Престариум® And

General characteristics. Structure:

Active agent:
tablets on 2,5 mg contain a perindopril of arginine of 2,5 mg that corresponds to 1,6975 mg of a perindopril.
tablets on 5 mg contain a perindopril of arginine of 5 mg that corresponds to 3,395 mg of a perindopril.
tablets on 10 mg contain a perindopril of arginine of 10 mg that corresponds to 6,790 mg of a perindopril.
Excipients
Lactoses monohydrate, magnesium stearate, maltodextrin, silicon dioxide colloid hydrophobic, sodium carboxymethylstarch, глицерол, gipromelloza, macrogoal 6000, titanium dioxide.
The structure of tablets on 5 mg and 10 mg includes dye copper chlorophyllin (E141ii).
Description
tablets on 2,5 mg: round, biconvex tablets, film coated, white color.
tablets on 5 mg: oblong tablets, film coated, rounded off from two parties, light green color, with notches from two lateral faces and an engraving in the form of a logo of firm on one of the faces.
tablets on 10 mg: round, biconvex tablets, film coated, green color, with an engraving in a look on one party and a logo of firm - on another.

Pharmacological properties:

Pharmacodynamics. Perindopril represents inhibitor of the enzyme turning angiotensin I into angiotensin II (APF inhibitor).
The angiotensin-converting enzyme, or kininaza, is ekzopeptidazy which carries out as transformation of angiotensin I into vasoconstrictive substance angiotensin II, and destruction of the bradikinin possessing vasodilating action to inactive heptapeptide.
Suppression of APF leads to decrease in content of angiotensin II in a blood plasma therefore activity of a renin in a blood plasma increases (owing to oppression of negative feedback which interferes with release of a renin) and secretion of Aldosteronum decreases. As APF is inactivated by bradikinin, 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 activated. Perindopril reduces the general peripheric vascular resistance that leads to a lowering of arterial pressure (ABP). At the same time the peripheral blood stream accelerates, however the heart rate (HR) does not increase.
Perindopril has therapeutic effect thanks to an active metabolite, a perindoprilat. Other metabolites of drug have no inhibiting effect on APF in vitro.
Arterial hypertension:
Perindopril is effective drug for treatment of arterial hypertension of any severity: soft, moderate and heavy. Against the background of its use decrease both the systolic, and diastolic ABP in a prone position is noted and standing. Decrease in the ABP is reached quickly enough. At patients with the positive response to treatment normalization of the ABP occurs within a month. At the same time the effect of "accustoming" is not observed.
The termination of treatment is not followed by development of "withdrawal". Perindopril has vasodilating effect, promotes recovery of elasticity of large arteries and structures of a vascular wall of small arteries, and also reduces a hypertrophy of a left ventricle. The accompanying purpose of thiazide diuretics strengthens hypotensive effect. Besides, the combination of APF inhibitor and thiazide diuretic also leads to decrease in risk of development of a hypopotassemia against the background of reception of diuretics.
Heart failure:
Perindopril normalizes cardiac performance, reducing preloading and an afterload.
At the patients with chronic heart failure receiving perindoprit, it was revealed:
- pressure decrease of filling in the left and right ventricles of heart;
- decrease in the general peripheric resistance of vessels;
- increase in cordial emission and increase in cardiac index.
The drug research in comparison with placebo showed that changes ABP after the first administration of drug Prestarium And 2,5 mg at patients with heart failure of easy and moderate severity statistically authentically did not differ from changes of the ABP observed after placebo reception.
Cerebrovascular diseases
In the course of the international multicenter research (PROGRESS) influence of active therapy perindoprily (monotherapy or at combinations with indapamidy) within 4 years on risk of development of a repeated stroke in the patients having cerebrovascular diseases in the anamnesis was estimated. After the introduction period of use of a perindopril of a tretbutilamin on 2 mg (an equivalent of a perindopril of arginine of 2,5 mg) once a day within two weeks and then on 4 mg (an equivalent of a perindopril of arginine of 5 mg) once a day within the next two weeks, 6105 patients there were randomizirovana on two groups: also perindoprit placebo (n = 3054) третбутиламин on 4 mg (there correspond 5 mg of a perindopril of arginine) (monotherapy) or in a combination with indapamidy (n = 3051). Indapamid was in addition appointed to the patients who do not have direct indications or contraindications for use of diuretics. This therapy was appointed in addition to standard therapy of a stroke and/or arterial hypertension or other morbid conditions. All randomized patients had in the anamnesis cerebrovascular diseases (a stroke or the tranzitorny ischemic attack) within the last 5 years. Size ABP was not criterion of inclusion: 2916 patients had arterial hypertension and 3189 – normal the ABP. After 3,9 years of therapy the size ABP (systolic / diastolic) decreased on average by 9,0/4,0 mm Hg. Also considerable decrease in risk of developing of a repeated stroke (both the ischemic, and hemorrhagic nature) of about 28% was shown (95% of CI (17; 38), p <0.0001) in comparison with placebo. (10,1% vs 13,8%).
Considerable decrease in risk was in addition shown:
- the fatal or resulting in disability strokes;
- 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 are observed 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.
Stable coronary heart disease (CHD)
During the international multicenter randomized, double blind person, placebo of the controlled research EUROPA lasting 4 years, the effect of a perindopril at patients from a stable ischemic heart disease was studied. 12218 patients took part in clinical trial 18 years are more senior: 6110 patients accepted perindoprit третбутиламин 8 mg (10 mg of a perindopril of arginine are equivalent) and 6108 patients – placebo.
Cardiovascular mortality, not fatal myocardial infarction and/or cardiac standstill with the subsequent successful resuscitation were the main evaluation criteria.
For participation in a research patients with an ischemic heart disease with the established myocardial infarction at least in 3 months before screening which passed coronary revascularization at least in 6 months prior to screening, the stenosis (at least 70% of narrowing of one or more main coronary arteries) angiographically revealed or positive stress test in the presence in the anamnesis of stethalgias were selected. Drug was appointed in addition to the standard therapy applied at a lipidemia, arterial hypertension and a diabetes mellitus.
Most of patients accepted antiagregant, hypolipidemic means and beta adrenoblockers. By the end of a research the ratio of number of the patients accepting the listed groups of drugs made 91%, 69% and 63% respectively. In 4,2 years considerable reduction of relative risk by 20% (95% of CI) of development of previously defined complications was result of therapy perindoprily tretbutilaminy in a dose of 8 mg once a day: at 488 (8%) patients from the group accepting perindoprit третбутиламин, and at 603 (9,9%) patients from group of placebo (р = 0,0003).
The result at the same time did not depend on a sex, age, the ABP and existence of a myocardial infarction in the anamnesis.

