Mircera®
Methoxy polyethylene glycol-epoetin beta is a hematopoietic agent.1
Anemia of Chronic Kidney Disease
Methoxy polyethylene glycol-epoetin beta is used for the treatment of anemia in adults with chronic kidney disease (CKD), on dialysis and not on dialysis, and in pediatric patients 5-17 years of age with CKD on hemodialysis who are converting from another erythropoiesis-stimulating agent (ESA) after their hemoglobin level was stabilized with an ESA.1 Safety and efficacy of methoxy polyethylene glycol-epoetin beta were established in 6 randomized controlled trials conducted in adults and in a single open-label trial in pediatric patients.1, 2, 3, 4, 5, 6, 7, 9 Guidelines generally support the use of ESAs for patients with anemia of CKD.48, 49
Methoxy polyethylene glycol-epoetin beta has not been shown to improve quality of life, symptoms, or physical functioning, and is not recommended for the treatment of anemia due to cancer chemotherapy or as a substitute for red blood cell (RBC) transfusions in patients who require immediate correction of anemia.1
Efficacy of methoxy polyethylene glycol-epoetin beta in adults with CKD was principally established in 6 randomized, open-label, multicenter studies.1 Two trials (ARCTOS and AMICUS) were conducted in anemic patients with CKD who were ESA-naïve.1, 2, 3 In the ARCTOS trial, 324 ESA-naïve patients not on dialysis were randomized to 28 weeks of treatment with either methoxy polyethylene glycol-epoetin beta every 2 weeks (starting dose: 0.6 mcg/kg subcutaneously) or darbepoetin alfa weekly (starting dose: 0.45 mcg/kg subcutaneously).1, 2 In the AMICUS trial, 181 ESA-naïve patients on dialysis were randomized to 24 weeks of treatment with either methoxy polyethylene glycol-epoetin beta every 2 weeks (starting dose: 0.4 mcg/kg IV) or another ESA (epoetin alfa or epoetin beta administered IV at the recommended dose 3 times weekly).1, 3 In these studies, the treatment goal was a hemoglobin increase of ≥1 g/dL from baseline to a minimum of 11 g/dL; hemoglobin levels were maintained at 11-13 g/dL.1 The treatment goal was achieved in 98% of patients receiving methoxy polyethylene glycol-epoetin beta versus 96% of those receiving darbepoetin alfa in the ARCTOS study, and in 93% of patients receiving methoxy polyethylene glycol-epoetin beta versus 91% of those receiving epoetin alfa or epoetin beta in the AMICUS study; the median dose of methoxy polyethylene glycol-epoetin beta in these studies was 0.6 mcg/kg administered once every 2 weeks.1
Four trials of methoxy polyethylene glycol-epoetin beta (MAXIMA, PROTOS, STRIATA, and RUBRA) were conducted in anemic patients with CKD on dialysis who were converting from treatment with another ESA.1, 4, 5, 6, 7 Initial doses of methoxy polyethylene glycol-epoetin beta were determined based on the patients' previous weekly ESA dose.1 The MAXIMA and PROTOS trials randomized 673 and 572 patients, respectively, to IV administration of methoxy polyethylene glycol-epoetin beta every 2 or 4 weeks or continuation of epoetin therapy; the STRIATA trial randomized 313 patients to IV administration of methoxy polyethylene glycol-epoetin beta every 2 weeks or continuation of darbepoetin alfa; and the RUBRA trial randomized 336 patients to IV or subcutaneous administration of methoxy polyethylene glycol-epoetin beta every 2 weeks or continuation of epoetin alfa.1, 4, 5, 6, 7 Treatment with methoxy polyethylene glycol-epoetin beta in these trials maintained hemoglobin levels within the target range of 10-13.5 g/dL, with between-group mean hemoglobin differences ranging from 0-0.2 g/dL.1
The CORDATUS trial was a randomized study in CKD patients not on dialysis and not currently treated with an ESA that compared methoxy polyethylene glycol-epoetin beta administered once montly to darbepoietin alfa administered every week or every 2 weeks.1, 11 Both treatments achieved a hemoglobin response rate that was significantly higher than the protocol-specified response rate of 60% (94% in both the methoxy polyethylene glycol-epoetin beta and darbepoietin groups).11 Patients receiving methoxy polyethylene glycol-epoetin beta showed a steady rise in hemoglobin, with fewer patients above the target range during the first 8 weeks compared with darbepoetin alfa.11
