Skip to main content

Advertisement

SpringerLink
Log in

Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region

  • Original Article
  • Published:
Journal of Nephrology Aims and scope Submit manuscript

Abstract

Background

The European Medicines Agency (EMA) has recommended measures to minimize the risk of hypersensitivity reactions (HSRs) to intravenous iron (IVFe). We analysed the effects of these recommendations on IVFe clinical management among haemodialysis centres (HDCs) in Lombardy, Italy.

Materials and methods

A questionnaire was sent to all 117 HDCs to collect information on centre characteristics, e.g. HDC type [hospital centre (HC) vs. centre with limited assistance (CAL)], presence/absence of intensive care unit (ICU) and/or emergency trained staff, IVFe therapy regarding molecules, administration modalities, side effects, and percentage variations in iron prescription between 2014 and 2013 (outcome, Δ-IVFe%). A linear regression model was applied to evaluate the focus effect (β) of HDC type on the outcome, controlling for possible confounding effects of the other characteristics.

Results

Response rate was 73.5 %. IVFe therapy was used in 69.1 % (HDC range 11–100) of patients. Following EMA recommendations, prescription was reduced by 12.6 %, with the largest reduction observed in CALs. No severe HSRs were reported. HCs had more frequently an ICU [97.2 vs. 20 %, odds ratio (OR) = 63.6 (95 % confidence interval 15.56; 537.47), p < 0.001], emergency trained staff [97.2 vs. 61.2 %, OR = 10.7 (2.68; 85.33), p < 0.001] and instrumental facilities (91.7 vs. 58 %, OR = 5.8 (2.03; 23.55), p < 0.001] than CALs. Linear regression demonstrated a significant raw effect of HDC type on Δ- IVFe% [β =  19.6 (9.82; 30.63), p < 0.001]. No association was found when HDC type was adjusted for ICU-presence [β = 6.7 (−2.32; 18.30), p = 0.199] or for all-confounding factors [β = 5.6 (−5.50; 17.08), p = 0.337].

Conclusions

This survey shows a disparity in IVFe therapy prescription following EMA recommendations, which is largely influenced by the presence/absence of ICUs in HD centres.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Sunder-Plassmann G, Hörl WH (1995) Importance of iron supply for erythropoietin therapy. Nephrol Dial Transplant 10(11):2070–2076

    CAS  PubMed  Google Scholar 

  2. Fishbane S, Frei GL, Maesaka J (1995) Reduction in recombinant human erythropoietin doses by the use of chronic intravenous iron supplementation. Am J Kidney Dis 26(1):41–46

    Article  CAS  PubMed  Google Scholar 

  3. Locatelli F, Aljama P, Canaud B, Covic A, De Francisco A, Macdougall IC et al (2010) Target haemoglobin to aim for with erythropoiesis-stimulating agents: a position statement by ERBP following publication of the Trial to reduce cardiovascular events with Aranesp therapy (TREAT) study. Nephrol Dial Transplant 25(9):2846–2850

    Article  PubMed  Google Scholar 

  4. KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease (2012) Chapter 2: Use of iron to treat anemia in CKD. Kidney Int Suppl 2(4):292–8

  5. Pfeffer MA, Burdmann EA, Chen C-Y, Cooper ME, de Zeeuw D, Eckardt K-U et al (2009) A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 361(21):2019–32

  6. Litton E, Xiao J, Ho KM (2013) Safety and efficacy of intravenous iron therapy in reducing requirement for allogeneic blood transfusion: systematic review and meta-analysis of randomised clinical trials. BMJ 347:f4822

    Article  PubMed  PubMed Central  Google Scholar 

  7. Allegra V, Mengozzi G, Vasile A (1991) Iron deficiency in maintenance hemodialysis patients: assessment of diagnosis criteria and of three different iron treatments. Nephron 57(2):175–182

    Article  CAS  PubMed  Google Scholar 

  8. Macdougall IC, Tucker B, Thompson J, Tomson CR, Baker LR, Raine AE (1996) A randomized controlled study of iron supplementation in patients treated with erythropoietin. Kidney Int 50(5):1694–1699

    Article  CAS  PubMed  Google Scholar 

  9. Albaramki J, Hodson EM, Craig JC, Webster AC (2012) Parenteral versus oral iron therapy for adults and children with chronic kidney disease. Cochrane Database Syst Rev 1:CD007857

