Amlodipine and Valsartan

Exforge is the combination tablet of amlodipine, a dihydropyridine calcium channel blocker (DHP CCB), and valsartan, an angiotensin II receptor blocker (ARB). Exforge is indicated for the treatment of hypertension, to lower blood pressure: In patients not adequately controlled on monotherapy. As initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Figure 1: Probability of Achieving Systolic Blood Pressure <140 mmHg at Week 8 Figure 2: Probability of Achieving Diastolic Blood Pressure <90 mmHg at Week 8 Figure 3: Probability of Achieving Systolic Blood Pressure <130 mmHg at Week 8 Figure 4: Probability of Achieving Diastolic Blood Pressure <80 mmHg at Week 8

Amlodipine Amlodipine is a dihydropyridine calcium channel blocker that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine.

General Considerations: Majority of effect attained within 2 weeks. May be administered with other antihypertensive agents. Hypertension: May be used as add-on therapy for patients not controlled on monotherapy. Patients who experience dose-limiting adverse reactions on monotherapy may be switched to Exforge containing a lower dose of that component. May be substituted for titrated components. When used as initial therapy: Initiate with 5/160 mg, then titrate upwards as necessary to a maximum of 10/320 mg once daily

Do not use in patients with known hypersensitivity to any component. Do not coadminister aliskiren with Exforge in patients with diabetes. Known hypersensitivity to any component, Do not coadminister aliskiren with Exforge in patients with diabetes

Boxed warning (fetal toxicity): When pregnancy is detected, discontinue Exforge as soon as possible. Drugs that act directly on the renin-angiotensin system can cause injury and death to the developing fetus. Hypotension: Correct volume depletion prior to initiation. Increased angina and/or myocardial infarction. Monitor renal function and potassium in susceptible patients

In placebo-controlled clinical trials, discontinuation due to side effects occurred in 1.8% of patients in the Exforge-treated patients and 2.1% in the placebo-treated group. The most common reasons for discontinuation of therapy with Exforge were peripheral edema and vertigo. The adverse experiences that occurred in clinical trials (≥ 2% of patients) at a higher incidence than placebo included peripheral edema, nasopharyngitis, upper respiratory tract infection, and dizziness.

No drug interaction studies have been conducted with Exforge and other drugs, although studies have been conducted with the individual amlodipine and valsartan components. Amlodipine Impact of Other Drugs on Amlodipine CYP3A Inhibitors Coadministration with CYP3A inhibitors (moderate and strong) results in increased systemic exposure to amlodipine and may require dose reduction. Monitor for symptoms of hypotension and edema when amlodipine is coadministered with CYP3A inhibitors to determine the need for dose adjustment. CYP3A Inducers No information is available on the quantitative effects of CYP3A inducers on amlodipine. Blood pressure should be closely monitored when amlodipine is coadministered with CYP3A inducers (e.g. rifampicin, St. John's Wort). Sildenafil Monitor for hypotension when sildenafil is coadministered with amlodipine.

Store at 20°C-25°C (68°F-77°F), excursions permitted between 15°C and 30°C (59°F and 86°F). Protect from moisture.