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

ABSTRACT

BACKGROUND: Iron chelators; deferasirox, deferiprone, and deferoxamine; used to treat iron toxicities due to excessive ingestions or blood transfusions, may cause serious adverse reactions. RESEARCH DESIGN AND METHODS: This study investigates pharmacovigilance data to uncover unknown safety information. Disproportionality analysis was conducted using VigiBase, the WHO global database of individual case safety reports, to known safety profile of products and the FDA Adverse Event Reporting System, reviewing over 117.000 iron chelator cases between 2010 and 2020. RESULTS: Commonly reported adverse events for iron chelators are general disorders and administration site conditions and GI-related disorders. Reporting Odds Ratio was calculated for iron chelator associations to headache (common), blurred vision (rare) and sepsis (serious). Strong association between deferoxamine and blurred vision (ROR 2.47 in VigiBase and 3.04 in FAERS), deferiprone and sepsis (ROR; 5.95 in VigiBase and 1.24 in FAERS) were identified. However, results showed some inconsistent associations, such as headache and deferiprone, blurred vision and deferasirox association as per FAERS data; sepsis and deferasirox and deferoxamine association as per VigiBase data. Forty-five new potential signals with different associative values were suggested. CONCLUSION: The study identified strong associations between specific iron chelators and adverse events, though some inconsistencies were observed in the data. These findings, including the 45 new potential signals, suggest areas for further review and validation with additional data.