Amlopril-Darnitsa of the tab. 0.01g No. 20

General characteristics. Structure:

Active ingredient: amlodipinum; 1 tablet contains an amlodipin of a besilat (in terms of 100% dry matter) – 6,9 mg or 13,9 mg; in terms of амлодипин – 5 mg or 10 mg.

excipients: lactoses monohydrate, cellulose microcrystallic, corn starch, silicon dioxide colloid anhydrous (aerosil), magnesium stearate, povidone (polyvinylpirrolidone low-molecular medical).

Pharmacological properties:

Pharmacodynamics. Амлоприл®-Дарница – the dihydropyridinic antagonist of calcium of the second generation. Blocks slow Sa2+-channels, transmembrane movement of ions of Sa2 + preferential in cells of unstriated muscles of vessels, and also a myocardium oppresses. Has vazodilyatatorny, anti-hypertensive, anti-anginal, spasmolytic properties.

The mechanism of anti-hypertensive action is caused by the direct weakening impact on unstriated muscles of vessels. Thanks to the slow beginning of action and the prolonged effect does not cause arterial hypotension, providing in a single (daily) dose clinically notable smooth lowering of arterial pressure for 24 h. Anti-anginal action of Amloprila®-Darnitsa is connected with expansion of both coronary vessels, and peripheral arterioles, reduction of an afterload by heart without reflex increase in heart rate which leads to decrease in consumption of energy and oxygen in a myocardium. Reduces a hypertrophy of a myocardium of a left ventricle. There are data on anti-atherosclerotic properties of drug. Амлоприл®-Дарница slows down aggregation of thrombocytes, increases a glomerular filtration rate, натриеурез and a diuresis. Unlike dihydropyridinic antagonists of calcium of the first generation, Amlopril®-Darnitsa does not increase significantly the level of catecholamines in a blood plasma and does not stimulate a renin-angiotenzivnuyu system. At intake it is quickly soaked up from a digestive tract (absorption – 100%).

Pharmacokinetics. After oral administration of Amlopril®-Darnitsa it is slowly absorbed from digestive tract. Average absolute bioavailability makes 64%, the maximum concentration in blood serum is observed in 6–    9 hours. Concentration of stable balance is reached after 7 days of therapy. Food does not influence absorption of Amlopril®-Darnitsa. The average volume of distribution makes 21 l/kg of body weight that indicates that the most part of drug is in fabrics, and rather smaller – in blood. The most part of the drug which is in blood (95%) contacts proteins of a blood plasma. Амлоприл®-Дарница is exposed to slow, but extensive metabolism (90%) in a liver with formation of inactive metabolites, has effect of "the first passing" through a liver. Metabolites have no significant pharmacological activity.

After single oral administration the elimination half-life (T1/2) varies from 31 to 48 hours, at repeated purpose of T1/2 makes about 45 hours. About 60% of the dose accepted inside are excreted with urine preferential in the form of metabolites,    10% in not changed look, and 20–25% with a stake, and also with breast milk. The general clearance of Amlopril®-Darnitsa makes 0,116 ml / with/kg (7 ml/min., 0,42 l/h/kg).

At elderly patients (65 years are more senior) removal of Amlopril®-Darnitsa is slowed down (   T1/2 65 of the h) in comparison with young patients, however this difference has no clinical value.

At patients with a liver failure lengthening of T1/2 is supposed, and at long appointment accumulation of drug in an organism will be higher (T1/2 to 60 h).

The renal failure has no significant effect on kinetics of Amlopril®-Darnitsa. Drug gets through a blood-brain barrier. At a hemodialysis it is not allocated.

Pharmaceutical characteristics.

main physical and chemical properties: tablets of color, white or white with a yellowish shade, a ploskotsilindrichesky form with a facet.

Indications to use:

Arterial hypertension, coronary heart disease: stable stenocardia and vasospastic stenocardia (Printsmetal's stenocardia or alternative stenocardia).

Route of administration and doses:

Амлоприл®-Дарница adults accept inside irrespective of meal of 1 times a day, washing down with enough water. The initial dose makes 5 mg, if necessary in 7–14 days the dose is increased to maximum – 10 mg.

To elderly patients and patients at a renal failure appoint in usual doses.

For patients with a liver failure the daily dose should not exceed 2,5 mg (drugs of an amlodipin with a possibility of such dosing are used).

Features of use:

During treatment control of body weight and consumption of sodium, purpose of the corresponding diet, and also daily control of arterial pressure is necessary.

