Престанс

General characteristics. Structure:

1 tablet of 5 mg + 5 mg: contains active agents of a perindopril of arginine 5 mg, there correspond 3,395 mg of a perindopril and the amlodipina безилат 6,935 mg corresponds to 5 mg of an amlodipin.
1 tablet of 10 mg + 10 mg: contains active agents of a perindopril of arginine 10 mg, there correspond 6,79 mg of a perindopril and the amlodipina безилат 13,87 mg corresponds to 10 mg of an amlodipin.
1 tablet of 5 mg + 10 mg: contains active agents of a perindopril of arginine 5 mg, there correspond 3,395 mg of a perindopril and the amlodipina безилат 13,87 mg corresponds to 10 mg of an amlodipin.
1 tablet of 10 mg + 5 mg: contains active agents of a perindopril of arginine 10 mg, there correspond 6,79 mg of a perindopril and the amlodipina безилат 6,935 mg corresponds to 5 mg of an amlodipin.
Excipients: cellulose microcrystallic, lactoses monohydrate, magnesium stearate, silicon dioxide colloid anhydrous.
DESCRIPTION
Tablets of 5 mg + 5 mg: oblong biconvex tablets of white color, with an engraving "5/5" on one party and a logo of firm on another.
Tablets of 5 mg + 10 mg: square biconvex tablets of white color, with an engraving "5/10" on one party and a logo of firm on another.
Tablets of 10 mg + 10 mg: round biconvex tablets of white color, with an engraving
"10 / 10" on one party and a logo of firm on another.
Tablets of 10 mg + 5 mg: triangular biconvex tablets of white color, with an engraving "10/5" on one party and a logo of firm on another.

Pharmacological properties:

Pharmacodynamics. Perindopril
Perindopril-inhibitor of the enzyme turning angiotensin I into angiotensin II (APF inhibitor). The angiotensin-converting enzyme, or a kininaza of II, 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.
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 also activated. Perindopril has therapeutic effect thanks to an active metabolite,
to perindoprilat. Other metabolites have no inhibiting effect on APF in vitro.
Arterial hypertension
Perindopril is drug for treatment of arterial hypertension of any severity. Against the background of its use decrease in both the systolic, and diastolic arterial pressure (AP) in situation is noted "lying" and "standing". Perindopril reduces the general peripheric vascular resistance that leads to decrease in the raised ABP and improvement of a peripheral blood-groove without change of the heart rate (HR). As a rule, reception of a perindopril increases a renal blood stream, the glomerular filtration rate at the same time does not change.
Anti-hypertensive effect of drug reaches a maximum in 4-6 hours after a single dose inside and remains within 24 hours. Anti-hypertensive action in 24 hours after a single dose inside makes about 87-100% of the maximum anti-hypertensive effect. Decrease in the ABP is reached quickly enough. The therapeutic effect occurs less than in 1 month from the beginning of therapy and is not followed by tachycardia. The termination of treatment does not cause a syndrome of "cancellation".
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.
Stable coronary heart disease (CHD)
Efficiency of use of a perindopril for patients (12218 patients are more senior than 18 years) from a stable ischemic heart disease without clinical symptoms of chronic heart failure was studied during the 4-year research (EUROPA). 90% of participants of a research had an acute myocardial infarction or coronary revascularization earlier.
Therapy perindoprily tretbutilaminy in a dose of 8 mg/days (10 mg of a perindopril of arginine are equivalent) led to essential decrease in absolute risk of complications by 1,9%, at the patients who earlier had a myocardial infarction or coronary revascularization, decrease in absolute risk made 2,2% in comparison with group of placebo.
Amlodipin
Amlodipin - BMKK derivative of a dihydropyridinic row. Amlodipin inhibits transmembrane transition of calcium ions to cardiomyocytes and smooth muscle cells of a vascular wall.
Anti-hypertensive action of an amlodipin is caused by direct impact on smooth muscle cells of a vascular wall. It is established that амлодипин
• causes expansion of peripheral arterioles, reducing the general peripheric resistance of vessels (afterload) as ChSS at the same time does not change, and the need of a myocardium for oxygen decreases.
• causes expansion of coronary arteries and arterioles both in ischemic, and in intact zones. At patients with Printsmetal's stenocardia at the same time the coronary blood stream improves.
At patients with the arterial hypertension (AH) reception of an amlodipin of 1 times a day provides clinically significant decrease in the ABP in a standing position and "lying" during 24 h. Anti-hypertensive action develops slowly in this connection development of acute arterial hypotension is uncharacteristic.
At patients with stenocardia reception of an amlodipin of 1 times a day increases tolerance to an exercise stress, approach of an attack of stenocardia and "ischemic" depression of a segment of ST detains, and also reduces the frequency of attacks of stenocardia and consumption of nitroglycerine (short-range forms).
Amlodipin does not exert impact on indicators of a lipidic profile and does not cause change of hypolipidemic indicators of a blood plasma. Drug can be used at patients with the accompanying bronchial asthma, a diabetes mellitus and gout.
Efficiency and safety of use of an amlodipin in a dose of 2,5-10 mg/days, lisinopril APF inhibitor in a dose of 10-40 mg/days and thiazide diuretic of Chlortalidonum in a dose of 12,5-25 mg/days as drug of "the first line" was studied in 5 the summer research ALLHAT (with participation of 33357 patients at the age of 55 years and is more senior) at patients with soft or moderate degree of AG and, at least, one of accessory factors of risk of coronary complications, such as: a myocardial infarction or the stroke which is had more than in 6 months prior to inclusion in a research, or other confirmed cardiovascular disease of atherosclerotic genesis; diabetes mellitus; level of cholesterol of lipoproteins of high density (XC LPVP) of less than 35 mg/dl; the hypertrophy of a left ventricle according to an electrocardiography was studied lisinopril APF inhibitor in a dose of 10-41 mg/days or an echocardiography; smoking.
The main criterion for evaluation of efficiency – the combined indicator of frequency of lethal outcomes from an ischemic heart disease and the frequency of not fatal myocardial infarction. Essential distinctions between groups of an amlodipin and Chlortalidonum on the main evaluation criterion were not revealed. Frequency of development of heart failure in group of an amlodipin was significantly higher, than in group of Chlortalidonum – 10,2% and 7,7%, respectively, the general frequency of lethal outcomes in group of an amlodipin and Chlortalidonum significantly did not differ.
Perindopril, амлодипин
Efficiency at prolonged use of an amlodipin in a combination with perindoprily and an atenolola in a combination with bendroflumetiazidy at patients aged from 40 up to 79 years with AG and, at least, 3 of accessory factors of risk: a hypertrophy of a left ventricle according to an ECG or an echocardiography; diabetes mellitus 2 types; atherosclerosis of peripheral arteries; earlier had stroke or the tranzitorny ischemic attack; male; the age of 55 years is also more senior; microalbuminuria or proteinuria; smoking; LPVP general cholesterol / HS ≥ 6; by an ischemic heart disease prematurity at the immediate family it was studied in the research ASCOT-BPLA.
The main criterion for evaluation of efficiency – the combined indicator of frequency of not fatal myocardial infarction (including, bezbolevy) and lethal outcomes of an ischemic heart disease.
Frequency of the complications provided by the main evaluation criterion in group of an amlodipina/perindopril was 10% lower, than in group of an atenolola/bendroflumetiazid, however this distinction was not statistically reliable. In group of an amlodipina/perindopril reliable decrease in frequency of the complications provided by additional criteria of efficiency was noted (except fatal and not fatal heart failure).

