Usage
- Pegylated Recombinant Human Erythropoietin is prescribed for the treatment of anemia caused by chronic kidney disease (CKD), chemotherapy for certain cancers (excluding cancers of the bone marrow and blood cells), zidovudine treatment in HIV-infected patients, or in patients scheduled for major surgeries (such as hip or knee replacement) where there is deemed a high risk of the patient requiring blood transfusions..
- Pharmacological Classification: Erythropoiesis-stimulating agent (ESA).
- Mechanism of Action: This medication mimics the action of endogenous erythropoietin, stimulating the production of red blood cells in the bone marrow.
Alternate Names
- Methoxy polyethylene glycol-epoetin beta
- Brand Names: Mircera®, Erypeg®
How It Works
- Pharmacodynamics: Pegylated Recombinant Human Erythropoietin binds to erythropoietin receptors on erythroid progenitor cells in the bone marrow, stimulating their proliferation and differentiation into mature red blood cells. This increases red blood cell counts, improving oxygen delivery to tissues.
- Pharmacokinetics:
- Absorption: Administered subcutaneously or intravenously. Pegylation enhances absorption and bioavailability.
- Metabolism: Primarily internalized and degraded after binding to erythropoietin receptors, with a small amount cleared by the reticuloendothelial and lymphatic systems.
- Elimination: Mainly through receptor-mediated endocytosis and intracellular catabolism. The pegylation extends the half-life, permitting less frequent administration.
Dosage
Standard Dosage
Adults:
- Starting dose for patients not currently on an ESA: 0.6 mcg/kg body weight once every two weeks, administered intravenously or subcutaneously. Alternatively, 1.2 mcg/kg subcutaneously monthly for non-dialysis CKD patients.
- Conversion from another ESA: Dosing adjusted to once monthly or every two weeks based on the total weekly dose of the prior ESA.
Children:
- Dosing is individualized based on weight, age, and underlying condition, following pediatric guidelines and studies like the DOLPHIN study.
Special Cases:
- Elderly Patients: No specific dosage adjustments are indicated for elderly patients unless significant renal or hepatic impairment is present.
- Patients with Renal Impairment: Dosing adjustments may be necessary depending on the degree of renal impairment and the patient’s response to therapy.
- Patients with Hepatic Dysfunction: No dose adjustments are required.
Clinical Use Cases
Dosage in these settings is individualized based on the patient’s hemoglobin level, response to therapy, and the specific clinical situation. Close monitoring of hemoglobin and other hematological parameters is critical.
Dosage Adjustments
- Dose adjustments should be made based on the patient’s hemoglobin response and target hemoglobin levels (generally 10-12 g/dL in CKD patients). Increases or decreases are typically made in 25% increments of the previous dose, not more frequently than once per month. If the rate of rise in hemoglobin is greater than 2 g/dl over a month or the hemoglobin is approaching 12 g/dl, reduce the dose by approximately 25%. If hemoglobin continues to increase, interrupt therapy until it begins to decrease, then restart at a 25% lower dose. A hemoglobin decrease of roughly 0.35 g/dl per week is expected after dose interruption. When target hemoglobin is reached, consider increasing dosing interval (e.g., from every two weeks to once monthly, using a dose equal to twice the previous two-weekly dose).
Side Effects
Common Side Effects:
- Nausea
- Vomiting
- Diarrhea
- Fever
- Injection site reactions (redness, tenderness)
Rare but Serious Side Effects:
- Thromboembolic events (stroke, myocardial infarction, pulmonary embolism)
- Hypertension
- Seizures
- Pure red cell aplasia (PRCA)
Long-Term Effects:
- Potential for cardiovascular complications with prolonged use, particularly when targeting hemoglobin levels above 11 g/dL.
Contraindications
- Hypersensitivity to pegylated recombinant human erythropoietin or any of its components
- Uncontrolled hypertension
- Pure red cell aplasia caused by prior ESA therapy.
Drug Interactions
- HIF-PHIs: concurrent use is not advisable due to synergism
- ACE inhibitors: may be associated with lower hemoglobin levels and higher EPO resistance, especially in patients with the ACE D/D genotype.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: The effect on the fetus is unknown. Use only if potential benefits outweigh the risk.
- Breastfeeding: It is unknown whether this drug is excreted in human milk. Recommend avoiding or discontinuing breastfeeding due to potential neonatal side effects.
Drug Profile Summary
- Mechanism of Action: Stimulates red blood cell production by binding to erythropoietin receptors.
- Side Effects: Nausea, vomiting, diarrhea, fever, hypertension, thromboembolic events, PRCA.
- Contraindications: Hypersensitivity, uncontrolled hypertension, PRCA induced by ESAs.
- Drug Interactions: HIF-PHIs, ACE inhibitors.
- Pregnancy & Breastfeeding: Use with caution if potential benefits outweigh risks. Avoid or discontinue breastfeeding.
- Dosage: See above for detailed dosing guidelines.
- Monitoring Parameters: Hemoglobin, blood pressure, iron levels.
Popular Combinations
- Iron supplements are often co-administered to enhance the effectiveness of erythropoietin therapy.
Precautions
- Monitor blood pressure closely, especially in patients with pre-existing hypertension.
- Monitor iron stores and provide supplementation as needed.
- Evaluate for other causes of anemia before initiating treatment.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Pegylated Recombinant Human Erythropoietin?
A: See the Dosage section above for comprehensive details.
Q2: How is Pegylated Recombinant Human Erythropoietin administered?
A: It is administered either subcutaneously or intravenously.
Q3: What are the common side effects?
A: Nausea, vomiting, diarrhea, and fever are among the common side effects.
Q4: What are the serious side effects?
A: Thromboembolic events, severe hypertension, and pure red cell aplasia are potential serious side effects.
Q5: What are the contraindications?
A: Contraindications include hypersensitivity to the drug, uncontrolled hypertension, and ESA-induced PRCA.
Q6: Can Pegylated Recombinant Human Erythropoietin be used in pregnant women?
A: Use with caution during pregnancy, weighing the potential benefits against the risks.
Q7: How does pegylation affect the drug’s properties?
A: Pegylation extends the drug’s half-life, allowing for less frequent administration.
Q8: What should be monitored during therapy?
A: Regular monitoring of hemoglobin, blood pressure, and iron status is necessary.
Q9: What are the indications for Pegylated Recombinant Human Erythropoietin?
A: Indicated for anemia due to CKD (dialysis and non-dialysis patients), chemotherapy, zidovudine treatment in HIV patients, and to reduce the need for allogeneic blood transfusions in certain surgical settings.
