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 empirical 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 white tablet form, with dosages equivalent to 2.5 mg, 5 mg, and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and magnesium stearate.

Uses and Indications

Amlodipine besylate, USP is indicated for the treatment of hypertension, coronary artery disease, chronic stable angina, and vasospastic angina (Prinzmetal’s or variant angina). This medication may be utilized as monotherapy or in combination with other antihypertensive and antianginal agents.

Amlodipine besylate 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 of amlodipine 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 can be taken with or without food, and it is advisable for patients to take their dose at the same time each day to enhance adherence, such as during breakfast, dinner, or at bedtime.

Patients should not exceed one dose of amlodipine besylate tablets at a time. In the event of a missed dose, it should be taken as soon as the patient remembers, provided it is within 12 hours of the scheduled dose. If more than 12 hours have passed since the missed dose, the patient should skip the missed dose and resume the regular dosing schedule.

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. It is important to note that due to the gradual onset of action of the medication, the risk of acute hypotension is considered unlikely.

Healthcare professionals should be vigilant for the potential exacerbation of angina and the risk of acute myocardial infarction following the initiation or dose escalation of amlodipine besylate tablets. This risk is particularly pronounced in patients with severe obstructive coronary artery disease, necessitating careful monitoring of these patients during treatment.

In patients with severe hepatic impairment, it is recommended to titrate the dosage of calcium channel blockers slowly. This precaution 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. Common adverse reactions reported include headache, edema, fatigue, nausea, abdominal pain, and somnolence. These reactions are generally mild to moderate in severity.

Serious side effects have also been observed. Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis. Additionally, worsening angina and acute myocardial infarction can 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, which should be considered when evaluating potential adverse reactions.

Drug Interactions

Co-administration of simvastatin with amlodipine may result in increased plasma concentrations of simvastatin due to the inhibitory effects of amlodipine on the metabolism of simvastatin. Therefore, it is recommended that the daily dose of simvastatin should not exceed 20 mg when used in conjunction with amlodipine to mitigate the risk of adverse effects associated with elevated simvastatin levels. Monitoring for signs of myopathy or other related side effects is advised in patients receiving this combination therapy.

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's effect on blood pressure in pediatric patients under 6 years of age has not been established. Therefore, caution is advised when considering the use of amlodipine in this age group, as the safety and efficacy profile remains unclear. Further studies are needed to determine appropriate dosing and outcomes for infants and young 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, leading to 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. Careful monitoring and dose adjustments are recommended to optimize treatment outcomes for geriatric patients.

Pregnancy

Amlodipine is classified as a Pregnancy Category C medication. There are no adequate and well-controlled studies in pregnant women; therefore, amlodipine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Animal studies have not demonstrated evidence of teratogenicity or other embryo/fetal toxicity when pregnant rats and rabbits were administered amlodipine maleate at doses up to 10 mg amlodipine/kg/day during their respective periods of major organogenesis. Notably, these doses correspond to approximately 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m² basis.

However, it is important to note that in rats receiving amlodipine maleate at a dose equivalent to 10 mg amlodipine/kg/day for 14 days prior to mating and throughout mating and gestation, there was a significant decrease in litter size (approximately 50%) and a marked increase in the number of intrauterine deaths (about 5-fold). Additionally, this dose of amlodipine maleate has been associated with prolonged gestation and an extended duration of labor in rats.

Healthcare professionals should carefully consider the potential risks and benefits when prescribing amlodipine to pregnant patients.

Lactation

It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that lactating mothers discontinue breastfeeding while receiving amlodipine.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment may require careful consideration when administering calcium channel blockers. It is recommended to titrate the dosage slowly in individuals with severe hepatic impairment to minimize the risk of adverse effects and ensure optimal therapeutic outcomes. Monitoring of liver function may be necessary to assess the patient's response to treatment and adjust the dosage accordingly.

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 should be provided, which includes elevating the extremities and judiciously administering fluids. If hypotension persists despite these conservative measures, 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 be effective in managing an 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 mg, 1.25 mg, or 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 amlodipine/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 an uncertain causal relationship. Additionally, cases of jaundice and elevations in hepatic enzymes, primarily consistent with cholestasis or hepatitis, have been observed. Some instances were severe enough to necessitate hospitalization in association with the use of amlodipine.

Patient Counseling

Healthcare providers should advise patients to read the provided information carefully before starting amlodipine besylate tablets and each time they refill their prescription, as there may be new information. It is important to emphasize that this information does not replace discussions with their doctor. Patients should be encouraged to ask their doctor any questions regarding the appropriateness of amlodipine besylate tablets for their condition.

Amlodipine besylate tablets are classified as a calcium channel blocker (CCB) and are indicated for the treatment of high blood pressure (hypertension) and angina, which is a type of chest pain. Patients should be informed that 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. This reduction in blood pressure can decrease the risk of stroke or heart attack. Regarding angina, patients should be made aware that it 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.

Patients should be cautioned against using amlodipine besylate tablets if they have a known allergy 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. They should specifically mention any history of heart disease or liver problems, as well as if they are pregnant, planning to become pregnant, or breastfeeding. The healthcare provider will determine if amlodipine besylate tablets are suitable for their treatment plan.

Patients should be instructed to take amlodipine once daily, with or without food, and to establish a routine by taking it 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 for angina, but they should not discontinue nitroglycerin without consulting their doctor. It is crucial 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 hospital emergency room. Patients should also be advised against breastfeeding while taking amlodipine besylate tablets, as it is unknown whether the medication passes into breast milk.

Patients should refrain from starting any new prescription or non-prescription medications or supplements without first consulting their doctor. They should be made aware of potential side effects, which may include headache, swelling of the legs or ankles, tiredness, extreme sleepiness, stomach pain, nausea, dizziness, flushing, arrhythmia, and heart palpitations. Patients should be informed that while most side effects are mild to moderate, there is a rare risk of experiencing a heart attack or worsening angina when initiating treatment or increasing the dose. They should be instructed to contact their doctor immediately or go to the emergency room if such symptoms occur.

Patients should be encouraged to report any side effects they experience to their doctor and to consult their healthcare provider or pharmacist for a complete list of possible side effects. It is important to keep amlodipine besylate tablets out of reach of children and to store them at room temperature, away from light and moisture, and not in the bathroom.

Finally, patients should be reminded that amlodipine besylate tablets should only be used as prescribed by their doctor and should not be shared with others, even if they exhibit similar symptoms. For additional information, patients can contact their pharmacist or doctor, visit the Camber Pharmaceuticals website, or call the provided customer service number. They should also be informed that they can report side effects to the FDA.

Storage and Handling

Amlodipine besylate tablets are supplied in various package configurations. It is essential to store the tablets at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines.

To ensure the integrity of the product, the tablets must be kept away from light and stored in a dry place. It is also important to avoid storing them in the bathroom. Additionally, these tablets should be kept 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 Aidarex Pharmaceuticals LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)