What is the first-line medication for maintaining an erection in erectile dysfunction (ED)?

First-Line Medication for Erectile Dysfunction

Oral phosphodiesterase type 5 inhibitors (PDE5i) are the first-line medication for maintaining an erection in erectile dysfunction. 1

PDE5 Inhibitors as First-Line Therapy

• PDE5 inhibitors have been extensively studied with high efficacy and safety profiles, making them the standard first-line treatment for erectile dysfunction (ED) 1
• The FDA-approved oral PDE5 inhibitors available in the U.S. include sildenafil, tadalafil, vardenafil, and avanafil 1
• These medications work by delaying cGMP degradation, which leads to decreased intracellular calcium levels, producing smooth muscle relaxation in the corpus cavernosum and enhancing blood flow resulting in erection during sexual stimulation 1

Efficacy of PDE5 Inhibitors

• High-quality evidence shows that PDE5 inhibitors significantly improve erections (73-88% of patients) compared to placebo (26-32%) 1
• PDE5 inhibitors are effective across various patient populations, including those with diabetes, depression, cardiovascular disease, and other medical conditions 1
• Dose titration to the maximum tolerated dose is strongly recommended as it increases efficacy and satisfaction from treatment 2

Comparing Different PDE5 Inhibitors

• Current evidence suggests that sildenafil, tadalafil, vardenafil, and avanafil have similar efficacy in the general ED population 1, 2
• In a trade-off analysis, sildenafil 50mg showed the greatest efficacy but also had the highest rate of overall adverse events, while tadalafil 10mg had intermediate efficacy with the lowest overall rate of adverse events 3
• The choice between different PDE5 inhibitors may be guided by:
  • Duration of action: tadalafil has a longer half-life (up to 36 hours) compared to others 4, 5
  • Onset of action: avanafil has the most rapid onset 6
  • Patient preference and response 5

Administration and Maximizing Benefit

• When prescribing a PDE5 inhibitor, proper instructions should be provided to maximize benefit/efficacy 1
• Common reasons for treatment failure include:
  • Lack of sexual stimulation
  • Taking medication with a large meal (particularly for sildenafil)
  • Insufficient dose titration 1, 7
• The dose should be titrated to provide optimal efficacy while minimizing side effects 1

Safety Considerations and Contraindications

• The most common adverse events with PDE5 inhibitors include headache, flushing, nasal congestion, dyspepsia, and back pain 1
• Absolute contraindications include:
  • Concurrent use of nitrates or nitric oxide donors (risk of severe hypotension) 1, 7
  • Use of guanylate cyclase stimulators such as riociguat 7
• Caution is advised in patients with:
  • Cardiovascular risk factors (patients should be categorized as low, intermediate, or high risk) 1
  • Severe renal or liver disease 1
  • Recent history of stroke or myocardial infarction 1

Alternative Options for Non-Responders

• For patients who fail PDE5 inhibitor therapy despite adequate trials, second-line options include:
  • Vacuum erection devices (VED) 1
  • Intraurethral alprostadil suppositories 1
  • Intracavernosal injection therapy with alprostadil, papaverine, or phentolamine 1, 2
• Penile prosthesis implantation is considered for patients who fail or cannot use other therapies 1

Follow-up and Monitoring

• Patients receiving continuing PDE5 inhibitor therapy should have periodic follow-up to assess:
  • Efficacy
  • Side effects
  • Any significant changes in health status or medications 1
• This monitoring is typically done at the time of prescription renewal 1

Common Pitfalls to Avoid

• Failure to titrate to an optimal dose before concluding treatment failure 1
• Not educating patients about proper use (timing relative to meals, need for sexual stimulation) 1
• Overlooking cardiovascular risk factors that may contraindicate therapy 1
• Not considering drug interactions, particularly with nitrates 7
• Using counterfeit medications from unauthorized sources 2