How prestarium works. Reducing the risk of cardiovascular complications

The medical preparation "Prestarium" is used in.

In accordance with the instructions for use, the drug has a positive effect not only on the vessels, but also on other tissues of the body.

Prestarium, like other high blood pressure pills, removes the total peripheral vascular resistance, improving pressure indicators.

Letters from our readers

Topic: Grandma's blood pressure returned to normal!

To: site administration

Kristina
Moscow city

My grandmother's hypertension is hereditary - most likely, the same problems await me with age.

Patients are interested in what else Prestarium is prescribed for. The drug includes a number of indications for use:

• arterial hypertension;
• heart failure;
• as a prevention of recurrent stroke;
• coronary heart disease.

The reasons for the increase in pressure are stress, excess salt, atherosclerosis of blood vessels, which provokes their spasm, as well as an increase in the volume of circulating blood. In accordance with the instructions for use, it does not increase the heart rate, that is, it does not increase the load on the heart. The price of the drug is due to its complex effect on the body, its modernity and other advantages.

In patients with arterial hypertension, the vessels of the whole body are affected. The cause of the violation is often coronary heart disease. The narrowing of the lumen of the vessels causes an increase in the load on the left atrium. Because of this, the muscle layer of the heart is stretched. Blood is worse removed from the lower extremities, edema appears.

Stroke - rupture of cerebral vessels with hemorrhage, caused by atherosclerosis, trauma, thinning of their walls. An increase in pressure enhances the effect on blood vessels. The expansion of the lumen causes an improvement in the patient's well-being, reduces the risk of recurrent cerebrovascular accident, exacerbation or ischemic attacks.

The coronary vessels nourish the heart and suffer the most from nutritional deficiencies. Therefore, when narrowing the lumen, care must be taken to make it easier for blood to pass through the arteries.

Effect on blood pressure

Tablets Prestarium A from pressure, in accordance with the instructions for use, are ACE inhibitors. The drug blocks the formation of angiotensin.

The substance is produced from a precursor in the liver, and is associated with another hormone, aldosterone. This bundle of components causes vasospasm, provokes a deterioration in blood flow, which contributes to an increase in pressure.

With constant use, the drug increases vascular tone and reduces the load on the heart.

Release form

The drug is available in the form of tablets. Due to the fact that the manufacturer offers several types of products, the external form differs in color. Since the action of the drug is not harmless, in order to prevent self-medication, it is prescribed only by prescription.

Compound

Studying the features of the drug, patients pay attention to the different names of the tablets. Because of this, the question arises of what Prestarium A is taken from, how it differs from a medicine without an additive. The main active ingredient of all types is perindopril.

Instructions for use indicate that Prestarium contains 2.4 or 8 mg of active ingredient. Added Substance A offers 2.5, 5, or 10 mg. In addition to the dosage, they differ in salt, which includes the active ingredient.

Perindopril, if auxiliary components are not used, will be destroyed by the action of gastric juice. Therefore, it is necessary to include it in a complex substance that will allow the main component to be delivered to the bloodstream. Prestarium consists of trebutylamine salt, variety A - perindopril arginine.

The composition of Prestarium B is supplemented with Amlodipine, for optimal dose selection it is found with 5 or 10 mg of each component. It improves coronary circulation.

Amlodipine belongs to the blockers of slow calcium channels, helps to reduce the rate of passage of ions through the vascular channels to the muscle layer. Due to this, it helps patients with angina pectoris.

Prestarium Combi - combination with. It has a moderate diuretic effect, removes excess sodium and fluid that cause an increase in pressure.

Price

The price of Prestarium depends on the dosage indicated in the instructions for use, the country of origin, how many tablets the package consists of.

For example, a Russian-made medicine, a dosage of 5 mg - costs 449-479 rubles, 10 mg - 592 rubles. Prestarium A of Irish origin with a lower dosage of 30 pcs. costs 369 rubles, with a larger one - 530, French - 388 and 600 rubles, respectively.

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Instructions for use

The instructions for use of Prestarium stipulate at what pressure and how to take it correctly so that the drug has the maximum effect. Tablets should be taken in the morning, before breakfast, preferably at the same time.

The initial dose of the drug is 5 mg, 1 use per day is enough. If within a month there is no improvement in the condition, then the dose is increased to 10 mg.

Complaints can be heard from patients that Prestarium does not reduce pressure quickly. But they forget that the drug has a different purpose. It has an effect 4-6 hours after ingestion, providing a long-lasting effect on blood vessels.

Perindopril fights with any degree, positively affecting blood circulation. Its accumulation occurs after 4-6 weeks of regular intake, so you need to ensure a daily dose of the drug for a long period.

special instructions

The drug is metabolized in the liver and excreted by the kidneys, and even if their function is not impaired, nothing bad happens. When a change in the structure of an organ is detected in a patient, some points must be taken into account when taking the medicine.

• in chronic pyelo-, glomerulonephritis, CRF can cause exacerbation, deterioration of laboratory markers;
• against the background of taking Prestarium, dose adjustment of hypoglycemic drugs may be required;
• if the patient has angina pectoris, then at the beginning of taking the remedy, attacks may become more frequent.

With the influence of other factors on the patient at the beginning of therapy, which contribute to a decrease in blood pressure, attacks of a sharp drop in pressure may be observed.

In chronic renal failure, Prestarium provokes the transition of pathology into an acute form. The blood of even a healthy person can react with an increase in creatinine and urea in a biochemical analysis.

The instructions state that the presence of liver problems is not a special condition for monitoring the patient, except for severe organ failure. But kidney problems require monitoring of biochemical analysis during therapy.

When detecting changes in the patient's condition, the doctor assesses the risk of a permanent health disorder and correlates it with the patient's need for Prestarium.

Application by children

The effectiveness of the treatment of children under 18 years of age with the drug has not been established, as well as the safety of the main substance on a growing organism. The doctor will not dare to adjust the dose empirically, therefore Prestarium is not intended for the treatment of the condition in children.

Application by the elderly

In patients after 65 years, the body is weakened, a person at this age has a number of chronic diseases. Therefore, for him, the full dose may seem excessive. The doctor prescribes the minimum dosage under the control of pressure, as well as the condition of the liver and kidneys.

Side effects

When taking Prestarium, especially at the beginning of the course, side effects may occur. Here is a list of the most common symptoms:

• persistent cough;
• a sharp decrease in pressure;
• nausea, dry mouth, lack of appetite;
• the appearance of rashes on the skin;
• headache;
• change in taste sensations;
• a feeling of fullness in the ear.

Some of these adverse reactions do not require discontinuation of the drug and quickly pass. Others, despite the indications for use, require the abolition of tablets.

Prestarium is also characterized by other, less common violations:

• pancreatitis;
• disturbance of consciousness;
• bronchospasm;
• arrhythmia or tachycardia;
• hepatitis, jaundice;
• violation of potency;
• weakness, fatigue;
• muscle pain;
• decreased vision, double vision.

Do not confuse the side effects associated with the action of the drug on organs affected by chronic processes with those conditions when Prestarium is contraindicated.

Contraindications

In a number of conditions, the appointment of an antihypertensive drug creates conditions that are life-threatening. Contraindications are:

• pregnancy and lactation;
• angioedema in the past;
• allergy to lactose;
• childhood;
• hypokalemia;
• with creatinine clearance below 30 ml / min;
• severe liver failure;
• metabolic disorder (phenylketonuria).

During treatment with Prestarium, a person should refrain from activities that require a reaction (including driving a vehicle), since the effect of the drug causes a loss of concentration and attention.

The effect of the drug on pregnancy and lactation has not been established, since testing on these categories of people has not been conducted. Due to the lack of data on the penetration of the main substance through the placenta and into breast milk, these 2 conditions are contraindicated.

Angioedema can be caused by other ACE inhibitor drugs, but in this case, experiments are inappropriate. Therefore, if there is a history of intolerance to Perindopril, auxiliary components or other agents from this group, this method of therapy is abandoned.

