Amlodipine besylate

Description

Amlodipine besylate tablets are the besylate salt of amlodipine, a long-acting calcium channel blocker. Chemically, amlodipine besylate 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 and a molecular weight of 567.1. The compound appears as a white crystalline powder, exhibiting slight solubility in water and sparing solubility in ethanol.

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

Uses and Indications

Amlodipine besylate tablets are indicated for the treatment of hypertension, effectively lowering blood pressure. This reduction in 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 the following conditions:

• Hypertension

• Chronic Stable Angina

• Vasospastic Angina (Prinzmetal's or Variant Angina)

• Angiographically Documented Coronary Artery Disease in patients who do not have heart failure or an ejection fraction less than 40%.

There are no specific 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 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 receiving treatment. 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% of participants.

Serious adverse reactions have also been reported. Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis, although acute hypotension is unlikely. Additionally, worsening angina can develop after initiating or increasing the dose, especially in patients with severe obstructive coronary artery disease. There is also a risk of acute myocardial infarction following the start or dose increase in these patients.

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

Drug Interactions

No specific drug interactions or drug and laboratory test interactions have been identified in the available data. Therefore, no 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 effect on blood pressure in this age group is not known. Caution is advised when considering treatment in this population.

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, leading to 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. 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.

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 when treated with amlodipine maleate at this dose for 14 days prior to mating and throughout gestation. Additionally, this treatment was associated with prolonged gestation and labor duration in rats.

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 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. 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

Limited available data from a published clinical lactation study indicate that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. 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 not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with reduced kidney function, as the absence of specific guidance necessitates careful clinical judgment.

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 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 equivalent to 4 mg amlodipine/kg or higher—exceeding the maximum recommended human dose by 11 times 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 careful administration of 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 tablets, 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 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 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 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.

Healthcare providers should 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. Additionally, patients should be informed that 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 must be cautioned against using amlodipine besylate tablets if they have a known allergy to amlodipine or any of the inactive ingredients. Healthcare providers should encourage patients to disclose all prescription and non-prescription medications they are currently taking, including natural or herbal remedies. It is particularly important to inform the doctor if the patient has a history of heart disease or liver problems, is pregnant or planning to become pregnant, or is breastfeeding, as amlodipine besylate 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. If a dose is missed, 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 the missed dose and resume their regular schedule.

It is permissible to use nitroglycerin in conjunction with amlodipine besylate tablets; however, patients should not discontinue nitroglycerin if it has been prescribed for angina. Patients must be advised not to stop taking 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. It is crucial to inform patients that, although rare, they may experience a heart attack or worsening angina when starting or increasing the dose of amlodipine besylate tablets. 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 to their healthcare provider and can also report side effects to the FDA. It is important to keep amlodipine besylate tablets out of reach of children and to store them at controlled room temperature, away from light and moisture.

Finally, patients should be reminded to use amlodipine besylate tablets only as directed by their healthcare provider and not to share their medication with others, even if they exhibit similar symptoms. For further information, patients can consult their pharmacist or healthcare provider.

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 Oxford Pharmaceuticals, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)