New antihypertensive first to combine ARB and CCB

Patients with uncontrolled hypertension (HTN) taking either a calcium-channel blocker (CCB) or an angiotensin-receptor blocker (ARB) alone may now find benefit from a new agent that combines the two. Exforge, from Novartis, was approved by the Food & Drug Administration in late June and is the first product to contain both classes of drugs. The once-daily tablet contains valsartan (Diovan, Novartis) plus amlodipine and, although it is indicated as a treatment for HTN, it should not be used as an initial form of treatment.

"Blocking the action of angiotensin II results in vasodilation leading to a decrease in total peripheral resistance and ultimately lowering of blood pressure," said Amy E. Miller, Pharm.D., BCPS, of ARB valsartan. Miller is an assistant professor of clinical pharmacy at the Philadelphia College of Pharmacy, University of the Sciences in Philadelphia. "Amlodipine blocks the influx of calcium into the vascular smooth muscle cells, resulting in vasodilation, a decrease in total peripheral resistance, and blood pressure lowering," she added.

In one of the studies leading to Exforge's approval, a total of 1,018 patients with mild to moderate HTN received treatments of three combinations of amlodipine and valsartan (5 mg/80 mg, 5 mg/160 mg, 5 mg/320 mg), or amlodipine alone (5 mg), valsartan alone (80, 160, or 320 mg), or placebo. At week eight, the combination treatments were statistically significantly superior to the monotherapy components in reduction of diastolic and systolic blood pressures.

The Exforge label contains a black box warning stating that drugs that act directly on the renin-angiotensin system can cause injury and even death to a developing fetus. When pregnancy is detected, Exforge should be discontinued as soon as possible. In addition, the combination drug should be used with caution in patients with heart failure, those who have experienced a recent myocardial infarction (MI), and patients undergoing surgery or dialysis. Adverse drug reactions occurring with Exforge during clinical trials in greater than 2% of patients included peripheral edema, nasopharyngitis, upper respiratory infection, and dizziness.

According to the manufacturer, excessive hypotension was experienced by 0.4% of patients with uncomplicated HTN in placebo-controlled studies. Also, the label warns that in patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients receiving high doses of diuretics, symptomatic hypotension may occur when taking ARBs. Increased frequency, duration, and/or severity of angina or acute MI when starting a CCB or at the time of dosage increase may also occur, especially in the presence of severe obstructive coronary artery disease.

"Exforge will likely be a great option for patients already stabilized on doses of valsartan and amlodipine in order to help decrease pill burden and increase compliance," Miller believes. She went on to say that cardiovascular morbidity and mortality are directly correlated with blood pressure control and only about 35% of people with HTN are properly controlled. Most patients will require more than one medication in order to obtain blood pressure goals, she pointed out.

The per-tablet wholesale acquisition cost for Exforge, according to Gold Standard's ProspectoRx, will be $2.16 for the 5 mg/10 mg strength and is less expensive than purchasing each component individually-currently about $1.38 for 5 mg amlodipine and $1.86 for 160-mg tablet of valsartan.

TIPS TO REMEMBER: Exforge

• Exforge combines ARB valsartan with CCB amlodipine.

• Exforge tablets are available in four dosage strengths (amlodipine/valsartan): 5 mg/160 mg, 10 mg/160 mg, 5 mg/320 mg, 10 mg/320 mg.

• Exforge should not be used as an initial therapy for the treatment of hypertension.

• Exforge is classified as Pregnancy Category C during the first trimester and Pregnancy Category D during the second and third trimesters of pregnancy.