Pharmacokinetics. The size of absorption of a perindopril and amlodipin at use of drug of Prestans significantly does not differ from that when using monodrugs.
Perindopril
At intake perindoprit quickly it is soaked up, the maximum concentration in a blood plasma is reached during 1 h. The elimination half-life (T1/2) makes 1 h of a blood plasma.
Perindopril has no pharmacological activity. About 27% of the total quantity accepted in a perindopril get to a blood stream in the form of an active metabolite of a perindoprilat. In addition to a perindoprilat 5 more metabolites which do not have pharmacological activity are formed. The maximum concentration of a perindoprilat in a blood plasma is reached in 3-4 hours after intake. Meal slows down transformation of a perindopril in периндоприлат, thus, influencing bioavailability. Therefore it is necessary to accept drug 1 time a day, in the morning, before meal.
There is a linear dependence of concentration of a perindopril in a blood plasma from its dose. The volume of distribution of a free perindoprilat makes about 0,2 l/kg. Communication of a perindoprilat with proteins of a blood plasma, mainly with APF, makes about 20% and. has dozozavisimy character.
Perindoprilat is brought from an organism by kidneys. The final elimination half-life (T1/2) of free fraction makes about 17 h therefore the equilibrium state is reached within 4 days.
Removal of a perindoprilat is slowed down at advanced age, and also at patients with a heart and renal failure (see the section "Route of Administration and Doses"). Therefore at these groups of patients it is regularly necessary to control concentration of creatinine and potassium in a blood plasma.
The dialysis clearance of a perindoprilat makes 70 ml/min.
The pharmacokinetics of a perindopril is changed at patients with cirrhosis: its hepatic clearance decreases twice. Nevertheless, the quantity of the formed perindoprilat does not decrease that does not demand dose adjustment (see the sections "Route of Administration and Doses" and "Special Instructions").
5amlodipin
The maximum concentration of an amlodipin in a blood plasma is reached in 6-12 h after administration of drug inside. Absolute bioavailability makes about 64-80%, distribution volume – about 21 l/kg. Meal does not influence bioavailability of an amlodipin. In the researches in vitro it was shown that about 97,5% of the circulating amlodipin are connected with proteins of a blood plasma.
Final T1/2 of an amlodipin makes 35-50 h of a blood plasma that allows to accept drug of 1 times a day. Amlodipin is metabolized in a liver with formation of inactive metabolites. About 60% of the accepted dose of an amlodipin are removed by kidneys, 10%– in not changed look.
Time from administration of drug before achievement of the maximum concentration of an amlodipin does not differ at patients of elderly and younger age. At patients of advanced age delay of clearance of an amlodipin is noted that "concentration time" (AUC) leads to increase in the area under a curve. Patients of advanced age do not need drug dose adjustment, but it is necessary to increase a dose of an amlodipin with care.
Use for patients with a renal failure (see the section "Route of Administration and Doses").
At patients with a liver failure of T1/2 of an amlodipin increases.

