Erythropoietin: Selecting Route of Administration

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

Intravenous

• Is commonly given intravenously to patients on maintenance hemodialysis

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:

1. Drug Information Leaflet
2. www.uptodate.com