Reported Severe Hypersensitivity Reactions after Intravenous Iron Administration in the European Economic Area (EEA) Before and After Implementation of Risk Minimization Measures.

Introduction: Severe hypersensitivity reactions (HSRs) such as anaphylaxis are of great clinical concern because of their life-threatening potential. The adverse events attributable to intravenous iron products include HSRs. An investigation by the European Medicines Agency presented in late 2013 resulted in the implementation of risk minimization measures (RMMs).

Objective: This study evaluated the number of severe HSRs reported for intravenous iron substances related to exposure for the 4-year periods before and after this implementation.

Methods: This was a retrospective pharmacoepidemiologic study with a case-population design. We obtained information from the safety surveillance database EudraVigilance on spontaneously reported severe HSRs using the Medical Dictionary for Regulatory Activities preferred terms "anaphylactic reaction/shock" and "anaphylactoid reaction/shock". Exposure was estimated using IQVIA MIDAS sales data in European economic area countries.

Results: Reporting rates for individual products were heterogenous, and the implementation of RMMs appeared to have no clear impact. Reporting rates remained low for the full study period for iron sucrose (0.03-0.20) and ferric gluconate (0.02-0.14) and were higher at the beginning and lower at the end of the study period for ferric carboxymaltose (1.47-0.18). No clear trend was detected for iron dextran (range 0.22-2.80) and iron (III) isomaltoside 1000 (range 0-7.94).

Conclusions: Future research is needed to investigate whether the wide variability in reporting rates for severe HSRs associated with these intravenous iron products are due to potential differences in the safety profiles of these substances.