What can be added to Cialis (tadalafil) 40mg for a patient who does not respond to 20mg?

Tadalafil Dose Optimization and Combination Therapy for Erectile Dysfunction

For patients responding to tadalafil 40 mg but not 20 mg, the most effective strategy is to continue the higher dose (40 mg) rather than adding another medication, as this represents appropriate dose titration within the therapeutic range.

Understanding the Dose-Response Relationship

The question implies you're using tadalafil 40 mg for erectile dysfunction (ED), which is double the standard maximum dose. However, the evidence supports this approach:

• Tadalafil does not demonstrate clear dose-related improvements in erectile function beyond standard dosing, meaning higher doses may not provide additional benefit 1
• In men with severe ED, tadalafil 20 mg showed statistically greater improvements compared to 10 mg in erectile function domain scores (13.6 vs. 10.4; P = 0.014) and successful intercourse attempts (56% vs. 43%, P = 0.019) 2
• The standard maximum dose for ED is 20 mg taken on-demand, though some studies have evaluated 40 mg dosing 3, 2

Alternative Dosing Strategy: Daily vs. On-Demand

If 40 mg on-demand is working but you're seeking optimization, consider switching to daily tadalafil dosing rather than adding medications:

• Daily tadalafil (10-20 mg) was effective in 69% of men who were previous non-responders to on-demand tadalafil, with significant improvements in erectile function scores (mean improvement of 8.2 points from on-demand baseline, P < 0.001) 4
• Daily dosing resulted in 58% successful intercourse attempts compared to previous on-demand failures 4
• Daily tadalafil 5 mg allowed 39-40% of men with incomplete response to maximum-dose on-demand PDE5 inhibitors to achieve normal erectile function (IIEF-EF ≥26) compared to 12% with placebo (P < 0.001) 5

What NOT to Add

Do not add other PDE5 inhibitors or combine with nitrates:

• Nitrate medications are absolutely contraindicated with tadalafil due to severe hypotension risk 1, 6
• Avoid nitrates for at least 48 hours after tadalafil use 6, 1
• Combining different PDE5 inhibitors is not evidence-based and increases adverse effect risk without proven benefit

Addressing Non-Response: Key Considerations

Before adding anything, ensure adequate trial:

• More than one trial may be required to establish efficacy, with an adequate trial defined as at least 5 separate occasions at the maximum dose 1
• Sexual stimulation is necessary for tadalafil to be effective 1
• Assess for organic comorbidities (diabetes, cardiovascular disease, hypogonadism) that may limit response 2

Common Adverse Effects to Monitor

With higher doses, expect increased frequency of:

• Headache (most common adverse effect) 7, 1
• Dyspepsia and flushing 7, 1, 4
• Back pain and myalgia 1
• Nasal congestion 7, 1
• Most adverse events are transient and mild to moderate in severity 1, 4

Critical Safety Assessment

Before continuing 40 mg dosing:

• Assess cardiovascular risk, particularly in patients unable to perform moderate exercise 1
• Verify no concurrent nitrate use (including recreational drugs) 6, 1
• Review for contraindications including severe hepatic impairment, recent stroke/MI, or uncontrolled hypertension

The Bottom Line on "Adding" Therapy

There is no evidence-based medication to add to tadalafil for ED. The appropriate clinical approach when 20 mg fails but 40 mg works is:

1. Continue the effective 40 mg dose (recognizing this exceeds standard FDA-approved dosing for ED)
2. Consider switching to daily low-dose tadalafil (5 mg) as an alternative strategy 5
3. Evaluate and treat underlying comorbidities (testosterone deficiency, diabetes control, cardiovascular disease) 2
4. Ensure adequate trial with proper sexual stimulation 1

Note: The evidence provided regarding pulmonary arterial hypertension (PAH) dosing is not applicable to ED treatment, as PAH uses different dosing strategies (40 mg daily for PAH vs. on-demand for ED) 6, 7.