vardenafil-dihydrochloride and Melanoma

Phosphodiesterase 5 inhibitors (PDE5-is) are used worldwide as first line therapy for erectile dysfunction (ED). Current literature reported data on the warning association between PDE5-is use and the development of cutaneous melanoma. However, these data are contrasting, thus we aim to summarise evidence regarding this association.. A systematic review of all published articles related to the effects of PDE5-is in the development of cutaneous melanoma was performed. PubMed, EMBASE, and Cochrane library were queried for all the published studies indexed up to the 26th of May 2023. A combination of keywords related to PDE5-is and melanoma were used. Only original studies based on human subjects in the English language were included in the analysis.. Of 505 articles identified, only eight original articles were considered for further analysis. Overall, five of the selected articles including 657,984 subjects agrees on an increased risk of developing melanoma in PDE5-is users. On the other hand, three original articles based on data regarding 360,915 subjects, disagree with the previous statement declaring any association between PDE5-i use and melanoma. Current literature still reports contrasting data regarding the association between PDE5-is assumption and increased risk of melanoma, but a possible association is described, bringing attention to higher risk melanoma category of patients. More clinical studies are needed to clarify the impact of PDE5-is in the development and progression of melanoma.

Topics: Humans; Male; Melanoma; Melanoma, Cutaneous Malignant; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Skin Neoplasms; Tadalafil; Vardenafil Dihydrochloride

Despite their efficacy and general safety, rare but devastating adverse drug reactions have been associated with phosphodiesterase type 5 inhibitors.. To determine the safety profile of oral phosphodiesterase type 5 inhibitors with a particular focus on priapism and malignant melanoma.. In 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.. A 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.. Phosphodiesterase 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.

Topics: Adolescent; Adult; Erectile Dysfunction; Humans; Male; Melanoma; Melanoma, Cutaneous Malignant; Pharmacovigilance; Phosphodiesterase 5 Inhibitors; Priapism; Sildenafil Citrate; Tadalafil; Vardenafil Dihydrochloride; World Health Organization

Interferon alpha2 is widely used in hepatitis and high-risk melanoma. Interferon-induced pulmonary arterial hypertension as a side effect is rare.. We describe a melanoma patient who developed severe pulmonary arterial hypertension 30 months after initiation of adjuvant interferon alpha2b therapy. Discontinuation of interferon did not improve pulmonary arterial hypertension. This patient could be treated successfully with phosphodiesterase-5 inhibitor therapy.. This is only the 5th case of interferon-induced pulmonary arterial hypertension and the first documented case where pulmonary arterial hypertension was not reversible after termination of interferon alpha2 therapy. If interferon alpha2 treated patients develop respiratory symptoms, pulmonary arterial hypertension should be considered in the differential diagnosis. For these patients phosphodiesterase-5 inhibitors, e.g. sildenafil or vardenafil, could be an effective therapeutic approach.

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Adult; Cyclic Nucleotide Phosphodiesterases, Type 5; Female; Humans; Hypertension, Pulmonary; Imidazoles; Interferon-alpha; Melanoma; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Piperazines; Purines; Sildenafil Citrate; Sulfones; Time Factors; Treatment Outcome; Triazines; Vardenafil Dihydrochloride