Indications to use:

Arterial hypertension and/or coronary heart disease (CHD): a stable angina of exertion at patients who need therapy perindoprily and amlodipiny.

Route of administration and doses:

Inside, on 1 tablet of 1 times a day it is preferable in the morning before meal.
The dose of drug of Prestans is selected after earlier carried out titration of doses of separate components of drug: a perindoprila and an amlodipina at patients with arterial hypertension and stable stenocardia.
At therapeutic need, the dose of drug of Prestans can be changed, on the basis of individual selection of doses of separate components.
5 mg of a perindopril + 5 mg of an amlodipin OR
5 mg of a perindopril + 10 mg of an amlodipin OR
10 mg of a perindopril + 5 mg of an amlodipin OR
10 mg of a perindopril + 10 mg of an amlodipin.
Престанс in doses of 10 mg of a perindopril + 10 mg of an amlodipin are the maximum daily dose of drug which is not recommended to be exceeded.
8 Patients of advanced age and patients with a renal failure (see the sections "Pharmacokinetics" and "Special Instructions")
Removal of a perindoprilat at patients of advanced age and patients with a renal failure is slowed down. Therefore at such patients it is regularly necessary to control concentration of creatinine and potassium in a blood plasma.
Престанс it can be appointed to patients with KK equal or exceeding 60 ml/min.
Престанс it is contraindicated to patients with KK less than 60 ml/min. Individual selection of doses of a perindopril and amlodipin is recommended to such patients. Change of concentration of an amlodipin in a blood plasma does not correlate with degree of manifestation of a renal failure.
Patients with a liver failure (see the sections "Route of Administration and Doses" and "Special Instructions")
It is necessary to be careful at purpose of drug of Prestans to patients with a liver failure due to the lack of recommendations about a drug dosing at such patients.
Children and teenagers
Престанс should not appoint children and teenagers up to 18 years due to the lack of data on efficiency and safety of use of a perindopril and amlodipin for these groups of patients both in the form of monotherapy, and in the form of a combination therapy.

Features of use:

The special instructions relating to a perindopril and an amlodipin are applicable to drug of Prestans.
Perindopril
The increased sensitivity / a Quincke's disease
At reception of APF inhibitors including the perindoprila, in rare instances can be observed development of a Quincke's disease of the person, extremities, lips, mucous membranes, language, a glottis and/or throat (see the section "Side effect"). At emergence of symptoms administration of drug has to be immediately stopped, and the patient has to be observed until symptoms of hypostasis do not disappear completely. If hypostasis affects only a face and lips, then its manifestations usually take place independently though antihistamines can be applied to treatment of symptoms.
The Quincke's disease which is followed by throat hypostasis can lead to a lethal outcome. The paraglossa, a glottis or a throat can lead to obstruction of respiratory tracts. At emergence of such symptoms it is necessary to enter immediately Epinephrinum (adrenaline) subcutaneously and/or to provide passability of respiratory tracts. The patient has to be under medical observation before total and permanent disappearance of symptoms.
At patients with the Quincke's edema in the anamnesis which is not connected with reception of APF inhibitors the risk of its development at administration of drugs of this group can be increased (see the section "Contraindications").
In rare instances against the background of therapy by APF inhibitors the Quincke's disease of intestines develops. At the same time at patients the abdominal pain as the isolated symptom or in combination with nausea and vomiting, in certain cases, without the previous Quincke's disease of the person is noted and at the normal C1 esterase level. The diagnosis is established by means of a computer tomography of belly area, ultrasonography or at the time of surgical intervention. Symptoms disappear after the termination of reception of APF inhibitors. Therefore at the patients with pain in a stomach receiving APF inhibitors when carrying out differential diagnosis it is necessary to consider a possibility of development of a Quincke's disease of intestines (see the section "Side effect").
Anaphylactoid reactions when carrying out an aferez of LPNP
In rare instances at the patients receiving APF inhibitors when carrying out an aferez of lipoproteins of the low density (LPNP) with use of a dextran life-threatening anaphylactoid reactions can develop. For prevention of anaphylactoid reaction it is necessary to stop temporarily therapy by APF inhibitor before each procedure of an aferez.
Anaphylactoid reactions when performing desensitization
There are separate messages on development of anaphylactoid reactions in the patients receiving APF inhibitors during desensibilizirushchy therapy (for example, poison of hymenopterous insects). At the same patients of anaphylactoid reaction it was possible to avoid by temporary cancellation of APF inhibitors, and at accidental administration of drug anaphylactoid reaction arose again.
Нейтропения/агранулоцитоз/тромбоцитопения/анемия
Against the background of reception of APF inhibitors there can be a neutropenia/agranulocytosis, thrombocytopenia and anemia. At patients with normal function of kidneys and in the absence of other burdening factors the neutropenia develops seldom. With extra care follow to apply perindoprit at patients with diffusion diseases of connecting fabric, against the background of reception of immunodepressants, Allopyrinolum or procaineamide, especially at patients with an impaired renal function.
Some patients had crushing infectious defeats, in some cases, steady against an intensive antibioticotherapia. At purpose of a perindopril such patients are recommended to control periodically quantity of leukocytes in blood. Patients have to report to the doctor about any symptoms of infectious diseases.
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 diuretics, at observance of a rigid electrolyte-deficient diet, a hemodialysis, diarrhea and vomiting, and also at patients with heavy degree of arterial hypertension with high activity of a renin (see the sections "Interaction with Other Medicines"). At patients with the increased risk of development of symptomatic arterial hypotension it is necessary to control carefully the ABP, function of kidneys and content of potassium in blood serum during therapy by drug of Prestans.
Similar approach is applied also at patients with stenocardia and cerebrovascular diseases at which the expressed arterial hypotension can lead to a myocardial infarction or disturbance of cerebral circulation.
In case of development of arterial hypotension of the patient it has to be transferred to situation "lying" on spin with the raised legs. If necessary it is necessary to fill the volume of the circulating blood by means of intravenous administration of 0,9% of solution of sodium of chloride. Passing arterial hypotension is not an obstacle for further administration of drug. After recovery of volume of the circulating blood and the ABP treatment can be continued.
Mitral stenosis / aortal stenosis / hypertrophic cardiomyopathy
Престанс, as well as other APF inhibitors, it has to be appointed with care to patients with obstruction of an output path of a left ventricle (an aortal stenosis, a hypertrophic cardiomyopathy), and also patients with a mitral stenosis.
Renal failure
