Epoetin Therapy Research Articles

Erythropoietin Use in the Critical Care Setting

Biotechnology products signify a major advancement in our world today. Products resulting from biotechnology will revolutionize how health care is delivered. One of these technologic breakthroughs is recombinant human erythropoietin (epoetin). Its impact on the delivery of care to the anemic renal patient is changing the roles of nurses who provide care for these patients. Epoetin alfa has virtually eliminated the necessity of transfusions in the renal patient population, while simultaneously improving the quality of life for those patients and their families. To appropriately monitor the patient receiving epoetin therapy, the nurse must understand iron physiology and metabolism, factors that influence blood pressure, and factors that can blunt the response to epoetin therapy, and still appreciate the individual nursing requirements of each patient. Such juggling of information demands that the critical care nurse be alert to the subtle changes occurring within the patient, thereby allowing sound decisions based on astute nursing assessment.

Controversies in Determination of Epoetin (Recombinant Human Erythropoietin) Dosages

Worldwide experience has confirmed the efficacy and safety of epoetin (recombinant human erythropoietin) therapy for renal anaemia and attention has focused on broader issues, including rational epoetin dosage and administration. Controversy regarding epoetin dosage has continued from the earliest multicentre clinical trials involving patients on haemodialysis. These trials examined 2 types of initial dosages: low doses which were titrated upwards (Sundal & Kaesar 1989) or high doses that were titrated downwards (Eschbach et al. 1989a). Intravenous administration was soon challenged by the success of low-dose subcutaneous epoetin given 3 times weekly (Bommer et al. 1988) or even daily (Granolleras et al. 1989). Early guidelines in the United States recommended initial dosages of 150 U /kg, reflecting experience with high-dose therapy (Ad Hoc Committee for the National Kidney Foundation 1989). Epoetin dosages have since been reduced by factors including clinical experience and US FDA approved labelling both for initial doses of 50 to 100 U/kg and a lower target haematocrit (30 to 33%) than was used in many clinical trials. Most notably, reimbursement constraints have reduced dosages (Sisk et al. 1991). This discussion focuses on clinical experience with epoetin as the determinant of rational and costeffective epoetin administration. While reimbursement policies have influenced epoetin dosage, these policies, which are not discussed here, are modified as the pharmacology of the drug becomes clearer. Similarly, the target haematocrit is a major determinant of epoetin dosage, but should be established by physiological studies and is not discussed.

Phase I-II Trial of Erythropoietin in the Treatment of Cisplatin-Associated Anemia

Cancer patients undergoing chemotherapy with cisplatin-containing regimens often develop anemia. Although the cause is multifactorial, erythropoietin deficiency appears to play an important role. Recombinant human erythropoietin (epoetin) has been reported to be effective in reversing cisplatin-associated anemia in animal studies but not in clinical trials. This pahse I-II clinical trial was designed to assess the safety and efficacy of treatment with epoetin for anemia associated with cisplatin chemotherapy. Twenty-one cancer patients treated with cisplatin and manifesting anemia (hemoglobin level less than 110 g/L) received epoetin at escalating doses (25, 50, 100, or 200 U/kg body weight) intravenously five times a week for 4 weeks. Epoetin was well tolerated, and a maximal tolerated dose was not reached. Two patients experienced hypertension, which responded to standard antihypertensive therapy. No dose-dependent severe toxic effects were seen. The increase in hemoglobin levels from baseline on day 1 of the study was statistically significant after 4 weeks of epoetin therapy in the groups receiving 100 U/kg (mean change +/- SD = 19 +/- 13 g/L; P = .03) or 200 U/kg (mean change = 24 +/- 17 g/L; P = .007). A clinical response--an increase in hemoglobin level greater than 10 g/L--was achieved in 12 patients after 4 weeks of treatment. For these responders, the mean increase in hemoglobin level was 25 +/- 3.3 g/L over the level observed at the same time in the chemotherapy cycle preceding epoetin treatment, and this increase was statistically significant (P = .0001). Neither serum erythropoietin level nor hemoglobin level predicted a patient's response to epoetin. These preliminary findings suggest that epoetin is effective and well tolerated for the reversal of cisplatin-associated anemia, with the 100-U/kg and 200-U/kg dose levels offering optimal clinical response. We are conducting a phase III trial to determine the effect of epoetin on transfusion requirements in patients undergoing chemotherapy.

