Post-marketing safety assessment of epinephrine: an analysis of the US FDA adverse event reporting system

Epinephrine, a sympathomimetic catecholamine, is extensively employed for the treatment of anaphylaxis. This research evaluates adverse events (AEs) associated with epinephrine, utilizing data from the US FDA Adverse Event Reporting System.

AE reports related to epinephrine submitted from Q1 2004 to Q4 2024 were extracted for analysis. Multiple signal detection methodologies were employed, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EBGM).

Out of 9,262 reports identifying epinephrine as the primary suspected medication, 24 system organ classes (SOCs) and 264 significant preferred terms (PTs) were recognized. General disorders and administration site conditions constituted the most common SOC (n = 6,112). At the PT level, drug ineffective was predominant (n = 1,867), whereas injection site ischemia demonstrated the strongest signal (ROR: 3242.28, PRR: 3236.49, IC: 10.43, EBGM: 1380.84). Additionally, several notable AEs not mentioned in current drug labeling exhibited substantial signals, such as myocardial stunning, systolic anterior motion of mitral valve, left ventricle outflow tract obstruction, harlequin syndrome, injection site nerve damage, and injection site movement impairment. The median interval to AE onset was 0 day (interquartile range [IQR] 0-0 day) with most of cases emerged within 24 h after application of epinephrine.

This investigation identified numerous previously unreported AE signals associated with epinephrine. Further clinical studies are necessary to substantiate these findings and elucidate the causal relationships.