Cordi COR^® (Tablets) Instructions for Use

Marketing Authorization Holder

Actavis hf. (Iceland)

ATC Code

C08CA01 (Amlodipine)

Active Substance

Amlodipine (Rec.INN registered by WHO)

Dosage Forms

	Cordi COR®	Tablets 5 mg: 30 pcs.
		Tablets 10 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Tablets are round, white or almost white, with a score on one side and the marking “AB5” on the other side.

Excipients: microcrystalline cellulose – 111 mg, calcium hydrogen phosphate dihydrate – 56.7 mg, sodium carboxymethyl starch – 3.6 mg, magnesium stearate – 1.75 mg.

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

Tablets are round, white or almost white, with a score on one side and the marking “AB10” on the other side.

Excipients: microcrystalline cellulose – 222 mg, calcium hydrogen phosphate dihydrate – 113.4 mg, sodium carboxymethyl starch – 7.2 mg, magnesium stearate – 3.5 mg.

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

Clinical-Pharmacological Group

Calcium channel blocker. Antianginal and antihypertensive drug.

Pharmacotherapeutic Group

BMCC (Bone Mineral Crystal Complex)

Pharmacological Action

A dihydropyridine derivative – a second-generation slow calcium channel blocker, it has antianginal and antihypertensive effects. By binding to dihydropyridine receptors, it blocks calcium channels, reduces the transmembrane transition of calcium ions into the cell (more so in vascular smooth muscle cells than in cardiomyocytes).

The antianginal effect is due to the dilation of coronary and peripheral arteries and arterioles: in angina, it reduces the severity of myocardial ischemia; by dilating peripheral arterioles, it reduces total peripheral vascular resistance, reduces cardiac preload, and reduces myocardial oxygen demand. By dilating the main coronary arteries and arterioles in unchanged and ischemic areas of the myocardium, it increases oxygen supply to the myocardium (especially in vasospastic angina); prevents the development of coronary artery constriction (including that caused by smoking).

In patients with angina, a single daily dose increases exercise tolerance, slows the development of angina and ischemic ST-segment depression, and reduces the frequency of angina attacks and nitroglycerin consumption.

It has a long-term dose-dependent antihypertensive effect. The antihypertensive effect is due to a direct vasodilating effect on vascular smooth muscles. In arterial hypertension, a single dose provides a clinically significant reduction in blood pressure over 24 hours (in both supine and standing positions).

It does not cause a sharp decrease in blood pressure, a decrease in exercise tolerance, or a decrease in left ventricular ejection fraction. It reduces the degree of left ventricular myocardial hypertrophy, has an antiatherosclerotic and cardioprotective effect in coronary artery disease. It does not affect myocardial contractility and conduction, does not cause a reflex increase in heart rate, inhibits platelet aggregation, increases glomerular filtration rate, and has a weak natriuretic effect.

In diabetic nephropathy, it does not increase the severity of microalbuminuria. It does not have adverse effects on metabolism and plasma lipids.

The time to onset of effect is 2-4 hours, the duration of effect is 24 hours.

Pharmacokinetics

After oral administration, Amlodipine is slowly absorbed from the gastrointestinal tract. The mean absolute bioavailability is 64%, C_max in serum is observed after 6-9 hours. Steady state is reached after 7 days of therapy. Food does not affect the absorption of amlodipine.

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. Most of the drug in the blood (95%) is bound to plasma proteins. Amlodipine undergoes slow but extensive metabolism (90%) in the liver to form inactive metabolites, has a “first-pass” effect through the liver. Metabolites do not have significant pharmacological activity. After a single oral dose, T_1/2 ranges from 31 to 48 hours, with repeated administration T_1/2 is approximately 45 hours. About 60% of the orally administered dose is excreted in the urine, mainly as metabolites, 10% unchanged, and 20-25% in feces, as well as in breast milk. The total clearance of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 L/h/kg).

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

In patients with hepatic impairment, a prolongation of T_1/2 is expected, and with long-term administration, the accumulation of the drug in the body will be higher (T_1/2 60 hours).

