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, with an empirical formula of C20H25ClN2O5 • C6H6O3S and a molecular weight of 567.1. The compound appears as a white crystalline powder, which is slightly soluble in water and sparingly soluble in ethanol.

NORVASC Tablets are formulated for oral administration and are available in strengths of 2.5 mg, 5 mg, and 10 mg of amlodipine. Each tablet contains inactive ingredients including 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%.

There are no teratogenic or nonteratogenic effects associated with 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 dosing regimen is tailored to the individual patient's needs, taking into account their specific health status and response to treatment.

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 a history of hypersensitivity to 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 individuals with known sensitivity to amlodipine may also experience adverse reactions.

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 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 of age has not been established. Caution is advised when considering treatment in this younger population due to the lack of data.

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, 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 recognize 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 the number of 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 baseline 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 maternal 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

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

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 peripheral vasodilation, resulting in pronounced hypotension and potentially reflex tachycardia. Clinical experience with intentional overdosage of NORVASC 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. Frequent blood pressure assessments are crucial. Should hypotension manifest, cardiovascular support should be provided, which includes elevating the extremities and judiciously administering fluids. If hypotension persists despite these conservative measures, 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 NORVASC, hemodialysis is unlikely to be effective in managing an 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 receiving treatment 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

Postmarketing experience has revealed infrequent reports of gynecomastia, 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 have also been reports suggesting a possible association between extrapyramidal disorder and amlodipine. 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 be advised to read the provided information carefully before starting NORVASC (amlodipine) 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 healthcare provider. Patients are encouraged to ask their doctor any questions they may have regarding NORVASC and to confirm whether it is the appropriate treatment for their condition.

NORVASC is classified as a calcium channel blocker (CCB) and is indicated for the treatment of high blood pressure (hypertension) and a type of chest pain known as angina. It can 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 the walls of blood vessels. NORVASC works 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 supply to the heart, NORVASC can help alleviate this pain, which may manifest as a pressing or squeezing sensation in the chest, shoulders, arms, neck, jaws, or back.

Patients should be informed that NORVASC is contraindicated in individuals who are allergic to amlodipine or any of the inactive ingredients. It is crucial for patients to disclose their complete medication history, including prescription and non-prescription drugs, as well as any natural or herbal remedies, to their healthcare provider. They should specifically inform their doctor if they have a history of heart disease or liver problems, if they are pregnant or planning to become pregnant, or if they are breastfeeding, as NORVASC can pass into breast milk.

Patients should take NORVASC once daily, with or without food, and it may be beneficial to take it at the same time each day, such as with breakfast or dinner, or at bedtime. They should not exceed one dose at a time and should take a missed dose 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 safely use nitroglycerin alongside NORVASC for angina; however, they should not discontinue nitroglycerin without consulting their healthcare provider. It is also important for patients to continue taking other prescribed medications, including other blood pressure medications, unless directed otherwise by 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 should be made aware of potential side effects associated with NORVASC, which may include mild to moderate symptoms such as swelling of the legs or ankles, tiredness, stomach pain, nausea, dizziness, flushing, arrhythmia, heart palpitations, and abnormal muscle movements. Although rare, patients should be informed that they may experience a heart attack or worsening angina when starting NORVASC or increasing the dose. If such symptoms occur, they should contact their doctor or go to the emergency room immediately. Patients should also be encouraged to report any side effects they experience to their healthcare provider, as this list does not encompass all possible side effects.

Storage instructions should be communicated to patients, advising them to keep NORVASC out of reach of children, store it at room temperature (between 59° and 86°F), protect it from light, and avoid storing it in the bathroom or in damp places.

Finally, patients should be reminded that NORVASC should only be used as prescribed by their healthcare provider and should not be shared with others, even if they exhibit similar symptoms. For additional information, patients can consult their pharmacist or healthcare provider, visit the Pfizer website, or call the provided contact number.

Storage and Handling

Bottles should be stored at a controlled room temperature ranging from 59° to 86°F (15° to 30°C). It is essential to dispense the product in tight, light-resistant containers that comply with United States Pharmacopeia (USP) standards to ensure optimal 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 PFIZER LABORATORIES DIV PFIZER INC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)