Erythropoietin: Subcutaneous administration
- Wajeh Y Qunibi, MD
Wajeh Y Qunibi, MD
- Professor of Medicine
- University of Texas Health Sciences Center
- William L Henrich, MD, MACP
William L Henrich, MD, MACP
- Professor of Medicine
- President of the Health Science Center
- University of Texas Health Science Center School of Medicine
Although erythropoietin (EPO) is commonly given intravenously to patients on maintenance hemodialysis, there are a number of advantages of subcutaneous administration in hemodialysis, peritoneal dialysis, and predialysis patients. These include longer half-life; more sustained plasma erythropoietin concentration, which contributes to the requirement for a lower dose; and possibly a lower risk of erythropoietin-induced hypertension. 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 (unless required for insurance reasons) and intravenous access. However, the 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 a specific erythropoietin product (Eprex) that was manufactured and marketed outside the United States. This disorder has also been reported less frequently with other preparations. 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. Erythropoietin-related pure red cell aplasia is now extremely rare. (See "Pure red cell aplasia due to anti-erythropoietin antibodies".)
The following is a brief overview of the use of subcutaneous erythropoietin among patients with CKD. A detailed discussion of the use of this agent in this patient population is presented separately. (See "Erythropoietin for the anemia of chronic kidney disease among predialysis and peritoneal dialysis patients" and "Erythropoietin for treatment of the anemia of chronic kidney disease in hemodialysis patients".)
Adverse effects of erythropoietin-stimulating agents (ESA), including erythropoietin, are discussed elsewhere. (See "Anemia of chronic kidney disease: Target hemoglobin/hematocrit for patients treated with erythropoietic agents", section on 'Adverse effects' and "Erythropoietin for treatment of the anemia of chronic kidney disease in hemodialysis patients", section on 'Adverse cardiovascular effects with high hemoglobin levels' and "Erythropoietin for the anemia of chronic kidney disease among predialysis and peritoneal dialysis patients", section on 'Adverse effects'.)
- Bommer J, Samtleben W, Koch KM, et al. Variations of recombinant human erythropoietin application in hemodialysis patients. Contrib Nephrol 1989; 76:149.
- McMahon LP, Dawborn JK. Experience with low dose intravenous and subcutaneous administration of recombinant human erythropoietin. Am J Nephrol 1990; 10:404.
- Besarab A. Optimizing epoetin therapy in end-stage renal disease: the case for subcutaneous administration. Am J Kidney Dis 1993; 22:13.
- Paganini EP, Eschbach JW, Lazarus JM, et al. Intravenous versus subcutaneous dosing of epoetin alfa in hemodialysis patients. Am J Kidney Dis 1995; 26:331.
- Levin NW, Lazarus JM, Nissenson AR. National Cooperative rHu Erythropoietin Study in patients with chronic renal failure--an interim report. The National Cooperative rHu Erythropoietin Study Group. Am J Kidney Dis 1993; 22:3.
- Kaufman JS, Reda DJ, Fye CL, et al. Subcutaneous compared with intravenous epoetin in patients receiving hemodialysis. Department of Veterans Affairs Cooperative Study Group on Erythropoietin in Hemodialysis Patients. N Engl J Med 1998; 339:578.
- Besarab A, Reyes CM, Hornberger J. Meta-analysis of subcutaneous versus intravenous epoetin in maintenance treatment of anemia in hemodialysis patients. Am J Kidney Dis 2002; 40:439.
- Pizzarelli F, David S, Sala P, et al. Iron-replete hemodialysis patients do not require higher EPO dosages when converting from subcutaneous to intravenous administration: results of the Italian Study on Erythropoietin Converting (ISEC). Am J Kidney Dis 2006; 47:1027.
- Kindler J, Eckardt KU, Ehmer B, et al. Single-dose pharmacokinetics of recombinant human erythropoietin in patients with various degrees of renal failure. Nephrol Dial Transplant 1989; 4:345.
- Besarab A. Physiological and pharmacodynamic considerations for route of EPO administration. Semin Nephrol 2000; 20:364.
- Granolleras C, Branger B, Beau MC, et al. Experience with daily self-administered subcutaneous erythropoietin. Contrib Nephrol 1989; 76:143.
- Parker KP, Sands JM. Weekly subcutaneous erythropoietin maintains hematocrit in chronic hemodialysis patients. J Am Soc Nephrol 1993; 3:1717.
