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, with a molecular weight of 567.1, represented by the formula C20H25ClN2O5 • C6H6O3S. Amlodipine besylate appears as a white crystalline powder and is slightly soluble in water and sparingly soluble in ethanol. The tablets are formulated as white to off-white tablets, available in strengths of 2.5 mg, 5 mg, and 10 mg of amlodipine for oral administration. Each tablet contains inactive ingredients including calcium phosphate dibasic anhydrous, magnesium stearate, microcrystalline cellulose, and sodium starch glycolate.

Uses and Indications

Amlodipine besylate tablets are indicated for the treatment of hypertension, serving to lower blood pressure. This reduction in 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. This includes the treatment of chronic stable angina and vasospastic angina (Prinzmetal’s or variant angina). Furthermore, amlodipine besylate is indicated for patients with angiographically documented coronary artery disease who do not have heart failure or an ejection fraction less than 40%.

No teratogenic or nonteratogenic effects have been 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 advisable to initiate treatment at a lower 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 higher doses.

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. 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 increase of amlodipine besylate tablets 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 tablets 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 therapy in this population.

Side Effects

Patients receiving treatment with amlodipine besylate tablets may experience a range of adverse reactions. The most common adverse reaction reported is edema, which is dose-related. Other common adverse reactions, occurring in more than 1.0% of participants, include fatigue, nausea, abdominal pain, and somnolence.

Serious adverse reactions have also been observed. 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. In cases of overdosage, excessive peripheral vasodilation may lead to marked hypotension and potentially a reflex tachycardia.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted 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 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 effect on blood pressure in this age group is not known.

Geriatric Use

Clinical studies of amlodipine besylate did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, other reported clinical experience has not identified significant differences in responses between elderly patients and younger patients.

In general, dose selection for geriatric 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 assessment of the patient's response to therapy are recommended to optimize treatment outcomes.

Pregnancy

The available data regarding the use of amlodipine in pregnant patients is limited, primarily derived from postmarketing 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.

In animal reproduction studies, no adverse developmental effects were 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. Notably, while no evidence of teratogenicity or other embryo/fetal toxicity was found 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 potential risks to both maternal and fetal health.

Lactation

The limited available data from postmarketing reports regarding the use of amlodipine 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. Therefore, caution should be exercised when administering amlodipine to lactating mothers.

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 approached with caution. In particular, those with severe hepatic impairment require careful titration of the dosage. It is recommended that the dosage be adjusted slowly to minimize the risk of adverse effects and to ensure patient safety. Regular monitoring of liver function is advised to assess the patient's response to treatment and to make any necessary adjustments to the therapeutic regimen.

Overdosage

Overdosage may lead to significant clinical manifestations, 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, it is recommended to provide cardiovascular support, which may include elevating the extremities and judicious administration of intravenous fluids.

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.

Due to the high protein binding of amlodipine besylate, hemodialysis is unlikely to provide any therapeutic benefit in cases of overdose. Therefore, management should focus on supportive care and monitoring of vital signs.

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. For mice, the highest dose was, on a mg/m² basis, similar to the maximum recommended human dose of 10 mg amlodipine/day. For rats, the highest dose was, on a mg/m² basis, about 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

Infrequent reports of gynecomastia have been documented in the postmarketing experience, although a 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.

Patients should be informed that amlodipine besylate tablets are classified as a calcium channel blocker (CCB) and are used to treat high blood pressure (hypertension) and a type of chest pain known as angina. They may be prescribed alone or in combination with other medications for these conditions.

It is essential to explain 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, which reduces the risk of stroke or heart attack. For angina, which is characterized by recurring pain or discomfort due to insufficient blood flow to the heart, 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. Healthcare providers should encourage patients to disclose all prescription and non-prescription medications they are currently taking, including any natural or herbal remedies. It is also important for patients to inform their doctor if they have a history of heart disease or liver problems.

Pregnant patients or those planning to become pregnant should discuss their situation with their doctor, who will determine if amlodipine besylate tablets are suitable. Additionally, breastfeeding patients should be informed that 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 take more than 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 wait until the next scheduled dose.

Patients can continue using nitroglycerin alongside amlodipine besylate tablets for angina, and 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 seek immediate medical attention by contacting their doctor, Poison Control Center, or going to the nearest emergency room.

Healthcare providers should inform patients about 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, 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 contact their doctor or go to the emergency room if such symptoms occur.

Patients should be encouraged to report any side effects they experience and to consult their doctor or pharmacist for a complete list of possible side effects. It is crucial to keep amlodipine besylate tablets out of reach of children and to store them at a temperature between 68° to 77°F (20° to 25°C), away from light and moisture, and not in the bathroom.

Finally, healthcare providers should remind patients that amlodipine besylate tablets should only be used as prescribed by their doctor, and they should not share their medication with others, even if they exhibit similar symptoms, as it may be harmful to them.

Storage and Handling

The product is supplied in a tight, light-resistant container that complies with USP standards and includes a child-resistant closure as required. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), adhering to USP Controlled Room Temperature guidelines.

Healthcare professionals are reminded to keep this and all medications out of the reach of children to ensure safety.

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 AvKARE. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)