Amlodipine besylate

Description

Amlodipine besylate, USP, is the besylate salt of amlodipine, a long-acting calcium channel blocker. It is chemically described as 3-Ethyl-5-methyl (±)-2-(2-aminoethoxy)methyl-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate. The molecular formula is C20H25ClN2O5 • C6H6O3S, and the molecular weight is 567.1. Amlodipine besylate appears as a white crystalline powder, which is slightly soluble in water and sparingly soluble in ethanol.

Amlodipine Besylate Tablets are available in formulations of white tablets, each equivalent to 5 mg and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine is a calcium channel blocker indicated for the treatment of hypertension and coronary artery disease.

In the management of hypertension, amlodipine besylate tablet, USP is utilized to lower blood pressure, thereby reducing the risk of fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

For coronary artery disease, amlodipine is indicated for the treatment of chronic stable angina and vasospastic angina (Prinzmetal's or variant angina). It is also indicated for patients with angiographically documented coronary artery disease who do not have heart failure or an ejection fraction less than 40%.

There are no teratogenic or nonteratogenic effects associated with amlodipine.

Dosage and Administration

The recommended starting dose for adults is 5 mg administered once daily, with a maximum allowable dose of 10 mg once daily. For small, fragile, or elderly patients, as well as those with hepatic insufficiency, it is advised to initiate treatment at a lower dose of 2.5 mg once daily.

In pediatric patients, the starting dose ranges from 2.5 mg to 5 mg once daily. It is important to note that doses exceeding 5 mg daily have not been studied in this population, and caution should be exercised when considering dosage adjustments.

Healthcare professionals should ensure that patients are monitored for efficacy and tolerability, adjusting the dosage as necessary within the established guidelines.

Contraindications

Use of this product is contraindicated in patients with a known sensitivity to amlodipine. Due to the potential for adverse reactions, individuals with this sensitivity should not be administered this medication.

Warnings and Precautions

Symptomatic hypotension may occur, especially in patients diagnosed with severe aortic stenosis. While acute hypotension is generally considered unlikely, healthcare professionals should remain vigilant for signs of symptomatic hypotension in this patient population.

The initiation or dose escalation of amlodipine may lead to worsening angina or acute myocardial infarction, particularly in individuals with severe obstructive coronary artery disease. It is crucial for healthcare providers to monitor patients closely during these periods to mitigate potential cardiovascular risks.

In patients with severe hepatic impairment, it is recommended to titrate the dosage of amlodipine slowly. This cautious approach is essential to ensure patient safety and to minimize the risk of adverse effects associated with hepatic dysfunction. Regular assessment of liver function may be warranted to guide appropriate dosing adjustments.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in more than 1% of participants, include edema, fatigue, nausea, abdominal pain, and somnolence. These reactions are generally dose-related and should be monitored throughout the course of therapy.

Serious side effects have also been reported. Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis; however, acute hypotension is considered unlikely. Additionally, there is a risk of worsening angina and acute myocardial infarction, especially after initiating or increasing the dose of amlodipine in patients with severe obstructive coronary artery disease.

It is important to note that some patients may have a known sensitivity to amlodipine, which should be taken into consideration when evaluating treatment options.

Drug Interactions

No drug interactions or drug and laboratory test interactions have been identified in the available data. Therefore, no specific recommendations for dosage adjustments or monitoring are necessary at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Amlodipine Besylate, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Amlodipine is effective in lowering blood pressure in pediatric patients aged 6 to 17 years, with a recommended dosage range of 2.5 to 5 mg daily. The effect of amlodipine on blood pressure in patients younger than 6 years of age has not been established. Caution is advised when considering treatment in this younger age group due to the lack of data on efficacy and safety.

Geriatric Use

Clinical studies of amlodipine did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger individuals.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to start at the low end of the dosing range, taking into account the increased likelihood of decreased hepatic, renal, or cardiac function, as well as the presence of concomitant diseases or other drug therapies.

Elderly patients exhibit decreased clearance of amlodipine, resulting in an increase in the area under the curve (AUC) of approximately 40–60%. Consequently, a lower initial dose may be necessary to ensure safety and efficacy in this population. Regular monitoring and assessment of the patient's response to therapy are recommended to optimize treatment outcomes.

Pregnancy

Amlodipine is classified as a Pregnancy Category C medication. There are no adequate and well-controlled studies in pregnant women; therefore, amlodipine should be used during pregnancy only if the potential benefit justifies the risk to the fetus.

Animal studies have not demonstrated evidence of teratogenicity or other embryo/fetal toxicity when pregnant rats and rabbits were administered amlodipine maleate at doses up to 10 mg amlodipine/kg/day, which corresponds to 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m² basis during their respective periods of major organogenesis. However, significant adverse effects were observed in rats receiving this dose, including a decrease in litter size by approximately 50% and an increase in the number of intrauterine deaths by about 5-fold. Additionally, amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dose.

Given these findings, healthcare professionals should carefully consider the risks and benefits of prescribing amlodipine to pregnant patients.

Lactation

It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that lactating mothers discontinue breastfeeding while receiving amlodipine. The potential effects on breastfed infants have not been established.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment should be managed with caution. In individuals with severe hepatic impairment, it is recommended to titrate the dosage slowly to minimize the risk of adverse effects. Close monitoring of liver function is advised to ensure patient safety and to adjust treatment as necessary.

Overdosage

Overdosage may lead to significant peripheral vasodilation, resulting in pronounced hypotension and potentially reflex tachycardia. Clinical experience with intentional overdosage of amlodipine is limited in human subjects.

