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Drug Insight: safety of intravenous iron supplementation with sodium ferric gluconate complex

Nature Clinical Practice Nephrology volume 2, pages 92–100 (2006)Cite this article

Abstract

Intravenous iron is necessary for optimal management of anemia in patients receiving hemodialysis and is utilized in the majority of these patients in the US. The availability of nondextran formulations of intravenous iron has significantly improved the safety of its use. The nondextran iron formulation sodium ferric gluconate complex (SFGC) has been extensively studied in the hemodialysis population, with two large phase IV trials documenting its safety. SFGC is efficacious and, at recommended doses, is associated with a low incidence of adverse events. There have been few comparative studies of the nondextran intravenous iron preparations; however, they are known to have different pharmacokinetic characteristics. There is also evidence to indicate that these compounds differ in terms of their cytotoxic and proinflammatory properties, and their propensity to induce oxidative stress. This paper reviews the current literature on the safety of SFGC and examines the emerging safety issues surrounding the use of intravenous iron.

Key Points

  • The nondextran iron formulation sodium ferric gluconate complex (SFGC; Ferrlecit®) was approved by FDA priority review in 1999

  • Phase IV data support the safety of SFGC for management of anemia in adult and pediatric hemodialysis patients

  • SFGC is associated with a reduced risk of anaphylactoid reactions compared with iron dextran formulations

  • Studies of other safety issues associated with SFGC use are ongoing

  • Limited data exist on the use of SFGC in patients with CKD or those receiving peritoneal dialysis

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Figure 1: Molecular structure of sodium ferric gluconate complex.
Figure 2: Plasma tumor-necrosis factor-α levels 2 h after intraperitoneal lipopolysaccharide injection in mice with and without concomitant intravenous iron therapy.

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References

  1. [No authors listed] (2001) NKF-K/DOQI clinical practice guidelines for anemia of chronic kidney disease: update 2000. Am J Kidney Dis 37 (Suppl 1): S182–S238

  2. Wingard RL et al. (1995) Efficacy of oral iron therapy in patients receiving recombinant human erythropoietin. Am J Kidney Dis 25: 433–439

    Article  CAS  Google Scholar 

  3. Markowitz GS et al. (1997) An evaluation of the effectiveness of oral iron therapy in hemodialysis patients receiving recombinant human erythropoietin. Clin Nephrol 28: 34–40

    Google Scholar 

  4. Fudin R et al. (1998) Correction of uremic iron deficiency anemia in hemodialyzed patients: a prospective study. Nephron 79: 299–305

    Article  CAS  Google Scholar 

  5. Besarab A et al. (1999) A study of parenteral iron regimens in hemodialysis patients. Am J Kidney Dis 34: 21–28

    Article  CAS  Google Scholar 

  6. Centers for Medicare and Medicaid Services (2004) 2004 Annual Report, End Stage Renal Disease Clinical Performance Measures Project. Baltimore, MD: Department of Health and Human Services, Centers for Medicare and Medicaid Services, Office of Clinical Standards and Quality

  7. Fishbane S et al. (1996) The safety of intravenous iron dextran in hemodialysis patients. Am J Kidney Dis 28: 529–534

    Article  CAS  Google Scholar 

  8. Hamstra RD et al. (1980) Intravenous iron dextran in clinical medicine. JAMA 243: 1726–1731

    Article  CAS  Google Scholar 

  9. Feridex® (ferumoxide injectible solution) label (Advanced Magnetics, Inc. 1997)

  10. Faich G and Strobos J (1999) Sodium Ferric Gluconate Complex in sucrose: Safer intravenous iron therapy than iron dextrans. Am J Kidney Dis 33: 464–470

    Article  CAS  Google Scholar 

  11. Fishbane S and Wagner J (2001) Sodium Ferric Gluconate Complex in the Treatment of Iron Deficiency for Patients on Dialysis. Am J Kidney Dis 37: 879–883

