Levamlodipine is a calcium channel blocker and may be used alone or in combination with other antihypertensive agents 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.

Levamlodipine is indicated for the treatment of hypertension in adults and pediatric patients 6 years and older to lower blood pressure. 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. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Amlodipine is a 1:1 racemic mixture of levamlodipine and dextroamlodipine; it has been demonstrated that levamlodipine is the pharmacologically active, antihypertensive isomer.

Absorption: Oral Levamlodipine has a Tmax of 6-12 hours and a bioavailability of 64-90%. Absorption of Levamlodipine is not significantly affected by food.

Distribution: The volume of distribution of Levamlodipine is similar to that of amlodipine. The volume of distribution of amlodipine is 21 L/kg.

Metabolism and Excretion: Levamlodipine is 90% metabolized to inactive metabolites. Incubation with liver microsomes has shown that this metabolism is primarily mediated by CYP3A4. This derivative can be further oxidatively deaminated or O-dealkylated, but does not appear to undergo O-demethylation like racemic amlodipine. Levamlodipine is 60% eliminated in urine, with 10% eliminated as the unmetabolized drug.

Route of administration: Should be taken orally.

Dosage: The usual initial antihypertensive oral dose of Levamlodipine is 2.5 mg once daily, and the maximum dose is 5 mg once daily.

Adult and elderly patients: Elderly patients, or patients with hepatic insufficiency may be started on 1.25 mg once daily and this dose may be used when adding Levamlodipine to other antihypertensive therapy. Dosage needs to be adjusted according to blood pressure goals. 7 to 14 days waiting period between titration steps is needed. Titration needs to be done more rapidly, however, if clinically warranted, provided the patient is assessed frequently.

Use in children and adolescents: The effective antihypertensive oral dose in pediatric patients ages 6-17 years is 1.25 mg to 2.5 mg once daily. Doses in excess of 2.5 mg daily have not been studied in pediatric patients.

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.

• CYP3A Inducers: No information is available on the quantitative effects of CYP3A inducers on amlodipine.

Impact of Amlodipine on other drugs:

• Simvastatin: Co-administration of simvastatin with amlodipine increases the systemic exposure of simvastatin. Limit the dose of simvastatin in patients on amlodipine to 20 mg daily.

• Immunosuppressants: Amlodipine may increase the systemic exposure of cyclosporine or tacrolimus when co-administered. Frequent monitoring of trough blood levels of cyclosporine and tacrolimus is recommended, and adjust the dose when appropriate.

• With food and others: Can be taken with or without food. The absorption is unaffected by food. Avoid grapefruit products and natural licorice.

S-Amlodipine is contraindicated in patients with known sensitivity to amlodipine.

Common: Difficulty in breathing, dizziness, reflex tachycardia, hypotension, abdominal pain, and edema.

Rare: Diarrhea, back pain, headache, fatigue, and nausea.

The limited available data based on post-marketing reports with amlodipine use in pregnant women are not sufficient to inform a drug-associated risk for major birth defects and miscarriage. No adverse effects of amlodipine on the breastfed infant have been observed.

Hypotension: Symptomatic hypotension is possible, particularly in patients with severe aortic stenosis. Because of the gradual onset of action, acute hypotension is unlikely.

Increased Angina or Myocardial Infarction: Worsening angina and acute myocardial infarction can develop after starting or increasing the dose of amlodipine, particularly in patients with severe obstructive coronary artery disease.

Patients with Hepatic Failure: Because amlodipine is extensively metabolized by the liver and the plasma elimination half-life (t½) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.

Overdosage might be expected to cause excessive peripheral vasodilation with marked hypotension and possibly a reflex tachycardia.

Calcium-channel blockers

Store in a cool and dry place, protect from light and moisture. Keep all medicines out of reach of children.