Maintenance of hygiene of teeth and frequentation of the stomatologist is necessary (for prevention of morbidity, bleeding and a hyperplasia of gums).

The dosing mode elderly patients the same, as well as for patients of other age groups, but at increase in a dose require careful observation of such patients.

Despite the absence of at blockers of "slow" calcium channels of a syndrome of "cancellation", before the termination of treatment gradual reduction of doses is recommended.

With care apply at an abnormal liver function.

Ability to influence the speed of reactions at control of motor transport or other mechanisms. During treatment it is necessary to abstain from driving of motor transport and from occupations potentially dangerous types of activity requiring special attention and speed of mental and motor reactions.

 

Side effects:

Are in some cases observed: peripheral hypostases, headache, increased fatigue, drowsiness, nausea, rushes of blood, heartbeat and dizziness. More rare – a skin itch, rash, suffocation, an adynamy, spasms, dyspepsia, a hyperplasia of gums, a polymorphic erythema. The alopecia, a lock, an altralgiya, a dorsodynia, a gynecomastia, a hyperglycemia, arterial hypotension, the increased urination frequency, change of mood, a mialgiya, a periodic neutropenia, a leukopenia, thrombocytopenia is in certain cases possible. Very seldom jaundice and increase in activity of liver enzymes meets.

Interaction with other medicines:

Inhibitors of a microsomal oxidation increase concentration of Amlopril®-Darnitsa in a blood plasma, strengthening risk of development of side effects, and inductors of microsomal enzymes of a liver reduce.

Hypotensive effect non-steroidal anti-inflammatory drugs, especially indometacin (a delay of sodium and blockade of synthesis of prostaglandins kidneys), alpha адреностимуляторы weaken, estrogen (a sodium delay), sympathomimetics. Thiazide and "loopback" diuretics, beta adrenoblockers, verapamil, APF inhibitors and nitrates strengthen anti-anginal and hypotensive effects.

Amiodaronum, quinidine, alfa1-adrenoblockers, antipsychotic medicines (neuroleptics) and blockers of "slow" calcium channels can strengthen hypotensive action. Does not exert impact on pharmacokinetic parameters of digoxin and warfarin.

Cimetidinum does not influence pharmacokinetics of an amlodipin.

At combined use with drugs of lithium strengthening of manifestations of their neurotoxicity (nausea, vomiting, diarrhea, an ataxy, a tremor, a sonitus) is possible.

Drugs of calcium can reduce effect of blockers of "slow" calcium channels.

The procaineamide, quinidine and other medicines causing lengthening of an interval of QT strengthen a negative inotropic effect and can increase risk of considerable lengthening of an interval of QT.

Grapefruit juice can increase concentration of Amlopril®-Darnitsa in a blood plasma, however this increase so is not enough that significantly does not change action of Amlopril®-Darnitsa.

Contraindications:

Arterial hypotension. Hypersensitivity to dihydropyridine derivatives. Feeding period breast. Children's age.

Use during pregnancy or feeding by a breast. Safety of use of Amloprila®-Darnitsa during pregnancy and feeding by a breast is not established. Purpose of drug is possible only if the expected therapeutic effect for mother exceeds potential risk for a fruit. During treatment it is necessary to cancel feeding by a breast.

Children. Амлоприл®-Дарница it is contraindicated to children up to 18 years.

Overdose:

Intoxication symptoms probably caused by the prolonged system hypotension and disturbance of perfusion of vitals. In hard cases tachycardia, a hypoxia, a collapse with a loss of consciousness, cardiogenic shock is possible.

Treatment: measures of acute management, first of all, have to be directed to recovery of a stable hemodynamics. At patients it is necessary to control constantly functions of cardiovascular and respiratory systems, a diuresis. Administration of drugs of calcium is possible. If administration of calcium insufficiently effective, is reasonable use of sympathomimetics (a dopamine or noradrenaline) for stabilization of arterial pressure. Doses of these drugs select taking into account the reached medical effect. Bradycardia can be eliminated with sympathomimetics. At delay of a cordial rhythm which threatens life use of an artificial pacemaker is recommended.

It is necessary to approach additional administration of liquid very carefully as at the same time danger of an overload of heart increases.

Considering that Amlopril®-Darnitsa substantially contacts proteins of plasma, use of a hemodialysis is inexpedient.

Storage conditions:

Period of validity. 3 years. To store in the place, unavailable to children, in original packaging, at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging, on two blister strip packagings in a pack.