What medications are used to treat erectile dysfunction?

Medications for Erectile Dysfunction

Phosphodiesterase type 5 inhibitors (PDE5i) are the first-line pharmacological treatment for erectile dysfunction, with sildenafil, tadalafil, vardenafil, and avanafil being the FDA-approved options in the United States. 1

First-Line Treatment: PDE5 Inhibitors

Available PDE5 Inhibitors

• Sildenafil (Viagra): 25mg, 50mg, 100mg as needed
• Tadalafil (Cialis): 2.5mg, 5mg daily or 5mg, 10mg, 20mg as needed
• Vardenafil (Levitra): 5mg, 10mg, 20mg as needed
• Avanafil (Stendra): 50mg, 100mg, 200mg as needed

Efficacy

PDE5 inhibitors have demonstrated high efficacy rates in clinical trials:

• Sildenafil: 77-84% improvement in erectile function 2
• Tadalafil: 69% improvement in erectile function 2
• Vardenafil: 68% successful sexual intercourse attempts vs. 35% for placebo 1
• Avanafil: Similar efficacy to other PDE5 inhibitors with potentially faster onset

In a trade-off analysis, sildenafil 50mg showed the greatest efficacy but also had higher rates of adverse events, while tadalafil 10mg demonstrated intermediate efficacy with the lowest rate of adverse events 3.

Dosing and Administration

• Starting doses:

  • Sildenafil: 50mg as needed
  • Tadalafil: 10mg as needed or 2.5mg daily
  • Vardenafil: 10mg as needed
  • Avanafil: 100mg as needed

• Dose titration: Doses should be titrated to provide optimal efficacy while minimizing side effects 1

• Timing:

  • Take 30-60 minutes before sexual activity (sildenafil, vardenafil, avanafil)
  • Tadalafil can be taken up to 36 hours before anticipated sexual activity or daily regardless of timing of sexual activity 4

Important Instructions for Patients

Proper medication use is crucial, as many treatment failures are due to incorrect use 2:

• Take on an empty stomach for sildenafil and vardenafil (food can delay absorption)
• Ensure adequate sexual stimulation (PDE5 inhibitors require sexual stimulation to work)
• Allow sufficient time for onset of action
• Try the medication multiple times before declaring treatment failure

Side Effects of PDE5 Inhibitors

Common side effects include:

• Headache
• Flushing
• Dyspepsia (lowest with avanafil)
• Nasal congestion
• Back pain (more common with tadalafil)
• Myalgia (lowest with vardenafil and avanafil)
• Visual disturbances (more common with sildenafil)
• Dizziness 1

Contraindications

• Absolute contraindication: Concurrent use of nitrates in any form due to risk of severe hypotension 4
• Caution in:
  • Patients taking alpha-blockers (start with lowest dose)
  • Patients with cardiovascular disease
  • Patients with hepatic or renal impairment (dose adjustment needed)
  • Patients taking CYP3A4 inhibitors like ketoconazole or ritonavir (dose reduction needed) 4

Management of Treatment Failure

If a patient fails to respond to one PDE5 inhibitor:

1. Ensure proper medication use and adequate sexual stimulation
2. Optimize the dose of the current PDE5 inhibitor
3. Consider switching to another PDE5 inhibitor
4. For men with testosterone deficiency, combination with testosterone therapy may improve response 1

Second-Line Treatments

For patients who do not respond to PDE5 inhibitors:

Vacuum Erection Devices (VEDs)

• Non-invasive mechanical option
• Can be used in combination with PDE5 inhibitors
• May help prevent penis length loss after prostate cancer treatment 1

Intraurethral Alprostadil

• Alprostadil pellet inserted into the urethra
• In-office test dose required before prescription
• Success rates of 29.5-78.1% reported 1

Intracavernosal Injections

• Direct injection of medication into the penis
• Options include alprostadil alone or in combination with papaverine, phentolamine, and/or atropine
• In-office test required before prescription
• Higher efficacy than oral medications but more invasive 1

Third-Line Treatment

• Penile prosthesis implantation: Surgical option for patients who fail or cannot use other treatments 1

Special Considerations

• Cardiovascular risk: ED is a risk marker for cardiovascular disease; appropriate referrals should be made 1
• Post-prostatectomy: PDE5 inhibitors are less effective but still first-line; early initiation may improve outcomes 1
• Diabetes: More severe ED at baseline with less robust response to PDE5 inhibitors 1

PDE5 inhibitors remain the cornerstone of ED treatment due to their efficacy, safety, and ease of use, with selection among them based on patient preference, side effect profile, and specific clinical circumstances.