Perindopril таб 4 mg No. 30

General characteristics. Structure:

Active agent: perindoprila эрбумин 2 mg and 4 mg.
 Excipients: lactose (sugar milk); cellulose microcrystallic;      croscarmellose sodium (primelloza); silicon dioxide colloid (aerosil); magnesium stearate.

Description: Tablets of white or almost white color, round, a ploskotsilindrichesky form with a facet.

Pharmacological properties:

Pharmacological properties. Pharmacodynamics. APF inhibitor. Suppression of APF leads to decrease in content of angiotensin II in a blood plasma therefore secretion of Aldosteronum decreases. Perindopril acts by means of the active metabolite of a perindoprilat. Eliminates vasopressor effect of angiotensin II, increases concentration of bradikinin and vazodilatatorny prostaglandins (APF transfers inactive angiotensin I to the angiotensin II having vasopressor effect and also causes degradation of bradikinin and prostaglandin, having vazodilatiruyushchy activity); reduces products and release of Aldosteronum, suppresses release of noradrenaline from the terminations of sympathetic nerve fibrils and formation of endothelin in a wall of vessels. Decrease in formation of angiotensin II is followed by increase in activity of a renin of a blood plasma (owing to oppression of negative feedback). Suppression of APF is followed by increase in the activity as circulating, and fabric kallikrein-kinin system, at the same time the system of prostaglandins is also activated.
Promotes recovery of elasticity of large arterial vessels (decrease in formation of excess amount of subendothelial collagen), reduces pressure in pulmonary capillaries, at long appointment reduces expressiveness of a hypertrophy of a myocardium of a left ventricle and intersticial fibrosis, normalizes an isofermental profile of a myosin; normalizes cardiac performance.
Reduces preloading and an afterload (reduces systolic and diastolic arterial pressure in situation "lying" and "standing"), filling pressure of the left and the right ventricles, the general peripheric resistance of vessels; increases the minute volume of blood circulation and cardiac index without change of heart rate (at patients with chronic heart failure), does not increase heart rate, strengthens a regional blood stream in muscles.
Increases concentration of lipoproteids of high density, at patients with a hyperuricemia reduces concentration of uric acid. Increases renal
the blood stream,      does not change         a glomerular filtration rate. With chronic heart failure causes reliable reduction of expressiveness of clinical signs of heart failure in patients, increases tolerance to an exercise stress (according to veloergometrichesky test), authentically does not reduce arterial pressure. After intake of an average single dose the maximum hypotensive effect is reached in 4-6 h and remains during 24 h. Stabilization of hypotensive effect is observed in 1 month of therapy and remains for a long time. The termination of treatment is not followed by development of a syndrome of "cancellation".

Pharmacokinetics. Absorption - 25%, bioavailability - 65-70%. Time of achievement of the maximum concentration in   a blood plasma   -   1   h,   a perindoprilata   -   3-4   h. In the course of metabolism of 20% it is transformed to an active metabolite - периндоприлат (reception of a perindopril after food reduces a share of the formed perindoprilat - has no essential clinical value); other quantity - in 5 inactive connections. T1/2 (elimination half-life) of a perindopril - 1 h. Communication of a perindoprilat with proteins of a blood plasma - insignificant, with APF - less than 30% (depends on concentration). The volume of distribution of a free perindoprilat -   0,2 l/kg. Perindoprilat is brought by kidneys, T1/2 of free fraction of a metabolite - 3-5 h. Dissociation of the perindoprilat connected with APF, slow. Thereof "effective" T1/2 makes 25 h. Repeated purpose of a perindopril does not lead to its cumulation, and T1/2 of a perindoprilat at repeated reception corresponds to the period of its activity.
Removal of a perindoprilat is slowed down at patients of advanced age, and also at patients with chronic heart failure and chronic renal failure (at the last dose adjustment should be carried out depending on clearance of creatinine). The dialysis clearance of a perindopril makes 70 ml/min.
At patients with cirrhosis the hepatic clearance of a perindopril decreases twice, at the same time total quantity of the formed perindoprilat does not change and correction of the mode of dosing is not required.