    Article  CAS  Google Scholar 

  12. Ferrlecit® (sodium ferric gluconate complex in sucrose injection) package insert (Watson Pharmaceuticals 2004)

  13. Seligman P et al. (2000) Fast IV Iron: Sodium ferric gluconate complex (SFGC) is Safe with No “Free” Iron Toxicity. J Am Soc Nephrol 11: A1560

    Google Scholar 

  14. Seligman PA et al. (2004) Single-Dose Pharmacokinetics of Sodium Ferric Gluconate Complex in Iron–Deficient Subjects. Pharmacotherapy 24: 574–583

    Article  CAS  Google Scholar 

  15. Agarwal R (2004) Transferrin saturation with intravenous irons: An in vitro study. Kidney Int 66: 1139–1144

    Article  CAS  Google Scholar 

  16. Venofer® (iron sucrose injection) package insert (American Reagent Labs 2004)

  17. Parkkinen J et al. (2000) Catalytically active iron and bacterial growth in serum of haemodialysis patients after i.v. iron-saccharate administration. Nephrol Dial Transplant 15: 1827–1834

    Article  CAS  Google Scholar 

  18. Kooistra MP et al. (2002) Nontransferrin-bound iron in the plasma of haemodialysis patients after intravenous iron saccharate infusion. Eur J Clin Invest 32 (Suppl 1): S36–S41

    Article  Google Scholar 

  19. Danielson BG et al. (1996) Pharmacokinetics of iron(III)-hydroxide sucrose complex after a single intravenous dose in healthy volunteers. Arzneimittelforschung 46: 615–621

    CAS  PubMed  Google Scholar 

  20. Van Wyck D et al. (2004): Labile iron in parenteral iron formulations: a quantitative and comparative study. Nephrol Dial Transplant 19: 561–565

    Article  CAS  Google Scholar 

  21. Infed® (iron dextran injection) package insert (Watson Pharma, Inc. 2001)

  22. Dexferrum® (iron dextran injection) package insert (American Reagent Labs 2001)

  23. Panesar A and Agarwal R (2002) Safety and Efficacy of Sodium Ferric Gluconate Complex in Patients with Chronic Kidney Disease. Am J Kidney Dis 40: 924–931

    Article  CAS  Google Scholar 

  24. Allegra V et al. (1991) Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments. Nephron 57: 175–182

    Article  CAS  Google Scholar 

  25. Pascual J et al. (1991) Sodium ferric gluconate complex given intravenously for iron deficiency in hemodialysis. Clin Nephrol 35: 87

    CAS  PubMed  Google Scholar 

  26. Navarro JF et al. (1996) Effectiveness of intravenous administration of Fe-gluconate–Na complex to maintain adequate body iron stores in hemodialysis patients. Am J Nephrol 16: 268–272

    Article  CAS  Google Scholar 

  27. Taylor JE et al. (1996) Regular low-dose intravenous iron therapy improves response to erythropoietin in haemodialysis patients. Nephrol Dial Transplant 11: 1079–1083

    Article  CAS  Google Scholar 

  28. Cortes MJC et al. (1997) Effect of intravenous Na–Fe-gluconate in hemodialysis patients treated with rHuEPO. Nefrologia 17: 424–429

    Google Scholar 

  29. Nissenson AR et al. (1999) Sodium ferric gluconate complex in sucrose is safe and effective in hemodialysis patients: North American Clinical Trial. Am J Kidney Dis 33: 471–482

    Article  CAS  Google Scholar 

  30. Michael B et al. (2002) Sodium ferric gluconate complex in hemodialysis patients: Adverse reactions compared to placebo and iron dextran. Kidney Int 61: 1830–1839

    Article  CAS  Google Scholar 

  31. Michael B et al. (2004) Sodium ferric gluconate complex in haemodialysis patients: a prospective evaluation of long-term safety. Nephrol Dial Transplant 19: 1576–1580

    Article  CAS  Google Scholar 

  32. Schwartz LB et al. (1989) Time course of appearance and disappearance of human mast cell tryptase in the circulation after anaphylaxis. J Clin Invest 83: 1551–1555