A Cochrane systematic review compared methoxy polyethylene glycol-epoetin beta to other ESAs using data from 27 randomized controlled trials evaluating ESAs for at least 3 months in 5410 patients with anemia of CKD.8 The meta-analysis indicated that based on low-certainty evidence, there was little or no difference between methoxy polyethylene glycol-epoetin beta and other ESAs in terms of mortality, major adverse cardiovascular events, hypertension, or need for RBC transfusion.8 The authors noted that there was insufficient evidence to compare clinical outcomes in patients receiving methoxy polyethylene glycol-epoetin beta relative to placebo.8
The NHS, TREAT, and CHOIR trials compared higher and lower hemoglobin target levels in patients with CKD receiving ESAs.1 None of these trials specifically examined the use of methoxy polyethylene glycol-epoetin beta.1 The yearly transfusion rate in NHS was 51.5% in the group targeting a lower hemoglobin concentration (10 g/dL) and 32.4% in the group targeting a higher hemoglobin concentration (14 g/dL).1 A post-hoc analysis of TREAT demonstrated that RBC transfusions were less frequent in the group of patients administered an ESA to target a hemoglobin concentration of 13 g/dL (15%) compared to the control group in which the ESA was administered intermittently when hemoglobin concentration was <9 g/dL (25%).1 In the CHOIR trial, administration of an ESA to target a higher (13.5 g/dL) or lower (11.3 g/dL) hemoglobin level did not affect use of RBC transfusions.1 In each trial, the potential benefit of ESA therapy was offset by worse cardiovascular safety outcomes, resulting in an unfavorable benefit-risk profile for higher hemoglobin targets.1
Efficacy of methoxy polyethylene glycol-epoetin beta in pediatric patients with CKD was established in a phase 2, single arm, open-label, multicenter study (DOLPHIN).1, 9 Sixty-four patients, 5-17 years of age with CKD on dialysis who had stable hemoglobin while receiving another ESA, were converted to methoxy polyethylene glycol-epoetin beta administered IV once every 4 weeks for 20 weeks.1, 9 The starting dosage of methoxy polyethylene glycol-epoetin beta was based on the previous ESA dosa 2 dosage conversion factors were tested sequentially.9 Efficacy was determined according to the change in hemoglobin from baseline.1, 9 Among 36 evaluable patients who received methoxy polyethylene glycol-epoetin beta according to the recommended conversion factor, the mean change in hemoglobin from baseline was -0.15 g/dL; 75% of patients who received methoxy polyethylene glycol-epoetin beta maintained hemoglobin levels within 1 g/dL of baseline, and 81% maintained hemoglobin levels of 10-12 g/dL.1, 9
The Kidney Disease Improving Global Outcomes (KDIGO) guideline recommends addressing all correctable causes of anemia prior to starting ESA therapy and weighing the potential benefits and risks of ESAs for each patient where therapy is considered.48 Individualization of therapy when using ESAs is stressed throughout this guideline, as patient responses to treatment may differ.48 ESAs are suggested for adults with CKD not receiving dialysis when the hemoglobin concentration is <10 g/dL and for adults receiving dialysis when the hemoglobin concentration falls to 9-10 g/dL.48 In all pediatric patients with CKD, the guideline suggests that the hemoglobin threshold for initiating ESA therapy should be individualized based on the balance of risks and benefits of treatment.48 Concerning maintenance therapy, the guideline suggests that ESAs should not be used to maintain hemoglobin concentrations >11.5 g/dL in adults with CKD; in pediatric patients with CKD, it is suggested that hemoglobin be maintained between 11-12 g/dL.48 Both IV and subcutaneous routes of administration are suggested for patients receiving dialysis, and the subcutaneous route is suggested for patients with CKD not receiving dialysis or receiving peritoneal dialysis.48 The guideline does not specify a preferred ESA and suggests that ‘copy' versions of ESAs should only be those which have been designated a true biosimilar.48 The Kidney Disease Outcomes Quality Initiative (KDOQI) US Commentary on the 2012 KDIGO guideline states that for maintenance therapy, KDOQI supports a lower limit goal hemoglobin of 11 g/dL.48, 49