Indications to use:

Arterial hypertension; chronic heart failure.

Route of administration and doses:

Inside, in the morning, before food.
The initial   dose for treatment of arterial hypertension makes 4 mg/days, if necessary (in 1 month) the dose can be increased to 8 mg/days in one step.
At purpose of APF inhibitors sharp decrease in the ABP for which prevention it is recommended to stop  reception  of diuretics  in  2-3 days  prior to  the estimated  beginning  of therapy by Perindopril can be noted by the patient receiving therapy by diuretics or to appoint drug in lower doses - 2 mg of 1 times a day.
At patients with renovascular hypertensia the initial dose makes 2 mg of 1 times a day. In need of the subsequent the dose can be increased.
At patients of advanced age therapy it is necessary to begin with a dose 2 mg a day, and further, if necessary, to gradually raise it up to the maximum dose of 8 mg a day.
Treatment of patients with heart failure in a combination with nekaliysberegayushchy diuretic and/or digoxin, it is recommended to begin under careful medical control, Perindopril to appoint in an initial dose 2 mg of 1 times a day, in the morning.
Further, in 1-2 weeks of therapy, the dose of drug can be increased to 4 mg of 1 times a day.
At patients with a renal failure, the dose of drug should be selected taking into account degree of a renal failure: depending on the clearance of creatinine (CC).
At KK of 30-60 ml/min. - 2 mg of 1 times a day; at KK of 15-30 ml/min. - 2 mg every other day; the patient who is on a hemodialysis (KK less than 15 ml/min.) - 2 mg in day of dialysis.  At KK more than 60 ml/min. 4 mg a day.
The patient with an abnormal liver function, changes of a dose of Perindopril are not required.

Features of use:

The risk of development of arterial hypotension and/or renal failure against the background of administration of drug increases at considerable loss of sodium and water (a rigid electrolyte-deficient diet, and/or reception of diuretics, diarrhea, vomiting) or a stenosis of renal arteries (blockade can give a renin-angiotenzinovoy of system in these situations, especially at the first administration of drug and within the first 2 weeks of treatment, to a sudden lowering of arterial pressure and development of a chronic renal failure).
Before the beginning and against the background of therapy it is recommended to define concentration of creatinine, electrolytes and urea (within 1 month).
At the patients with arterial hypertension who are already receiving therapy by diuretics it is necessary to stop their reception (in 3 days prior to Perindopril's appointment) and in need of further to add to treatment again.
At the patients with chronic heart failure receiving therapy by diuretics, whenever possible, their dose also has to be reduced some days before the beginning of reception.
At the patients belonging to risk group, especially with chronic heart failure in a stage of a decompensation, patients of advanced age, and also patients with initially low arterial pressure, a renal failure or receiving high doses of diuretics, the beginning of use of drug has to be carried out under control.
At the patients who are on a hemodialysis it is necessary to avoid use of polyacrylonitrile membranes (possibly development of anaphylactoid reactions).
It is necessary to stop reception before the forthcoming surgical treatment for 12 h and to warn the anesthesiologist about administration of drug.

Side effects:

- From warmly vascular system: often - excessive decrease arterial, pressure and symptoms connected with it, is rare - arrhythmia, stenocardia, a myocardial infarction and a stroke.
- From an urinary system: depression of function of kidneys,  acute renal failure.
- From a respiratory organs: often - Sukhoi cough, breath difficulty; seldom - a bronchospasm, a rhinorrhea.
- From the alimentary system: often - nausea, vomiting, an abdominal pain, taste change, diarrhea or a lock, dryness in a mouth, a loss of appetite, cholestatic jaundice, pancreatitis, intestinal hypostasis.
- From the central nervous system: often - a headache, an adynamy, increased fatigue, dizziness, a ring in ears, vision disorders, muscular spasms, paresthesias; seldom - decrease in mood, sleeplessness; extremely seldom - confusion of consciousness.
- Allergic reactions: often - skin rash, an itch; seldom - a small tortoiseshell, a Quincke's  disease;   extremely seldom  - a multiformny  exudative  erythema.
- Laboratory indicators: often - a giperkreatininemiya, a proteinuria, a hyperpotassemia; hyperuricemia; seldom (at prolonged use in high doses) - a neutropenia, a leukopenia, a hypohaemoglobinaemia, thrombocytopenia, decrease in a hematocrit; extremely seldom - an agranulocytosis, a pancytopenia, increase in activity of "hepatic" enzymes, a hyperbilirubinemia, hemolitic anemia (against the background of deficit glyukozo-6-fosfatdegidrogenazy).
- Other: the increased sweating, disturbance of sexual function.