To patients with a renal failure (KK less than 60 ml/min.) recommends individual selection of doses of a perindopril and amlodipin. Regular control of content of potassium and creatinine in blood serum is necessary for such patients (see the section "Side effect").
At patients with a bilateral renal artery stenosis or a stenosis of an artery of the only kidney against the background of therapy by APF inhibitors the increase in content of urea and creatinine in blood serum which is usually taking place at therapy cancellation is possible. More often this effect is noted at patients with a renal failure. Additional existence of renovascular hypertensia causes the increased risk of development of heavy arterial hypotension and renal failure in such patients.
At some patients with arterial hypertension without signs of defeat of vessels of kidneys increase in concentration of urea and creatinine in blood serum is possible, especially at joint purpose of a perindopril with diuretic, usually insignificant and passing. More often this effect is noted at patients with the previous renal failure.
Liver failure
In rare instances against the background of reception of APF inhibitors there is cholestatic jaundice. When progressing this syndrome the fulminantny necrosis of a liver, sometimes with a lethal outcome develops. The mechanism of development of this syndrome is not clear. At emergence of jaundice or substantial increase of activity of "hepatic" enzymes against the background of reception of APF inhibitors it is necessary to stop administration of drug and to see a doctor (see the section "Side effect").
Ethnic distinctions
At patients of negroid race more often than at representatives of other races, against the background of reception of APF inhibitors the Quincke's disease develops.
Perindopril, as well as other APF inhibitors, perhaps, has less expressed hypotensive effect at patients of negroid race in comparison with representatives of other races. Perhaps, this distinction is caused by the fact that at patients with arterial hypertension of negroid race low activity of a renin is more often noted.
Cough
Against the background of therapy dry cough can arise APF inhibitor. Cough it is long remains against the background of administration of drugs of this group and disappears after their cancellation. At emergence in the patient of dry cough it is necessary to remember possible iatrogenic character of this symptom.
Surgical intervention / general anesthesia
Use of APF inhibitors for the patients who are exposed to extensive surgical intervention and/or the general anesthesia can lead to the expressed decrease in the ABP, means for the general anesthesia with hypotensive action esliispolzutsya. It is connected with blocking of formation of angiotensin II against the background of compensatory increase in activity of a renin. If development of arterial hypotension is connected with the described mechanism, it is necessary to increase the volume of the circulating plasma. It is recommended to stop administration of drug for 24 h to surgical intervention.
Hyperpotassemia
The hyperpotassemia can develop in treatment time APF inhibitors, including, and perindoprily. Risk factors of a hyperpotassemia are the renal failure, advanced age (70 years), a diabetes mellitus, some accompanying states (dehydration, an acute decompensation of chronic heart failure, a metabolic acidosis), a concomitant use of kaliysberegayushchy diuretics (such as Spironolactonum and its derivative эплеренон, Triamterenum, amiloride), and also drugs of potassium or kaliysoderzhashchy substitutes of edible salt, and also use of other drugs promoting increase the content of potassium in a blood plasma (for example, heparin are more senior). Use of drugs of potassium, kaliysberegayushchy diuretics, kaliysoderzhashchy substitutes of edible salt can lead to substantial increase of level of potassium in blood, especially at patients with reduced function of kidneys. The hyperpotassemia can bring to serious, sometimes to fatal disturbances of a cordial rhythm. If the concomitant use of a perindopril and the drugs stated above is necessary, treatment has to be carried out with care against the background of regular control of content of potassium in blood serum (see the section "Interaction with Other Medicines").
Patients with a diabetes mellitus
At purpose of drug patients with the diabetes mellitus receiving hypoglycemic means for oral administration or insulin within the first month of therapy need to control carefully concentration of glucose in blood (see the section "Interaction with Other Medicines").
Amlodipin
Liver failure
At patients with an abnormal liver function of T1/2 of an amlodipin increases. At purpose of drug such patients should be careful and to regularly control activity of "hepatic" enzymes.
Chronic heart failure
At purpose of an amlodipin patients should be careful with chronic heart failure.
20 Престанс
Excipients
Because of availability of lactose as a part of drug patients should not appoint drug with a hereditary lactose intolerance, a lactose intolerance and glyukozo-galaktozny malabsorption.
Influence on ability to drive the car and to perform the works demanding the increased speed of physical and mental reactions
Due to the possible development of weakness and dizziness, it is necessary to be careful at control of vehicles and occupations the certain types of activity demanding the increased concentration of attention and bystry motor reaction.

