Geometric mean weekly PEG-Epo dose at Month 1 post-switch was 26.7g (95% CI 24.4, 29.3), rising to 29g (95% CI 26.2, 32.2) by Month 7 post-switch. By Month 7 post-switch, the proportions of patients with Hb in these ranges were 9.7%, 48.1%, and 30.1%, respectively. Hrl WH. Eligible patients were randomized, either to continue on the previous regimen of Epoetin, or to receive Darbepoetin alfa or continuous erythropoietin receptor activator (C.E.R.A) for a total period of 40 weeks. However, the relationship between the pre- and post-switch ESA doses during the two evaluation periods was non-linear. See this image and copyright information in PMC. In order to compare stable clinical scenarios for the purposes of DCR calculation, data evaluation periods (EPs) were utilized: Months 2 and 1 were defined as the pre-switch EP and Months +6 and +7 were defined as the post-switch EP. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. ^D[5j@%e Over the last 25years, several originator and biosimilar ESAs have been introduced for the management of CKD anemia, starting with the first generation short-acting recombinant erythropoietin agents (epoetin alfa and beta) and latterly with two longer-acting molecules, darbepoetin alfa (DA) and methoxy polyethylene glycol-epoetin beta (PEG-Epo), which combine a significantly increased half-life and lower binding affinity for the EPO receptor, allowing them to stimulate erythropoiesis for longer periods and to be administered less frequently [5, 6]. x]r9r}W#k Due to the skewed nature of the dosing data, mean weekly ESA doses were reported using geometric means; these were derived by calculating the arithmetic mean of the data transformed on the natural logarithmic scale. MIRCERA is a registered trademark of F. Hoffmann-La Roche Ltd. All Vifor Pharma Groups intellectual rights, including copyright, are, The information provided in this site is intended only for healthcare. -, Eschbach JW, Adamson JW. The relationship between the DA and PEG-Epo doses during the evaluation periods was explored through linear and quadratic regression. Patients included in the analysis were less likely to be diabetic (32% vs. 40%), more likely to be receiving DA at a longer dosing interval (60% vs. 73% at QW; 19% vs. 3% less frequently than Q2W), and received a lower geometric mean weekly dose of DA during the pre-switch EP (24.1 vs. 37.7g). eCollection 2020 Jun. Publication management support was provided by Caterina Hatzifoti, PhD, of Amgen Europe GmbH. Use the lowest Mircera dose sufficient to reduce the need for red blood cell (RBC) transfusions. This site needs JavaScript to work properly. A single hemoglobin excursion may not require a dosing change. 2008;23:365461. Anemia: an early complication of chronic renal insufficiency. Please enable it to take advantage of the complete set of features! 1:1 reference line indicates equal PEG-Epo and darbepoetin alfa doses. The primary outcome measure, the geometric mean maintenance DCR, was calculated to be 1.17 (95% CI 1.05, 1.29). DA, launched in 2001 [5, 7], contains 5 N-linked oligosaccharide chains, rather than the 3 contained in short-acting epoetins, which confer an approximately threefold longer serum half-life and mean residence time, allowing extended inter-dosing intervals [6]. ARANESP (darbepoetine alfa) 1 injection/sem. The pre-transfusion Hb concentrations were similar for transfusions occurring both pre- and post-switch (Fig. Editorial assistance in the preparation of this manuscript was provided by W. Mark Roberts, PhD, Montreal, Canada. 4 0 obj
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. Results of the BlandAltman analysis investigating the concordance between mean weekly ESA doses in both evaluation periods are presented in Fig. 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). Treatment: Treat to anemia in people with chronic kidney disease. }"nUEcJumC0ooF 1 0 obj
Administer Mircera as an intravenous injection at the dose (in micrograms) based on the total weekly ESA dose at the time of conversion (see Table 2). Please click to see accompanying Aranesp full prescribing information and EPOGEN full prescribing information, including Boxed WARNINGS and Medication Guide. Once Every Two Weeks (mcg/every two weeks). darbepoetin alfa (Aransep) pre-filled syringe, injectable vial epoetin alfa (Epogen; Procrit) injectable methoxy polyethylene glycol-epoetin beta (Mircera) pre-filled syringe Conditions Medications Dialysis patients can . Examine each prefilled syringe for the expiration date. Federal government websites often end in .gov or .mil. 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. Anemia of end-stage renal disease (ESRD). History of serious or severe allergic reactions to Mircera (e.g., anaphylactic reactions, angioedema, bronchospasm, pruritus, skin rash, and urticaria). The number of RBC transfusions and units transfused in the post-switch period was approximately threefold higher compared to the pre-switch period. 