EsCordi Cor (Tablets) Instructions for Use

Marketing Authorization Holder

Emcure Pharmaceuticals, Ltd. (India)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Levamlodipine (Rec.INN registered by WHO)

Dosage Forms

	EsCordi Cor	Tablets 2.5 mg: 30 or 50 pcs.
		Tablets 5 mg: 30 or 50 pcs.

Dosage Form, Packaging, and Composition

Tablets flat, light yellow with specks, heart-shaped with beveled edges, with the inscription “A” on one side and “2.5” on the other.

Excipients: microcrystalline cellulose – 50 mg, lactose – 41.427 mg, colloidal silicon dioxide – 1.4 mg, magnesium stearate – 4.2 mg, croscarmellose sodium – 4.2 mg, yellow iron oxide – 0.14 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Tablets flat, yellow with specks, heart-shaped with beveled edges, with the inscription “A” on one side and “5” on the other.

Excipients: microcrystalline cellulose – 46.367 mg, lactose – 40.767 mg, colloidal silicon dioxide – 1.4 mg, magnesium stearate – 4.2 mg, croscarmellose sodium – 4.2 mg, yellow iron oxide – 0.8 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Clinical-Pharmacological Group

Calcium channel blocker

Pharmacotherapeutic Group

Calcium channel blockers; selective calcium channel blockers with predominant vascular action; dihydropyridine derivatives

Pharmacological Action

A slow calcium channel blocker, a dihydropyridine derivative. The S(-) isomer has a more pronounced pharmacological action than R(+) amlodipine. It has antianginal and antihypertensive effects. By binding to dihydropyridine receptors, S(-) amlodipine is more potent compared to the R(+) isomer, blocks calcium channels, and reduces the transmembrane transition of calcium ions into the cell (more so in vascular smooth muscle cells than in cardiomyocytes).

It exerts a long-term, dose-dependent antihypertensive effect. The antihypertensive action is due to a direct vasodilating effect on vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction in BP for 24 hours (in the supine and standing positions). The onset of action is 2-4 hours, and the duration of the effect is 24 hours.

Pharmacokinetics

Absorption and Distribution

After oral administration (single dose of 2.5 mg), S(-) amlodipine is absorbed from the gastrointestinal tract. The mean absolute bioavailability is 65%. C_max in blood serum (8.30±1.071 ng/ml) is observed after 2.73±0.88 hours. C_ss is achieved after 7 days of therapy. Food intake does not affect the absorption of S(-) amlodipine. Plasma protein binding is 93%. The mean V_d is 21 L/kg of body weight, indicating that most of the drug is in the tissues, and a relatively smaller part is in the blood. The drug penetrates the BBB.

Metabolism

S(-) amlodipine undergoes slow but extensive metabolism (90%) in the liver to form inactive metabolites. It undergoes a significant first-pass effect through the liver. Metabolites do not possess significant pharmacological activity.

Excretion

After a single oral dose, T_1/2 ranges from 14.62 to 68.88 hours. With repeated administration, T_1/2 is approximately 45 hours. About 60% of the orally administered dose is excreted by the kidneys, mainly as metabolites; 10% – unchanged, and 20-25% through the intestines, as well as with breast milk. The total clearance of S(-) amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 L/h/kg).

Pharmacokinetics in Special Clinical Cases

In elderly patients (over 65 years), the elimination of S(-) amlodipine is slowed (T_1/2 – about 65 hours) compared to younger patients, but this difference is not clinically significant.

Prolongation of T_1/2 in patients with hepatic impairment suggests that with long-term use, the accumulation of the drug in the body will be higher (T_1/2 – up to 60 hours).

Renal impairment does not significantly affect the pharmacokinetics of S(-) amlodipine.

S(-) amlodipine is not removed by hemodialysis.

Indications

• Stage I (mild) arterial hypertension (in combination with other antihypertensive agents or as monotherapy).

ICD codes

Dosage Regimen

Initiate treatment with a 2.5 mg dose taken once daily.

The maximum recommended dose is 5 mg once daily.

Titrate the dose gradually, increasing to the next strength only if the therapeutic response is inadequate.

Dosage adjustment is not typically required based on age alone; however, monitor elderly patients closely during titration.

Administer the tablet with or without food; food intake does not significantly affect absorption.

For patients with hepatic impairment, use with caution and consider a lower initial dose due to prolonged elimination half-life and potential for increased systemic exposure.

No dosage adjustment is required for patients with renal impairment.

Adhere to a consistent daily dosing schedule.

Do not abruptly discontinue therapy; a gradual dose reduction is recommended prior to cessation.

