Norvasc

Description

NORVASC is the besylate salt of amlodipine, a long-acting calcium channel blocker. Amlodipine besylate is chemically described as 3-Ethyl-5-methyl (±)-2-(2-aminoethoxy)methyl-4‑(2‑chlorophenyl)‑1,4‑dihydro‑6‑methyl‑3,5‑pyridinedicarboxylate, monobenzenesulphonate. Its empirical formula is C20H25ClN2O5 • C6H6O3S. Amlodipine besylate appears as a white crystalline powder with a molecular weight of 567.1. It is slightly soluble in water and sparingly soluble in ethanol. NORVASC (amlodipine besylate) Tablets are available as white tablets equivalent to 2.5, 5, and 10 mg of amlodipine for oral administration. Each tablet contains the following inactive ingredients: microcrystalline cellulose, dibasic calcium phosphate anhydrous, sodium starch glycolate, and magnesium stearate.

Uses and Indications

NORVASC is a calcium channel blocker indicated for the treatment of hypertension and coronary artery disease.

For hypertension, NORVASC is utilized to lower blood pressure, thereby reducing the risk of both fatal and nonfatal cardiovascular events, including strokes and myocardial infarctions.

In the context of coronary artery disease, NORVASC is indicated for the management of 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%.

No teratogenic or nonteratogenic effects have been reported with the use of NORVASC.

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, and caution should be exercised when considering dosage adjustments.

Healthcare professionals should ensure that the medication is taken consistently at the same time each day to maintain optimal therapeutic levels.

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 dose escalation of NORVASC 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 NORVASC slowly. This cautious approach is essential to ensure patient safety and to minimize the risk of adverse effects associated with hepatic dysfunction. 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 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, although acute hypotension is unlikely. Additionally, worsening angina can develop after initiating or increasing the dose, especially in patients with severe obstructive coronary artery disease. There is also a risk of acute myocardial infarction following the start or dose increase in these patients.

It is important to note that some individuals may have a known sensitivity to amlodipine, which should be considered when evaluating potential adverse reactions.

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 warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Norvasc (amlodipine besylate), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients aged 6 to 17 years have demonstrated effective blood pressure reduction with NORVASC at dosages ranging from 2.5 to 5 mg daily. However, the effect of NORVASC on blood pressure in patients younger than 6 years has not been established, and caution is advised when considering treatment in this age group.

Geriatric Use

Clinical studies of NORVASC 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 40–60%. 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 maleate) in pregnant women is limited and primarily derived from post-marketing reports, which are 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 in pregnant rats and rabbits treated orally with 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 same doses. Additionally, amlodipine maleate has been shown 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 2%-4% and 15%-20%, respectively, and all pregnancies carry a background risk of birth defects, loss, or other 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 hypertension include intrauterine growth restriction and intrauterine death.

Given these considerations, pregnant women with hypertension should be closely monitored and managed appropriately to mitigate risks to both maternal and fetal health.

Lactation

Limited available data from a published clinical lactation study indicate that amlodipine is present in human milk at an estimated median relative infant dose of 4.2%. No adverse effects of amlodipine on breastfed infants have been observed. Additionally, there is no available information regarding the effects of amlodipine on milk production in 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 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 clinical manifestations, 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 crucial to initiate active cardiac and respiratory monitoring. Frequent blood pressure measurements are essential to assess the patient's hemodynamic status. Should hypotension occur, cardiovascular support should be provided, which includes elevating the extremities and judicious administration of intravenous fluids.

If hypotension persists despite these conservative measures, the administration of vasopressors, such as phenylephrine, may be warranted. Careful attention should be given 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 NORVASC, hemodialysis is unlikely to provide any significant benefit in the management 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 per 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. Males were 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. Furthermore, NORVASC 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 NORVASC (amlodipine) 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 NORVASC to determine if it is the appropriate treatment for them.

NORVASC 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. NORVASC works by relaxing blood vessels, facilitating easier blood flow, and ultimately lowering blood pressure, which can reduce 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. NORVASC can help alleviate this pain.

Patients must inform their healthcare provider if they have a known allergy to amlodipine or any of the inactive ingredients in NORVASC. It is also essential to disclose all prescription and non-prescription medications being taken, including natural or herbal remedies. Patients should notify their doctor if they have a history of heart disease or liver problems. Additionally, those who are pregnant, planning to become pregnant, or breastfeeding should discuss this with their healthcare provider, as NORVASC can pass into breast milk.

NORVASC is typically taken once daily, with or without food. Patients may find it beneficial to take their dose at the same time each day, such as during breakfast, dinner, or at bedtime. They 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, patients should skip it and resume their regular dosing schedule. Patients can continue using nitroglycerin alongside NORVASC for angina but 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 hospital emergency room. Patients are advised not to start any new prescription or non-prescription medications or supplements without first consulting their healthcare provider.

Common side effects of NORVASC 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. Although rare, patients should be aware that starting NORVASC or increasing the dose may lead to a heart attack or worsening angina. If such symptoms occur, patients should contact their doctor immediately or go to the nearest hospital emergency room. Patients should report any side effects of concern to their healthcare provider, as this list does not encompass all possible side effects. For a complete list, patients should consult their doctor or pharmacist.

Patients should store NORVASC Tablets at room temperature (between 59° and 86°F), away from light, and out of reach of children. It should not be stored in the bathroom or in damp places. Patients should only use NORVASC as directed by their healthcare provider and should not share it with others, even if they exhibit similar symptoms, as it may be harmful to them.

For additional information about NORVASC, patients can consult their pharmacist or healthcare provider, or contact Viatris at 1-877-446-3679 (1-877-4-INFO-RX).

Storage and Handling

Bottles are supplied in tight, light-resistant containers as per USP standards. It is essential to store the bottles at a controlled room temperature, maintaining a range of 59° to 86°F (15° to 30°C) to ensure product stability and efficacy.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Norvasc as submitted by Viatris Specialty LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)