Renal impairment does not significantly affect the kinetics of amlodipine. The drug crosses the blood-brain barrier. It is not removed by hemodialysis.

Indications

• Arterial hypertension (monotherapy or in combination with other antihypertensive agents);
• Stable exertional angina, vasospastic angina (Prinzmetal’s angina).

ICD codes

Dosage Regimen

Orally, the initial dose for treatment of arterial hypertension and angina is 5 mg of the drug once a day. The dose can be increased to a maximum of 10 mg once a day. For arterial hypertension, the maintenance dose may be 5 mg/day.

For stable exertional angina (vasospastic angina) — 5-10 mg once a day.

No dose adjustment is required when taken concomitantly with thiazide diuretics, beta-blockers and ACE inhibitors.

No dose adjustment is required in patients with renal impairment.

Adverse Reactions

From the cardiovascular system palpitations, shortness of breath, marked decrease in blood pressure, fainting, vasculitis, edema (swelling of the ankles and feet), flushing; rarely – arrhythmias (bradycardia, ventricular tachycardia, atrial flutter), chest pain, orthostatic hypotension; very rarely – development or worsening of heart failure, extrasystole, migraine.

From the central and peripheral nervous system headache, dizziness, fatigue, drowsiness, mood changes, convulsions; rarely – loss of consciousness, hypoesthesia, 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 levels of liver transaminases and jaundice (due to cholestasis), pancreatitis, dry mouth, flatulence, gingival hyperplasia, constipation or diarrhea; very rarely – gastritis, increased appetite.

From the urinary system rarely – pollakiuria, painful urge to urinate, nocturia, sexual dysfunction (including decreased potency); very rarely – dysuria, polyuria.

From the skin very rarely – xeroderma, alopecia, dermatitis, 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, diplopia, conjunctivitis, eye pain, tinnitus, back pain, dyspnea, nosebleed, increased sweating, thirst; very rarely – cold clammy sweat, cough, rhinitis, parosmia, taste disturbance, accommodation disturbance, xerophthalmia.

Contraindications

• Hypersensitivity to amlodipine and other dihydropyridine derivatives;
• Severe arterial hypotension;
• Collapse, cardiogenic shock;
• Unstable angina (except for Prinzmetal’s angina);
• Pregnancy and lactation;
• Age under 18 years (efficacy and safety have not been established).

With caution impaired liver function, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure in the stage of decompensation, mild or moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), diabetes mellitus, impaired lipid profile, elderly age.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Use with caution in case of impaired liver function.

Pediatric Use

The efficacy and safety of the drug in children under 18 years of age have not been established.

Geriatric Use

Use with caution in the elderly.

Special Precautions

During treatment, 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). 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 calcium channel blockers do not have a withdrawal syndrome, it is recommended to gradually reduce the doses before discontinuing treatment.

Amlodipine does not affect plasma concentrations of potassium ions, glucose, triglycerides, total cholesterol, LDL, uric acid, creatinine and blood urea nitrogen.

Effect on ability to drive vehicles and operate machinery

There have been no reports of the effect of amlodipine on driving or operating machinery. Nevertheless, some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. If they occur, the patient should take special precautions when driving and operating machinery.

Overdose

Symptoms marked decrease in blood pressure, 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 limbs, monitoring of circulating blood volume and diuresis. To restore vascular tone – use of vasoconstrictor drugs (if there are no 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 concentration of amlodipine in plasma, increasing the risk of side effects, and inducers of liver microsomal enzymes decrease it.

The hypotensive effect is weakened by NSAIDs, especially indomethacin (sodium retention and blockade of prostaglandin synthesis by the kidneys), alpha-adrenergic stimulants, estrogens (sodium retention), sympathomimetics.

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

Amiodarone, quinidine, alpha₁-blockers, antipsychotic drugs (neuroleptics) and slow calcium channel blockers may enhance the hypotensive 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, it is possible to enhance the manifestations of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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 effect of amlodipine.

Storage Conditions

In a dry, light-protected place, out of the reach of children, at a temperature not exceeding 30°C (86°F).

Shelf Life

The shelf life is 2 years. Do not use after the expiration date printed on the package.

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.