- Locatelli F, Baldamus CA, Villa G, et al. Once-weekly compared with three-times-weekly subcutaneous epoetin beta: results from a randomized, multicenter, therapeutic-equivalence study. Am J Kidney Dis 2002; 40:119.
- Mircescu G, Gârneată L, Ciocâlteu A, et al. Once-every-2-weeks and once-weekly epoetin beta regimens: equivalency in hemodialyzed patients. Am J Kidney Dis 2006; 48:445.
- Rice L, Alfrey CP, Driscoll T, et al. Neocytolysis contributes to the anemia of renal disease. Am J Kidney Dis 1999; 33:59.
- Means RT Jr. Neocytolysis: from outer space to the dialysis unit. Am J Kidney Dis 1999; 33:140.
- Navarro JF, Teruel JL, Marcén R, Ortuño J. Improvement of erythropoietin-induced hypertension in hemodialysis patients changing the administration route. Scand J Urol Nephrol 1995; 29:11.
- Centers for Medicare and Medicaid Services, Kinney R. 2005 Annual Report: ESRD Clinical Performance Measures Project. Am J Kidney Dis 2006; 48:S1.
- Thamer M, Zhang Y, Kaufman J, et al. Factors influencing route of administration for epoetin treatment among hemodialysis patients in the United States. Am J Kidney Dis 2006; 48:77.
- Hynes DM, Stroupe KT, Kaufman JS, et al. Adherence to guidelines for ESRD anemia management. Am J Kidney Dis 2006; 47:455.
- http://www.usrds.org/adr.aspx (Accessed on September 04, 2013).
- NKF-DOQI Clinical Practice Guidelines for Anemia of Chronic Renal Failure. IV. Administration of epoetin. Am J Kidney Dis 2001; 37(Suppl 1):S207.
- K/DOQI Clinical Practice Guidelines for Anemia of Chronic Renal Failure. IV. Administration of epoetin. Am J Kidney Dis 2006; 47(Suppl 3):S1.
- Kidney Disease: Improving Global Outcomes (KDIGO) anemia work group. KDIGO clinical practice guidelines for anemia in chronic kidney disease. Kidney Int 2012; Suppl 2:279.
- Aarup M, Bryndum J, Dieperink H, Joffe P. Clinical implications of converting stable haemodialysis patients from subcutaneous to intravenous administration of darbepoetin alfa. Nephrol Dial Transplant 2006; 21:1312.
- Lim WH, Chan D, Boudville N, et al. Patients' perceptions of subcutaneous delivery of darbepoetin alfa by autoinjector prefilled pen versus prefilled syringe: a randomized, crossover study. Clin Ther 2012; 34:1948.
- Macdougall IC, Robson R, Opatrna S, et al. Pharmacokinetics and pharmacodynamics of intravenous and subcutaneous continuous erythropoietin receptor activator (C.E.R.A.) in patients with chronic kidney disease. Clin J Am Soc Nephrol 2006; 1:1211.
- Macdougall IC, Walker R, Provenzano R, et al. C.E.R.A. corrects anemia in patients with chronic kidney disease not on dialysis: results of a randomized clinical trial. Clin J Am Soc Nephrol 2008; 3:337.
- Jarsch M, Brandt M, Lanzendörfer M, Haselbeck A. Comparative erythropoietin receptor binding kinetics of C.E.R.A. and epoetin-beta determined by surface plasmon resonance and competition binding assay. Pharmacology 2008; 81:63.
- Sulowicz W, Locatelli F, Ryckelynck JP, et al. Once-monthly subcutaneous C.E.R.A. maintains stable hemoglobin control in patients with chronic kidney disease on dialysis and converted directly from epoetin one to three times weekly. Clin J Am Soc Nephrol 2007; 2:637.
- Levin NW, Fishbane S, Cañedo FV, et al. Intravenous methoxy polyethylene glycol-epoetin beta for haemoglobin control in patients with chronic kidney disease who are on dialysis: a randomised non-inferiority trial (MAXIMA). Lancet 2007; 370:1415.
- Klinger M, Arias M, Vargemezis V, et al. Efficacy of intravenous methoxy polyethylene glycol-epoetin beta administered every 2 weeks compared with epoetin administered 3 times weekly in patients treated by hemodialysis or peritoneal dialysis: a randomized trial. Am J Kidney Dis 2007; 50:989.
- Curran MP, McCormack PL. Methoxy polyethylene glycol-epoetin beta: a review of its use in the management of anaemia associated with chronic kidney disease. Drugs 2008; 68:1139.