Amlodipine

Amlodipine besylate is a calcium channel blocker and may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of: • Hypertension o Amlodipine besylate tablets are indicated for the treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. • Coronary Artery Disease o Chronic Stable Angina o Vasospastic Angina (Prinzmetal’s or Variant Angina) o Angiographically Documented Coronary Artery Disease in patients without heart failure or an ejection fraction < 40%

Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-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.

• Adult recommended starting dose: 5 mg once daily with maximum dose 10 mg once daily. o Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 2.5 mg once daily. • Pediatric starting dose: 2.5 mg to 5 mg once daily. Important Limitation: Doses in excess of 5 mg daily have not been studied in pediatric patients.

Amlodipine besylate tablets are contraindicated in patients with known sensitivity to amlodipine. • Known sensitivity to amlodipine

• Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. However, acute hypotension is unlikely. • Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine besylate tablets, particularly in patients with severe obstructive coronary artery disease. • Titrate slowly in patients with severe hepatic impairment.

Most common adverse reaction to amlodipine is edema which occurred in a dose related manner. Other adverse experiences not dose related but reported with an incidence >1.0% are fatigue, nausea, abdominal pain, and somnolence.

• Do not exceed doses greater than 20 mg daily of simvastatin. Impact of Other Drugs on Amlodipine CYP3A Inhibitors Co-administration 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 co-administered 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 co-administered with CYP3A inducers. Sildenafil Monitor for hypotension when sildenafil is co-administered with amlodipine.

Storage Store bottles at controlled room temperature, 59° to 86°F (15° to 30°C) and dispense in tight, light-resistant containers (USP). Store amlodipine besylate tablets at room temperature (between 59° and 86°F). How do I store amlodipine besylate tablets? Do not store in the bathroom.