Methoxy polyethylene glycol-epoetin beta is administered by IV or subcutaneous injection.1 Administer by IV or subcutaneous injection in adult patients, and only by IV injection in pediatric patients.1 For subcutaneous administration, inject methoxy polyethylene glycol-epoetin beta in the abdomen, arm, or thigh.1
Methoxy polyethylene glycol-epoetin beta injection is available as single-dose prefilled syringes in various strengths for IV or subcutaneous administration.
Methoxy polyethylene glycol-epoetin beta is preservative-free; discard any unused portions.1 Do not mix the drug with any parenteral solution.1
Inspect the prefilled syringes visually for particulate matter and/or discoloration prior to administration; do not use if either is observed.1 Avoid vigorous shaking of the syringes or prolonged exposure to light.1
Do not pool unused portions from the prefilled syringes.1 Do not use the prefilled syringe more than once.1
Store methoxy polyethylene glycol-epoetin beta syringes in the refrigerator at 2-8°C in the original carton to protect from light.1 Do not freeze or shake.1 The patient may store methoxy polyethylene glycol-epoetin beta at room temperature up to 25°C in the original carton for up to 30 days.1
Individualize dosing and use the lowest dosage of methoxy polyethylene glycol-epoetin beta sufficient to reduce the need for RBC transfusions.1 In clinical trials, administration of ESAs, to targethemoglobin levels >11 g/dL increased the risk of death, serious adverse cardiovascular reactions, and stroke.1 No target hemoglobin level, erythropoiesis-stimulating agent (ESA) dose, or dosing strategy has been identified that decreases these risks.1 Weigh the possible benefits of decreasing transfusions against the increased risks of death and other serious cardiovascular adverse events.1
When initiating or adjusting therapy, monitor hemoglobin levels at least weekly until stable, then monitor at least monthly.1 When adjusting therapy, consider the rate of increase or decrease in hemoglobin concentration, responsiveness to the ESA, and hemoglobin concentration variability.1 A single hemoglobin excursion may not require a dosage change.1
Avoid frequent dosage adjustments of methoxy polyethylene glycol-epoetin beta.1 Do not increase dosage more frequently than once every 4 weeks; decreases in dosage can occur more frequently.1 If the hemoglobin concentration rises rapidly (e.g., >1 g/dL in any 2-week period), reduce the dosage by ≥25% as needed to reduce rapid responses.1 If the hemoglobin concentration has not increased by >1 g/dL after 4 weeks of therapy, increase the dosage by 25%.1
If an adequate response is not obtained over a 12-week period of escalating dosages, evaluate the patient for other causes of anemia; further dosage increases are unlikely to improve patient response and may increase risks of therapy.1 Use the lowest dosage that will maintain a hemoglobin concentration sufficient to reduce the need for RBC transfusions.1 If responsiveness does not improve, discontinue the drug.1
Anemia of Chronic Kidney Disease (CKD): ESA-naïve Patients Receiving Dialysis
Initiate methoxy polyethylene glycol-epoetin beta when the hemoglobin level is <10 g/dL.1 The recommended starting dosage of methoxy polyethylene glycol-epoetin beta in adults who are not currently treated with an ESA is 0.6 mcg/kg body weight administered as a single subcutaneous or IV injection once every 2 weeks.1 In patients on hemodialysis, IV is the preferred route because it may be less immunogenic.1 Reduce or interrupt the dosage if the hemoglobin level approaches or exceeds 11 g/dL.1 Once the hemoglobin level stabilizes, methoxy polyethylene glycol-epoetin beta may be administered once monthly at a dosage that is twice that of the every-2-week dosage and subsequently titrated as necessary.1
