Amlodipine besylate

Description

Amlodipine besylate 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 empirical formula is C₂₀H₂₅ClN₂O₅ • C₆H₆O₃S, and the molecular weight is 567.1. Amlodipine besylate appears as a white or almost white powder, which is slightly soluble in water and sparingly soluble in ethanol.

Amlodipine besylate tablets, USP, are available in formulations equivalent to 2.5 mg, 5 mg, and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including anhydrous dibasic calcium phosphate, colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, sodium starch glycolate, and stearic acid.

Uses and Indications

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

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

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

This drug may be administered as monotherapy or in combination with other antihypertensive and antianginal agents. There are no teratogenic or nonteratogenic effects associated with amlodipine besylate.

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, treatment may be initiated at a lower dose of 2.5 mg once daily to ensure safety and tolerability.

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 assess individual patient needs and adjust dosing accordingly, while adhering to the specified limits to optimize therapeutic outcomes.

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 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, USP, 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 and to assess the risk versus benefit of continuing therapy in such cases.

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

Side Effects

Patients receiving amlodipine besylate may experience a range of adverse reactions. The most common adverse reactions observed in clinical trials, with an incidence greater than 1.0%, include edema, fatigue, nausea, abdominal pain, and somnolence.

Serious adverse reactions warranting caution include symptomatic hypotension, which 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 dosage of amlodipine besylate in patients with severe obstructive coronary artery disease.

It is important to note that patients with known sensitivity to amlodipine should avoid its use. In cases of overdosage, excessive peripheral vasodilation may lead to marked hypotension and potentially reflex tachycardia.

Drug Interactions

There are no specific drug interactions or interactions with laboratory tests identified for the drug in question. As such, no dosage adjustments or monitoring recommendations are necessary based on the available data.

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 safety and efficacy of amlodipine in patients younger than 6 years of age have not been established, and its effect on blood pressure in this age group is not known.

Geriatric Use

Clinical studies of amlodipine 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 to 60%. Consequently, a lower initial dose may be necessary to ensure safety and efficacy in this population. Careful monitoring and dose adjustments are recommended to optimize treatment outcomes for geriatric patients.

Pregnancy

Pregnancy Category C. Limited available data from post-marketing reports regarding the use of amlodipine in pregnant women are insufficient to establish a drug-associated risk for major birth defects and miscarriage. However, it is important to note that poorly controlled hypertension during pregnancy poses risks to both the mother and fetus.

In animal reproduction studies, no evidence of adverse developmental effects was observed 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. Nonetheless, in rats, there was a significant reduction in litter size (approximately 50%) and a notable increase in the number of intrauterine deaths (about 5-fold) at the higher dose. Additionally, 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 in the general population is unknown; however, all pregnancies carry a baseline risk of birth defects, 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 approximately 2%-4% and 15%-20%, respectively.

Hypertension during pregnancy increases the maternal risk for conditions such as pre-eclampsia, gestational diabetes, premature delivery, and complications during delivery, including the need for cesarean section and post-partum hemorrhage. Furthermore, hypertension elevates the fetal risk for intrauterine growth restriction and intrauterine death. Therefore, pregnant women with hypertension should be closely monitored and managed appropriately.

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. Additionally, there is no available information on the effects of amlodipine on milk production.

Renal Impairment

Patients with renal impairment may not have specific information regarding dosage adjustments, special monitoring, or safety considerations outlined in the prescribing information. Therefore, healthcare professionals should exercise caution when prescribing this medication to individuals with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment and monitoring of these patients.

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 in humans is limited, underscoring the need for caution.

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 severe 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 should be provided, which includes elevating the extremities and administering fluids judiciously. If hypotension persists despite these conservative measures, 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, hemodialysis is unlikely to be effective in managing an 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 administered was, on a mg/m² basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. In rats, the highest dose was approximately twice the maximum recommended human dose when adjusted for body surface area.

Mutagenicity studies conducted with amlodipine maleate revealed no drug-related effects at either the gene or chromosome level, indicating a lack of mutagenic potential.

There was no effect on the fertility of rats treated orally with amlodipine maleate, with males treated for 64 days and females for 14 days prior to mating at doses up to 10 mg/kg/day. This dosage is eight times the maximum recommended human dose of 10 mg/day when adjusted for body surface area.

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 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 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. This medication can be used alone or in combination with other treatments for these conditions. Patients should understand that high blood pressure results from blood exerting excessive force against blood vessel walls. Amlodipine besylate tablets work by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure, which reduces the risk of stroke or heart attack. Angina is characterized by recurring pain or discomfort due to insufficient blood supply to the heart, often described as a pressing or squeezing sensation in the chest, which may radiate to the shoulders, arms, neck, jaws, or back. Amlodipine besylate tablets can help alleviate this pain.

Patients should not use amlodipine besylate tablets if they are allergic 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. It is particularly important to notify the doctor if they have a history of heart disease or liver problems, are pregnant or planning to become pregnant, or are breastfeeding, as amlodipine can pass into breast milk.

Patients are advised to take amlodipine besylate tablets once daily, with or without food. To aid in adherence, it may be beneficial to take the medication at the same time each day, such as with breakfast or dinner, or at bedtime. They 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, 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 emergency room.

Patients should refrain from starting any new prescription or non-prescription medications or supplements without first consulting their healthcare provider. Common side effects of amlodipine besylate tablets may include 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 aware that starting or increasing the dose of amlodipine besylate tablets may lead to a heart attack or worsening angina; in such cases, they should contact their doctor or go to the emergency room immediately. Patients should communicate any concerns regarding side effects to their healthcare provider, as this list does not encompass all possible side effects.

Amlodipine besylate tablets should be stored out of reach of children, at temperatures between 20º to 25ºC (68º to 77ºF), with permissible excursions between 15º to 30ºC (59º to 86ºF). They should be kept away from light, in a dry place, and not stored 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

Bottles should be stored at a temperature range of 20º to 25ºC (68º to 77ºF), with permissible excursions between 15º to 30ºC (59º to 86ºF) in accordance with USP Controlled Room Temperature guidelines. It is essential to dispense the product in tight, light-resistant containers to ensure its integrity and efficacy.

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 Bi‐Coastal Pharma International LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)