Abstract
BACKGROUND: Itraconazole (ITZ) is a broad-spectrum antifungal agent widely used for the treatment and prevention of fungal infections, particularly systemic and cutaneous infections. Although considered safe, recent clinical reports and studies have indicated that ITZ can cause a range of adverse events (AEs), particularly affecting vital organs such as the heart and liver. The objective of this study was to evaluate ITZ-associated adverse events by conducting data mining using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) to assess potential safety risks. METHODS: A retrospective pharmacovigilance analysis was performed using FAERS data from Q1 2019 to Q2 2024. Four disproportionality algorithms were applied to identify significant signals related to ITZ-AEs, including the Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM). RESULTS: From a total of 6,191,576 case reports in FAERS, 1,041 reports identified ITZ as the primary suspected (PS) agent linked to AEs. A total of 323 ITZ-associated AEs were identified across 16 organ systems at the preferred terms (PTs) level. Expected AEs, including general disorders, administration site conditions, cardiac disorders, and hepatobiliary disorders, were identified, consistent with the drug label. In addition, 31 unexpected AEs were detected, including left ventricular dysfunction (39 cases, EBGM 31.81/EBGM05 15.83), myositis (38 cases, EBGM 29.75/EBGM05 15.94), both associated with vascular disorders at the system organ class (SOC) level. These findings suggest the presence of potential adverse effects that are not currently addressed in the drug’s labeling. CONCLUSIONS: This study identified 31 novel and unexpected AE signals associated with ITZ, which are consistent with clinical observations. These findings provide new insights into the safety profile of ITZ, highlighting the need for increased vigilance in clinical practice regarding its potential adverse effects. Future studies should validate these signals and explore their clinical implications to enhance drug safety monitoring and labeling updates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00228-025-03931-6.