristics. _____ (if . Evaluate the iron status in all patients before and during treatment. Active ingredient: methoxy polyethylene glycol-epoetin beta Inactive ingredients: mannitol, methionine, poloxamer 188, sodium phosphate monobasic monohydrate, and sodium sulfate. Initial Treatment: 0.6 mcg/kg body weight administered once every two weeks (2.2). Conclusion: The odds ratio for receiving a transfusion was twice as high in patients switched at a dose ratio less than 1 when compared to those switched at 1:1 or higher. 1985;28:15. However, the relationship between the pre- and post-switch ESA doses during the two evaluation periods was non-linear. official website and that any information you provide is encrypted Epoetin beta and methoxy polyethylene glycol may increase tumor growth or decrease survival time in people with certain types of cancer. Use caution in patients with coexistent cardiovascular disease and stroke. Use the lowest Mircera dose sufficient to reduce the need for red blood cell (RBC) transfusions. Aranesp (darbepoetin alfa) prescribing information, Amgen. Months 7 to 1 constituted the pre-switch period, with switch defined as the date of first administration of PEG-Epo, and Months +1 to +7 constituted the post-switch period. a Mutually exclusive categories; patients are censored in the following, Analysis of relationship between pre- and post-switch erythropoiesis-stimulating agent dose. Mechanism of Action. Of the 29 patients transfused during the post-switch period, 20 had a dose ratio at switch <1, and 9 had a dose ratio at switch 1 (odds ratio 2.39, 95% CI 1.05, 5.44; P=0.038). The data from this study were analyzed using SAS Statistical Software v9.2 (SAS Institute Inc., Cary, NC, USA). Mircera (methoxy polyethylene glycol / epoetin beta) dosing, indications, interactions, adverse effects, and more Drugs & Diseases methoxy polyethylene glycol / epoetin beta (Rx) Brand and. -, Kazmi WH, Kausz AT, Khan S, et al. There is no evidence that Mircera alters the metabolism of other medicinal products. Conversion - Epoetin alfa (Procrit) to Darbepoetin alfa (Aranesp) #Epoetin #Darbepoetin #Erythropoietin #Conversion #Table #ESAs #Procrit #Aranesp GrepMed. ARANESP single-dose strengths can be combined 4,* You can more . Cochrane Database Syst Rev. Dialysis centers were expected to adhere to European Best Practice Guidelines for iron repletion [9]. OZZ Methoxy polyethylene demonstrated that the dose efficiency after SC and IV ad- glycol-epoetin b (PEG-epoetin b; Mircera; F. Hoffmann- ministration was . The distribution of transfusions (Fig. Analysis of relationship between pre- and post-switch erythropoiesis-stimulating agent dose. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Nephrol Dial Transplant. Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Adult Patients with CKD. 2001;38:803812. There was neither any requirement for a center to have been using DA as their sole long-acting ESA pre-switch, nor for every DA-treated patient to have been switched to PEG-Epo. Publication management support was provided by Caterina Hatzifoti, PhD, of Amgen Europe GmbH. PubMed In the absence of PRCA, follow dosing recommendations for management of patients with an insufficient response to MIRCERA, Cases of PRCA and of severe anemia, with or without other cytopenias that arise following the development of neutralizing antibodies to erythropoietin have been reported in the postmarketing setting in patients treated with MIRCERA, PRCA has also been reported in patients receiving ESAs for anemia related to hepatitis C treatment (an indication for which MIRCERA, If severe anemia and low reticulocyte count develop during treatment with MIRCERA, Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, tachycardia, pruritus, skin rash and urticaria have been reported in patients treated with MIRCERA, Blistering and skin exfoliation reactions including Erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), have been reported in patients treated with ESAs (including MIRCERA, Patients may require adjustments in their dialysis prescription after initiation of MIRCERA, Most frequent adverse reactions ( 5%) in adult patients with CKD treated with MIRCERA. Janet Addison is an employee of Amgen with Amgen stock options. )E]$&m"t "N5LQmgh-QZi`T0 hacpBYKUYRw@aMB/|n|'Y#h$8]#|zf. 4 0 obj There were 16 transfusions and 34 units transfused in the pre-switch period, versus 48 transfusions and 95 units transfused post-switch. The majority of patients who were transfused during the pre- and post-switch observation periods had Hb 10g/dL within the 14days prior to transfusion; only 1 patient during each period had Hb >11g/dL within the 14-day pre-transfusion interval. Finally, our study indicates that the risk of transfusion was higher in the post-switch compared with the pre-switch period, with an approximate threefold rise observed in the number of transfusions and units transfused post-switch. A rate of hemoglobin rise of greater than 1 g/dL over 2 weeks may contribute to these risks. There is limited information published on switching erythropoiesis-stimulating agent (ESA) treatment for anemia associated with chronic kidney disease (CKD) from darbepoetin alfa (DA) to methoxy polyethylene glycol-epoetin beta (PEG-Epo) outside the protocol of interventional clinical studies.