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. Excluding patients receiving a transfusion within 90days of or during either EP, the DCR was 1.21 (95% CI 1.09, 1.35). The conversion rate was 354:1 in patients requiring high (>200 IU/kg/week) doses of epoetin and 291:1 in patients requiring low doses. m+KqXAXOkS@,1C0VgzXzeWU},4 RBC transfusions were reported in terms of number of transfusions and number of units transfused, using descriptive statistics. 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 Values are means (arithmetic for hemoglobin, geometric for dose) with 95% confidence intervals. WARNING: ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS and TUMOR PROGRESSION OR RECURRENCE CHRONIC KIDNEY DISEASE: Please see full Prescribing Information including Boxed WARNING, and Medication Guide(English, Espaol) for MIRCERA (methoxy polyethylene glycol-epoetin beta) Injection, for Intravenous or Subcutaneous Use. }"nUEcJumC0ooF Administer MIRCERA intravenously once every 4 More ways to get app. 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. Carrera F, Lok CE, de Francisco A, et al. MIRCERA is contraindicated in patients with: Please seefull Prescribing Information including Boxed WARNING, and Medication Guide(English, Espaol)for MIRCERA (methoxy polyethylene glycol-epoetin beta) Injection, for Intravenous or Subcutaneous Use. Mircera contains no preservatives. Please see full Prescribing Information including Boxed WARNING, and Medication Guide for MIRCERA (methoxy polyethylene glycol-epoetin beta) Injection, for Intravenous or Subcutaneous Use. Clipboard, Search History, and several other advanced features are temporarily unavailable. Evaluation of Iron Stores and Nutritional Factors. Horowitz J, Agarwal A, Huang F, Gitlin M, Gandra SR, Cangialose CB. 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). Cochrane Database Syst Rev. Mircera is administered by subcutaneous (SC) or intravenous (IV) injection (2.2). 8600 Rockville Pike 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. Discard any unused portion. 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. A rate of hemoglobin rise of > 1 g/dL over 2 weeks may contribute to these 4! <>/Font<>/XObject<>/ProcSet[/PDF/Text/ImageB/ImageC/ImageI] >>/MediaBox[ 0 0 612 792] /Contents 4 0 R/Group<>/Tabs/S/StructParents 0>> 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 thrombosis (DVT) in patients undergoing orthopedic procedures. The number of transfusions and units transfused increased approximately threefold from the pre-switch to the post-switch period. Unauthorized use of these marks is strictly prohibited. pee`T"c+l_WB,`km^;6#j(*m`&E`l${F6Q`&^=e`f(6]8ZE[VHNx-FRIhE&iJKvW`Vz^p@?Yk+S.DgR1rrB6yq2N$| PEG-Epo was approved in 2009 for administration Q2W or once a month (QM) to patients on dialysis [5, 8]. volume30,pages 10071017 (2013)Cite this article. In pediatric patients, Mircera is administered by intravenous injection only (2.2). You may also report negative side effects of prescription drugs to the Food and Drug Administration (FDA). 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. Peter Choi. As shown in Tables2 and 3, the mean (standard error) monthly Hb remained stable across the observation period, with mean monthly concentration ranging from 11.42 (0.09) g/dL (Month 4) to 11.60 (0.09) g/dL (Month 2) pre-switch, and from 11.26 (0.10) g/dL (Month 4) to 11.67 (0.09) g/dL (Month 1) post-switch. Physicians and patients should weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events. No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks. Recombinant human erythropoietin is effective in Dosing patterns, drug costs, and hematologic outcome in anemic patients with chronic kidney disease switching from darbepoetin alfa to epoetin alfa. 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 . Patients stable on intravenous (iv) epoetin alfa will be randomized either to receive standard of care therapy (epoetin alfa (iv) 3 times weekly), or to receive Mircera 120-360 micrograms (iv), monthly. 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. There are limitations in generalizing the findings of this study to the broader hemodialysis population. MIRCERA has an approximate molecular weight of 60 kDa. Department of Nephrology, John Hunter Hospital, Lookout Road, New Lambton Heights, NSW, 2305, Australia, Amgen (Europe) GmbH, Dammstrasse 23, P.O. Table 1 Mircera Starting Doses for Adult Patients Currently Receiving an ESA, Table 2 Mircera Starting Doses for Pediatric Patients Currently Receiving an ESA. EXTON, Pa., July 31, 2018 /PRNewswire/ -- Plagued by regulatory delays, the FDA finally granted approval for Retacrit in May 2018, making it the first biosimilar erythropoietin-stimulating agent (ESA) to become available in the US market. St. Gallen, Switzerland: Vifor (International) Inc.; June 2018. By Month 7 post-switch, the proportions of patients with Hb in these ranges were 9.7%, 48.1%, and 30.1%, respectively. Mourad Farouk is an employee of Amgen with Amgen stock ownership. as a substitute for red blood cell transfusions in patients who require immediate correction of anemia. Reasons for low Hb, e.g., acute intercurrent events such as bleeding, were not reported. When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly. Always store Mircera prefilled syringes in their original cartons. Report to the Judicial Council. The geometric mean weekly dose of DA was 23.2g (95% CI 20.6, 26.3) in the month prior to switch. The .gov means its official. Disclaimer. risks. MIRCERA is indicated for the treatment of anemia associated with CKD in adult patients on dialysis and adult patients not on dialysis. Mircera ceiling is 200 mcg every two weeks (or 3.0 mcg/kg/2 weeks, whichever is lower). Adv Ther 30, 10071017 (2013). 