Decreased potassium levels are a relative contraindication. This means that Perindopril can be prescribed, but after the value rises to normal.

Overdose

The instruction does not exactly specify what dose of the drug is associated with an overdose. Even 1 tablet, taken according to the rules, can provoke a deterioration in well-being, collapse, fainting. Therefore, the dose at which signs of an overdose occur is individual.

Interaction with other drugs

Prestarium affects some drugs:

• together with lithium preparations increases its toxicity;
• enhances the action of insulin and other hypoglycemic agents;
• together with non-steroidal anti-inflammatory drugs contributes to hyperkalemia;
• when taken with drugs containing calcium, the likelihood of hypercalcemia increases;
• co-administration with increases the level of potassium;
• increases the diuretic effect of anesthetics;
• the toxic effect of cardiac glycosides is enhanced;
• drugs with immunosuppressive action, cytostatics, novocainamide and corticosteroids increase the risk of developing leukopenia;
• when using the version with a diuretic and prescribing an examination with a contrast agent, there is a risk of AKI.

Other drugs also affect the absorption and action of the antihypertensive agent.

ACE inhibitor

Active substance

Release form, composition and packaging

Excipients: acesulfame potassium - 0.2 mg, aspartame - 0.2 mg, magnesium stearate - 0.4 mg, colloidal anhydrous silicon dioxide - 0.4 mg, dry mixture of lactose and starch (lactose monohydrate 85%, corn starch 15%) - 73.8 mg.

Orally dispersible tablets white, round, biconvex.

Excipients: acesulfame potassium - 0.4 mg, aspartame - 0.4 mg, magnesium stearate - 0.8 mg, colloidal anhydrous silicon dioxide - 0.8 mg, dry mixture of lactose and starch (lactose monohydrate 85%, corn starch 15%) - 147.6 mg.

29 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.
30 pcs. - polypropylene bottles with a dispenser and a stopper containing a moisture-absorbing gel (1) - cardboard packs with first opening control.

pharmachologic effect

Pharmacodynamics

Mechanism of action

Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II. ACE, or kininase II, is an exopeptidase that both converts angiotensin I to the vasoconstrictor angiotensin II and breaks down the vasodilator bradykinin to an inactive heptapeptide.

Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood, which causes an increase in plasma renin activity (by the "negative feedback" mechanism) and a decrease in aldosterone secretion.

Since ACE inactivates bradykinin, ACE suppression is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin systems, while the prostaglandin system is also activated. It is possible that this effect is part of the mechanism of the antihypertensive action of ACE inhibitors, as well as the mechanism for the development of some side effects of drugs of this class (for example, cough).

Perindopril has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites do not have an inhibitory effect on ACE in vitro.

Clinical efficacy and safety

Arterial hypertension

Perindopril is effective in the treatment of arterial hypertension of any severity. Against the background of the use of the drug, there is a decrease in both systolic and diastolic blood pressure in the patient's position "lying" and "standing". Perindopril reduces OPSS, which leads to a decrease in blood pressure, while peripheral blood flow is accelerated without a change in heart rate.

As a rule, perindopril leads to an increase in renal blood flow, while GFR does not change.

The antihypertensive effect of the drug reaches a maximum after 4-6 hours after a single oral administration and lasts for 24 hours. After 24 hours after ingestion, a pronounced (about 87-100%) residual ACE inhibition is observed. The reduction in blood pressure is achieved fairly quickly. In patients with a positive response to treatment, normalization of blood pressure occurs within a month and persists without the development of tachyphylaxis.

Termination of treatment is not accompanied by the development of the "rebound" effect.

Perindopril has a vasodilating effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy.

The simultaneous appointment of thiazide diuretics enhances the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of developing hypokalemia while taking diuretics.

failure

Perindopril normalizes the work of the heart, reducing preload and afterload. In patients with chronic heart failure treated with perindopril, it was revealed: a decrease in filling pressure in the left and right ventricles of the heart; decrease in OPSS; an increase in cardiac output and an increase in cardiac index. A study of the drug compared with placebo showed that changes in blood pressure after the first dose of the drug Prestarium A 2.5 mg in patients with chronic heart failure (FC II-III according to the NYHA classification) were not statistically significantly different from changes in blood pressure observed after taking placebo.

Cerebrovascular diseases

The results of the PROGRESS study, which evaluated the effect of active therapy with perindopril (monotherapy or in combination with) for 4 years on the risk of recurrent stroke in patients with a history of cerebrovascular disease. After a run-in period of perindopril tert-butylamine 2 mg (perindopril arginine equivalent 2.5 mg) once daily for 2 weeks followed by 4 mg (perindopril arginine equivalent 5 mg) once daily for a further 2 weeks, 6105 patients were randomized into two groups: placebo (n=3054) and perindopril tertbutylamine 4 mg each (corresponding to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n=3051). Indapamide was additionally administered to patients who did not have direct indications or contraindications for the use of diuretics. This therapy was administered in addition to standard therapy for stroke and/or arterial hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular disease (stroke or transient ischemic attack) within the past 5 years. BP was not an inclusion criterion: 2916 patients had arterial hypertension and 3189 had normal BP. After 3.9 years of therapy, the BP value (systolic/diastolic) decreased by an average of 9/4 mm Hg. It also showed a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic) of the order of 28% compared with placebo (10.1% and 13.8%).

In addition, a significant reduction in the risk of: fatal or disabling strokes has been shown; major cardiovascular complications, including myocardial infarction, incl. fatal; stroke-related dementia; severe cognitive impairment.

This was noted both in patients with arterial hypertension and in those with normal blood pressure, regardless of age, gender, presence or absence of diabetes mellitus, and type of stroke.

Stable coronary artery disease

The efficacy of perindopril in patients (12,218 patients over 18 years of age) with stable coronary artery disease without clinical symptoms of chronic heart failure was studied during a 4-year study. 90% of study participants had previously had an acute myocardial infarction and/or a revascularization procedure. Most patients received standard therapy in addition to the study drug, including antiplatelet agents, lipid-lowering agents, and beta-blockers. The composite endpoint of cardiovascular death, non-fatal myocardial infarction, and/or cardiac arrest with successful resuscitation was selected as the primary outcome measure.

Therapy with perindopril erbumine at a dose of 8 mg/day (equivalent to 10 mg perindopril arginine) led to a significant reduction in the absolute risk of the combined endpoint by 1.9% (relative risk reduction - 20%). In patients with a previous myocardial infarction or a revascularization procedure, the absolute risk reduction was 2.2% (relative risk reduction - 22.4%) compared with the placebo group.

Pediatric patients (under 18 years of age)

The efficacy and safety of perindopril in children and adolescents under 18 years of age has not been established.

There are data from clinical studies involving 62 patients with arterial hypertension aged 2 to 15 years with GFR> 30 ml / min / 1.73 m 2 of body surface area, who received perindopril at a dose of 0.07 mg / kg on average. The dose was selected individually, depending on the general condition of the patient and his blood pressure indicators in response to therapy, while the maximum dose was 0.135 mg/kg/day.

59 patients participated in the study for 3 months and 36 patients completed an extended study period of at least 24 months (mean duration of study participation was 44 months).

Systolic and diastolic blood pressure remained stable throughout the study period (from enrollment to the final assessment) in patients previously treated with other antihypertensive drugs, and decreased in patients who had not previously received antihypertensive therapy.

More than 75% of children at the last determination had systolic and diastolic blood pressure less than the 95th percentile.

The safety data obtained in this study are consistent with the information already available regarding the safety of the use of perindopril.

Double blockade of the RAAS

There are data from clinical studies of combination therapy with an ACE inhibitor and an angiotensin II receptor antagonist (ARA II).

A clinical study was conducted in patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus, accompanied by confirmed target organ damage, as well as studies in patients with type 2 diabetes mellitus with diabetic nephropathy.

These studies did not reveal a significant positive effect of combination therapy on the occurrence of renal and / or cardiovascular events and on mortality rates, while the risk of developing hyperkalemia, acute renal failure and / or arterial hypotension increased compared with monotherapy.

