What are stronger prescription medicines to treat erectile dysfunction when Viagra (sildenafil) is no longer effective?

When Sildenafil (Viagra) Is No Longer Effective

Before switching to a "stronger" medication, you must first ensure the sildenafil trial was adequate—at least 5 separate attempts at maximum dose (100 mg) with proper timing, adequate sexual stimulation, and correction of modifiable factors such as hormonal abnormalities, excessive alcohol use, and relationship issues. 1, 2

Step 1: Verify Adequate Trial of Sildenafil

Many apparent "failures" are actually inadequate trials. Before declaring treatment failure, systematically evaluate:

• Dosing adequacy: Confirm patient tried 100 mg (maximum dose) for at least 5 separate attempts 2
• Timing: Sildenafil should be taken approximately 1 hour before sexual activity, and fatty foods can impair absorption 3, 4
• Sexual stimulation: The medication requires adequate sexual arousal to work—it does not create spontaneous erections 5, 2
• Hormonal status: Check total testosterone and free testosterone, as low testosterone significantly impairs PDE5 inhibitor response 1, 2
• Alcohol consumption: Heavy alcohol use is a common cause of treatment failure and must be addressed 2
• Drug interactions: CYP3A4 inhibitors (ketoconazole, erythromycin, ritonavir) can affect sildenafil metabolism 3

Step 2: Switch to a Different PDE5 Inhibitor

If sildenafil truly failed after an adequate trial, switching to vardenafil or tadalafil is the next appropriate step—these are not necessarily "stronger" but have different pharmacokinetic profiles that may work better for individual patients. 1

Vardenafil (Levitra)

• Dosing: Start at 10 mg, can increase to 20 mg 1
• Advantages: Shows dose-dependent efficacy (20 mg > 10 mg > 5 mg), faster onset of action (successful intercourse reported in 21% of patients within 10 minutes) 1, 4
• Efficacy: 68% successful intercourse attempts vs 35% with placebo 1
• Considerations: Similar to sildenafil, food (especially fatty meals) can delay absorption 4

Tadalafil (Cialis)

• Dosing: 10-20 mg as-needed, OR 2.5-5 mg daily 2, 6
• Advantages: Longest duration of action (up to 36 hours), not affected by food intake, allows for spontaneous sexual activity without timing medication 2, 4
• Efficacy: 69% successful intercourse attempts vs 33% with placebo 1, 6
• Unique feature: Unlike sildenafil and vardenafil, tadalafil does NOT show dose-dependent improvement between 5-20 mg, so choose dose based on tolerability rather than expecting better efficacy at higher doses 2
• Daily dosing option: For couples preferring spontaneous rather than scheduled sexual activity, tadalafil 2.5-5 mg once daily eliminates need to time medication 2

Step 3: Consider Combination Therapy

If testosterone deficiency is identified (total testosterone <288 ng/dL), combining a PDE5 inhibitor with testosterone replacement therapy is more effective than either alone. 2

• Testosterone therapy alone is NOT effective monotherapy for ED 2
• The combination addresses both vascular and hormonal components of erectile dysfunction 2

Step 4: More Invasive Options if All PDE5 Inhibitors Fail

If adequate trials of multiple PDE5 inhibitors fail, consider:

• Alprostadil intraurethral suppositories: Less invasive than injections but less effective; first dose must be administered under medical supervision due to 3% risk of syncope 1
• Intracavernous injection therapy: More invasive but higher efficacy rates 1
• Vacuum constriction devices: Non-pharmacologic option 1
• Penile prostheses: Surgical option for refractory cases 1

Critical Safety Considerations

All PDE5 inhibitors are absolutely contraindicated with nitrate use due to potentially fatal hypotension. 2, 7

• Wait at least 24 hours after sildenafil before nitrate administration 1, 5
• Wait at least 48 hours after tadalafil before nitrate administration 1, 2
• Assess cardiovascular risk before prescribing any PDE5 inhibitor; refer patients unable to perform moderate physical activity to cardiology 2

Common Pitfalls to Avoid

• Declaring failure too early: Most "failures" are inadequate trials with correctable factors 1, 2
• Not checking testosterone: Hormonal deficiency is a common modifiable factor that significantly impairs PDE5 inhibitor response 1, 2
• Expecting dramatically better results with higher tadalafil doses: Unlike sildenafil and vardenafil, tadalafil efficacy is NOT dose-dependent 2
• Ignoring relationship issues: Partner dynamics and inadequate sexual stimulation are frequently overlooked causes of treatment failure 1