Is it safe to combine Viagra (sildenafil) and Cialis (tadalafil) with apomorphine for the treatment of erectile dysfunction?

Combining PDE5 Inhibitors (Viagra/Cialis) with Apomorphine for Erectile Dysfunction

Direct Answer

Do not combine sildenafil (Viagra) or tadalafil (Cialis) with apomorphine for erectile dysfunction—there is no evidence supporting improved efficacy with combination therapy, and the risk of additive adverse effects, particularly severe hypotension, outweighs any theoretical benefit. 1

Evidence Against Combination Therapy

Lack of Efficacy Data

• The American College of Physicians explicitly recommends optimizing the dose of a single PDE5 inhibitor rather than adding a second agent or combining with other oral ED medications, as combination therapy increases the risk of severe hypotension and other adverse effects without proven additional benefit. 2

• No high-quality evidence demonstrates that combining PDE5 inhibitors with apomorphine improves erectile function outcomes compared to either agent alone. 1, 3

Safety Concerns with Combination

• Both PDE5 inhibitors and apomorphine can cause significant hypotension, particularly when combined with nitrates (which is absolutely contraindicated). 1, 4

• Apomorphine's side effect profile includes dose-dependent nausea (common), dizziness, severe sweating, drowsiness, syncope, and hypotension—effects that could be potentiated when combined with PDE5 inhibitors. 4, 5

• The combination of vasoactive agents increases cardiovascular risk without established safety data, particularly concerning in patients with underlying cardiovascular disease. 1

Comparative Efficacy: Monotherapy Approach

PDE5 Inhibitors as First-Line

• Sildenafil and tadalafil are equally effective first-line treatments, achieving 69% success rates for sexual intercourse versus 33-35% with placebo. 6

• Both agents improve erections in 73-88% of patients compared to 26-32% with placebo. 6

• An adequate trial consists of at least 5 separate attempts at maximum dose before declaring treatment failure—many apparent failures result from inadequate trials, improper timing, or lack of sexual stimulation. 2

Apomorphine as Alternative, Not Additive

• Apomorphine sublingual (2-3 mg) shows significantly lower efficacy than sildenafil, with nearly 90% of patients preferring doses of at least 4 mg, which are not commercially available in most markets. 4, 5

• Direct comparative studies show sildenafil is more effective than apomorphine (83.3% vs 40.3% successful intercourse), with 93.8% of patients preferring sildenafil after trying both agents. 7

• Apomorphine represents an alternative for patients who cannot use PDE5 inhibitors (e.g., those on nitrates), not a complementary therapy. 3, 5

Recommended Clinical Algorithm

Step 1: Optimize Single-Agent PDE5 Inhibitor Therapy

• Start with sildenafil 50 mg or tadalafil 10 mg as needed, or tadalafil 2.5-5 mg daily for spontaneous activity preference. 2, 6

• Titrate to maximum tolerated dose (sildenafil 100 mg, tadalafil 20 mg as needed, or tadalafil 5 mg daily) based on efficacy and tolerability. 2

• Ensure proper use: sexual stimulation required, correct timing (sildenafil 30-60 minutes before, tadalafil up to 36 hours), avoid heavy meals with sildenafil. 2

Step 2: Address Treatment Failures Before Switching

• Evaluate for inadequate trial: verify at least 5 attempts at maximum dose. 2

• Screen for modifiable factors: hormonal abnormalities (check testosterone), drug interactions, heavy alcohol use, relationship issues. 2

• For men with testosterone deficiency (<300 ng/dL), combine PDE5 inhibitor with testosterone therapy—this is the only evidence-based combination approach. 2

Step 3: Switch to Alternative PDE5 Inhibitor

• If first PDE5 inhibitor fails after adequate trial, switch to a different PDE5 inhibitor (e.g., sildenafil to tadalafil or vice versa) rather than adding apomorphine. 2, 6

Step 4: Consider Apomorphine Only as Alternative

• Reserve apomorphine for patients with absolute contraindications to PDE5 inhibitors (concurrent nitrate use, recent cardiovascular events). 4, 5

Critical Safety Screening

Absolute Contraindications to PDE5 Inhibitors

• Concurrent nitrate use (oral, sublingual, transdermal, or recreational) due to risk of potentially fatal hypotension. 1, 2

• Wait 24 hours after sildenafil or 48 hours after tadalafil before administering nitrates in emergency situations. 1, 2

Cardiovascular Risk Assessment

• Low-risk patients (asymptomatic CAD with <3 risk factors, controlled hypertension, mild stable angina, successful revascularization, uncomplicated past MI, mild valvular disease, CHF NYHA class I) can safely receive PDE5 inhibitors. 2

• Refer to cardiology before prescribing if patient cannot perform moderate physical activity (3-5 METs) or has indeterminate cardiovascular risk. 1, 2

Common Pitfalls to Avoid

• Do not combine oral ED medications without evidence—polypharmacy increases adverse effects without proven benefit. 1, 2

• Do not declare treatment failure without ensuring adequate trial parameters (dose, frequency, timing, sexual stimulation). 2

• Do not prescribe PDE5 inhibitors without explicitly asking about all forms of nitrate use, including recreational ("poppers"). 2

• Do not assume apomorphine is safer than PDE5 inhibitors—both have significant cardiovascular effects and interact with nitrates. 4, 5