Objective  Based on the mining of the Food and Drug Administration Adverse Events Reporting System (FAERS) database, to investigate adverse drug event (ADE) signals associated with the use of four β1-blockers (metoprolol, bisoprolol, atenolol, and esmolol) in children under 18 years of age, and to provide references for the clinical safety of drug use.

Methods  The FAERS database was searched from the first quarter of 2004 to the first quarter of 2025 to collect ADE reports of metoprolol, bisoprolol, atenolol, and esmolol use in children under 18 years old. Signal mining was conducted using the reporting odds ratio (ROR) method, Medicines and Healthcare products Regulatory Agency (MHRA) method, the multi-item gam-ma-Poisson shrinker (MGPS) method, and the Bayesian confidence propagation neural network (BCPNN) method. The ADE signal mining results were systematically classified according to Medical Dictionary for Regularly Activities 27.1.

Results  A total of 976 ADE reports involving 4 types of β1-blockers were collected, including 515 for metoprolol, 200 for bisoprolol, 227 for atenolol, and 34 for esmolol. Among the reported pediatric patients, males outnumbered females (489 cases vs. 439 cases), with the majority aged under 3 years (54.63%-64.71%). Reports were mainly submitted from Germany and the United States, slightly more were recorded by non-professionals than by professionals, and the reported outcomes included congenital malformations, death and hospitalization. A total of 202 signals were identified, involving 21 system organ classes (SOC), predominantly concentrated in various injuries, such as poisoning and procedural complications, congenital familial and genetic disorders, pregnancy, childbirth and puerperium conditions, cardiac disorders and psychiatric disorders. A total of 46 positive signals were detected in key systems (cardiac disorders, psychiatric disorders): 19 for metoprolol, 11 for bisoprolol, 15 for atenolol, and 1 for esmolol. Among them, metoprolol, bisoprolol, and atenolol had 9, 6, and 8 positive signals, respectively, that were not included in the drug instructions.

Conclusion  When applying the 4 types of β1-blockers in pediatric patients, particular attention should be paid to common ADEs such as cardiac organ diseases, psychiatric disorders, and vigilance should be maintained for ADEs not documented in the prescribing information, such as suicidal behavior (bisoprolol, atenolol) and completed suicide (metoprolol, atenolol), to ensure medication safety.

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