The real-world safety of Pexidartinib: a pharmacovigilance analysis based on the FDA adverse event reporting system

Tenosynovial giant cell tumor (TGCT) is a rare neoplasm closely associated with dysregulation of the colony-stimulating factor 1(CSF1)/CSF1R signaling pathway, faces high recurrence rates despite surgical intervention, prompting exploration of CSF1R inhibitors like pexidartinib. This retrospective pharmacovigilance study analyzed pexidartinib-associated adverse events (AEs) from FDA Adverse Event Reporting System (FAERS) data (Q4 2019–Q3 2024), employing disproportionality analyses (ROR, PRR, BCPNN, EBGM) and sensitivity assessments to evaluate 844 reports. Hepatic events (46.7% occurring within 30 days) and systemic reactions (fatigue, hair discoloration) dominated AE profiles, with median onset at 35 days (IQR 14–94). Sex-specific susceptibilities emerged, as females comprised 71.3% of cases and exhibited stronger signals for constipation and alopecia. Disproportionality analysis identified 84 significant Preferred Terms, while sensitivity analyses excluding confounders reinforced signal robustness. Despite therapeutic efficacy, hepatotoxicity and delayed-onset AEs (18.2% occurring after 6 months) necessitate rigorous adherence to risk mitigation protocols and long-term monitoring. These real-world data underscore sex-dimorphic AE patterns and validate FAERS as a critical tool for post-marketing surveillance, informing risk-benefit optimization in TGCT management.