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, with an empirical formula of C20H25ClN2O5•C6H6O3S. Amlodipine besylate appears as a white crystalline powder and has a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate tablets, USP are available as white tablets, each equivalent to 2.5, 5, and 10 mg of amlodipine for oral administration. 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 in blood pressure is associated with a decreased risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

This medication 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 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 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 studied in this population, and caution should be exercised when considering higher doses.

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 need for adjustments in therapy based on clinical response.

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 therapy in this population.

Side Effects

Patients may experience a range of adverse reactions while using the medication. The most common adverse reactions include edema, which is dose-related, as well as fatigue, nausea, abdominal pain, and somnolence, each occurring in more than 1.0% of participants in clinical trials.

Serious adverse reactions 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 besylate tablets 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 prescribing this medication.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted 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 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 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 patients. However, other reported clinical experiences have not identified significant differences in responses between elderly and younger patients.

In general, dose selection for geriatric patients should be approached with caution. It is advisable to start at the lower 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

The available data regarding the use of Amlodipine besylate tablets in pregnant women is limited and 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.

In animal reproduction studies, no adverse developmental effects were 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 notable decrease in litter size (approximately 50%) and a significant increase in the number of intrauterine deaths (about 5-fold) at the dose equivalent to 10 mg amlodipine/kg/day. Additionally, this dose was associated with prolonged gestation and extended duration of labor in rats.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is 2%-4% and 15%-20%, respectively, and all pregnancies carry a baseline risk of birth defects, loss, or other adverse outcomes. Hypertension in pregnancy is associated with increased maternal risks, including pre-eclampsia, gestational diabetes, premature delivery, and complications during delivery, such as the need for cesarean section and postpartum hemorrhage. Furthermore, 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

There are no specific statements regarding the use of this medication in nursing mothers or its effects during lactation. Additionally, there is no available data on the excretion of this medication in breast milk or its potential effects on breastfed infants. Healthcare professionals should consider the absence of information when advising lactating mothers about the use of this medication.

Renal Impairment

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this population to ensure safety and efficacy.

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 clinical manifestations, primarily characterized by excessive peripheral vasodilation resulting in marked hypotension, which may be accompanied by reflex tachycardia.

In animal studies, 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. Additionally, doses of 4 mg amlodipine/kg or greater in dogs have been associated with pronounced peripheral vasodilation and hypotension.

In the event of a massive overdose, it is imperative to initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential to assess the patient's hemodynamic status. Should hypotension occur, cardiovascular support should be provided, which includes elevating the extremities and judicious administration of intravenous fluids.

If hypotension persists despite these conservative measures, the administration of vasopressors, such as phenylephrine, should be considered to restore hemodynamic stability. It is important to note that hemodialysis is unlikely to be beneficial in cases of overdose, as amlodipine besylate is highly protein-bound, limiting its removal from the bloodstream through this method.

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, with males treated 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. It is important to emphasize that this information does not replace discussions with their healthcare provider. Patients are encouraged to ask their doctor any questions they may have regarding the appropriateness of amlodipine besylate tablets for their condition.

Amlodipine besylate tablets are classified as a calcium channel blocker (CCB) and are indicated for the treatment of high blood pressure (hypertension) and a specific 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 effectively.

Patients should be informed that high blood pressure results from excessive force exerted by blood against the walls of blood vessels. Amlodipine besylate tablets work by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure. This reduction in blood pressure is crucial as it decreases the risk of stroke or heart attack.

For those experiencing angina, which is characterized by recurring pain or discomfort due to insufficient blood supply to the heart, patients should recognize that amlodipine besylate tablets can help alleviate this pain. Angina may present as a pressing or squeezing sensation in the chest, and it can radiate to the shoulders, arms, neck, jaws, or back.

Patients must be cautioned against using amlodipine besylate tablets if they have a known allergy to amlodipine or any of the inactive ingredients. They should be encouraged to discuss all prescription and non-prescription medications they are currently taking, including any natural or herbal remedies, with their healthcare provider.

It is essential for patients to inform their doctor if they have a history of heart disease or liver problems, are pregnant, or plan to become pregnant, as these factors may influence the suitability of amlodipine besylate tablets for their treatment. Additionally, breastfeeding patients should notify their doctor, as the medication can pass into breast milk.

Patients should be instructed to take amlodipine besylate tablets once daily, with or without food, and to establish a routine by taking the medication at the same time each day. They should not exceed one dose at a time. In the event of a missed dose, patients should take it as soon as they remember, unless more than 12 hours have passed since the missed dose, in which case they should skip it and resume their regular dosing schedule.

Patients can safely use nitroglycerin in conjunction with amlodipine besylate tablets for angina, but they should not discontinue nitroglycerin without consulting their doctor. It is also critical that patients do not stop taking any other prescribed medications, including other blood pressure medications, without first discussing it with their healthcare provider.

In cases of overdose, patients should seek immediate medical attention by contacting their doctor, the Poison Control Center, or going to the nearest hospital emergency room. Patients should refrain from starting any new prescription or non-prescription medications or supplements without prior consultation with their doctor.

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, fatigue, extreme sleepiness, stomach pain, nausea, dizziness, flushing, irregular heartbeat, heart palpitations, muscle rigidity, tremors, and abnormal muscle movements. It is important to inform patients that, although rare, they may experience a heart attack or worsening angina when initiating treatment or increasing the dose. In such cases, they should contact their doctor immediately or go to the emergency room.

Patients should be encouraged to report any side effects they experience and to consult their healthcare provider for a complete list of possible side effects. It is crucial 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.

Finally, patients should be reminded that their doctor may prescribe amlodipine besylate tablets for conditions not specified in the patient information leaflets. They should only use the medication as directed by their healthcare provider and should not share it 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 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 Legacy Pharmaceutical Packaging, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)