Toxicological studies indicate that single oral doses of amlodipine maleate equivalent to 40 mg amlodipine/kg in mice and 100 mg amlodipine/kg in rats have resulted in fatalities. In canine models, doses of 4 mg amlodipine/kg or higher—exceeding 11 times the maximum recommended human dose on a mg/m² basis—have also produced marked peripheral vasodilation and hypotension.

In the event of a massive overdose, it is imperative to initiate active cardiac and respiratory monitoring. Frequent blood pressure assessments are crucial to manage the patient's condition effectively. Should hypotension manifest, cardiovascular support measures should be implemented, including the elevation of the extremities and the careful administration of intravenous fluids.

If hypotension persists despite these conservative interventions, the use of vasopressors, such as phenylephrine, may be warranted. Careful attention should be given to the patient's circulating volume and urine output during this process.

Due to the high protein binding of amlodipine, hemodialysis is unlikely to provide any therapeutic benefit in cases of overdose.

Nonclinical Toxicology

Rats and mice treated with amlodipine maleate in the diet for up to two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day, showed no evidence of a carcinogenic effect of the drug. In mice, the highest dose was, on a mg/m² basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. In rats, the highest dose was, on a mg/m² basis, approximately twice the maximum recommended human dose.

Mutagenicity studies conducted with amlodipine maleate revealed no drug-related effects at either the gene or chromosome level. Additionally, there was no effect on the fertility of rats treated orally with amlodipine maleate (males for 64 days and females for 14 days prior to mating) at doses up to 10 mg/kg/day, which is eight times the maximum recommended human dose of 10 mg/day on a mg/m² basis.

Postmarketing Experience

Postmarketing experience has revealed several events reported voluntarily or through surveillance programs. Gynecomastia has been reported infrequently, with an uncertain causal relationship. Additionally, cases of jaundice and hepatic enzyme elevations, primarily consistent with cholestasis or hepatitis, have been documented; some instances were severe enough to necessitate hospitalization. There is also a possible association between extrapyramidal disorder and amlodipine noted in postmarketing reports. Despite these findings, amlodipine has been used safely in patients with chronic obstructive pulmonary disease, well-compensated congestive heart failure, coronary artery disease, peripheral vascular disease, diabetes mellitus, and abnormal lipid profiles.

Patient Counseling

Patients should be advised to read the provided information carefully before starting amlodipine besylate tablets and each time they refill their prescription, as there may be new information. This information does not replace discussions with their healthcare provider. If patients have any questions regarding amlodipine besylate tablets, they should consult their doctor, who can determine if this medication is appropriate for them.

Amlodipine is classified as a calcium channel blocker (CCB) and is indicated for the treatment of high blood pressure (hypertension) and a specific type of chest pain known as angina. It may be prescribed alone or in combination with other medications to manage these conditions. Patients should understand that high blood pressure results from excessive force exerted by blood against blood vessel walls. Amlodipine works by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure, which reduces the risk of stroke or heart attack.

Patients experiencing angina may feel recurring pain or discomfort due to insufficient blood supply to the heart. This discomfort typically manifests as a pressing or squeezing sensation in the chest, which may radiate to the shoulders, arms, neck, jaws, or back. Amlodipine can help alleviate this pain.

It is crucial for patients to inform their healthcare provider if they have a known allergy to amlodipine or any of the inactive ingredients in amlodipine besylate tablets. Patients should also disclose all prescription and non-prescription medications they are currently taking, including natural or herbal remedies. They should inform their doctor if they have a history of heart disease or liver problems, are pregnant or planning to become pregnant, or are breastfeeding. Amlodipine besylate tablets are not recommended for breastfeeding mothers.

Patients should take amlodipine besylate tablets once daily, with or without food. It may be beneficial to take the medication at the same time each day, such as during breakfast, dinner, or at bedtime. Patients should not take more than one dose at a time. If a dose is missed, it should be taken as soon as remembered, but if more than 12 hours have passed since the missed dose, they should skip it and resume their regular dosing schedule.

Patients can continue using nitroglycerin alongside amlodipine besylate tablets if prescribed for angina; however, they should not discontinue any other prescribed medications, including other blood pressure medications, without consulting their healthcare provider. In the event of an overdose, patients should seek immediate medical attention by contacting their doctor, Poison Control Center, or going to the nearest hospital emergency room.

Patients should be made aware of potential side effects associated with amlodipine besylate tablets, which may include mild to moderate symptoms such as swelling of the legs or ankles, tiredness, extreme sleepiness, stomach pain, nausea, dizziness, flushing, arrhythmia, heart palpitations, and muscle rigidity or tremors. Although rare, patients should be informed that starting or increasing the dose of amlodipine may lead to a heart attack or worsening angina, necessitating immediate medical attention.

Patients should communicate any concerns regarding side effects to their healthcare provider. For a comprehensive list of possible side effects, they should consult their doctor or pharmacist. It is essential to keep amlodipine besylate tablets out of reach of children and store them at a temperature of 20°-25°C (68°-77°F), away from light and moisture, and not in the bathroom.

Patients should only use amlodipine besylate tablets as directed by their healthcare provider and should not share their medication with others, even if they exhibit similar symptoms, as it may be harmful to them.

Storage and Handling

The product is supplied in tight, light-resistant containers to ensure optimal stability and efficacy. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity of the product throughout its shelf life.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Amlodipine Besylate as submitted by BIOMES PHARMACEUTICALS LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)