Levamlodipine Maleate (Monograph)

Brand name: Conjupri
Drug class: Dihydropyridines

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Levamlodipine maleate is the pharmacologically active isomer of amlodipine, a long-acting calcium channel blocker.

Uses for Levamlodipine Maleate

Levamlodipine maleate has the following uses:

Levamlodipine maleate is used alone or in combination with other antihypertensive and antianginal agents for the treatment of hypertension in adults and pediatric patients ≥6 years of age, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including levamlodipine.

Levamlodipine Maleate Dosage and Administration

General

Levamlodipine maleate is available in the following dosage form(s) and strength(s):

• Tablets: 2.5 mg (functionally scored) and 5 mg of levamlodipine; the 2.5 mg tablets can be split for a 1.25-mg dose

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Pediatric Patients

The effective antihypertensive oral dose of levamlodipine in pediatric patients 6–17 years of age 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.

Adults

The recommended starting dosage of levamlodipine in adults is 2.5 mg once daily with maximum dose of 5 mg once daily.

Small, fragile, or elderly patients, or patients with hepatic insufficiency may be started on 1.25 mg once daily and this dosage may be used when adding levamlodipine to other antihypertensive therapy.

Cautions for Levamlodipine Maleate

Contraindications

• Known sensitivity to amlodipine.

Warnings/Precautions

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 (t _1/2) is 56 hours in patients with impaired hepatic function, titrate slowly when administering amlodipine to patients with severe hepatic impairment.

Specific Populations

Pregnancy

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. There are risks to the mother and fetus associated with poorly controlled hypertension in pregnancy. In animal reproduction studies, there was no evidence of adverse developmental effects when pregnant rats and rabbits were treated orally with amlodipine during organogenesis at doses approximately 10 and 20-times the maximum recommended human dose (MRHD), respectively. However for rats, litter size was significantly decreased (by about 50%) and the number of intrauterine deaths was significantly increased (about 5-fold). Amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dose.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). Hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. Pregnant women with hypertension should be carefully monitored and managed accordingly.

Lactation

Limited available data from a published clinical lactation study reports that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on the breastfed infant have been observed. There is no available information on the effects of amlodipine on milk production.

Pediatric Use

Levamlodipine (1.25 to 2.5 mg daily) is effective in lowering blood pressure in patients 6 to 17 years. Effect of levamlodipine on blood pressure in patients less than 6 years of age is not known.

Geriatric Use

Clinical studies of amlodipine did not include sufficient numbers of subjects 65 years of age and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Elderly patients have decreased clearance of amlodipine with a resulting increase of AUC of approximately 40–60%, and a lower initial dose may be required.

Common Adverse Effects

Most common adverse reactions 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.

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

• Do not exceed doses greater than 20 mg daily of simvastatin.

Actions

Mechanism of Action

Levamlodipine is the pharmacologically active isomer of amlodipine. 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. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.

Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.

Amlodipine is a 1:1 racemic mixture of levamlodipine and dextro amlodipine, it has been demonstrated that levamlodipine is the pharmacologically active, anti-hypertensive isomer.

Additional Information

AHFSfirstRelease^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Reload page with references included

Medical Disclaimer