Pharmacokinetics. After oral administration perindoprit quickly it is soaked up (the maximum concentration in a blood plasma is reached in 1 hour).
About 27% of total quantity of the absorbed perindopril turn in периндоприлат – an active metabolite. Except a perindoprilat in the course of metabolism 5 more metabolites are formed - all of them are inactive substances.
The elimination half-life (T1/2) of a perindopril of plasma makes 1 hour. The maximum concentration of a perindoprilat in a blood plasma is reached in 3-4 hours.
Administration of drug during food is followed by reduction of transformation of a perindopril in периндоприлат, respectively reducing bioavailability of drug.
The volume of distribution of a free perindoprilat makes about 0,2 l/kg. Communication of a perindoprilat with proteins of a blood plasma makes 20%, generally with APF, and has dozozavisimy character.
Perindoprilat is brought by kidneys and the general period of T1/2 of untied fraction makes 17 hours that leads to an equilibrium state within four days.
Removal of a perindoprilat is slowed down at advanced age, and also at patients with a heart and renal failure. At a renal failure it is desirable to carry out dose adjustment of drug taking into account degree of a renal failure (clearance of creatinine).
The dialysis clearance of a perindoprilat makes 70 ml/min.
At patients with cirrhosis the hepatic clearance of a perindopril decreases half. Nevertheless, the quantity of the formed perindoprilat does not decrease and changes in a dosage of drug are not required.

