Evaluation of the Reported Rates of Severe Hypersensitivity Reactions Associated with Ferric Carboxymaltose and Iron (III) Isomaltoside 1000 in Europe Based on Data from EudraVigilance and VigiBase™ between 2014 and 2017

Birgit Ehlken, Lennart Nathell, Annegret Gohlke, Derya Bocuk, Massoud Toussi, Stefan Wohlfeil, Birgit Ehlken, Lennart Nathell, Annegret Gohlke, Derya Bocuk, Massoud Toussi, Stefan Wohlfeil

Abstract

Introduction: Hypersensitivity reactions (HSRs) are among the known adverse events of intravenous (i.v.) iron products. Of these, particularly severe HSRs such as anaphylaxis are of great clinical concern due to their life-threatening potential.

Methods: This was a retrospective pharmacoepidemiological study with a case-population design evaluating the number of reported severe HSRs following administration of the two i.v. iron products-ferric carboxymaltose and iron (III) isomaltoside 1000-in relation to exposure in European countries from January 2014 to December 2017. Exposure to both products was estimated using IQVIA MIDAS sales data in European countries. Information on spontaneously reported severe HSRs was obtained from and analysed separately for the two established safety surveillance databases EudraVigilance and VigiBase™ using the MedDRA® Preferred Terms anaphylactic reaction, anaphylactic shock, anaphylactoid reaction and anaphylactoid shock associated with administration of either product.

Results: Between 2014 and 2017, the reporting rate of severe HSRs per 100,000 defined daily doses (100 mg dose equivalents of iron) varied from 0.3 to 0.5 for ferric carboxymaltose and from 2.4 to 5.0 for iron (III) isomaltoside 1000. The reporting rate ratio for iron (III) isomaltoside 1000 versus ferric carboxymaltose was between 5.6 (95% CI 3.5-9.0) and 16.2 (95% CI 9.4-27.8).

Conclusions: Findings suggest that iron (III) isomaltoside 1000 is associated with a higher reporting rate of severe HSRs related to estimated exposure than ferric carboxymaltose in European countries. Future research investigating the occurrence of severe HSRs associated with i.v. ferric carboxymaltose and iron (III) isomaltoside 1000 is needed to broaden the evidence for benefit-risk assessment.

Conflict of interest statement

Stefan Wohlfeil is an employee of Vifor Pharma Management Ltd. Lennart Nathell is a former employee of Vifor Pharma, and during the planning, execution and publishing of the study was working for a company on a contract with Vifor Pharma Management Ltd. Vifor Pharma is the manufacturer for Ferinject® (ferric carboxymaltose). Birgit Ehlken, Annegret Gohlke, Derya Bocuk and Massoud Toussi are employees of IQVIA which received funding from Vifor Pharma International AG for the conduct of the study.

Figures

Fig. 1
Fig. 1
Sales of intravenous iron products (ferric carboxymaltose and iron (III) isomaltoside 1000) in EEA plus Switzerland from 2014 to 2017 in million DDDs (100 mg dose equivalents of iron = 1 DDD). DDD defined daily dose, EEA European Economic Area
Fig. 2
Fig. 2
Reporting rates of severe hypersensitivity reactions (HSRs) per 100,000 DDDs of ferric carboxymaltose and iron (III) isomaltoside 1000 in the EudraVigilance and VigiBase™ databases. DDD defined daily dose

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