Amlodipine besylate

Description

Amlodipine besylate tablets consist of the besylate salt of amlodipine, a long-acting calcium channel blocker. The chemical structure of amlodipine besylate is defined as 3-Ethyl-5-methyl (±)-2-(2-aminoethoxy)methyl-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate, monobenzenesulphonate, with a molecular formula of C20H25ClN2O5 • C6H6O3S and a molecular weight of 567.1 g/mol.

Amlodipine besylate appears as a white crystalline powder, exhibiting slight solubility in water and sparing solubility in ethanol. The tablets are formulated for oral administration, available in strengths of 2.5 mg, 5 mg, and 10 mg of amlodipine. Each tablet contains inactive ingredients including colloidal silicon dioxide, magnesium stearate, mannitol, 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 the following conditions:

• Hypertension

• Chronic Stable Angina

• Vasospastic Angina (Prinzmetal’s or Variant Angina)

• 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.

Contraindications

Use of this product is contraindicated in patients with a known sensitivity to amlodipine. This contraindication is based on the potential for severe allergic reactions in individuals with such sensitivities.

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 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 reported include edema, fatigue, nausea, abdominal pain, and somnolence, each occurring in more than 1% of participants in clinical trials.

Serious adverse reactions have also been noted. Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis, although 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 in patients with severe obstructive coronary artery disease.

Patients with known sensitivity to amlodipine should be monitored closely, as they may be at increased risk for adverse effects. In cases of overdosage, excessive peripheral vasodilation may lead to marked hypotension and potentially reflex tachycardia.

In the event of a massive overdose, active cardiac and respiratory monitoring is recommended. Frequent blood pressure measurements are essential, and if hypotension occurs, cardiovascular support should be provided, including elevation of the extremities and judicious administration of fluids. Should hypotension remain unresponsive to these conservative measures, the administration of vasopressors, such as phenylephrine, may be necessary, with careful attention to circulating volume and urine output.

Drug Interactions

There are currently no documented drug interactions or interactions with laboratory tests associated with the use of this medication. As such, no specific recommendations for dosage adjustments or monitoring are necessary. Healthcare professionals should continue to assess individual patient circumstances and consider any other medications or conditions that may influence treatment outcomes.

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 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

There are no adequate and well-controlled studies in pregnant patients. Amlodipine is classified as Pregnancy Category C, indicating that it should be used during pregnancy only if the potential benefit justifies the risk to the fetus. Animal studies have not demonstrated evidence of teratogenicity or other embryo/fetal toxicity when pregnant rats and rabbits were treated orally with amlodipine maleate at doses up to 10 mg amlodipine/kg/day, which corresponds to 8 times and 23 times the maximum recommended human dose of 10 mg on a mg/m² basis during their respective periods of major organogenesis.

However, significant adverse effects were observed in rats receiving amlodipine maleate at this dose. Specifically, there was a marked decrease in litter size (approximately 50%) and a notable increase in the number of intrauterine deaths (about 5-fold). Additionally, amlodipine maleate has been shown to prolong both the gestation period and the duration of labor in rats at this dosage. Given these findings, healthcare professionals should carefully consider the risks and benefits of amlodipine use in pregnant patients.

Lactation

It is not known whether amlodipine is excreted in human milk. In the absence of this information, it is recommended that nursing be discontinued while amlodipine besylate is administered.

Renal Impairment

Patients with renal impairment have not been specifically addressed in terms of dosage adjustments, monitoring, or precautions in the available prescribing information. Therefore, healthcare professionals should exercise caution and consider individual patient factors when prescribing this medication to patients with reduced kidney function. Regular monitoring of renal function may be warranted in these patients, although specific recommendations are not provided.

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 peripheral vasodilation, resulting in pronounced hypotension and potentially reflex tachycardia. Clinical experience with intentional overdosage of amlodipine besylate 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 the maximum recommended human dose by 11 times on a mg/m² basis—have also led to significant peripheral vasodilation and hypotension.

In the event of a massive overdose, it is imperative to initiate active cardiac and respiratory monitoring. Continuous blood pressure assessments are crucial. Should hypotension manifest, cardiovascular support measures should be implemented, including the elevation of the extremities and careful administration of intravenous fluids. If hypotension persists despite these conservative interventions, 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 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

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 a type of chest pain known as angina. 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 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. Additionally, patients should be made aware that 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.

It is crucial to inform patients not to use amlodipine besylate tablets if they have a known allergy to amlodipine or any of the inactive ingredients. Patients should be encouraged to disclose all prescription and non-prescription medications they are currently taking, including natural or herbal remedies. They should also inform their doctor if they have a history of heart disease, liver problems, or if they are pregnant or planning to become pregnant, as this information will assist the doctor in determining the suitability of amlodipine besylate tablets for their treatment.

Patients should be advised against breastfeeding while taking amlodipine besylate tablets and may need to consider stopping breastfeeding or switching to an alternative medication. The recommended dosing schedule is 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 or dinner, or at bedtime. They should be instructed not to take more than one dose at a time and to take a missed dose as soon as they remember, unless it has been more than 12 hours since the last dose, in which case they should wait until the next scheduled dose.

Patients can continue using nitroglycerin alongside amlodipine besylate tablets for angina, but they should not discontinue any other prescribed medications, including other blood pressure medications, without consulting their doctor. In the event of an overdose, patients should be instructed to contact their doctor, the Poison Control Center, or go to the nearest hospital emergency room immediately.

Healthcare providers should inform patients of potential side effects associated with amlodipine besylate tablets, which may include mild to moderate symptoms such as swelling of the legs or ankles, tiredness, extreme sleepiness, stomach pain, nausea, dizziness, flushing, arrhythmia, heart palpitations, muscle rigidity, tremors, and abnormal muscle movements. Patients should be made aware that, although rare, there is a risk of experiencing a heart attack or worsening angina when starting or increasing the dose of amlodipine besylate tablets. They should be instructed to seek immediate medical attention if such symptoms occur.

Patients should be encouraged to communicate any concerns regarding side effects to their doctor, as this list does not encompass all possible side effects. For a comprehensive list, patients should consult their doctor or pharmacist.

It is important to remind patients to keep amlodipine besylate tablets out of reach of children and to store them at room temperature, away from light, and in a dry place, avoiding storage in the bathroom. Patients should be cautioned against sharing their medication with others, even if they exhibit similar symptoms, as this could be harmful. Lastly, patients should only use amlodipine besylate tablets as directed by their healthcare provider, even if prescribed for conditions not explicitly mentioned in the patient information leaflets.

Storage and Handling

The product is supplied in tight, light-resistant containers to ensure optimal stability and efficacy. It should be stored at a controlled room temperature of 20 to 25° C (68 to 77° F), in accordance with USP guidelines. Proper storage conditions are essential to maintain the integrity of the product 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 Ranbaxy Pharmaceuticals Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)