Erythropoietin use

Cancer patients also may have concurrent iron deficiency secondary to erythropoietin use ( functional iron deficiency) or to cancer. Therefore, it is imperative that these patients have iron studies done to assess adequate iron stores needed to drive hematopoiesis. If the patient is determined to have sub-optimal iron stores or is iron deficient, then replacement either orally or intravenously may be necessary, in addition to the use of erythropoietin products. The use of iron in these patients is the same as discussed previously under Iron-Deficiency Anemia. ... 

The pathogenesis of hypertension in patients with CKD is multifactorial and includes fluid retention, increased sympathetic activity, an endogenous digitalis-like substance, elevated levels of endothelin-1, erythropoietin use, hyperparathyroidism, and structural arterial changes. 

Morlock, M., Koll, H., Winter, G., and Kissel, T. (1997), Microencapsulation of rh-erythropoietin using biodegradable poly(D,L-lactide-co-glycolide) Protein stability and the effects of stabilizing excipients, Ear. I. Pharm. Biopharm., 43, 29-36. 

Darveau M, Notebaert E, Denault AY, et al. Recombinant human erythropoietin use in intensive care. Ann Pharmacother 2002 36 1068—1074. Hebert PC, Wells G, Martin C, et al. Do blood transfusions improve outcomes related to mechanical ventilation Chest 2001 119 1850—1857. Hebert PC, Wells G, Blajchman MA, et al, for the transfusion requirements in critical care investigators, Canadian critical care trials group. A multicenter, randonuzed, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999 340 409-417. 

JC Ergrie, et al. Development of radioimmunoassays for human erythropoietin using recombinant erythropoietin as tracer and immunogen. J Immunol Meth 99 235, 1987. 

K Matsubara, et al. Radioimmunoassay for erythropoietin using anti-recombinant erythropoietin antibody with high affinity. Clin Chim Acta 185 177, 1989. 

JW Fisher, et al. Development of a new radioimmunoassay for erythropoietin using recombinant erythropoietin. Kidney Int 38 969, 1990. 

TABLE 6.2 Selectivity Test of Erythropoietin Using Spike Recovery... 

Nieto, O., Hernandez, R, and Hernandez, L., Capillary zone electrophoresis of human recombinant erythropoietin using Cg coated columns without additives in the running buffer. Anal. Commun., 33, 425, 1996. 

Richard P, Pollard H, Lanctin C, Bello-Roufai M, Desigaus L, Escande D, Pitard B, Inducible production of erythropoietin using intramuscular injection of block copolymer/DNA formulation. J Gene Med, 2005, 7, 80-6. 

Li, L., H. Okada, G. Takemura et al. 2009b. Sustained release of erythropoietin using biodegradable gelatin hydrogel microspheres persistently improves lower leg ischemia. J Am Coll Cardiol 53 2378-88. 

Groleau, P.E., Deshamais, P, Cote, L., and Ayotte, C. (2008) Low LC-MS/ MS detection of glycopeptides released from pmol levels of recombinant erythropoietin using nanoflow HPLC-chip electrospray ionization. Journal of Mass Spectrometry, 43,924-935. 

Center for Biologies Evaluation and Research (CBER). This center is responsible for the regulation and approval of ah biological products intended for use in the treatment, prevention, or cure of diseases or injuries to humans. A biological product is any vims, therapeutic semm, toxin, antitoxin, vaccine, blood or blood component or derivative, or analogous product (5). It also includes products produced by biotechnology, such as interferons and erythropoietins. 

Erythropoietin (Eprex ) is physiologically produced in the kidney and regulates proliferation of committed progenitors of red blood cells. It is used to substitute erythropoietin in severe anemias due to end stage renal disease or treatment of cancer with cytostatic agents. Side effects include hypertension and increased risk of thrombosis. 

Erythropoietin is a growth factor produced by interstitial cells of the kidney in response to hypoxia. Erythropoietin stimulates haematopoiesis in the bone marrow. Recombinant human erythropoietin is used to treat anemias, e.g. anemia caused by chronic renal failure and anemia in AIDS and cancer patients. 

