EsCordi Cor, tablets 2.5mg 30 pcs

Pharmacotherapeutic group:

Slow calcium channel blocker

ATX CODE : C08CA01

Pharmacological Properties

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

Pharmacodynamics

Dihydropyridine derivative – “slow” calcium channel blocker, S (-) isomer is highlighted because it has a more pronounced pharmacological action 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 transfer 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 “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. The average absolute bioavailability is 65%, the maximum serum concentration (8.30 +/- 1.071 ng/ml) is observed after 2.73 +/- 0.88 hours. 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

Arterial hypertension of the 1st degree (mild severity) (in monotherapy or in combination with other antihypertensive drugs).

Pharmacological effect

PHARMACOTHERAPEUTIC GROUP:

Blocker of “slow” calcium channels

ATX CODE: C08CA01

PHARMACOLOGICAL PROPERTIES

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

Pharmacodynamics

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

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

Pharmacokinetics:

After oral administration (single dose of 2.5 mg), S(-) amlodipine is absorbed from the gastrointestinal tract. The average absolute bioavailability is 65%, the maximum serum concentration (8.30 +/- 1.071 ng/ml) is observed after 2.73 +/- 0.88 hours. Equilibrium concentration is achieved after 7 days of therapy. Food intake does not affect the absorption of S (-) amlodipine. The mean volume of distribution is 21 L/kg body weight, indicating that most of the drug is in the tissues and a relatively smaller portion is in the blood. Most of the drug in the blood (93%) binds to blood plasma proteins. S (-) Amlodipine undergoes slow but extensive metabolism (90%) in the liver with the formation of inactive metabolites and has a “first pass” effect through the liver. Metabolites do not have significant pharmacological activity. After a single oral dose, the half-life (T1/2) varies from 14.62 to 68.88 hours; with repeated administration, T1/2 is approximately 45 hours. About 60% of the dose taken orally is excreted by the kidneys, mainly in the form of metabolites, 10% unchanged, and 20-25% through the intestines, as well as in breast milk. The total clearance of S(-) amlodipine is 0.116 ml/s/kg (7 ml/min/kg, 0.42 l/h/kg). In elderly patients (over 65 years of age), the elimination of S(-) amlodipine is slowed down (T>/, 65 hours) compared to young patients, but this difference is not clinically significant. Prolongation of T1/2 in patients with liver failure suggests that with long-term administration, the accumulation of the drug in the body will be higher (T1/2 up to 60 hours). Renal failure does not significantly affect the kinetics of S(-)amlodipine. The drug penetrates the blood-brain barrier. It is not removed by hemodialysis.

Special instructions

During treatment with EsCordi Core, it is necessary to monitor body weight and sodium intake and prescribe an appropriate diet. It is necessary to maintain dental hygiene and frequent visits to the dentist (to prevent soreness, bleeding and gum overgrowth). In elderly patients, the half-life 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. Despite the absence of withdrawal syndrome with slow calcium channel blockers, a gradual dose reduction is recommended before stopping treatment.

Impact on the ability to drive a car and operate machinery

Some patients, mainly at the beginning of treatment, may experience drowsiness and dizziness. If they occur, the patient must take special precautions when driving and operating machinery.

Active ingredient

Levamlodipine

Composition

2.5 mg tablets:

Active substance:

S(-)amlodipine besylate in terms of

S(-)amlodipine 2.5 mg

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; iron oxide yellow 0.14 mg.

Contraindications

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

– Prinzmetal’s angina;

– severe arterial hypotension;

– collapse, cardiogenic shock;

– pregnancy and lactation period;

– age under 18 years (efficacy and safety have not been established).

With caution:

Liver dysfunction, sick sinus syndrome (severe bradycardia, tachycardia), chronic heart failure of non-ischemic etiology in the decompensation stage, moderate arterial hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and within 1 month after), diabetes mellitus, lipid profile disorder, elderly age.

Side Effects

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

From the central nervous system: dizziness, headache, fatigue, drowsiness, mood changes; rarely – convulsions, loss of consciousness, hypersthesia, nervousness, parasthesia, 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 enzymes and jaundice (caused by cholestasis), pancreatitis, dry mouth, flatulence, gum hyperplasia, constipation or diarrhea, very rarely – gastritis, increased appetite, impaired taste.

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.

Others: rarely – gynecomastia, polyuricemia, weight gain/loss, thrombocytopenia, leukopenia, hyperglycemia, blurred vision, conjunctivitis, diplopia, eye pain, tinnitus, back pain, dyspnea, nosebleeds, increased sweating, thirst; very rarely – cold sticky sweat, cough, rhinitis, parosmia, accommodation disturbance, xerophthalmia.

Interaction

Inhibitors of microsomal oxidation increase the concentration of amlodipine in the blood plasma, increasing the risk of side effects, and inducers of microsomal liver enzymes reduce it.

The hypotensive effect is weakened by alpha-agonists, estrogens (sodium retention), and sympathomimetics.

Thiazide and loop diuretics, beta-blockers,
verapamil, angiotensin-converting enzyme (ACE) inhibitors and nitrates enhance the antianginal and hypotensive effects.

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

Does not affect the pharmacokinetic parameters of digoxin and warfarin.
Cimetidine does not affect the pharmacokinetics of amlodipine.

When used together with lithium preparations, it is possible to increase the appearance of their neurotoxicity (nausea, vomiting, diarrhea, ataxia, tremor, tinnitus).

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

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

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

Overdose

Symptoms: marked decrease in blood pressure, tachycardia, excessive peripheral vasodilation.

Treatment: gastric lavage, administration of activated charcoal, maintaining the function of the cardiovascular system, monitoring indicators of heart and lung function, elevated position of the extremities, monitoring the volume of circulating blood and diuresis. To restore vascular tone – use vasoconstrictors (in the absence of contraindications to their use); to eliminate the consequences of blockade of calcium channels – intravenous administration of calcium gluconate.

Hemodialysis is not effective.

Storage conditions

In a dry place at a temperature not exceeding 25 °C. Keep out of the reach of children.

Shelf life

3 years.
Do not use after expiration date.

Manufacturer

Emcure Pharmaceuticals Ltd, India