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 g/mol. 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, either as monotherapy or in combination with other antihypertensive and antianginal agents. The primary purpose of this medication is to lower blood pressure, which in turn reduces the risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

Additionally, amlodipine besylate is indicated for the management of coronary artery disease, specifically for patients experiencing 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 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.

Healthcare professionals should ensure that the dosing regimen is tailored to the individual patient's needs, taking into account their specific circumstances and health status.

Contraindications

Use of this product is contraindicated in patients with a known sensitivity to amlodipine. This is due to the potential for adverse reactions in individuals with hypersensitivity to the active ingredient.

Warnings and Precautions

Symptomatic hypotension may occur, especially in patients diagnosed with severe aortic stenosis. While acute hypotension is 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 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 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 dosing decisions in this population.

Side Effects

Patients may experience a range of adverse reactions while receiving treatment. Common adverse reactions, occurring in more than 1.0% of participants, include edema, fatigue, nausea, abdominal pain, and somnolence.

Serious side effects have been observed, particularly in patients with specific cardiovascular conditions. Symptomatic hypotension may occur, especially in those with severe aortic stenosis, although acute hypotension is unlikely. Additionally, worsening angina can develop after initiating or increasing the dose, particularly in patients with severe obstructive coronary artery disease. There is also a risk of acute myocardial infarction under similar circumstances in this patient population.

It is important to note that individuals with known sensitivity to amlodipine should exercise caution. In cases of overdosage, excessive peripheral vasodilation may lead to marked hypotension and potentially reflex tachycardia.

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 is indicated for the management of hypertension in pediatric patients aged 6 to 17 years, with a recommended dosage range of 2.5 to 5 mg daily. The efficacy of amlodipine besylate in lowering blood pressure has been established within this age group. However, the effects of amlodipine besylate on blood pressure in patients younger than 6 years of age have not been determined, and caution is advised when considering treatment in this population.

Geriatric Use

Clinical studies of amlodipine besylate did not include a sufficient number of subjects aged 65 and older 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, 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, including increased maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications, as well as fetal risks such as intrauterine growth restriction and intrauterine death.

Animal reproduction studies have shown 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. Nonetheless, in rats, there was a notable decrease in litter size (approximately 50%) and a significant increase in the number of intrauterine deaths (about 5-fold) at the same doses. Additionally, amlodipine maleate has been observed 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. Given these considerations, pregnant women with hypertension should be closely monitored and managed to mitigate potential risks to both maternal and fetal health.

Lactation

The safety of amlodipine in lactating mothers has not been established. Caution should be exercised when administering amlodipine to nursing women. There is a potential for excretion of amlodipine in human breast milk; however, the effects on breastfed infants and on milk production are unknown.

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 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 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 necessary. This may include elevating the extremities and administering fluids judiciously to restore blood pressure.

If hypotension persists despite these conservative measures, the administration of vasopressors, such as phenylephrine, should be considered. Careful attention must be paid to the patient's circulating volume and urine output 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, with males treated 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. Despite these findings, 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 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 exerted by blood 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.

Patients experiencing angina may feel recurring pain or discomfort due to insufficient blood flow to the heart. This pain typically manifests as a pressing or squeezing sensation in the chest, which may also radiate to the shoulders, arms, neck, jaws, or back. Amlodipine besylate tablets can help alleviate this discomfort.

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 Amlodipine besylate tablets. Additionally, patients should disclose all prescription and non-prescription medications they are currently taking, including any 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 besylate can pass into breast milk.

Patients should 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 during breakfast, dinner, or at bedtime. Patients 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; however, they should not discontinue nitroglycerin without consulting their healthcare provider. It is important for patients to continue taking all prescribed medications, including other blood pressure medications, unless directed otherwise by their doctor. 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 refrain from starting any new prescription or non-prescription medications or supplements without first consulting their healthcare provider. Amlodipine besylate tablets 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, and muscle rigidity or tremors. It is rare, but patients may experience a heart attack or worsening angina when first starting the medication or increasing the dose. If this occurs, they should contact their doctor immediately or go to the emergency room.

Patients should communicate any concerns regarding side effects to their healthcare provider. This summary does not encompass all possible side effects; for a complete list, patients should consult their doctor or pharmacist. Amlodipine besylate tablets should be stored away from children and kept at a temperature between 20°C to 25°C (68°F to 77°F), protected from light and moisture. 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 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 must be adhered to in order to ensure optimal product quality.

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)