methoxy polyethylene glycol / epoetin beta (Rx)

Brand and Other Names:Mircera
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

methoxy polyethylene glycol/epoetin beta

injectable solution, single-dose prefilled syringe

  • 30mcg/0.3mL
  • 50mcg/0.3mL
  • 75mcg/0.3mL
  • 100mcg/0.3mL
  • 120mcg/0.3mL
  • 150mcg/0.3mL
  • 200mcg/0.3mL
  • 250mcg/0.3mL
  • 360mcg/0.6mL
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Anemia Associated with Chronic Renal Failure

Do not increase dose more frequently than q4weeks; decreases in dose can occur more frequently; avoid frequent dose adjustments

If hemoglobin rises rapidly (eg, >1 g/dL in any 2-week period), reduce dose by 25% or more as needed to reduce rapid responses

For patients who do not respond adequately, if hemoglobin has not increased by >1 g/dL after 4 weeks of therapy, increase dose by 25%

For patients who do not respond adequately over a 12-week escalation period, increasing Mircera dose further is unlikely to improve response and may increase risks; use lowest dose that will maintain a hemoglobin level sufficient to reduce need for RBC transfusions; evaluate other causes of anemia; discontinue Mircera if responsiveness does not improve

Patients with chronic renal failure on dialysis

  • Initiate Mircera treatment when hemoglobin level < 10 g/dL
  • If hemoglobin level (Hgb) ≥11 g/dL, reduce or interrupt dose
  • Dose if not currently on ESA therapy: 0.6 mcg/kg IV/SC q2week initially 
  • Once hemoglobin has been stabilized, administer dose once monthly using a dose that is twice that of every-two-week dose and subsequently titrated as necessary

Patients with chronic renal failure not on dialysis

  • Consider initiating treatment only when hemoglobin level is <10 g/dL and the following considerations apply
  • Rate of hemoglobin decline indicates likelihood of requiring a RBC transfusion and reducing risk of alloimmunization and/or other RBC transfusion-related risks is a goal
  • If hemoglobin level >10 g/dL, reduce or interrupt dose, and use lowest dose sufficient to reduce need for RBC transfusions
  • Dose if not currently on ESA therapy: 0.6 mcg/kg IV/SC q2week initially 
  • Once hemoglobin has been stabilized, administer dose once monthly using a dose that is twice that of the every-two-week dose and subsequently titrated as necessary

Switching Patients Currently on Other ESA

  • Receiving epoetin <8000 units/week or darbepoetin <40 mcg/week: 120 mcg/qMonth or 60 mcg/q2Week IV/SC
  • Receiving epoetin 8000-16000 units/week or darbepoetin 40-80 mcg/week: 200 mcg/qMonth or 100 mcg/q2Week IV/SC
  • Receiving epoetin >16000 units/week or darbepoetin >80 mcg/week:360 mcg/qMonth or 180 mcg/q2Week IV/SC

Dosage Modifications

Pharmacokinetics of methoxy polyethylene glycol-epoetin beta were not altered by age (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

Dosing Considerations

Limitations of use

  • Not indicated and is not recommended for use in the treatment of anemia due to cancer chemotherapy; as a substitute for RBC transfusions in patients who require immediate correction of anemia
  • Mircera has not been shown to improve quality of life, fatigue, or patient wellbeing

Dosage Forms & Strengths

methoxy polyethylene glycol/epoetin beta

injectable solution, single-dose prefilled syringe

  • 30mcg/0.3mL
  • 50mcg/0.3mL
  • 75mcg/0.3mL
  • 100mcg/0.3mL
  • 120mcg/0.3mL
  • 150mcg/0.3mL
  • 200mcg/0.3mL
  • 250mcg/0.3mL
  • 360mcg/0.6mL
more...

Anemia Associated with Chronic Renal Failure

Indicated for the treatment of anemia associated with chronic kidney disease (CKD) in pediatric patients (5-17 years) on hemodialysis who are converting from another ESA after their hemoglobin level was stabilized with an ESA

<5 years: Safety and efficacy not established

5-17 years

  • Administer IV once q4Weeks whose hemoglobin level has been stabilized by treatment with an ESA
  • Starting doses for patients currently receiving an ESA
    • Epoetin alfa: 4 x previous weekly epoetin alfa dose (Units)/125 (eg, 4 x 1500 Units of epoetin alfa per week/125 = 48 mcg of Mircera IV once q4Weeks)
    • Darbepoetin alfa: 4 x previous weekly darbepoetin alfa dose (mcg)/0.55 (eg, 4 x 20 mcg of darbepoetin alfa per week/0.55 = 145.5 mcg of Mircera IV once q4weeks)

Dosage Modifications

Pharmacokinetics of methoxy polyethylene glycol-epoetin beta were not altered by age (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

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Adverse Effects

>10%

Hypertension (13%)

Diarrhea (11%)

Nasopharyngitis (11%)

1-10%

Headache (9%)

Upper respiratory tract infection (9%)

Muscle spasms (8%)

Procedural hypotension (8%)

Fluid overload (7%)

Back pain (6%)

Cough (6%)

Vomiting (6%)

Hypotension (5%)

Urinary tract infection (5%)

Arteriovenous fistula thrombosis (5%)

Arteriovenous fistula site complication (5%)

Pain in extremity (5%)

Constipation (5%)

Frequency Not Defined

Cases of pure red cell aplasia (PRCA) and of severe anemia, with or without other cytopenias

Stevens-Johnson syndrome

Toxic epidermal necrolysis

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Warnings

Black Box Warnings

Erythropoiesis-stimulating agents (ESAs) increase the risk of the death, myocardial infarction, stroke, and venous thromboembolism, thrombosis of vascular access, and tumor progression or recurrence

