Adverse reactions of PDE5 inhibitors: An analysis of the World Health Organization pharmacovigilance database

Abstract

BackgroundDespite their efficacy and general safety, rare but devastating adverse drug reactions have been associated with phosphodiesterase type 5 inhibitors.ObjectivesTo determine the safety profile of oral phosphodiesterase type 5 inhibitors with a particular focus on priapism and malignant melanoma.Materials and methodsIn this case–non‐case study, we queried the individual case safety reports for phosphodiesterase type 5 inhibitors within the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021. We included all individual case safety reports for sildenafil, tadalafil, vardenafil, and avanafil in men. For comparison, we also extracted the safety data from the Food and Drug Administration trials for these drugs. We assessed the safety profile of phosphodiesterase type 5 inhibitors by disproportionality analysis by measuring reporting odds ratio for their most commonly reported adverse drug reactions, once for all phosphodiesterase type 5 inhibitor reports and once for reports of oral phosphodiesterase type 5 inhibitor use in adult men (≥18 years old) with sexual dysfunction.ResultsA total of 94,713 individual case safety reports for phosphodiesterase type 5 inhibitors were extracted. A total of 31,827 individual case safety reports were identified relating to adult men taking oral sildenafil, tadalafil, vardenafil, or avanafil for sexual dysfunction. The most common adverse drug reactions included poor drug efficacy (42.5%), headache (10.4% vs. 8.5%–27.6% [Food and Drug Administration]), abnormal vision (8.4% vs. ≤4.6% [Food and Drug Administration]), flushing (5.2% vs. 5.1%–16.5% [Food and Drug Administration]), and dyspepsia (4.2% vs. 3.4%–11.1% [Food and Drug Administration]). Priapism showed significant signals for sildenafil (reporting odds ratio = 13.81, 95% confidence interval: 11.75–16.24), tadalafil (reporting odds ratio = 14.54, 95% confidence interval: 11.56–18.06), and vardenafil (reporting odds ratio = 14.12, 95% confidence interval: 8.36–22.35). Comparing with other medications in VigiBase, sildenafil (reporting odds ratio = 8.73, 95% confidence interval: 7.63–9.99) and tadalafil (reporting odds ratio = 4.25, 95% confidence interval: 3.19–5.55) had significantly higher reporting odds ratios for malignant melanoma.ConclusionPhosphodiesterase type 5 inhibitors 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 phosphodiesterase type 5 inhibitor use and malignant melanoma, which warrants additional study to better understand causation.

Ischemic priapism caused by self intracavernous injection of tadalafil

“…The causes of priapism included sickle cell disease in 26 (65%), malignant hemopathy in 4 (10%), idiopathic in 4 (10%), neuroleptic drugs in 3 (7.5%), and sildenafil in 3 (7.5%) 2 . According to the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021, a total of 31 827 individual case safety reports were identified relating to PDE5 inhibitors for sexual dysfunction 3 . Among them, the total number of priapism events was 258 (0.8%).…”

“…2 According to the World Health Organization global database of individual case safety reports (VigiBase) between 1983 and 2021, a total of 31 827 individual case safety reports were identified relating to PDE5 inhibitors for sexual dysfunction. 3 Among them, the total number of priapism events was 258 (0.8%). Rezaee et al found 411 cases of drug-induced priapism secondary to PDE5 inhibitors reported to the Food and Drug Administration since 1998.…”

Seltene primäre Kopfschmerzen

“…2 Diagnostische Kriterien der Internationalen Kopfschmerzgesellschaft für einen primären Anstrengungskopfschmerz [1]. [23]. So berichten 10% aller Männer über Kopfschmerzen nach dem Gebrauch von Sildenafil [23].…”

A Review on Risk Factors, Diagnostic Innovations, and Plant Based Therapies for the Management of Erectile Dysfunction

“…PDE5 inhibitors have been used for the improvement of ED. However, the use of phosphodiesterase type 5 inhibitors has many side effects, like malignant melanoma [160,161]. Food deficits brought on by a poor diet will almost definitely exacerbate chronic diseases [162].…”