Amlodipine besylate

Description

Amlodipine besylate tablets, USP, are the besylate salt of amlodipine, a long-acting calcium channel blocker. The chemical composition of amlodipine besylate, USP, is described as 3-Ethyl-5-methyl (±)-2-(2-aminoethoxy)methyl-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate, with an empirical formula of C20H25ClN2O5 • C6H6O3S. The structural formula is provided in the accompanying documentation.

Amlodipine besylate appears as a white crystalline powder with a molecular weight of 567.1. It exhibits slight solubility in water and sparing solubility in ethanol. The tablets are formulated as white tablets, each equivalent to 2.5 mg, 5 mg, or 10 mg of amlodipine for oral administration. Each tablet also contains inactive ingredients, including microcrystalline cellulose, dibasic calcium phosphate dihydrate, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine besylate tablets are indicated for the treatment of hypertension, serving to lower blood pressure. The reduction of blood pressure is associated with a decreased risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

In addition to hypertension, amlodipine besylate tablets are indicated for the management of coronary artery disease, which includes the treatment of chronic stable angina and vasospastic angina (Prinzmetal’s or variant angina). Furthermore, this medication is indicated for patients with angiographically documented coronary artery disease who do not have heart failure or an ejection fraction of less than 40%.

There are no teratogenic or nonteratogenic effects associated with amlodipine besylate tablets.

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 advisable 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 therefore should not be administered.

Healthcare professionals should ensure that dosing is tailored to the individual patient's needs, taking into consideration factors such as age, weight, and hepatic function.

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 dosage increase of amlodipine besylate tablets 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 besylate tablets 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 1.0% of participants, include edema, fatigue, nausea, abdominal pain, and somnolence.

Serious adverse reactions have also been reported. Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis. Additionally, worsening angina can develop after initiating or increasing the dose, especially in individuals with severe obstructive coronary artery disease. There is also a risk of acute myocardial infarction, which may arise under similar circumstances of dose adjustment 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 considered when evaluating potential adverse reactions.

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 besylate tablets, administered at doses of 2.5 to 5 mg daily, have been shown to be effective in lowering blood pressure in pediatric patients aged 6 to 17 years. The safety and efficacy of amlodipine besylate in patients younger than 6 years have not been established, and its effects on blood pressure in this age group remain unknown.

Geriatric Use

Clinical studies of amlodipine besylate tablets did not include a sufficient number of subjects aged 65 and over to determine whether these elderly patients respond differently from younger individuals. However, other reported clinical experiences have not identified significant differences in responses between geriatric patients and their younger counterparts.

In general, dose selection for elderly 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 careful assessment of the patient's overall health status are recommended to optimize treatment outcomes.

Pregnancy

The available data regarding the use of amlodipine besylate in pregnant women is limited, primarily derived from post-marketing reports, and is insufficient to establish a definitive drug-associated risk for major birth defects or miscarriage. However, it is important to recognize that poorly controlled hypertension during pregnancy poses significant risks to both the mother and fetus.

Animal reproduction studies have demonstrated no evidence of adverse developmental effects when pregnant rats and rabbits were administered amlodipine maleate during organogenesis at doses approximately 10 and 20 times the maximum recommended human dose (MRHD), respectively. Notably, while no teratogenicity or other embryo/fetal toxicity was observed at doses up to 10 mg amlodipine/kg/day, there were significant findings in rats, including a 50% reduction in litter size and a five-fold increase in intrauterine deaths. Additionally, amlodipine maleate was associated with prolonged gestation and extended labor duration in rats at this dosage.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is approximately 2%–4% and 15%–20%, respectively. All pregnancies inherently carry a background risk of birth defects, loss, or other adverse outcomes. Furthermore, hypertension in pregnancy is linked to increased maternal risks, including pre-eclampsia, gestational diabetes, premature delivery, and complications during delivery, such as the need for cesarean section and postpartum hemorrhage. Fetal risks associated with maternal hypertension include intrauterine growth restriction and intrauterine death.

Given these considerations, pregnant women with hypertension should be closely monitored and managed to mitigate potential risks to both maternal and fetal health.

Lactation

Amlodipine is present in human milk, with a reported estimated median relative infant dose of 4.2% based on limited available data from a published clinical lactation study. No adverse effects of amlodipine on breastfed infants have been observed. Additionally, there is no available information regarding the effects of amlodipine on milk production in lactating mothers.

Renal Impairment

Patients with renal impairment have no specific information regarding dosage adjustments or monitoring provided in the text. Therefore, healthcare professionals should exercise caution when prescribing to this population, as the absence of guidance may necessitate individualized assessment and monitoring based on the patient's renal function.

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 besylate tablets in humans is limited, underscoring the need for caution.

Toxicological studies in animal models 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 significant 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. 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, with careful monitoring of circulating volume and urine output.

Due to the high protein binding of amlodipine besylate, hemodialysis is unlikely to provide 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, jaundice and elevations in hepatic enzymes, primarily consistent with cholestasis or hepatitis, have been documented; in some instances, these events were severe enough to necessitate hospitalization. There is also a possible association between extrapyramidal disorder and the use of amlodipine. Notably, amlodipine besylate tablets have been utilized 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 besylate tablets are classified as a calcium channel blocker (CCB) and are indicated for the treatment of high blood pressure (hypertension) and a type of chest pain known as angina. Patients should understand that this medication can be used alone or in combination with other medications to manage these conditions.

It is important to explain that high blood pressure occurs when blood exerts excessive force against blood vessel walls. Amlodipine besylate tablets work by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure. This reduction in blood pressure can decrease the risk of stroke or heart attack.

Patients experiencing angina may feel recurring pain or discomfort due to insufficient blood flow to the heart. This pain is often described as a pressing or squeezing sensation, typically located in the chest under the breastbone, but it may also radiate to the shoulders, arms, neck, jaws, or back. Amlodipine besylate tablets can help alleviate this discomfort.

Patients should be cautioned against using amlodipine besylate tablets if they have a known allergy to amlodipine or any of the inactive ingredients. They should inform their healthcare provider about all prescription and non-prescription medications they are taking, including any natural or herbal remedies. Additionally, patients should disclose any history of heart disease or liver problems, as well as their pregnancy status or plans to become pregnant, as these factors may influence the appropriateness of amlodipine besylate tablets for their treatment. Breastfeeding patients should also inform their doctor, as amlodipine can pass into breast milk.

Patients are instructed to 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 with breakfast, dinner, or at bedtime. They should not take more than one dose at a time. If a dose is missed, patients should take it as soon as they remember, but if it has been more than 12 hours 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, and 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.

Common side effects of amlodipine besylate tablets may include mild to moderate swelling of the legs or ankles, tiredness, extreme sleepiness, stomach pain, nausea, dizziness, flushing, arrhythmia, heart palpitations, muscle rigidity, tremors, and abnormal muscle movements. Patients should be informed that while it is rare, there is a possibility of experiencing a heart attack or worsening angina when starting or increasing the dose of amlodipine besylate tablets. If such symptoms occur, patients should contact their doctor immediately or go to the emergency room.

Patients should be encouraged to discuss any side effects they experience with their healthcare provider, as this list does not encompass all possible side effects. For a complete list, patients should consult their doctor or pharmacist.

It is essential to keep amlodipine besylate tablets out of reach of children and to store them at room temperature (between 68° and 77°F), away from light, and in a dry place, avoiding storage in the bathroom. Patients should only use amlodipine besylate tablets as directed by their healthcare provider and should not share this 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 POLYGEN PHARMACEUTICALS INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)