Is tadalafil (PDE5 inhibitor) similar to sildenafil (PDE5 inhibitor)?

Tadalafil and Sildenafil: Comparative Analysis

Tadalafil and sildenafil are essentially equivalent in efficacy for treating erectile dysfunction, with both achieving approximately 69% success rates for sexual intercourse compared to 33-35% with placebo, but tadalafil's significantly longer duration of action (up to 36 hours versus 4-5 hours) makes it the preferred choice for most patients seeking spontaneity in sexual activity. 1

Efficacy Comparison

Both medications demonstrate nearly identical effectiveness:

• Success rates for intercourse: Sildenafil achieves 69% success (range 52-85%) while tadalafil achieves 69% success (range 50-85%), compared to placebo at 33-35% 1
• Erection improvement: Both agents improve erections in 73-88% of patients versus 26-32% with placebo 1, 2
• Head-to-head evidence: Low-quality studies comparing the two drugs provide insufficient evidence to determine superiority of one over the other for erectile function outcomes 3

Critical Pharmacological Distinctions

The key differences lie in pharmacokinetics rather than efficacy:

• Duration of action: Tadalafil remains effective up to 36 hours versus sildenafil's 4-5 hours 1
• Half-life: Tadalafil has a 17.5-hour half-life compared to approximately 4 hours for sildenafil 4, 5
• Food interactions: Fatty food significantly affects sildenafil and vardenafil absorption but does not affect tadalafil 4
• Nitrate washout period: Sildenafil requires at least 24 hours before nitrate administration, while tadalafil requires 24-48 hours due to its longer half-life 1, 6

Dose-Response Characteristics

An important distinction exists in how these medications respond to dose escalation:

• Sildenafil: Shows dose-related improvement from 25 mg to 50 mg, but less additional benefit when increasing from 50 mg to 100 mg 1, 2
• Tadalafil: Demonstrates NO significant dose-response difference between 5 mg, 10 mg, and 20 mg for on-demand dosing, meaning dose selection should be based on tolerability rather than expecting better efficacy at higher doses 1, 6

Adverse Effect Profiles

Both medications share similar safety profiles with minor differences:

• Common side effects (both agents): Headache, flushing, dyspepsia, nasal congestion, myalgia, visual disturbances, and dizziness 1, 2
• Serious adverse events: Less than 2% incidence for both, with no significant difference between agents 3, 2
• Specific differences: Tadalafil causes more myalgia and back pain but significantly less flushing compared to sildenafil 6, 7
• Visual disturbances: Tadalafil has lower rates of ocular side effects, likely due to less PDE6 inhibition 5
• Overall tolerability: Very-low-quality evidence shows adverse events do not statistically differ between the two agents 3

Patient Preference Data

Real-world preference studies consistently favor tadalafil:

• Preference rates: In crossover studies of PDE5 inhibitor-naïve patients, 66-71% preferred tadalafil over sildenafil 8, 9
• Psychological outcomes: Tadalafil significantly improves sexual confidence compared to sildenafil 7
• Partner preference: Partners also prefer tadalafil over sildenafil 7

The preference for tadalafil appears driven by its longer duration allowing for spontaneous sexual activity rather than scheduled intercourse 6

Special Populations

Both agents perform similarly in challenging populations:

• Diabetes patients: Both are effective though response is less robust than in the general ED population 1
• Post-prostatectomy: Both remain effective but with diminished response compared to general ED patients 1, 6
• Testosterone deficiency: Combining either agent with testosterone therapy may be more effective than monotherapy 6

Practical Prescribing Algorithm

First-line choice: The American Urological Association suggests both are equally appropriate first-line treatments 1

Choose tadalafil when:

• Patient desires spontaneous sexual activity without timing medication 6
• Patient has concurrent BPH (tadalafil 5 mg daily treats both conditions) 6
• Patient experienced flushing with sildenafil 7

Choose sildenafil when:

• Patient prefers shorter duration of action 1
• Cost is a primary concern (sildenafil typically less expensive as generic)
• Shorter nitrate washout period is clinically relevant 1

Dosing strategy:

• Sildenafil: Start 50 mg, titrate to 25-100 mg based on response 2
• Tadalafil: Start 10 mg, adjust to 5-20 mg based on tolerability (not efficacy, as no dose-response exists) 6

Adequate trial definition: At least 4-8 attempts at proper dosing before declaring treatment failure 1, 6

Critical Safety Warnings

Absolute contraindication: Never combine with nitrates due to potentially fatal hypotension risk 1, 6

Cardiovascular screening: Before prescribing either agent, assess ability to perform moderate physical activity; refer to cardiology if unable 6

Emergency nitrate protocol: If patient requires emergency nitrates, wait 24 hours after sildenafil or 48 hours after tadalafil before administration under close medical supervision 6, 2

Common Pitfalls to Avoid

• Inadequate trial: Many apparent failures result from inadequate attempts, improper timing, lack of sexual stimulation, or modifiable factors 6
• Missing sexual stimulation requirement: Both medications require sexual arousal to work; this must be explicitly explained to patients 6, 2
• Premature dose escalation with tadalafil: Since tadalafil shows no dose-response relationship, increasing from 10 mg to 20 mg rarely improves efficacy and only increases side effects 6
• Food timing with sildenafil: Fatty meals significantly impair sildenafil absorption but not tadalafil 4