Skin cancer signal associated with phosphodiesterase inhibitors: gaining insight through the FDA pharmacovigilance database

ABSTRACT

Background

Panoramic views of post-marketing safety profiles, such as cancer signal, of phosphodiesterase 5A (PDE5A) inhibitors have yet to be fully evaluated.

Research design and methods

Data from the FDA Adverse Event Reporting System (FAERS) concerning the timeframe between January 1^st, 2004 to 30 June 2022 was analyzed through a disproportionality study to understand the association between sildenafil, tadalafil, and vardenafil and cancer. This association was identified using the Reporting odds ratio (ROR) and Bayesian Confidence Propagation Neural Network (BCPNN) approaches.

Results

Sildenafil associated ROR values and IC₀₂₅ ranged from 9.19 (95% CI 7.72–10.94, IC₀₂₅ 2.77) for metastatic malignant melanoma to 132.23 (95% CI 95.49–183.11, IC₀₂₅ 4.69) for malignant melanoma stage II. Tadalafil associated ROR and IC₀₂₅ ranged from 6.79 (95% CI 5.41–8.54, IC₀₂₅ 2.27) for metastatic malignant melanoma to 180.17 (95% CI 130.11–249.50, IC₀₂₅ 4.89) for malignant melanoma stage II. Vardenafil associated ROR and IC₀₂₅ ranged from 23.38 (95% CI 15.20–35.96, IC₀₂₅ 2.63) for metastatic malignant melanoma to 245.77 (95% CI 154.42–391.16, IC₀₂₅ 2.10) for malignant melanoma stage III.

Conclusions

This study supports the association between sildenafil, tadalafil, and vardenafil with skin cancer signal in erectile dysfunction (ED) patients.

KEYWORDS:

• Drug safety
• pharmacovigilance
• reporting odds ratio
• bayesian confidence propagation neural network
• sildenafil
• tadalafil
• vardenafil

Author contribution

All authors discussed and commented on the results of the manuscript. XY Qiu and MK Zhong designed the study; MM Yan, JW Chow and ZR Li performed the study; H Zhao and JW Chow analyzed and interpreted data; JW Chow, Q Zhang, and ZR Li contributed production of form, figures and analytic tools; MM Yan and JW Chow drafted the manuscript; XY Qiu and MM Yan revised the manuscript; MK Zhong and XY Qiu finally approved the version to be published.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This study was funded by 2020 Shanghai ‘Rising Stars of Medical Talent’ Youth Development Program-Clinical Pharmacist Program (SHWSRS (2021) 099).