Pulmonary adverse events associated with amiodarone: a real-world pharmacovigilance study based on the FDA adverse event reporting system

Background: Amiodarone is used to treat cardiac arrhythmias but carries a risk of pulmonary toxicity. Despite this well-known side effect, there is currently no large descriptive case series studying amiodarone-induced pulmonary toxicity. Methods: The reporting odds ratio (ROR) was utilized to quantify signals of amiodarone-related pulmonary adverse events (AEs) from 2004 to 2023. Severity comparisons between serious and non-serious cases were conducted using the Mann-Whitney U test or chi-square (χ2) test, and signal prioritization was achieved through rating scales. Results: A total of 4896 cases of amiodarone-related pulmonary AEs were found, and 56 signals were detected. 27 AEs were classified as serious adverse reactions, and 21 AEs were identified as new and unexpected signals. Even when stratified by age, weight, sex, and reporter type, the association between amiodarone and pulmonary diseases persisted. Seven strong clinical priority signals were defined. The median time to onset (TTO) for strong, moderate, and weak clinical priority signals was 221, 126, and 227 days, respectively. All disproportional signals exhibited an early failure-type pattern. Conclusion: Our study offers a deeper and broader understanding of the pulmonary safety profile of amiodarone, which will aid healthcare professionals in mitigating the risk of pulmonary adverse events in clinical practice.