Taking into account the similar intragroup pharmacodynamic properties of ACE inhibitors and ARA II, these results can be expected for the interaction of any other drugs, representatives of the classes of ACE inhibitors and ARA II. Therefore, the use of ACE inhibitors in combination with ARA II is contraindicated in patients with diabetic nephropathy.

There is evidence from a clinical study investigating the beneficial effects of adding aliskiren to standard therapy with an ACE inhibitor or ARA II in patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, or a combination of these diseases. The study was terminated early due to an increased risk of adverse outcomes. Cardiovascular death and stroke were more common in the aliskiren group than in the placebo group; also adverse events and serious adverse events of special interest (hyperkalemia, arterial hypotension and impaired renal function) were recorded more often in the aliskiren group than in the placebo group.

Pharmacokinetics

Suction

When taken orally, perindopril is rapidly absorbed from the gastrointestinal tract, C max in the blood plasma is reached after 1 hour. Perindopril does not have pharmacological activity. Approximately 27% of the total absorbed perindopril enters the bloodstream as the active metabolite of perindoprilat. In addition to perindoprilat, 5 more metabolites are formed that do not have pharmacological activity. C max perindoprilat in plasma is achieved 3-4 hours after ingestion.

Food intake slows down the conversion of perindopril to perindoprilat, thus affecting bioavailability. Therefore, the drug should be taken 1 time / day, in the morning, before meals.

It has been shown that the relationship between the dose of perindopril and its plasma concentration is linear.

Distribution

The binding of perindoprilat to plasma proteins, mainly to ACE, is 20% and is dose-dependent. V d free perindoprilat is approximately 0.2 l / kg.

breeding

T 1/2 of perindopril from plasma is 1 hour. Perindoprilat is excreted from the body by the kidneys, the final T 1/2 of the free fraction is approximately 17 hours, as a result, an equilibrium state is reached within 4 days.

Special patient groups

Excretion of perindoprilat is slowed down in the elderly, as well as in patients with heart and kidney failure.

The dialysis clearance of perindoprilat is 70 ml/min.

In patients with cirrhosis of the liver, the hepatic clearance of perindopril is reduced by 2 times. However, the amount of perindoprilat formed does not decrease and dose adjustment of the drug is not required (see sections "Dosage regimen" and "Special instructions").

Indications

- arterial hypertension;

- chronic heart failure;

- prevention of recurrent stroke (combination therapy with indapamide) in patients who have had a stroke or transient ischemic cerebrovascular accident;

— stable coronary artery disease: reduced risk of cardiovascular complications in patients with stable coronary artery disease.

Contraindications

- hypersensitivity to the active substance and excipients that make up the drug (see section "Dosage form, composition and packaging");

- hypersensitivity to other ACE inhibitors;

- angioedema (Quincke's edema) in history associated with taking an ACE inhibitor;

- hereditary / idiopathic angioedema;

- simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and / or moderate or severe impaired renal function (GFR<60 мл/мин/1.73 м 2 площади поверхности тела) (см. разделы "Лекарственное взаимодействие" и "Фармакологическое действие");

- simultaneous use with angiotensin II receptor antagonists in patients with diabetic nephropathy (see section "Special Instructions");

- pregnancy (see section "Pregnancy and lactation");

- the period of breastfeeding (see section "Pregnancy and lactation");

- age up to 18 years (efficacy and safety have not been established);

- lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome;

- phenylketonuria (the drug contains aspartame).

Carefully(see also sections "Special Instructions" and "Drug Interactions"), the drug should be prescribed for bilateral renal artery stenosis or the presence of only one functioning kidney; renal failure; systemic connective tissue diseases (systemic lupus erythematosus, scleroderma and others); therapy with immunosuppressants, allopurinol, procainamide (risk of developing neutropenia, agranulocytosis); reduced BCC (taking diuretics, salt-free diet, vomiting, diarrhea); angina; cerebrovascular diseases; renovascular hypertension; diabetes mellitus; chronic heart failure IV FC according to the NYHA classification; concomitant use of potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes and lithium; hyperkalemia; surgery/general anesthesia; hemodialysis using high-flow membranes; desensitizing therapy; LDL apheresis; condition after kidney transplantation; aortic stenosis/mitral stenosis/hypertrophic obstructive cardiomyopathy; in black patients.

Dosage

Inside, 1 tablet 1 time / day, preferably in the morning, before meals.

The tablet should be put on the tongue and after it disintegrates on the surface of the tongue, swallow it with saliva.

When choosing a dose, one should take into account the characteristics of the clinical situation (see section "Special Instructions") and the degree of reduction in blood pressure against the background of ongoing therapy.

Arterial hypertension

Prestarium A can be used both in monotherapy and as part of combination therapy (see sections "Contraindications", "Special instructions" and "Pharmacological action").

In patients with severe RAAS activity (especially with renovascular hypertension, hypovolemia and / or a decrease in plasma electrolytes, decompensation of chronic heart failure or severe arterial hypertension), after taking the first dose of the drug, a pronounced decrease in blood pressure may develop. At the beginning of therapy, such patients should be under close medical supervision. The recommended starting dose for these patients is 2.5 mg once daily. To ensure this dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet. If necessary, one month after the start of therapy, you can increase the dose of the drug to 10 mg 1 time / day.

At the beginning of therapy with Prestarium A, symptomatic arterial hypotension may occur. In patients receiving diuretics at the same time, the risk of arterial hypotension is higher due to possible hypovolemia and a decrease in the content of electrolytes in the blood plasma. Caution should be exercised when using the drug Prestarium A in this group of patients. It is recommended, if possible, to stop taking diuretics 2-3 days before the intended start of therapy with the drug Prestarium A (see section "Special Instructions").

If it is impossible to cancel diuretics, the initial dose of Prestarium A should be 2.5 mg. To ensure this dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet. In this case, it is necessary to monitor kidney function and the content of potassium in the blood serum. In the future, if necessary, the dose of the drug can be increased. If necessary, diuretics can be resumed.

At elderly patients treatment should begin with a dose of 2.5 mg / day. To ensure this dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet. If necessary, one month after the start of therapy, the dose can be increased to 5 mg / day, and then to a maximum dose of 10 mg / day, taking into account the state of kidney function (see table 1).

The maximum daily dose is 10 mg.

Heart failure

It is recommended to start treatment of patients with chronic heart failure with Prestarium A in combination with potassium-sparing diuretics and / or digoxin and / or beta-blockers under close medical supervision, prescribing the drug at an initial dose of 2.5 mg 1 time / day, in the morning. To ensure this dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet. After 2 weeks of treatment, the dose of the drug can be increased to 5 mg 1 time / day, provided that the dose of 2.5 mg is well tolerated and the response to therapy is satisfactory.

In patients with severe heart failure, as well as in patients at high risk (patients with impaired renal function and a tendency to disturb the water and electrolyte balance, patients simultaneously receiving diuretics and / or vasodilator drugs), treatment should be initiated under close medical supervision (see section "Special Instructions").

In patients at high risk of developing symptomatic arterial hypotension, for example, with a reduced content of electrolytes with or without hyponatremia, with hypovolemia or with intensive diuretic therapy, before starting the drug Prestarium A, if possible, the listed conditions should be corrected. Indicators such as blood pressure, kidney function and plasma potassium should be monitored both before and during therapy.

Prevention of recurrent stroke (combination therapy with indapamide)

In patients with a history of cerebrovascular disease, therapy with Prestarium A should be initiated at a dose of 2.5 mg for the first 2 weeks. To ensure this dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet. Then, increasing the dose to 5 mg over the next 2 weeks before the use of indapamide.

Therapy should begin at any time (from 2 weeks to several years) after a stroke.

CHD: reduced risk of cardiovascular complications in patients with prior myocardial infarction and/or coronary revascularization

In patients with a stable course of coronary artery disease, therapy with the drug Prestarium A should be started with a dose of 5 mg 1 time / day.

