Management of Erectile Dysfunction After Vardenafil Failure
Before abandoning PDE5 inhibitors entirely, verify you completed an adequate trial: at least 5 separate attempts at maximum dose (20mg) vardenafil, taken 1 hour before sexual activity with adequate sexual stimulation, avoiding heavy alcohol and large meals. 1, 2
Immediate Steps: Optimize the Current Trial
Most "treatment failures" are actually inadequate trials with correctable factors:
- Check testosterone levels (morning total testosterone, free testosterone, SHBG) - testosterone deficiency (<300 ng/dL) dramatically reduces PDE5 inhibitor response and is present in 12-36% of ED patients 1, 2
- Verify proper timing: Vardenafil requires 1 hour before sexual activity, not taken with large/fatty meals which reduce absorption 2
- Confirm adequate sexual stimulation: PDE5 inhibitors are conditioners, not initiators - they require sexual arousal to work 1, 2
- Assess alcohol consumption: Heavy alcohol use impairs erectile function independent of medication and reduces PDE5 inhibitor efficacy 2
- Screen for relationship issues: Partner problems, inadequate foreplay, or performance anxiety prevent adequate sexual stimulation 2
- Review medications: Antihypertensives (especially beta-blockers, thiazides), antidepressants (SSRIs, tricyclics), and opioids worsen ED 1, 3
After addressing these factors and re-education on proper use, 30% of initial non-responders become successful responders. 1
Switch to a Different PDE5 Inhibitor
Try tadalafil 10-20mg before declaring PDE5 inhibitor class failure - individual response varies between agents despite similar mechanisms. 1, 2
Key advantages of tadalafil over vardenafil:
- 36-hour duration allows spontaneous sexual activity without precise timing 4
- Lower flushing rates compared to other PDE5 inhibitors 5, 4
- No dose-response relationship between 5-20mg (unlike vardenafil), so start at 10mg and increase to 20mg only if poorly tolerated side effects aren't limiting 1, 4
- Alternative daily dosing (2.5-5mg once daily) eliminates timing concerns entirely 1, 4
Add Testosterone Replacement if Deficient
If morning total testosterone <300 ng/dL, add testosterone replacement therapy to the PDE5 inhibitor regimen - combination therapy is more effective than either alone in hypogonadal men. 2, 4
Testosterone alone is NOT effective monotherapy for ED, but dramatically improves PDE5 inhibitor response when deficient. 4
Second-Line Therapies (After Failure of ≥2 Different PDE5 Inhibitors)
Proceed in order of invasiveness based on patient preference:
Intraurethral alprostadil (MUSE): 50-90% success rate, peripheral initiator that works independent of sexual stimulation 1, 2, 6
Intracavernosal injection therapy (alprostadil, papaverine, phentolamine combinations): Up to 90% success rate 1, 7, 6
Vacuum erection devices: Safe, effective non-pharmacologic option for well-selected patients 1, 7
Penile prosthesis implantation: Definitive treatment with high patient/partner satisfaction, especially inflatable devices 7
Critical Safety Reminders
- Never combine PDE5 inhibitors with nitrates - potentially fatal hypotension 1, 2
- Reassess cardiovascular risk - ED is a marker for underlying cardiovascular disease requiring evaluation 1
- Consider mental health referral - psychotherapy reduces performance anxiety and improves treatment adherence, particularly important after medication "failure" 1, 2
Common Pitfalls to Avoid
The most critical error is declaring treatment failure without completing an adequate trial - this requires minimum 5 attempts at maximum dose with proper technique, not just "tried it a few times and it didn't work." 1, 2 Many apparent failures are actually improper use: wrong timing, inadequate stimulation, heavy alcohol, or undiagnosed testosterone deficiency. 1, 2