Recombinant erythropoietin epoetin

Blood corpuscles develop from stem cells through several cell divisions (n = 17 ). Hemoglobin is then synthesized and the cell nucleus is extruded. Erythropoiesis is stimulated by the hormone erythropoietin (a glycoprotein), which is released from the kidneys when renal oxygen tension declines. A nephrogenic anemia can be ameliorated by parenteral administration of recombinant erythropoietin (epoetin alfa) or hyperglyco-sylated erythropoietin (darbepoetin longer half-life than epoetin). 

Pure red cell aplasia (PRCA) PRCA has been reported in a limited number of patients exposed to epoetin alfa. This has been reported predominantly in patients with CRF. Evaluate any patient with loss of response to epoetin alfa for the etiology of loss of effect. Discontinue epoetin alfa in any patient with evidence of PRCA and evaluate the patient for the presence of binding and neutralizing antibodies to epoetin alfa, native erythropoietin, and any other recombinant erythropoietin administered to the patient. In patients with PRCA secondary to neutralizing antibodies to erythropoietin, do not administer epoetin alfa, and do not switch such patients to another product as anti-erythropoietin antibodies cross-react with other erythropoietins. 

A. General description Erythropoietin is a glycoprotein normally produced in the kidneys and is responsible for the stimulation of red blood cell production. Epoetin alfa is derived via recombinant DNA techniques by mammalian cells after the insertion of the human erythropoietin gene its amino-acid sequence is identical to that of endogenous erythropoietin. Epoetin alfa... 

Epoetin alfa, recombinant erythropoietin, is a glycoprotein that simulates erythrocyte production. Epoetin alfa is administered three times weekly subcutaneously or intravenously. Epoetin is used to treat anemia in patients with chronic renal failure, HIV infection, and patients receiving chemotherapy [104]. Development of a safe, effective nasal formulation of epoetin alfa, containing an absorption enhancer could once again improve the efficacy of epoetin alfa therapy, and reduce the number of injections required in these sensitive patient populations. 

Recombinant human erythropoietin (epoetin and darbepoetin) provides effective therapy with a very favorable risk-benefit ratio in hemodialysis patients with end-stage chronic renal insufficiency, and in patients with progressive renal insufficiency who are not yet being dialysed (1). It improves cognitive function and the quality of life of patients with chronic uremia (2-5) and is very effective in children with chronic renal graft rejection and anemia (6). It also offers new opportunities for treating anemia in non-uremic patients. In patients with chemotherapy-induced anemia, epoetin increases hemoglobin concentration, reduces transfusion requirements, and improves quality of life (7,8). The response rate to epoetin in patients with multiple myeloma and anemia, which is 55-85% (9), increases when GM-CSF or G-CSF is... 

Podesta A, Carmagnini E, Parodi E, Dottori V, Crivellari R, Barberis L, Audo A, Lijoi A, Passerone G. Elective coronary and valve surgery without blood transfusion in patients treated with recombinant human erythropoietin (epoetin-alpha). Minerva Cardioangiol 2000 48(ll) 341-7. 

Human recombinant erythropoietin (rhEPO or epoetin) is is a synthetic version of human EPO that is used to treat anemia. Following replenished iron stores and exclusion of other causes of anemia, the addition of recombinant epoetin is indicated for the treatment of CKD-related anemia. The gene for human EPO was cloned in 1985 and epoetin was introduced into clinical practice shortly afterwards.It is effective at correcting the anemia of CKD in 90% to 95% of patients. The most common side effect is hypertension and therefore blood pressure should be well controlled before the introduction of treatment. Hypertension may develop or worsen in 23% of patients. Failure to respond to treatment requires thorough investigation for many potential causes (Box 45-2). It is estimated that 3 million patients worldwide have received treatment with epoetin. Pure red cell aplasia (PRCA) has occurred in patients treated with epoetin. This has been described in a small number of patients receiving epoetin via the subcutaneous route. In the majority of cases, neutralizing antibodies to EPO have been detected. If a case of PRCA is proven, then no further recombinant erythropoietin products can be administered. 

The human gene for erythropoietin, a hormone produced in the kidney, was first cloned in the 1980s (Jacobs et al, 1985), and the recombinant form was developed soon after that (Flaherty etal, 1989). The recombinant alpha form of erythropoietin, epoetin, is now very widely used in the context of the anaemia associated with... 

Flaharty KK, Grimm AM and Vlasses PH (1989). Epoetin human recombinant erythropoietin. Clin Pharm, 8, 769-782. 

Recombinant erythropoietin therapy, in conjunction with adequate iron intake, can be highly effective in a number of anemias, especially those associated with a poor erythropoietic response. There is a clear dose-response relationship between the epoetin alfa dose and the rise in hematocrit in anephric patients, with eradication of their anemia at higher doses. Epoetin alfa is also effective in the treatment of anemias associated with surgery, acquired immunodeficiency syndrome (AIDS), cancer chemotherapy,... 

More recently, novel erythropoiesis-stimulating protein (NESP) or darbapoetin alfa (Aranesp) has been approved for clinical use in patients with indications similar to those for epoetin alfa. It is a genetically modified form of erythropoietin in which four amino acids have been mutated such that additional carbohydrate side chains are added during its synthesis, prolonging the circulatory survival of the dmg to 24 to 26 hours. Recombinant erythropoietin therapy, in conjunction with adequate iron intake, can be highly effective... 