Chronic kidney disease

  • In controlled trials, patients experienced greater risks for death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a Hgb <11 g/dL
  • No trial has identified a hemoglobin target level, ESA dose, or dosing strategy that does not increase these risks
  • Use the lowest dose sufficient to reduce the need for red blood cell (RBC) transfusions

Cancer

  • Not indicated and not recommended for the treatment of anemia due to cancer chemotherapy
  • A dose-ranging study ended early owing to the increased deaths among patients receiving Mircera than another ESA
  • ESAs shortened overall survival and/or increased the risk of tumor progression or recurrence in clinical studies in patients with breast, non-small cell lung, head and neck, lymphoid, and cervical cancers

Contraindications

Uncontrolled hypertension

PRCA beginning after treatment or other erythropoietin protein

History of serious or severe allergic reactions

Cautions

In controlled clinical trials of patients with CKD comparing higher hemoglobin targets (13-14 g/dL) to lower targets (9-11.3 g/dL), ESAs increased the risk of death, myocardial infarction, stroke, congestive heart failure, thrombosis of hemodialysis vascular access, and other thromboembolic events in the higher target groups; use caution in patients with coexistent cardiovascular disease and stroke (see Black Box Warnings)

Increased mortality and/or tumor progression in patients with cancer

Not approved for chemotherapy-induced anemia

Caution in history of cardiovascular disease or HTN; control hypertension prior to initiating and during therapy

Risk of HTN, encephalopathy early in treatment

Seizures reported in chronic kidney disease patients participating in clinical studies; increase monitoring of these patients for changes in seizure frequency or premonitory symptoms

Risk of developing treatment-associated antibodies (Abs) if: sudden loss of treatment response; severe anemia & low reticulocyte count

Risk of developing pure red cell aplasia (PRCA) & severe anemia, with or w/out other cytopenias

Evaluate for PRCA if lack/loss of response to Micera develops, in absence of other etiology; if severe anemia and low reticulocyte count develop during treatment, withhold therapy and evaluate for PRCA

Not for use as substitute for RBC transfusions in patients who require immediate correction of anemia

Serious allergic reactions, including anaphylactic reactions, angioedema, bronchospasm, tachycardia, pruritus skin rash, urticaria, and Stevens-Johnson syndrome/toxic epidermal necrolysis reported; if serious allergic or anaphylactic reaction occurs due to therapy, immediately and permanently discontinue treatment and administer appropriate therapy

Blistering and skin exfoliation reactions including erythema multiforme and Stevens-Johnson Syndrome (SJS)/Toxic Epidermal Necrolysis (TEN), in the postmarketing setting; discontinue therapy immediately if a severe cutaneous reaction, such as SJS/TEN, is suspected

Patients may require adjustments in their dialysis prescription after initiation treatment; patients may require increased anticoagulation with heparin to prevent clotting of the extracorporeal circuit during hemodialysis

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Pregnancy & Lactation

Pregnancy

Available data from published case reports and postmarketing experience with use in pregnancy are insufficient to identify a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Chronic kidney disease is associated with maternal and embryo-fetal risks

Animal data

  • In animal reproduction studies, administration of methoxy polyethylene glycolepoetin beta to rats and rabbits during pregnancy and lactation adversely affected offspring at doses 17-fold and greater than the recommended human dose

Clinical consideration

  • Pregnancy in women with chronic kidney disease has been associated with adverse outcomes (eg, hypertension, pre-eclampsia, miscarriage, premature birth, low-birth-weight, polyhydramnios, and intrauterine growth restriction)

Lactation

There are no data on the presence of methoxy polyethylene glycol-epoetin beta in human milk, the effects on the breastfed child, or the effects on milk production

However, endogenous erythropoietin is present in human milk

Animal data

  • In rats, methoxy polyethylene glycol-epoetin beta was present in maternal milk

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

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Pharmacology

Mechanism of Action

Erythropoietin receptor activator with greater activity in vivo as well as increased half-life, in contrast to erythropoietin

Erythropoietin is produced in the kidney and released into the bloodstream in response to hypoxia

In response to hypoxia, erythropoietin interacts with erythroid progenitor cells to increase red cell production; production of endogenous erythropoietin is impaired in patients with CKD and erythropoietin deficiency is the primary cause of their anemia

Absorption

Peak plasma time: SC: 72 hr

Bioavailability: SC: 62%

Onset: 7-15 day post-initial dose

Distribution

Vd (steady-state): 61 mL/kg

Excretion

Total clearance (0.4 mcg/kg IV dose, peritoneal dialysis) 0.47 mL/hr/kg

Half-life

  • IV, peritoneal dialysis: 119 hr
  • SC, peritoneal dialysis: 124 hr
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Administration

IV Incompatibilities

Do not dilute or administer with other solutions

IV Preparation

DO NOT pool unused portions or use vial or syringe more than once

DO NOT shake vigorously or prolong exposure to light

Do not mix Mircera w/ any parenteral solution

Do not dilute or administer in conjunction with other drug solutions

Inspect visually for particulate matter & coloration prior to administration

Do not use if particulate matter or coloration besides colorless to slight yellowish present

Discard unused portion

IV Administration

Single injection

SC Administration

Administer in the abdomen, arm, or thigh

Administer either IV/SC in adult patients and only IV in pediatric patients

Using the prefilled syringe, fully depress the plunger during injection in order for the needle guard to activate

Following administration, remove needle from the injection site and then release the plunger to allow the needle guard to move up until the entire needle is covered

Storage

Refrigerate at 2-8°C (36-46°F) in the original carton to protect from light

Do not freeze or shake

The end-user may store at room temperature <25°C (77°F) in the original carton <30 days; discard after 30 days

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
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  • Compare formulary status to other drugs in the same class.
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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.