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:

Inside.
It is recommended to accept once a day, in the morning, before meal.
Arterial hypertension
The recommended initial dose makes 5 mg once a day, in the morning. At inefficiency of therapy within a month, the dose can be raised to 10 mg once a day.
At purpose of APF inhibitors to patients with the expressed system activated renin-angiotensin-aldosteronovoy (at renovascular arterial hypertension, disturbance of water-salt balance, therapy by diuretics, heavy arterial hypertension, a cordial decompensation) unpredictable 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 drug Prestarium A. can be noted.
At impossibility to cancel diuretics, an initial dose of drug Prestarium And has to make 2,5 mg. At the same time it is necessary to control functions of kidneys and the content of potassium in blood serum. In the subsequent, if necessary, the dose can be raised.
At patients of advanced age treatment it is necessary to begin with a dose 2,5 mg a day, and further, if necessary, to gradually raise it up to the maximum dose of 10 mg a day.
Heart failure
Treatment of patients with heart failure with drug Prestarium And in a combination with nekaliysberegayushchy diuretics and/or digoxin and/or beta adrenoblockers, is recommended to begin under careful medical observation, appointing drug in an initial dose of 2,5 mg once a day, in the morning. In the subsequent, depending on portability and the response to therapy, in two weeks of treatment the dose of drug can be raised to 5 mg once a day.
Patients with high risk have development of symptomatic arterial hypotension, for example, with the reduced content of salts at existence or without hyponatremia, a hypovolemia or reception of diuretics, before administration of drug Prestarium And, whenever possible, listed states have to be skorregirovana. Such indicators as size ABP, functions of kidneys and the content of potassium in a blood plasma have to be controlled both before the beginning, and in the course of therapy.
Prevention of a repeated stroke
At patients with cerebrovascular diseases in the anamnesis, therapy of drug Prestarium And it is necessary to begin with a dose 2,5 mg within the first two weeks before introduction of an indapamid. Therapy should be begun in any (from two weeks to several years) time after the had stroke.
Decrease in risk of cardiovascular complications
At patients from a stable ischemic heart disease therapy Prestarium And it is necessary to begin with drug with a dose 5 mg within two weeks once a day. Then the daily dose has to be increased to 10 mg once a day (depending on function of kidneys).
Elderly patients should begin therapy with a dose of 2,5 mg within one week once a day, then on 5 mg within the next week before increase in a dose up to 10 mg once a day once a day (depending on function of kidneys).
Selection of doses at a renal failure: in the presence the patient of renal failures, a dose of drug has Prestarium And it is necessary to select taking into account degree of a renal failure and at regular control of content of potassium and the clearance of creatinine (CC).
The following mode of dosing is recommended:
Clearance of creatinine (ml/min.) of KK                 the Recommended dose
KK ≥ 60                                                            5 mg/days
30 <KK <                                                    60 2,5 mg/days
15 <KK <                                                    30 2,5 mg every other day
Patients on a hemodialysis * KK <                15 2,5 mg in day of dialysis

* dialysis clearance of a perindoprilat: 70 ml/min.
Liver failure:
At purpose of drug the patient with an abnormal liver function, changes of a dose are not required.

Features of use:

