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Observational Study
. 2021 Oct;30(10):1447-1457.
doi: 10.1002/pds.5319. Epub 2021 Jul 12.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe

Joan Fortuny  1 , Gero von Gersdorff  2 , Régis Lassalle  3 , Marie Linder  4 , Jetty Overbeek  5 , Jonas Reinold  6 , Gunnar Toft  7 , Antje Timmer  8 , Jochen Dress  9 , Patrick Blin  3 , Cécile Droz-Perroteau  3 , Vera Ehrenstein  7 , Carla Franzoni  1 , Ron Herings  5   10 , Bianca Kollhorst  6 , Nicholas Moore  3 , Ingvild Odsbu  4 , Susana Perez-Gutthann  1 , Tania Schink  6 , Katherine Rascher  2 , Lawrence Rasouliyan  1 , Kenneth J Rothman  11 , Nuria Saigi-Morgui  1 , Mathias Schaller  2 , Elisabeth Smits  5 , Michael Forstner  12 ; Intravenous Iron Consortium; Jacques Bénichou  13 , Andreas J Bircher  14   15 , Edeltraut Garbe  6 , David S Rampton  16 , Lia Gutierrez  1
Affiliations
Observational Study

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe

Joan Fortuny et al. Pharmacoepidemiol Drug Saf. 2021 Oct.

Abstract

Purpose: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments.

Methods: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control.

Results: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments).

Conclusion: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Keywords: IV iron; anaphylaxis; cohort study; dextran; multidatabase; severe hypersensitivity reactions.

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Conflict of interest statement

The study was funded by a consortium of IV iron marketing authorisation holders and was conducted under a contract including the ENCePP Seal granting the research team independent publication rights.

Figures

FIGURE 1
FIGURE 1
Study inclusion and exclusion criteria
FIGURE 2
FIGURE 2
Main and expanded anaphylaxis algorithms. ICD‐10, International Classification of Diseases, Tenth Revision
FIGURE 3
FIGURE 3
Study follow‐up. DK, Denmark; GePaRD, German Pharmacoepidemiological Research Database; KfH QiN, Board of Trustees for Dialysis and Kidney Transplantation and its Quality in Nephrology programme; PHARMO, PHARMO Database Network; SE, Sweden; SNDS, Système National des Données de Santé (French National Health Care Insurance System Database, previously named SNIIRAM)
FIGURE 4
FIGURE 4
Number of first, second and third or subsequent IV iron treatments stratified by data source and showing the percentage of administrations of iron dextran. Numbers for the Central Denmark Region data were rounded to the nearest 10 to comply with Danish data protection and reporting regulations aimed at prevention of identification of individuals. GePaRD, German Pharmacoepidemiological Research Database; IV, intravenous; KfH QiN, Board of Trustees for Dialysis and Kidney Transplantation and its Quality in Nephrology programme; PHARMO‐NL, PHARMO Database Network in the Netherlands; SNDS, Système National des Données de Santé (French National Health Care Insurance System Database, previously named SNIIRAM)
See this image and copyright information in PMC

References

    1. Auerbach M, Ballard H. Clinical use of intravenous iron: administration, efficacy, and safety. Hematology Am Soc Hematol Educ Program. 2010;2010:338‐347. - PubMed
    1. Bailie GR, Verhoef JJ. Differences in the reporting rates of serious allergic adverse events from intravenous iron by country and population. Clin Adv Hematol Oncol. 2012. Feb;10(2):101‐108. - PubMed
    1. Walsh K, Andrade S, Cocoros N, et al. Sentinel assessment report: parenteral iron and anaphylactoid reactions. US Food and Drug Administration; 22 July 2016. https://www.sentinelinitiative.org/sites/default/files/surveillance‐tool.... Accessed 6 October 2020.
    1. Wang C, Graham DJ, Kane RC, et al. Comparative risk of anaphylactic reactions associated with intravenous iron products. JAMA. 2015;314(19):2062‐2068. - PubMed
    1. Chertow GM, Mason PD, Vaage‐Nilsen O, Ahlmen J. On the relative safety of parenteral iron formulations. Nephrol Dial Transplant. 2004;19(6):1571‐1575. - PubMed

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