amlodipine besylate
Norvasc

Available forms
Available by prescription only
Tablets: 2.5 mg, 5 mg, 10 mg

Indications and dosages
 Chronic stable angina, vasospastic angina (Prinzmetal’s or variant angina). Adults: Initially, 5 to 10 mg P.O. daily.
 Hypertension. Adults: Initially, 2.5 to 5 mg P.O. daily. Adjust dosage based on patient response and tolerance every 7 to 14 days. Maximum daily dose is 10 mg.
≡ Dosage adjustment. For small, frail, or geriatric patients, those receiving other antihypertensives, or those with hepatic insufficiency, give 2.5 mg daily.

Pharmacodynamics
Antianginal and antihypertensive actions: Contractility of cardiac muscle and vascular smooth muscle depends on movement of extracellular calcium ions into cardiac and smooth-muscle cells through specific ion channels. Amlodipine inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle, thus decreasing myocardial contractility and oxygen demand. As a peripheral arterial vasodilator, the drug acts directly on vascular smooth muscle to reduce peripheral vascular resistance and blood pressure. It also dilates coronary arteries and arterioles.

Pharmacokinetics
Absorption: Absolute bioavailability has been estimated at 64% to 90%.
Distribution: About 93% of the circulating drug is bound to plasma proteins in hypertensive patients.
Metabolism: Extensively metabolized in the liver, with about 90% converted to inactive metabolites.
Excretion: Excreted primarily in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients receiving other peripheral dilators and in those with aortic stenosis, heart failure, or severe hepatic disease.

Interactions
Drug-food. Grapefruit juice: Elevates amlodipine levels, increasing its pharmacologic and adverse effects. Discourage use together.

Adverse reactions
CNS: headache, somnolence, fatigue, dizziness, light-headedness, paresthesia.
CV: edema, flushing, palpitations.
GI: nausea, abdominal pain.
Musculoskeletal: muscle pain.
Respiratory: dyspnea.
Skin: rash, pruritus.

Effects on lab test results
None reported.

Overdose and treatment
Symptoms of overdose include nausea, weakness, dizziness, drowsiness, confusion, and slurred speech. Overdose also can cause excessive peripheral vasodilation with marked hypotension and bradycardia, both of which may reduce cardiac output. Junctional rhythms and second- or third-degree AV block also can occur.
 Massive overdose warrants active cardiac and respiratory monitoring and frequent blood pressure measurements. Treatment of hypotension consists of CV support, including elevation of the limbs and judicious administration of fluids. If hypotension remains unresponsive to these conservative measures, consider administration of vasopressors (such as phenylephrine), with attention to circulating volume and urine output. I.V. calcium gluconate may help reverse the effects of calcium entry blockade. Because amlodipine is highly protein-bound, hemodialysis isn’t likely to benefit the patient.

Special considerations
• Because the vasodilation induced by amlodipine is gradual in onset, acute hypotension has rarely been reported after oral administration. However, use caution when administering drug, particularly if patient has severe aortic stenosis.
• Some patients, especially those with severe obstructive coronary artery disease, have developed increased frequency, duration, or severity of angina or even acute MI after calcium channel blocker therapy starts or dosage increases.
• Monitor blood pressure closely, especially at the start of therapy.
Breast-feeding patients
• Because it isn’t known if amlodipine appears in breast milk, breast-feeding isn’t recommended during amlodipine therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Geriatric patients may require a smaller dosage of amlodipine.

Patient education
• Tell patient to take nitroglycerin S.L. as needed for acute anginal symptoms. If patient continues nitrate therapy during titration of amlodipine dosage, urge continued compliance.
• Caution patient to continue taking amlodipine even when feeling better.
• Tell patient to report signs of heart failure, such as swelling of hands and feet or shortness of breath.
• Tell patient to take drug with a liquid other than grapefruit juice.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use