What is the difference between Darbepoetin (darbepoetin alfa) and Retacrit (epoetin alfa) in treating anemia?

From the Guidelines

Darbepoetin alfa (Aranesp) and epoetin alfa (Retacrit) are both effective erythropoiesis-stimulating agents (ESAs) used to treat anemia, with darbepoetin having a longer half-life allowing for less frequent dosing. The main difference between darbepoetin and epoetin alfa is the dosing frequency, with darbepoetin typically administered once weekly or once every 2-3 weeks, compared to epoetin alfa which is usually administered 1-3 times weekly 1. This difference occurs because darbepoetin contains additional sialic acid residues that extend its circulation time in the body. Both medications work by stimulating red blood cell production in the bone marrow by mimicking the action of natural erythropoietin. Some key considerations for the use of these medications include:

• The FDA-approved starting dose of epoetin is 150 U/kg TIW or 40,000 U weekly subcutaneously, while the FDA-approved starting dose of darbepoetin is 2.25 g/kg weekly or 500 micrograms every 3 wk subcutaneously 1.
• Alternative starting doses or dosing schedules have shown no consistent difference in effectiveness on outcomes including transfusion and Hb response, although they may be considered to improve convenience 1.
• Dose escalation should follow FDA-approved labeling; no convincing evidence exists to suggest differences in dose escalation schedules are associated with different effectiveness 1.
• The use of epoetin or darbepoetin is recommended as a treatment option for patients with chemotherapy-associated anemia and a Hb concentration that is approaching, or has fallen below, 10 g/dL, to increase Hb and decrease transfusions 1.
• Clinicians should carefully weigh the risks of thromboembolism in patients for whom epoetin or darbepoetin are prescribed, as randomized clinical trials and systematic reviews of available randomized clinical trials demonstrate an increased risk of thromboembolism in patients receiving epoetin or darbepoetin 1. Darbepoetin is often preferred for patients who value convenience and fewer injections, while Retacrit (a biosimilar to the original Epogen/Procrit) may be more cost-effective. The efficacy of both medications in treating anemia is comparable when dosed appropriately, though individual patient factors like the cause of anemia, kidney function, and treatment goals should guide selection. Both medications carry similar safety profiles, including risks of cardiovascular events and thrombosis, and require careful hemoglobin monitoring during treatment. In terms of specific patient populations, the guidelines recommend considering other correctable causes of anemia before initiating therapy with stimulants of erythropoiesis, and minimizing use of ESAs in patients with high risk of thromboembolic events 1. Ultimately, the choice between darbepoetin and epoetin alfa should be based on individual patient needs and clinical circumstances.

From the FDA Drug Label

The t1/2 of Aranesp was approximately 3-fold longer than that of epoetin alfa when administered intravenously. Aranesp apparent clearance was approximately 1.4 times faster on average in patients receiving dialysis compared to patients not receiving dialysis. The bioavailability of Aranesp in patients with CKD receiving dialysis after subcutaneous administration was 37% (range: 30% to 50%)

The main difference between Darbepoetin alfa and Epoetin alfa is their pharmacokinetic properties. Darbepoetin alfa has a:

• Longer half-life (approximately 3-fold longer) compared to epoetin alfa when administered intravenously
• Faster apparent clearance in patients receiving dialysis
• Lower bioavailability after subcutaneous administration in patients with CKD receiving dialysis These differences may affect the dosing frequency and administration route of the two medications. However, the clinical implications of these differences are not explicitly stated in the provided drug labels. 2 3

From the Research

Comparison of Darbepoetin and Retacrit

• Darbepoetin alfa and epoetin alfa (Retacrit) are both used to treat anemia in patients with chronic kidney disease (CKD) [(4,5,6)].
• Darbepoetin alfa has a longer circulating half-life compared to epoetin alfa, allowing for less frequent dosing [(5,6)].
• Studies have shown that darbepoetin alfa can maintain hemoglobin concentrations as effectively and safely as epoetin alfa, but with a reduced dosing frequency [(4,6)].

Efficacy and Safety

• A randomized, open-label, parallel-group, non-inferiority Phase III trial found that darbepoetin alfa was not inferior to epoetin alfa in maintaining hemoglobin levels within the target range 4.
• The incidence of adverse events was similar between the two groups, with no obvious differences in the target hemoglobin achievement cumulative rates and maintenance rates 4.
• Another study found that darbepoetin alfa had a similar safety profile to epoetin alfa, with no antibody formation detected 6.

Dosage and Administration

• Darbepoetin alfa can be administered once weekly or once every other week, while epoetin alfa is typically administered two to three times a week [(5,6,7)].
• The recommended starting dose for darbepoetin alfa is 0.45 microg/kg once weekly, with subsequent titration based on hemoglobin concentration 5.

Clinical Outcomes

• A trial of darbepoetin alfa in patients with type 2 diabetes and CKD found that it did not reduce the risk of cardiovascular or renal events, but was associated with an increased risk of stroke 8.
• Another study found that darbepoetin alfa improved patient-reported fatigue in patients with CKD, but the improvement was modest 8.