10-Year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors.
BACKGROUND
To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective.


OBJECTIVE
We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years.


METHODS
Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology.


METHODS
The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths.


RESULTS
Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers.


CONCLUSIONS
Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270.
Department of Urology, Ohio State University Medical Center, Columbus, OH 43210, USA. gregory.lowe@osumc.edu
Gregory
G
Lowe
Raymond A
RA
Costabile
D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000139:chemically induced; D007172:Erectile Dysfunction / Q000188:drug therapy; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use; D011358:Product Surveillance, Postmarketing / Q000706:statistics & numerical data; D011687:Purines / Q000009:adverse effects / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use; D000068581:Tadalafil; D014227:Triazines / Q000009:adverse effects / Q000627:therapeutic use; D014481:United States; D014486:United States Food and Drug Administration / Q000706:statistics & numerical data; D000069058:Vardenafil Dihydrochloride
D002243:Carbolines; D007093:Imidazoles; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride; D000068581:Tadalafil; D000068677:Sildenafil Citrate