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 C20H25ClN2O5S, and it has a molecular weight of 567.1. Amlodipine besylate appears as a white crystalline powder that is slightly soluble in water and sparingly soluble in ethanol. The drug is available in tablet form for oral administration, with strengths of 2.5 mg, 5 mg, and 10 mg of amlodipine. Each tablet contains inactive ingredients including microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine besylate is a calcium channel blocker indicated for the treatment of hypertension and coronary artery disease.

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

In the context of coronary artery disease, amlodipine besylate is indicated for the management 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%.

This drug may be used alone 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 of amlodipine besylate 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.

Amlodipine besylate tablets should be taken once daily, with or without food. It is advisable for patients to take their dose at the same time each day, which may facilitate adherence; options include taking the medication with breakfast, dinner, or at bedtime. Patients should not exceed one dose at a time.

In the event of a missed dose, patients should take the missed dose as soon as they remember. However, if more than 12 hours have passed since the missed dose, they should skip that dose and resume their regular dosing schedule at the next scheduled time.

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. Common adverse reactions observed in clinical trials include edema, fatigue, nausea, abdominal pain, and somnolence, with an incidence greater than 1.0%.

Serious adverse reactions warranting attention include symptomatic hypotension, which 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 also 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 currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted 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 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 besylate tablets did not include a sufficient number of subjects aged 65 and older to determine whether these elderly patients respond differently from younger patients. However, other reported clinical experiences have not identified significant differences in responses between elderly and younger patients.

In general, dose selection for geriatric 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, resulting in an increase in the area under the curve (AUC) of approximately 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 besylate 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 note 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 in pregnant rats and rabbits treated orally with 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 reduction in litter size (approximately 50%) and a notable increase in the number of intrauterine deaths (about 5-fold) at these doses. Additionally, amlodipine has been shown to prolong both the gestation period and the duration of labor in rats.

The estimated background risk of major birth defects and miscarriage in the general population remains unknown; however, all pregnancies carry a baseline risk of adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2%-4% and 15%-20%, respectively.

Hypertension during 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. Therefore, pregnant women with hypertension should be closely monitored and managed appropriately to mitigate these risks.

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 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 cardiovascular effects, primarily characterized by excessive peripheral vasodilation resulting in marked hypotension, which may be accompanied by reflex tachycardia.

Toxicological studies have demonstrated 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 have also induced pronounced peripheral vasodilation and hypotension.

In the event of a massive overdose, it is imperative to initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential to assess the patient's hemodynamic status. Should hypotension occur, immediate cardiovascular support is recommended, which includes 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 to restore hemodynamic stability. It is important to note that 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

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. 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 is classified as a calcium channel blocker (CCB) and is utilized to treat high blood pressure (hypertension) and a specific type of chest pain known as angina. It may be prescribed alone or in conjunction with other medications for these conditions. Patients should understand that high blood pressure results from blood exerting excessive force against blood vessel walls. Amlodipine besylate works by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure, which 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 can help alleviate this pain.

Patients should not use amlodipine besylate tablets if they are allergic to amlodipine or any of the inactive ingredients. It is essential for patients to inform their doctor 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 if they are pregnant, plan to become pregnant, or are breastfeeding, since amlodipine besylate can pass into breast milk.

Amlodipine besylate tablets should be taken once daily, with or without food. Patients may find it helpful to take their dose at the same time each day, such as with breakfast, 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 it has been more than 12 hours since the missed dose, they should wait and take the next dose at the regular time.

Patients can use nitroglycerin alongside amlodipine besylate. If they are prescribed nitroglycerin for angina, they should not discontinue its use while taking amlodipine besylate. It is crucial for patients to continue taking their other prescribed medications, including any other blood pressure medications, unless directed otherwise by their doctor. In the event of an overdose, patients should contact their doctor, Poison Control Center, or go to the nearest hospital emergency room immediately.

Patients should avoid starting any new prescription or non-prescription medications or supplements without consulting their doctor first. Amlodipine besylate may cause side effects, most of which are mild to moderate, including swelling of the legs or ankles, tiredness, extreme sleepiness, stomach pain, nausea, dizziness, flushing, arrhythmia, heart palpitations, muscle rigidity, tremors, and/or abnormal muscle movements. Although rare, patients may experience a heart attack or worsening angina when first starting amlodipine besylate or increasing the dose; in such cases, they should seek immediate medical attention.

Patients should communicate any concerns regarding side effects to their doctor, as this list does not encompass all possible side effects of amlodipine besylate tablets. 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 store them at room temperature (between 59° and 86°F), away from light, and in a dry place, avoiding storage in the bathroom.

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

Storage and Handling

Amlodipine besylate tablets are supplied in tight, light-resistant containers as per USP standards. It is essential to store these tablets at controlled room temperature, specifically between 59°F to 86°F (15°C to 30°C).

To ensure the integrity of the product, it is crucial to keep the tablets away from light and to store them in a dry place. Additionally, these tablets should not be stored in the bathroom. Care should be taken to keep amlodipine besylate tablets out of reach of children to prevent accidental ingestion.

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

View full prescribing information (PDF)