What is the preferred alternative, Levitra (vardenafil) or Cialis (tadalafil), and at what dose, for a patient with erectile dysfunction who has not responded to Viagra (sildenafil) 100mg?

Switching from Sildenafil to Alternative PDE5 Inhibitors

Switch to tadalafil 10 mg as needed (not Levitra/vardenafil), and titrate to 20 mg if needed after at least 5 attempts, as tadalafil offers superior patient preference and a longer 36-hour window of effectiveness compared to vardenafil, which has no demonstrated advantage over sildenafil. 1, 2, 3

Why Tadalafil Over Vardenafil

Tadalafil is the preferred alternative to sildenafil failure for several compelling reasons:

• Patient preference data strongly favors tadalafil: In head-to-head crossover trials, 66.3% of patients preferred tadalafil 20 mg over sildenafil 50 mg for initiating ED treatment 3, and when patients already taking sildenafil were switched to tadalafil, 90.5% elected to continue with tadalafil versus only 9.5% returning to sildenafil 4

• Extended duration of action: Tadalafil remains effective for up to 36 hours, eliminating the need to precisely time medication with sexual activity, whereas vardenafil has a similar short duration to sildenafil 1, 2

• Vardenafil offers no meaningful advantage: Vardenafil is more potent and selective than sildenafil at inhibiting PDE5, but clinical trials show similar efficacy rates between all three agents (69-77% success vs 33-35% placebo) 1, 5. The only theoretical advantage of vardenafil is less PDE6 inhibition (reduced color vision changes), which is a rare side effect 5

Specific Dosing Protocol for Tadalafil

Start with tadalafil 10 mg as needed, taken prior to anticipated sexual activity 2:

• The FDA-approved starting dose for as-needed use is 10 mg 2
• Titrate to 20 mg if 10 mg is inadequate after at least 5 separate attempts, as many apparent failures result from inadequate trials, improper timing, or lack of sexual stimulation 1, 6
• Maximum dosing frequency is once per day 2
• Unlike sildenafil and vardenafil, tadalafil does NOT show strict dose-dependent improvement between 5-20 mg, but higher doses do benefit some patients 1, 7

Critical Pre-Treatment Safety Assessment

Before prescribing any PDE5 inhibitor, verify the following absolute contraindications and risk factors:

• Nitrate use is an absolute contraindication due to potentially fatal hypotension 1, 2. Ask explicitly about all forms: nitroglycerin, isosorbide, recreational "poppers" 1
• Assess cardiovascular fitness: Can the patient walk 1 mile in 20 minutes or climb 2 flights of stairs without symptoms? If not, refer to cardiology before prescribing 1
• High-risk cardiac conditions requiring stabilization first: unstable angina, uncontrolled hypertension, recent MI/stroke (within 2 weeks), NYHA Class II-IV heart failure 1, 6

Defining an Adequate Trial Before Declaring Failure

Do not declare tadalafil a failure without completing at least 5 separate attempts at maximum tolerated dose (20 mg) 1, 6:

• Many "treatment failures" are actually due to modifiable factors 1, 6:
  • Inadequate sexual stimulation (PDE5 inhibitors require arousal to work) 1, 7
  • Heavy alcohol use (impairs erectile function independently) 1
  • Improper timing (though less critical with tadalafil's 36-hour window) 1
  • Undiagnosed testosterone deficiency (check total testosterone if tadalafil fails) 1

Expected Outcomes and Side Effects

• Efficacy: 69% of men report successful intercourse attempts with tadalafil versus 33% with placebo 1, 2
• Common adverse effects: headache, dyspepsia, back pain, nasal congestion, myalgia 1, 7. Notably, tadalafil has lower rates of flushing compared to sildenafil 1
• Back pain and myalgia are more specific to tadalafil compared to other PDE5 inhibitors 1, 4, 3

Alternative Dosing Strategy

If the patient prefers spontaneous sexual activity without timing medication:

• Consider tadalafil 2.5-5 mg once daily instead of as-needed dosing 1, 2
• This eliminates the need to plan sexual activity around medication timing 1
• Daily dosing is particularly useful for couples who prefer spontaneity over scheduled encounters 1

When to Consider Combination Therapy

If tadalafil fails at maximum dose after adequate trial, check testosterone levels 1, 6:

• Men with testosterone <300 ng/dL respond less robustly to PDE5 inhibitors alone 1
• Combination of tadalafil plus testosterone replacement is more effective than either alone in hypogonadal men 1, 6
• Testosterone monotherapy is NOT effective for ED 1

Common Pitfalls to Avoid

• Don't assume all PDE5 inhibitors are interchangeable: The 36-hour duration of tadalafil provides a clinically meaningful advantage over vardenafil's shorter action 1, 2, 5
• Don't prescribe tadalafil 5 mg daily for ED alone: This dose is primarily for urinary symptoms from BPH, not optimized for erectile function 7
• Don't forget the 48-hour nitrate washout: If emergency nitrates are needed, wait at least 48 hours after tadalafil (versus 24 hours for sildenafil) 1