Arentopres

General characteristics. Structure:

Active ingredient: 2 mg or 4 mg of a perindopril of an erbumin.

Anti-hypertensive drug.

Pharmacological properties:

Pharmacodynamics. APF inhibitor. Is pro-medicine of which in an organism the active metabolite периндоприлат is formed. Believe that the mechanism of anti-hypertensive action is connected with competitive inhibition of activity of APF which leads to reduction in the rate of transformation of angiotensin I into the angiotensin II which is powerful vasoconstrictive substance. Reduction of concentration of angiotensin II is resulted by secondary increase in activity of a renin of plasma due to elimination of negative feedback at release of a renin and direct decrease in secretion of Aldosteronum. Thanks to vasodilating action, reduces OPSS (afterload), jamming pressure in pulmonary capillaries (preloading) and resistance in pulmonary vessels; increases the minute volume of heart and tolerance to loading.

The hypotensive effect develops within the first hour after reception of a perindopril, reaches a maximum in 4-8 h and proceeds during 24 h.

In clinical trials at use of a perindopril (monotherapy or in a combination with diuretic) considerable decrease in risk of developing of a repeated stroke (both ischemic, and hemorrhagic), and also risk of the fatal or resulting in disability strokes is shown; the main cardiovascular complications, including a myocardial infarction, including with a lethal outcome; dementia connected with a stroke; serious deteriorations in cognitive functions. These therapeutic advantages were noted both at patients with arterial hypertension, and at the normal ABP, irrespective of age, sex, existence or lack of a diabetes mellitus and type of a stroke.

It is shown that against the background of use of a perindopril of a tretbutilamin in a dose of 8 mg/days (10 mg of a perindopril of arginine are equivalent) at patients from a stable ischemic heart disease, essential decrease in absolute risk of the complications provided by the main criterion of efficiency (cardiovascular diseases mortality, frequency of not fatal myocardial infarction and/or a cardiac standstill with the subsequent successful resuscitation) for 1.9% is noted. At the patients who earlier had a myocardial infarction or the procedure of coronary revascularization, decrease in absolute risk made 2.2% in comparison with group of placebo.

Perindopril is applied both in the form of monotherapy, and in the form of the fixed combinations with indapamidy, with amlodipiny.

Pharmacokinetics. After intake perindoprit quickly it is absorbed from a GIT. Cmax is reached in 1 h. Bioavailability makes 65-70%.

In the course of metabolism perindoprit it biotransformirutsya with formation of an active metabolite - a perindoprilata (about 20%) and 5 inactive connections. Cmax of a perindoprilat in plasma is reached between 3 and 5 h after reception. Linkng of a perindoprilat with proteins of a blood plasma insignificant (less than 30%) also depends on concentration of active agent. Vd of a free perindoprilat is close to 0.2 l/kg.

Does not kumulirut. Repeated reception does not lead to cumulation and T1/2 corresponds to the period of its activity.

At inclusion in food time metabolism of a perindopril is slowed down.

T1/2 of a perindopril makes 1 h.

Perindoprilat is brought from an organism by kidneys; T1/2 of its free fraction makes 3-5 h.

At elderly patients, and also at renal and heart failure removal of a perindoprilat is slowed down.

Indications to use:

Arterial hypertension.

Chronic heart failure.

Prevention of a repeated stroke (a combination therapy with indapamidy) at the patients who had a stroke or tranzitorny disturbance of cerebral circulation on ischemic type.

Stable ischemic heart disease: decrease in risk of cardiovascular complications at patients from a stable ischemic heart disease.

Route of administration and doses:

Initial dose - 1-2 mg/days in 1 reception. Maintenance doses - 2-4 mg/days at congestive heart failure, 4 mg (is more rare - 8 mg) - at arterial hypertension in 1 reception.

At renal failures correction of the mode of dosing depending on KK values is required.

Features of use:

Use at pregnancy and feeding by a breast. Perindopril is contraindicated to use at pregnancy and in the period of a lactation (breastfeeding).

Use at renal failures. At renal failures correction of the mode of dosing depending on KK values is required.

Use for children. It is contraindicated at children's age.

