Amlodipine besylate

Description

Amlodipine besylate, USP 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 is presented as a white crystalline powder with a molecular weight of 567.1. It exhibits slight solubility in water and sparing solubility in ethanol. Amlodipine besylate tablets, USP are available in white tablet form, each equivalent to 2.5 mg, 5 mg, and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine besylate tablets, USP, are indicated for the treatment of hypertension and coronary artery disease.

In the management of hypertension, amlodipine besylate is utilized to lower blood pressure, thereby reducing the risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

For coronary artery disease, amlodipine besylate is indicated for the treatment of 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%.

Amlodipine besylate may be administered as monotherapy or in combination with other antihypertensive and antianginal agents.

There are no teratogenic or nonteratogenic effects associated with 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, the initial dose may be reduced to 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 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 1.0% of participants.

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, worsening angina and acute myocardial infarction can develop after initiating or increasing the dose of amlodipine besylate tablets, especially 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 treatment options.

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 have not included a sufficient number of subjects aged 65 and over to determine whether these elderly patients respond differently compared to 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, 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. Careful monitoring and dose adjustments are recommended to optimize treatment outcomes for geriatric patients.

Pregnancy

The available data regarding the use of amlodipine in pregnant patients is limited, primarily derived from post-marketing reports, and is 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 intrauterine deaths (about 5-fold) at the dose equivalent to 10 mg amlodipine/kg/day. Additionally, amlodipine maleate was associated with prolonged gestation and extended duration of labor in rats at this dosage.

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 linked to 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

Amlodipine is present in human milk, with a reported estimated median relative infant dose of 4.2% based on limited available data from a published clinical lactation study. 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 no specific information regarding dosage adjustments or monitoring provided in the text. Therefore, healthcare professionals should exercise caution when prescribing this medication to individuals with reduced kidney function, as the absence of guidance necessitates careful consideration of potential risks and benefits. Regular monitoring of renal function may be advisable in these patients 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 peripheral vasodilation, resulting in pronounced hypotension and potentially reflex tachycardia. Clinical experience with intentional overdosage of amlodipine 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 produced severe 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 intravenous 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, hemodialysis is unlikely to provide 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 per 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. 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, 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 should understand that this medication can be used alone or in combination with other medications to manage these conditions.

It is important to 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. Patients should be informed that controlling high blood pressure reduces the risk of stroke and heart attack.

Patients experiencing angina may feel recurring pain or discomfort due to insufficient blood flow to the heart. This pain is often described as a pressing or squeezing sensation, typically located in the chest but may also radiate to the shoulders, arms, neck, jaws, or back. Amlodipine besylate tablets can help alleviate this discomfort.

Patients should be cautioned against using amlodipine besylate tablets if they have a known allergy to amlodipine or any of the inactive ingredients. They should inform their healthcare provider about all medications they are currently taking, including prescription and non-prescription drugs, as well as any natural or herbal remedies. It is particularly important to disclose any history of heart disease or liver problems, and to inform the doctor if they are pregnant, planning to become pregnant, or breastfeeding, as amlodipine can pass into breast milk.

Patients should take amlodipine besylate tablets once daily, with or without food, and it may be beneficial to take the medication at the same time each day. 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 for angina, and they should not discontinue 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 emergency room.

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 made aware that while most side effects are mild to moderate, there is a rare risk of experiencing 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 seek emergency care immediately.

Patients should be encouraged to report any side effects they experience to their healthcare provider. For a comprehensive list of potential side effects, they should consult their doctor or pharmacist.

It is essential 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 prescribed by their healthcare provider 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 can consult their pharmacist or healthcare provider, or visit Exelan Pharmaceuticals' website at www.exelanpharma.com or call 1-866-604-3268.

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

View full prescribing information (PDF)