Epoetin alfa - Drug Monograph

Introduction

Epoetin alfa is a recombinant human erythropoietin (EPO) analog used to stimulate erythropoiesis in patients with anemia. It is a glycoprotein produced through recombinant DNA technology that is functionally and structurally similar to endogenous erythropoietin. First approved by the FDA in 1989, epoetin alfa has become a cornerstone therapy for anemia management in various clinical settings, particularly in chronic kidney disease and cancer chemotherapy-induced anemia.

Mechanism of Action

Epoetin alfa binds to the erythropoietin receptor on erythroid progenitor cells in the bone marrow, activating intracellular signaling pathways that promote erythrocyte proliferation, differentiation, and survival. This mechanism mimics the action of endogenous erythropoietin, which is primarily produced by the kidneys in response to tissue hypoxia. The drug stimulates the division and differentiation of committed erythroid progenitor cells, increases reticulocyte release from the bone marrow, and stimulates hemoglobin synthesis, ultimately increasing red blood cell production and improving oxygen-carrying capacity.

Indications

• Anemia associated with chronic kidney disease (CKD) in patients on dialysis and not on dialysis
• Anemia in patients with non-myeloid malignancies where anemia is due to the effect of concomitant chemotherapy
• Reduction of allogeneic red blood cell transfusions in patients scheduled for elective, noncardiac, nonvascular surgery
• Anemia in zidovudine-treated HIV-infected patients
• Off-label uses may include anemia of critical illness and perioperative blood conservation

Dosage and Administration

• Initial dose: 50-100 units/kg IV or SC three times weekly
• Maintenance: Adjust to maintain Hgb between 10-11 g/dL

• Initial dose: 150 units/kg SC three times weekly or 40,000 units SC weekly
• Maximum dose: Not to exceed Hgb >11 g/dL

• 300 units/kg SC daily for 10 days before surgery, on day of surgery, and 4 days after surgery

• Renal impairment: Dose adjustment required based on Hgb response
• Hepatic impairment: No specific recommendations; use with caution
• Pediatrics: Safety and efficacy established for CKD patients ≥1 month old
• Elderly: No specific dose adjustment required

Pharmacokinetics

Contraindications

• Uncontrolled hypertension
• Pure red cell aplasia (PRCA) that begins after treatment with epoetin alfa
• Known hypersensitivity to epoetin alfa or any component of the formulation
• Patients with hemoglobin >11 g/dL who are not scheduled for surgery

Warnings and Precautions

• Increased risk of death, myocardial infarction, stroke, venous thromboembolism, and thrombosis of vascular access
• Increased risk of tumor progression or recurrence in patients with cancer
• ESAs shortened overall survival and/or increased risk of tumor progression or recurrence in clinical studies

• Hypertension: Monitor blood pressure closely
• Seizures: Risk increased during first 90 days of therapy
• Pure red cell aplasia: Monitor for sudden loss of response
• Thrombotic events: Increased risk, especially when targeting higher Hgb levels
• Cardiovascular events: Higher risk in patients with underlying cardiovascular disease

Drug Interactions

• ACE inhibitors: May diminish therapeutic effect
• Anticoagulants: May increase bleeding risk
• Iron supplements: Required for optimal response; iron deficiency may impair efficacy
• Cyclosporine: May increase erythropoietin levels
• Zidovudine: Enhanced erythropoietic effect

Adverse Effects

• Hypertension (25%)
• Headache (15%)
• Arthralgia (11%)
• Nausea/vomiting (10%)
• Injection site reaction (10%)

• Thrombotic events (myocardial infarction, stroke, pulmonary embolism)
• Seizures
• Pure red cell aplasia
• Hypertensive encephalopathy
• Thrombosis of vascular access
• Anaphylactic reactions

Monitoring Parameters

• Hemoglobin: Weekly until stable, then monthly
• Blood pressure: Before each dose during titration phase
• Iron studies: Transferrin saturation ≥20% and ferritin ≥100 ng/mL
• Complete blood count with reticulocyte count
• Renal function and electrolytes
• Signs of thrombosis or cardiovascular events
• Response to therapy and need for dose adjustment

Patient Education

• Purpose of therapy and expected benefits
• Importance of regular monitoring and follow-up visits
• Proper injection technique if self-administering
• Recognition and reporting of adverse effects (headache, dizziness, shortness of breath)
• Importance of blood pressure monitoring and compliance with antihypertensive medications
• Need for adequate iron supplementation
• Signs of thrombosis (leg pain/swelling, chest pain, sudden vision changes)
• Storage requirements: Refrigerate at 2-8°C; do not freeze or shake
• Proper disposal of needles and syringes

References

1. FDA Prescribing Information: Epogen® (epoetin alfa) 2. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease. Kidney Int Suppl. 2012 3. National Comprehensive Cancer Network (NCCN) Guidelines: Cancer- and Chemotherapy-Induced Anemia 4. Rizzo JD, et al. American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood. 2010 5. Pfeffer MA, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009 6. Bennett CL, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA. 2008 7. Locatelli F, et al. Erythropoiesis-stimulating agents in renal medicine. Kidney Int. 2017