Pharmacoeconomics of Genetically Engineered Drugs

Biotechnology is a rapidly developing area of drug development which has great growth potential. Development of genetically engineered drugs is very expensive and as these products become available the impact on healthcare costs could be vast. The cost-benefit ratio of biotechnology products needs to be established, but few relevant pharmacoeconomic studies are available. Issues in pharmacoeconomic analysis of genetically engineered drugs can be exemplified by the data available for alteplase, epoetin and interferon alpha-2b. One study concluded that thrombolysis with streptokinase rather than alteplase would substantially reduce the percentage of total hospital costs that were not reimbursed. However, differences in efficacy were not accounted for. Based on the superior efficacy of alteplase, a more extensive pharmacoeconomic analysis found that alteplase was more cost-effective than streptokinase when the agents were combined with aggressive reocclusion management. However, this conclusion may be altered by the finding of a more recent study that streptokinase may be at least as effective as alteplase. Economic factors involved in epoetin treatment of anaemia associated with chronic renal disease have been studied thoroughly. However, cost-effectiveness or cost-benefit analysis was not attempted, and improvement in quality of life with epoetin therapy also needs to be considered, to facilitate cost-utility analysis. Compared with chlorambucil, the use of interferon alpha-2b for hairy cell leukaemia resulted in significant direct and indirect cost savings, in a retrospective cost-benefit analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Epoetin therapy may reduce dialyser efficiency

Epoetin therapy may reduce dialyser efficiency

A detailed investigation of the cause of anaemia should precede epoetin therapy

A detailed investigation of the cause of anaemia should precede epoetin therapy

ADRs complicating epoetin therapy in patients with uraemia

ADRs complicating epoetin therapy in patients with uraemia

The benefits of epoetin therapy are not maintained upon withdrawal

The benefits of epoetin therapy are not maintained upon withdrawal

Preference given to short term epoetin therapy

Preference given to short term epoetin therapy

No money allocated for epoetin therapy in a UK renal unit

No money allocated for epoetin therapy in a UK renal unit

Epoetin (recombinant human erythropoietin). A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in anaemia and the stimulation of erythropoiesis.

Epoetin (recombinant human erythropoietin) is a sialoglycoprotein hormone that appears to be immunologically and biologically equivalent to the endogenous compound, enhancing erythropoiesis dose-proportionally. The therapeutic efficacy of epoetin in the treatment of anaemia associated with chronic renal failure has been established, with almost all patients responding with increases in haematocrit and haemoglobin levels, and improvements in quality of life. Some patients demonstrate relative epoetin resistance and require a higher dosage to achieve target haemoglobin and haematocrit levels. Maintenance of an adequate iron supply is essential and iron supplementation is recommended if serum ferritin is below 100 to 150 micrograms/L or transferrin saturation is less than 20%. The incidence of serious adverse effects may be reduced by maintaining a moderate rate of increase in the haematocrit with close monitoring of blood pressure and dialysis efficacy. Individual titration of epoetin dosage is recommended, with increases made in small increments to achieve haematocrit and haemoglobin levels of 30 to 33% and 10 to 12 g/dl, respectively, although the optimal haematocrit for each patient should be individually determined. Some patients will also require a modest increase in heparin dosage because of a possible increase in clotting tendency. Hypertension is the most common adverse effect in patients with chronic renal failure, occurring partially as a result of increasing blood viscosity and peripheral vascular resistance with the correction of anaemia. Maintenance epoetin therapy has been given for more than 2 years without a decrease in responsiveness and does not appear to adversely affect the outcome of renal transplantation. Thus, epoetin represents a significant therapeutic advance in the treatment of anaemia associated with chronic renal failure and should be considered a first option for these patients. Its potential value in the treatment of anaemia associated with other disorders and in facilitating autologous blood donation remains to be fully determined.