What is the next best step for a patient with erectile dysfunction who has failed to respond to Cialis (tadalafil) and Viagra (sildenafil)?

Next Best Step for Erectile Dysfunction After Failed PDE5 Inhibitors

Before abandoning oral therapy, first verify that the patient received an adequate trial of PDE5 inhibitors with proper dosing, timing, and sexual stimulation, as re-education and optimization can convert up to 30% of initial non-responders into responders. 1

Step 1: Evaluate for Modifiable Factors Contributing to PDE5 Inhibitor Failure

Before proceeding to more invasive therapies, assess and address potentially reversible causes of treatment failure 1:

• Hormonal abnormalities - Check morning total testosterone; consider testosterone therapy if low, as hypogonadal men may respond to combination PDE5 inhibitor plus testosterone therapy 1
• Suboptimal dosing - Ensure maximum dose was attempted (sildenafil 100mg, tadalafil 20mg as needed or 5mg daily) 2
• Timing issues - Verify patient took medication 30-60 minutes before sexual activity with adequate sexual stimulation 2
• Food/drug interactions - High-fat meals can delay sildenafil absorption; review concurrent medications 1
• Heavy alcohol use - Excessive alcohol impairs erectile function 1
• Relationship factors - Partner involvement and expectations affect outcomes 1

Step 2: Consider Alternative PDE5 Inhibitor or Combination Therapy

If modifiable factors are addressed and an adequate trial confirmed:

• Trial a different PDE5 inhibitor (e.g., vardenafil or avanafil if not yet tried) - While evidence is limited, some patients respond to one agent after failing another 1
• Combination therapy with vacuum erection device (VED) plus PDE5 inhibitor - This combination showed 79% success rate (SEP-2) and 70% success rate (SEP-3) in PDE5 inhibitor non-responders, with significant IIEF-5 score improvement from 9.0 to 17.6 3

Step 3: Second-Line Therapies (In Order of Invasiveness)

Vacuum Erection Device (VED) alone 1:

• 90% initial efficacy, though drops to 50-64% at 2 years 1
• Only use devices with vacuum limiters to prevent penile injury 1
• Best suited for older patients with infrequent intercourse 1
• Contraindicated in bleeding disorders 1

Intraurethral alprostadil suppositories 1:

• Less invasive than injection therapy
• First dose must be administered under healthcare supervision due to 3% risk of syncope 1
• Lower efficacy than intracavernosal injection in post-marketing studies 1
• Can be combined with VED or PDE5 inhibitors for enhanced efficacy 1

Intracavernosal injection therapy 1:

• Most effective non-surgical treatment with up to 90% success rates 1, 4
• Options include alprostadil (PGE1), papaverine, phentolamine, or combinations (bimix/trimix) 1
• First dose must be administered under healthcare supervision to determine effective dose and monitor for prolonged erection 1
• Highest risk of priapism among ED treatments 1
• Patients must be counseled that erections lasting >4 hours require immediate medical attention 1

Step 4: Emerging and Surgical Options

Low-intensity shockwave therapy (LI-SWT) 1:

• May be used in men with mild vasculogenic ED
• Shows benefit in PDE5 inhibitor non-responders with mean IIEF-EF improvement 1
• Enhanced results when combined with VED or daily tadalafil 1
• Still considered investigational by some authorities 5

Penile prosthesis implantation 1:

• Definitive surgical option when all medical therapies fail or cause intolerable side effects 1, 5
• Modern devices have low failure and infection rates 4, 5
• Inflatable prostheses best mimic physiologic erection 4
• High patient and partner satisfaction rates 4

Critical Pitfalls to Avoid

• Do not proceed to invasive therapies without confirming adequate PDE5 inhibitor trial - Many "failures" are due to improper use, inadequate dosing, or insufficient attempts 1
• Do not overlook testosterone deficiency - Hypogonadal men often fail PDE5 inhibitors until testosterone is replaced 1
• Do not prescribe intraurethral or intracavernosal therapy without in-office supervision of first dose - This is a safety standard to prevent syncope and priapism 1
• Do not use VEDs without vacuum limiters - These prevent penile injury from excessive negative pressure 1