Abstract
This study aimed to assess infection-related adverse events (AEs) associated with calcineurin inhibitors (CNIs), including cyclosporine (CsA) and tacrolimus (TAC), in the pediatric population using combined postmarketing surveillance databases. Data from the FDA Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) were analyzed for pediatric patients. Disproportionality analysis was conducted to evaluate AEs. Additionally, subgroup analysis, fatal outcome assessment, and time-to-onset (TTO) analysis were also performed. A total of 426 CsA-related and 1284 TAC-related infection reports were identified in FAERS, with corresponding findings in JADER (CsA, n = 140; TAC, n = 323). Cross-database analysis identified positive overlapping signals for BK virus, cytomegalovirus, and Epstein-Barr virus infections for both drugs. Age- and sex-stratified analysis revealed differences in infection-related reporting patterns, with the percentage of fatal outcomes varying significantly across age groups and being highest in the youngest subgroups: 3-5 years for CsA (29.2%) and 0-2 years for TAC (18.4%) (P < 0.05). This study provides real-world evidence on infection-related safety signals associated with CNIs in pediatric patients, particularly for viral infections. The distinct signal profiles and age- and sex-specific patterns highlight the importance of individualized infection risk monitoring and immunosuppressive management strategies. • Calcineurin inhibitors (CNIs), including cyclosporine (CsA) and tacrolimus (TAC), are widely used in pediatric transplantation and immune-mediated diseases, but infection remains an important safety concern during CNI-based immunosuppression. • Evidence on the comparative infection-related safety profiles of these two agents in children remains limited. • This is the first dual-database pharmacovigilance analysis to characterize infection-related safety signals associated with CsA and TAC in pediatric patients. • Age- and sex-specific patterns were identified, with fatal outcomes significantly associated with younger age groups for both drugs.