Hepatotoxicity of newer antiseizure medications in children: an overview and disproportionality analysis of VigiBase

Abstract

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 hypersensitivity 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 topiramate. 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.