Darbepoetin alfa dosing

Previous Epoetin Alfa Dose (units/week) Weekly Darbepoetin Alfa Dose (mcg/week)... 

For patients requiring darbepoetin alfa every other week, the weekly dose of epoetin alfa should be multiplied by two and this dose used in the conversion chart to determine the appropriate darbepoetin alfa dose. 

Subcutaneous (SC) administration of ESA produces a more predictable and sustained response than IV administration, and is therefore the preferred route of administration for both agents. Intravenous administration is often utilized in patients who have established IV access or are receiving hemodialysis. Starting doses of ESAs depend on the patient s Hgb level, the target Hgb level, the rate of Hgb increase and clinical circumstances.31 The initial increase in Hgb should be 1-2 g/dL (0.6206-1.2404 mmol/L) per month. The starting doses of epoetin alfa previously recommended are 80 to 120 units/kg per week for SC administration and 120 to 180 units/kg per week for IV administration, divided two to three times per week. The starting dose of darbepoetin alfa is 0.45 mcg/kg administered SC or IV once weekly (Table 23-3). 

TABLE 23-3. Estimated Starting Doses of Darbepoetin Alfa Based on Previous Epoetin Alfa Dose... 

Darbepoetin alfa has a longer half-life than epoetin alfa and prolonged biologic activity. Doses are administered less frequently, starting at once a week when administered IV or SC. 

Conversion from epoetin alfa to darbepoetin Estimate the starting weekly dose of darbepoetin based on the weekly epoetin alfa dose at the time of substitution. Titrate doses to maintain the target hemoglobin. Due to the longer serum half-life, administer darbepoetin less frequently than epoetin alfa. Administer once a week if... 

Aranesp (Darbepoetin alfa) Amgen Liquid single-dose... 

Darbepoetin alfa is a second-generation ESA. It is a 165-amino-acid protein, with five N-linked oligosaccharide chains resulting from five amino acid substitutions in the erythropoietin peptide backbone. As a result of this, it has a longer half-life than erythropoietin, and so is given either once a week or in some patients, every two weeks. In addition, due to its longer duration of action, the intravenous and subcutaneous doses of darbepoetin alfa are the same. 

Both epoetin alfa and beta and darbepoetin alfa are quite well tolerated (47). Common adverse effects are infection, hypertension, hypotension, shunt thrombosis, myalgia, nausea, headache, and chest pain (34,48). After the first few doses of epoetin, flu-like sjmptoms occur transiently, with an incidence of 5.4-18% (34,49). These can be avoided by injecting epoetin subcutaneously rather than intravenously (31,33,50,51). It has also been suggested that such symptoms can be avoided by dose escalation, starting with an ultra-low dose (49). Subcutaneous injection can cause local reactions, probably due to allergy (52). 

FIGURE 33.6 Scatterplot of mean Hgb change from baseline over time in the simulated treatment arms and in 33 patients who were dosed once every other week subcutaneously with 3 mL darbepoetin alfa. Data are reported as the mean + standard deviation. (Reprinted with permission from Ref. 25.)... 

N. Jumbe, B. Yao, R. Rovetti, G. Rossi, and A. C. Heatherington, Clinical trial simulation of a 200-microgram fixed dose of darbepoetin alfa in chemotherapy-induced anemia. Oncology 16(Suppl ll) 37-44 (2002). 

Generally the response to erythropoietic therapy shonld be evaluated over at least 2 to 4 weeks before a change in the dose of epoetin alfa or darbepoetin alfa is made. If the change in Hgb is <1 g/dL (Hct less than 2% to 3%), over this time interval the dose of erythropoietic agent should be increased by 50% for epoetin alfa or 25% for darbepoetin alfa. If the change in Hgb is >2 to 3 g/dL (Hct greater than 6% to 8%) the dose of epoetin alfa or darbepoetin alfa shonld be rednced by 25%. 

Considerations are a bit different in patients with early CKD since Medicare does not cover medication costs for this population. The lack of payment is a deterrent to timely implementation of therapy and likely contributes to the development of secondary complications such as anemia. A recent pharmacoeconomic consideration in the CKD population is whether the addition of darbepoetin alfa offers a financial incentive in addition to advantages of less frequent dosing from a patient s perspective. As use of darbepoetin has become more widespread and the costs more stable, clinicians involved in the care of this patient population are begiiming to consider economic factors that influence selection of erythropoietic therapy. ... 

Recombinant erythropoietin therapy, in conjunction with adequate iron intake, can be highly ejfective in a number of anemias, especially those associated with a poor erythropoietic response. There is a clear dose-response relationship between the epoetin alfa dose and the rise in hematocrit in anephric patients. Epoetin alfa is effective in the treatment of anemias associated with surgery, AIDS, cancer chemotherapy, prematurity, and certain chronic inflammatory conditions. Darbepoetin alfa also is approved for use in patients with anemia associated with chronic kidney disease and is under review for several other indications. 

Darbepoetin alfa also is approved for use in patients who are anemic secondary to chronic kidney disease. The recommended starting dose is 0.45 pg/kg administered intravenously or subcutaneously once weekly, with dose adjustments depending on the response. Like epoetin alfa, side effects tend to occur when patients ejq)erience a rapid rise in Hb concentration a rise of less than 1 g/dL every 2 weeks generally is considered safe. 

Bommer J, Asmus G, Wenning M, Bommer G. A comparison of haemoglobin levels and doses in haemodialysis patients treated with subcutaneous or intravenous darbepoetin alfa a German prospective, randomized, multicentre study. Nephrol Dial Transplant 2008 23(12) 4002-8. 

The National Comprehensive Cancer Network (NCCN) recommends an anemia work-up for patients with hemoglobin of less than 11 g/dL (110 g/L or 6.8 mmol/L). Patients who are symptomatic or asymptomatic with significant risk factors (e.g., extensive transfusion history, myelosuppressive chemotherapy, etc) may qualify for treatment with erythropoietic agents such as epoetin-alfa or darbepoetin. Data do not support the use of one agent over another they are both equally effective in treating this type of anemia.12 Table 63-4 provides dosing recommendations for chemotherapy-related anemia. 

Amgen has recently introduced darbe-poetin Aranesp), a long-acting version of human erythropoietin. With two additional N-linked carbohydrate chains, darbepoetin contains more sialic acid than epoetin alfa and has an approximately threefold longer half-life, which leads to less frequent dosing than epoetin alfa. Darbepoetin is approved for both the treatment of anemia due to chronic renal failure and the treatment of chemotherapy-induced anemia. 

---