Assessment of the Clinical Value of Voriconazole Drug Interactions: A Real-world Disproportionality-Based Analysis

Voriconazole (VCZ) has a narrow therapeutic window and is metabolized by CYP450 enzymes, predisposing it to adverse drug events (ADEs) and drug-drug interactions (DDIs), yet its multisystem safety profile and combination-therapy characteristics in real‑world practice remain inadequately understood. To address this gap, we extracted VCZ-related ADE reports from the FDA Adverse Event Reporting System (FAERS) between Q1 2004 and Q1 2025 and applied four disproportionality methods (ROR, PRR, BCPNN, and MGPS) for single-drug signal detection, alongside additive, multiplicative, and Ω shrinkage models to assess superadditive or supermultiplicative DDI risks. A total of 36,854 reports from 12,505 patients were analyzed, revealing that males (52.73%) and individuals aged ≥64 years (31.38%) were high-prevalence groups, and most ADEs occurred within 30 days of dosing (median time-to-onset: 6.00 days). Single-drug signals predominantly affected infections/invasive diseases (21.74%), ocular disorders (9.18%), and neurological conditions (7.25%), with newly identified strong positive signals for osteochondritis dissecans and trichotheliomycosis. The DDI analysis identified 355 strong-positive combinations involving 117 drugs from 16 classes, with antineoplastics, systemic antifungals, and cardiovascular agents being the most frequent, and 49 rare combination risks (e.g., belintuzumab, ertapenem) that impacted neurological, hepatic, and renal systems. Collectively, these findings demonstrate that VCZ carries multifaceted safety risks in real-world settings, with DDI hazards spanning diverse drug classes and including rare but highly lethal signals; therefore, precise clinical monitoring should be prioritized for high-prevalence populations, early-onset periods, and high-risk drug pairs, with particular vigilance for newly recognized adverse reactions and uncommon DDI threats.