Hematocrit stability following intravenous versus subcutaneous administration of epoetin alfa to dialysis patients: a post hoc analysis

Background. subjects and methods: A previous study of epoetin alfa dose req uirements [Paganini et al. 1995] among hemodialysis patients who were switc hed from thrice weekly intravenous (i.v.) to thrice weekly subcutaneous (s. c.) administration showed that the weekly epoetin alfa dose requirement dec reased by 18.5% after 13 to 16 weeks s.c. treatment and 26.5% after 21 to 2 4 weeks, without significant change in hematocrit. There was patient-to-pat ient variation in response, however, and 39% of the patients required the s ame or greater doses of epoetin alfa after the change from i.v. to s.c. adm inistration. The present study reexamines the database to compare hematocri t stability between the two routes of administration. Results: During 4 wee ks of i.v. epoetin alfa administration, the pooled standard deviation (SD) for the patients' (n = 72) weekly hematocrit measurements was 1.40, compare d with weeks 13 to 16 of s.c, epoetin alfa administration when the SD was 1 .66 (p < 0.01). Among 41 patients who completed 24 weeks of s.c. therapy, t he pooled SD for the 4 weeks of i.v. treatment was 1.37 compared with 2.02 during weeks 21-24 of s.c. treatment (p < 0.01). Sixty-eight percent of pat ients had lower hematocrit SD during 4 weeks of i.v. therapy than during th e 4 weeks of s.c. therapy (p = 0.03). Conclusion: These data suggest that h ematocrits may be more stable when epoetin alfa is administered i.v. rather than s.c. to patients on dialysis. These results would be expected since 1 00% of i.v.-administered epoetin alfa reaches the systemic circulation comp ared with 18% to 80% bioavailability of s.c.-administered epoetin alfa. Wit hin-patient variation in s.c. epoetin alfa absorption may be related to non -uniformity of adipose tissue, blood supply, lymphatic drainage, and other factors at sequential injection sites, and may explain the variability in h ematocrit after s.c. administration.