Revatio (sildenafil) is a U.S. Food and Drug Administration (FDA)-approved medication used to slow the progression of pulmonary arterial hypertension (PAH) and improve the ability to exercise. It is marketed by Pfizer.

How Revatio works

PAH symptoms are caused by narrowing of the pulmonary arteries (blood vessels connecting the heart and lungs). This restricts the blood flow, causing strain to the right side of the heart, and reducing the circulation of blood through the lungs.

The active ingredient of Revatio is sildenafil, a citrate salt. This ingredient is found in several other medications, the most common being Viagra, which is used to treat erectile dysfunction. It acts to dilate (widen) the walls of the arteries, increasing blood flow and reducing the strain on the heart.

Revatio is a phosphodiesterase-5 (PDE-5) inhibitor. Phosphodiesterases (PDEs) are a group of enzymes that are present in the walls of both the arteries and the lungs. PDE-5 normally breaks down the small molecule cGMP. So, by inhibiting PDE-5, Revatio increases the levels of cGMP in the lungs. cGMP acts to relax and widen the artery muscles, leading to vasodilation (widening of the arteries) and a reduction in blood pressure. This increases circulation through the lungs, which helps transport oxygen around the body and reduces the burden on the heart.

Revatio in clinical trials

The oral tablet form of Revatio was approved originally by the FDA in June 2005, and by the European Commission (EC) in October 2005. The formulation that is injected into the blood stream was approved in November 2009.

There were four key studies that led to the FDA approval of Revatio for the treatment of PAH.  

The first study, published in the New England Journal of Medicine, was a double-blind, placebo-controlled, randomized clinical trial with 278 patients. Patients were assigned either 20mg, 40mg, or 80mg of Revatio or a placebo three times a day for 12 weeks, followed by an optional long-term extension study lasting up to one year. The treatment was well-tolerated, and patients experienced a significant decrease in pulmonary arterial pressure and a significant increase in distance walked in the six-minute walk test. There was no additional benefit seen in higher doses compared to the 20mg dose of Revatio.

The second study (NCT00159861), called PACES-1 assessed the safety and effectiveness of Revatio in combination with epoprostenol. The double-blind, placebo-controlled, randomized trial assessed 267 patients with PAH for 16 weeks. The results, published in the journal Annals of Internal Medicine, demonstrated that patients who were given Revatio experienced a significant improvement in the six-minute walk test, a reduction in pulmonary blood pressure, and slower progression of the disease.

The third study ended prematurely due to insufficient numbers of participants, although 129 patients still completed the trial. It aimed to compare the effect of 1 mg, 5 mg, and 20 mg doses of Revatio. Overall, the 5 and 20 mg doses showed a comparable improvement in distance walked in six minutes after 12 weeks of treatment, and both groups showed significantly more improvement compared to patients receiving 1 mg of the drug.

The fourth trial (NCT00323297) assessed Revatio in 103 PAH patients who had received Tracleer (bosentan) treatment for at least three months. The results of the study suggested there was no benefit of taking Revatio with Traceleer compared to Tracleer alone.

Other Information

Common adverse effects associated with Revatio include nose bleeds, flushing, headache, upset stomach,  difficulty sleeping, shortness of breath, and nasal congestion. If severe adverse effects that include allergic reaction, convulsions, hearing loss, or edema occur, a doctor should be called immediately.

The EC recommends that a maximum dose of 20 mg of Revatio three times a day is safe in children with PAH. However, in August 2012, the FDA warned against using Revatio in children.

Note: Pulmonary Hypertension News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.