what is the difference between erythropoietin and darbepoetin

Two multicentre studies with once‐weekly epoetin‐alfa have also recently been reported, one at the American Society of Nephrology meeting last year [27], and one at the recent European Renal Association meeting in Copenhagen [28]. Darbepoetin-alfa (Aranesp®, Amgen, Thousand Oaks, CA, USA) is a hyperglycosylated EPO analogue designed for prolonged survival in the circulation and with consequent greater bioavailability than epoetins. Therefore, the diffusion time in lean patients is shorter and the increase in plasma epoetin concentration is more pronounced but of shorter duration after each injection. Other studies (some comparative) using a once‐weekly treatment regimen of epoetin are summarized in Table 1. Song X, Long SR, Marder WD, Sullivan SD, Kallich J. Ann Pharmacother. It is possible that higher doses of epoetin may have to be used to obtain the same biological response, and this is of course also dependent on what conversion factor is used to compare epoetin with darbepoetin alfa.

Provenzano R, Morrison L. Once‐weekly treatment with epoetin alfa in patients with anemia due to chronic kidney disease: preliminary analysis.

It also has been used to treat chronic anemia associated with chronic renal failure.

The safety findings are consistent with what was previously reported in the literature in regards to the use of EPO. They were switched to once‐weekly administration, as in the Weiss study [22], and there was a significant fall in the mean haemoglobin over the subsequent 16 weeks despite a significant increase in epoetin dose. Darbepoetin-alfa was approved by the FDA and the EMA in 2001.31 The terminal half-life of intravenous darbepoetin-alfa was estimated to be three-fold longer than intravenous epoetin-alfa (25.3 vs. 8.5 h).

The first of these studies to be published (the Swedish Study) [22] was an open‐label comparison of once‐weekly dosing of epoetin‐beta compared with twice‐ or thrice‐weekly dosing. Novel erythropoiesis stimulating protein (NESP) maintains hemoglobin in ESRD patients when administered once weekly or once every other week.

More frequent injections of reduced amounts of epoetin creates an absorption curve whose area is more congruent with the area of the therapeutic plasma concentration.

[1] treated 12 CAPD patients with s.c. epoetin 4000 U once weekly, and found a similar efficacy to thrice‐weekly epoetin at the same dose.

All studies examining hematological parameters found a statistically significant increase in hemoglobin levels with active treatment versus placebo. Geddes C, Worjtzcak V, Adams A, McPherson M, French C. Does erythropoietin requirement increase with reduced frequency of administration? Two studies treated 10 [2] and six [4] CAPD children with once‐weekly epoetin, and increases in haemoglobin concentration were seen in both studies. Pharmacoeconomics.

This site needs JavaScript to work properly. Again, similar haemoglobin responses were seen with an equivalent dose of epoetin given two or three times weekly.

Lago M, Perez‐Garcia R, Garcia de Vinuesa MS, Anaya F, Valderrabano F. Efficiency of once‐weekly subcutaneous administration of recombinant human erythropoietin versus three times a week administration in hemodialysis patients. Thank you for submitting a comment on this article. With the recent introduction of darbepoetin alfa as a once‐weekly erythropoietic therapy, either deliberately, or incidentally, there was renewed interest in the concept of once‐weekly epoetin administration, particularly epoetin‐beta [22,23]. It is possible that higher doses of epoetin may have to be used to obtain the same biological response, and this is of course also dependent on what conversion factor is used to compare epoetin with darbepoetin alfa. Jones CH, Ridley L, Richardson D. Which EPO dose per week? Again, a significantly lower mean haemoglobin was found after conversion to once‐weekly epoetin (P=0.002) along with a trend towards higher weekly epoetin doses [26]. This observation has led to modification in the storage, handling, and administration of Eprex favoring IV administration, especially with Eprex stabilized with HSA-free formulation, and avoidance of the subcutaneous (SC) non–HSA stabilized Eprex. METHOD: Thirty-four (13 female, 21 male) CKD patients were enrolled in the study. By month 3, the equivalent dosing to maintain the haemoglobin concentration was 232 U of epoetin to 1 μg of darbepoetin alfa, and by month 4 the conversion factor was 238:1. Erythropoietin receptor-mediated clearance and degradation in bone marrow has also been hypothesized to play a prominent role; however, evaluation of rHuEPO variants with different receptor affinities failed to identify a significant role of receptor-mediated uptake in drug clearance [15]. Although previously rare, in the early 1990s there was a substantial increase in patients receiving rHuEPO who developed antibody-positive PRCA, with over 160 cases reported by 2003 [24]. The SPC for darbepoetin alfa suggests a conversion factor of 200 U of epoetin to 1 μg of darbepoetin alfa, but this ratio may alter, particularly at higher dosage levels.

Austrian Multicenter Study Group in Predialysis Patients.

Grzeszczak W, Sulowicz W, Rutowski B et al. Correspondence and offprint requests to: Dr Iain C. Macdougall, Consultant Nephrologist, Renal Unit, King's College Hospital, East Dulwich Grove, London SE22 8PT, UK. Epoetin can also be given orally in premature infants, resulting in a significant increase in plasma epoetin concentration, increased peak reticulocyte counts, and reduced blood transfusion requirements [62,81]. The Austrian multicentre study in 123 pre‐dialysis patients utilized a once‐weekly dose of 10 000 U of epoetin s.c. and found this treatment regimen effective.

