Developing an algorithm to convert erythropoietin dosing to darbepoetin alfa

The erythropoietic-stimulating hormone, darbepoetin alfa (Aranesp; DPO; Amgen, Thousand Oaks, California) is a long-acting agent growing in popularity as the preferred anemia management agent for patients with chronic kidney disease. Use of this drug in existing patients treated with rHu-EPO (epoetin alfa; EPO) requires conversion dosing and the potential for serious alterations in previously stable and satisfactory hemoglobin levels. This study analyzed the dosing conversion recommended by Amgen to determine if the regimen resulted in stable hemoglobin values during the conversion.

Twenty-nine stable patients on hemodialysis were selected for conversion from EPO to DPO. The dose of DPO was taken from the conversion table recommended by Amgen and based upon the patient's weekly EPO dose. The mean conversion dose was 40 mcg weekly. The patients were monitored monthly with hemoglobin, hematocrit routine chemistries, and iPTH levels according to unit policy. The dose of DPO was individually titrated to maintain the hemoglobin concentrations at target levels between 11.5 gm/dL and 13.3 gm/dL. At the end of six months, there was an analysis of the data to determine if the results warranted an adjustment in the DPO dose and if so, what the adjusted dosing factor should be.

Fifty-seven percent of the patients in the study group experienced a drop in hemoglobin levels below pre-DPO baseline levels (13.1 +/- 0.6 gm/dL) by the third month. The mean hemoglobin level dropped to 11.0 +/- 1.2 gm/dL for the entire group, representing a mean 2 +/- 1.42 gm/dL reduction. Forty-five percent of patients had a 15% to 40% drop in hemoglobin (1.9 gm/dL-5.0gm/dL). By the sixth month, patients were back to baseline hemoglobin (13.2 +/- 2.0 gm/dL). The adjusted dose at this point averaged 107 mcg weekly. Statistical analysis suggested an adjustment of 48.4 mcg to each of the Amgen recommended dose conversion values.

The current Amgen recommended DPO dose regimen for conversion from EPO resulted in a drop in hemoglobin from baseline levels in 57.2% of patients, suggesting that the current conversion table may underestimate the dose. Based upon a statistical analysis, an additional 48.4 (50) mcg to each recommended dose is needed to maintain baseline levels.