Recombinant human erythropoietin epoetin cdfa) is nearly identical to the endogenous hormone. The carbohydrate modification pattern of the recombinant form differs slightly from that of the native protein, but this difference apparently does not alter kinetics, potency, or immunoreac-tivity of the drug. However, modem assays can detect these differences, which is of significance for detecting athletes who use the recombinant product for blood doping. ... 

Epoetin alfa therapy, 150 U/kg 3 times/week or 450-600 U/kg once a week, can reduce the transfusion requirement in cancer patients undergoing chemotherapy when Hb levels fall below 10 g/dL. For anemia associated with hematologic malignancies, recombinant erythropoietin is useful in patients with low-grade myelodysplastic syndrome. A baseline serum erythropoietin level may help to predict the response most patients with blood levels of more than 500 U/L are unlikely to respond to any dose of the drug. Most patients treated with epoetin alfa experienced an improvement in their anemia, sense of well being, and quality of life. This improved sense of well being, particularly in cancer patients, may not be solely due to the rise in the hematocrit. 

Recombinant DNA technology products aldesleukin (IL-2, used in renal cancer) erythropoietin (epoetin alfa, used in anemias) filgrastim (G-CSF, used in neutropenia) interferon alpha (used in hepatitis B and C and in cancer), interferon beta (used in multiple sclerosis) interferon gamma (used in chronic granulomatous disease) oprelvekin (IL-11, used in thrombocytopenia) thrombopoietin (used in thrombocytopenia) and sargramostim (GM-CSF, used in neutropenia). 

The most frequently reported adverse events are headache, polycythemia, tiredness, common cold, diarrhea, nausea, stomach pains, chest pressure sensation, back pain, leg pain, and dizziness, as confirmed in a phase I open bioequivalence parallel group study of two recombinant human epoetin alfa products the pattern of the adverse events revealed no relevant differences between the erythropoietin derivatives [95 ]. Patients who were randomized to early intervention with immediate epoetin alfa (n = 68) or to standard intervention with epoetin alfa (n = 68), and a further 50 who were not randomized, pain, injection-site pain, bone pain, and deep vein thrombosis were observed [96 ]. 

Studies have shown that in patients with chemotherapy-related anemia, therapy with erythropoietin products (epoetin-alfa and darbepoetin) can increase hemoglobin, decrease transfusion requirements, and improve quality of life.12 Epoetin is recombinant human erythropoietin, and darbepoetin is structurally similar to endogenous erythropoietin. Both bind to the same receptor to stimulate red blood cell production. Darbepoetin differs from epoetin in that it is a glycosylated form and exhibits a longer half-life in the body. The half-lives of a single subcutaneous injection of epoetin or darbepoetin in patients are roughly 27 and 43 hours, respectively. 

Epoetin Alfa [Erythropoietin/ EPO] (Epogen/ Procrit) [Recombinant Human Erythropoietin] WARNING Use lowest dose possible may be associated w/1 CV, thromboembolic events /or mortality D/C if Hgb >12 g/dL Uses CRF associated anemia zidovudine Rx in HIV-infected pts, CA chemo -1- transfusions associated w/ surgery Action Induces ery-thropoiesis Dose Adul Peds. 50-150 Units/kg IV/SQ 3x/wk adjust dose q4-6wk PRN Surgery 300 Units/kg/d x 10 d before to 4 d after -I dose if Hct 36% or Hgb, T > 12 g/dL or Hgb t >1 g/dL in 2-wk pmod hold dose if Hgb >12 g/dL Caution [C, +] Contra Uncontrolled HTN Disp Inj SE HTN, HA, fatigue, fever, tach, NA Interactions None noted EMS Monitor ECG for hypokalemia (peaked T waves) t risk of CV thrombotic events OD May cause HA, dizziness, SOB and polycythemia symptomatic and supportive... 

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. 

Erythropoietin, a 34-39 kDA glycoprotein, was the first human hematopoietic growth factor to be isolated. It was originally purified from the urine of patients with severe anemia. Recombinant human erythropoietin (rHuEpo, epoetin alfa) is produced in a mammalian cell expression system... 

Epoetin-oc (recombinant human erythropoietin) is approved for the treatment of anemia in hemodialysis patients and those receiving chemotherapy. A hyperglyco-sylated analogue of erythropoietin (darbepoetin-oc) that has a lower clearance rate and can be dosed less frequently has also been approved. Erythropoietin stimulates the proliferation of erythrocyte progenitor cells in bone marrow and increases peripheral red blood cell (RBC) counts. 

Epoetin (recombinant derived human erythropoietin) must be given s.c. (which may be more effective) or i.v. the t) is 4 h and appears not to be affected by dialysis. Maximum reticulocyte response... 

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. 

Epoetin Alfa. Epoetin alfa. rEPO (Epogen. Procrii). is the recombinant human erythropoietin producc d in Chinese hamster ovary cells into which the human erylhropoielin gene has been inserted. These mammalian cells glycosylate the protein in a manner similar to (hat observed in human cells. ... 

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