Amlodipine besylate

Description

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

The tablets are formulated for oral administration and are available in strengths of 2.5 mg, 5 mg, and 10 mg of amlodipine. Each tablet contains inactive ingredients, including microcrystalline cellulose, dibasic calcium phosphate dihydrate, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine besylate tablets are indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive and antianginal agents. The primary purpose of this medication is to lower blood pressure, which in turn reduces the risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

In addition to hypertension, amlodipine besylate is indicated for the management of coronary artery disease, specifically for patients experiencing chronic stable angina and vasospastic angina (Prinzmetal’s or variant angina). It is also indicated for patients with angiographically documented coronary artery disease who do not have heart failure or an ejection fraction 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 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 caution should be exercised when considering dosage adjustments.

Healthcare professionals should ensure that patients are monitored for efficacy and tolerability, adjusting the dosage as necessary within the established guidelines.

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 increase 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

No drug interactions or drug and laboratory test interactions have been identified in the available data. Therefore, no specific 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 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 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 approximate 40–60% increase in the area under the curve (AUC). 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 limited available data from post-marketing reports regarding the use of amlodipine besylate 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.

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. Nonetheless, in rats, there was a significant decrease in litter size (approximately 50%) and a notable increase in the number of intrauterine deaths (about 5-fold) at the equivalent dose of 10 mg amlodipine/kg/day. Additionally, amlodipine maleate 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 U.S. population is 2%–4% and 15%–20%, respectively, and all pregnancies carry a background 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 delivery complications such as the need for cesarean section and postpartum hemorrhage. Furthermore, hypertension can elevate fetal risks for intrauterine growth restriction and intrauterine death.

Given these considerations, pregnant women with hypertension should be carefully 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

There is no specific information available 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 patient population.

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 of 4 mg amlodipine/kg or higher—exceeding 11 times the maximum recommended human dose on a mg/m² basis—have also led to 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 should be provided, which includes elevating the extremities and judiciously administering 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.

Due to the high protein binding of amlodipine besylate, hemodialysis is unlikely to be effective in managing an overdose. Therefore, healthcare professionals should focus on supportive care and monitoring to address the symptoms and complications associated with overdosage.

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 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. Patients are encouraged to ask their doctor if they have 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 type of chest pain known as angina. This medication can be utilized alone or in conjunction with other medications to manage 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 consequently lowering blood pressure. Lowering blood pressure is crucial as it 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 must inform their healthcare provider if they have a known allergy to amlodipine or any of the inactive ingredients in the tablets. It is also important for patients to disclose all prescription and non-prescription medications they are currently taking, including any natural or herbal remedies.

Patients should notify their doctor if they have a history of heart disease or liver problems, are pregnant or planning to become pregnant, or are breastfeeding, as amlodipine besylate can pass into breast milk.

Amlodipine besylate tablets should be taken once daily, with or without food. To aid in adherence, patients may find it beneficial to take their dose at the same time each day, such as with breakfast or 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, the patient should wait and take the next scheduled dose.

Patients can continue using nitroglycerin alongside amlodipine besylate tablets for angina; however, they should not discontinue nitroglycerin without consulting their doctor. It is crucial that patients do not stop taking any other prescribed medications, including other blood pressure medications, without first discussing it with 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 also refrain from starting any new prescription or non-prescription medications or supplements without prior consultation with 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. Patients should be aware that it is rare, but possible, to experience a heart attack or worsening angina when first starting the medication or increasing the dose. If such symptoms occur, patients should contact their doctor immediately or go to the nearest emergency room.

Patients are encouraged to discuss any side effects they experience with their healthcare provider, as this list does not encompass all possible side effects. For a complete list, patients should consult their doctor or pharmacist.

Amlodipine besylate tablets should be stored out of reach of children, at room temperature (between 68° and 77°F), away from light, and in a dry place, avoiding storage in the bathroom. Patients should only use amlodipine besylate tablets as prescribed by their doctor and should not share their medication with others, even if they exhibit similar symptoms, as it may be harmful.

For additional information about amlodipine besylate tablets, patients may contact their pharmacist or healthcare provider, or reach out to Marlex Pharmaceuticals at 1-888-582-1953 or via email at drugsafety@marlexpharm.com.

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

View full prescribing information (PDF)