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 Aranesp, Serious and fatal reactions including gasping syndrome can occur in neonates and infants treated with benzyl alcohol-preserved drugs, including EPOGEN. Randomized clinical studies have reported data on switching from DA to PEG-Epo (Stabilizing haemoglobin TaRgets in dialysis following IV C.E.R.A. ONLY administer MIRCERA intravenously in pediatric patients. 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. 2020 Mar 26;2(3):286-296. doi: 10.1016/j.xkme.2020.01.007. Mircera contains no preservatives. Evaluation of Iron Stores and Nutritional Factors. 2010;25:400917. [3] It is the first approved, chemically modified erythropoiesis-stimulating agent (ESA). If the hemoglobin rises rapidly (e.g., more than 1 g/dL in any 2-week period), reduce the dose of MIRCERA. Slider with three articles shown per slide. 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. PEG-Epo methoxy polyethylene glycol-epoetin beta. %
The majority of patients with CKD will require supplemental iron during the course of ESA therapy. More severe cases were recorded with long-acting agents (darbepoetin alfa and methoxy polyethylene glycol-epoetin beta). If you are a healthcare professional outside of the US, please, visit www.mircera.global, The rate of hemoglobin decline indicates the likelihood of requiring a RBC transfusion, and, Reducing the risk of alloimmunization and/or other RBC transfusion-related risks is a goal, For adverse event reports, please contact us at, You may also report negative side effects of prescription drugs to, the Food and Drug Administration (FDA). Anemia response to Methoxy Polyethylene Glycol-Epoetin Beta (Mircera) versus Epoetin Alfa (Eprex) in patients with chronic Kidney disease on Hemodialysis Published: September 05, 2017 42/47 is common in patients with a GFR below 30 ml/min/1.73m2 and contributes to many of the speciic symptoms of CKD. 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. (0.6MB), Anemia Assessment and Management Brochure, Pathophysiology of Anemia in Patients with CKD, * Case studies and patient profiles are hypothetical, WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE. If Hb exceeds a level needed to avoid RBC transfusions, withhold dose until Hb approaches a level where RBC transfusions may be required and reinitiate at a dose 40% below the previous dose. When administered subcutaneously, Mircera should be injected in the abdomen, arm or thigh. Nephrol Dial Transplant. Dose Conversion Ratio in Hemodialysis Patients Switched from Darbepoetin Alfa to PEG-Epoetin Beta: AFFIRM Study, https://doi.org/10.1007/s12325-013-0063-y, CERA conversion to darbepoetin alfa in 154 hemodialysis patients, Long-term maintenance of hemoglobin levels in hemodialysis patients treated with bi-weekly epoetin beta pegol switched from darbepoetin alfa: a single-center, 12-month observational study in Japan, Efficacy, tolerability and safety of darbepoetin alfa injection for the treatment of anemia associated with chronic kidney disease (CKD) undergoing dialysis: a randomized, phase-III trial, Safety of Roxadustat Versus Erythropoiesis-Stimulating Agents in Patients with Anemia of Non-dialysis-Dependent or Incident-to-Dialysis Chronic Kidney Disease: Pooled Analysis of Four Phase 3 Studies, Initial responsiveness to darbepoetin alfa and its contributing factors in non-dialysis chronic kidney disease patients in Japan, Comparison of darbepoetin alpha and recombinant human erythropoietin for treatment of anemia in pediatric chronic kidney disease: a non-inferiority trial from India, Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study, In Search of Predictors of Switching Between Erythropoiesis-Stimulating Agents in Clinical Practice: A Multi-Regional Cohort Study, Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000332/WC500026149.pdf, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000739/WC500033672.pdf, https://creativecommons.org/licenses/by/2.0. A motion conversion mechanism 123 includes a yoke 153 and a rotatable member 149, which causes the yoke 152, . Report to the Judicial Council. Visit. Hymes J, Bickimer T, Jackson JH, Bookhart BK, Mody SH, Tak Piech C. Curr Med Res Opin. 4. 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. Unauthorized use of these marks is strictly prohibited. Studies of erythropoietin therapy in patients with chronic anemia of cancer as well as CIA document response rates ranging from ~60% to 85%. Mean Hb was 11.5g/dL in the pre-switch EP and 11.4g/dL in the post-switch EP. 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. The primary outcome (DCR) for each patient was calculated as the mean weekly dose of PEG-Epo during the post-switch EP divided by the mean weekly dose of DA during the pre-switch EP. Am J Kidney Dis. Conversion Dosing Guide: From epoetin alfa to Aranesp in patients with anemia due to CKD on dialysis. Adverse reactions ( 5%) in EPOGEN clinical studies in patients with CKD were hypertension, arthralgia, muscle spasm, pyrexia, dizziness, medical device malfunction, vascular occlusion, and upper respiratory tract infection. PubMedGoogle Scholar. For recommended dose equivalency, see Tables A and B (below). The mean (95% CI) monthly Hb immediately prior to switch, in Month 1 post-switch, and in Month 7 post-switch was 11.5g/dL (11.3, 11.7), 11.7g/dL (11.5, 11.9), and 11.4g/dL (11.3, 11.6), respectively. 3 0 obj