Anemia of CKD: ESA-naïve Patients Not Receiving Dialysis
Consider initiation of methoxy polyethylene glycol-epoetin beta treatment when the hemoglobin level is <10 g/dL and the following conditions apply: the hemoglobin decline rate indicates the likelihood of requiring a RBC transfusion and a goal of therapy is to reduce the risk of alloimmunization and/or other RBC transfusion-related risks.1 The recommended starting dosage of methoxy polyethylene glycol-epoetin beta in adults who are not currently treated with an ESA is 1.2 mcg/kg body weight given once monthly as a single subcutaneous injection.1 Alternatively, a starting dose of 0.6 mcg/kg body weight as a single IV or subcutaneous injection once every 2 weeks may be administered.1 Reduce or interrupt the dosage if the hemoglobin level is >10 g/dL; use the lowest dosage sufficient to reduce the need for RBC transfusions.1 Once the hemoglobin stabilizes, methoxy polyethylene glycol-epoetin beta may be administered once monthly at a dosage that is twice that of the every-2-week dosage and subsequently titrated as necessary.1
Patients Converting from Epoetin Alfa or Darbepoetin Alfa
Administer methoxy polyethylene glycol-epoetin beta as a single subcutaneous or IV injection once every 2 weeks or once monthly in patients whose hemoglobin has been stabilized by treatment with an ESA.1 Estimate the initial dosage of methoxy polyethylene glycol-epoetin beta based on the total weekly ESA dosage at the time of conversion (See Table 1).1
Previous Weekly Epoetin Alfa Dose (units/week) | Previous Weekly Darbepoetin Alfa Dose (mcg/week) | Once Monthly (mcg/month) Methoxy Polyethylene Glycol-epoetin Beta Dose | Once Every 2 Weeks (mcg/every 2 weeks) Methoxy Polyethylene Glycol-epoetin Beta Dose |
|---|---|---|---|
<8000 | <40 | 120 | 60 |
8000-16,000 | 40-80 | 200 | 100 |
>16,000 | >80 | 360 | 180 |
Anemia of CKD: Patients Receiving Dialysis and Converting from Epoetin Alfa or Darbepoetin Alfa
Administer methoxy polyethylene glycol-epoetin beta IV once every 4 weeks in pediatric patients (5-17 years of age) whose hemoglobin level has been stabilized by treatment with an ESA.1 Dosage of methoxy polyethylene glycol-epoetin beta is based on the total weekly ESA dosage at the time of conversion (See Table 2).1
Epoetin alfa | Darbpoetin alfa |
|---|---|
4 x previous weekly epoetin alfa dose (units)/125 | 4 x previous weekly darbepoetin alfa dose (mcg)/0.55 |
Example: 4 x 1500 units of epoetin alfa per week/125 = 48 mcg of methoxy polyethylene glycol-epoetin beta once every 4 weeks | Example: 4 x 20 mcg of darbepoetin alfa per week/0.55 = 145.5 mcg of methoxy polyethylene glycol-epoetin beta once every 4 weeks |
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients, but recommends cautious dosage selection, usually starting at the low end of the dosing range, due to the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.1
Increased Mortality, Myocardial Infarction, Stroke, and Thromboembolism
A boxed warning about the increased risk of death, myocardial infarction (MI), stroke, venous thromboembolism (VTE), and thrombosis of vascular access is included in the prescribing information for methoxy polyethylene glycol-epoetin beta.1 Erythropoiesis-stimulating agents (ESAs) increase the risk of death, serious and life-threatening cardiovascular (CV) events (e.g., MI, stroke, VTE, thrombosis of vascular access) when targeted to achieve hemoglobin concentrations >11 g/dL in patients with chronic kidney disease (CKD).1 Using ESAs to target a hemoglobin level >11 g/dL does not provide additional benefit and may contribute to these risks.1 Use ESAs with caution in patients with concurrent CV disease and stroke.1 Patients with CKD and an insufficient hemoglobin response to ESA therapy may be at greater risk for CV reactions and mortality than other patients; an increase in hemoglobin concentration >1 g/dL in a 2-week period may contribute to these risks.1 Increased risks of serious adverse CV events (MI and stroke) and death have been observed in controlled clinical trials of ESAs in patients with cancer; increased risk of death has been observed in controlled clinical trials of ESAs in patients undergoing coronary artery bypass graft (CABG) surgery.1 An increased risk of deep venous thrombosis (DVT) in patients undergoing orthopedic procedures has also been observed.1 No trial has identified a target hemoglobin level, ESA dose, or dosing strategy that does not increase these risks.1 Use the lowest methoxy polyethylene glycol-epoetin beta dose sufficient to reduce the need for RBC transfusions.1
