Disproportionality Analysis of Fentanyl in Children Using Real-world Data from the FDA Adverse Event Reporting System (FAERS) Database

Fentanyl, a potent synthetic opioid, is widely used in pediatric pain management, for cancer-related pain, post-surgical care, and palliative scenarios. Its use carries the possibility of significant adverse events (AEs) due to its unique metabolic and physiological characteristics. The lack of pediatric-specific clinical trial data underscores the need for real-world safety information. This study aimed to evaluate the AE profile associated with fentanyl in children aged 0–17 years through AE reports from the FDA’s Adverse Event Reporting System from Q1 2004 to Q2 2024 using OpenVigil 2.1. After deduplication of 14,184 from 16,955 initially obtained individual safety reports (ISRs), 2,771 ISRs were retrieved, followed by exclusion of reports unrelated to therapeutic fentanyl use (579 ISRs), and 2,192 ISRs were included in the final analysis. AEs were classified using the Medical Dictionary for Regulatory Activities (version 27.1), and disproportionality analyses were performed using reporting odds ratios and proportional reporting ratios. Among 2,192 reports,137 preferred terms (PT) were identified. Frequently reported AEs included somnolence, neonatal drug withdrawal syndrome, and respiratory depression, stressing the need for continuous monitoring of fentanyl in children. Disproportionality analysis identified 88 safety signals, particularly for amnestic disorder and neonatal drug withdrawal syndrome. Concordance testing between the structured product label and OpenVigil-derived terms showed only 6.72% agreement at the PT level, showing a need for increased identification and reporting of AEs. Continuous pharmacovigilance is essential to improve understanding of fentanyl associated AEs and enhance clinical safety.