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Darbepoetin (Aranesp) is a recombinant form of the renal hormone erythropoietin (EPO). Darbepoetin alpha stimulates erythropoiesis by the same mechanism as endogenous erythropoietin (EPO). EPO is a glycoprotein that regulates the production of red blood cells by stimulating the division and differentiation of committed erythroid progenitor cells in the bone marrow. In adults, almost 90% of EPO is produced in the kidney with the remainder produced by the liver. Cells are activated to produce EPO as the hematocrit drops. Erythropoietin activates the synthesis of hemoglobin and other proteins found in normal erythroblasts. The production and activity of EPO is linked in a negative feedback loop, which maintains optimal red cell mass for oxygen transport. Darbepoetin alfa produces a dose-dependent increase in hemoglobin. The stimulation of erythropoiesis increases the demand for iron, making iron supplementation necessary for many patients.

Darbepoetin (Aranesp) dosage:

Adults: Initially, 0.45 mcg/kg SC or IV once weekly. For many patients, especially dialysis-independent patients, a lower maintenance dose may be necessary. Reduce dose of darbepoetin alfa by approximately 25% if there is a rapid increase (i.e., more than 1 g/dl in any 2-week period) in hemoglobin (Hgb) or if the Hgb is increasing and approaches 12 g/dl. If the Hgb does not increase by 1 g/dl after 4 weeks of therapy and iron stores are adequate, increase the dose by approximately 25%. The manufacturer suggests a target Hgb of 12 g/dl. Any clinically significant change in Hgb (increase or decrease) following a dosage adjustment may take 2-6 weeks. Do not make dosage adjustments more frequently than once a month unless clinically indicated. Following a dose change, check the Hgb at least once a week for at least 4 weeks. If the Hgb remains below or falls below the target range, re-evaluate reasons for diminished response, including iron stores. Once the target Hgb is achieved, doses should continue to be adjusted to maintain Hgb concentrations within range (not to exceed 12 g/dl). The median maintenance dose for adult hemodialysis patients is 0.41-0.53 mcg/kg SC/IV once weekly (range: 0.26-0.93 mcg/kg once weekly).

Adolescents and Children weighing 56-75 kg: Limited data indicate 30 mcg SC or IV every 7 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 40 mcg SC or IV every 7 days. If the patient's Hgb is higher than 12.5 g/dl, 30 mcg SC or IV can be administered every 10 days

Adolescents and Children weighing 46-55 kg: Limited data indicate 30 mcg SC or IV every 10 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 30 mcg SC or IV every 7 days. If the patient's Hgb is higher than 12.5 g/dl, 30 mcg SC or IV can be administered every 14 days.

Adolescents and Children weighing 38-45 kg: Limited data indicate 20 mcg SC or IV every 7 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 30 mcg SC or IV every 7 days. If the patient's Hgb is higher than 12.5 g/dl, 20 mcg SC or IV can be administered every 10 days.

Adolescents and Children weighing 26-37 kg: Limited data indicate 20 mcg SC or IV every 10 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 20 mcg SC or IV every 7 days. If the patient's Hgb is higher than 12.5 g/dl, 20 mcg SC or IV can be administered every 14 days.

Adolescents and Children weighing 23-25 kg: Limited data indicate 20 mcg SC or IV every 14 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 20 mcg SC or IV every 10 days. If the patient's Hgb is higher than 12.5 g/dl, 20 mcg SC or IV can be administered every 21 days.
Adolescents and Children weighing 20-22 kg: Limited data indicate 10 mcg SC or IV every 7 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 20 mcg SC or IV every 10 days. If the patient's Hgb is higher than 12.5 g/dl, 10 mcg SC or IV can be administered every 10 days.
Adolescents and Children weighing 14-19 kg: Limited data indicate 10 mcg SC or IV every 10 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 10 mcg SC or IV every 7 days. If the patient's Hgb is higher than 12.5 g/dl, 10 mcg SC or IV can be administered every 14 days.
Children weighing 10-13 kg: Limited data indicate 10 mcg SC or IV every 14 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 10 mcg SC or IV every 10 days. If the patient's Hgb is higher than 12.5 g/dl, 10 mcg SC or IV can be administered every 21 days.
Children weighing 8-9 kg: Limited data indicate 10 mcg SC or IV every 21 days (~0.45 mcg/kg/week). If the patient does not achieve a Hgb > 10 g/dl, the dose can be increased to 10 mcg SC or IV every 14 days. If the patient's Hgb is higher than 12.5 g/dl, 10 mcg SC or IV can be administered every 28 days
Children weighing <8 kg: Safety and efficacy have not been established.

The most common serious adverse reactions include vascular access thrombosis, congestive heart failure, sepsis, and cardiac arrhythmia. The most frequently reported adverse reactions resulting in clinical intervention (e.g., discontinuation of Aranesp^®, adjustment in dosage, or the need for concomitant medication to treat an adverse reaction symptom) were hypotension, hypertension, fever, myalgia, nausea, and chest pain.

Darbepoetin (Aranesp) is pregnancy category C.

References:

Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med. 1998; 339:584 590.

Aranesp® prescribing information

Glaspy J. Optimizing the dose and schedule of darbepoetin alfa in patients with chemotherapy-induced anemia. Oncology (Williston Park). 2006 Jul; 20(8 Suppl 6):29-32.

Geary DF, Keating LE, Vigneux A, et al. Darbepoetin alfa (Aranesp™) in children with chronic renal failure. Kidney Int 2005; 68:1759-65.