Combo antihypertensive gets FDA nod

February 5, 2007

Two commonly prescribed antihypertensive medications have now been combined into one tablet. With an anticipated availability this September, valsartan (Diovan, Novartis) and amlodipine (Norvasc, Pfizer) will be sold as a combination product under the trade name Exforge (Novartis). The Food & Drug Administration approval is tentative, pending expiration of market exclusivity and patent protection for amlodipine in September.

Hypertension affects nearly one in three American adults. Untreated elevations in blood pressure (BP) predispose patients to heart failure, aneurysms, atherosclerosis, strokes, kidney failure, and blindness. Since hypertension usually has no symptoms, patients may not realize they have it until one or more of these complications develops.

Amlodipine, the most frequently prescribed dihydropyridine-type CCB, prevents calcium from entering the cells that line the vasculature, thus preventing blood vessel constriction. Because the vessels relax with CCB therapy, the most common dose-limiting side effects are edema, dizziness, and flushing.

Valsartan is the most commonly prescribed ARB. Similar to amlodipine, valsartan also relaxes blood vessels but does so by blocking the actions of a hormone called angiotensin II, a potent vasoconstrictor. As the vasculature relaxes with amlodipine and valsartan, blood flows more easily as total peripheral resistance falls, and blood pressure is lowered.

In clinical studies, Exforge safely and effectively lowered blood pressure. In an abstract presented at the American Society of Hypertension meeting in May 2006, data from 79 patients who received Exforge revealed an average drop in BP of 35.8 mmHg for systolic pressure and 28.6 mmHg for diastolic after six weeks of treatment. Additionally, in a subset of patients with baseline systolic pressure ≥180 mmHg, an average systolic reduction of 43 mmHg was observed. These results were clinically comparable to those seen in a group of 77 patients receiving a lisinopril/hydrochlorothiazide combination.

Side effects of Exforge in clinical studies-peripheral edema, nasopharyngitis, upper respiratory tract infections, and dizziness-were mild and short-lived. Women who are pregnant or may become pregnant should avoid taking valsartan because of the risk of injury or death to the developing fetus. Serum potassium should be monitored, especially in patients with renal dysfunction. Cautioned Sarah Spinler, Pharm.D., and professor of clinical pharmacy at University of the Sciences in Philadelphia and adjunct faculty with the cardiovascular division of the department of medicine, University of Pennsylvania, "Pharmacists should watch for duplication of ARB/ACE inhibitors, especially in patients taking combination products."

Exforge tablets will be available in the following amlodipine/valsartan combinations: 5/160 mg, 10/160 mg, 5/320 mg, and 10/320 mg.

TIPS TO REMEMBER Exforge

THE AUTHOR is a medical writer based in Pennsylvania.