methoxypolyethylene glycol-epoetin beta

Action and Spectrum

Actions and Spectrum: 

Actions: 

Adult patients with anemia linked to chronic kidney disease (CKD) can be treated with methoxy polyethylene glycol-epoetin beta. It is a long-acting erythropoiesis-stimulating agent (ESA) that is intended to increase bone marrow synthesis of red blood cells. In contrast to conventional erythropoietin products, the drug is a fusion protein that combines polyethylene glycol and the hormone erythropoietin to prolong its activity and enable less frequent dosage. 

Spectrum: 

The spectrum of methoxy polyethylene glycol-epoetin beta are: 

Treatments for anemia in patients with chronic kidney disease (CKD) include raising hemoglobin levels, decreasing blood transfusions, stimulating the production of red blood cells, and reducing the need for blood transfusions. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10 % 

Diarrhea (11%) 

HTN (13%) 

Nasopharyngitis (11%) 

1-10 % 

Constipation (5%) 

Muscle spasms (8%) 

Headache (9%) 

UTI (5%) 

Pain in extremity (5%) 

Cough (6%) 

Back pain (6%) 

Upper RTI (9%) 

Procedural hypotension (8%) 

Arteriovenous fistula site complication (5%) 

Vomiting (6%) 

Arteriovenous fistula thrombosis (5%) 

Hypotension (5%) 

Fluid overload (7%)  

Frequency not defined 

Toxic epidermal necrolysis 

Red cell aplasia 

Severe anemia 

Stevens-Johnson syndrome

Black Box Warning

Black Box Warning: 

The use of erythropoiesis-stimulating agents (ESAs) raises the risk of thrombosis of vascular access, myocardial infarction, stroke, mortality, and venous thromboembolism. 

Chronic kidney disease: 

When ESAs were used to target a Hgb <11 g/dL, patients in controlled trials had increased risks of death, significant adverse cardiovascular events, and stroke. 

There isn’t a trial that has found an ESA dose, hemoglobin target level, or dosing regimen that doesn’t raise these hazards. 

Use the lowest amount necessary to minimize the requirement for transfusions of red blood cells (RBCs).  

Cancer: 

Not approved or authorized for the treatment of anemia brought on by chemotherapy for cancer 

Due to a higher fatality rate among patients on Mircera compared to another ESA, a dose-ranging trial had to be discontinued early. 

In clinical investigations, ESAs decreased overall survival and/or raised the chance of tumor progression or recurrence in patients with cervical, head and neck, breast, lymphoid, and non-small cell lung malignancies. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• History of severe allergic reactions 
• Uncontrolled HTN 
• Sign of PRCA after the start of treatment regimen or other erythropoietin protein 

Cautions 

• 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 in clinical trials of patients which are controlled with CKD with  higher targets of hemoglobin comparision (13 to 14 g/dL) to targets which are lower (9 to 11.3 g/dL); In patients with coexisting cardiovascular disease and stroke use caution (for reference see warnings in the black box) 
• Higher chances of tumor growth or risk of cancer-related death.  
• Not authorized for anemia brought on by chemotherapy 
• If there is a history of heart disease or high blood pressure use caution; manage hypertension before starting and throughout treatment 
• Early in therapy, encephalopathy and HTN risk 
• Patients with chronic kidney illness who are enrolled in clinical studies have reported having seizures; these patients should be closely watched for any changes in the frequency of their seizures or symptoms or premonitoring. 
• Factors of risk for the development of antibodies (Abs) which are associated with treatment include anemia which is severe, reduced count of reticulocyte, and abrupt loss of treatment response. 
• Possibility of severe anemia and pure red cell aplasia (PRCA), with or without further cytopenias 
• Assessment of PRCA, If there is no other cause and there is no response to Micera, stop treatment and consider PRCA if anemia is severe and reduced count of reticulocyte which occur during treatment. 
• Not to be used in place of red blood cell transfusions in individuals who need anemia corrected right away. 
• When reported reactions of allergy are serious, such as tachycardia, anaphylactic reactions, urticaria, bronchospasm, angioedema, pruritus, skin rash, and Stevens-Johnson syndrome or toxic epidermal necrolysis; if such a reaction is brought on by medication, it should be stopped right away and appropriately treated. 
• In the postmarketing context, skin exfoliation reactions and blistering, such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN) and erythema multiforme should be avoided. If SJS/TEN, is detected which is severe, stop treatment right once. 
• After starting treatment, patients might need to modify their dialysis prescription; for example, during dialysis heparin is given to prevent the clotting in extracorporeal circuit. 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

