Use of Phosphodiesterase-5 Inhibitors and the Risk of Melanoma

Wayne, George; Atri, Elias; Demus, Tim; Jivanji, Dhaval; Herzog, Bryan; Wong, Vivian C.; Garcia, Maurilio; Cedeno, Juan D.; Nagoda, Elizabeth; Polackwich, A. Scott

doi:10.2139/ssrn.4095052

Cited by 1 publication

(3 citation statements)

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“…found that the association between malignant melanoma and sildenafil use persisted even after controlling for family history, sun exposure, and ultraviolet index of patients’ state of residence. Contrarily, in a recent study of the Surveillance, Epidemiology, and End Results (SEER) database, it was found that after the introduction of PDE5is in 1998, the trend for the rate of malignant melanoma diagnosis did not change significantly 22 . However, by design, the SEER did not allow for controlling for the intensity of sun exposure, which could potentially confound their results 22 .…”

Section: Discussionmentioning

confidence: 99%

“…Contrarily, in a recent study of the Surveillance, Epidemiology, and End Results (SEER) database, it was found that after the introduction of PDE5is in 1998, the trend for the rate of malignant melanoma diagnosis did not change significantly 22 . However, by design, the SEER did not allow for controlling for the intensity of sun exposure, which could potentially confound their results 22 . In our study, reports of malignant melanoma were frequent and disproportionately positive for adults’ use of sildenafil and tadalafil for sexual dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…22 However, by design, the SEER did not allow for controlling for the intensity of sun exposure, which could potentially confound their results. 22 In our study, reports of malignant melanoma were frequent and disproportionately positive for adults' use of sildenafil and tadalafil for sexual dysfunction. Further, when not controlling for gender, age, indication, and route of administration, we observed 40-fold greater RORs for sildenafil and tadalafil for malignant melanoma.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%