After 2 weeks, with good tolerability of the drug and taking into account the state of kidney function, the dose can be increased to 10 mg 1 time / day.

Elderly patients therapy should be started with a dose of 2.5 mg 1 time / day for one week. To ensure this dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet. Then 5 mg 1 time / day for the next week. Then, taking into account the state of kidney function, the dose can be increased to 10 mg 1 time / day (see table. 1). It is possible to increase the dose of the drug only if it is well tolerated at the previously recommended dose.

Table 1. Dosage of the drug Prestarium A in renal failure

* Dialysis clearance of perindoprilat - 70 ml / min. The drug should be taken after the dialysis procedure.

**To ensure the indicated dosing regimen, perindopril-containing preparations should be used at a dosage of 5 mg in the form of a divisible tablet.

Liver failure

Patients with impaired liver function dose adjustment is not required (see sections "Pharmacokinetics" and "Special Instructions").

Currently, there are no sufficient data on the safety and efficacy of perindopril in children and adolescents under the age of 18. The available data described in the "Pharmacological action" section does not allow recommendations on the method of administration and dosages of the drug in patients of this age group (see section "Contraindications").

Side effects

The safety profile of perindopril is consistent with that of ACE inhibitors.

The most common adverse events reported in clinical studies and observed with the use of perindopril are: dizziness, headache, paresthesia, vertigo, visual disturbances, tinnitus, excessive decrease in blood pressure, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disturbance, dyspepsia, nausea, vomiting, pruritus, skin rash, muscle spasms and asthenia.

The frequency of adverse reactions that were noted during clinical trials and / or post-registration use of perindopril is given as the following gradation: very often (≥1 / 10); often (≥1/100,<1/10); нечасто (≥1/1000, <1/100); редко (≥1/10 000, <1/1000); очень редко (<1/10 000); неуточненной частоты (частота не может быть подсчитана по доступным данным). Классификация показателей частоты рекомендована ВОЗ.

From the blood and lymphatic system: infrequently * - eosinophilia; very rarely - a decrease in hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase (see section "Special Instructions").

From the side of metabolism and nutrition: infrequently * - hypoglycemia (see sections "Special Instructions" and "Drug Interactions"), hyperkalemia, reversible after discontinuation of the drug (see section "Special Instructions"), hyponatremia.

From the nervous system: often - paresthesia, headache, dizziness, vertigo; infrequently - drowsiness *, fainting *; very rarely - confusion.

Mental disorders: infrequently - sleep disturbances, mood lability.

From the side of the organ of vision: often visual impairment.

On the part of the organ of hearing and labyrinth disorders: often - tinnitus.

From the side of the heart: infrequently * - palpitations, tachycardia; very rarely - cardiac arrhythmias, angina pectoris (see section "Special instructions"), myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients (see section "Special instructions").

From the vascular side: often - an excessive decrease in blood pressure and related symptoms; infrequently * - vasculitis; very rarely - a stroke, possibly due to an excessive decrease in blood pressure in patients at high risk (see section "Special Instructions").

From the respiratory system, chest organs and mediastinum: often - cough, shortness of breath; infrequently - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.

From the gastrointestinal tract: often - constipation, nausea, vomiting, abdominal pain, taste disturbance, dyspepsia, diarrhea; infrequently - dryness of the oral mucosa; very rarely - pancreatitis.

From the side of the liver and biliary tract: very rarely - hepatitis (cholestatic or cytolytic) (see section "Special Instructions").

From the skin and subcutaneous tissues: often - skin itching, skin rash; infrequently - angioedema of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal folds and / or larynx, urticaria (see section "Special instructions"), photosensitivity *, pemphigus *, increased sweating; rarely * - exacerbation of psoriasis; very rarely - erythema multiforme.

From the musculoskeletal system and connective tissue: often - muscle spasms; infrequently * - arthralgia, myalgia.

From the side of the kidneys and urinary tract: infrequently - renal failure; very rarely - acute renal failure.

From the genitals and mammary gland: infrequently - erectile dysfunction.

General disorders and disorders at the injection site: often - asthenia; infrequently - chest pain *, peripheral edema *, general malaise *, fever *, falls *.

From the side of laboratory and instrumental indicators: infrequently * - an increase in the concentration of urea and creatinine in the blood plasma; rarely - an increase in the activity of liver enzymes and bilirubin in the blood serum.

* Estimation of the frequency of adverse reactions identified by spontaneous reports was carried out on the basis of data from the results of clinical studies.

Adverse events noted in clinical studies

In the EUROPA study, only serious adverse events were recorded. Serious adverse events were observed in 16 (0.3%) patients in the perindopril group and in 12 (0.2%) patients in the placebo group. In the perindopril group, 6 patients had a pronounced decrease in blood pressure, 3 patients had angioedema, and 1 patient had sudden cardiac arrest. The frequency of discontinuation of the drug due to cough, a pronounced decrease in blood pressure or other cases of intolerance was higher in the perindopril group compared to the placebo group.

Overdose

Data on drug overdose are limited.

Symptoms: pronounced decrease in blood pressure, shock, water and electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough.

Treatment: with a pronounced decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs; if necessary, an intravenous 0.9% solution should be administered. If necessary, you can enter an intravenous solution of catecholamines and / or angiotensin II. Perindopril can be removed from the body by dialysis. With the development of therapy-resistant bradycardia, it may be necessary to install an artificial pacemaker. It is necessary to constantly monitor the indicators of the main vital functions of the body, the concentration of creatinine and electrolytes in the blood serum.

drug interaction

Data from clinical studies show that dual blockade of the RAAS as a result of the simultaneous administration of ACE inhibitors, ARA II or aliskiren leads to an increase in the incidence of adverse events such as arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure), compared with situations when only one drug is used that affects the RAAS (see sections "Contraindications", "Special instructions" and "Pharmacological action").

Drugs that cause hyperkalemia

Some drugs or drugs from other pharmacological classes may increase the risk of developing hyperkalemia: aliskiren and aliskiren-containing drugs, potassium salts, potassium-sparing diuretics, ACE inhibitors, ARA II, NSAIDs, heparin, immunosuppressants such as cyclosporine or tacrolimus, drugs containing trimethoprim, in including fixed combination of trimethoprim and sulfamethoxazole. The combination of these drugs increases the risk of hyperkalemia.

Simultaneous use is contraindicated (see section "Contraindications")

Aliskiren and medicines containing aliskiren

Contraindicated in patients with diabetes mellitus and / or moderate or severe renal impairment and not recommended in other patients: increased risk of hyperkalemia, deterioration of renal function and increased incidence of cardiovascular morbidity and mortality.

Aliskiren. In patients who do not have diabetes mellitus or impaired renal function, there may be an increased risk of hyperkalemia, deterioration of renal function, and an increased incidence of cardiovascular morbidity and mortality.

Concomitant therapy with ACE inhibitors and angiotensin receptor antagonists

It has been reported in the literature that in patients with established atherosclerotic disease, heart failure, or diabetes mellitus with target organ damage, concomitant therapy with an ACE inhibitor and ARA II is associated with a higher incidence of arterial hypotension, syncope, hyperkalemia, and deterioration of renal function (including acute renal failure). insufficiency) compared with the use of only one drug that affects the RAAS. Double blockade (for example, when an ACE inhibitor is combined with ARA II) should be limited to individual cases with careful monitoring of renal function, potassium levels and blood pressure.

Estramustine

Simultaneous use may lead to an increased risk of side effects such as angioedema.

Racecadotril

It is known that ACE inhibitors (for example, perindopril) can cause the development of angioedema. The risk of its development may be increased when used together with racecadotril (a drug used to treat acute diarrhea).

InhibitorsmTOR(mammalian targets of rapamycin) (eg, sirolimus, everolimus, temsirolimus)

In patients receiving concomitant therapy with mTOR inhibitors, the risk of developing angioedema may increase (see section "Special Instructions").

Potassium-sparing diuretics (such as triamterene, amiloride), potassium salts

Hyperkalemia (with a possible fatal outcome), especially with impaired renal function (additional effects associated with hyperkalemia).

