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 or almost white powder, which is slightly soluble in water and sparingly soluble in ethanol.

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

Uses and Indications

Amlodipine besylate is 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 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 in 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.

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 higher doses.

Healthcare professionals should ensure that dosing is tailored to the individual patient's needs, taking into account 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 increase of amlodipine besylate tablets, USP, 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 any changes in their clinical status.

In patients with severe hepatic impairment, it is recommended to titrate the dosage of amlodipine besylate tablets, USP, 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 appropriate dosing adjustments 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, worsening angina and acute myocardial infarction can develop after initiating or increasing the dose of amlodipine besylate, 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 prescribing this medication.

Drug Interactions

There are no specific drug interactions or interactions with laboratory tests identified for the drug in question. As such, no dosage adjustments or monitoring recommendations are necessary based on the available data.

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 is effective in lowering blood pressure in pediatric patients aged 6 to 17 years, with a recommended dosage range of 2.5 to 5 mg daily. The safety and efficacy of amlodipine in patients younger than 6 years of age have not been established, and its effect on blood pressure in this age group is not known. Caution is advised when considering treatment in younger children.

Geriatric Use

Clinical studies of amlodipine 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 women 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 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. 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

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 regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution and consider individual patient factors when prescribing to patients with renal impairment, as the absence of detailed 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 adverse effects, primarily characterized by excessive peripheral vasodilation resulting in marked hypotension, which may be accompanied by 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 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 to evaluate the patient's hemodynamic status. Should hypotension manifest, immediate cardiovascular support is recommended, which may include elevating the extremities and judicious administration of intravenous fluids.

If hypotension persists despite these conservative measures, the administration of vasopressors, such as phenylephrine, should be considered, 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. For mice, the highest dose was, on a mg/m² basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. For rats, the highest dose was, on a mg/m² basis, about 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

Infrequent reports of gynecomastia have been documented in the postmarketing experience, with the causal relationship remaining uncertain. Additionally, cases of jaundice and elevations in hepatic enzymes, primarily consistent with cholestasis or hepatitis, have been reported. Some instances were severe enough to necessitate hospitalization. Furthermore, postmarketing surveillance has indicated a possible association between extrapyramidal disorder and the use of amlodipine.

Patient Counseling

Patients should read the provided information carefully before starting amlodipine besylate tablets and each time they refill their prescription. This information is not a substitute for discussions with their healthcare provider. If patients have any questions regarding amlodipine besylate tablets, they should consult their doctor.

Healthcare providers should ensure that patients understand that amlodipine besylate tablets are a calcium channel blocker (CCB) used to treat high blood pressure (hypertension) and a type of chest pain known as angina. It can be prescribed alone or in combination with other medications for these conditions. Patients should be informed that high blood pressure results from blood exerting excessive force against blood vessel walls, and that 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.

Patients should be made aware that angina 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.

It is crucial to advise patients not to use amlodipine besylate tablets if they are allergic to amlodipine or any of the inactive ingredients. Patients should be encouraged to inform their healthcare provider 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 their pregnancy status or plans to become pregnant, since the healthcare provider will determine if amlodipine besylate tablets are appropriate for them. Breastfeeding patients should be informed that 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, such as with breakfast or 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.

While taking amlodipine besylate tablets, patients 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 hospital emergency room.

Patients should be advised against starting any new prescription or non-prescription medications or supplements without first consulting 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 informed that it is rare, but possible, to experience a heart attack or worsening angina when first starting the medication or increasing the dose, and they should seek immediate medical attention if this occurs.

Patients should communicate any concerns regarding side effects to their healthcare provider, as this list does not encompass all possible side effects. For a complete list, patients should consult their doctor or pharmacist. It is important to keep amlodipine besylate tablets out of reach of children and to store them at temperatures between 20º to 25º C (68º to 77ºF), with permissible excursions between 15º to 30ºC (59º to 86ºF). The medication should be kept away from light and stored in a dry place, not in the bathroom.

Patients should only use amlodipine besylate tablets as directed by their healthcare provider and should not share the medication with others, even if they exhibit similar symptoms, as it may be harmful to them. For additional information about amlodipine besylate tablets, patients can consult their pharmacist or healthcare provider, or contact ACI Healthcare USA, Inc at 1-888-802-1213.

Storage and Handling

The product is supplied in tight, light-resistant containers as per USP guidelines. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F) in accordance with USP Controlled Room Temperature standards.

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 ACI Healthcare USA, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)