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. 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 strengths of 2.5 mg, 5 mg, and 10 mg for oral administration. Each tablet contains inactive ingredients including colloidal silicon dioxide, dicalcium phosphate anhydrous, FD & C red no. 40 aluminum lake (only for 2.5 mg strength), magnesium stearate, microcrystalline cellulose, and povidone.

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%.

No teratogenic or nonteratogenic effects have been reported with the use of 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, treatment may be initiated at a lower dose of 2.5 mg once daily to ensure safety and tolerability.

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 therefore should not be administered.

Healthcare professionals should assess individual patient needs and adjust dosing accordingly, while adhering to the specified limits to optimize therapeutic outcomes.

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.

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.

In 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. Common adverse reactions, occurring in more than 1.0% of participants, include edema, fatigue, nausea, abdominal pain, and somnolence.

Serious adverse reactions have also been reported. Symptomatic hypotension may occur, particularly in patients with severe aortic stenosis. Additionally, worsening angina can develop after initiating or increasing the dose, especially in individuals with severe obstructive coronary artery disease. There is also a risk of acute myocardial infarction under similar circumstances in these patients.

It is important to note that individuals with known sensitivity to amlodipine should exercise caution. Furthermore, overdosage may lead to excessive peripheral vasodilation, resulting in marked hypotension and potentially 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 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 they respond differently from younger patients. However, other reported clinical experiences have not identified significant differences in responses between elderly patients and their younger counterparts.

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. Careful monitoring and dose adjustments are recommended to optimize treatment outcomes for elderly 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 dose.

The estimated background risk of major birth defects and miscarriage in the general population remains unknown; however, 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% to 4% and 15% to 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

Amlodipine is excreted in human breast milk; however, the effects of amlodipine on breastfed infants are unknown. Limited available data from post-marketing reports in nursing mothers do not provide sufficient information to assess a drug-associated risk for major adverse effects in breastfed infants. Caution should be exercised when administering amlodipine to lactating mothers.

The developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for amlodipine and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition. The decision to continue breastfeeding or to discontinue the drug should be made based on the importance of the drug to the mother.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to 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.

In animal studies, 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. Additionally, doses of 4 mg amlodipine/kg or more in dogs have been associated with pronounced peripheral vasodilation and hypotension.

In the event of a massive overdose, it is critical 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 process.

It is important to note that due to the high protein binding of amlodipine, hemodialysis is unlikely to be beneficial in the management of overdose cases.

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. Despite these findings, amlodipine 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 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. Patients are encouraged to ask their doctor any questions regarding the appropriateness of amlodipine besylate tablets for their condition.

Amlodipine besylate is classified as a calcium channel blocker (CCB) and is indicated for the treatment of high blood pressure (hypertension) and a specific type of chest pain known as angina. It may be prescribed 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 works by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure, which reduces the risk of stroke or heart attack.

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 can help alleviate this pain.

Patients should not use amlodipine besylate if they are allergic to amlodipine or any of the inactive ingredients. It is important for patients to inform their healthcare provider about all prescription and non-prescription medications they are taking, including any natural or herbal remedies. Additionally, patients should disclose any history of heart disease, liver problems, or if they are pregnant or planning to become pregnant, as this information will assist the healthcare provider in determining the suitability of amlodipine besylate for their treatment.

Amlodipine besylate tablets should be taken 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, 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; however, they should not discontinue nitroglycerin if it has been prescribed for angina. It is crucial that patients do not stop taking any other prescribed medications, including other blood pressure medications, without consulting their healthcare provider.

In the event of an overdose, patients should seek immediate medical attention by contacting their doctor, the Poison Control Center, or going to the nearest hospital emergency room.

Common side effects of amlodipine besylate may include mild to moderate 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 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. If such symptoms occur, patients should contact their doctor or seek emergency care immediately.

Patients are encouraged to report any side effects they experience to their healthcare provider. For a complete list of potential side effects, they should consult their doctor or pharmacist. To report side effects, patients can contact the FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

Amlodipine besylate tablets should be stored out of reach of children, at temperatures between 20° to 25°C (68° to 77°F), away from light, and in a dry place, avoiding storage in the bathroom. Patients should only use amlodipine besylate as directed by their healthcare provider and should not share their medication with others, even if they have similar symptoms, as it may be harmful.

For additional information about amlodipine besylate tablets, patients can consult their pharmacist or healthcare provider, or visit the Lupin website at www.lupinpharmaceuticals.com or call 1-800-399-2561.

Storage and Handling

The product is supplied in tight, light-resistant containers to ensure optimal stability and efficacy. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature 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 Lupin Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)