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

Adverse Reactions

From the cardiovascular system palpitations, dyspnea, marked decrease in BP, fainting, vasculitis, edema (swelling of the ankles and feet), facial flushing; rarely – arrhythmia (bradycardia, ventricular tachycardia, atrial fibrillation), chest pain, orthostatic hypotension; very rarely – development or worsening of heart failure, migraine.

From the central and peripheral nervous system: dizziness, headache, fatigue, drowsiness, mood changes; rarely – convulsions, loss of consciousness, hyperesthesia, nervousness, paresthesia, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams; very rarely – ataxia, apathy, agitation, amnesia.

From the digestive system: nausea, vomiting, epigastric pain; rarely – increased activity of liver enzymes, jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation, diarrhea; very rarely – gastritis, increased appetite, taste perversion.

From the genitourinary system: rarely – pollakiuria, painful urge to urinate, nocturia, decreased potency; very rarely – dysuria, polyuria.

From the skin: very rarely – xeroderma, alopecia, dermatitis, purpura, skin discoloration.

Allergic reactions: skin itching, rash (including erythematous, maculopapular rash, urticaria), angioedema.

From the musculoskeletal system: rarely – arthralgia, arthrosis, myalgia (with long-term use); very rarely – myasthenia.

Other rarely – gynecomastia, polyuricemia, increase/decrease in body weight, thrombocytopenia, leukopenia, hyperglycemia, visual impairment, conjunctivitis, diplopia, eye pain, tinnitus, back pain, dyspnea, epistaxis, increased sweating, thirst; very rarely – cold clammy sweat, cough, rhinitis, parosmia, accommodation disturbance, xerophthalmia.

Contraindications

• Hypersensitivity to S(-) amlodipine and other dihydropyridine derivatives;
• Prinzmetal’s angina;
• Severe arterial hypotension;
• Collapse;
• Cardiogenic shock;
• Pregnancy;
• Lactation period (breastfeeding);
• Age under 18 years (efficacy and safety not established).

With caution: impaired liver function, SSS (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology in the stage of decompensation, moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), diabetes mellitus, impaired lipid profile, elderly patients.

Use in Pregnancy and Lactation

The use of the drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

The drug should be prescribed with caution in case of impaired liver function.

Pediatric Use

The use of the drug is contraindicated in children and adolescents under 18 years of age (efficacy and safety not established).

Geriatric Use

The drug should be used with caution in elderly patients.

Special Precautions

During treatment with EsCordi Cor, it is necessary to control body weight and sodium intake, and prescribe an appropriate diet. It is necessary to maintain dental hygiene and visit the dentist frequently (to prevent soreness, bleeding, and gingival hyperplasia).

In elderly patients, T_1/2 and clearance of the drug may be prolonged. The dosage regimen for the elderly is the same as for patients of other age groups. When increasing the dose, careful monitoring of elderly patients is necessary.

Although slow calcium channel blockers do not have a “withdrawal” syndrome, it is recommended to gradually reduce the dose before discontinuing treatment.

Effect on the ability to drive vehicles and operate machinery

Some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. If they occur, special precautions should be observed when driving a car and working with machinery.

Overdose

Symptoms excessive decrease in BP, tachycardia, excessive peripheral vasodilation.

Treatment: gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, monitoring of heart and lung function parameters, elevated position of the lower extremities, control of circulating blood volume and diuresis. To restore vascular tone – use of vasoconstrictors (in the absence of contraindications to their use). To eliminate the consequences of calcium channel blockade – intravenous administration of calcium gluconate. Hemodialysis is not effective.

Drug Interactions

Inhibitors of microsomal oxidation increase the plasma concentration of amlodipine, increasing the risk of side effects, while inducers of hepatic microsomal enzymes decrease it.

The antihypertensive effect is weakened by alpha-adrenergic stimulants, estrogens (sodium retention), and sympathomimetics.

Thiazide and “loop” diuretics, beta-blockers, verapamil, ACE inhibitors, and nitrates enhance the antianginal and antihypertensive effects.

Amiodarone, quinidine, alpha₁-blockers, antipsychotic agents (neuroleptics), and slow calcium channel blockers may enhance the antihypertensive effect.

It does not affect the pharmacokinetic parameters of digoxin and warfarin.

Cimetidine does not affect the pharmacokinetics of amlodipine.

When used concomitantly with lithium preparations, an increase in their neurotoxicity manifestations (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus) is possible.

Calcium preparations may reduce the effect of slow calcium channel blockers.

Procainamide, quinidine, and other drugs that cause QT interval prolongation enhance the negative inotropic effect and may increase the risk of significant QT interval prolongation.

Grapefruit juice may reduce the plasma concentration of amlodipine, but this reduction is so small that it does not significantly change the action of amlodipine.

Storage Conditions

The drug should be stored out of the reach of children, in a dry place at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.