@article{
author = "Petrović, Sanja and Kovačević, Milena and Vezmar-Kovačević, Sandra and Miljković, Branislava",
year = "2024",
abstract = "Background: We aimed to characterize newer antiseizure medications (ASMs)-induced hepatotoxicity
in children and identify signals of disproportionate reporting of hepatotoxicity-related adverse drug
events (ADEs).
Research Design and Methods: Case reports reported to VigiBase were accessed using Empirica™
Signal software. To summarize characteristics of the retrieved cases, descriptive statistics were used.
A disproportionality analysis was conducted using the Multi-item Gamma Poisson Shrinker algorithm,
which calculates Empirical Bayesian Geometric Mean value and its lower and upper 95% confidence
limits (EB05 and EB95, respectively). EB05 > 2, N > 0 was considered a signal.
Results: Based on 870 analyzed cases, a higher proportion of cases was reported in girls than in boys
and in patients aged 2–11 years than in other age groups. Most cases were serious. In 25 cases,
hepatotoxicity resulted in death. A high proportion of patients (n = 275, 31.61%) experienced hyper-
sensitivity reactions, mostly due to lamotrigine. The disproportionality analysis yielded 17 signals
concerning felbamate, lamotrigine, levetiracetam, oxcarbazepine, stiripentol, and topiramate. Four
signals were for severe liver injury and concerned felbamate, lamotrigine, levetiracetam, and topira-
mate. Gender-biased reporting frequency was detected for four ASM-ADE combinations.
Conclusion: Our results should serve to raise clinicians’ awareness about the potential association
between several newer ASMs and drug-induced liver injury in children.",
publisher = "Taylor & Francis",
journal = "Expert Opinion on Drug Metabolism & Toxicology",
title = "Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase",
volume = "20",
number = "3",
pages = "165-173",
doi = "10.1080/17425255.2024.2322114"
}
