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 strengths of 2.5 mg, 5 mg, and 10 mg for oral administration. Each tablet contains inactive ingredients including 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 drug 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 reported for 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, it is advisable 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 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. This contraindication is based on the potential for severe allergic reactions in individuals with a history of hypersensitivity to 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 carries the risk of exacerbating angina or precipitating an acute myocardial infarction, particularly in individuals with severe obstructive coronary artery disease. It is imperative 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. Common adverse reactions, occurring in more than 1.0% of participants, include edema, fatigue, nausea, abdominal pain, and somnolence. These reactions are generally dose-related and should be monitored throughout treatment.

Serious side effects 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 evaluating the risk of adverse reactions.

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 of age have not been established, and therefore, its effect on blood pressure in this age group is not known.

Geriatric Use

Clinical studies of amlodipine besylate tablets did not include a sufficient number of subjects aged 65 and older 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 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 approximate increase in the area under the curve (AUC) of 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 tablets in pregnant women is limited and primarily derived from post-marketing reports, which are 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, including increased maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and complications during delivery, such as the need for cesarean section and post-partum hemorrhage. Additionally, hypertension can elevate the fetal risk for intrauterine growth restriction and intrauterine death.

Animal reproduction studies have shown 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, no teratogenicity or other embryo/fetal toxicity was observed at doses up to 10 mg amlodipine/kg/day during critical periods of organ development. However, in rats, there was a significant reduction in litter size (approximately 50%) and a five-fold increase in the number of intrauterine deaths when treated with amlodipine maleate at the aforementioned dose for 14 days prior to mating and throughout mating and gestation. Furthermore, this treatment 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. 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 is no specific information available regarding the use of this medication in nursing mothers. Additionally, there is no data on the potential for excretion of this medication in breast milk or its effects on breastfed infants. Healthcare professionals should consider the lack of information when advising lactating mothers on the use of this medication.

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 to ensure patient safety and to adjust treatment as necessary.

Overdosage

Overdosage may lead to significant adverse effects, primarily characterized by excessive peripheral vasodilation resulting in marked hypotension, which may be accompanied by reflex tachycardia.

Toxicological studies have demonstrated 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 have also induced 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 manifest, immediate cardiovascular support is recommended. This may include elevating the extremities and administering fluids judiciously to restore blood pressure.

If hypotension persists despite these conservative measures, the administration of vasopressors, such as phenylephrine, should be considered. Careful monitoring of circulating volume and urine output is crucial during this intervention.

It is important to note that due to the high protein binding of amlodipine besylate, 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 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 infrequent reports of gynecomastia, 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 have also been reports suggesting a possible association between extrapyramidal disorder and amlodipine. Furthermore, 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 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 medicines to manage these conditions. Patients should understand that high blood pressure results from excessive force exerted by blood 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. It is essential for patients to inform their doctor about all prescription and non-prescription medications they are taking, including natural or herbal remedies. Additionally, patients should disclose any history of heart disease or liver problems, as well as if they are pregnant, plan to become pregnant, or are breastfeeding, since amlodipine besylate tablets 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, dinner, or at bedtime. Patients 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 wait and take the next dose at the regular time.

Patients can use nitroglycerin in conjunction with amlodipine besylate tablets; however, they should not discontinue nitroglycerin if it has been prescribed for angina. It is crucial for patients to continue taking all other prescribed medications, including other blood pressure medications, unless directed otherwise by 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 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. Although rare, patients may experience 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 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.

Patients should store amlodipine besylate tablets out of reach of children, at room temperature (20° to 25°C or 68° to 77°F), away from light, and in a dry place, avoiding storage in the bathroom. It is important for patients to use amlodipine besylate tablets only as prescribed by their doctor and not to 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 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 Epic Pharma, LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)