What is the dosing regimen for erythropoietin (Epoetin alfa) in patients with End-Stage Kidney Disease (ESKD) and anemia?

From the Guidelines

For patients with End-Stage Kidney Disease (ESKD) and anemia, the recommended dosing regimen for erythropoietin (Epoetin alfa) is 50-100 units/kg three times weekly, with the subcutaneous route of administration being preferred over intravenous due to its effectiveness and ability to provide elevated blood levels of Epoetin for a longer duration 1.

Key Considerations

• The goal of Epoetin alfa therapy is to achieve and maintain hemoglobin levels between 10-11.5 g/dL, avoiding rapid increases (>1 g/dL per month) or levels above 12 g/dL due to cardiovascular risk.
• Dosing should be individualized based on the patient's response, with adjustments made every 2-4 weeks.
• Before initiating therapy, ensure adequate iron stores (ferritin >100 ng/mL and transferrin saturation >20%) and rule out other causes of anemia.
• During treatment, monitor hemoglobin levels every 2-4 weeks initially, then monthly once stable.
• If the patient shows resistance to EPO (requiring >300 units/kg three times weekly), investigate for causes such as iron deficiency, inflammation, malignancy, or hyperparathyroidism.

Iron Supplementation

• IV iron therapy is recommended to maintain adequate iron stores, with a frequency of thrice weekly (with every hemodialysis), twice weekly, weekly, or every other week, providing 250 to 1,000 mg of iron within 12 weeks 1.
• Iron status during the maintenance phase of Epoetin treatment should be monitored by measuring the TSAT and serum ferritin every 3 months.

Pediatric Patients

• Dosing of IV iron in pediatric patients should be adjusted to weight, with recommended regimens employed for a 10-dose course of IV iron in pediatric hemodialysis patients shown in Table IV-4, and dosing recommendations for pediatric CKD and PD patients shown in Table IV-5 1.

From the Research

Dosing Regimen for Erythropoietin (Epoetin alfa) in Patients with End-Stage Kidney Disease (ESKD) and Anemia

• The dosing regimen for erythropoietin (Epoetin alfa) in patients with End-Stage Kidney Disease (ESKD) and anemia can vary depending on the route of administration and the patient's response to treatment 2, 3, 4, 5, 6.
• According to the study by 2, ESA resistance was defined as failure to achieve or maintain haemoglobin/haematocrit levels within the desired target range despite appropriate ESA doses (erythropoietin ≥ 450 U/kg/wk intravenously or ≥ 300 U/kg/wk subcutaneously).
• The study by 3 states that epoetin alfa and epoetin beta have been used 1-3 times weekly, but extended-interval dosing up to every 4 weeks is also effective in a substantial majority of CKD patients.
• A study by 4 evaluated the clinical safety and efficacy of a less frequent dosing regimen (once weekly) of epoetin alfa in patients with CKD not on dialysis, and found that once-weekly epoetin alfa therapy is safe and effective for treating anemia in these patients.
• Another study by 5 compared the safety and efficacy of intravenous epoetin alfa-epbx, an epoetin alfa biosimilar, to epoetin alfa in patients on hemodialysis with ESKD and anemia, and found that there is no clinically meaningful difference in efficacy or safety between the two treatments.
• The study by 6 found that treatment of patients on hemodialysis with subcutaneous epoetin is associated with more favorable clinical outcomes than those associated with intravenous epoetin treatment, likely due to the dose-sparing advantages of subcutaneous administration.

Route of Administration

• The route of administration (intravenous or subcutaneous) can affect the dosing regimen, with subcutaneous administration being more effective than intravenous administration 3, 6.
• The study by 6 found that epoetin doses used to achieve equivalent hemoglobin responses were, on average, 25% higher when epoetin was administered intravenously rather than subcutaneously.

Dose Adjustment

• Dose adjustment may be necessary to achieve and maintain target hemoglobin levels, and to minimize the risk of adverse events 2, 5.
• The study by 5 found that dosing was adjusted according to the epoetin alfa prescribing information, and that the least squares mean difference between epoetin alfa-epbx and epoetin alfa in weekly epoetin dose per kilogram of body weight was 0.37 U/kg per week.