Update on the Safety of Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction

Sex Med Rev. 2018 Apr;6(2):242-252. doi: 10.1016/j.sxmr.2017.08.001. Epub 2017 Oct 12.


Introduction: Phosphodiesterase type 5 inhibitors (PDE5Is) have demonstrated efficacy in the treatment of erectile dysfunction (ED). Although historically found to have limited drug-related adverse events, emerging data have suggested that PDE5Is might be associated with melanoma or recurrence of prostate cancer after radical prostatectomy.

Aim: To summarize the literature on the safety of PDE5Is.

Methods: A literature review was performed through PubMed from 1990 through 2016 regarding ED. Keywords used for the search were erectile dysfunction, phosphodiesterase type 5 inhibitors, sildenafil, vardenafil, tadalafil, avanafil, safety, side effects, and adverse events, among others.

Main outcome measures: Visual, auditory, cardiovascular, renal, hepatic, priapic, and oncologic outcomes associated with the intake of PDE5Is for the treatment of ED, in addition to drug interactions, abuse, overdose, and the phenomenon of counterfeit medications.

Results: PDE5Is are safe drugs for the management of ED. Although recent studies have shown an increased risk of non-arteritic ischemic optic neuropathy with PDE5Is, the magnitude of that risk is small. The possibility that PDE5Is cause sensorineural hearing loss remains uncertain. PDE5Is display a safe cardiovascular profile if used according to the Princeton III Consensus guidelines. There appears to be an association between PDE5I use and melanoma but the absence of a mechanism of causation raises doubt that the association is cause and effect. PDE5Is do not increase the risk of biochemical recurrence after prostate cancer management. PDE5I abuse and use of counterfeit medications present serious global health concerns.

Conclusion: Current data strongly support the efficacy, tolerability, and overall safety of PDE5Is for the treatment of ED. PDE5Is probably cause a small increase in the risk of non-arteritic ischemic optic neuropathy. Evidence on increased rates of melanoma and prostate cancer recurrence is weak and controversial. PDE5Is should still be considered first-line therapy for the treatment of most etiologies of ED. Yafi FA, Sharlip ID, Becher EF. Update on the Safety of Phosphodiesterase Type 5 Inhibitors for the Treatment of Erectile Dysfunction. Sex Med Rev 2018;6:242-252.

Keywords: Erectile Dysfunction; Melanoma; Phosphodiesterase Type 5 Inhibitors; Prostate Cancer; Safety.

Publication types

  • Review

MeSH terms

  • Adult
  • Erectile Dysfunction / drug therapy*
  • Humans
  • Male
  • Melanoma
  • Middle Aged
  • Phosphodiesterase 5 Inhibitors / adverse effects*
  • Phosphodiesterase 5 Inhibitors / therapeutic use*
  • Prostatic Neoplasms
  • Vision Disorders


  • Phosphodiesterase 5 Inhibitors