Safety analysis of long-acting dual bronchodilator after market approval: a real-world study from FDA Adverse Event...

Long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) combinations are widely prescribed for chronic obstructive pulmonary disease (COPD). This study evaluated post-marketing safety signals for four dual bronchodilators (formoterol/glycopyrronium, indacaterol/glycopyrronium, vilanterol/umeclidinium, and olodaterol/tiotropium).

A retrospective pharmacovigilance study of four bronchodilators was conducted using the data from Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 1, 2014 and March 31, 2025. The association between drugs and adverse events (AEs) was evaluated using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPN), and multi-item gamma Poisson shrinker (MGPS). Venn analysis was performed to identify drug-specific disproportionality signals for the four bronchodilators.

A total of 18,677 cases were included. Venn analysis identified 13 common safety signals and various drug-specific disproportionality safety signals, including 56 important medical events (IMEs) that met signaling thresholds for only one drug. Urinary retention emerged as a common IME among four bronchodilators. Indacaterol/glycopyrronium was associated with distinct cardiovascular risks, including arrhythmia, cardiac arrest, myocardial infarction, angina pectoris, and coronary artery disease. Olodaterol/tiotropium showed signals for ileus, retinal vein occlusion, cataract, and hip fracture, and exhibited the longest latency period among the other three bronchodilators.

This pharmacovigilance study identified significant safety signals associated with four bronchodilators, highlighting both common and drug-specific disproportionality signals and thereby providing essential evidence to support drug monitoring in clinical practice.