Influence of patient age and sex on drug-induced liver injury caused by antiseizure medications: a disproportionality analysis of VigiBase.

Background: While it has been recognised that children may be at a greater risk of developing valproic acid-induced hepatotoxicity, it is less known if age and sex represent risk factors for drug-induced liver injury (DILI) caused by other antiseizure medications (ASMs).

Aim: To investigate the influence of patient age and sex on DILI caused by ASMs.

Method: To estimate hepatotoxic potential of 24 ASMs, deduplicated safety reports from VigiBase were accessed and disproportionality analysis was conducted by calculating Empirical Bayesian Geometric Mean and its 90% confidence interval (EB05, EB95). For ASMs with identified signals of disproportionate reporting (EB05 > 2, N > 0) for at least one hepatotoxicity-related event, we compared reporting frequency of overall hepatotoxicity among different age groups and between males and females by combining all events of interest into one custom term "overall DILI". The same analysis was conducted using the custom term "liver failure".

Results: Signals of disproportionate reporting were identified for 14 (58.33%) ASMs. Valproic acid and carbamazepine had the highest number of identified signals (25 and 17, respectively). Among the 14 ASMs with identified signals, seven (50%) had disproportionally higher reporting of overall DILI in children, one (7.14%) in older people, and nine (64.29%) in females. Further, six (42.86%) ASMs had disproportionally higher reporting of liver failure in children and three (21.43%) in females.

Conclusion: Our study suggests the importance of considering patient age and sex when assessing the risk of DILI from specific ASMs. However, the results are mainly hypothesis-generating and the identified signals require further investigation.