Stable ischemic heart disease
In case of an episode of unstable stenocardia (considerable or not) during the first month of therapy by Prestarium And, it is necessary to estimate advantages and risk before treatment continuation.
Arterial hypotension
APF inhibitors can cause sharp decrease in the ABP. Symptomatic arterial hypotension seldom develops at patients without associated diseases. The risk of excessive decrease in the ABP is increased at patients with a reduced volume of the circulating blood that can be noted against the background of therapy by diuretic means, at observance of a rigid electrolyte-deficient diet, a hemodialysis, and also at vomiting and diarrhea. In most cases episodes of the expressed decrease in the ABP are noted at patients with heavy heart failure both in the presence of the accompanying renal failure, and at its absence. Most often this side effect is noted at the patients receiving "loopback" diuretics in high doses and also against the background of a hyponatremia or at renal failures. At such patients treatment has to begin under careful medical control, it is desirable in the conditions of a hospital. At the same time drug is appointed in small doses, with the subsequent careful titration of a dose. Whenever possible, it is necessary to stop temporarily therapy by diuretic means. Similar approach is also applied at patients with stenocardia or with cerebrovascular diseases at which the expressed arterial hypotension can lead to development of a myocardial infarction or cerebrovascular complications.
Before purpose of drug Prestarium And, as well as other APF inhibitors, and during his reception it is necessary to control carefully the ABP level, indicators of function of kidneys and concentration of potassium ions in blood serum.
For the purpose of reduction of probability of development of symptomatic arterial hypotension in the patients receiving therapy by diuretics in high doses, the dose of diuretics, whenever possible, has to be reduced some days before the beginning of use of drug Prestarium A.
In case of development of arterial hypotension of the patient it has to be transferred to a dorsal decubitus. If necessary it is necessary to make completion of volume of the circulating blood by means of intravenous administration of normal saline solution. The expressed decrease in the ABP at the first administration of drug is not an obstacle for further purpose of drug. After recovery of volume of the circulating blood and the ABP treatment can be continued using careful selection of a dose of drug.
Aortal stenosis / Hypertrophic cardiomyopathy
APF inhibitors have to be appointed with care the patient with these diseases.
Renal failure
At a renal failure (KK <60 ml/min.) at the beginning of therapy of a dose of drug Prestarium And have to be selected according to size KK (see. "A route of administration and doses") and then depending on the therapeutic answer. Regular control of KK and content of potassium in a blood plasma is necessary for such patients.
Patients with symptomatic heart failure have an arterial hypotension developing in an initial stage of therapy by APF inhibitors, can lead to deterioration in function of kidneys. Sometimes the acute renal failure developing at the same time has, as a rule, reversible character.
At patients with a bilateral renal artery stenosis or a stenosis of an artery of the only kidney (especially in the presence of a renal failure) against the background of therapy by APF inhibitors concentration of urea and creatinine in blood serum can increase.
Use of APF inhibitors for patients with renovascular arterial hypertension is followed by increase in risk of development of heavy arterial hypotension and renal failure. Treatment of such patients is begun under careful medical observation with purpose of small doses of drug and further adequate selection of a dose. For the first several weeks of therapy it is necessary to stop temporarily treatment by diuretic means and to carry out control of function of kidneys.
At some patients with arterial hypertension, in the presence of earlier not revealed renal failure, especially at the accompanying purpose of diuretic means, concentration of urea and creatinine in blood serum can increase.
These changes are usually expressed slightly and have reversible character. In this case the drug dose decline Prestarium And yes/or diuretic cancellation is recommended.
Hemodialysis
At the patients who are on a hemodialysis with use of high-flowing membranes several cases of development of permanent, life-threatening anaphylactic reactions were noted. It is necessary to avoid purpose of APF inhibitors when using this kind of membranes.
Transplantation of kidneys
Data on drug use Prestarium And at transplantation of kidneys are absent.
The Quincke's disease of the person, extremities, lips, mucous membranes, language, glottis and/or throat can develop at the patients receiving APF inhibitors, especially within the first several weeks of therapy. In rare instances the heavy Quincke's disease can arise against the background of long use of APF inhibitor. In similar cases treatment by APF inhibitor has to be immediately stopped, as replacement it is necessary to appoint drugs of other pharmakoterapevtichesky group.
The Quincke's disease of language, glottis or throat can lead to a lethal outcome. At its development the emergency therapy includes, in addition to other appointments, immediate hypodermic administration of solution of Epinephrinum (adrenaline) 1:1000 (1 mg/ml) 0,3-0,5 ml or its slow intravenous administration (according to the instruction for preparation of infusion solution) under control of an ECG and the ABP. The patient has to be hospitalized for treatment and observation not less than for 12 - 24 hours and before total disappearance of symptoms of this reaction.
Anaphylactic reactions at an afereza of lipoproteins of the low density (LPNP)
When holding a procedure of an aferez of lipoproteins of low density with the help a dextran - sulfate absorption, at purpose of APF inhibitors at patients anaphylactic reactions can develop.
Anaphylactic reactions when performing desensitization
There are separate messages on development of life-threatening anaphylactic reactions in the patients receiving APF inhibitors during the desensibilizing therapy by apitoxin (bees, wasps). APF inhibitors need to be applied with care at the patients with predisposition to allergic reactions undergoing procedures of desensitization. It is necessary to avoid purpose of APF inhibitors to the patients receiving an immunotherapy apitoxin. Nevertheless, this reaction can be avoided by temporary cancellation of APF inhibitor prior to the procedure.
Liver failure
Reception of APF inhibitors sometimes is associated with the syndrome beginning with development of the cholestatic jaundice progressing in a fulminantny necrosis of a liver, and (sometimes) with a lethal outcome. The mechanism of development of this syndrome is not clear. At emergence of symptoms of jaundice or increase in activity of enzymes of a liver in the patients accepting APF inhibitors it is necessary to stop therapy by drug and to conduct the corresponding examination.
Neutropenia / Agranulocytosis / Thrombocytopenia / Anemia can develop against the background of therapy by APF inhibitors. At normal function of kidneys and lack of other complications the neutropenia arises seldom. APF inhibitors are appointed only in case of emergency in the presence of system vasculites, performing immunodepressive therapy, reception of Allopyrinolum or procaineamide, and also at a combination of all listed factors, especially against the background of the previous renal failure. There is a risk of development of serious infectious diseases, resistant to an intensive antibioticotherapia. When performing therapy perindoprily at patients with above-mentioned factors it is regularly necessary to control quantity of leukocytes and to warn the patient about need to inform the attending physician on emergence of any symptoms of an infection.
Negroid race
It is necessary to consider that at patients of negroid race the risk of development of a Quincke's disease is higher. As well as other APF inhibitors, perindoprit is less effective concerning decrease in the ABP at patients of negroid race.
This effect is perhaps connected with the expressed dominance of the lowrenine status at patients of negroid race with arterial hypertension.
Cough
Against the background of therapy dry unproductive cough which stops after drug withdrawal can arise APF inhibitor.
Surgical intervention / General anesthesia
Use of APF inhibitors for patients whose condition demands surgical intervention and/or in need of the general anesthesia can lead to development of arterial hypotension or a collapse that is caused by sharp strengthening of anti-hypertensive action. Reception of a perindopril needs to be stopped one day before surgical intervention. At development of arterial hypotension it is necessary to support the ABP by completion of volume of the circulating blood.
Hyperpotassemia
The hyperpotassemia can develop in treatment time APF inhibitors, especially in the presence at the patient of renal and/or heart failure, an uncontrollable diabetes mellitus. Usually it is not recommended to appoint the potassium drugs, kaliysberegayushchy diuretics and other drugs associated with risk of increase in content of potassium (for example, heparin) because of possibility of the expressed hyperpotassemia. If joint reception of the specified drugs is necessary, then therapy has to be followed by regular control of content of potassium in blood serum.
Diabetes mellitus
At the patients accepting hypoglycemic means for intake or insulin within the first month of therapy glycemia level has to be controlled by APF inhibitors carefully.
Lithium
Joint administration of drugs of lithium and perindopril is not recommended.
The Kaliysberegayushchy diuretics, drugs containing potassium, kaliysoderzhashchy products and nutritional supplements
Combined use with APF inhibitors is not recommended (see. "Interaction with other medicines").
Influence on ability to driving of the car and to performance of work, the psychophysical reactions demanding high speed
The persons managing motor transport and who are engaged in the types of activity demanding the increased concentration of attention and bystry motor reaction in connection with danger of development of arterial hypotension and dizziness should appoint APF inhibitors with care.

