Disproportionality analysis of data from vigibase and other global product safety databases on toxicity of iron chelating agents

Iron supplements are commonly prescribed for treatment of iron deficiencies, associated complications, for its immune and cognition improving activities. Due to this common practice, also after blood transfusions and unintentional ingestions; iron toxicities may occur. Iron chelators; deferasirox, deferiprone and deferoxamine, are used to treat toxicities. Unfortunately, iron chelators are also likely to cause serious adverse reactions. The purpose of this retrospective study is to review iron chelators' pharmacovigilance data by analyzing different sources and comparing real life results, to introduce unknown safety information, and potential new signals. Disproportionality analysis was conducted using safety databases including VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and FAERS, the FDA Adverse Event Reporting System, for iron chelator cases between 2010 and 2021, to investigate the AE associations. Unlisted AEs from databases with strong associations (Reporting odds ratio; ROR≥1) were revealed as potential signals. RORs were calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious), using 24581 cases from FAERS and 383361 cases from VigiBase. Results were within 95% Confidence Interval (CI). Strong association between deferoxamine and blurred vision (ROR: 2.83, 95% CI 2.01, 4.27), deferiprone and sepsis (ROR: 135.20, 95% CI 132.88, 135.12) were identified. However, upon comparing RORs results from different databases, inconsistencies between chelator-AE associations were obtained. Fatal cases had common patient characteristics, which may effect the warnings and contraindications in local labels. findings suggest that it is essential to combine different resources while reviewing safety data, to promote reporting awareness and safety studies to discover unknown parts of safety profiles.