People with pulmonary hypertension (PH) have a new therapy option available to them, if the government clears the way for its approval. Drug manufacturer Pfizer announced this month that it has filed an application with the Food and Drug Administration for approval of its medication, sildenafil citrate, marketed as Revatio, as a treatment for the disease.
The new drug application, or NDA, was filed simultaneously with applications for approval in Europe, the company stated.
'Desperately Needed' Therapies
"The regulatory filings for sildenafil usage in PAH [pulmonary arterial hypertension] demonstrate Pfizer's commitment to address unmet medical conditions by exploring new uses for our existing medicines, together with our significant efforts to discover and develop new compounds," said Joseph Feczko, MD, president of Worldwide Development at Pfizer, in a press release. "PAH is a condition for which new treatment options are desperately needed."
Dilating Narrowed Blood Vessels
Sildenafil is not a cure for PAH, but it has been shown in clinical trials to improve the symptoms of the disease by helping to open narrowed arteries.1-3 In one study,2 pulmonary artery pressure, artery oxygen level, and heart function were tested in people taking either sildenafil or a placebo at low or high altitude. The high-altitude participants were located at a Mount Everest base camp.
All patients were tested at rest and during exercise. The investigators from University Hospital Giessen and Justus-Liebig University in Giessen, Germany found that doses of 50 mg of sildenafil increased the amount of arterial oxygen in the patients, and reduced pulmonary artery pressure, both at rest and during exercise. It also improved cardiac function. At high altitude, the drug had no effect on arterial oxygen levels, yet it did reduce pulmonary artery pressure, both at rest and during exercise.
In an earlier trial,3 sildenafil in combination with conventional inhaled nitric oxide was shown to be more effective inhaled nitric oxide alone. "The decrease in pulmonary vascular resistance was similar with inhaled nitric oxide and sildenafil, whereas sildenafil plus inhaled nitric oxide was more effective than inhaled nitric oxide alone," wrote the physicians at the University of Alberta in Canada.
Increased Vascular Tension
Pulmonary hypertension is a rare lung disorder in which the arteries in the lung become narrowed, making it difficult for blood to flow through. As a result, the blood pressure in the pulmonary artery, which carries blood from the heart's right ventricle to the lungs, rises far above normal levels. This increases the workload on the heart, causing it to expand abnormally. The right ventricle gradually becomes weaker and loses its ability to pump enough blood to the lungs. As a result, right heart failure may occur.
Common symptoms of the disease, likely manifested in its later stages, include shortness of breath with exercise; dizziness; fainting spells; swelling in the ankles, abdomen or legs; bluish lips and skin; and possible chest pain.4
PH is caused by various other diseases, including some forms of congenital heart disease, lung disease, and blood clots in pulmonary arteries. It's also linked with collagen vascular disease, portal hypertension, diet drugs, HIV infection, and some other rare diseases. In some cases, there is no known cause for PH.5
Symptom Improvement Seen
According to Pfizer, studies using the 20 mg dose of sildenafil had a positive effect on PH patients, such as improved walking distance in a six-minute standard test. Patients on the drug also had a reduction in arterial blood pressure, and an increase in cardiac output.
Common side effects in the studies included headaches, flushing and digestive problems, according to Pfizer.
Revatio will be manufactured and marketed in a different dosage, color and shape than Viagra, which is also manufactured by Pfizer and contains sildenafil as its main ingredient. Viagra (sildenafil citrate) is indicated solely as a treatment for erectal dysfunction. The company says Viagra is not intended for patients who use nitrates.
There's no word on when an FDA decision will be made. However, it could come sometime next year.
1. Ghofrani HA, Voswinckel R, Reichenberger F et al. Differences in hemodynamic and oxygenation responses to three different phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension: a randomized prospective study. J Am Coll Cardiol 2004 Oct 6;44(7):1488-96.
2. Ghofrani HA, Reichenberger F, Kohstall MG et al. Sildenafil increased exercise capacity during hypoxia at low altitudes and at Mount Everest base camp: a randomized, double-blind, placebo-controlled crossover trial. Ann Intern Med 2004 Aug 3;141(3):169-77.
3. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 2002 May 21;105(20):2398-403.
4. The Cleveland Clinic. Department of Patient Education and Health Information. What You Need to Know About Living with Pulmonary Hypertension.
5. Pulmonary Hypertension Association. General FAQ.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