Data from several controlled clinical studies in patients with CKD comparing higher hemoglobin targets (13-14 g/dL) to lower hemoglobin targets (9-11.3 g/dL) indicate higher hemoglobin targets are associated with an increased risk of death, MI, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events.1 These trials (NHS, CHOIR, and TREAT) were conducted using ESAs other than methoxy polyethylene glycol-epoetin beta (i.e., epoetin alfa, darbepoetin alfa).1
An increased incidence of thromboembolic reactions, some serious and life-threatening, has also been observed in patients with cancer treated with ESAs.1 A randomized, placebo-controlled study in patients with metastatic breast cancer receiving cancer chemotherapy was terminated early after finding higher mortality and a higher rate of fatal thrombotic events in patients who received epoetin alfa.1 In a randomized, controlled trial of epoetin alfa in 681 patients undergoing orthopedic spinal surgery, an increased incidence of DVT was observed in patients receiving epoetin alfa in addition to standard of care treatment.1
In a randomized, placebo-controlled trial of epoetin alfa in patients undergoing CABG surgery, 7 deaths occurred in 126 patients treated with perioperative epoetin alfa; 4 of these deaths were associated with thromboembolic events.1 No deaths occurred among the 56 patients receiving placebo.1 Methoxy polyethylene glycol-epoetin beta is not approved for reduction of RBC transfusions in patients scheduled for surgical procedures.1
Increased Mortality and/or Increased Risk of Tumor Progression or Recurrence in Patients with Cancer
A boxed warning about increased mortality and/or increased risk of tumor progression or recurrence in patients with cancer is included in the prescribing information for methoxy polyethylene glycol-epoetin beta.1 Methoxy polyethylene glycol-epoetin beta is not indicated or recommended for treatment of anemia due to cancer chemotherapy.1 In a dose-ranging trial of methoxy polyethylene glycol-epoetin beta in patients undergoing chemotherapy for non-small cell lung cancer, more deaths occurred among patients receiving methoxy polyethylene glycol-epoetin beta than another ESA, resulting in early study termination.1
Several studies in patients with various cancers have found decreased locoregional control, progression-free survival, and/or overall survival with ESA (epoetin alfa/beta or darbepoetin alfa) use.1 These include studies of patients with advanced head and neck cancer receiving radiation therapy, patients receiving chemotherapy for metastatic breast cancer or lymphoid malignancy, and patients with non-small cell lung cancer or various malignancies who were not receiving chemotherapy or radiotherapy.1
Other Warnings and Precautions
Methoxy polyethylene glycol-epoetin beta is contraindicated in patients with uncontrolled hypertension.1 In clinical studies, intensification of antihypertensive therapy was required in approximately 27% of patients with CKD, including patients on dialysis and not on dialysis.1 Hypertensive encephalopathy and/or seizures have been observed in patients with CKD treated with methoxy polyethylene glycol-epoetin beta.1
Appropriately control hypertension prior to initiation of and during treatment with methoxy polyethylene glycol-epoetin beta.1 Reduce or withhold methoxy polyethylene glycol-epoetin beta if blood pressure becomes difficult to control.1 Advise patients to maintain compliance with antihypertensive therapy and dietary restrictions.1
