KARDILOPIN

Active material: Amlodipine
When ATH: C08CA01
CCF: Kalьcievыh channel blocker
ICD-10 codes (testimony): I10, i20, I20.1
When CSF: 01.03.02
Manufacturer: EGIS PHARMACEUTICALS Plc (Hungary)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Pills white, almost white or off-white color, round, flat, chamfered, Engraved shaped “E” on one side and the number “251” – another.

Excipients: microcrystalline cellulose, sodium karboksikrahmal (Type A), magnesium stearate, Colloidal anhydrous silica.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Pills white, almost white or off-white color, round, flat, chamfered, Engraved shaped “E” on one side and the number “252” – another.

Excipients: microcrystalline cellulose, sodium karboksikrahmal (Type A), magnesium stearate, Colloidal anhydrous silica.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Pills white, almost white or off-white color, round, flat, chamfered, Engraved shaped “E” on one side and the number “253” – another.

Excipients: microcrystalline cellulose, sodium karboksikrahmal (Type A), magnesium stearate, Colloidal anhydrous silica.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (2) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Kalьcievыh channel blocker. Amlodipine inhibits the transmembrane incoming current of calcium ions into smooth muscle cells of the heart and blood vessels by blocking the slow calcium channels.

The antihypertensive effect of amlodipine is due to a direct relaxant effect on vascular smooth muscle cells, It is leading to reduced peripheral vascular resistance.

The mechanism of anti-anginal action is not well understood, However, most likely it is related to the following two effects:

1.Expansion of peripheral arterioles reduces peripheral vascular resistance, ie. afterload. Since amlodipine does not cause reflex tachycardia, energy consumption and reduced myocardial oxygen.

2. Expansion of the large coronary arteries and coronary arterioles improves the supply of oxygen as a normal, and ischemic areas of the myocardium. Because of these effects improves oxygen supply to the myocardium, even at vasospasm (Prinzmetal angina or unstable angina).

In patients with hypertension taking the drug 1 time / day cause clinically significant reduction in blood pressure in the supine position and standing throughout the 24-hour interval between doses of the drug. Due to the slow development of the effect of the drug does not cause acute hypotension. In patients with angina, the drug 1 time / day increases the total time of possible exercise before the development of attack of angina and time to a significant reduction of the interval ST, and also reduces the frequency of angina attacks and the need for sublingual nitroglycerin.

There were no negative influence on metabolism amlodinina. The drug has no effect on lipid levels, glucose and serum uric acid. Safe for patients with bronchial asthma.

Pharmacokinetics

Absorption

After oral administration of amlodipine is well absorbed from the gastrointestinal tract; wherein C_max amlodipine plasma levels observed after 6-12 no. Simultaneous food intake does not alter the absorption of amlodipine. The absolute bioavailability is approximately 64-80%.

Distribution

In Кажущийся_d – 21 l / kg. Plasma protein binding is 93-98%. C_ss achieved at 7-8 day administration of the drug and is 5-15 ng / ml.

Metabolism and excretion

Amlodipine undergoes extensive metabolism in the liver. About 90% the dose converted into inactive derivatives pyridine. The total clearance of 7 ml / min / kg (25 l / h for a patient weighing 60 kg). Write mainly in the form of metabolites: 60% – urine, 20-25% – with feces, about 10% excreted unchanged in the urine. T_1/2 – 30-35 no (that allows you to assign the drug 1 time / day).

Pharmacokinetics in special clinical situations

The pharmacokinetic parameters of amlodipine remain unchanged in renal failure.

In the elderly total body clearance is approximately 19 l /, the other parameters are not changed.

By reducing the clearance in patients with hepatic insufficiency drug should be prescribed in smaller doses.

Testimony

- Arterial hypertension (alone or optionally in combination therapy with other antihypertensives);

- Stable angina (as monotherapy or in combination therapy with other antianginal drugs);

- Angiospastic angina (Prinzmetal angina) (as monotherapy or in combination therapy with other antianginal drugs).

Dosage regimen

To the treatment of hypertension or angina The usual starting dose is 5 mg 1 time / day (preferably at the same time). Given the initial response of the patient the dose may be increased to 10 mg 1 time / day. Dose Cardilopin^® do not change in the case of simultaneous application of thiazide diuretics from the group, beta-blockers or ACE inhibitors.

At renal failure and elderly patients correction dosing regime is not required.

In appointing Cardilopin^® patients with impaired liver function The recommended dose is 2.5 mg / day, tk. in these patients increases T_1/2 product.

Side effect

From the nervous system: headache, dizziness, excessive fatigue, drowsiness, mood changes, convulsions; rarely – loss of consciousness, gipesteziya, paresthesia, tremor, asthenia, malaise, insomnia, nervousness, depression, unusual dreams, alarm; rarely – ataxia, apathy, ažitaciâ, amnesia.

From the digestive system: nausea, abdominal pain; rarely – giperʙiliruʙinemija, jaundice, increase in liver transaminases, dry mouth, anorexia, vomiting, constipation or diarrhea, dyspepsia, flatulence, giperplaziya right; rarely – dysgeusia, gastritis, increased appetite, pancreatitis.

