Differences in Intravenous and Subcutaneous Application of Recombinant Human Erythropoietin: A Multicenter Trial

Abstract

The aims of this clinical study were to compare the maintenance doses for intravenous (i.v.) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under i.v. and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end-stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1-week pretreatment phase, a subsequent 8-week double-blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol.% was 33 U/kg body weight three times a week in the i.v. group compared with 22 U/kg in the SC group (i.e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the i.v. group. During the maintenance phase, there was no essential difference between the two groups.

Subcutaneous Compared with Intravenous Epoetin in Patients Receiving Hemodialysis

“…Many, [12][13][14][15][16][17][18][19][20][21] but not all, [22][23][24][25][26][27] previous trials also concluded that the doses of epoetin required to maintain the hematocrit at a given level were lower with a subcutaneous route of administration, but most of those studies were nonrandomized crossover studies in which the patients were switched from the intravenous to the subcutaneous route of administration. This design does not take into consideration the possibility of crossover effects that would, owing to the long half-life of red cells, delay the decrease in hematocrit resulting from an inadequate dose.…”

Haemoglobin response to subcutaneous versus intravenous epoetin alfa administration in iron‐replete haemodialysis patients

“…The introduction of recombinant human erythropoietin (epoetin) in the late 1980s revolutionized the management of anaemia in these patients by increasing the haemoglobin (Hb) concentration and reducing transfusion requirements. It was initially administered intravenously (IV), however, early trials of subcutaneous (SC) use demonstrated a possible improvement in efficacy with a variably lower dose required to maintain a target Hb concentration or haematocrit 9–12 . This was supported by pharmacokinetic studies in haemodialysis patients where SC dosing was found to have a markedly prolonged elimination despite a reduction in bioavailability 13,14 .…”

Administration of the same dose of epoetin-beta intravenously and subcutaneously to patients with renal anaemia

“…The results of this study seem to endorse this when iron status is optimal, but the same cannot be said when there is a deficit in the level of available iron. In previous studies many included patients had suboptimal iron status at baseline, and the parameters were poorly or not described during the trials [3,[5][6][7][8].…”

“…route of administration is more comfortable. The evidence for these recommendations comes from studies [3][4][5][6][7][8] that included many patients with suboptimal iron stores by current standards. Optimal iron treatment has since shown to be important for the optimal effect of EPO [9][10][11] and recent studies correcting for iron deficiency have found a much lower, if any, increase in EPO dosage and/or decrease in haemoglobin (Hb) level after conversion from s.c. to i.v.…”