Sildenafil Dosing After Tadalafil Failure
Start with sildenafil 50 mg taken as needed approximately 1 hour before sexual activity, with the option to increase to 100 mg if the 50 mg dose is well-tolerated but provides insufficient efficacy. 1, 2
Rationale for Dose Selection
Sildenafil demonstrates dose-dependent efficacy, unlike tadalafil, making it a logical choice when switching from tadalafil failure. 1, 2 The key pharmacological difference is that sildenafil shows meaningful improvement from 25 mg to 50 mg, with some additional benefit when increasing from 50 mg to 100 mg, whereas tadalafil shows no dose-response difference between 5-20 mg. 1, 2
Starting Dose Strategy
Begin with sildenafil 50 mg as this represents the standard starting dose that balances efficacy and tolerability, with 69% of men achieving successful sexual intercourse compared to 35.5% with placebo. 2
Sildenafil 50 mg provides the highest global efficacy among PDE5 inhibitors at starting doses, though it also carries the highest rate of overall adverse events. 3
The 50 mg dose is rapidly absorbed with peak plasma concentrations within 1 hour and an elimination half-life of 3-5 hours. 4
Dose Titration
If 50 mg is well-tolerated but provides insufficient efficacy, increase to 100 mg (the maximum dose), as sildenafil shows continued dose-related improvement at this level, though the incremental benefit from 50 mg to 100 mg is less pronounced than from 25 mg to 50 mg. 1, 2
The most commonly effective doses in clinical trials were 50 mg or 100 mg, though lower doses were effective in some patients. 4
Critical Pre-Treatment Evaluation
Before declaring tadalafil a true failure and switching to sildenafil, verify that the tadalafil trial was adequate:
Ensure at least 5 separate attempts at maximum tadalafil dose (20 mg) were completed. 5
Confirm adequate sexual stimulation was present, as PDE5 inhibitors require sexual arousal to work. 5, 1
Rule out hormonal abnormalities (check total testosterone, free testosterone, SHBG), as testosterone deficiency reduces PDE5 inhibitor response. 5
Assess for heavy alcohol use, which impairs erectile function and increases adverse effects. 5, 1
Verify proper timing of medication relative to sexual activity. 5, 1
Safety Considerations
Absolute contraindication: Never use sildenafil with nitrates due to severe hypotension risk. 2
Wait at least 24 hours after sildenafil before administering emergency nitrates (compared to 48 hours for tadalafil). 5, 2
Common adverse effects include headache, flushing, dyspepsia, nasal congestion, and abnormal vision, occurring transiently and typically mild to moderate. 1, 4
Serious adverse events occur in <2% of patients, with no significant difference compared to placebo. 1
Optimizing Treatment Success
Ensure 4-8 attempts at proper dosing before declaring sildenafil failure, as many apparent treatment failures result from inadequate trials. 2
Take sildenafil approximately 1 hour before sexual activity, no more than once daily. 4
Maximum frequency is once daily. 2
Consider lower starting doses (25 mg) in elderly patients or those with hepatic/renal impairment or taking CYP3A4 inhibitors (ritonavir, ketoconazole, erythromycin, cimetidine). 4
Expected Outcomes
Sildenafil improves erections in 73-88% of patients compared to 26-32% with placebo. 2
Success rates for sexual intercourse range from 52-85% with sildenafil versus 35.5% with placebo. 2
Efficacy is maintained in long-term (1-year) studies. 4
Patients with diabetes or post-prostatectomy have more severe ED at baseline and may respond less robustly, but sildenafil remains effective in these populations. 5, 2