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 molecular formula is C20H25ClN2O5 • C6H6O3S, and it has a molecular weight of 567.1. Amlodipine besylate appears as a white crystalline powder that is slightly soluble in water and sparingly soluble in ethanol.

Amlodipine besylate Tablets, USP are available in two formulations: yellow tablets equivalent to 2.5 mg of amlodipine and white tablets equivalent to 5 mg and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate. The 2.5 mg strength also contains ferric oxide yellow as a coloring agent.

Uses and Indications

Amlodipine besylate tablets 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 tablets are indicated for the management of coronary artery disease, which includes the treatment of chronic stable angina and vasospastic angina (Prinzmetal's or variant angina). Furthermore, this medication is 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 tablets.

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 dosage adjustments.

Healthcare professionals should ensure that patients are monitored for efficacy and tolerability, adjusting the dosage as necessary within the established guidelines.

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 generally considered unlikely, healthcare professionals should remain vigilant for signs of symptomatic hypotension in this patient population.

Additionally, there is a risk of worsening angina and acute myocardial infarction following the initiation or dose escalation of amlodipine. This risk is particularly pronounced in patients with severe obstructive coronary artery disease. Close monitoring of these patients is recommended to promptly identify and manage any adverse cardiovascular events.

For patients with severe hepatic impairment, it is crucial to titrate the dosage of amlodipine slowly. This precaution helps to mitigate the risk of potential adverse effects associated with altered drug metabolism in this population. Regular assessment of liver function may be warranted to ensure safe and effective dosing.

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. 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, 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 treatment options.

Drug Interactions

No drug interactions or drug and laboratory test interactions have been identified in the available data. Therefore, 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 is 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 in patients younger than 6 years of age have not been established, and its effect on blood pressure in this age group is not known.

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, resulting in an approximate increase in the area under the curve (AUC) of 40–60%. 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

The available data regarding the use of amlodipine in pregnant patients 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 note that poorly controlled hypertension during pregnancy poses significant risks to both the mother and fetus.

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 higher dose. Additionally, amlodipine has been shown to prolong both the gestation period and the duration of labor in rats at this dosage.

The estimated background risk of major birth defects and miscarriage in the general population remains unknown; however, it is acknowledged that all pregnancies carry a baseline risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2%-4% and 15%-20%, respectively.

Hypertension during 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. Therefore, pregnant women with hypertension should be closely monitored and managed appropriately to mitigate these risks.

Lactation

There is no specific information available regarding the use of this medication in nursing mothers. Additionally, there is no data on the potential for excretion of this medication in breast milk or its effects on breastfed infants. Healthcare professionals should consider the lack of information when advising lactating mothers about 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 during treatment to ensure patient safety and therapeutic efficacy. Adjustments to the dosing regimen may be necessary based on the patient's response and any changes in liver function.

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. 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, 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 administered was, on a mg/m² basis, similar to the maximum recommended human dose of 10 mg amlodipine/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, indicating a lack of mutagenic potential.

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. This dosage is eight times the maximum recommended human dose of 10 mg/day when adjusted for body surface area.

Postmarketing Experience

Infrequent reports of gynecomastia have been documented in the postmarketing experience, although the causal relationship remains uncertain. Additionally, cases of jaundice and elevations in hepatic enzymes, primarily consistent with cholestasis or hepatitis, have been reported. Some instances were severe enough to necessitate hospitalization. Furthermore, postmarketing surveillance has indicated a possible association between extrapyramidal disorder and 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 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 specifically 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 can pass into breast milk.

Patients should be instructed to take amlodipine besylate tablets once daily, with or without food, and to establish a routine by taking the medication at the same time each day. They should not exceed one dose at a time. If a dose is missed, patients should take it as soon as they remember, unless it has been more than 12 hours since the missed dose, in which case they should skip it and resume their regular dosing schedule.

While on amlodipine besylate tablets, patients should not discontinue any other prescribed medications, including other blood pressure medications, without consulting 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 be cautioned against 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 mild to moderate symptoms such as 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, and they should seek immediate medical attention if this occurs.

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.

Finally, patients should be instructed to keep amlodipine besylate tablets out of reach of children and to store them at temperatures between 20º to 25°C (68° to 77°F), with permissible excursions between 15° to 30°C (59° to 86°F). They should be kept away from light, not stored in the bathroom, and maintained in a dry environment. Patients should also 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, as it may be harmful to them.

Storage and Handling

The product is supplied in tight, light-resistant containers to ensure its integrity and efficacy. 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). Proper storage conditions are essential to maintain the quality of the product.

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 Unichem Pharmaceuticals (USA) , Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)