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 it has a molecular weight of 567.1. Amlodipine besylate appears as a white crystalline powder, which is slightly soluble in water and sparingly soluble in ethanol.

Amlodipine besylate tablets, USP, are available in white tablet form, with each tablet containing 2.5 mg, 5 mg, or 10 mg of amlodipine for oral administration. In addition to the active ingredient, the tablets contain the following inactive ingredients: microcrystalline cellulose, corn starch, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine besylate tablets are indicated for the treatment of hypertension, effectively lowering 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.

Amlodipine besylate tablets may be utilized as monotherapy or in conjunction with other antihypertensive and antianginal agents for the management of chronic stable angina, vasospastic angina (Prinzmetal’s or variant angina), and angiographically documented coronary artery disease in patients who do not have heart failure or an ejection fraction less than 40%.

There are no teratogenic or nonteratogenic effects associated with the use of 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 advised to initiate treatment with a reduced 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 evaluated in this population.

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

Serious warnings associated with the use of this medication include the potential for symptomatic hypotension, 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 besylate tablets in patients with severe obstructive coronary artery disease.

In cases of overdosage, patients may experience excessive peripheral vasodilation leading to marked hypotension, which could be accompanied by reflex tachycardia. It is important for healthcare providers to monitor patients for these adverse reactions and manage them appropriately.

Drug Interactions

There are no specific drug interactions or interactions with laboratory tests reported for the drug. 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 besylate tablets at doses of 2.5 mg 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 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

There are no adequate and well-controlled studies in pregnant patients. Amlodipine is classified as Pregnancy Category C, indicating that it 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 amlodipine maleate at this dose. Specifically, there was a notable decrease in litter size by approximately 50% and a five-fold increase in the number of intrauterine deaths. Additionally, amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dosage. Given these findings, healthcare professionals should carefully weigh the potential risks and benefits when considering the use of amlodipine in pregnant patients.

Lactation

It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while amlodipine besylate tablets are administered.

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 during treatment to ensure patient safety and therapeutic efficacy.

Overdosage

Overdosage of amlodipine besylate may lead to significant clinical manifestations, primarily characterized by excessive peripheral vasodilation resulting in marked hypotension and potentially reflex tachycardia. Clinical experience with intentional overdose in humans is limited, underscoring the need for caution and prompt management in suspected cases.

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 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 to evaluate the patient's hemodynamic status. Should hypotension be observed, immediate cardiovascular support should be provided, which includes elevating the extremities and judiciously administering intravenous fluids. 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.

It is important to note that due to the high protein binding of amlodipine besylate, hemodialysis is unlikely to be effective in managing overdose cases. Therefore, supportive care and monitoring remain the cornerstone of treatment in such scenarios.

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 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 may use this medication alone or in combination with other treatments for these conditions. It is important to explain 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.

Patients should be informed that angina manifests as recurring pain or discomfort due to insufficient blood supply to the heart. This pain typically feels like pressure or squeezing in the chest and may radiate to the shoulders, arms, neck, jaws, or back. Amlodipine besylate tablets can help alleviate this discomfort.

It is crucial to instruct patients not to use amlodipine besylate tablets if they are allergic to amlodipine or any of the inactive ingredients. Patients should disclose all prescription and non-prescription medications they are taking, including natural or herbal remedies, to their healthcare provider. Additionally, 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, as these factors may influence the appropriateness of amlodipine besylate tablets for their treatment.

Patients should take amlodipine besylate tablets once daily, with or without food, and may find it helpful to take their dose at the same time each day. They should not exceed one dose at a time. If a dose is missed, patients should take it as soon as they remember, 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 doctor. 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.

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

Patients should be encouraged to report any side effects they experience to their healthcare provider. For a comprehensive list of possible side effects, they should consult their doctor or pharmacist. It is important to keep amlodipine besylate tablets out of reach of children and to store them at room temperature, 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 this medication with others, even if they exhibit similar symptoms, as it may be harmful. For additional information about amlodipine besylate tablets, patients can consult their pharmacist or doctor.

Storage and Handling

Bottles should be stored at a temperature range of 20° to 25°C (68° to 77°F), 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. Additionally, the product must be protected from light exposure to maintain its quality.

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 Marlex Pharmaceuticals Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)