Side effects:

Frequency of side reactions which were noted during monotherapy perindoprily and amlodipiny is specified in a type of the following gradation: very often (≥1/10); often (≥1/100, <1/10); infrequently (≥1/1000, <1/100); seldom (≥1/10000, <1/1000); very seldom (<1/10000), including separate messages; not specified frequency (frequency cannot be counted according to available data).
From circulatory and lymphatic system:
Very seldom: a leukopenia/neutropenia, an agranulocytosis, a pancytopenia, thrombocytopenia, hemolitic anemia at patients with inborn deficit glyukozo-6-fosfatdegidrogenazy, decrease in concentration of hemoglobin and a hematocrit.
From immune system:
9 Infrequently: small tortoiseshell.
Metabolic disturbances:
Infrequently: increase in body weight, body degrowth;
Very seldom: hyperglycemia.
From the central nervous system:
Often: drowsiness, dizziness, headache, paresthesias;
Infrequently: sleeplessness, lability of mood, sleep disorder, tremor, hypesthesias;
Very seldom: peripheral neuropathy, confusion of consciousness.
From an organ of sight:
Often: visual disturbances.
From an acoustic organ:
Often: sonitus.
From cardiovascular system:
Often: heartbeat, "inflows" of blood to face skin, the expressed decrease in the ABP;
Infrequently: syncope;
Seldom: pain behind a breast;
Very seldom: stenocardia, a myocardial infarction, perhaps, owing to excess decrease in the ABP at patients from group of high risk (see the section "Special Instructions"), arrhythmias (including, bradycardia, ventricular tachycardia and a ciliary arrhythmia), a stroke, perhaps, owing to excess decrease in the ABP at patients from group of high risk (see the section "Special Instructions"), a vasculitis.
From respiratory system:
Often: short wind, cough;
Infrequently: rhinitis, bronchospasm;
Very seldom: eosinophilic pneumonia.
From the alimentary system:
Often: abdominal pain, nausea, vomiting, dyspepsia, disturbance of flavoring perception, diarrhea, lock;
10 Infrequently: lock, dryness of a mucous obolocha of an oral cavity;
Very seldom: pancreatitis, hyperplasia of gums, gastritis.
From a liver and biliary tract:
Very seldom: hepatitis, cholestatic jaundice, cytolytic or cholestatic hepatitis (see the section "Special Instructions").
From integuments and a hypodermic fatty tissue:
Often: skin itch, rash;
Infrequently: a Quincke's disease of the person, extremities, lips, mucous membranes, language, a glottis and/or throat (see the section "Special Instructions"), an alopecia, hemorrhagic rash, a photosensitization, the increased perspiration;
Very seldom: Quincke's edema, multiformny erythema, Stephens-Johnson's syndrome.
From a musculoskeletal system and connecting fabric:
Often: spasms of muscles;
Infrequently: arthralgia, mialgiya, dorsodynia.
From kidneys and urinary tract:
Infrequently: disturbance of an urination, a nocturia, the speeded-up urination, a renal failure;
Very seldom: heavy renal failure.
From reproductive system and chest glands
Infrequently: impotence, gynecomastia;
General frustration and symptoms:
Often: peripheral hypostases, adynamy, increased fatigue;
Infrequently: thorax pain, indisposition.
Laboratory indicators:
Seldom: increase in level of bilirubin;
Very seldom: increase in activity of "hepatic" enzymes: aspartate aminotransferases (nuclear heating plant), alaninaminotranspherase (ALT) (it is the most frequent – in combination with a cholestasia); Not specified frequency: increase in concentration of urea and creatinine in blood serum, a hyperpotassemia (see the section "Special Instructions").