Special instructions. With care it is necessary to apply perindoprit at a bilateral stenosis of renal arteries or a renal artery stenosis of the only kidney; renal failure; general diseases of connecting fabric; therapies by immunosuppressors, Allopyrinolum, procaineamide (risk of development of a neutropenia, agranulocytosis); reduced OTsK (reception of diuretics, a diet with salt restriction, vomiting, diarrhea); stenocardias; cerebrovascular diseases; renovascular hypertensia; diabetes mellitus; chronic heart failure of the IV functional class on NYHA classification; along with kaliysberegayushchy diuretics, potassium drugs, kaliysoderzhashchy substitutes of edible salt, with lithium drugs; at a hyperpotassemia; surgical intervention / general anesthesia; a hemodialysis with use of high-flowing membranes; the desensibilizing therapy; to LPNP afereza; a state after transplantation of a kidney; aortal stenosis / mitral stenosis / hypertrophic subaortic stenosis; at patients of negroid race.

It was reported about cases of arterial hypotension, a faint, a stroke, a hyperpotassemia and renal failures (including an acute renal failure) at predisposed patients, especially at simultaneous use with medicines which influence RAAS. Therefore double blockade of RAAS as a result of an APF inhibitor combination to the antagonist of receptors of angiotensin II or aliskireny is not recommended.

Before an initiation of treatment perindoprily the research of function of kidneys is recommended to all patients.

During treatment perindoprily it is regularly necessary to control function of kidneys, activity of liver enzymes in blood, to carry out analyses of peripheral blood (especially at patients with diffusion diseases of connecting fabric, at patients who receive immunodepressive means, Allopyrinolum). Patients with deficit of sodium and liquid before an initiation of treatment need to carry out correction of water and electrolytic disturbances.

Side effects:

From system of a hemopoiesis: an eosinophilia, decrease in hemoglobin and a hematocrit, thrombocytopenia, a leukopenia/neutropenia, an agranulocytosis, a pancytopenia, hemolitic anemia at patients with inborn deficit glyukozo-6-fosfatdegidrogenazy.

From a metabolism: a hypoglycemia, a hyperpotassemia, reversible after drug withdrawal, a hyponatremia.

From a nervous system: paresthesia, headache, dizziness, вертиго, sleep disorders, lability of mood, drowsiness, syncope, confusion of consciousness.

From sense bodys: vision disorders, sonitus.

From cardiovascular system: excessive decrease in the ABP and the symptoms connected with it, a vasculitis, tachycardia, a heart consciousness, disturbances of a cordial rhythm, stenocardia, a myocardial infarction and a stroke, perhaps, owing to excessive decrease in the ABP at patients from group of high risk.

From respiratory system: cough, short wind, bronchospasm, eosinophilic pneumonia, rhinitis.

From the alimentary system: lock, nausea, vomiting, abdominal pain, taste disturbance, dyspepsia, diarrhea, dryness of a mucous membrane of an oral cavity, pancreatitis, hepatitis (cholestatic or cytolytic).

From integuments and a hypodermic fatty tissue: a skin itch, rash, a photosensitization, a pemphigus, the increased sweating.

Allergic reactions: Quincke's disease, small tortoiseshell, mnogoformny erythema.

From a musculoskeletal system: spasms of muscles, arthralgia, mialgiya.

From an urinary system: renal failure, acute renal failure.

From reproductive system: erectile dysfunction.

General reactions: adynamy, thorax pain, peripheral hypostases, weakness, fever, falling.

From laboratory indicators: increase in activity of hepatic transaminases and bilirubin in blood serum, increase in concentration of urea and creatinine in a blood plasma.

Interaction with other medicines:

The risk of development of a hyperpotassemia increases at simultaneous use of a perindopril with other drugs which are capable to cause a hyperpotassemia: алискирен and aliskirensoderzhashchy drugs, potassium salts, kaliysberegayushchy diuretics, APF inhibitors, antagonists of receptors of angiotensin II, NPVS, heparin, immunopodepressant, such as cyclosporine or такролимус, Trimethoprimum.

At simultaneous use with aliskireny for patients with a diabetes mellitus or renal failures (SKF <60 ml/min.) increases risk of a hyperpotassemia, deterioration in function of kidneys and increase in frequency of cardiovascular incidence and mortality (at patients of these groups this combination is contraindicated).

Simultaneous use with aliskireny for the patients who do not have a diabetes mellitus or renal failures since increase in risk of a hyperpotassemia, deterioration in function of kidneys and increase in frequency of cardiovascular incidence and mortality is possible is not recommended.

In literature it was reported that at patients with the established atherosclerotic disease, heart failure or a diabetes mellitus with damage of target organs, simultaneous therapy of APF inhibitor and the antagonist of receptors of angiotensin II is connected with higher frequency of development of hypotension, faint, a hyperpotassemia and deterioration in function of kidneys (including an acute renal failure) in comparison with use only of one drug influencing RAAS. Double blockade (for example, at an APF inhibitor combination from the antagonist of receptors of angiotensin II) has to be limited to separate cases with careful monitoring of function of kidneys, contents of potassium and the ABP.