  10. Susantitaphong P, Alqahtani F, Jaber BL (2014) Efficacy and safety of intravenous iron therapy for functional iron deficiency anemia in hemodialysis patients: a meta-analysis. Am J Nephrol 39(2):130–141

    Article  CAS  PubMed  Google Scholar 

  11. Macdougall IC, Bock A, Carrera F, Eckardt K-U, Gaillard C, Van Wyck D et al (2014) The FIND-CKD study—a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale. Nephrol Dial Transplant 29(4):843–850

    Article  CAS  PubMed  Google Scholar 

  12. Rampton D, Folkersen J, Fishbane S, Hedenus M, Howaldt S, Locatelli F et al (2014) Hypersensitivity reactions to intravenous iron: guidance for risk minimization and management. Haematologica 99(11):1671–1676

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Behera V, Chauhan R, Sinha S, Nair V (2015) Anaphylactic shock secondary to intravenous iron sucrose in chronic kidney disease. Indian J Hematol Blood Transfus 31(3):391–393

    Article  PubMed  Google Scholar 

  14. Bailie GR, Verhoef J-J (2012) Differences in the reporting rates of serious allergic adverse events from intravenous iron by country and population. Clin Adv Hematol Oncol HO 10(2):101–108

    Google Scholar 

  15. Bircher AJ, Auerbach M (2014) Hypersensitivity from intravenous iron products. Immunol Allergy Clin North Am 34(3):707–23, x–xi

  16. Auerbach M, Adamson J, Bircher A, Breymann C, Fishbane S, Gafter-Gvili A et al (2015) On the safety of intravenous iron, evidence trumps conjecture. Haematologica 100(5):e214–e215

    Article  PubMed  PubMed Central  Google Scholar 

  17. European Medicines Agency—News and Events—New recommendations to manage risk of allergic reactions with intravenous iron-containing medicines [Internet]. http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2013/06/news_detail_001833.jsp&mid=WC0b01ac058004d5c1

  18. Agenzia Italiana del Farmaco (AIFA). Nota Informativa Importante su medicinali contenenti ferro (25/10/2013). http://www.agenziafarmaco.gov.it/it/content/nota-informativa-importante-su-medicinali-contenenti-ferro-25102013

  19. Jewell NP (2004) Statistics for epidemiology, 1st edn. Chapman and Hall/CRC, Boca Raton, p 352

    Google Scholar 

  20. Fox J, Weisberg S (2011) An R companion to applied regression, 2nd edn. Sage Publications, Thousand Oaks

    Google Scholar 

  21. Heine-Bröring RC, Winkels RM, Botma A, van Duijnhoven FJB, Jung AY, Kleibeuker JH et al (2013) Dietary supplement use and colorectal adenoma risk in individuals with lynch syndrome: the GEOLynch Cohort Study. PLoS One 8(6):e66819

    Article  PubMed  PubMed Central  Google Scholar 

  22. Rosseel Y (2012) Lavaan: an R package for structural equation modeling. J Stat Softw 48(2):1–36

    Article  Google Scholar 

  23. Chertow GM, Mason PD, Vaage-Nilsen O, Ahlmén J (2006) Update on adverse drug events associated with parenteral iron. Nephrol Dial Transplant 21(2):378–382

    Article  CAS  PubMed  Google Scholar 

  24. Wysowski DK, Swartz L, Borders-Hemphill BV, Goulding MR, Dormitzer C (2010) Use of parenteral iron products and serious anaphylactic-type reactions. Am J Hematol 85(9):650–654

    Article  PubMed  Google Scholar 

  25. Avni T, Bieber A, Grossman A, Green H, Leibovici L, Gafter-Gvili A (2015) The safety of intravenous iron preparations: systematic review and meta-analysis. Mayo Clin Proc 90(1):12–23

    Article  PubMed  Google Scholar 

  26. Bailie GR (2012) Comparison of rates of reported adverse events associated with i.v. iron products in the United States. Am J Health-Syst Pharm 69(4):310–20

  27. Intravenous iron-containing products (2014) EMA procrastination. Prescrire Int 23(151):184–185

    Google Scholar 

  28. McClellan WM, Frankenfield DL, Frederick PR, Helgerson SD, Wish JB, Sugarman JR (2003) Improving the care of ESRD patients: a success story. Health Care Financ Rev 24(4):89–100