The combination of perindopril with the above-mentioned drugs is not recommended (see section "Special Instructions"). If, however, simultaneous use is indicated, they should be used with precautions and regularly monitoring the content of potassium in the blood serum.

Features of the use of spironolactone in heart failure are described below.

lithium preparations. With the simultaneous use of lithium preparations and ACE inhibitors, there may be a reversible increase in the concentration of lithium in the blood serum and associated toxic effects. The simultaneous use of perindopril and lithium preparations is not recommended. If it is necessary to carry out such therapy, regular monitoring of the concentration of lithium in the blood plasma should be carried out (see section "Special Instructions").

Simultaneous use, which requires special care

Hypoglycemic agents (insulin, oral hypoglycemic agents). The use of ACE inhibitors can enhance the hypoglycemic effect of insulin and oral hypoglycemic agents up to the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and in patients with impaired renal function.

Baclofen enhances the antihypertensive effect of ACE inhibitors. The level of blood pressure and, if necessary, the dosage of antihypertensive drugs should be carefully monitored.

Potassium-sparing diuretics. In patients receiving diuretics, especially those that remove fluid and / or salts, at the beginning of therapy with an ACE inhibitor, an excessive decrease in blood pressure may be observed, the risk of which can be reduced by discontinuing the diuretic, replenishing the loss of fluid or salts before starting therapy with perindopril, and also by prescribing perindopril in low dose followed by a gradual increase. With arterial hypertension in patients receiving diuretics, especially fluid and/or salt-removing agents, the diuretic should either be discontinued prior to starting the ACE inhibitor (and a non-potassium-sparing diuretic may be reintroduced later) or the ACE inhibitor should be given at a low dose and increased gradually . When using diuretics in case of chronic heart failure an ACE inhibitor should be given at a low dose, possibly after a dose reduction of the concomitant potassium-sparing diuretic. In all cases, renal function (creatinine concentration) should be monitored during the first weeks of ACE inhibitor use.

Potassium-sparing diuretics (eplerenone, spironolactone). The use of eplerenone or spironolactone in doses from 12.5 mg to 50 mg per day and low doses of ACE inhibitors: in the treatment of heart failure II-IV FC according to the NYHA classification with left ventricular ejection fraction<40% и ранее применявшимися ингибиторами АПФ и "петлевыми" диуретиками, существует риск гиперкалиемии (с возможным летальным исходом), особенно в случае несоблюдения рекомендаций относительно этой комбинации препаратов. Перед применением данной комбинации лекарственных препаратов, необходимо убедиться в отсутствии гиперкалиемии и нарушений функции почек. Рекомендуется регулярно контролировать концентрацию креатинина и калия в крови: еженедельно в первый месяц лечения и ежемесячно в последующем.

NSAIDs, including high doses (≥3 g/day): the simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid at a dose that has an anti-inflammatory effect, COX-2 inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs can lead to deterioration of renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced renal function. Caution should be exercised when prescribing this combination, especially in elderly patients. Patients should receive adequate fluids, and careful monitoring of renal function is recommended, both at the beginning and during treatment.

Simultaneous use, which requires some caution

Antihypertensive drugs and vasodilators

The antihypertensive effect of perindopril may be enhanced when used concomitantly with other antihypertensives, vasodilators, including short and long acting nitrates.

Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin): combined use with ACE inhibitors may increase the risk of angioedema due to the suppression of dipeptidyl peptidase IV (DPP-IV) activity by gliptin.

Tricyclic antidepressants, antipsychotics (neuroleptics) and general anesthetics: simultaneous use with ACE inhibitors may lead to an increase in the antihypertensive effect (see section "Special Instructions").

Sympathomimetics may weaken the antihypertensive effect of ACE inhibitors.

When using ACE inhibitors, incl. perindopril, patients receiving intravenous gold preparation (sodium aurothiomalate), in rare cases, the development of nitritoid reactions was reported - a symptom complex, including flushing of the skin of the face, nausea, vomiting, arterial hypotension.

special instructions

With the development of unstable angina during the first month of therapy with perindopril, the benefits and risks should be assessed before continuing therapy.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive decrease in blood pressure is increased in patients with reduced BCC, which may occur during diuretic therapy, with a strict salt-free diet, hemodialysis, with vomiting and diarrhea, as well as in patients with severe arterial hypertension with high renin activity (see sections " drug interactions" and "side effects"). Symptomatic arterial hypotension can be observed in patients with clinical manifestations of heart failure, both with and without renal failure. This risk is more likely in patients with severe heart failure as a reaction to high-dose loop diuretics, hyponatremia, or functional renal failure. In patients with an increased risk of developing symptomatic arterial hypotension, blood pressure, renal function and serum potassium should be carefully monitored during therapy with Prestarium A.

A similar approach is also used in patients with coronary artery disease and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.

In the event of arterial hypotension, the patient should be transferred to the "lying" position on the back with raised legs. If necessary, the BCC should be replenished with the help of an intravenous injection of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further use of the drug. After the restoration of BCC and blood pressure, treatment can be continued.

In some patients with chronic heart failure and normal or reduced blood pressure, Prestarium A may cause an additional decrease in blood pressure. This effect is predictable and usually does not require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, reduce the dose of the drug or stop taking it.

Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy

Prestarium A, like other ACE inhibitors, should be used with caution in patients with left ventricular outflow tract obstruction (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as in patients with mitral stenosis.

Impaired kidney function

Patients with renal insufficiency (KK<60 мл/мин) начальную дозу периндоприла следует подбирать в зависимости от значения КК (см. раздел "Режим дозирования") и затем - в зависимости от терапевтического эффекта. Для таких пациентов необходим регулярный контроль концентрации креатинина и калия в сыворотке крови (см. раздел "Побочное действие").

Arterial hypotension, which sometimes develops at the beginning of the use of ACE inhibitors in patients with symptomatic chronic heart failure, can lead to a deterioration in renal function. Perhaps the development of acute renal failure, usually reversible.

In patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney (especially in the presence of renal insufficiency), during therapy with ACE inhibitors, an increase in the concentration of urea and creatinine in the blood serum is possible, which usually disappears when therapy is discontinued. The additional presence of renovascular hypertension causes an increased risk of developing severe arterial hypotension and renal failure in such patients. Treatment of such patients begins under close medical supervision with the use of low doses of the drug and further adequate selection of doses. It is necessary to temporarily stop treatment with diuretics and regularly monitor the content of potassium and creatinine in the blood plasma during the first few weeks of therapy.

In some patients with arterial hypertension, without indicating the presence of a previous vascular disease of the kidneys, the concentration of urea and creatinine in the blood serum may increase, especially with the simultaneous use of diuretics. These changes are usually expressed insignificantly and are reversible. The likelihood of developing these disorders is higher in patients with a history of renal failure. In such cases, it may be necessary to cancel or reduce the dose of Prestarium A and / or diuretic.

Hemodialysis

In patients on hemodialysis using high-flow membranes, there have been cases of anaphylactic reactions during therapy with ACE inhibitors. In such situations, the possibility of prescribing a different class of antihypertensive drug or using a different type of dialysis membrane should be considered.

kidney transplant

There are no data on the use of Prestarium A in patients after kidney transplantation.

Hypersensitivity/angioneurotic edema

When taking ACE inhibitors, incl. perindopril, in rare cases and in any period of therapy, the development of angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and / or larynx may be observed (see section "Side Effects"). If symptoms appear, the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling only affects the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. When such symptoms appear, emergency treatment is required, incl. s / c administration of epinephrine (adrenaline) and / or ensuring airway patency. The patient should be under medical supervision until the symptoms disappear completely and permanently.

In patients with a history of angioedema, not associated with the use of ACE inhibitors, there may be an increased risk of its development when taking this group of drugs (see section "Contraindications").