Seizures have been reported in patients receiving methoxy polyethylene glycol-epoetin beta.1 Monitor patients closely for premonitory neurologic symptoms during the first few months of therapy.1 Advise patients to contact their clinician for new-onset seizures, premonitory symptoms, or change in seizure frequency.1
Lack or Loss of Hemoglobin Response
Investigate potential causative factors (e.g., iron deficiency, infection, inflammation, bleeding) in patients who fail to respond or experience a loss of hemoglobin response to methoxy polyethylene glycol-epoetin beta.1 Evaluate for PRCA if typical causes of lack or loss of hemoglobin response are excluded.1 If PRCA is excluded, adjust dosage as recommended for management of patients with an insufficient response to methoxy polyethylene glycol-epoetin beta therapy.1
Cases of PRCA and 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 methoxy polyethylene glycol-epoetin beta.1 These cases have been observed predominantly in patients with CKD receiving ESAs by subcutaneous administration.1 Pure red cell aplasia was not observed in clinical studies of methoxy polyethylene glycol-epoetin beta.1
Pure red cell aplasia has also been reported in patients receiving ESAs for anemia related to treatment of hepatitis C (an indication for which methoxy polyethylene glycol-epoetin beta is not approved).1
Withhold methoxy polyethylene glycol-epoetin beta and evaluate patients for neutralizing antibodies to erythropoietin if severe anemia and low reticulocyte count develop during treatment.1 Obtain serum samples ≥1 month after the last methoxy polyethylene glycol-epoetin beta administration to prevent interference of the drug with the assay.1 Contact the manufacturer at 1-800-576-8295 to perform assays for binding and neutralizing antibodies.1 Permanently discontinue methoxy polyethylene glycol-epoetin beta in patients who develop PRCA following treatment with methoxy polyethylene glycol-epoetin beta or other erythropoietin protein drugs; do not switch patients to other ESAs as antibodies may cross-react.1
Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, tachycardia, pruritus, skin rash, and urticaria have been reported in patients treated with methoxy polyethylene glycol-epoetin beta.1 Discontinue the drug immediately and administer appropriate therapy if a serious allergic or anaphylactic reaction occurs; do not reinitiate therapy.1
Blistering and skin exfoliation reactions, including erythema multiforme, Stevens-Johnson Syndrome, and toxic epidermal necrolysis have been reported in patients treated with ESAs (including methoxy polyethylene glycol-epoetin beta) in the postmarketing setting.1 Discontinue therapy immediately if a severe skin reaction is suspected.1
Adjustments to the dialysis prescription may be required after initiation of methoxy polyethylene glycol-epoetin beta.1 Increased anticoagulation with heparin may be required to prevent clotting of the extracorporeal circuit during hemodialysis in patients treated with methoxy polyethylene glycol-epoetin beta.1
As with all therapeutic proteins, there is potential for immunogenicity with methoxy polyethylene glycol-epoetin beta therapy.1 The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay.1 Additionally, the observed incidence of antibody positivity may be influenced by several factors (e.g., assay methodology, sample handling, timing of sample collection, underlying disease, concomitant medications); for these reasons, comparison of the incidence of antibodies to methoxy polyethylene glycol-epoetin beta across studies and to other products may be misleading.1
Severe anemia or PRCA may result from neutralizing antibodies to methoxy polyethylene glycol-epoetin beta that cross-react with endogenous erythropoietin and other ESAs.1 Intravenous administration may decrease the risk for development of antibodies to methoxy polyethylene glycol-epoetin beta compared to subcutaneous administration.1
Antibody development was not detected in any patients who received methoxy polyethylene glycol-epoetin beta in clinical studies.1