The introduction of exogenous erythropoiesis-stimulating agents (ESAs) to clinical practice has transformed the care of patients with CKD, by ameliorating anemia, reducing transfusion requirements, and improving quality of life [4]. For the purposes of this policy, a conversion factor of 3 should be used to estimate hematocrit when only the hemoglobin is measured, e.g., hemoglobin of 10 g/dL is approximately equal to a hematocrit of 30%, a hemoglobin of 11 g/dL is . When adjusting therapy consider hemoglobin rate of rise, rate of decline, ESA responsiveness and hemoglobin variability. The information provided in this site is intended only for healthcare professionals in the United States. Eligible patients had received hemodialysis for 12months and DA for 7months. 2007 Aug;23(8):1931-7. doi: 10.1185/030079907X210705. Active ingredient: methoxy polyethylene glycol-epoetin beta Inactive ingredients: mannitol, methionine, poloxamer 188, sodium phosphate monobasic monohydrate, and sodium sulfate. Kazmi WH, Kausz AT, Khan S, et al. 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. Action Stimulates erythropoesis (production of red blood cells). MIRCERA, methoxy polyethylene glycol-epoetin beta, is an ESA which differs from erythropoietin through formation of a chemical bond between an amino group present in erythropoietin beta and methoxy polyethylene glycol (PEG) butanoic acid. Administer MIRCERA intravenously once every 4 More ways to get app. [citation needed] 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 . volume30,pages 10071017 (2013)Cite this article. The remaining enrolment was at four sites divided between three other countries. St. Gallen, Switzerland: Vifor (International) Inc.; June 2018. Am J Kidney Dis. 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. Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. Epub 2022 Apr 22. stream
Clin Kidney J. Although the reasons for transfusion were not recorded, the pre-transfusion Hb concentrations within 14days prior to transfusion remained similar for transfusions occurring both pre- and post-switch. Bookshelf Logistic regression analysis showed a higher likelihood of a transfusion during the post-switch period among patients with a dose ratio at switching of <1. endobj
EPOGEN from multidose vials contains benzyl alcohol and is contraindicated in neonates, infants, pregnant women, and lactating women. Do not mix Mircera with any parenteral solution. Article Adverse Reactions: Hypertension, diarrhea,. Anemia Associated with Chronic Renal Failure, Methoxy polyethylene glycol-epoetin beta 30ug in 0.3mL, Drug class: recombinant human erythropoietins. For Pediatric Patients with CKD on hemodialysis: Conversion from Epoetin alfa or Darbepoetin alfa to Mircera in Pediatric Patients with CKD Treated with Hemodialysis. Table 1 Mircera Starting Doses for Adult Patients Currently Receiving an ESA, Table 2 Mircera Starting Doses for Pediatric Patients Currently Receiving an ESA. 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. Am J Kidney Dis. Nick Manamley, MSc, is an employee of Amgen with Amgen stock ownership. This study and the article processing charges were funded by Amgen Europe GmbH, Zug, Switzerland. Internal You are now leaving AnemiaHub.com. Introduction: Am J Kidney Dis. 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 patients treated with Aranesp or EPOGEN. Of 302 patients enrolled, 206 had data available for DCR analysis. before initiating MIRCERA. Department of Nephrology, John Hunter Hospital, Lookout Road, New Lambton Heights, NSW, 2305, Australia, Amgen (Europe) GmbH, Dammstrasse 23, P.O. The baseline (i.e., at time of switch) demographic and clinical characteristics of enrolled patients and those included in and excluded from the DCR analysis are displayed in Table1. Hb concentrations were reported as arithmetic means for each month. Revised European Best Practice Guidelines for the management of anaemia in patients with chronic renal failure. This paper presents the findings of a retrospective, multi-center, observational study of hemodialysis patients switched from DA to PEG-Epo for the treatment of anemia. Immediately and permanently discontinue Aranesp or EPOGEN if a serious allergic
