Despite their efficacy and general safety, rare but devastating adverse drug reactions (ADR) have been associated with phosphodiesterase type 5 inhibitors (PDE5is).
To determine the safety profile of oral PDE5is with a particular focus on priapism and malignant melanoma.
In this case-non-case study, we queried the individual case safety reports (ICSR) for PDE5is within the World Health Organization global database of ICSRs (VigiBase) between 1983 to 2021. We included all ICSRs for sildenafil, tadalafil, vardenafil, and avanafil in men. For comparison, we also extracted the safety data from the Food and Drug Administration (FDA) trials for these drugs. We assessed the safety profile of PDE5is by disproportionality analysis through measuring reporting odds ratio (ROR) for their most commonly reported ADRs, once for all PDE5i reports and once for reports of oral PDE5i use in adult men (≥18 years old) with sexual dysfunction.
A total of 94,713 ICSRs for PDE5is were extracted. 31,827 ICRS were identified relating to adult men taking oral sildenafil, tadalafil, vardenafil, or avanafil for sexual dysfunction. The most common ADRs included poor drug efficacy (42.5%), headache (10.4% vs. 8.5-27.6% [FDA]), abnormal vision (8.4% vs. ≤4.6 [FDA]), flushing (5.2% vs. 5.1-16.5% [FDA]), and dyspepsia (4.2% vs. 3.4-11.1% [FDA]). Priapism showed significant signals for sildenafil (ROR = 13.81, 95% CI: 11.75-16.24), tadalafil (ROR = 14.54, 95% CI: 11.56-18.06) and vardenafil (ROR = 14.12, 95% CI: 8.36-22.35). Compared to other medications in VigiBase, sildenafil (ROR = 8.73, 95% CI: 7.63-9.99) and tadalafil (ROR = 4.25, 95% CI: 3.19-5.55) had significantly higher RORs for malignant melanoma.
PDE5is show significant signals correlating with priapism among a large international cohort. Further clinical study is needed to elucidate whether this is from proper or inappropriate use or other confounding conditions, as analysis of pharmacovigilance data does not allow for quantifying the clinical risk. Also, there appears to be a relationship between PDE5i use and malignant melanoma which warrants additional study to better understand causation. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.