Available data from a small number of published case reports and postmarketing experience with methoxy polyethylene glycol-epoetin beta in pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.1 Chronic kidney disease is associated with maternal and embryo-fetal risks (e.g., hypertension, pre-eclampsia, miscarriage, premature birth, low-birth-weight, polyhydramnios, intrauterine growth restriction).1
In animal reproduction studies, subcutaneous administration of methoxy polyethylene glycol-epoetin beta to rats and rabbits during pregnancy adversely affected offspring at doses 17-fold greater than the recommended human dose.1
It is not known whether methoxy polyethylene glycol-epoetin beta is distributed into human milk; however, endogenous erythropoietin is present in human milk.1 When methoxy polyethylene glycol-epoetin beta was administered to lactating rats, the drug was detected in maternal milk.1 The effects of methoxy polyethylene glycol-epoetin beta on breast-fed infants or on milk production are unknown.1
A clear determination of the risks of methoxy polyethylene glycol-epoetin beta to breast-fed infants cannot be made due to lack of clinical data during lactation.1 Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for methoxy polyethylene glycol-epoetin beta and any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.1
The efficacy and safety of methoxy polyethylene glycol-epoetin beta for the treatment of anemia due to CKD have been established in pediatric patients 5-17 years of age on hemodialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA.1 Use of methoxy polyethylene glycol-epoetin beta in this age group is supported by evidence from adequate and well-controlled studies in adults and a dose-finding study in 64 pediatric patients 5-17 years of age with CKD on hemodialysis.1 The observed safety profile in pediatric patients was similar to that found in adults.1
The efficacy and safety of methoxy polyethylene glycol-epoetin beta have not been established in pediatric patients <5 years of age.1 The efficacy and safety of subcutaneously-administered methoxy polyethylene glycol-epoetin beta have not been established in pediatric patients of any age.1 Efficacy and safety of methoxy polyethylene glycol-epoetin beta have not been established for the treatment of anemia in pediatric patients with CKD on peritoneal dialysis; the treatment of anemia in pediatric patients with CKD who are not yet on dialysis; and for pediatric patients whose hemoglobin level has not been previously stabilized by treatment with an ESA.1
Clinical studies of methoxy polyethylene glycol-epoetin beta did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger patients.1 Other reported clinical experience has not identified differences in responses between the elderly and younger patients.1
In general, select dosage with caution in geriatric patients, usually starting at the low end of the dosing ran geriatric patients have a greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and drug therapy.1
The pharmacokinetics of methoxy polyethylene glycol-epoetin beta were not altered in severe hepatic impairment (Child-Pugh class C).1 No pharmacokinetic data are available for patients with mild or moderate hepatic impairment.1
Methoxy polyethylene glycol-epoetin beta is indicated for use in patients with anemia of CKD, including patients requiring hemodialysis.1 Pharmacokinetics of methoxy polyethylene glycol-epoetin beta were not altered by the use of dialysis.1
The most common adverse reactions (≥10%) are hypertension, diarrhea, and nasopharyngitis.1
No formal drug interaction studies have been performed with methoxy polyethylene glycol-epoetin beta.1
Methoxy polyethylene glycol-epoetin beta is an erythropoiesis-stimulating agent (ESA).1 Erythropoietin is a primary growth factor for erythroid development; it is produced in the kidneys and released into the bloodstream in response to hypoxia.1 Erythropoietin interacts with erythroid progenitor cells to increase red cell production.1 In patients with chronic kidney disease (CKD), production of endogenous erythropoietin is impaired, which is the primary cause of anemia in these patients.1