    Article  CAS  Google Scholar 

  33. Schwartz LB et al. (1987) Tryptase levels as an indicator of mast-cell activation in systemic anaphylaxis and mastocytosis. N Engl J Med 316: 1622–1626

    Article  CAS  Google Scholar 

  34. Coyne DW et al. (2003) Sodium ferric gluconate complex in hemodialysis patients: II. Adverse reactions in iron dextran-sensitive and dextran-tolerant patients. Kidney Int 63: 217–224

    Article  CAS  Google Scholar 

  35. Rolla G et al. (1994) Systemic reactions to intravenous iron therapy in patients receiving angiotensin converting enzyme inhibitor. J Allergy Clin Immunol 93: 1074–1075

    Article  CAS  Google Scholar 

  36. Parnes EL and Shapiro WB (1991) Anaphylactoid reactions in hemodialysis patients treated with the AN69 dialyzer. Kidney Int 40: 1148–1152

    Article  Google Scholar 

  37. Pegues DA et al. (1992) Anaphylactoid reactions associated with reuse of hollow-fiber hemodialyzers and ACE inhibitors. Kidney Int 42: 1232–1237

    Article  CAS  Google Scholar 

  38. Warady BA et al. (2005) Sodium ferric gluconate complex therapy in anemic children on hemodialysis. Pediatr Nephrol 20: 1320–1327

    Article  Google Scholar 

  39. Folkert VW et al. (2003) Chronic use of sodium ferric gluconate complex (SFGC) in hemodialysis patients: safety of higher dose (≥250 mg) administration. Am J Kidney Dis 41: 651–617

    Article  CAS  Google Scholar 

  40. Javier AM (2002) Weekly administration of high-dose sodium ferric gluconate is safe and effective in peritoneal dialysis patients. Nephrol Nurs J 29: 183–186

    PubMed  Google Scholar 

  41. Kosch M et al. (2001) A randomized, controlled parallel-group trial on efficacy and safety of iron sucrose (Venofer) vs iron gluconate (Ferrlecit) in haemodialysis patients treated with rHuEpo. Nephrol Dial Transplant 16: 1239–1244

    Article  CAS  Google Scholar 

  42. Esposito BP et al. (2002) Labile iron in parenteral iron formulations and its potential for generating plasma nontransferrin-bound iron in dialysis patients. Eur J Clin Invest 32 (Suppl 1): S42–S49

    Article  Google Scholar 

  43. Sengoelge G et al. (2003) Impairment of transendothelial leukocyte migration by iron complexes. J Am Soc Nephrol 14: 2639–2644

    Article  CAS  Google Scholar 

  44. Patruta SI et al. (1998) Neutrophil impairment associated with iron therapy in hemodialysis patients with functional iron deficiency. J Am Soc Nephrol 9: 655–663

    CAS  PubMed  Google Scholar 

  45. Zager RA et al. (2004) Parenteral iron therapy exacerbates experimental sepsis. Kidney Int 65: 2108–2112

    Article  CAS  Google Scholar 

  46. Feldman HI et al. (2004) Administration of parenteral iron and mortality among hemodialysis patients. J Am Soc Nephrol 15: 1623–1632

    Article  CAS  Google Scholar 

  47. Zager RA et al. (2005) Parenteral iron compounds sensitize mice to injury-initiated TNF-α mRNA production and TNF-α release. Am J Physiol Renal Physiol 288: F290–F297

    Article  CAS  Google Scholar 

  48. Zager RA et al. (2002) Parenteral Iron Formulations: A Comparative Toxicologic Analysis and Mechanisms of Cell Injury. Am J Kidney Dis 40: 90–103

    Article  CAS  Google Scholar 

  49. Zager RA et al. (2004) Parenteral iron nephrotoxicity: Potential mechanisms and consequences. Kidney Int 66: 144–156

    Article  CAS  Google Scholar 

  50. Roob JM et al. (2000) Vitamin E attenuates oxidative stress induced by intravenous iron in patients on hemodialysis. J Am Soc Nephrol 11: 539–549

