Sildenafil for hypertension: Old drug, new use

Sildenafil for hypertension: Old drug, new use

The Food & Drug Administration has approved Revatio (sildenafil citrate, Pfizer) for pulmonary arterial hypertension (PAH). If the drug sounds familiar, that’s because Viagra, Pfizer’s famed erectile dysfunction medication, contains the same active ingredient.

PAH is a rare disease that affects approximately 100,000 people worldwide. It is characterized by sustained pulmonary arterial pressure of more than 25 mm Hg at rest or more than 30 mm Hg during exercise. The normal range is 12-16 mm Hg at rest.

Sildenafil for hypertension: Old drug, new use drtp071105 017 0181 tn 169471 1351664094157 c8a06b0a e6c9 4905 bf30 48115a8fa68a
Tips to Remember

Sildenafil works on the pulmonary blood vessels the same way it works in the penile vessels. Sildenafil is an inhibitor of cGMP specific phosphodiesterase type-5 (PDE5), found in the smooth muscle of the pulmonary vasculature, where PDE5 is responsible for degradation of cGMP. The increase of cGMP within pulmonary vascular smooth muscle cells results in relaxation. In patients with pulmonary hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser extent, vasodilatation in systemic circulation.

The World Health Organization classifies pulmonary hypertension into five groups, based on mechanism. Group I, PAH, is subdivided into three subgroups: idiopathic PAH; PAH caused by another condition such as lung or heart disease, HIV infection, or scleroderma; and persistent pulmonary hypertension of the newborn. The New York Heart Association (NYHA) scale is based on ability to function, class I having the least limitation and class IV the most. Revatio is indicated for WHO group I patients, and all NYHA classes, to improve exercise ability. It is the first oral medication to be approved for an early stage of the disease.

“What this means,” said Daniel J. Watts, Pfizer spokesman, “is that physicians can now begin to treat patients earlier in the disease process.”

In a major trial submitted to the FDA last fall, patients taking 20, 40, or 80 mg of Revatio three times daily increased six-minute walking distance by an average of 147 feet, which was significantly better than patients in the placebo group (P<0.001). That study enrolled 277 patients with PAH, 38% of whom were in NYHA class II and 58% in NYHA class III.

Revatio will be produced as a 20-mg, film-coated, white, round tablet, to differentiate it from Viagra’s blue diamond tablet. The recommended dose is 20 mg three times a day (every four to six hours) with or without food.

Revatio has the advantage over previously available medications of a proven safety record and a convenient dosing schedule. Tracleer (bosentan, Actelion Pharmaceuticals), the first oral treatment for PAH, has a dual black box warning for liver toxicity and the drug’s potential to cause fetal harm. Revatio’s efficacy has not been evaluated in patients currently on bosentan therapy. And Ventavis (iloprost, CoTherix) Inhalation Solution, the other approved treatment for PAH, needs to be given six to nine times a day, no more than every two hours.

There is a lot of talk about using sildenafil for children with PAH as well. A small study was conducted in which 14 children with pulmonary hypertension were given sildenafil for one year. Children with PAH usually die within one year and within five years with treatment, said Ian Adatia, M.D., associate professor of pediatrics at the University of California, San Francisco Children’s Hospital. “Blood vessels in the penis and the lungs act in the same way,” said Adatia, which is how he came up with idea. At the end of the first year, all the children were alive, and the average distance they were able to walk in six minutes increased by 508 feet. However, at this time the drug is not approved for pediatric pulmonary hypertension patients, although larger trials are ongoing.

Adverse effects reported in clinical trials are similar to those of Viagra and include headache, flushing, dyspepsia, and insomnia. There has been recent news about sildenafil and the other PDE5 inhibitors concerning optic nerve damage. This is due to its minimal inhibitor effect on PDE6, which regulates signal transduction pathways in the retinal photoreceptors. It is yet unknown if there are concerns about vision loss with Revatio. Revatio will be available in pharmacies in mid-July.

The Author, a Brooklyn, N.Y., resident, has just completed his five-week externship at Drug Topics.

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