Pharmacovigilance profiles of three generations of mineralocorticoid receptor antagonists and network toxicology analysis

This study compared the post-marketing safety profiles of spironolactone, eplerenone, and finerenone. These drugs are mineralocorticoid receptor antagonists, cornerstone therapies in cardiovascular and renal diseases. The analysis utilized 11,556 primary suspect reports from the FAERS database, covering Q1 2004 to Q3 2025. Spironolactone exhibited the broadest safety profile, with disproportionate reporting indicating congenital malformations, acute pulmonary edema, serious cutaneous reactions, and antiandrogenic effects. Eplerenone showed a more focused yet severe profile, with signals for serious cardiac events and renal/hepatic failure. Finerenone demonstrated the most targeted profile, with signals predominantly confined to renal and metabolic domains. Hyperkalemia was a consistent moderate-priority signal across all three drugs. Network toxicology analysis further supported these findings.