Interaction with other medicines:

Not recommended combinations of medicines
Kaliysberegayushchy diuretics, drugs of potassium and kaliysoderzhashchy substitutes of edible salt: APF inhibitors reduce the potassium loss by kidneys caused by diuretic. Kaliysberegayushchy diuretics (for example, Spironolactonum, Triamterenum, amiloride), can lead drugs of potassium and kaliysoderzhashchy substitutes of edible salt to essential increase in content of potassium in blood serum (see the section "Special Instructions"). If combined use of APF inhibitor and the means stated above is necessary (in case of the confirmed hypopotassemia), it is necessary to be careful and carry out regular control of content of potassium in a blood plasma and the ECG parameters.
Lithium drugs: at simultaneous use of drugs of lithium and APF inhibitors there can be a reversible increase in content of lithium in a blood plasma and the toxic effects connected with it. Simultaneous use of a perindopril and drugs of lithium is not recommended. In need of performing such therapy regular control of content of lithium in a blood plasma is necessary (see the section "Special Instructions").
Estramustinum: the combined use is followed by the increased risk of development of a Quincke's disease.
The combination of medicines requiring special attention
Non-steroidal anti-inflammatory drugs (NPVP), including high doses of acetylsalicylic acid (more than 3 g/days): purpose of NPVP can lead to decrease in diuretic, natriuretic and hypotensive effects. At considerable loss of liquid, and also at elderly patients, the acute renal failure can develop (owing to reduction in the rate of glomerular filtering). Patients need to offset loss of liquid and in an initiation of treatment carefully to control function of kidneys.
Hypoglycemic means (insulin, sulphonylurea derivatives): APF inhibitors can strengthen hypoglycemic effect of insulin and derivatives of sulphonylurea at patients with a diabetes mellitus. Development of a hypoglycemia is observed very seldom (possibly, due to increase in tolerance to glucose and decrease in need for insulin).
The combination of medicines requiring attention 13 Diuretics (thiazide and loopback): at the patients receiving diuretics, especially at excess removal of liquid and/or electrolytes at the beginning of therapy considerable decrease in the ABP which risk of development can be reduced by cancellation of diuretic, introduction of the increased amount of liquid and/or sodium of chloride can be observed by APF inhibitor, and also appointing perindoprit in a low dose with its further gradual increase.
Sympathomimetics: can weaken hypotensive effect of APF inhibitors.
Gold drugs: at purpose of APF inhibitors, including, perindoprit to the patients receiving injection drugs of gold (sodium ауротиомалат) nitratopodobny reactions (a dermahemia of the person, nausea, vomiting, arterial hypotension) were noted.
Allopyrinolum, cytostatic and immunosuppressive means, kortikosteroda (at system use) and procaineamide: simultaneous use with APF inhibitors can be followed by the increased risk of a leukopenia.
Means for the general anesthesia: combined use of APF inhibitors and means for the general anesthesia can lead to strengthening of hypotensive effect.
Amlodipin
Not recommended combinations of medicines
Dantrolen (intravenous administration): at laboratory animals cases of fibrillation of ventricles with a lethal outcome against the background of use of verapamil and intravenous administration of a dantrolen were noted. Extrapolating the available data, it is necessary to avoid the combined use of a dantrolen and an amlodipin.
The combination of medicines requiring special attention
CYP3A4 cytochrome inductors (rifampicin, drugs of the St. John's Wort which is made a hole, anticonvulsants, such as carbamazepine, phenobarbital, Phenytoinum, фосфенитоин, Primidonum): decrease in plasma concentration of an amlodipin because of strengthening of his metabolism in a liver is possible. It is necessary to be careful at simultaneous use of an amlodipin and inductors of a microsomal oxidation and if necessary to adjust a dose of an amlodipin.
CYP3A4 cytochrome inhibitors (итраконазол, кетоконазол): increase in plasma concentration of an amlodipin and increase in risk of side effects is possible. It is necessary to be careful at simultaneous use of an amlodipin and itrakonazol or ketokonazol, if necessary to adjust a dose of an amlodipin. The combination of medicines requiring attention
The beta adrenoblockers applied at chronic heart failure (бисопролол, карведилол, метопролол): risk of development of arterial hypotension and deterioration in a course of chronic heart failure at patients with uncontrollable or latent chronic heart failure (strengthening of a negative inotropic effect). Also beta adrenoblockers can reduce excessive reflex cordial sympathetic activation against the background of the accompanying chronic heart failure.
Other combinations of medicines:
Safety of use of an amlodipin when sharing in a combination with thiazide diuretics, beta adrenoblockers, APF inhibitors, nitrates in the prolonged dosage forms is noted, nitroglycerine (for hypoglossal use), digoxin, warfarin, atorvastatiny, sildenafily, antacids (алгелдрат, magnesium hydroxide), simetikony, Cimetidinum, NPVP, antibiotics and hypoglycemic means for intake.
Besides, in special researches lack of interaction of the following medicines with amlodipiny was shown:
- at combined use of an amlodipin and Cimetidinum pharmacokinetic parameters of an amlodipin did not change;
- at combined use of an amlodipin and sildenafil strengthening of hypotensive effect of each of drugs is noted;
- grapefruit juice: in a research with participation of 20 healthy volunteers it is shown that reception of 240 ml of grapefruit juice together with a single dose of an amlodipin (10 mg inside) did not exert significant impact on pharmacokinetics of an amlodipin.
Amlodipin does not influence pharmacokinetics of the following medicines:
- аторвастатин: reception of repeated doses of an amlodipin of 10 mg in a combination with atorvastatiny in a dose of 80 mg does not lead to essential change of equilibrium pharmacokinetic parameters of an atorvastatin;
- digoxin: joint purpose of an amlodipin and digoxin is not followed by change of content of digoxin in blood serum and renal clearance of digoxin at healthy volunteers;
15 warfarin: at healthy volunteers is a male, receiving warfarin, addition of an amlodipin had no significant effect on change of size of the prothrombin time caused by warfarin;
- cyclosporine: амлодипин has no significant effect on pharmacokinetic parameters of cyclosporine.
The combination of medicines requiring special attention:
Baclofenum: strengthening of hypotensive effect is possible. It is necessary to control the ABP and function of kidneys, if necessary – to adjust a dose of an amlodipin.
The combination of drugs requiring attention:
Antihypertensives (for example, beta adrenoblockers) and vazodilatator: strengthening of hypotensive effect of a perindopril and amlodipin is possible. It is necessary to be careful at co-administration with nitroglycerine, other nitrates or other vazodilatator as at the same time perhaps additional decrease in the ABP.
Corticosteroids (mineralo-and glucocorticosteroids), тетракозактид: decrease in hypotensive action (a delay of liquid and ions of sodium as a result of action of corticosteroids).
Alpha adrenoblockers (Prazozinum, альфузозин, доксазозин, тамсулозин, теразозин): strengthening of hypotensive action and increase in risk of orthostatic hypotension.
Amifostin: strengthening of hypotensive action of an amlodipin is possible.
Tricyclic antidepressants / neuroleptics / means for the general anesthesia: strengthening of hypotensive action and increase in risk of orthostatic hypotension.

