What is the recommended dose of sildenafil (Revatio) for pulmonary hypertension?

Sildenafil Dosing for Pulmonary Hypertension

The FDA-approved dose of sildenafil for pulmonary arterial hypertension is 20 mg three times daily (TID), administered 4-6 hours apart, though dose titration up to 80 mg TID is now permitted for patients with inadequate response. 1, 2

Standard Initial Dosing

• Start with 20 mg orally three times daily (TID), with doses spaced 4-6 hours apart 1, 3
• The FDA label explicitly states that in clinical trials, no greater efficacy was achieved with higher doses at the outset 1
• This 20 mg TID dose improves 6-minute walk distance, WHO functional class, and cardiopulmonary hemodynamics 3

Dose Titration Strategy for Inadequate Responders

For patients who fail to demonstrate or maintain adequate clinical response to 20 mg TID, titrate upward in 20 mg increments to a maximum of 80 mg TID. 3, 4

• A landmark 2024 randomized controlled trial (n=385) demonstrated that 80 mg TID was noninferior to 5 mg TID for all-cause mortality (HR 0.51,99.7% CI 0.22-1.21, P<0.001) and superior for time to clinical worsening (HR 0.44,99.7% CI 0.22-0.89, P<0.001) 2
• Based on this trial, the FDA recently revoked approval of the 5 mg dose, reinforced 20 mg TID as the recommended starting dose, and now allows titration up to 80 mg TID 2
• Clinical trials showed dose-response relationships in hemodynamic parameters, with mean placebo-corrected improvements in 6-minute walk distance of 45 m, 46 m, and 50 m for 20 mg, 40 mg, and 80 mg TID respectively 3

Pediatric Dosing (Critical Distinction)

Avoid higher dosing in children—use weight-based dosing only, as high-dose sildenafil monotherapy was associated with increased mortality in the STARTS-2 pediatric trial. 3

• Age <1 year: 0.5-1 mg/kg three times daily 3
• Weight <20 kg: 10 mg three times daily 3
• Weight >20 kg: 20 mg three times daily 3
• The FDA issued a warning against use in children aged 1-17 years due to mortality concerns at higher doses 3

Combination Therapy Considerations

• When adding sildenafil to stable IV epoprostenol (10-50 ng/kg/min), start at 20 mg every 8 hours and titrate up to 80 mg every 8 hours over 8 weeks, which showed an adjusted treatment difference in 6-minute walk distance of 28.8 meters (95% CI 13.9-43.8 m) 4
• Patients with baseline 6-minute walk distance >325 meters are more likely to benefit from adding sildenafil to epoprostenol 4
• Do not coadminister with riociguat due to risk of systemic hypotension 3, 4
• Male patients on riociguat should avoid PDE5 inhibitors for erectile dysfunction 3

Common Adverse Effects

• Headache (most common, related to vasodilation) 3, 4
• Flushing, dyspepsia, nasal congestion, and epistaxis 3, 4
• When combined with IV epoprostenol, expect increased headaches and dyspepsia 4
• Most adverse effects are transient and mild-to-moderate in severity 4
• Discontinuation rates due to adverse effects are approximately 3% 4

Critical Pitfalls to Avoid

• Do not assume 20 mg TID is optimal for all patients—inadequate responders require dose titration rather than premature addition of second agents 4
• Do not extrapolate adult high-dose data to pediatric patients—the mortality signal in children makes this dangerous 3
• Do not use with nitrates—absolute contraindication due to life-threatening hypotension risk 4
• Do not add a second PAH-specific drug without first ensuring adequate trial of sildenafil at optimal doses (up to 80 mg TID if tolerated) 4