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. The molecular 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 two formulations: yellow tablets equivalent to 2.5 mg of amlodipine and white tablets equivalent to 5 mg and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The 2.5 mg strength also contains ferric oxide yellow as a coloring agent.

Uses and Indications

Amlodipine besylate tablets are indicated for the treatment of hypertension, serving to lower 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.

In addition to hypertension, amlodipine besylate tablets are indicated for the management of coronary artery disease, which includes the treatment of chronic stable angina and vasospastic angina (Prinzmetal's or variant angina). Furthermore, this medication is indicated for patients with angiographically documented coronary artery disease who do not have heart failure or an ejection fraction of 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 advisable 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 the risk of acute hypotension is considered low, healthcare professionals should remain vigilant in monitoring these patients for any signs of symptomatic changes.

Additionally, there is a potential for worsening angina and the occurrence of acute myocardial infarction following the initiation or dose escalation of amlodipine. This risk is particularly pronounced in patients with severe obstructive coronary artery disease. It is imperative that healthcare providers closely monitor these patients for any exacerbation of symptoms during treatment.

In patients with severe hepatic impairment, it is recommended to titrate the dosage of amlodipine slowly. This cautious approach is essential to minimize the risk of adverse effects and ensure patient safety. Regular assessment of liver function may be warranted to guide appropriate dosing adjustments.

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, 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

The use of simvastatin is associated with specific dosage considerations to mitigate the risk of adverse effects. It is recommended that the daily dose of simvastatin should not exceed 20 mg. This limitation is crucial to ensure patient safety and to minimize the potential for drug-related complications.

Healthcare professionals should monitor patients closely when prescribing simvastatin, particularly in those who may be taking other medications that could interact with its metabolism or efficacy. Adjustments to the dosage of simvastatin may be necessary based on individual patient factors and concurrent therapies.

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 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 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 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 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.

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. Notably, while no teratogenicity or other embryo/fetal toxicity was observed 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%-4% and 15%-20%, respectively, and all pregnancies carry a baseline risk of 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

There is limited available data from post-marketing reports regarding the use of amlodipine in nursing mothers, which are insufficient to determine a drug-associated risk for major adverse effects in breastfed infants.

Amlodipine may be excreted in human breast milk; therefore, caution should be exercised when administering amlodipine to lactating mothers.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, monitoring requirements, or precautions outlined for individuals with reduced kidney function. Healthcare professionals should exercise clinical judgment when considering the use of this medication in patients with renal impairment, as the lack of specific guidance necessitates careful evaluation of individual patient circumstances.

Hepatic Impairment

Patients with hepatic impairment should be approached 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 during treatment to ensure patient safety and therapeutic efficacy. Adjustments to the dosing regimen may be necessary based on the patient's response and any changes in liver function.

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 the 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 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

Infrequent reports of gynecomastia have been documented in the postmarketing experience, although a causal relationship remains 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 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. This medication can be used alone or in combination with other treatments for these conditions. Patients should understand that high blood pressure results from excessive force against blood vessel walls, and 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 experiencing angina may feel recurring pain or discomfort due to insufficient blood flow 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 for patients to inform their healthcare provider if they have a known allergy to amlodipine or any of the inactive ingredients in the tablets. Additionally, patients should disclose all prescription and non-prescription medications they are currently taking, including natural or herbal remedies. They should also inform 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 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 not 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 safely use nitroglycerin alongside amlodipine besylate tablets; however, they should not discontinue nitroglycerin if it has been prescribed for angina. It is important for patients to continue taking all other prescribed medications, including other blood pressure medications, unless directed otherwise by 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. Patients should also refrain from starting any new prescription or non-prescription medications or supplements without consulting their healthcare provider first.

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, although rare, they may 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 emergency room.

Patients should report any side effects they experience 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.

Amlodipine besylate tablets should be stored out of reach of children, at temperatures between 20º to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F). They should be kept away from light, in a dry place, and not stored in the bathroom.

Finally, patients should only use amlodipine besylate tablets as prescribed by their healthcare provider and should not share this medication with others, even if they exhibit similar symptoms, as it may be harmful to them.

Storage and Handling

The product is supplied in tight, light-resistant containers to ensure its integrity and efficacy. 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) as defined by USP Controlled Room Temperature guidelines. Proper adherence to these storage conditions is essential for maintaining the quality of the product.

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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)