Side effects:

System, bodies           Frequent collateral                 Rare collateral               Extremely rare
                                   effects> 1/100, <1/10      effects> 1/1000,          side effects
                                                                               <1/100                            <1/10 000
Urinary                                                Depression of function         Acute renal
system                                                                 of kidneys                                insufficiency
Respiratory organs        Cough, difficulty           Bronchospasm,                      Eosinophilic
                                  breath.                            angioneurotic          pneumonia,
                                                                              hypostasis.                                 rhinitis.
Digestive       Nausea, vomiting, pain in        Dryness in a mouth                  Cholestatic or
system                      stomach, taste disturbance                                              cytolytic
                                   diarrhea, lock, decrease                                             jaundice, pancreatitis.
                                   appetite.
Allergic          Skin rash, skin           Krapivnitsa                       Multiformnaya
reactions                    itch                                                                               erythema.
Nervous system      Headache, adynamy,         Decrease                          Confusion
                                 dizziness, ring in       moods,                       consciousnesses.
                                 ears, vision disorders,     sleep disorders.
                                 muscular spasms,
                                 paresthesias.
Others:                                                                 Perspiration.
                                                                              Disturbance of sexual
                                                                              functions.
Cardiovascular disturbances: excessive decrease in the ABP and related symptoms. Extremely seldom: arrhythmia, stenocardia, a myocardial infarction and a stroke, development of the secondary expressed arterial hypotension in patients of risk group is possible.
Laboratory indicators: extremely seldom: decrease in concentration of hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, isolated cases of an agranulocytosis or pancytopenia. A possibility of development of hemolitic anemia against the background of deficit glyukozo-6-fosfatdegidrogenazy. Seldom: increase in content of urea and creatinine of a blood plasma, the passing hyperpotassemia, especially against the background of a renal failure, increase in activity of "hepatic" enzymes and bilirubin of a liver.