    CAS  PubMed  Google Scholar 

  51. Michelis R et al. (2003) Carbonyl stress induced by intravenous iron during haemodialysis. Nephrol Dial Transplant 18: 924–930

    Article  CAS  Google Scholar 

  52. Rooyakkers TM et al. (2002) Ferric saccharate induces oxygen radical stress and endothelial dysfunction in vivo. Eur J Clin Invest 32 (Suppl 1): S9–S16

    Article  Google Scholar 

  53. Shah SV (2001) Role of iron in progressive renal disease. Am J Kidney Dis 37 (Suppl 1): S30–S33

    Article  CAS  Google Scholar 

  54. Remuzzi A et al. (1991) Renoprotective effect of low iron diet and its consequence on glomerular hemodynamics. Kidney Int 39: 647–652

    Article  CAS  Google Scholar 

  55. Nankivell BJ et al. (1992) Iron accumulation in human chronic renal disease. Am J Kidney Dis 20: 580–584

    Article  CAS  Google Scholar 

  56. Alfrey AC et al. (1989) Role of iron in the tubulo-interstitial injury in nephrotoxic serum nephritis. Kidney Int 36: 753–759

    Article  CAS  Google Scholar 

  57. Leehey DJ et al. (2005) Sodium Ferric Gluconate causes oxidative stress but not acute renal injury in patients with chronic kidney disease: a pilot study. Nephrol Dial Transpl 20: 135–140

    Article  CAS  Google Scholar 

  58. Agarwal R et al. (2004) Oxidative stress and renal injury with intravenous iron in patients with chronic kidney disease. Kidney Int 65: 2279–2289

    Article  CAS  Google Scholar 

  59. Sato K and Shiraki M (1998) Saccharated ferric oxide-induced osteomalacia in Japan: iron-induced osteopathy due to nephropathy. Endocr J 45: 431–439

    Article  Google Scholar 

  60. Besarab A (1999) Iron and cardiac disease in the end-stage renal disease setting. Am J Kidney Dis 34 (Suppl 2): S18–S24

    Article  CAS  Google Scholar 

  61. Drueke T et al. (2002) Iron therapy, advanced oxidation protein products, and carotid artery intima-media thickness in end-stage renal disease. Circulation 106: 2212–2217

    Article  Google Scholar 

  62. Boaz M et al. (2000) Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomized placebo-controlled trial. Lancet 356: 1213–1218

    Article  CAS  Google Scholar 

  63. Tepel M et al. (2003) The antioxidant acetylcysteine reduces cardiovascular events in patients with end-stage renal failure: a randomized, controlled trial. Circulation 107: 992–995

    Article  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Thomas Jefferson University, Philadelphia, PA

    Beckie Michael, Steven Fishbane, Daniel W Coyne, Rajiv Agarwal & David G Warnock

  2. Nephrology Section at Winthrop University Hospital, Mineola, New York, NY

    Beckie Michael, Steven Fishbane, Daniel W Coyne, Rajiv Agarwal & David G Warnock

  3. Washington University School of Medicine, St. Louis, MO

    Beckie Michael, Steven Fishbane, Daniel W Coyne, Rajiv Agarwal & David G Warnock

  4. Indiana University School of Medicine, Indianapolis, IN

    Beckie Michael, Steven Fishbane, Daniel W Coyne, Rajiv Agarwal & David G Warnock

  5. University of Alabama at Birmingham, Birmingham, AL, USA

    Beckie Michael, Steven Fishbane, Daniel W Coyne, Rajiv Agarwal & David G Warnock

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  1. Beckie Michael
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Correspondence to Beckie Michael.

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Competing interests

The authors have participated in clinical research studies funded by, or hold or have held consulting agreements in which they were compensated on an occasional basis for hourly work performed, with no prescribed minimal number of hours, from Watson Pharmaceuticals, Inc, the manufacturer of sodium ferric gluconate complex.

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Michael, B., Fishbane, S., Coyne, D. et al. Drug Insight: safety of intravenous iron supplementation with sodium ferric gluconate complex. Nat Rev Nephrol 2, 92–100 (2006). https://doi.org/10.1038/ncpneph0068

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