In rare cases, during therapy with ACE inhibitors, angioedema of the intestine developed. At the same time, patients had abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with a normal level of C1-esterase. Diagnosis was established by computed tomography of the abdominal region, ultrasound or surgical intervention. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, in patients with pain in the abdomen receiving ACE inhibitors, when conducting differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine (see section "Side effects").

Co-administration with mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus)

Patients concomitantly receiving therapy with mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) may be at increased risk of developing angioedema (eg, swelling of the airways or tongue with or without impaired respiratory function) (see section "Drug Interactions").

Anaphylactoid reactions during LDL apheresis

Rarely, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There are separate reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy, for example, hymenoptera venom. In these patients, such reactions could be prevented by temporarily discontinuing ACE inhibitors, but with an accidental or inaccurate resumption of treatment, the reactions could develop again.

Impaired liver function

In rare cases, against the background of taking ACE inhibitors, a syndrome of development of cholestatic jaundice was observed with a transition to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism by which this syndrome develops is unclear. If jaundice occurs or a significant increase in the activity of liver enzymes against the background of the use of ACE inhibitors, the drug should be discontinued (see the "Side Effects" section), the patient should be under appropriate medical supervision.

Neutropenia/agranulocytosis/thrombocytopenia/anemia

Against the background of the use of ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. With extreme caution, perindopril should be used in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially in the presence of initial renal dysfunction.

Some patients have experienced severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril in such patients, it is recommended to periodically monitor the content of leukocytes in the blood. Patients should report any signs of an infectious disease (eg, sore throat, fever) to their physician.

ethnic differences

It should be borne in mind that in patients of the Negroid race, the risk of developing angioedema is higher. Like other ACE inhibitors, Prestarium A is less effective in lowering blood pressure in black patients. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Cough

Against the background of therapy with an ACE inhibitor, a persistent dry cough may occur, which stops after discontinuation of the drug. This should be considered in the differential diagnosis of cough.

Surgery/general anesthesia

In patients who are planned to undergo major surgery or the use of anesthesia agents that cause arterial hypotension, the use of perindopril may block the formation of angiotensin II against the background of compensatory renin release. Treatment should be stopped one day before surgery. With the development of arterial hypotension according to the indicated mechanism, blood pressure should be maintained by replenishing the BCC.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, incl. perindopril. Risk factors for hyperkalemia are renal failure, decreased renal function, age over 70 years, diabetes mellitus, certain concomitant conditions (dehydration, acute heart failure, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride) , dietary supplements/potassium preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase the content of potassium in the blood (for example, heparin). The use of potassium supplements/preparations, potassium-sparing diuretics, potassium-containing table salt substitutes can lead to a significant increase in the content of potassium in the blood, especially in patients with reduced kidney function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If the simultaneous use of the drug Prestarium A and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of the content of potassium in the blood serum (see section "Drug Interactions").

Patients with diabetes

When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, during the first month of therapy with an ACE inhibitor, it is necessary to regularly monitor the concentration of glucose in the blood (see section "Drug Interactions").

Lithium preparations

The simultaneous use of perindopril and lithium preparations is not recommended (see section "Drug Interactions").

Potassium-sparing diuretics, potassium preparations, potassium-containing table salt substitutes and dietary supplements

The simultaneous appointment of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended (see the section "Drug Interactions").

Double blockade of the RAAS

There is evidence that the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure). Thus, dual blockade of the RAAS by the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections "Drug Interactions" and "Pharmacological Effects"). If double blockade therapy is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, blood electrolytes and blood pressure.

The use of ACE inhibitors in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").

Influence on the ability to drive vehicles and mechanisms

The drug Prestarium A should be used with caution in patients who drive vehicles and engage in activities that require increased concentration and quick response, due to the risk of developing arterial hypotension and dizziness.

Pregnancy and lactation

Pregnancy

Prestarium A is contraindicated for use during pregnancy (see section "Contraindications").

At the moment, there are no conclusive epidemiological data on the teratogenic risk when taking ACE inhibitors in the first trimester of pregnancy. However, a slight increase in the risk of fetal developmental disorders cannot be ruled out. When planning pregnancy or its occurrence during the use of the drug Prestarium A, you should immediately stop taking the drug and, if necessary, prescribe another antihypertensive therapy with a proven safety profile for use in pregnancy.

It is known that the effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to a violation of its development (decrease in kidney function, oligohydramnios, slowing of the ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the patient received ACE inhibitors in the II and III trimesters of pregnancy, an ultrasound is recommended to assess the condition of the skull and kidney function.

Newborns whose mothers received ACE inhibitors during pregnancy should be monitored because of the risk of developing arterial hypotension.

breastfeeding period

At the moment, it has not been established whether perindopril is excreted in breast milk. Due to the lack of information regarding the use of perindopril during breastfeeding, its use is not recommended. It is preferable to use other drugs with a more studied safety profile during breastfeeding, especially when feeding newborns or premature babies.

Fertility

In preclinical studies, there was no effect of perindopril on reproductive function in rats of both sexes.

Application in childhood

The drug is contraindicated for use in children under 18 years of age (efficacy and safety have not been established).

For impaired renal function

Carefully the drug should be prescribed for bilateral renal artery stenosis or the presence of only one functioning kidney; renal failure, condition after kidney transplantation.

At patients with renal insufficiency the dose of the drug should be selected taking into account QC.

Table 1. Dosage of Prestarium A in renal failure

* dialysis clearance of perindoprilat - 70 ml/min. The drug should be taken after the dialysis procedure.

For impaired liver function

Patients with impaired liver function dose adjustment is not required.

In rare cases, against the background of taking ACE inhibitors, a syndrome of development of cholestatic jaundice was observed with a transition to fulminant liver necrosis, sometimes with a fatal outcome. The mechanism by which this syndrome develops is unclear. With the appearance of jaundice or a significant increase in the activity of liver enzymes against the background of the use of ACE inhibitors, the drug should be discontinued; the patient must be under appropriate medical supervision.

Use in the elderly

In arterial hypertension elderly patients treatment should begin with a dose of 2.5 mg / day. If necessary, one month after the start of therapy, the dose can be increased to 5 mg / day, and then to a maximum dose of 10 mg / day, taking into account the state of kidney function.

With coronary artery disease elderly patients therapy should be started with a dose of 2.5 mg 1 time / day for one week, then 5 mg 1 time / day for the next week. Then, taking into account the state of kidney function, the dose can be increased to 10 mg 1 time / day. It is possible to increase the dose of the drug only if it is well tolerated at the previously recommended dose.

Terms of dispensing from pharmacies

The drug is dispensed by prescription.

Terms and conditions of storage

The drug should be stored out of the reach of children at a temperature not exceeding 25 ° C. Shelf life - 2 years.

Hypertension is a disease that negatively affects the general condition of the body. Associated with increased blood pressure (BP). Due to the large volume of blood ejected by the heart, the pressure on the vessels increases, they are compressed, a spasm is formed. Consequences of hypertension - hypertensive crisis, stroke, cardiovascular disease. As medical practice has shown, if the disease is not treated in time, hypertension can cause serious complications, such as cerebral hemorrhage and death. The disease extends to the age category of 40 years. Women and men are equally affected by it. In the fair sex, the ailment manifests itself due to hormonal changes in the body (menopause period), a manifestation during pregnancy is possible. And in men - because of the wrong lifestyle, alcohol abuse.

Arterial hypertension is a fairly common vascular pathology.

Healthy blood vessels are the key to longevity. Improper nutrition leads to an increase in cholesterol levels in the blood. Over time, cholesterol plaques form, covering the lumen of the vessel. Most patients seek medical help too late, when it is necessary to prescribe a long course of treatment. Therapy of hypertension is based on the use of antispasmodics that relax the walls of blood vessels, restoring the heartbeat. One of the effective drugs is Prestarium for pressure.

Pressure medicine Prestarium

The main active ingredient is perindopril, which is available in dosages of 5 and 10 mg. Subdivided according to the concentration of the active ingredient. Additional components:

• lactose (monohydrates);
• magnesium (stearate);
• silicon (dioxide);
• sodium starch (glycolate).

