Drugs associated with epidermal necrolysis in children: A World Health Organization pharmacovigilance database analysis

Abstract

AbstractBackgroundStevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare life‐threatening mucocutaneous reactions most often induced by drugs. To date, no large pharmacovigilance study has been conducted in the paediatric population.ObjectivesTo describe the spectrum of drugs associated with SJS‐TEN in children through the analysis of cases reported in the WHO pharmacovigilance database (VigiBase).MethodsDisproportionality study using data from VigiBase. All paediatric (age under 18 years) cases reported between January 1, 1967, and July 6, 2022, were included. For each molecule, a case–non‐case study was performed to assess a potential pharmacovigilance signal by computing the lower end of the 95% credibility interval for the information component (IC025). We performed sensitivity analyses, (i) taking into account only cases reported by physicians and (ii) taking into account only cases reported in the last 10 years.ResultsAmong 31,376,783 adverse drug reactions reported in VigiBase, 2,248,727 were paediatric cases and 7342 were encoded as paediatric SJS‐TEN. Significant statistical pharmacovigilance signals were observed for 165 drugs. The two most represented drug classes were antiepileptics and anti‐infectious drugs. The five drugs with the highest IC025 were lamotrigine (IC025 4.99), carbamazepine (IC025 4.88), phenobarbital (IC025 4.67), phenytoin (IC025 4.52) and nimesulide (IC025 4.23). Acetaminophen was significantly associated with paediatric SJS‐TEN (IC025 2.85) and we also described various new suspected drugs. Vaccines had no significant pharmacovigilance signal. These results were confirmed with the sensitivity analyses.ConclusionsThis study updates the spectrum of drugs potentially associated with paediatric SJS‐TEN.