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. Nephrol Dial Transplant. For more information, please see the full Prescribing Information, including Boxed WARNING, and Medication Guide(English, Espaol) for MIRCERA. MIRCERA [prescribing information]. Results of the BlandAltman analysis investigating the concordance between mean weekly ESA doses in both evaluation periods are presented in Fig. Association of erythropoietin resistance and fibroblast growth factor 23 in dialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study. The WHO has set the daily-defined dose (DDD) for epoetin beta and darbepoetin at 1000 U and 4.5 g respectively, which gives a conversion factor of 222:1 . In an additional analysis performed to assess the sensitivity of this result to the effects of transfusion by excluding those patients who received an RBC transfusion within 90days prior to or during either evaluation period, the DCR was 1.21 (95% CI 1.09, 1.35). Initial Treatment: 0.6 mcg/kg body weight administered once every two weeks (2.2). 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. Contributed by. MIRCERA (methoxy polyethylene glycol-epoetin beta) is the first erythropoiesis-stimulating agent (ESA) approved by FDA for once-monthly administration. The primary finding of the study is that the DCR of PEG-Epo to DA was 1.17 (95% CI 1.05, 1.29). Cost (BNF 60, March 2013) Aranesp (darbepoetin alfa) - 14.68-220.22 (10 micrograms syringe to 150 microgram syringe) NeoRecormon Mircera (methoxy polyethylene glycol-epoetin beta) - 44.05-220.22 (30 microgram syringe to 150 microgram syringe . Correct or exclude other causes of anemia (e.g., vitamin deficiency, metabolic or chronic inflammatory conditions, bleeding, etc.) 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 . Mean Hb was 11.5g/dL in the pre-switch EP and 11.4g/dL in the post-switch EP. 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. Astor BC, Muntner P, Levin A, Eustace JA, Coresh J. Inflammation and Erythropoiesis-Stimulating Agent Response in Hemodialysis Patients: A Self-matched Longitudinal Study of Anemia Management in the Dialysis Outcomes and Practice Patterns Study (DOPPS). For patients who do not respond adequately over a 12-week escalation period, increasing the MIRCERA, Evaluate other causes of anemia. Mircera is used to treat anemia caused by chronic kidney disease in adults, or in children at least 5 years old who are on hemodialysis. 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). government site. 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. When a patient with a darbepoetin (Aranesp) or erythropoietin order switches to . In controlled clinical trials of patients with cancer, ESAs increased the risks for death and serious adverse cardiovascular reactions. Dose Conversion Ratio in Hemodialysis Patients Switched from Darbepoetin Alfa to PEG-Epoetin Beta: AFFIRM Study. 2013;28:10929. In the first month after switch, these proportions were 10.2%, 48.5% and 37.4%, respectively. Erythropoiesis-stimulating agents for anaemia in adults with chronic kidney disease: a network meta-analysis. Accessed 18 October 2013. 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. 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]. The initial conversion factor was 200:1. AFFIRM demonstrated non-linearity of the dose relationship curve, with DCR decreasing as pre-switch DA dose increased. Pure red cell aplasia (PRCA) that begins after treatment with MIRCERA, History of serious or severe allergic reactions to MIRCERA. -, Macdougall IC. % For lack or loss of hemoglobin response to Aranesp or EPOGEN, initiate a search for causative factors. A single hemoglobin excursion may not require a dosing change. Each dosage strength of MIRCERA is designated by a unique syringe plunger color. Part of Springer Nature. 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. The study comprised a 14-month observation period. The number of transfusions and units transfused increased approximately threefold from the pre-switch to the post-switch period. Dr. Peter Choi is the guarantor for this article, and takes responsibility for the integrity of the work as a whole. 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). See Instructions for Use for complete instructions on the preparation and administration of MIRCERA, If the hemoglobin level approaches or exceeds 11 g/dL, reduce or interrupt the dose of MIRCERA.