Long-term intravenous epoetin-alpha / darbepoetin-alpha ratio in iron-replete hemodialysis patients.
BACKGROUND
Equivalence of intravenous (i.v.) and subcutaneous (s.c.) dosage requirements is a notable characteristic of darbepoetin-alpha (DPO), as opposed to other epoetins (EPOs). Currently in Europe, the EPOs/DPO conversion factor (200 IU EPOs = 1 microg DPO) does not take into account the route of drugs administration. To better define this ratio we have conducted a prospective, long-term trial in a group of hemodialysis patients.


METHODS
At the start, we evaluated 40 iron-replete hemodialysis patients, but the final study was performed in the remaining 25 patients. During the first 6 months, patients were on i.v. epoetin-alpha (EPOalpha) maintenance therapy (phase 1: T-6 to T0). After conversion to i.v. DPO (initial 200:1 ratio) the observation was prolonged for a period of 12 months (phase 2: T0 to T12). DPO was administered at extended dose intervals and the EPOalpha/DPO rate was adjusted every month to maintain hemoglobin (Hgb) stability. Iron status and factors inhibiting erythropoiesis were continually checked to exclude unstable patients.


RESULTS
Phase 1: EPOalpha weekly mean dose showed no significant variation. Phase 2: EPOalpha/DPO conversion factor progressively rose from 200 to 256.7 +/- 86.9 IU/microg at T7 (p<0.005) and 336.8 +/- 104.3 IU/microg at T12 (p<0.0005). DPO weekly mean dosage decreased from 40.0 +/- 12.0 microg/week at T0 to 31.6 +/- 3.7 microg/week at T7 (p<0.005) and 24.6 +/- 7.0 microg/week at T12 (p<0.0005). Mean weekly/patient acquisition cost of EPOalpha was euro 70.6 +/- 21.3 (T-6 to T0); after switching, the cost of DPO was euro 72.4 +/- 22.7 (T0) and fell to euro 53.1 +/- 11.2 during T6 to T12.


CONCLUSIONS
The progressive increase of EPOalpha/DPO ratio demonstrated that i.v. DPO requires lower doses compared with i.v. EPOalpha. When drugs are administered i.v., the starting EPOalpha/DPO conversion factor should be increased over the 200:1 ratio, similar to recommendations outlined in the United States and Japan. DPO dose reduction translated to notable cost-savings.
Icardi
Andrea
A
Nephrology and Dialysis Unit, Department of Internal Medicine, La Colletta Hospital, Arenzano, Genoa - Italy. andrea.icardi.usl3@libero.it
Sacco
Paolo
P
Salvatore
Francesca
F
Romano
Umberto
U
D000368:Aged; D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D000068256:Darbepoetin alfa; D004305:Dose-Response Relationship, Drug; D000068817:Epoetin Alfa; D004920:Erythropoiesis / Q000187:drug effects; D004921:Erythropoietin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000191:economics; D005060:Europe; D005260:Female; D006397:Hematinics / Q000008:administration & dosage* / Q000191:economics; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007501:Iron / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood / Q000191:economics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D009752:Nutritional Status; D010280:Parathyroid Glands / Q000502:physiology; D011446:Prospective Studies; D011994:Recombinant Proteins; D006435:Renal Dialysis / Q000009:adverse effects
D006397:Hematinics; D006454:Hemoglobins; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D000068817:Epoetin Alfa; D007501:Iron