Erythropoiesis‐stimulating agents (ESAs) are recombinant versions of erythropoietin; these drugs include epoetin alfa, epoetin-beta, darbepoetin alfa, and methoxy polyethylene glycol‐epoetin beta.10 Darbepoetin alfa was produced by adding N‐linked carbohydrate chains to epoetin to improve stability and increase its half-life 3‐fold (25 hours) compared to epoetin alfa (8.5 hours).10 With the addition of a methoxy polyethylene glycol polymer chain, the half-life of methoxy polyethylene glycol‐epoetin beta is even greater (130 hours), allowing for less frequent dosing compared to other ESAs (i.e., once every 2-4 weeks).10 Methoxy polyethylene glycol-epoetin beta is produced in Chinese hamster ovary cells using recombinant DNA technology.1 It has greater activity in vivo and a longer half-life compared to endogenous erythropoietin.1
Following a single dose of methoxy polyethylene glycol-epoetin beta in adult patients with CKD, the onset of hemoglobin increase (>0.4 g/dL from baseline) was 7-15 days after initiating therapy.1 The pharmacokinetics of methoxy polyethylene glycol-epoetin beta were studied in adult patients with anemia and CKD, including those on dialysis and those not on dialysis.1 Methoxy polyethylene glycol-epoetin beta did not accumulate following administration every 4 weeks; however, steady state serum concentrations increased by 12% when administered every 2 weeks.1
Following subcutaneous administration, the maximum serum concentrations of methoxy polyethylene glycol-epoetin beta were observed at a median time of 72 hours; the absolute bioavailability was 62%.1 Following IV administration of methoxy polyethylene glycol-epoetin beta 0.4 mcg/kg in adult patients with CKD who were receiving peritoneal dialysis, the observed terminal half-life of the drug was 119 hours.1 Following subcutaneous administration of methoxy polyethylene glycol-epoetin beta 0.8 mcg/kg in adult patients with CKD who were receiving peritoneal dialysis, the observed terminal half-life was 124 hours.1 The apparent half-life of methoxy polyethylene glycol-epoetin beta in pediatric patients 5-17 years of age with CKD on dialysis was 121 hours.1
Multiple dosing did not affect bioavailability, volume of distribution, or clearance of methoxy polyethylene glycol-epoetin beta.1 The pharmacokinetics of the drug were not altered by age (range, 6-89 years), gender, race, severe hepatic impairment (Child-Pugh class C), site of subcutaneous injection (abdomen, arm, or thigh), or the use of dialysis.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection, for IV or subcutaneous use | 30 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) |
50 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
75 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
100 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
120 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
150 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
200 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
250 mcg /0.3 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) | ||
360 mcg /0.6 mL | Mircera® (available as single-dose prefilled syringes) | Vifor (International) |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions September 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Vifor (International) Inc. Mircera® (Methoxy polyethylene glycol-epoetin beta) INTRAVENOUS prescribing information. 2023 Mar. [Web]
2. Macdougall IC, Walker R, Provenzano R et al. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol. 2008; 3:337-47.
3. Klinger M, Arias M, Vargemezis V et al. Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomized trial. Am J Kidney Dis. 2007; 50:989-1000.
4. Levin NW, Fishbane S, Valdés Cañedo F et al. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet. 2007; 370:1415-21.
5. Sulowicz W, Locatelli F, Ryckelynck JP et al. Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly. Clin J Am Soc Nephrol. 2007; 2:637-46.
6. Canaud B, Mingardi G, Braun J et al. Intravenous C.E.R.A. maintains stable haemoglobin levels in patients on dialysis previously treated with darbepoetin alfa: results from STRIATA, a randomized phase III study. Nephrol Dial Transplant. 2008; 23:3654-61.
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