In a further uncontrolled study, Simon Roger (personal communication) switched patients from epoetin‐alfa to darbepoetin alfa with a conversion factor of 200 U of epoetin to 1 μg of darbepoetin alfa. rHuEPO in maintaining target Hb concentrations in patients with renal anaemia.

A similar study was conducted by the same authors in haemodialysis patients [5], and again equivalent responses were seen with once‐ or twice‐weekly epoetin. Thus, this agent can generally be given less frequently than the standard epoetins, with dosing intervals of once weekly and once every alternate week.27 In contrast to the epoetins, dosage requirements for darbepoetin alfa for the correction of anemia and maintenance of Hb concentration in CKD patients are the same for intravenous and subcutaneous administration. Cost control is becoming an increasingly important consideration for clinicians when planning how to provide the best treatment for anaemic cancer patients.

Once weekly versus twice weekly subcutaneous administration of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.

Hussain R, Naqvi SA. Results and discussion:

Epub 2009 Jul 7.

Epoetin ζ (zeta) is a designation used for two biosimilar forms of epoetin alfa that are marketed as Silapo (Stada) and Retacrit (Hospira) (Table 7.2). In general, the degree of glycosylation is positively correlated with drug half-life but as glycosylation increases binding affinity to EPO receptors diminishes [21]. A systematic review and economic evaluation of epoetin alpha, epoetin beta and darbepoetin alpha in anaemia associated with cancer, especially that attributable to cancer treatment. Anemia Drugs: Darbepoetin Alfa, Epoetin Alfa, and Methoxy Polyethylene Glycol-Epoetin Beta Page 3 of 13 UnitedHealthcare Oxford Clinical Policy Effective 10/01/2017 ©1996-2017, Oxford Health Plans, LLC ESAs are unproven and not medically necessary to treat anemia of CKD in patients NOT on dialysis for a hematocrit greater than 30%.1,4,5,42 Analyses showed significantly lower costs for epoetin alpha ( 2,743.27 euros) than for darbepoetin alpha (3,627.98 euros ) or epoetin beta ( 3,292.28 euros): epoetin alpha vs. darbepoetin alpha (P < 0.0001); epoetin beta vs. darbepoetin alpha (P = 0.0001); epoetin alpha vs. epoetin beta (P = 0.0009). They include the presence of pre-existing hypertension, rapid increase in hematocrit, a low baseline hematocrit before r-HuEPO administration, high doses and intravenous route of administration, the presence of native kidneys, a genetic predisposition to hypertension, and possibly a younger age.1,2,56 There are several potential mechanisms by which r-HuEPO therapy may increase BP in hemodialysis patients. Nevertheless, a number of efficacy studies of darbepoetin alfa have confirmed that the drug is effective with a once‐weekly dosing schedule [15–20], and indeed some patients have managed to get away with once every 2 weeks [18] (or even once every 4 weeks [21]) administration. HHS 2006 Jan;40(1):58-65; quiz 169-70. doi: 10.1345/aph.1G042. In a recent issue of Nephrology Dialysis Transplantation, Jones et al. Patients who develop neutralizing anti-erythropoietin antibodies are at risk for pure red cell aplasia (PRCA), which can require red blood cell transfusions. rHuEPOα contains over 35 different N-linked and 6 O-linked oligosaccharides and manufacturing controls to ensure lot-to-lot consistency are challenging for this class of drugs [22]. Alison Brophy, ... Maria Cardinale, in Side Effects of Drugs Annual, 2016. Recombinant human erythropoietins (rHuEPO) are erythropoiesis-stimulating agents (ESA) used in the treatment of anemia resulting from chronic kidney disease, treatments for cancer or HIV infection. Initially, it was hypothesized that the replacement of human serum albumin (HSA) with polysorbate 80 (PS80) in the formulation may have led to the formation of drug-laden PS80 micelles, which could act in an adjuvant manner to break immune tolerance. The EXTEND trial is a multicenter, longitudinal observational study involving 4278 non-dialysis CKD patients initiated on darbepoetin-alfa doses either every 2 weeks or every 4 weeks to maintain an Hb of approximately 11.5 g/dL in ESA-pretreated and ESA-naïve patients.39 Route of administration was subcutaneous for 95% of patients and intravenous for 5%.

A follow-up study is required to determine if the risk of peritonitis is increased by intraperitoneal epoetin [120].

Once‐weekly administration of both epoetin and darbepoetin alfa is possible provided the drug is given s.c.

Saleh A, Krane NK, Caballero M, Starks E. Once weekly subcutaneous erythropoietin is an effective therapy in the treatment of anemia of end stage renal disease patients on CAPD. Once‐weekly compared with three‐times‐weekly subcutaneous epoetin beta: results from a randomized, multicenter, therapeutic‐equivalence study.

Derek G. Waller BSc (HONS), DM, MBBS (HONS), FRCP, Anthony P. Sampson MA, PhD, FHEA, FBPhS, in Medical Pharmacology and Therapeutics (Fifth Edition), 2018. What we are lacking now is a head‐to‐head study comparing once‐weekly epoetin with darbepoetin alfa. 2009 Jul;25(7):1775-84. doi: 10.1185/03007990903001150. Given these properties, the control of glycosylation is highly critical in maintaining product quality.

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