    PubMed  PubMed Central  Google Scholar 

  29. St Peter WL, Obrador GT, Roberts TL, Collins AJ (2005) Trends in intravenous iron use among dialysis patients in the United States (1994–2002). Am J Kidney Dis Off J Natl Kidney Found 46(4):650–660

  30. Irving MJ, Craig JC, Gallagher M, McDonald S, Polkinghorne KR, Walker RG et al (2006) Implementing iron management clinical practice guidelines in patients with chronic kidney disease having dialysis. Med J Aust 185(6):310–314

  31. Sepandj F, Jindal K, West M, Hirsch D (1996) Economic appraisal of maintenance parenteral iron administration in treatment of anaemia in chronic haemodialysis patients. Nephrol Dial Transplant 11(2):319–322

    Article  CAS  PubMed  Google Scholar 

  32. Valenzuela TD, Roe DJ, Nichol G, Clark LL, Spaite DW, Hardman RG (2000) Outcomes of rapid defibrillation by security officers after cardiac arrest in casinos. N Engl J Med 343(17):1206–1209

  33. Weaver WD, Hill D, Fahrenbruch CE, Copass MK, Martin JS, Cobb LA et al (1988) Use of the automatic external defibrillator in the management of out-of-hospital cardiac arrest. N Engl J Med 319(11):661–666

Download references

Author information

Author notes

    Authors and Affiliations

    1. Division of Nephrology and Dialysis, San Gerardo Hospital, Pergolesi 33, 20090, Monza, Italy

      Rodolfo F. Rivera

    2. Medical and Genomic Statistics Unit, Department of Brain and Behavioural Sciences, University of Pavia, Via Bassi 21, 27100, Pavia, Italy

      Davide Guido

    3. Biostatistics and Clinical Epidemiology Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, Pavia, Italy

      Davide Guido

    4. Division of Nephrology and Dialysis, A. Manzoni Hospital, Via dell’Eremo 9/11, 23900, Lecco, Italy

      Lucia Del Vecchio, Giuseppe Pontoriero & Francesco Locatelli

    5. Division of Nephrology and Dialysis, Bassini Hospital, via Gorki 50, 20092, Cinisello Balsamo (MI), Italy

      Enzo Corghi & Claudio Pozzi

    6. Division of Nephrology and Dialysis, Sant’Anna Hospital, via Ravona 20, 22020, San Fermo della Battaglia, Como, Italy

      Marco D’Amico

    7. Operative Unit of Nephrology, A.O. Spedali Civili and University of Brescia, Ple Spedali Civili 1, 25123, Brescia, Italy

      Corrado Camerini & Giovanni Cancarini

    8. Operative Unit of Nephrology and Dialysis, San Raffaele, via Olgettina 60, 20132, Milan, Italy

      Donatella Spotti

    9. Division of Nephrology and Dialysis, Desio Hospital, Via Mazzini 1, 20832, Desio, Italy

      Andrea Galassi

    Authors
    1. Rodolfo F. Rivera
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Davide Guido
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Lucia Del Vecchio
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Enzo Corghi
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Marco D’Amico
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Corrado Camerini
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Donatella Spotti
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Andrea Galassi
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Claudio Pozzi
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Giovanni Cancarini
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Giuseppe Pontoriero
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Francesco Locatelli
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Rodolfo F. Rivera.

    Ethics declarations

    Conflict of interest

    The authors declare the following disclosure: Lucia Del Vecchio was in an advisory Board by Astellas. Francesco Locatelli was a member of an advisory board and or speaker at symposia supported by Akebia, Amgen, Astellas, Pharmacosmos, Janssen, Keryx, Roche.

    Ethical approval

    This article does not contain any studies with human participants or animals performed by any of the authors.

    Informed consent

    Informed consent was obtained from all participant centers in the study.

    Financial support

    The authors did not receive any financial support for this study.

    Additional information

    All the authors listed in the author group belongs to the study group ‘The Lombardy Section of Italian Society of Nephrology’ and they are contributed equally to this study.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Rivera, R.F., Guido, D., Del Vecchio, L. et al. Impact of European medicines agency recommendations for hypersensitivity reactions on intravenous iron prescription in haemodialysis centres of the Lombardy region. J Nephrol 29, 673–681 (2016). https://doi.org/10.1007/s40620-015-0254-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s40620-015-0254-5

    Keywords

    Search

    Navigation