The drug with a concentration of 5 mg is an oval-shaped capsule. From above, the shell has a greenish tint. The capsule can be easily divided into two equal parts. In the middle it is divided by a strip. "Prestarium" 10 mg is available in capsules convex on both sides, shaped like a circle. Above the shell is green.

Prestarium is a medicine for hypertension and chronic heart failure.

The drug is prescribed for hypertension, to strengthen blood vessels, in the treatment of pathology of the left ventricle of the heart.

Prestarium from pressure - release form

The medicine is available in tablets, on top they have a shell. The concentration volume of the active ingredient perindopril is 2.5 mg, 5 mg, 8 mg, 10 mg. The blister contains fourteen or thirty pieces. The package consists of one, two or three plates. The drug is dispensed in a pharmacy by prescription. Shelf life - 730 days.

Pharmacological purpose

The active substance perindopril acts as an angiotensin-converting enzyme (ACE) inhibitor. Promotes the formation of angiotensin II, which is responsible for vasodilation. With normal perception of the drug by the patient, a positive result is observed within thirty days from the start of therapy. Prescribe medication for all stages of high blood pressure (mild, moderate, severe). Hypotension occurs due to the use of a daily dosage. The effect is achieved by dilating blood vessels. Perindopril actively affects the work of the heart, normalizing the work of the ventricles. It is prescribed for the pathology of the cardiac system. The agent is actively absorbed by the gastrointestinal tract. Bioactivity - 65%. Weakly binds to protein compounds, about 27%. Excreted by the kidneys within an hour. With severe kidney or heart failure, the excretion process slows down. The active substance does not have a cumulative effect in organs and tissues. It is prescribed to be taken on an empty stomach, before meals.

Due to medicinal properties, the risk of arrhythmia, justified by excess subendocardial collagen, is reduced, the work of heart valves is normalized.

Prestarium tablets - indications for use

The main purpose of the drug:

• lowering blood pressure. The active substance perindopril reduces blood pressure, is used to treat hypertension of all types (mild, moderate, complex). The component has a lowering effect on vascular resistance. Decreased systolic and diastolic blood pressure. After taking the drug, the effect of hypotension occurs after 6 hours, lasts 24 hours with a single dose. The effectiveness of the tool reaches 95%. After the end of the course of treatment, relapse is not observed;
• reduction of hypertrophy of the left side of the cardiac ventricle. Perindopril dilates blood vessels, reduces the wall thickness in relation to the lumen of large arteries. Do not use Prestarium at low pressure;
• pathology of the heart. During therapy, perindopril removes squeezing of the ventricles, reduces the level of resistance, increases the volume of cardiac output;
• eliminates the recurrence of strokes;
• reducing the risk of developing cardiovascular pathology.

Contraindications

When treating with the drug, there are a number of complications in which it is forbidden to use a course of therapy. Main contraindications:

• hypersensitivity to the components of the drug;

The drug has undergone many clinical trials and a number of contraindications for use have been identified: pregnancy (fetal malformation may develop) and the period of breastfeeding

• lactation;
• the period of bearing a child;
• age restrictions - children under 18 years old.

There are a number of restrictions under which Prestarium is prescribed with caution, solely at the discretion of the attending physician, when the benefit to the patient is higher than the risk of side effects:

• hemodialysis;
• use of diuretics, salt-free diet, vomiting, diarrhea;
• kidney failure;
• treatment with antidepressants, with connective tissue pathology;
• diabetes;
• during surgical intervention;
• age restrictions - old age from 70 years.

Treatment with Prestarium is associated with the risk of a sharp decrease in blood pressure. At what pressure to use, the answer is obvious. When prescribing the remedy, contraindications and side effects should be taken into account. There is a risk of reactions that threaten the life of the patient.

Side effect

Well tolerated by the body. When studying contraindications in the appointment and the correct dosage, the risk of side effects is excluded. Like other medicines, they still exist.

Side effects may develop if the doctor's recommendations are not followed.

These include:

• dry type cough;
• dizziness;
• headache;
• temporary partial loss of vision;
• constipation or diarrhea;
• allergic reactions in the form of rashes, itching, irritation;
• muscle spasms;
• change in heart rate - angina pectoris;
• stroke;
• preinfarction state;
• emotional disorders
• sexual disorders.

If the first signs of poor health appear, the remedy is stopped taking. You need to see a doctor, he will prescribe another medication.

Prestarium instructions for use, dosage

Tablets are designed for oral use, they are prescribed on an empty stomach once every 24 hours. It is recommended to drink plenty of liquid. Tablets with a concentration of the active ingredient of 0.0025 g, 0.010 g are designed for a single use, 0.005 g can be divided into two equal doses. The necessary dosage is prescribed by the doctor, based on the individual indicator of the patient's condition, the pressure change index. The initial stage of treatment is characterized by a sharp indicator of hypotension, especially when combined with a diuretic. It is recommended for complex therapy to start with a minimum volume of 0.0025 g, guided by the indicator of individual perception of the drug.

The medicine is taken in the morning, at the same time

Normative dosage for Prestarium therapy:

• with hypertension - appoint adults from 0.0025 g to 0.005 g per 24 hours. In the first days there is drowsiness, loss of strength. You can take the remedy at night, while the body is hard to cope with the load. A month later, the dose increases to 0.01 g of a single dose;
• for the treatment of heart failure, the course begins with 0.0025 g in the morning. After 14-16 days, in the absence of side effects, the dosage is increased to 0.005 g per 24 hours. Be sure to monitor the content of potassium in the plasma, the level of blood pressure and renal activity;
• to exclude the recurrence of strokes, preventive measures are taken from 0.005 g, after two weeks, depending on the patient's condition, the dose is increased to 0.01 g once a day;
• for elderly people, the dosage is prescribed in the amount of 0.0025 g. The adjustment is carried out by the doctor based on the patient's condition and the tolerability of the medication.

Self-medication is excluded, the medication is dispensed in pharmacies as prescribed by the doctor.

High blood pressure medication - overdose

With the wrong dosage, an increased concentration of perindopril in the blood is possible. The main symptoms of an overdose:

• low heart rate;

The instructions for use indicate the following signs of an overdose: dizziness and weakness

• dizziness;
• a sharp decrease in blood pressure;
• cough;
• psychological shock.

At the first symptoms, flush the stomach with plenty of liquid, drink five tablets of activated charcoal or two Sorbeks, consult a doctor. The body's water balance is restored with sodium chloride. Complication - loss of consciousness.

Directions for use during pregnancy and lactation

The drug, like other drugs of the group of hypertensive drugs, is prohibited during the period of gestation. No application data available. The components are passed to the baby through breast milk. There is a risk of developing fetal pathology. It is forbidden to use when planning conception. When determining pregnancy, the medicine must be discarded, you should immediately consult a doctor. The fetus will be prescribed an ultrasound of the renal system and bones. There may be a risk of chronic hypotension in infants.

Appointment for use during lactation is similar to the period of gestation.

High pressure drug interactions

Medicines used together with Prestarium can increase the level of potassium in the plasma, causing hyperkalemia.

Side effect - cardiac arrest. The drug is incompatible with potassium-sparing diuretics, Ibuprofen, Heparin, immunosuppressants, a group of medicines for the treatment of heart failure. Before using the medication, inform your doctor about all the drugs you are taking, including dietary supplements. It is not recommended to combine with lithium, insulin. Take the medicine at the discretion of the doctor, read the instructions.

Analogues of "Prestarium", at what pressure to take

Treatment with Prestarium is started when hypertension occurs. The deviation of the blood pressure indicator from the norm (120 to 80 mm Hg. Art.) in the direction of increase is considered elevated blood pressure. In these cases, Prestarium is prescribed, and not another remedy. There are a number of analogues that have a similar pharmacological purpose. These include: "Bisoprolol", "Trimetazidine", "Metoprolol", "Perineva", "Koversil", "Koversum". In the absence of "Prestarium" therapy can be carried out by one of the listed means. Under reduced pressure, choose the appropriate agent for the situation.

