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 molecular formula is C20H25ClN2O5 •C6H6O3S, and it has a molecular weight of 567.1. Amlodipine besylate USP 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 as white to off-white tablets, each equivalent to 2.5, 5, and 10 mg of amlodipine for oral administration. The tablets contain the following inactive ingredients: dibasic calcium phosphate 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.

This drug 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 reported for 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 with a reduced 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 the dosing regimen 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 severe allergic reactions, administration in such cases may pose significant health risks.

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% 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, 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 potential adverse reactions.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring 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 has been shown to be 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 besylate in patients younger than 6 years have not been established, and its effects in this age group remain 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 to 60%. Consequently, a lower initial dose may be necessary to ensure safety and efficacy in this population. Regular monitoring and careful assessment of the patient's overall health status are recommended to optimize treatment outcomes.

Pregnancy

The available data regarding the use of amlodipine besylate 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.

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, significant concerns arose in rats, where litter size was reduced by approximately 50% and the incidence of intrauterine deaths increased fivefold. 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 2% to 4% and 15% to 20%, respectively, and all pregnancies inherently carry a background 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 risks to both maternal and fetal health.

Lactation

The limited available data from post-marketing reports regarding the use of amlodipine besylate in nursing mothers do not provide sufficient information to assess the drug-associated risk for major adverse effects in breastfed infants. There is a potential for excretion of amlodipine in human breast milk; however, the effects on the breastfed infant and on milk production remain unknown. Caution should be exercised when administering amlodipine to a nursing woman.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, monitoring, or precautions. As such, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, given the absence of detailed guidance on its use in this population. Regular monitoring of renal function may be advisable to ensure patient safety and therapeutic 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 during treatment to ensure patient safety and therapeutic efficacy.

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.

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 may include elevating the extremities and the 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 amlodipine besylate is highly protein-bound, and therefore, hemodialysis is unlikely to provide any significant benefit in the management 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 administered was, on a mg/m² basis, similar to the maximum recommended human dose of 10 mg amlodipine per day. In rats, the highest dose was approximately twice the maximum recommended human dose when adjusted for body surface area.

Mutagenicity studies conducted with amlodipine maleate revealed no drug-related effects at either the gene or chromosome level. Additionally, there was no observed effect on the fertility of rats treated orally with amlodipine maleate. Male rats were treated for 64 days, and female rats 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 per 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. Furthermore, there has been a possible association noted 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 specific type of chest pain known as angina. These tablets can be utilized alone or in conjunction with other medications to manage these conditions.

Patients should understand that high blood pressure results from blood exerting excessive force against blood vessel walls. Amlodipine besylate tablets work by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure. Medications that reduce blood pressure can decrease the risk of stroke or heart attack.

Angina is characterized by recurring pain or discomfort due to insufficient blood supply to the heart. Patients may experience a pressing or squeezing sensation, typically in the chest beneath the breastbone, but it can also 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 disclose any history of heart disease or liver problems, as well as if they are pregnant, planning to become pregnant, or breastfeeding, since amlodipine besylate can pass into breast milk.

Patients are instructed to take amlodipine besylate tablets once daily, with or without food. 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, it should be taken as soon as remembered, 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. If they are prescribed nitroglycerin for angina, they should not discontinue its use while taking amlodipine besylate tablets. Additionally, patients should not stop taking 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 refrain from 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 mild to moderate swelling of the legs or ankles, tiredness, extreme sleepiness, stomach pain, nausea, dizziness, flushing, arrhythmia, heart palpitations, and muscle rigidity or tremors. It is important to inform patients 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, they should contact their doctor immediately or go to the nearest hospital emergency room.

Patients should be encouraged to discuss any side effects they experience with their healthcare provider, as this list does not encompass all possible side effects. For a complete list, they should consult their doctor or pharmacist.

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

Patients should only use amlodipine besylate tablets as directed by their healthcare provider, even if they have similar symptoms to others. Sharing this medication with others could be harmful.

For additional information about amlodipine besylate tablets, patients can consult their pharmacist or healthcare provider, or contact the provided helpline at 1-866-850-2876.

Storage and Handling

The product is supplied in tight, light-resistant containers as defined by the United States Pharmacopeia (USP). 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 guidelines.

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 Aurobindo Pharma Limited. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)