Amlodivel (Tablets) Instructions for Use

Marketing Authorization Holder

Velpharm, LLC (Russia)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Amlodivel	Tablets 5 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42, 50, 56, 60, 70, 80, 90 or 100 pcs.
		Tablets 10 mg: 7, 10, 14, 20, 21, 28, 30, 40, 42, 50, 56, 60, 70, 80, 90 or 100 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, flat-cylindrical, with a bevel; marbling is allowed.

Excipients: lactose monohydrate (milk sugar), microcrystalline cellulose, crospovidone (Kollidon CL, Kollidon CL-M), colloidal silicon dioxide (aerosil), talc, calcium stearate.

7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (7) – cardboard packs.
10 pcs. – contour cell packaging (8) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (3) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – polymer jars (1) – cardboard packs.
20 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.

Tablets white or almost white, round, flat-cylindrical, with a bevel; marbling is allowed.

Excipients: lactose monohydrate (milk sugar), microcrystalline cellulose, crospovidone (Kollidon CL, Kollidon CL-M), colloidal silicon dioxide (aerosil), talc, calcium stearate.

7 pcs. – contour cell packaging (1) – cardboard packs.
7 pcs. – contour cell packaging (2) – cardboard packs.
7 pcs. – contour cell packaging (3) – cardboard packs.
7 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (5) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (7) – cardboard packs.
10 pcs. – contour cell packaging (8) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
14 pcs. – contour cell packaging (1) – cardboard packs.
14 pcs. – contour cell packaging (2) – cardboard packs.
14 pcs. – contour cell packaging (3) – cardboard packs.
14 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – polymer jars (1) – cardboard packs.
20 pcs. – polymer jars (1) – cardboard packs.
30 pcs. – polymer jars (1) – cardboard packs.

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 effect on vascular smooth muscles.

The antianginal action of amlodipine is presumably associated with its ability to dilate peripheral arterioles; this leads to a decrease in total peripheral vascular resistance, without causing reflex tachycardia. 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 coronary arteries and coronary arterioles in both intact and ischemic areas of the myocardium. This ensures the supply of oxygen to the myocardium during spasms of the coronary arteries.

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 to form metabolites with insignificant pharmacological activity.

T_1/2 averages 35 hours and in arterial hypertension can increase on average to 48 hours, in elderly patients – up to 65 hours, and in liver function disorders – 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

Take the tablet once daily at the same time each day, with or without food.

Swallow the tablet whole with a glass of water; do not crush or chew.

For arterial hypertension and chronic stable angina, the initial adult dose is 5 mg once daily.

For vasospastic angina (Prinzmetal’s), the initial adult dose is 5 mg once daily.

For unstable angina, use as part of a comprehensive treatment regimen; initial dose is 5 mg once daily.

Based on individual therapeutic response and tolerability, the dose may be increased.

The maximum recommended daily dose is 10 mg.

Dose titration should proceed gradually, with increases typically occurring at 7 to 14-day intervals.

For geriatric patients or patients with hepatic impairment, initiate therapy at 2.5 mg (half a 5 mg tablet) once daily.

Use caution when increasing the dose in these patient populations due to a potentially prolonged elimination half-life.

For renal impairment, no initial dose adjustment is typically required; monitor clinical response.

Do not abruptly discontinue therapy; taper the dose gradually under medical supervision.

The safety and efficacy in pediatric patients under 18 years have not been established.

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 if 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 decided.

Use in Hepatic Impairment

Use with caution in liver function disorders.

Use in Renal Impairment

Use with caution in renal function disorders.

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, with simultaneous use 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 clearance may decrease. Dose changes 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, 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 drugs that cause QT interval prolongation (for example, amiodarone and quinidine).

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

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

With simultaneous use of sympathomimetics, 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 simultaneous use of inhalation anesthetics, an enhancement of the hypotensive effect is possible.

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

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

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

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

Calcium preparations may reduce the effect of calcium channel blockers.

With simultaneous 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 amlodipine plasma concentrations 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.