Supplementary Material for: Clinical Validation of Pharmacovigilance Algorithms in Suspected Hypersensitivity to Vitamin and Iron Preparations

Introduction: Vitamin- and iron-containing medicinal preparations are widely perceived as safe; however, hypersensitivity reactions may pose diagnostic challenges. Standardized diagnostic pathways for suspected hypersensitivity are limited. This study aimed to compare pharmacovigilance-based causality assessment tools with allergist-defined clinical outcomes in patients evaluated for suspected hypersensitivity to vitamin- and iron-containing preparations. Methods: A retrospective review was performed in 40 patients referred to a tertiary allergy center for suspected adverse reactions to vitamin- or iron-containing medicinal preparations. Demographic characteristics, index reaction features, diagnostic testing results, and clinical outcomes were collected. Causality classifications using the World Health Organization–Uppsala Monitoring Centre (WHO–UMC) system and the Naranjo algorithm were compared with allergist-defined final evaluations. Results: The cohort was predominantly female (97.5%) and atopic. Iron-containing products were most commonly implicated (40%), followed by B-complex vitamins (27.5%) and combined formulations (12.5%). Most reactions reflected Type B hypersensitivity (67.5% immediate; 10% delayed). Diagnostic testing was feasible in 82.5% of patients, and confirmed hypersensitivity was uncommon (10%), with most reactions classified as probable or non-allergic. WHO–UMC and Naranjo showed significant correlation (χ² = 74.7, p < 0.001), with fair categorical agreement (κ = 0.28) and strong rank correlation (ρ = 0.78). Concordance with allergist-defined clinical outcomes was weak (WHO–UMC κ = 0.09; Naranjo κ = 0.18). Conclusion: Immunologically mediated hypersensitivity to vitamin and iron preparations appears uncommon in this tertiary allergy cohort. Pharmacovigilance-based causality assessment tools and allergist-led diagnostic evaluation demonstrate complementary but non-interchangeable roles, highlighting the importance of clinical verification in hypersensitivity reactions.