Adverse Effects of Sildenafil

Common Adverse Effects

The European Society of Cardiology notes that headache is the most common adverse effect reported across all clinical trials, related to the drug's vasodilatory mechanism 1, 2, 3
The American Heart Association reports that flushing, or facial redness/warmth, is a common adverse effect related to the drug's vasodilatory mechanism 1, 2, 3
Dyspepsia, or upset stomach/epigastric discomfort, is a common adverse effect, as reported by the European Heart Journal 3
Nasal congestion and epistaxis, or nosebleeds, are common adverse effects related to the drug's vasodilatory mechanism, according to the European Heart Journal 1, 2, 4
Rhinitis is a common adverse effect, as reported by the Annals of Internal Medicine 3

The American College of Cardiology notes that very-low-quality evidence from a study of 4 million veterans showed PDE-5 inhibitors were not associated with increased risk for nonarteritic anterior ischemic optic neuropathy (NAION), but were associated with increased risk for "possible NAION" 3
Priapism, or erections lasting more than 4 hours, is a rare but serious adverse effect that requires immediate medical attention, as reported by the Annals of Internal Medicine 3

The American Heart Association states that there is an absolute contraindication with nitrates, such as nitroglycerin and isosorbide dinitrate, due to synergistic potentiation of vasodilation and potentially life-threatening hypotension 3

The European Society of Cardiology reports that most adverse effects are transient, mild to moderate in severity, and related to the drug's vasodilatory mechanism, with an overall discontinuation rate due to adverse effects in clinical trials of approximately 3% 1, 2, 5

The American Thoracic Society suggests that sildenafil can be considered for patients with pulmonary arterial hypertension associated with systemic sclerosis in whom bosentan has been ineffective or cannot be used for safety reasons 6, 7

In patients who do not show an adequate clinical response to 20 mg three times a day, some experts suggest considering increasing the dose in increments of 20 mg up to a maximum of 80 mg three times a day 8, 9

Sildenafil should not be administered with riociguat due to the risk of hypotension 10
Male patients treated with riociguat should also avoid the use of phosphodiesterase-5 inhibitors for erectile dysfunction 8

Combination therapy with other medications for pulmonary arterial hypertension may be considered if the response to sildenafil is inadequate 11

The American College of Cardiology recommends a dose of 20 mg administered orally three times daily (TID) for pulmonary arterial hypertension (PAH), with doses showing similar improvements in exercise capacity with mean placebo-corrected treatment effects of 45, 46, and 50 m respectively 12

The FDA-approved dose for PAH is 20 mg administered orally three times daily (TID), with clinical trials demonstrating similar improvements in exercise capacity with doses of 20 mg, 40 mg, or 80 mg TID 12

Common adverse events of sildenafil include headache, flushing, dyspepsia, nasal congestion, and abnormal vision, with most side effects being transient and mild to moderate in severity 12

The CHEST guidelines indicate that optimal effect of sildenafil often required titrating doses up to 80 mg every 8 hours over a period of 8 weeks in patients on background IV epoprostenol 13
Tadalafil 40 mg daily provided clinical benefit as monotherapy, though data did not support additional benefit when combined with background bosentan therapy 13

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, showing an adjusted treatment difference in 6-minute walk distance of 28.8 meters (95% CI, 13.9-43.8 m) 13
Patients with baseline 6-minute walk distance >325 meters appeared more likely to benefit from adding sildenafil to epoprostenol 13
Adding inhaled treprostinil (titrated to 54 μg four times daily) to stable sildenafil or bosentan improved exercise capacity by 20 meters at 12 weeks 13
Patients with baseline 6-minute walk distance <300 meters were more likely to benefit from adding inhaled treprostinil 13

Do not assume the FDA-approved 20 mg TID dose is optimal for all patients—clinical trials and expert consensus support titration up to 80 mg TID for inadequate responders 13
Do not add a second PAH-specific drug without first ensuring adequate trial of initial monotherapy at optimal doses 13
Do not use tadalafil on background bosentan therapy, as data do not support additional benefit of this specific combination 13
When combined with IV epoprostenol, sildenafil causes more headaches and dyspepsia 13

The American Thoracic Society recommends sildenafil to improve exercise ability and delay clinical worsening in adults with PAH (WHO Group I), with effectiveness demonstrated primarily in patients with NYHA functional class II-III symptoms and idiopathic etiology or connective tissue disease-associated PAH 14
Sildenafil reduces mean pulmonary arterial pressure, improves WHO functional class, and enhances cardiopulmonary hemodynamics, with a significant improvement in 6-minute walk distance of 45-50 meters compared to placebo (p<0.001 for all doses) 14
Long-term data (1 year) show sustained improvement in 6-minute walk distance of 51 meters from baseline with a dose of 80 mg TID 14
The addition of bosentan to sildenafil does not have sufficient evidence to recommend for or against, as the between-group mean difference in 6-minute walk distance did not meet the minimally important difference of 33 meters 15
Common adverse effects of sildenafil include headache, flushing, dyspepsia, nasal congestion, and epistaxis, related to its vasodilatory mechanism 14