Adverse events reported for hereditary angioedema medications: a retrospective study of spontaneous reports submitted to the EudraVigilance database, 2007-2013

Lise Aagaard,1 Anette Bygum,2 1Section for Clinical Pharmacology, Institute of Public Health, Faculty of Health Sciences, University of Southern Denmark, 2Department of Dermatology and Allergy Centre, Odense University Hospital, Odense, Denmark Abstract: Information about long-term safety issues from use of orphan drugs in treatment of hereditary angioedema (HAE) is limited and must be studied further. As clinical trials in patients with rare diseases are limited, prescribers and patients have to rely on spontaneous adverse drug reaction (ADR) reports for obtaining major information about the serious, rarely occurring, and unknown ADRs. In this study, we aimed to characterize ADRs reported for HAE medications in Europe from 2007 to 2013. ADR reports submitted for C1-inibitors and bradykinin receptor antagonists to the European ADR database, EudraVigilance (EV), were included in this study. The ADR reports were categorized with respect to age and sex of the patients, category of the reporter, type and seriousness of the reported ADRs, and medications. The unit of analysis was one adverse event (AE). Totally, 187 AEs were located in EV, and of these, 138 AEs were reported for Cinryze® (C1-inhibitor) (73% of the total) and 49 AEs for Firazyr® (icatibant) (26% of the total AEs). Approximately 60% of all AEs were serious, including three fatal cases. Less than 5% of AEs were reported in children. In total, 62% of AEs were reported for women and 38% for men. For both Cinryze® and Firazyr®, the majority of reported AEs were of the type “general disorders and administration site conditions”. For Cinryze®, a large number of AEs of the type “HAE” and “drug ineffective” was reported, but only few of these were serious. For Firazyr®, several nonserious reports on injection site reactions were reported. In conclusion, this study showed that in EV, several ADR reports from use of HAE medications were identified, and a large number of these were serious, including fatal cases. Keywords: orphan drugs, hereditary angioedema, adverse drug reactions, adverse events, C1-inhibitor, Cinryze®, icatibant, Firazyr®, EudraVigilanc