Interaction with other medicines:

Diuretic means
In an initial stage of treatment at some patients against the background of therapy with diuretic means, especially at excess removal of liquid and/or salts, at the very beginning of therapy perindoprily excessive decrease in the ABP which risk of development can be reduced by cancellation of diuretic means, introduction of the raised amount of water and/or sodium chloride can be observed, and also appointing APF inhibitor in lower doses. Further increase in a dose of a perindopril has to be carried out with care.
Kaliysberegayushchy diuretics or drugs of potassium, kaliysoderzhashchy products and nutritional supplements
Against the background of therapy by APF inhibitors, as a rule, the content of potassium in blood serum remains within norm, but the hyperpotassemia can sometimes develop.
The combined use of APF inhibitors and kaliysberegayushchy diuretics (Spironolactonum, Triamterenum and amiloride) and drugs of potassium, kaliysoderzhashchy products and nutritional supplements can lead to essential increase in potassium concentration in blood serum. In this regard their joint appointment with APF inhibitors is not recommended. It is necessary to appoint these combinations only in case of a hypopotassemia, observing precautionary measures and constantly controlling the content of potassium in blood serum.
Lithium
Joint purpose of APF inhibitors and drugs of lithium can lead to reversible increase in concentration of lithium in blood serum and to development of lithium toxicity.
Additional use of thiazide diuretics against the background of the combined use of lithium and APF inhibitors increases already existing risk of development of lithium toxicity. Joint reception of APF inhibitors and lithium is not recommended. At impossibility to avoid this combination, it is necessary to carry out regular control of content of lithium in blood serum.
Non-steroidal anti-inflammatory drugs (NPVP), including acetylsalicylic acid (aspirin) ≥ 3 g/days.
Purpose of NPVP can be followed by easing of anti-hypertensive effect of APF inhibitors. Moreover, it is established that NPVP and APF inhibitors have the additive effect concerning increase in content of potassium in blood serum, at the same time also deterioration in function of kidneys is possible. As a rule, these effects have reversible character. In rare instances the acute renal failure arising, as a rule, at already existing renal failure at elderly patients or against the background of organism dehydration can develop.
Anti-hypertensive and vasodilators
The anti-hypertensive effect of drugs can amplify against the background of the combined use with APF inhibitors. Use of nitroglycerine and/or other vasodilators can result in additional hypotensive effect.
Allopyrinolum, immunodepressants, including cytostatic means and system glucocorticosteroids, procaineamide
Combined use with APF inhibitors can lead to increase in risk of development of a leukopenia.
Hypoglycemic means
Purpose of APF inhibitors can strengthen hypoglycemic effect of insulin and peroral hypoglycemic means up to development of a hypoglycemia. As a rule, this phenomenon is observed in the first weeks of the combined use of these drugs and at patients with a renal failure.
Tricyclic antidepressants / Antipsychotic means (neuroleptics) / Means for the general anesthesia
Joint appointment with APF inhibitors can lead to strengthening of hypotensive effect.
Sympathomimetics
Can weaken anti-hypertensive effect of APF inhibitors. At purpose of a similar combination it is necessary to estimate efficiency of APF inhibitors regularly.
Antiacid means
Reduce bioavailability of APF inhibitors.
Acetylsalicylic acid, thrombolytic means, beta adrenoblockers, nitrates
Perindopril can be appointed together with acetylsalicylic acid (as a trombolitik), thrombolytic means, beta adrenoblockers and/or nitrates.
Alcohol strengthens hypotensive effect of APF inhibitors.

Contraindications:

- hypersensitivity to the perindopril or excipients which are a part of drug and also to other APF inhibitors;
- a Quincke's disease in the anamnesis (the inborn/idiopathic or connected with the previous treatment by APF inhibitor reaction);
- pregnancy and the period of feeding by a breast (see. "Pregnancy and period of feeding by a breast").
WITH CARE
(see also "Special instructions")
· decrease in volume of the circulating blood (reception of diuretics, an electrolyte-deficient diet, vomiting, diarrhea, a hemodialysis), a hyponatremia, cerebrovascular diseases, stenocardia - risk of sharp decrease in the ABP;
· renovascular hypertensia, a bilateral stenosis of renal arteries or existence only one functioning kidney - risk of development of heavy arterial hypotension and renal failure;
· chronic renal failure;
· general diseases of connecting fabric (a system lupus erythematosus, a scleroderma) and therapy by immunodepressants – risk of development of an agranulocytosis and neutropenia;
· a hyperpotassemia (see. "Interaction with other medicines");
· stenosis of the aortal valve, hypertrophic subaortic stenosis;
· the procedure of a hemodialysis with use of high-flowing poliakrilnitrilovy membranes;
· before the procedure of an aferez of lipoproteins of the low density (LPNP) (hardware removal of cholesterol from blood);
· use for patients after transplantation of kidneys (there is no experience of a clinical use);
· simultaneous performing the desensibilizing therapy by allergens;
· surgical intervention (general anesthesia);
· with the diabetes mellitus receiving hypoglycemic means or insulin sugar level in blood is recommended to control patients
• age up to 18 years (efficiency and safety of use are not investigated).
Because monohydrate is a part of excipients of drug lactoses, Prestarium And is contraindicated to patients with a lactose intolerance, a galactosemia or a syndrome glucosic / галактозной malabsorption.
Prestarium And on 2,5 mg, 5 mg and 10 mg contains in drug tablets 36,29 mg, 72,58 mg and 145,16 mg of lactose of monohydrate respectively.
PREGNANCY AND PERIOD OF FEEDING BY THE BREAST
Drug use Prestarium But is not recommended in the I trimester of pregnancy. During the planning or confirmation of pregnancy it is necessary to pass to alternative therapy. The corresponding controlled researches at people were not conducted therefore there is no enough clinical data on effect of APF inhibitors in the I trimester of pregnancy. On limited quantity of cases of use of APF inhibitors in the I trimester of pregnancy, emergence of any malformations connected with a fetotoksichnost (see below) it was not observed.
Perindopril is contraindicated in II and III trimesters of pregnancy since there are fetotoksichnost given about manifestation (depression of function of kidneys, олигоамнион (the expressed reduction of volume of amniotic liquid), a delay of formation of bones of a skull) and neonatal toxicity (disturbance of functions of kidneys, hypotension, a hyperpotassemia). If therapy perindoprily was carried out in II and/or III trimesters of pregnancy, it is necessary to conduct ultrasonic examination of function of kidneys and a skull of a fruit.
Feeding period breast
Use of a perindopril during feeding by a breast is not recommended due to the lack of data on a possibility of its penetration into breast milk.

Overdose:

Symptoms: the expressed decrease in the ABP, shock, disturbances of electrolytic balance (such as increase in concentration of potassium ions, decrease in sodium); renal failure, hyperventilation, tachycardia, dizziness, bradycardia, concern and cough.
Treatment: at considerable decrease in the ABP it is necessary to transfer the patient to a prone position and to immediately make completion of volume of the circulating blood, whenever possible to enter infusion of angiotensin II and/or intravenous solution of catecholamines. At development of the steady expressed bradycardia use of the artificial driver of heart can be required. The main vital signs of an organism, electrolytes of blood serum and KK have to is under constant control. Perindopril can be removed from a system blood-groove with a hemodialysis method. It is necessary to avoid use of high-flowing poliakrilnitrilovy membranes.

Storage conditions:

To store in the place, unavailable to children. Special storage conditions are not required. PERIOD OF VALIDITY 3 years.
NOT TO APPLY AFTER THE TERMINATION OF THE PERIOD OF VALIDITY SPECIFIED ON PACKAGING.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 2.5 mg, 5 mg and 10 mg.
Tablets on 2.5 mg, 10 mg
On 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel. On 1 bottle with the instruction on a medical use in a pack cardboard with control of the first opening.
Tablets on 5,0 mg On 14 and 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel. On 1 bottle with the instruction on a medical use in a pack cardboard with control of the first opening.
When packaging (packaging) / production on LLC Serdiks, Russia
Release form
Tablets, film coated, 5 mg and 10 mg.
Tablets on 5,0 mg
On 14 and 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel. On 1 bottle with the instruction on a medical use in a pack cardboard with control of the first opening.
Tablets on 10 mg
On 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel. On 1 bottle with the instruction on a medical use in a pack cardboard with control of the first opening.
Packaging for hospitals: On 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel.
On 3 bottles on 30 tablets with instructions on a medical use in a pack cardboard with control of the first opening.
On 30 bottles on 30 tablets in the cardboard pallet for bottles with instructions on a medical use in a box cardboard with control of the first opening.