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 a structural formula of C₁₈H₂₅ClN₂O₅ • C₆H₆O₃S and 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 white to off-white formulations, equivalent to 2.5 mg, 5 mg, and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including calcium phosphate dibasic 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. The reduction of 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 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 less than 40%.

There are no teratogenic or nonteratogenic effects associated with the use of 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, 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.

Contraindications

Use of this product is contraindicated in patients with a known sensitivity to amlodipine. This is due to the potential for adverse reactions in individuals with hypersensitivity to the active ingredient.

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.

Additionally, there is a risk of worsening angina and acute myocardial infarction following the initiation or dose escalation of amlodipine besylate tablets. This risk is particularly pronounced in patients with severe obstructive coronary artery disease. Close monitoring of these patients is recommended to promptly identify and manage any adverse cardiovascular events.

For patients with severe hepatic impairment, it is essential to titrate the dosage of amlodipine besylate tablets slowly. This cautious approach helps mitigate the risk of potential adverse effects associated with altered drug metabolism in this population. Regular assessment of liver function may be warranted to ensure safe and effective dosing.

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 during treatment.

Drug Interactions

There are no specific drug interactions or drug and laboratory test interactions identified in the available data. Therefore, no dosage adjustments or monitoring recommendations 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 is effective in lowering blood pressure in pediatric patients aged 6 to 17 years when administered at a dosage of 2.5 to 5 mg daily. 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.

Geriatric Use

Clinical studies of amlodipine besylate 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 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 in pregnant patients is limited, primarily derived from postmarketing 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. Notably, while teratogenicity and other embryo/fetal toxicities were not evident 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. Additionally, amlodipine maleate was associated with prolonged gestation and extended labor duration in rats at this dosage.

The estimated background risk of major birth defects and miscarriage in the general U.S. population is approximately 2% to 4% and 15% to 20%, respectively. All pregnancies inherently carry a background risk of birth defects, loss, or other adverse outcomes. Furthermore, 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. 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 is no specific information available regarding the use of amlodipine in lactating mothers or its effects on breast milk. Additionally, there is no data on the potential for excretion of amlodipine in breast milk or any associated risks to 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 of these patients.

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 resulted in fatalities. In canine models, doses equivalent to 4 mg amlodipine/kg or higher—representing more than 11 times the maximum recommended human dose on a mg/m² basis—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 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 consideration 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, supportive care remains the cornerstone of treatment in such cases.

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 amlodipine/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 has 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

Healthcare providers should advise patients 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 doctor. Patients should be 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 angina, a type of chest pain. Patients should be informed that these tablets can be used alone or in combination with other medications to manage these conditions.

Patients should understand 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, which reduces the risk of stroke or heart attack. Regarding angina, patients should be made aware that it manifests as 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. They should be encouraged to inform their doctor about all prescription and non-prescription medications they are taking, including any natural or herbal remedies.

It is essential for patients to disclose any history of heart disease or liver problems, as well as their pregnancy status or plans to become pregnant, since the doctor will determine if amlodipine besylate tablets are suitable for them. Additionally, breastfeeding patients should be informed that amlodipine 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 their dose at the same time each day, such as with breakfast, dinner, or at bedtime. They should be cautioned not to take more than one dose at a time. 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 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.

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 abnormal muscle movements. It is important 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, and they should seek immediate medical attention if this occurs. Patients should be encouraged to discuss any side effects they experience with their doctor, as this list does not encompass all possible side effects.

Patients should be instructed to store amlodipine besylate tablets out of reach of children, at temperatures between 68°F to 77°F (20°C to 25°C), away from light, and in a dry place, avoiding storage in the bathroom. They should also be reminded that amlodipine besylate tablets should only be used as prescribed by their doctor and not shared with others, even if they exhibit similar symptoms, as this could be harmful.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and features a child-resistant closure as required. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Additionally, it is crucial to keep this medication, along with all other medications, out of the reach of children to ensure safety.

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

View full prescribing information (PDF)