Epoetin Alfa

Epoetin alfa is recombinant human erythropoietin, an erythropoiesis-stimulating agent used to treat anaemia of chronic kidney disease, chemotherapy-induced anaemia and, in selected cases, perioperative anaemia. It is available as originator and biosimilar products and is given intravenously or subcutaneously.

Classification. Erythropoiesis-stimulating agent.

Mechanism. Binds the erythropoietin receptor on erythroid progenitors, activating JAK2 and STAT5 signalling, which reduces apoptosis and increases red cell production.

Pharmacokinetics. Subcutaneous bioavailability is 20 to 40%, with peak levels at 12 to 18 hours. Intravenous half-life is 4 to 13 hours, longer in the subcutaneous route. Reticulocytes rise within 7 to 10 days, and the haemoglobin response takes 2 to 6 weeks.

Anaemia of chronic kidney disease (adults, haemoglobin under 10 g/dL after iron stores are replete).

• Dose: 50 to 100 IU/kg three times weekly intravenously or subcutaneously; the subcutaneous route needs about 30% less drug.
• Titration: raise by 25 IU/kg three times weekly at intervals of at least 4 weeks if haemoglobin rises by less than 1 g/dL in a month. Reduce by 25% when haemoglobin rises more than 2 g/dL in a month or approaches the target; interrupt if it exceeds 12 g/dL.
• Target: haemoglobin 10 to 12 g/dL; do not exceed 12 g/dL. Maximum: 300 IU/kg three times weekly; lack of response at this dose needs investigation. Loading dose: none. Maintenance: the lowest dose that holds the target.
• Children with chronic kidney disease: 50 IU/kg three times weekly.

Chemotherapy-induced anaemia (haemoglobin 10 g/dL or less, palliative intent).

• Dose: 150 IU/kg subcutaneously three times weekly, or 40 000 IU weekly.
• If the rise is under 1 g/dL after 4 weeks, increase to 300 IU/kg three times weekly. Stop if there is no response after 8 weeks, and 4 weeks after chemotherapy ends. Aim for haemoglobin no higher than 12 g/dL.

Perioperative blood conservation (selected adults, haemoglobin 10 to 13 g/dL, expected blood loss 900 to 1800 mL). 600 IU/kg subcutaneously weekly for 3 weeks before surgery and on the day of surgery, with thromboprophylaxis.

Adjustments. Kidney: dose by haemoglobin. Liver: none. Age: no adjustment.

Contraindications. Uncontrolled hypertension, pure red cell aplasia after any erythropoietin, hypersensitivity. Perioperative use is avoided after recent myocardial infarction or stroke, or when thromboprophylaxis cannot be given.

Boxed-warning-level risk. Increased risk of death, myocardial infarction, stroke, venous thromboembolism, vascular access thrombosis and tumour progression or recurrence. Use the lowest dose that avoids transfusion and avoid when cure is the intent in cancer.

Adverse effects. Hypertension, seizures, headache, influenza-like symptoms, injection-site pain, thrombosis. Pure red cell aplasia from anti-erythropoietin antibodies is rare and suspected when haemoglobin falls abruptly with a very low reticulocyte count.

Interactions. None major; response is blunted by iron deficiency, inflammation, hyperparathyroidism, aluminium toxicity, haemoglobinopathy and angiotensin-converting-enzyme inhibitors.

Pregnancy and breastfeeding. Use only if benefit outweighs risk; unlikely to enter breast milk in significant amounts.

Regional points. Treat malaria, haemolysis, bleeding, hookworm, iron, cobalamin and folate deficiency before attributing anaemia to erythropoietin deficiency. Cost and cold chain limit supply.

Common errors. Starting without correcting iron deficiency; chasing haemoglobin above 12 g/dL; continuing despite no response.

Administration. Store at 2 to 8°C; do not shake or freeze. Subcutaneous injection is preferred outside haemodialysis. Intravenous use is given into the dialysis circuit.

Baseline. Haemoglobin, ferritin (aim over 100 µg/L), transferrin saturation (aim over 20%), blood pressure, vitamin B12 and folate.

Monitoring. Haemoglobin every 2 weeks until stable, then monthly. Blood pressure at every visit. Iron indices every 3 months.

Referral and escalation. Stop for suspected pure red cell aplasia, severe hypertension not controlled, or thrombotic event, and refer to nephrology or haematology.