Vero-Amlodipine (Tablets) Instructions for Use

Marketing Authorization Holder

Veropharm, JSC (Russia)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Vero-Amlodipine	Tablets 5 mg: 10 or 30 pcs.
		Tablets 10 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Tablets white or white with a creamy tint, round, flat-cylindrical in shape; the presence of “marbling” is allowed.

Excipients: calcium hydrogen phosphate dihydrate – 53 mg, potato starch – 32 mg, sodium starch glycolate type A – 3 mg, microcrystalline cellulose (type 102) – 3.57 mg, colloidal silicon dioxide – 0.5 mg, magnesium stearate – 1 mg.
* tablet weight 100 mg

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.

Tablets white or white with a creamy tint, round, flat-cylindrical in shape; the presence of “marbling” is allowed.

Excipients: calcium hydrogen phosphate dihydrate – 106 mg, potato starch – 64 mg, sodium starch glycolate type A – 6 mg, microcrystalline cellulose (type 102) – 7.14 mg, colloidal silicon dioxide – 1 mg, magnesium stearate – 2 mg.
* tablet weight 200 mg

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

“Slow” calcium channel blocker

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 related to 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 slowly and almost completely from the gastrointestinal tract; 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 may increase to an average of 48 hours, in elderly patients – up to 65 hours, and in patients with impaired liver function – up to 60 hours.

It is excreted mainly as metabolites: 59-62% by the kidneys, 20-25% via the intestine.

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 adults, take the initial dose of 5 mg once daily.

If necessary, increase the dose. The maximum daily dose is 10 mg.

For small or fragile patients, initiate therapy at 2.5 mg once daily.

In patients with hepatic impairment, use a lower initial dose and titrate cautiously.

No dose adjustment is required for renal impairment or elderly patients.

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

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

Dose titration should proceed over 7 to 14 days based on clinical response.

For angina, the typical maintenance dose is 5 mg to 10 mg once daily.

For hypertension, the typical maintenance dose is 2.5 mg to 10 mg once daily.

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

Adverse Reactions

From the cardiovascular system: peripheral edema, tachycardia, skin flushing; 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 on 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 patients with impaired liver function.

Use in Renal Impairment

Use with caution in patients with 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 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

The antianginal and antihypertensive effects of slow calcium channel blockers may be enhanced when used concomitantly with thiazide and “loop” diuretics, ACE inhibitors, beta-blockers, and nitrates, and their antihypertensive effect may be enhanced when used concomitantly with alpha₁-blockers, and antipsychotics.

Although negative inotropic effects were not usually observed in studies of amlodipine, some calcium channel blockers may enhance the negative inotropic effect of antiarrhythmic drugs that cause QT interval prolongation (e.g., amiodarone and quinidine).

Concomitant multiple administration of amlodipine 10 mg and simvastatin 80 mg leads to a 77% increase in the bioavailability of simvastatin. 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.

Concomitant use with sympathomimetics and estrogens may reduce the antihypertensive effect due to sodium retention in the body.

Antipsychotics and isoflurane enhance the antihypertensive effect of dihydropyridine derivatives. Concomitant use with inhalation anesthetics may enhance the hypotensive effect.

Concomitant use with amiodarone may enhance the antihypertensive effect.

Concomitant use with lithium carbonate may lead to manifestations of neurotoxicity (including nausea, vomiting, diarrhea, ataxia, tremor and/or tinnitus).

Concomitant use with orlistat reduces the antihypertensive effect of amlodipine, which may lead to a significant increase in BP and the development of a hypertensive crisis.

Concomitant use with indomethacin and other NSAIDs may reduce the antihypertensive effect of amlodipine due to inhibition of prostaglandin synthesis in the kidneys and fluid retention under the influence of NSAIDs.

Concomitant use with quinidine may enhance the antihypertensive effect.

Calcium supplements may reduce the effect of calcium channel blockers.

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 (69 to 87 years) with arterial hypertension leads to a 57% increase in the bioavailability of amlodipine.

Concomitant use of amlodipine and erythromycin in healthy volunteers (18 to 43 years) does not lead to significant changes in amlodipine exposure (22% increase in AUC). Although the clinical significance of these effects is not fully understood, 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 30°C (86°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.