Contraindications:

Perindopril
- Hypersensitivity to a perindopril or other APF inhibitors.
- A Quincke's disease (Quincke's edema) in the anamnesis (including against the background of reception of other APF inhibitors).
- Hereditary/idiopathic Quincke's disease.
- Age up to 18 years (efficiency and safety are not established).
Amlodipin
- Hypersensitivity to an amlodipin or other derivatives of dihydropyridine.
- The expressed arterial hypotension (systolic the ABP less than 90 mm hg).
- Obstruction of an output path of a left ventricle (for example, the expressed aorta stenosis).
- Unstable stenocardia (except for Printsmetal's stenocardia).
- Age up to 18 years (efficiency and safety are not established).
Престанс
- Hypersensitivity to the excipients which are a part of drug.
- Renal failure (clearance of creatinine (CC) less than 60 ml/min.).
- Age up to 18 years (efficiency and safety are not established).
- Hereditary lactose intolerance, lactose intolerance and glyukozo-galaktozny malabsorption.
WITH CARE
Renal artery stenosis (including, bilateral), the only functioning kidney, a liver failure, a renal failure, general diseases of connecting fabric (including, a system lupus erythematosus, a scleroderma), therapy by immunodepressants, Allopyrinolum, procaineamide (risk of development of a neutropenia, agranulocytosis), the reduced volume of the circulating blood (reception of diuretics, an electrolyte-deficient diet, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertensia, a diabetes mellitus, chronic heart failure, use of a dantrolen, estramustinum, kaliysberegayushchy diuretics, drugs of potassium, kaliysoderzhashchy substitutes of edible salt and drugs of lithium, a hyperpotassemia, surgical intervention / the general anesthesia, advanced age, carrying out a hemodialysis with use of high-flowing membranes (for example, AN69®), the desensibilizing therapy, аферез lipoproteins of the low density (LPNP), aortal stenosis / mitral stenosis / hypertrophic cardiomyopathy, patients of negroid race.
Pregnancy and period of feeding by a breast
Pregnancy
Drug is contraindicated to use at pregnancy.
Except for cases when therapy by drug of Prestans is necessary according to vital indications, when planning pregnancy it is necessary to cancel drug and to appoint other anti-hypertensive means allowed for use at pregnancy. At approach of pregnancy it is necessary to cancel immediately administration of drug of Prestans and, if necessary, to appoint other therapy.
7 It is known that impact of APF inhibitors on a fruit in II and III trimesters of pregnancy can lead to disturbance of its development (depression of function of kidneys, олигогидрамнион, delay of ossification of bones of a skull) and to development of complications in the newborn (a renal failure, arterial hypotension, a hyperpotassemia).
If the patient received APF inhibitors in II or III trimesters of pregnancy, it is recommended to conduct ultrasonic examination of a fruit for assessment of a condition of a skull and function of kidneys.
Newborns whose mothers received APF inhibitors at pregnancy need careful medical observation because of risk of development of arterial hypotension, an oliguria and a hyperpotassemia (see sections of "Contraindication" and "Special Instructions").
The available limited data on reception of an amlodipin and other BMKK at pregnancy demonstrate that drug does not make negative impact on a fruit. However, there is a risk of lengthening of childbirth.
Feeding period breast
It is not recommended to accept Prestans in the period of a lactation due to the lack of the corresponding clinical experience of use of a perindopril and an amlodipin both in the form of monotherapy, and in a combination.
In need of administration of drug, it is necessary to stop breastfeeding.

Overdose:

Information on overdose of drug of Prestans is absent.
Amlodipin
Information on overdose of an amlodipin is limited.
Symptoms: the expressed decrease in the ABP with possible development of reflex tachycardia and an excessive peripheral vazodilatation (risk of development of the expressed and persistent arterial hypotension, including with development of shock and a lethal outcome).
Treatment: a gastric lavage, purpose of absorbent carbon (especially in the first 2 h after overdose), maintenance of function of cardiovascular system, sublime position of extremities, control of OTsK and a diuresis, a symptomatic and maintenance therapy, in/in administration of calcium of a gluconate and dopamine. Dialysis is inefficient. At considerable decrease in the ABP it is necessary to make observation of the patient in the conditions of cardiological intensive care unit. In the absence of contraindications for recovery of a tone of vessels and the ABP it is possible to use vasoconstrictors.
Perindopril
Data on overdose of a perindopril are limited.
Symptoms: considerable decrease in the ABP, shock, electrolytic disturbances, renal failure, hyperventilation, tachycardia, heartbeat, bradycardia, dizziness, concern and cough.
Treatment: at considerable decrease in the ABP it is necessary to transfer the patient to situation "lying" on spin with the raised legs, if necessary to carry out correction of a hypovolemia (for example, intravenous infusion of 0,9% of solution of sodium of chloride). Also perhaps intravenous administration of angiotensin II and/or catecholamines. By means of a hemodialysis it is possible to remove perindoprit from a system blood-groove (see the section "Special Instructions"). At bradycardia, resistant to therapy, installation of an artificial pacemaker can be required. Dynamic control of a physical state, concentration of creatinine and electrolytes of a blood plasma is necessary.
Measures of acute management come down to removal of drug from an organism: to a gastric lavage and/or purpose of absorbent carbon with the subsequent recovery of water and electrolytic balance.

Storage conditions:

Special storage conditions are not required. To store a bottle densely closed. To store in original packaging. To store in the place, unavailable to children. PERIOD OF VALIDITY
2 years.
NOT TO APPLY AFTER THE PERIOD OF VALIDITY SPECIFIED ON PACKAGING.

Issue conditions:

According to the recipe

Packaging:

The tablets containing 5 mg of a perindopril of arginine + 5 mg of an amlodipin, 10 mg of a perindopril of arginine + 10 mg of an amlodipin, 5 mg of a perindopril of arginine + 10 mg of an amlodipin, 10 mg of a perindopril of arginine + 5 mg of an amlodipin.
On 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel (silica gel).
On 1 bottle with the instruction on a medical use in a pack cardboard with control of the first opening.
When packaging (packaging) at the Russian enterprise LLC Serdiks:
On 30 tablets in the bottle from polypropylene supplied with the doser and the stopper containing the moisture absorbing gel (silica 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 30 bottles in the cardboard pallet with cells for bottles, with the equal number of instructions on a medical use in a box cardboard with control of the first opening.
On 3 bottles with the equal number of instructions on a medical use in a pack cardboard with control of the first opening.