Cardio-vascular system: heartbeat, swelling of the ankles and feet, breathlessness, flushing; rarely – arrhythmias (bradycardia, ventricular tachycardia, auricular flutter), chest pain, excessive reduction of blood pressure, orthostatic hypotension; rarely – development or exacerbation of congestive heart failure, arrythmia, migraine.

With the genitourinary system: rarely – thamuria, tenesmus, nocturia, sexual dysfunction (incl. reduced potency); rarely – dizurija, polyuria.

The respiratory system: rarely – dyspnoea; rarely – cough, rhinitis.

From the senses: rarely – blurred vision, conjunctivitis, diplopia, sore eyes, ccomodation, xerophthalmia, tinnitus.

On the part of the musculoskeletal system: rarely – arthralgia, arthrosis, myalgia (prolonged use), backache; rarely – myasthenia.

For the skin: rarely – dermatoxerasia, alopecia, dermatitis, purpura.

Allergic reactions: itching, rash (incl. эritematoznaya, maculo-papular rash, hives).

Other: rarely – gynecomastia, feeling the heat, chills, weight gain, nose bleed, increased perspiration, thirst; rarely – cold clammy sweat, parosmija, giperglikemiâ.

Contraindications

- Unstable angina;

- Clinically significant aortic stenosis;

- Severe hypotension;

- Childhood and adolescence up 18 years (due to lack of clinical experience);

- Pregnancy;

- Lactation (breast-feeding);

- Hypersensitivity to amlodipine and other ingredients.

FROM caution should be prescribed with abnormal liver function, SSS (vыrazhennaya bradycardia, tachycardia), chronic heart failure, decompensated, mild or moderate hypotension, aortic stenosis, mitral stenosis, hypertrophic obstructive cardiomyopathy, acute myocardial infarction (and for 1 months after), diabetes, elderly patients.

Pregnancy and lactation

Given the lack of clinical experience with amlodipine in pregnancy and lactation, the drug should not be prescribed to pregnant women, as well as women of reproductive age, do not use effective methods of contraception, except, when the therapeutic benefit of the drug justifies the potential risk.

If necessary, use during lactation should stop breastfeeding.

Cautions

Studies in patients with heart failure II and III functional class NYHA classification while taking amlodipine showed no decrease in exercise tolerance, left ventricular ejection function or worsening of clinical symptoms. Results from clinical studies in patients with heart failure III-IV functional class NYHA classification shown, that amlodipine did not increase the frequency of cardiovascular events or mortality or combined with ACE inhibitors, diuretics or digoxin.

In the period of treatment is necessary to maintain dental hygiene and visit the dentist (to prevent pain, krovotochivosti and giperplazii right).

The dosage regimen for the elderly is the same, as well as for patients in other age groups. By increasing the dose should be closely monitored for elderly patients.

Vasodilator effect of amlodipine develops gradually. Therefore, acute hypotension after its application notes are very rare, However, before the termination of treatment is recommended a gradual reduction in dose.

Amlodipine has no effect on plasma concentrations of potassium, Glucose, triglycerides, total cholesterol, LDL, Uric acid, creatinine and uric acid nitrogen.

Effects on ability to drive vehicles and management mechanisms

There were no reports on the influence of amlodipine on driving or using machinery. Nonetheless, advantageously in some patients, early treatment can occur drowsiness and dizziness. If this happens, the patient has to take special precautions while driving and operating machinery.

Overdose

Symptoms: marked reduction in blood pressure, tachycardia, chrezmernaya perifericheskaya vasodilation.

Treatment: the patient should be given a horizontal position with raised legs. Perform gastric lavage, appointment of activated carbon, To maintain the function of the cardiovascular system, control performance of the heart and lungs, kontroly for OCK and diurezom. Conducted intensive symptomatic therapy. To restore vascular tone shows the use of vasopressors (in the absence of contraindications to their use); to eliminate the effects of calcium channel blockade – / in the administration of calcium gluconate. Hemodialysis is not effective.

Drug Interactions

Simultaneous administration of amlodipine with thiazide diuretics, beta-blockers, Long-acting nitrates, sublingual formulation of nitroglycerin, NSAIDs, antibiotics and oral hypoglycemic agents.

And thiazide “loop” Diuretic, beta-blockers, verapamil, ACE inhibitors and nitrates increase antianginal and hypotensive effects of amlodipine.

Amiodarone, quinidine, alpha₁-adrenoblokatorы, antipsychotic drugs (neuroleptics) and calcium channel blockers slow may increase the hypotensive effect of amlodipine.

Calcium can reduce the effect of calcium channel blockers slow (incl. amlodipina).

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

The hypotensive effect of amlodipine weaken NSAIDs, especially indomethacin (due to sodium retention and blockade of prostaglandin synthesis by the kidneys), alpha-adrenergic agonists, Estrogens (due to sodium retention), sympathomimetic.

Prokaynamyd, quinidine and other drugs, causing prolongation of the QT interval, reinforce the negative inotropic effect of amlodipine and may increase the risk of significant lengthening of the QT interval.

Cimetidine have no influence on amlodipine farmakokinetiku.

Amlodipine has no effect on the pharmacokinetic parameters of digoxin and warfarin.

Grapefruit juice may slightly improve amlodipine serum, However, this does not lead to significant changes in blood pressure.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in the dark, inaccessible to children at temperature from 15 ° to 25 ° C. Shelf life – 5 years.