Drug-induced fever: a pharmacovigilance analysis based on the FDA adverse event reporting system

INTRODUCTION: Drug-induced fever is a common but often under-recognized adverse reaction that can complicate clinical management. AIM: This study aimed to systematically evaluate the risk of drug-induced fever using real-world pharmacovigilance data and to characterize its temporal onset patterns and clinical features. METHOD: A pharmacovigilance study was conducted utilizing data from the FAERS, covering reports from the first quarter of 2004 to the fourth quarter of 2024. The detection of adverse drug event signals was conducted using disproportionality analysis. The robustness of identified fever signals was assessed through sensitivity analysis. Furthermore, a time-to-onset analysis was undertaken to elucidate factors associated with the development of drug-induced fever. RESULTS: Disproportionality analysis revealed that antineoplastic and immunomodulating agents were the most frequently associated, followed by antiinfectives for systemic use, alimentary tract and metabolism, musculo-skeletal system, nervous system, blood and blood forming organs, dermatologicals, genito urinary system and sexhormones. The top-five drugs with drug-induced fever signals by case number were rituximab (3650 cases), immunoglobulin human normal (2478 cases), zoledronic acid (2304 cases), lamotrigine (1843 cases), dabrafenib (1803 cases). Sensitivity analysis confirmed that the majority of the positive signals remained robust. Analysis of the time-to-onset revealed that drug-induced fever occurred predominantly during the early phase of treatment. Furthermore, female patients experienced an earlier onset compared to males. CONCLUSION: This large-scale pharmacovigilance analysis identified drugs and patient characteristics associated with drug-induced fever and revealed early-onset patterns, providing evidence to support its early recognition and monitoring in clinical practice.