A disproportionality analysis of adverse events associated with loop diuretics in the FDA Adverse Event Reporting System (FAERS).

Abstract

Background: Loop diuretics, including furosemide, torsemide, and bumetanide, are widely utilized in the management of volume overload-related conditions. Although previous studies have extensively documented risks such as electrolyte imbalances, ototoxicity, and nephrotoxicity, real-world evidence regarding novel or underrecognized adverse event (AE) signals remains limited and underexplored.

Methods: Using data from the Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the third quarter of 2024, we conducted a disproportionality analysis integrating Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM), combined with multivariate logistic regression. It is considered a significant signal when one of the four indicators meets the criteria. The temporal characteristics were elucidated via time-to-onset (TTO) analysis.

Results: A total of 24,875 AE reports were analyzed, with furosemide accounting for 89.18%, torsemide for 8.33%, and bumetanide for 2.47%. Commonly reported risks included electrolyte imbalances, fluid balance disorders, and nephrotoxicity. Several novel safety signals were identified: furosemide was significantly associated with vitamin B1 deficiency (TTO = 71 days), Wernicke's encephalopathy (TTO = 2167 days), and gastrointestinal mucosal pigmentation (TTO = 549.1 days). Torsemide was associated with palisaded neutrophilic granulomatous dermatitis (TTO = 62.8 days), systemic infection (TTO = 548.3 days), pemphigoid (TTO = 470.6 days), bleeding events (involving the respiratory, gastrointestinal, and urinary tracts), and prolonged prothrombin time (TTO = 159.4 days). Bumetanide was linked to blood ketone body increased (TTO = 9.0 days), metabolic encephalopathy (TTO = 1786.0 days), and immune hypersensitivity reactions (Stevens-Johnson syndrome, pemphigoid, and lip swelling).

Conclusion: This study identified both common and drug-specific AEs associated with loop diuretics, particularly focusing on the metabolic and immune risks of long-term use. To enhance patient safety, clinicians are advised to develop personalized monitoring strategies based on individual patient characteristics. For furosemide, monitoring and supplementation of vitamin B1 and magnesium are recommended. For torsemide, attention should be given to coagulation function and delayed hypersensitivity reactions. For bumetanide, close monitoring of metabolic disorders and immune-related skin lesions is essential. These findings support individualized therapy and precise pharmacovigilance, ensuring safer and more effective use of loop diuretics.