Amlokard-sanovel (Tablets) Instructions for Use

Marketing Authorization Holder

Sanovel Pharmaceutical Products Ind., Inc. (Turkey)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Amlokard-sanovel	Tablets 5 mg: 30 pcs.
		Tablets 10 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Tablets white or almost white, round, biconvex, with a score on one side.

Excipients: microcrystalline cellulose – 124.065 mg, calcium phosphate dihydrate – 63 mg, sodium carboxymethyl starch – 4 mg, magnesium stearate – 2 mg.

10 pcs. – blisters (3) – cardboard packs.

Tablets white or almost white, round, biconvex, with a score on one side.

Excipients: microcrystalline cellulose – 248.13 mg, calcium phosphate dihydrate – 126 mg, sodium carboxymethyl starch – 8 mg, magnesium stearate – 4 mg.

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

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 delivery 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 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 cases of impaired liver function – up to 60 hours.

It is excreted mainly as 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 adults, take the initial dose of 5 mg once daily.

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

For small or fragile patients, or those with hepatic impairment, initiate therapy at 2.5 mg once daily.

Dosage adjustment is not typically required for elderly patients or those with renal impairment.

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

Do not crush or chew the tablets; swallow them whole.

The score line is for dividing the tablet to aid in swallowing and not for dividing into equal doses.

For patients with unstable angina, begin treatment under close medical supervision.

Regularly monitor blood pressure and clinical response during dose titration.

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 central 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 possible only 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 changes 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 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 a negative inotropic effect was not usually observed in studies of amlodipine, nevertheless, 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 of 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 of orlistat reduces the antihypertensive effect of amlodipine, which can lead to a significant increase in blood pressure and the development of a hypertensive crisis.

Concomitant use of 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 preparations 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 (from 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 (from 18 to 43 years) does not lead to significant changes in amlodipine exposure (AUC increase by 22%). 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 CYP3A4 isoenzyme inhibitors 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.