ASK DIS: Erythropoietin: Selecting Route of Administration

Availability: Recombinant human erythropoietin (r-HuEpo)/epoetin alfa 10,000 IU/ml Inj

Intravenous

Subcutaneous

Indicated when access is not readily available (patient not yet on dialysis and peritoneal dialysis patients)
there are a number of advantages of subcutaneous administration in hemodialysis, peritoneal dialysis, and predialysis patients
longer half-life(24 hours versus 4 to 9 hours when given intravenously); more sustained plasma erythropoietin concentration, which contributes to the requirement for a lower dose; and possibly a lower risk of erythropoietin-induced hypertension
The bioavailability of subcutaneous injectable erythropoietin is much lower than that of the intravenous drug: approximately 20-30%
Of practical consideration, subcutaneous erythropoietin offers chronic kidney disease (CKD) patients who are not on hemodialysis the option to self-administer the drug without the need for a clinic visit

Side Effect Comparison

adverse effects of subcutaneous erythropoietin are generally similar to those for intravenous erythropoietin
Some patients complain of pain at the site of injection, possibly induced by the citrate used as a stabilizer; this may be minimized by using a concentrated formulation
The development of pure red cell aplasia has principally been associated with the subcutaneous administration of Eprex
Based upon some analysis, the manufacturer instituted a "best handling practice" program, which coincided with a change in labeling in which subcutaneous administration of Eprex is contraindicated in patients with CKD

Haemodialysis Patients

Erythropoietin given subcutaneously three times a week will maintain the hemoglobin at the same level, albeit at a lower dose than intravenous erythropoietin.
In most published studies, subcutaneous administration is associated with a 25 to 50 percent erythropoietin dose reduction
Concentrations achieved with SC may be more metabolically (as well as economically) efficient than the peak levels observed with IV
erythropoietic response is not dependent on the peak concentration of erythropoietin achieved, but rather on the duration of time that erythropoietin levels are maintained above baseline concentration
A once weekly or once every two weeks SC regimen has been used successfully in small groups of hemodialysis patients

Supporting Evidence

a study of 13 hypertensive hemodialysis patients who were receiving IV erythropoietin therapy and were switched to SC administration reported a reduction in erythropoietin dose by one-third
Concomitantly, predialysis mean arterial pressure significantly decreased during the first month of SC administration without relevant changes in hematocrit.
After six months, five patients remained normotensive without antihypertensive medications, and six of the remaining eight patients required antihypertensive drugs at lower doses

Recomendations:

based on general guides, both route of administration are almost equivalent, with IV not having pure red cell aplasia while SC offers a longer action and allows for self administration
if SC is chosen, CBC count, RBC indices, a reticulocyte count, and a differential analysis of WBCs should be obtained and monitored

References:

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