Factors Associated with Epoetin Response: DISCUSSION
We found that the lower the baseline hemoglobin level, the more likely a patient was to respond to epoetin. It is possible that the patients with lower baseline hemoglobin levels had a greater degree of erythropoietin deficiency. Studies have shown that low baseline endogenous erythropoietin levels are associated with an epoetin response. However, endogenous erythropoietin levels are not routinely checked at our facility.
Other studies have not shown an association between baseline hemoglobin and epoetin response. The definitions of epoetin response varied from an increase of 2 g/dl at four weeks to an increase of 2 g/dl at 12 weeks in these studies. In our study, hemoglobin response was assessed at eight weeks because practice guidelines suggest that epoetin response be assessed at four weeks and at eight weeks.
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Some studies have found that the two-week hemoglobin level was associated with an epoetin response. In our study, 33 of 121 patients (27%) were not checked for hemoglobin levels after two weeks of epoetin therapy. For this reason, our study did not include two-week hemoglobin values in the logistic regression model; this omission may have introduced bias into the result.
Study Limitations
Our study had several limitations. The small sample size might had led to a lack of power to show statistically significant associations between factors that were evaluated. Because of the retrospective design, our study can show only associations between epoetin response and factors analyzed in the model. Because of incomplete documentation in the charts, epoetin dose adjustments were not accounted for in the analysis. As a consequence, bias might have been introduced into the result.
The patient population at our facility consists primarily of older males, and caution is warranted in applying the study findings to the general population.
We did not differentiate between various types of malignancy, and a potential difference in epoetin response may have existed.
Epoetin Drug Utilization
Thirty-five percent of patients in our drug utilization evaluation (DUE) experienced a 2-g/dl or greater hemoglobin increase at eight weeks; response rates in other studies have ranged from 32°% to 85°%.
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Littlewood et al. conducted a retrospective study of pooled data from four epoetin clinical cancer trials. The combined response rate was 68.1% (n = 382), defined as an increase in hemoglobin of 2 g/dl or greater or an increase in hematocrit of 6% or greater. The median age of the pooled patients was 62 years (range, 18-92 years).
Elderly patients tend to require higher doses of epoetin. The mean age of patients in our DUE was about 70 years. The lower response rate in our DUE may indicate usage of insufficient doses of epoetin to achieve a response in our elderly patients.
The patients who did not respond to epoetin in our DUE may have lacked sufficient iron stores. Iron deficiency is a common cause of a suboptimal response to epoetin. All patients who begin epoetin therapy should be evaluated for baseline ferritin and transferrin saturation, and iron supplementation should be considered if necessary. Epoetin usage guidelines suggest iron supplementation when ferritin levels are below 100 ng/ml and when transferrin saturation is less than 20%.
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Compliance with baseline ferritin (64% of patients) and transferrin saturation testing (50%) was poor. Of the patients with baseline ferritin values below 100 ng/ml and a transferrin saturation below 20%, only about 50% were receiving iron supplementation. Therefore, a better epoetin response might have occurred if all patients had been evaluated for iron deficiency and had been given iron supplementation when indicated.
Another possible explanation of the response rate could be inappropriate epoetin dose adjustments. Practice guidelines recommend that if patients do not achieve more than a 1-g/dl increase in hemoglobin after four weeks of therapy, the epoetin dose should be increased. In our DUE, 37 of 121 patients (31%) had a suboptimal hemoglobin increase at four weeks. The epo-etin dose was not increased in 26 of 37 patients (70%), and this may have affected the response rate at eight weeks.
CONCLUSION
In our study, baseline hemoglobin was inversely associated with epoetin response in elderly men. Additional prospective studies, with larger sample sizes, are warranted to verify our result. Further research is needed to identify an optimal baseline hemoglobin level at which to initiate epoetin in a cost-effective manner.
In the drug utilization analysis, the response rate to epoetin was low. This low rate may have been attributable, in part, to sub-optimal monitoring of hemoglobin levels and iron stores, low rates of iron supplementation, and poor compliance with epoetin dose titration. buy kamagra
It is clear that there is room for improvement at our institution. Guidelines for epoetin dosing and monitoring have been established to assist providers when ordering epoetin. The guidelines encourage providers to document baseline ferritin and transferrin saturation and to ensure iron supplementation when indicated. The guideline also recommends that providers evaluate hemoglobin response at four and eight weeks with the appropriate dosage titrations suggested.
