Epoetin beta

Neorecormon (epoetin beta, rEPO) Anaemia associated with various medical conditions Boehringer-Mannheim... 

Neorecormon (tradename, also known as epoetin beta) is a recombinant human EPO first approved for medical use in the EU in 1997. It is indicated for the treatment of anaemia associated with various medical conditions, most commonly chronic renal failure and cancer patients receiving chemotherapy. Neorecormon is produced by recombinant DNA technology in a CHO cell line and is manufactured as outlined in Figure 10.5. It is presented in lyophilized format at various strengths (500-10 000 IU/vial) and contains phosphate buffer, sodium chloride, calcium chloride, urea, polysorbate and various amino acids as excipients. 

Pegzerepoetin alfa (also known as methoxy polyethylene glycol-epoetin beta) is a continuous erythropoietin-receptor activator that is licensed for... 

Recombinant human erythropoietin for intravenous or subcutaneous injection is available as epoetin alfa, epoetin beta and since 2001 as darbe-poeitin alfa. Epoetin alfa and epoetin beta have different carbohydrate moieties. When administered intravenously the elimination half-life of epoetin alfa is approximately 10 hours. Subcutaneous bioavailability is 20-50% of IV and peak concentrations are achieved after some 20 hours. The recommended initial dose is 50-100 units/kg three times a week in patients with chronic renal failure. 

Methoxy polyethylene glycol-epoetin beta Long-acting form administered 1-2 times per month... 

Epoetin beta (Methoxy polyethylene glycol-epoetin beta) (Mircera)... 

Erythropoietin, epoetin alfa, epoetin beta, epoetin gamma, and darbepoetin... 

Renal anaemia is generally treated with erythropoiesis-stimulating agents (ESAs), of which three are currently in general use the erythropoietins, namely epoetin alfa (Eprex), epoetin beta (NeoRecormon) and darbepoetin alfa (Aranesp). 

Erythropoietin is an endogenous glycosylated protein hormone that is produced mainly in the kidneys and stimulates the production of members of the erythroid series of blood cells. Epoetin is the name that has been given to recombinant forms, of which there are four epoetin alfa, epoetin beta, epoetin omega, and darbepoetin alfa. Darbepoetin alfa is a supersialylated form of erythropoietin with a longer half-Ufe. 

In 194 patients a low dose of epoetin beta before elective surgery was well tolerated and reduced the need for transfusions (43). 

In a randomized study of 180 patients with anemia due to hormone-refractory prostate cancer, who were treated with epoetin beta 1000 lU or 5000 lU subcutaneously 3 times a week for 12 weeks, cardiovascular events were more frequent with the higher dosage. Four patients had deep vein thrombosis and two had myocardial infarctions all were taking the higher dosage. However, only one of the patients with deep vein thrombosis had a high hemoglobin concentration (21). 

In a placebo-controlled study of severely anemic patients with low-grade non-Hodgkin s lymphoma, chronic lymphocytic leukemia, or multiple myeloma, a fatal case of pulmonary embolism was thought to have been related to treatment with epoetin beta (95). Thrombotic events, such as vascular access thrombosis, venous thrombosis, and pulmonary embolism, have occurred after treatment with epoetin or darbepoetin alfa (96). It is therefore recommended that a rapid rise in the hemoglobin concentration be avoided and that care should be taken that the hemoglobin concentration does not exceed 12.1 g/dl (7.5 mmol/1) (97). 

In 173 renal patients with anemia, in which once-weekly administration of subcutaneous epoetin beta was compared with thrice-weekly administration, there were seven serious adverse events, possible related to epoetin beta (98). There were two cases of arteriovenous fistula thrombosis in the once-weekly group and three in the thrice-weekly group. A transient ischemic attack and a hypertensive crisis occurred in one patient in the once-weekly group. 

In the past, subcutaneous epoetin alfa resulted in more pain than epoetin beta, owing to citrate buffer in the product. Although the formulation of epoetin alfa has been changed to a phosphate buffer, discomfort after epoetin alfa is still greater than after epoetin beta (115,116). 

Johansson JE, Wersall P, Brandberg Y, Andersson SO, Nordstrom L EPO-Study Group. Efficacy of epoetin beta on hemoglobin, quality of life, and transfusion needs in patients with anemia due to hormone-refractory... 

Locatelh F, Baldamus CA, ViUa G, Ganea A, Martin de Francisco AL. Once-weekly compared with three-times-weekly subcutaneous epoetin beta results from a randomized, multicenter, therapeutic-equivalence study. Am J Kidney Dis 2002 40(l) 119-25. 

Veys N, Dhondt A, Lameire N. Pain at the injection site of subcutaneously administered erythropoietin phosphate-buffered epoetin alpha compared to citrate-buffered epoetin alpha and epoetin beta. Chn Nephrol 1998 49(1) 41. ... 

Raftery MJ, Auinger M, Hertlova M. Safety and tolerability of a multidose formulation of epoetin beta in dialysis patients. Collaborative Study Group. Chn Nephrol 2000 54(3) 240-5. 

Ruiz PG, Balcke P, Martinez JM, Harris K. Tolerability of the epoetin-beta multidose formulation (Reco-Pen) in patients with renal anaemia. Chn Drug Invest 2000 20 151-8. 

Neutralizing antibodies to epoetin have been identified in a small number (less than 200) of patients treated with either epoetin alfa or epoetin beta. These patients developed an absolute resistance to epoetin therapy which relegates them to intermittent blood transfusions as the primary therapeutic option. Cases have been reported, primarily with one epoetin alfa product manufactured outside the United States, Eprex (Johnson Johnson, Manati, Puerto Rico), and have occurred in parallel with the increase in SC administration. Although the case reports are relatively few in number, clinicians should be aware of this thus far rare phenomenon in patients resistant to erythropoietic... 

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