Real-world safety profile of givinostat: an early post-marketing pharmacovigilance study based on the FAERS database

Givinostat is a novel histone deacetylase inhibitor, which was approved by the US Food and Drug Administration (FDA) in 2024 for treatment of Duchenne muscular dystrophy (DMD). This early post-marketing pharmacovigilance study aimed to explore the adverse events (AEs) caused by givinostat through data mining of the US FDA Adverse Event Reporting System (FAERS), and provide reference for clinical safety.

Data of givinostat were collected from the FAERS database covering the period from the first quarter of 2024 to the fourth quarter of 2025. Disproportionality analyses were employed to quantify the associated AE signals of givinostat and detect the risk signals from the data in the FAERS database. Four algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), were used to detect the risk signals from the data in the FAERS database. The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA).

In total, 402 reports of givinostat were identified as the "primary suspected (PS)" AEs. Givinostat-associated AEs were identified across 23 organ systems. Significant disproportionality PTs simultaneously meeting the criteria of all four algorithms. Expected AEs, including decreased platelet count, diarrhoea, and increased blood triglycerides, were identified. Unexpected significant signals such as lower limb fracture, femur fracture, anger, and mood swings were also detected, although these are likely heavily confounded by the underlying disease progression and concurrent corticosteroid use.

Based on early post-marketing data, this study provides a preliminary real-world safety assessment of givinostat. In addition to validating known hematological and gastrointestinal toxicities, it identifies potential signals for orthopedic complications, psychiatric events, and hypertriglyceridemia. While these novel signals are heavily confounded by the natural history of DMD and chronic corticosteroid exposure, they warrant continuous multidisciplinary monitoring. As hypothesis-generating signals derived from spontaneous reports, these initial findings require future prospective validation. They expand the current understanding of givinostat's safety profile and highlight the necessity for continuous pharmacovigilance.