Maximum Dose of Sildenafil
The maximum recommended dose of sildenafil for pulmonary arterial hypertension (PAH) is 20 mg three times daily, while for erectile dysfunction it is 100 mg once daily. 1, 2
Sildenafil Dosing for Different Indications
Pulmonary Arterial Hypertension (PAH)
- The FDA-approved dose for PAH is 20 mg administered orally three times daily (TID) 3, 1
- Doses should be administered 4-6 hours apart 1
- Higher doses are not recommended for PAH treatment, as clinical trials did not demonstrate greater efficacy with doses higher than 20 mg TID 1
- In clinical studies, sildenafil at doses of 20 mg, 40 mg, or 80 mg TID showed similar improvements in exercise capacity with mean placebo-corrected treatment effects of 45,46, and 50 m respectively 3
Erectile Dysfunction (ED)
- For erectile dysfunction, the maximum recommended dose is 100 mg once daily 2, 4
- Starting dose is typically 50 mg taken as needed approximately 1 hour before sexual activity 2
- Lower doses (25 mg) may be appropriate for elderly patients, those with hepatic or renal impairment, or patients taking CYP3A4 inhibitors 2
Safety Considerations
Adverse Effects
- Common adverse events include headache, flushing, dyspepsia, nasal congestion, and abnormal vision 3, 2
- Most side effects are transient and mild to moderate in severity 2
- Higher doses are associated with increased incidence of adverse effects 5
Special Populations Requiring Dose Adjustment
- Elderly patients (>65 years) may require lower starting doses 2
- Patients with hepatic or renal impairment should start with lower doses 2
- Patients taking CYP3A4 inhibitors (ritonavir, saquinavir, ketoconazole, erythromycin, cimetidine) should use reduced doses 2, 6
Contraindications
- Concurrent use with nitrates or nitric oxide donors is absolutely contraindicated due to risk of severe hypotension 6
- Caution is advised in patients with certain cardiovascular conditions 6
High-Dose Sildenafil as Salvage Therapy
- Some studies have investigated higher doses (up to 200 mg) as salvage therapy for severe erectile dysfunction in patients who failed to respond to the standard 100 mg dose 5
- While 24.1% of previous non-responders showed improvement with doses up to 200 mg, these higher doses were associated with significantly more adverse effects 5
- 63% of patients on high-dose sildenafil reported adverse effects, and 31% of responders discontinued treatment due to these effects 5
- These higher doses exceed FDA-approved recommendations and should be considered experimental 1, 2
Clinical Practice Points
- Always start with the recommended dose based on the specific indication (20 mg TID for PAH; 50 mg as needed for ED) 3, 1, 2
- Dose adjustments should be based on efficacy and tolerability 2, 4
- For PAH, treatment with doses higher than 20 mg TID is not recommended as no greater efficacy was demonstrated in clinical trials 1
- For ED, doses can be titrated up to 100 mg or down to 25 mg based on response and side effects 2, 4