Norvadin (Tablets) Instructions for Use

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

A selective class II calcium channel blocker.

The antihypertensive effect is due to a direct relaxing influence on vascular smooth muscles.

It is assumed that the antianginal action of amlodipine is associated with its ability to dilate peripheral arterioles; this leads to a reduction in total peripheral vascular resistance, with no reflex tachycardia occurring.

As a result, the myocardial oxygen demand and the energy consumption of the heart muscle are reduced.

On the other hand, Amlodipine appears to cause dilation of large-caliber coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium.

This ensures the supply of oxygen to the myocardium during coronary artery spasms.

Pharmacokinetics

When taken orally, it is absorbed from the gastrointestinal tract slowly and almost completely; C_max in blood plasma is reached within 6-9 hours.

Protein binding is 95-98%.

It undergoes minimal metabolism during the “first pass” through the liver and slow but significant hepatic metabolism with the formation of metabolites with insignificant pharmacological activity.

T_1/2 averages 35 hours and in arterial hypertension can increase to an average of 48 hours, in elderly patients – up to 65 hours, and in cases of impaired liver function – up to 60 hours.

It is excreted mainly in the form of metabolites: 59-62% by the kidneys, 20-25% through the intestines.

Indications

Arterial hypertension (as monotherapy or as part of combination therapy).

Stable angina, unstable angina, Prinzmetal’s angina (as monotherapy or as part of combination therapy).

ICD codes

Dosage Regimen

For arterial hypertension and chronic stable angina, initiate therapy at 5 mg orally once daily.

For vasospastic angina, the recommended starting dose is 5 mg to 10 mg once daily.

Titrate the dose based on individual therapeutic response and tolerability.

The maximum recommended daily dose is 10 mg.

For geriatric patients or patients with hepatic impairment, initiate therapy at 2.5 mg once daily.

Use a 2.5 mg dose as the starting dose for small, fragile, or elderly patients.

Monitor patients closely during the titration period.

Dosage adjustment in patients with renal impairment is not usually required.

Administer the tablet with or without food. Swallow the tablet whole with a glass of water.

Do not crush or chew the tablets.

Adverse Reactions

From the cardiovascular system peripheral edema, tachycardia, skin hyperemia; when used in high doses – arterial hypotension, arrhythmias, shortness of breath.

From the digestive system nausea, abdominal pain; rarely – gingival hyperplasia.

From the CNS and peripheral nervous system headache, fatigue, drowsiness, dizziness; with long-term use – paresthesia.

Allergic reactions skin rash, itching.

Other with long-term use – limb pain.

Contraindications

Severe arterial hypotension (systolic BP less than 90 mm Hg); obstruction of the left ventricular outflow tract (including severe aortic stenosis); hemodynamically unstable heart failure after myocardial infarction; children and adolescents under 18 years of age (efficacy and safety not established); hypersensitivity to amlodipine and other dihydropyridine derivatives.

Use in Pregnancy and Lactation

The safety of amlodipine use during pregnancy has not been established, so use is only possible when the intended benefit to the mother outweighs the potential risk to the fetus.

There are no data indicating the excretion of amlodipine in breast milk. However, it is known that other slow calcium channel blockers (dihydropyridine derivatives) are excreted in breast milk. In this regard, if it is necessary to use amlodipine during lactation, the issue of discontinuing breastfeeding should be considered.

Use in Hepatic Impairment

Use with caution in cases of impaired liver function.

Use in Renal Impairment

Use with caution in cases of impaired renal function.

Pediatric Use

There are no clinical data on the use of amlodipine in pediatrics.

Geriatric Use

No dose reduction is required for elderly patients.

Special Precautions

Use with caution in patients with hepatic insufficiency, chronic heart failure of non-ischemic etiology NYHA functional class III-IV, unstable angina, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after it), sick sinus syndrome (severe tachycardia, bradycardia), arterial hypotension, and when used concomitantly with inhibitors or inducers of the CYP3A4 isoenzyme.

During the use of amlodipine in patients with chronic heart failure (NYHA class III and IV) of non-ischemic origin, an increased incidence of pulmonary edema was noted, despite the absence of signs of worsening heart failure.

In elderly patients, the T_1/2 of amlodipine may increase and its clearance may decrease. Dose adjustments are not required, but more careful monitoring of patients in this category is necessary.

The efficacy and safety of amlodipine use in hypertensive crisis have not been established.

Although calcium channel blockers do not have a withdrawal syndrome, it is advisable to discontinue treatment with amlodipine gradually.

There are no clinical data on the use of amlodipine in pediatrics.

Drug Interactions

It is possible to enhance the antianginal and antihypertensive effects of calcium channel blockers when used concomitantly with thiazide and “loop” diuretics, ACE inhibitors, beta-blockers, and nitrates, as well as to enhance their antihypertensive effect when used concomitantly with alpha₁-blockers, and antipsychotics.

Although a negative inotropic effect was usually not observed in studies of amlodipine, nevertheless, some calcium channel blockers may enhance the severity of the negative inotropic effect of antiarrhythmic agents that cause QT interval prolongation (for example, amiodarone and quinidine).

Concomitant multiple administration of amlodipine at a dose of 10 mg and simvastatin at a dose of 80 mg leads to a 77% increase in the bioavailability of simvastatin. In such cases, the simvastatin dose should be limited to 20 mg.

Antiviral drugs (e.g., ritonavir) increase the plasma concentrations of calcium channel blockers, including amlodipine.

With concomitant use of sympathomimetics and estrogens, a decrease in the antihypertensive effect is possible due to sodium retention in the body.

Antipsychotics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives. With concomitant use of agents for inhalation anesthesia, an enhancement of the hypotensive effect is possible.

With concomitant use of amiodarone, an enhancement of the antihypertensive effect is possible.

With concomitant use of lithium carbonate, manifestations of neurotoxicity are possible (including nausea, vomiting, diarrhea, ataxia, tremor, and/or tinnitus).

With concomitant use, orlistat reduces the antihypertensive effect of amlodipine, which can lead to a significant increase in BP and the development of a hypertensive crisis.

With concomitant use of indomethacin and other NSAIDs, a decrease in the antihypertensive effect of amlodipine is possible due to inhibition of prostaglandin synthesis in the kidneys and fluid retention under the influence of NSAIDs.

With concomitant use of quinidine, an enhancement of the antihypertensive effect is possible.

Calcium preparations may reduce the effect of calcium channel blockers.

With concomitant use of diltiazem (an inhibitor of the CYP3A4 isoenzyme) at a dose of 180 mg and amlodipine at a dose of 5 mg in elderly patients (from 69 to 87 years) with arterial hypertension, an increase in the bioavailability of amlodipine by 57% is noted. Concomitant use of amlodipine and erythromycin in healthy volunteers (from 18 to 43 years) does not lead to significant changes in amlodipine exposure (increase in AUC by 22%). Although the clinical significance of these effects is not entirely clear, they may be more pronounced in elderly patients. Potent inhibitors of the CYP3A4 isoenzyme (e.g., ketoconazole, itraconazole) may lead to an increase in the plasma concentration of amlodipine to a greater extent than diltiazem. Amlodipine and inhibitors of the CYP3A4 isoenzyme should be used with caution.

There are no data on the effect of inducers of the CYP3A4 isoenzyme on the pharmacokinetics of amlodipine. Blood pressure should be carefully monitored when amlodipine and inducers of the CYP3A4 isoenzyme are used concomitantly.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.