Darbepoetin alfa

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

Epoetin alfa (erythropoietin EPO) and darbepoetin alfa are usually well tolerated. The most common adverse reactions include hypertension, headache, tachycardia, nausea, vomiting, diarrhea, skin rashes, fever, myalgia, and skin reaction at tlie injection site. See the Summary Drug Table Drug Used in the Treatment of Anemia for more information on these drug. 

Epoetin alfa is contraindicated in patients with uncontrolled hypertension, those needing an emergency transfusion, or those with a hypersensitivity to human albumin. Darbepoetin alfa (Aranesp) is contraindicated in patients with uncontrolled hypertension or in those allergic to the drug. 

Epoetin alfa and darbepoetin alfa are used with caution in patients with hypertension, heart disease, congestive heart failure, or a history of seizures. Both of these drains are Pregnancy Category C dru and are used cautiously during pregnancy and lactation. 

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... 

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

Epoetin-alfa (Epogen, Procrit) Darbepoetin-alfa (Aranesp)... 

Aranesp (darbepoetin alfa, a rEPO analogue) Anaemia associated with various medical conditions Amgen... 

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. 

Aranesp, Darbepoetin alfa Amgen, Inc. Anemia associated with chronic renal failure Chemotherapy-induced anemia in patients with non-myeloid malignancies Sept. 2001 July 2002... 

Pharmacology Darbepoetin alfa is an erythropoiesis-stimulating protein produced by recombinant DNA technology. Darbepoetin stimulates erythropoiesis by the same mechanism as endogenous erythropoietin. 

Pure red cell aplasia (PRCA) PRCA, in association with neutralizing antibodies to native erythropoietin, has been observed in patients treated with recombinant erythropoietins. This has been reported predominantly in patients with CRF. Discontinue darbepoetin alfa in any patient with evidence of PRCA and evaluate the patient for the presence of binding and neutralizing antibodies to darbepoetin alfa, native erythropoietin, and any other recombinant erythropoietin administered to the patient. 

Growth factor potential Darbepoetin alfa is a growth factor that primarily stimulates RBC production. The possibility that darbepoetin alfa can act as a growth factor for any tumor type, particularly myeloid malignancies, has not been evaluated. 

The most frequently reported serious adverse events reported with cancer chemotherapy patients included death, fever, pneumonia, dehydration, vomiting, and dyspnea. The most commonly reported adverse events were fatigue, edema, nausea, vomiting, diarrhea, fever, and dyspnea. The most frequently reported reasons for discontinuation of darbepoetin alfa were progressive disease, death, discontinuation of the chemotherapy, asthenia, dyspnea, pneumonia, Gl hemorrhage, thrombotic events, rash, dehydration. 

Erythropoiesis stimulants darbepoetin alfa epoetin alfa... 

Erythropoietin, darbepoetin alfa Anemia Patients with chronic renal failure... 

Darbepoetin alfa Long-acting glycosylated form administered weekly... 

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

Source Adapted 2007 ODAC Meeting, Information Package Darbepoetin alfa (BLA 103951) and Epoetin alfa (BLA 103234)... 

Describe the differences between erythropoietin and darbepoetin alfa. 

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