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, with an empirical formula of C20H25ClN2O5•C6H6O3S. Amlodipine besylate appears as a white or almost white powder and has a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. Amlodipine besylate tablets, USP, are available as white to off white tablets, each equivalent to 2.5, 5, and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including microcrystalline cellulose, dibasic calcium phosphate dihydrate, sodium starch glycolate, colloidal silicon dioxide, and magnesium stearate.

Uses and Indications

Amlodipine besylate tablets, USP, 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 is indicated for the management of coronary artery disease, which includes 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%.

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

Contraindications

Use of this product is contraindicated in patients with a known sensitivity to amlodipine.

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 dose escalation of Amlodipine besylate 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 to mitigate potential cardiovascular risks.

In patients with severe hepatic impairment, it is recommended to titrate the dosage of Amlodipine besylate slowly. This cautious approach is essential to avoid exacerbating hepatic conditions and to 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. These include symptomatic hypotension, particularly in patients with severe aortic stenosis, although acute hypotension is unlikely. Additionally, worsening angina and acute myocardial infarction may develop after initiating or increasing the dose, especially in patients with severe obstructive coronary artery disease.

It is important to note that some patients may have a known sensitivity to amlodipine. In cases of overdosage, excessive peripheral vasodilation may occur, leading to marked hypotension and potentially reflex tachycardia.

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 is indicated for the management of hypertension in pediatric patients aged 6 to 17 years, with an effective dosage range 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 unknown.

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 40–60%. 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 NORVASC (amlodipine) in pregnant women is limited and primarily derived from post-marketing reports, which are 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, including increased likelihood of pre-eclampsia, gestational diabetes, premature delivery, and complications during delivery such as the need for cesarean section and postpartum hemorrhage.

In animal reproduction studies, no evidence of adverse developmental effects was 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 same doses. Additionally, amlodipine maleate was found 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 U.S. population is approximately 2%-4% and 15%-20%, respectively. All pregnancies carry a background risk of birth defects, loss, or other adverse outcomes. Therefore, it is crucial for pregnant women with hypertension to be closely monitored and managed to mitigate these risks.

While no evidence of teratogenicity or other embryo/fetal toxicity has been identified in studies involving pregnant rats and rabbits treated with amlodipine maleate at doses up to 10 mg amlodipine/kg/day, the potential for adverse outcomes necessitates careful consideration and management of hypertension in pregnant patients.

Lactation

No specific information is available regarding the use of this medication in nursing mothers or its potential for excretion in breast milk. Consequently, the effects on breastfed infants are also not established. Healthcare professionals should consider the lack of data when advising lactating mothers on the use of this medication.

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 this patient population.

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 clinical manifestations, 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 been associated with 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. This may include elevating the extremities and administering fluids judiciously to restore circulating volume.

If hypotension persists despite these conservative measures, the administration of vasopressors, such as phenylephrine, should be considered. Careful monitoring of circulating volume and urine output is crucial during this intervention.

It is important to note that due to the high protein binding of amlodipine besylate, 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 amlodipine noted in postmarketing reports. 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

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 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 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.

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 tablets can help alleviate this pain.

Patients should not use Amlodipine besylate tablets if they are allergic to amlodipine or any of the inactive ingredients. They should inform their healthcare provider about all prescription and non-prescription medications they are taking, including natural or herbal remedies. It is particularly important to notify the doctor if they have a history of heart disease or liver problems, are pregnant or planning to become pregnant, or are breastfeeding, as Amlodipine besylate can pass into breast milk.

Patients are advised to take Amlodipine besylate tablets once daily, with or without food. To aid in adherence, it may be beneficial to take the medication 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 more than 12 hours have passed since the missed dose, they should skip it and resume their regular dosing schedule.

Patients can use nitroglycerin in conjunction with Amlodipine besylate tablets; however, they should not discontinue nitroglycerin without consulting their doctor. It is crucial that patients do not stop taking any other prescribed medications, including other blood pressure medications, without first discussing it with 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.

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. While most side effects are mild to moderate, patients should be aware that it is rare but possible to experience 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 immediately or go to the emergency room.

Patients should communicate any concerns regarding side effects to their healthcare provider. This information does not encompass all potential side effects; for a complete list, patients should consult their doctor or pharmacist.

Amlodipine besylate tablets should be stored away from children, at temperatures between 20°C to 25°C (68°F to 77°F), and protected from light and moisture. 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

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), in accordance with USP controlled room temperature guidelines. It is essential to protect the product from light and moisture to maintain its integrity and efficacy. Proper handling and storage conditions are crucial to ensure the product's quality 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 REMEDYREPACK INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)