Cochrane Database Syst Rev. When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. 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. Unable to load your collection due to an error, Unable to load your delegates due to an error. MIRCERA is indicated for the treatment of anemia associated with CKD in adult patients on dialysis and adult patients not on dialysis. 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. However, healthcare-resource utilization and cost data were not collected in this study, preventing comparison of these variables between the pre-switch and post-switch periods. Matsumura K, Okumiya T, Sugiura T, Takahashi N, Yamamoto Y, Kikuchi S, Fujii K, Otagaki M, Shiojima I. BMC Nephrol. 2022;53(5):333-342. doi: 10.1159/000523947. Nephrol Dial Transplant. 2012;59:44451. 2012 Jun;27(6):2303-11. doi: 10.1093/ndt/gfr677. 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). Karaboyas A, Morgenstern H, Fleischer NL, Vanholder RC, Dhalwani NN, Schaeffner E, Schaubel DE, Akizawa T, James G, Sinsakul MV, Pisoni RL, Robinson BM. Mourad Farouk is an employee of Amgen with Amgen stock ownership. Use caution in patients with coexistent cardiovascular disease and stroke. Aranesp (darbepoetin alfa) Summary of product characteristics. 1MIRCERA [prescribing information]. It is not known if Mircera is safe and effective in children younger than 5 years of age. The study sample comprised adult patients (age 18years) with CKD who received maintenance hemodialysis between January 2008 and August 2011 and whose ESA treatment was switched from IV DA to IV PEG-Epo. Nephrol Dial Transplant. Low hemoglobin at hemodialysis initiation: an international study of anemia management and mortality in the early dialysis period. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. - 94.130.71.173. BlandAltman analysis of agreement between pre- and post-switch erythropoiesis-stimulating agent dose (. chemotherapy, MDS or MF, continued therapy) Please provide a hemoglobin level (g/dL) for your patient taken within the first 12 weeks of therapy with epoetin and include the date the lab was drawn. 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. This has been reported predominantly in patients with CKD receiving ESAs by subcutaneous administration. Epub 2011 Dec 2. doi: 10.1038/ki.1985.109. For adverse event reports, please contact us at safety@viforpharma.com,mircera@viforpharma.com or at 1-800-576-8295. The AFFIRM study was designed as a retrospective, longitudinal cohort analysis to estimate the DCR in a population of hemodialysis patients achieving comparable Hb after switching from IV DA to IV PEG-Epo in a real-world setting. Further exploration of the relationship between DA and PEG-Epo doses using the BlandAltman method [10], which circumvents the limitations of the regression method in this type of investigation, indicated that the variability in the dose differences increased as doses increased, while the level of concordance decreased with increasing ESA dose. risks. Mircera is a prescription medicine used to treat the symptoms of Anemia associated with Chronic Renal Failure. Aranesp (darbepoetin alfa) Epogen (epoetin alfa) Mircera . Regression analysis indicated a non-linear relationship between pre- and post-switch ESA doses; DCR decreased with increasing pre-switch DA dose. endobj
Please know that the sponsors of this site are not responsible for content on the site you are about to enter. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these
Injection: 2,000 Units/mL, 3,000 Units/mL, 4,000 Units/mL, 10,000 Units/mL, and 40,000 Units/mL of RETACRIT as a clear and colorless liquid in single-dose vials. Control hypertension prior to initiating and during treatment with Aranesp or EPOGEN. 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. Strength: 100 mcg / 0.3ml. Show detailed description Study Design Go to In CKD, anemia results primarily from decreased production of endogenous erythropoietin (EPO) by the kidney [3]. Anemia: an early complication of chronic renal insufficiency. Do not use any prefilled syringes exhibiting particulate matter or a coloration other than colorless to slightly yellowish. 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. Please click the OK button below to continue. %PDF-1.7
Available for Android and iOS devices. Vigorous shaking or prolonged exposure to light should be avoided. Association of kidney function with anemia: the Third National Health and Nutrition Examination Survey (19881994) Arch Intern Med.
When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. An additional analysis was performed to explore the effect of transfusions on the DCR, by exclusion of patients with a transfusion within 90days prior to or during either EP from the analysis.