Anemia may occur in patients with chronic renal failure as tlie result of the inability of the kidney to produce erythropoietin. Erythropoietin is a glycoprotein hormone synthesized mainly in the kidneys and used to stimulate and regulate the production of erythrocytes or red blood cells (RBCs). Failure to produce the needed erythrocytes results in anemia Two examples of drug used to treat anemia associated with chronic renal failure are epoetin alfa (Epogen) and darbepoetin alfa (Aranesp). 

Epoetin alfa (erythropoietin EPO) and darbepoetin alfa are usually well tolerated. The most common adverse reactions include hypertension, headache, tachycardia, nausea, vomiting, diarrhea, skin rashes, fever, myalgia, and skin reaction at tlie injection site. See the Summary Drug Table Drug Used in the Treatment of Anemia for more information on these drug. 

The availability of a cDNA for erythropoietin has made it possible to produce substantial amounts of this hormone for analysis and for therapeutic purposes previously the isolation of erythropoietin from human urine yielded very small amounts of the protein. The major use of recombinant erythropoietin has been in the treatment of a small number of anemic states, such as that due to renal failure. 

Use of Packed Red Blood Cell Transfusions and Erythropoietin in Critically 111 Patients"... 

About 10% to 25% of patients treated with interferon and ribavirin require dosage reductions when hemoglobin levels decrease or they develop intolerable symptoms such as shortness of breath or severe fatigue. If warranted, erythropoietin may be used as adjunctive therapy for ribavirin-induced hemolytic anemia.45... 

The first-line treatment for anemia of CKD involves replacement of erythropoietin with erythropoiesis-stimulating agents (ESAs). Use of ESAs increases the iron demand for RBC production and iron deficiency is common, requiring iron supplementation to correct and maintain adequate iron stores to promote RBC production. Androgens were used extensively... 

Although EPO deficiency is the primary cause of CKD anemia, iron deficiency is often present, and it is essential to assess and monitor the CKD patient s iron status (NKF-K/DOQI guidelines). Iron stores in patients with CKD should be maintained so that transferrin saturation (TSAT) is greater than 20% and serum ferritin is greater than 100 ng/mL (100 mcg/L or 225 pmol/L). If iron stores are not maintained appropriately, epoetin or darbepoetin will not be effective, and most CKD patients will require iron supplementation. Oral iron therapy can be used, but it is often ineffective, particularly in CKD patients on dialysis. Therefore, intravenous iron therapy is used extensively in these patients. Details of the pharmacology, pharmacokinetics, adverse effects, interactions, dose, and administration of erythropoietin and iron products have been discussed previously. 

Besides anemia associated with cancer and CKD, anemia of chronic disease can result from inflammatory processes and occurs commonly in autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus. In treating these types of anemia of chronic disease, the most important principle is treating the underlying disease. These patients also may have iron deficiency and should be treated in the manner already discussed. Erythropoietin therapy such as epoetin-alfa therapy at a dose of 150 units/kg three times a week also may be used in these patients. 

Do not exceed more than 1 g/dL (10 g/L or 0.62 mmol/L) every 2 weeks when using erythropoietin products to increase hemoglobin. Otherwise, decrease the dose of the erythropoietin product. 

Very limited information is available on the use of combination therapy for potentiation of HbF production. Erythropoietin has shown inconsistent results in small numbers of patients. When used with hydroxyurea, erythropoietin has been shown to increase HbF to a greater extent than hydroxyurea alone, and although more studies are needed, this may provide an option for patients who do not respond to hydroxyurea alone.27... 

Bone marrow suppression ZDV Onset Few weeks to months Symptoms Fatigue, risk of T bacterial infections due to neutropenia anemia, neutropenia 1. Advanced HIV 2. High dose ZDV 3. Preexisting anemia or neutropenia 4. Concomitant use of bone marrow suppressants Avoid in patients with high risk for bone marrow suppression avoid other suppressing agents monitor CBC with differential at least every 3 months Switch to another NRTI D/C concomitant bone marrow suppressant, if possible for anemia Identify and treat other causes consider erythropoietin treatment or blood transfusion, if indicated for neutropenia Identify and treat other causes consider filgrastim treatment, if indicated... 

Yuen, C.T., Stoning, P.L., Tiplady, R.J. et al. (2003) Relationships between the A-glycan structures and biological activities of recombinant human erythropoietins produced using different culture conditions and purification procedures. British Journal of Haematology, 121 (3), 511-526. 

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