Interaction with other medicines:

Increases expressiveness of hypoglycemic effect of insulin and derivatives of sulphonylurea. Baclofenum, tricyclic antidepressants, antipsychotic medicines (neuroleptics), saluretics strengthen hypotensive action and increase risk of development of orthostatic hypotension (the additive effect), antiacid means reduce bioavailability of APF inhibitors.
Glucocorticosteroids, non-steroidal anti-inflammatory drugs reduce expressiveness of hypotensive action (a delay of liquid and electrolytes).
Kaliysberegayushchy diuretics (Spironolactonum, Triamterenum, amiloride), drugs of potassium increase risk of development of a hyperpotassemia. Simultaneous use of the medicines capable to cause a hyperpotassemia, and APF inhibitors, except for cases of a heavy hypopotassemia is not recommended (control of content of potassium in blood serum).
At simultaneous use with drugs of lithium delay of its removal from an organism is possible (regular control of content of lithium in blood is necessary).
Diuretics, medicines for the general anesthesia and muscle relaxants, ethanol increase risk of development of an excessive lowering of arterial pressure. The risk of development of clinically expressed arterial hypotension can be reduced, having stopped reception of diuretics some days before an initiation of treatment by Perindopril.

Contraindications:

Contraindications: Hypersensitivity to a perindopril and other components of drug or other APF inhibitors, a Quincke's disease in the anamnesis against the background of, therapies by inhibitors. APF, a hereditary or idiopathic Quincke's disease, pregnancy, the lactation period, age up to 18 years (efficiency and safety are not established).

With care: A stenosis of the aortal valve, a hypertrophic subaortic stenosis, cerebrovascular diseases (including insufficiency of cerebral circulation, coronary heart disease, coronary insufficiency - danger of development of an excessive lowering of arterial pressure and the accompanying ischemia).
Serious autoimmune general diseases of connecting fabric (including a system lupus erythematosus, a scleroderma), oppression of a marrowy hemopoiesis against the background of reception   of immunodepressants    (increase   in probability    of development    of a neutropenia).
Renovascular hypertensia, bilateral stenosis of renal arteries, stenosis of an artery of the only kidney, state after transplantation of kidneys (risk of development of a renal failure and agranulocytosis), the chronic renal failure (which is especially followed by a hyperpotassemia), a hyperpotassemia, a diet with restriction of sodium, the states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting, reception of diuretics), a diabetes mellitus, advanced age, surgical intervention (the general anesthesia).

Overdose:

Symptoms: the expressed lowering of arterial pressure, shock, a stupor, bradycardia, electrolytic disturbances (a hyperpotassemia, a hyponatremia), a renal failure.
Treatment: gastric lavage, recovery of a water and electrolytic state, intravenous administration of 0.9% of solution of sodium of chloride. In case of the expressed lowering of arterial pressure of the patient it is necessary to put horizontally, having raised legs up. The hemodialysis is effective (not to use high-permeability poliakrilnitrilovy membranes). At development of bradycardia - atropine, statement of an artificial pacemaker can be required.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to use after the date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets on 2 mg, 4 mg. On 10 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 10, 15, 20 or 30 tablets in bank of light-protective glass either in bank polymeric or in a bottle polymeric. Each can or a bottle or the 1,2 or 3 blister strip packaging together with the application instruction are placed in a pack from a cardboard.