Pregnancy category: 

Category A: well-controlled and satisfactory studies show no risk to the fetus in the first or later trimester. 

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

Methoxy polyethylene glycol-epoetin beta is a continuous activator of the erythropoietin receptor that binds to the receptor more slowly than epoetin beta but dissociates from it a little quicker. Research on cell stimulation revealed that this substance exhibits a lower specific activity in vitro but a higher specific activity in vivo when compared to epoetin beta.  

Methoxy polyethylene glycolepoetin beta administered subcutaneously or intravenously to patients with chronic kidney disease (CKD) elicited a dose-dependent reticulocyte response that was unaffected by the delivery frequency.

Pharmacodynamics: 

Activator of the erythropoietin receptor that has a longer half-life and more action in vivo than erythropoietin. 

In reaction to hypoxia, the kidneys create erythropoietin, which is then released into the bloodstream.  

Erythropoietin interacts with erythroid progenitor cells to boost red cell formation in response to hypoxia; endogenous erythropoietin production is compromised in individuals with chronic kidney disease (CKD), and erythropoietin insufficiency is the main cause of their anemia. 

Pharmacokinetics: 

Absorption 

The bioavailability is 62% (SC) 

The time to achieve peak effect is 72 hours (SC) 

Onset: 7 to 15 day post-starting dose 

Distribution 

The volume of distribution of methoxypolyethylene glycol-epoetin beta is 61 mL/kg 

Metabolism 

Not metabolized 

Elimination and Excretion 

The half-life is 119 hours (IV, Peritoneal dialysis) and 124 hours (SC, Peritoneal dialysis) 

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

Adminstartion

Administration: 

IV Incongruities: 

Never dilute or use different solutions when administering  

IV prep: 

NEVER reuse a vial or syringe more than once, nor combine unwanted pieces.  

NEVER tremble violently or spend too much time in the light.  

Avoid combining Mircera with any intravenous solution.  

Don’t dilute or use this medication in combination with other liquids.  

Before administering, visually check for particle matter and coloring.  

Use caution if there are any particles or colors other than colorless to slightly yellowish present.  

Throw away any unused portion.  

IV Dosage: Individual injection 

SC Management 

Administer in the thigh, arm, or abdomen.  

For adult patients, administer either IV or SC; for pediatric patients, administer IV alone.  

To engage the needle guard during injection, fully depress the plunger on the prefilled syringe.  

After injection, take the needle out of the injection site and release the plunger to cause the needle guard to rise until the needle is fully covered.  

Storage: 

To prevent from light, refrigerate in the original carton at 2–8°C (36–46°F).  

Don’t tremble or freeze.  

The final user may keep the product in the original carton for up to 30 days at room temperature (77°F); after that, dispose of it. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: methoxypolyethylene glycol-epoetin beta 

Pronounced: METH-oks-ee-pol-ee-ETH-i-leen GLY-kol-eh-POH-e-tin BAY-ta 

Why do we use methoxypolyethylene glycol-epoetin beta? 

Adult patients with chronic kidney disease (CKD) who have anemia are treated with methoxy polyethylene glycol-epoetin beta. The following are the main justifications for the use of methoxypolyethylene glycol-epoetin beta: Treatments for anemia in patients with chronic kidney disease (CKD) include raising hemoglobin levels, decreasing blood transfusions, stimulating the production of red blood cells, and reducing the need for blood transfusions.