Unit dosing of darbepoetin alfa for thetreatment of anemia in patients with end-stage renal disease being switched from recombinant human erythropoietin: Results of a phase IIIb, 27-week, multicenter, open-label study in Greek patients

Abstract

Background: Darbepoetin alfa is an erythropoiesis-stimulating glycoprotein with a -3-fold longer tl/2 and greater biological activity compared with recombinant human erythropoietin (rHuEPO).Objective: The objective of this study was to evaluate the efficacy and tolerability of long-term (24-week) darbepoetin alfa treatment in maintaining hemoglobin (Hb) concentrations in the target range of 10 to 13 g/dL in patients undergoing dialysis; the patients were switched from rHuEPO to a less-frequent dosing regimen of darbepoetin alfa without an increase in dose. Methods:In this Phase IIIb, open-label, multicenter study, patients with endstage renal disease (ESRD) undergoing dialysis who were receiving rHuEPO BIW or TIW at baseline were switched to darbepoetin alfa QW; patients receiving rHuEPO QW were switched to darbepoetin alfa Q2W. Administration of darbepoetin alfa was by the same route as previous rHuEPO administration (IV or SC). Patients received darbepoetin alfa for 24 weeks, including a 20-week drug titration period followed by a 4-week, stable-dose evaluation period. The mode, dose, and frequency of administration of darbepoetin alfa were compared with those of baseline rHuEPO. Tolerability assessment was based on spontaneous reporting and laboratory tests (hematology, vital sign measurement, iron status, and biochemistry). Results:The study comprised 173 patients who were divided into 2 groups by route of administration (IV group, n = 146; SC group, n = 27). Mean (SE) adjusted increases in Hb concentration from baseline to the evaluation period for patients receiving darbepoetin alfa QW were 0.94 (0.32) g/dL and 0.38 (0.30) g/dL for the IV or SC routes, respectively (P = 0.004 and NS, respectively). For patients receiving darbepoetin alfa Q2W, the mean (SE) adjusted increases in Hb concentration were 0.08 (0.53) g/dL and 0.48 (0.35) g/dL for the IV and SC routes, respectively (both, P = NS). No significant differences in IV/SC dose ratio were observed between the 2 routes of administration. In addition, no increases in darbepoetin alfa dose were observed. The most commonly reported adverse events were hypertension (8 patients [5%]) and vascular access thrombosis (4 [2%]). The incidence of treatment-related adverse events was 6 (3%). Conclusions: Darbepoetin alfa effectively maintained Hb concentrationswithin the target range without an increase in dose, even at a reduced dosing frequency. Overall, darbepoetin alfa was well tolerated. (Curr Ther Res Clin Exp. 2005;66:195-211)

Darbepoetin, effective treatment of anaemia in paediatric patients with chronic renal failure

“…By contrast, darbepoetin alpha (DA) that has an increased sialic acid carbohydrate content promotes decreased clearance and has a longer serum halflife than r-HuEPO [12][13][14], allowing a single weekly administration. Previous studies showed a similar potent effect of darbepoetin in adult as well as in paediatric patients either in pre-dialysis chronic renal failure or in end stage renal failure [8,[14][15][16][17][18][19]. The present study aims to determine the mean dose of darbepoetin necessary to achieve and maintain haemoglobin levels between 11.0 g/dl and 13.0 g/dl in CRF patients aged from 11 years to 18 years.…”

Darbepoetin alfa: review in the management of anemia in patients with chronic kidney disease

“…Treatment-related adverse events were observed in 3% patients. 26 Many hemodialysis centers use darbepoetin-alfa as the preferred agent for the treatment of anemia in CKD patients. In a study 98 hemodialysis outpatients, were switched from twice to thrice weekly epoetin alfa to darbepoetin alfa.…”