Clinical Validation of Pharmacovigilance Algorithms in Suspected Hypersensitivity to Vitamin and Iron Preparations

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.

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.

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 nonallergic. In a subgroup analysis restricted to single-agent exposures, delayed or probable allergic reactions were more frequent with vitamin B preparations than iron (p = 0.03), and vitamin B complex products were also among the most frequently contraindicated or withheld pending diagnostic testing. 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).

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.