Assessing post-marketing safety of PDE5Is in erectile dysfunction: real-world evidence from the FDA adverse event reporting system

Abstract Erectile dysfunction (ED) is a common condition affecting men worldwide. The U.S. Food and Drug Administration (FDA) has approved phosphodiesterase type 5 inhibitors (PDE5Is), including sildenafil, tadalafil, vardenafil, and avanafil, for treating ED. However, real-world studies on adverse events (AEs) linked to PDE5Is are limited. This study comprehensively assessed the safety of PDE5Is based on reports from the FDA adverse event reporting system (FAERS) database from January 2004 to June 2024. The disproportionality analysis was used to evaluate the safety profiles of PDE5Is. Based on demographic stratification, correlational analysis and signal differences examination in subgroups were performed in different PDE5Is. Among the 53 517 AEs reports collected from the FAERS database, we identified 135, 73, 72, and 7 preferred terms associated with sildenafil, tadalafil, vardenafil, and avanafil, respectively. The study detected AEs listed on the FDA-approved label of each PDE5I. However, some AEs not listed on the labels were also identified. Some AEs listed by the FDA for PDE5Is were insignificant signals in our analysis. Significant differences were found among PDE5Is across age, weight, and onset time categories. We detected AEs related to the nervous, cardiovascular, and ocular systems that were not listed on the labels of the four PDE5Is, warranting further research on the underlying mechanisms. Additionally, significant differences in PDE5I-associated AEs were observed across age, weight, and onset time, highlighting the need for tailored patient management.