Is it okay for a primary care provider (PCP) to prescribe both tadalafil (Cialis) and sildenafil (Viagra) together?

Prescribing Tadalafil and Sildenafil Together

Primary care providers should NOT prescribe tadalafil and sildenafil together for erectile dysfunction, as this combination is explicitly contraindicated by FDA labeling and clinical guidelines. 1

Why This Combination is Contraindicated

FDA Labeling Prohibition

• The FDA drug label for tadalafil explicitly states: "Do not use other ED medicines or ED treatments while taking tadalafil tablets" and specifically warns against combining tadalafil with other PDE5 inhibitors 1
• The safety and efficacy of combinations of tadalafil with other PDE5 inhibitors have not been studied, and patients must be informed not to take tadalafil with other PDE5 inhibitors 1

Clinical Guideline Consensus

• The American Urological Association guidelines emphasize that PDE5 inhibitors (sildenafil, tadalafil, vardenafil, avanafil) should be used as monotherapy, not in combination with each other 2
• Guidelines consistently recommend choosing ONE PDE5 inhibitor and optimizing its dose rather than combining multiple agents 2, 3

The Exception: Sequential Use in Research Settings

One low-quality study from 2015 examined combining daily tadalafil 5mg with sildenafil 50mg "as needed" in severe ED, showing some benefit, but this does NOT translate to standard clinical practice. 4

• This single study enrolled 180 patients and found improved IIEF-5 scores in severe ED patients using tadalafil 5mg daily plus sildenafil 50mg as needed 4
• However, this research protocol contradicts FDA labeling and has not been validated in higher-quality studies or incorporated into clinical guidelines 1
• The study's design (combining a daily low-dose agent with an as-needed agent) differs fundamentally from prescribing two as-needed agents or two daily agents together 4

What PCPs Should Do Instead

Optimize Single-Agent Therapy First

• Start with ONE PDE5 inhibitor and titrate to maximum tolerated dose before considering alternatives 2, 3
• For tadalafil: begin at 10mg as needed, increase to 20mg if inadequate response 3
• For sildenafil: titrate dose appropriately with proper instructions on timing and sexual stimulation 2

Consider Switching, Not Combining

• If one PDE5 inhibitor fails at maximum dose, switch to a different PDE5 inhibitor rather than combining them 2
• Tadalafil offers longer duration (17.5-hour half-life vs. 4 hours for sildenafil), which may benefit some patients 2, 3
• Patient preference studies show 66.3% preferred tadalafil 20mg over sildenafil 50mg for treatment initiation 5

Add Non-PDE5 Therapies if Monotherapy Fails

• Consider testosterone replacement therapy for men with low testosterone (<230 ng/dL) or intermediate levels (230-350 ng/dL) either as initial treatment or added after PDE5 inhibitor failure 2
• Combination of sildenafil with non-PDE5 therapies (psychotherapy, other medications) showed greater improvement than sildenafil alone 2
• Refer to urology for specialized treatments (intracavernosal injection, vacuum devices, penile prosthesis) if oral monotherapy inadequate 2

Critical Safety Considerations

Absolute Contraindications Apply to All PDE5 Inhibitors

• Never prescribe any PDE5 inhibitor with nitrates—this applies whether using one or attempting to use two PDE5 inhibitors 2, 6, 1
• Tadalafil requires 48-hour nitrate-free interval (vs. 24 hours for sildenafil) due to its longer half-life 2, 6
• Avoid in patients with systolic blood pressure <100 mmHg 6

Cardiovascular Risk Stratification Required

• All patients with ED require cardiovascular risk assessment before any PDE5 inhibitor prescription, as ED is a marker for cardiovascular disease 2
• Sexual activity requires 3-5 metabolic equivalents; patients unable to achieve this on exercise testing should defer sexual activity until cardiac condition stabilized 2

Common Pitfalls to Avoid

• Do not prescribe two PDE5 inhibitors simultaneously thinking it will enhance efficacy—this violates FDA labeling and lacks safety data 1
• Do not assume that because both drugs are "safe" individually, combining them is acceptable—drug interactions and cumulative vasodilatory effects are unpredictable 1
• Do not attempt the research protocol from the 2015 study in routine practice without specialty consultation—this remains investigational 4

When to Refer to Urology

• Failure of maximum-dose monotherapy with at least two different PDE5 inhibitors 2
• Complex medical history requiring specialized testing (nocturnal penile tumescence, penile duplex ultrasound, intracavernosal injection testing) 2
• Consideration of non-oral therapies or surgical interventions 2
• Desire to attempt combination therapy protocols—this requires specialty oversight, not PCP management 4