EsCordi Cor, tablets 5 mg 30 pcs

Pharmacotherapeutic group:

Slow calcium channel blocker

ATH CODE : C08CA01

Pharmacological Properties

S (-) amlodipine is the pharmacologically active isomer of amlodipine.

Pharmacodynamics

A dihydropyridine derivative is a “slow” calcium channel blocker, S (-) isomer is highlighted because it has a more pronounced pharmacological effect than R (+) amlodipine. It has antianginal and hypotensive effects. Binding to dihydropyridine receptors S (-) amlodipine is more potent compared to R (+) isomer, blocks calcium channels, reduces transmembrane transition of calcium ions into the cell (more in vascular smooth muscle cells than in cardiomyocytes).

It has a long-term dose-dependent hypotensive effect. The hypotensive effect is due to the direct vasodilating effect on the vascular smooth muscles. In arterial hypertension, a single dose provides clinically significant reduction of arterial pressure (BP) for 24 hours (in patient’s “lying” and “standing” positions). Time of onset of effect is 2-4 hours, duration of effect is 24 hours.

Pharmacokinetics:

After oral administration (single dose of 2.5 mg), S(-) amlodipine is absorbed from the gastrointestinal tract. Mean absolute bioavailability is 65%, maximum serum concentration (8.30 +/- 1.071 ng/ml) is observed after 2.73 +/- 0.88 hours. The equilibrium concentration is reached after 7 days of therapy. Food intake has no effect on the absorption of S (-) amlodipine. The average volume of distribution is 21 l/kg body weight, indicating that most of the drug is in the tissues and relatively less in the blood. Most of the drug that is in the blood (93%) is bound to plasma proteins. S (-) Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites, has a “first pass” effect through the liver. Metabolites have no significant pharmacological activity. After a single oral administration, the elimination half-life (T1/2) varies from 14.62 to 68.88 hours, with a repeated administration T1/2 of approximately 45 hours. About 60% of the oral dose is excreted by the kidneys mainly as metabolites, 10% unchanged, and 20-25% through the intestine, as well as with the breast milk. Total clearance S(-) of amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg). Elevation of S(-) amlodipine is slower (T >/, 65 h) in elderly patients (over 65 years) compared to younger patients, but this difference is not clinically relevant. The prolonged T1/2 in patients with hepatic insufficiency suggests that the accumulation of the drug in the body will be higher (T1/2 up to 60 h) with long-term administration. Renal insufficiency has no significant effect on the kinetics of S (-)amlodipine. The drug penetrates through the blood-brain barrier. It is not eliminated by hemodialysis.

Indications

Active ingredient

Composition

Tablets 5 mg:

Active substance:

S(-)amlodipine besilate converted to S(-)amlodipine 5 mg

Auxiliary substances: 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; iron oxide yellow 0.8 mg.

How to take, the dosage

Interaction

Microsomal oxidation inhibitors increase the plasma concentration of amlodipine, increasing the risk of side effects, and microsomal liver enzyme inducers decrease it.

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

Tiazide and “loop” diuretics, beta-adrenoblockers,
verapamil, angiotensin-converting enzyme (ACE) inhibitors and nitrates enhance antianginal and hypotensive effects.

Amiodarone, quinidine, alpha1-adrenoblockers, antipsychotics (neuroleptics) and slow calcium channel blockers may increase the hypotensive effect.

It has no effect on the pharmacokinetic parameters of digoxin and warfarin.
Cimetidine does not affect the pharmacokinetics of amlodipine.

In co-administration with lithium preparations there may be increased appearance of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

Calcium preparations may decrease the effect of “slow” calcium channel blockers.

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

Grapefruit juice may decrease the plasma concentration of amlodipine, but this decrease is so small that it does not significantly alter the effect of amlodipine.

Special Instructions

At the time of treatment with EsCordi Cor it is necessary to control body weight and sodium intake, prescribing an appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (prevention of soreness, bleeding and overgrowth of gums). The elimination half-life and clearance of the drug may be prolonged in elderly patients. Dosing regimen for the elderly is the same as for patients in other age groups. Careful monitoring of elderly patients is necessary when increasing the dose. Although slow calcium channel blockers have no “withdrawal” syndrome, a gradual reduction in doses is recommended before discontinuing treatment.

Influence on driving and operating ability

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.

Synopsis

Contraindications

– Hypersensitivity to S(-)amlodipine and other dihydropyridine derivatives;

– Prinzmetal angina;

– severe arterial hypotension;

– collapse, cardiogenic shock;

-pregnancy and lactation;

– age less than 18 years (efficacy and safety not established).

With caution:

.Impaired liver function, sinus node weakness syndrome (marked bradycardia, tachycardia), chronic heart failure of nonischemic etiology in decompensation stage, moderate degree of arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), diabetes mellitus, lipid profile disorders, advanced age.

Side effects

Cardiovascular system: palpitations, shortness of breath, marked BP decrease, fainting, vasculitis, edema (swollen ankles and feet), “flushes” of blood to the face, rarely – arrhythmias (bradycardia, ventricular tachycardia, atrial fibrillation), chest pain, orthostatic hypotension, very rarely – development or aggravation of heart failure, migraine.

Central nervous system: dizziness, headache, fatigue, somnolence, mood changes; rarely – seizures loss of consciousness, hypersthesia, nervousness, parasthesias, tremor, vertigo, asthenia, malaise, insomnia, depression, unusual dreams, very rarely – ataxia, apathy, agitation, amnesia.

Digestive system disorders: nausea, vomiting, epigastric pain; rarely – increased liver enzymes and jaundice (caused by cholestasis), pancreatitis, dry mouth, flatulence, gum hyperplasia, constipation or diarrhea; very rarely – gastritis, increased appetite, violation of sense of taste.

Urogenital system disorders: rarely – pollakiuria, painful urge to urinate, nycturia, decreased potency; very rarely – dysuria, polyuria.

Skin: very rare – xeroderma, alopecia, dermatitis, purpura, changes in skin color.

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

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

Others: rare – gynecomastia, polyuricemia, weight gain/decrease, thrombocytopenia, leukopenia, hyperglycemia, visual disturbances, conjunctivitis, diplopia, eye pain, tinnitus, back pain, dyspnea, nosebleed, increased sweating, thirst; very rare – cold sticky sweat, cough, rhinitis, parasmia, accommodation disorders, xerophthalmia.

Overdose

Symptoms: marked BP decrease, tachycardia, excessive peripheral vasodilation.

Treatment: gastric lavage, administration of activated charcoal, maintenance of cardiovascular function, control of heart and lung function parameters, elevation of extremities, control of circulating blood volume and diuresis. To restore vascular tone – use vasoconstrictors (if there are no contraindications for their use); to eliminate the effects of calcium channel blockade – intravenous administration of calcium gluconate.

Hemodialysis is not effective.