Simultaneous use with estramustinum can lead to increase in risk of side effects, such as a Quincke's disease.

At simultaneous use of drugs of lithium also perindoprit perhaps reversible increase in concentration of lithium in blood serum and the toxic effects connected with it (this combination is not recommended).

Simultaneous use with hypoglycemic drugs (insulin, hypoglycemic means for intake) demands extra care since APF inhibitors, including perindoprit, can strengthen hypoglycemic effect of these drugs up to development of a hypoglycemia. As a rule, it is observed in the first weeks of performing simultaneous therapy and at patients with a renal failure.

Baclofenum strengthens anti-hypertensive effect of a perindopril, at simultaneous use dose adjustment of the last can be required.

At the patients receiving the diuretics which are especially removing liquid and/or salts at the beginning of therapy perindoprily excessive decrease in the ABP which risk of development can be reduced by cancellation of diuretic means, completion of loss of liquid or salts before therapy perindoprily, and also use of a perindopril in a low initial dose with its further gradual increase can be observed.

At chronic heart failure in case of use of diuretics perindoprit it is necessary to apply in a low dose, perhaps after reduction of a dose of the applied at the same time kaliynesberegayushchy diuretic. In all cases function of kidneys (concentration of creatinine) should be controlled in the first weeks of use of APF inhibitors.

Use of an eplerenon or Spironolactonum in doses from 12.5 mg to 50 mg/days and APF inhibitors (including perindoprit) in low doses: at therapy of heart failure of the II-IV functional class on classification of NYHA with fraction of emission of a left ventricle <40% and the diuretics which were earlier applied by inhibitors APF and "loopback", there is a risk of development of a hyperpotassemia (with a possible lethal outcome), especially in case of non-compliance with recommendations concerning this combination. Before use of this combination it is necessary to be convinced of lack of a hyperpotassemia and renal failures. It is regularly recommended to control concentration of creatinine and potassium in blood - weekly in the first month of treatment and monthly in the subsequent.

Simultaneous use of a perindopril with NPVS (acetylsalicylic acid in the dose having antiinflammatory effect, TsOG-2 inhibitors and non-selective NPVS) can lead to decrease in anti-hypertensive effect of APF inhibitors. Simultaneous use of APF and NPVS inhibitors can lead to deterioration in function of kidneys, including development of an acute renal failure, and to increase in content of potassium in blood serum, especially at patients with reduced function of kidneys. With care to apply this combination at patients of advanced age. Patients have to receive adequate amount of liquid; it is recommended to control carefully function of kidneys, both at the beginning, and in the course of treatment.

The hypotensive effect of a perindopril can amplify at simultaneous use with other anti-hypertensive drugs, vasodilators, including nitrates of the short and prolonged action.

Simultaneous use of gliptin (линаглиптин, саксаглиптин, ситаглиптин, витаглиптин) with APF inhibitors (including with perindoprily) can increase risk of development of a Quincke's disease owing to suppression of activity of a dipeptidilpeptidaza the IV gliptiny.

Simultaneous use of a perindopril with tricyclic antidepressants, antipsychotic drugs and means for the general anesthesia can lead to strengthening of anti-hypertensive action.

Sympathomimetics can weaken anti-hypertensive effect of a perindopril.

At use of APF inhibitors, including perindoprit, at the patients receiving in/in gold drug (sodium ауротиомалат), the symptom complex at which the dermahemia of the person, nausea, vomiting, arterial hypotension were observed was described.

Contraindications:

Quincke's disease in the anamnesis, simultaneous use with aliskireny and aliskirensoderzhashchy drugs at patients with a diabetes mellitus or renal failures (SKF <60 ml/min. / 1,73 sq.m), pregnancy, a lactation, children's and teenage age up to 18 years, hypersensitivity to a perindopril, hypersensitivity to other APF inhibitors.

Overdose:

Symptoms: acute arterial hypotension, Quincke's edema.

Treatment: reduction of a dose or full drug withdrawal; gastric lavage, holding actions for increase in OTsK (introduction of normal saline solution, etc. blood-substituting liquids), symptomatic therapy: Epinephrinum (п / to or in/in), antihistamines, a hydrocortisone (in/in); holding dialysis procedures.

Storage conditions:

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 of 24 months.

Issue conditions:

According to the recipe

Packaging:

10 pieces - planimetric strip packagings (3) - packs cardboard.
10 pieces - planimetric strip packagings (10) - packs cardboard.