Perindopril is an ACE inhibitor, an enzyme that converts angiotensin I to angiotensin II. ACE, or kinase, is an exopeptidase that promotes the conversion of angiotensin I to the vasoconstrictor angiotensin II, and also causes the breakdown of bradykinin, which has vasodilating properties, to an inactive heptapeptide. Inhibition of ACE leads to a decrease in the concentration of angiotensin II, an increase in plasma renin activity and a decrease in aldosterone secretion. Since ACE inactivates bradykinin, ACE inhibition leads to an increase in bradykinin levels, activity of the circulating and tissue kallikrein-kinin system, and activation of the prostaglandin system. This mechanism of action determines the decrease in blood pressure by ACE inhibitors and is partially responsible for the appearance of some of their side effects (dry cough).
Perindopril increases the level of bradykinin, which leads to an improvement in endothelial function and vascular relaxation and plays a leading role in reducing cardiovascular remodeling, improving the fibrinolytic balance of the blood.
Perindopril promotes the expansion of peripheral vessels and a decrease in their resistance. Peripheral blood flow increases, but heart rate does not increase. When using perindopril, renal blood flow usually increases, but the glomerular filtration rate does not change.
Due to the complex mechanism of action, perindopril reduces elevated blood pressure.
Perindopril acts through its active metabolite, perindoprilat.

Perindopril effectively reduces blood pressure in all degrees of hypertension (hypertension): mild, moderate and severe; reduces systolic and diastolic blood pressure. Perindopril effectively acts for 24 hours. The maximum hypotensive effect is achieved 4-6 hours after a single dose of the drug. The T/P ratio (peak/plateau) of perindopril is 87-100%. Perindopril reduces blood pressure from the very beginning of treatment, stabilization of blood pressure occurs for 1 month and persists for a long time without the occurrence of tachyphylaxis. When you stop taking the drug, the withdrawal effect is not noted.
In addition to effectively lowering blood pressure, perindopril improves the elasticity of large-caliber arteries, corrects structural changes in small-caliber arteries, reduces left ventricular hypertrophy, prevents the progression of atherosclerosis, and has anti-ischemic properties.
Heart failure
Perindopril reduces the work of the heart by reducing pre- and afterload on the heart. Studies involving patients with heart failure have demonstrated a decrease in filling pressure in the right and left ventricles, a decrease in peripheral vascular resistance, an increase in cardiac index and cardiac output. In comparative studies using placebo and other ACE inhibitors, the use of perindopril at an initial dose of 2.5 mg in patients with mild to moderate heart failure did not cause arterial hypotension after taking the first dose compared with placebo.
Patients with cerebrovascular disease
The PROGRESS study of more than 6,000 patients demonstrated the benefit of 4-year treatment of patients with a history of stroke or transient cerebrovascular accident with perindopril tertbutylamine 4 mg, which is equivalent to perindopril arginine 5 mg (Prestarium 5 mg), on the prevention of recurrent stroke in patients with cerebrovascular disease ( in monotherapy or in combination with the diuretic indapamide in addition to basic therapy).
A statistically significant reduction in the risk of occurrence was noted: recurrent ischemic and 28% (including 50%); cases of fatal or disabling stroke by 33%; dementia and severe cognitive impairment associated with stroke, by 34 and 45%, respectively; myocardial infarction by 38%; heart failure by 26%.
These therapeutic outcomes were noted regardless of the presence of concomitant hypertension (arterial hypertension) or diabetes mellitus, age and gender, type of stroke.
Prevention of cardiovascular complications in patients with documented stable CAD.
A four-year EUROPA study involving 12,218 patients demonstrated that treatment with perindopril tertbutylamine 8 mg, which is equivalent to perindopril arginine 10 mg (Prestarium 10 mg): significantly reduced the likelihood of fatal and non-fatal myocardial infarction by 24%; significantly reduces the likelihood of developing heart failure requiring hospitalization by 39%.
Bioequivalence studies have confirmed bioequivalence between perindopril arginine at doses of 2.5; 5; 10 mg and perindopril with tertbutylamine in doses of 2; four; 8 mg.
After oral administration, perindopril is rapidly absorbed, the maximum plasma concentration is reached within 1 hour. The half-life of perindopril from blood plasma is 1 hour. Perindopril is a prodrug. 27% of the total amount of perindopril taken is determined in the blood as an active metabolite - perindoprilat. In addition to the active metabolite, 5 more inactive metabolites of the drug have been identified. The maximum concentration of perindoprilat in plasma is reached 3-4 hours after administration. Simultaneous food intake somewhat slows down the conversion of perindopril to perindoprilat, so perindopril arginine should be taken before meals. There is a linear relationship between the dose of perindopril and its concentration in blood plasma. In plasma, perindoprilat is in the form of free and ACE-bound fractions (the latter is responsible for the antihypertensive effect of the drug). The binding of perindoprilat to plasma proteins (mainly ACE) is 20%, this figure is dose-dependent.
Perindoprilat is excreted in the urine, the half-life of its free fraction is 17 hours. The state of equilibrium concentration in blood plasma is reached after 4 days from the start of treatment.
Removal of perindoprilat is slowed down in the elderly, in patients with heart and kidney failure. Doses of the drug for patients with renal insufficiency are recommended to be selected taking into account the degree of insufficiency and creatinine clearance. Dialysis clearance of perindoprilat is 70 ml/min.
The pharmacokinetics of perindopril changes in patients with cirrhosis of the liver. The hepatic clearance of perindopril is halved, but the amount of perindoprilat formed does not decrease, so dose adjustment in such patients is not required.

Indications for use of the drug Prestarium

AG (arterial hypertension); heart failure; in order to prevent recurrent stroke in patients with; prevention of cardiovascular complications in patients with proven stable coronary artery disease. Long-term treatment reduces the risk of myocardial infarction and heart failure (according to the EUROPA study).

The use of the drug Prestarium

Take orally 1 time per day before meals, preferably in the morning. The dose is selected individually for each patient, taking into account the indications for use and the level of blood pressure. Use in patients at risk - see. Tablets of 10 mg (Prestarium 10 mg) are not subject to division; 5 mg tablets (Prestarium 5 mg) can be divided.
AG (arterial hypertension)
Prestarium 5 or 10 mg may be given as monotherapy or in combination with other antihypertensive classes. The recommended starting dose is 5 mg (Prestarium 5 mg).
Patients with high activity of the renin-angiotensin-aldosterone system (especially patients with renovascular hypertension, impaired water and electrolyte balance, decompensated heart failure or severe hypertension (arterial hypertension), as well as elderly patients) due to the possibility of a sudden decrease in blood pressure (hypotension of the first dose) it is recommended to start treatment with a dose of 2.5 mg under the supervision of a physician, if necessary - in a hospital.
If necessary and well tolerated, the dose is gradually (over 1 month) increased to 5-10 mg (1 tablet Prestarium 5 mg or Prestarium 10 mg / day).
Heart failure
The recommended starting dose is 2.5 mg once daily before meals, preferably in the morning. After 2 weeks, subject to good tolerance, the dose can be increased to 5 mg and switched to the use of the drug Prestarium 5 mg. Use in patients at risk - see.
Prevention of recurrent stroke in patients with cerebrovascular disease(according to the results of the PROGRESS study).
The recommended starting dose is 2.5 mg (1/2 ton of Prestarium 5 mg tablets) once a day before meals, preferably in the morning. After 2 weeks of treatment, the dose is increased to 5 mg (Prestarium 5 mg). In case of insufficient hypotensive effect, it can be prescribed in combination with indapamide or switch to the use of a fixed combination of perindopril and indapamide (Prestarium Arginine Combi).
Treatment begins within 2 weeks to several years after the primary stroke.
Prevention of cardiovascular complications in patients with proven stable CAD
Long-term therapy reduces the risk of myocardial infarction and heart failure (according to the results of the 4-year EUROPA study). Treatment begins with the appointment of a dose of 5 mg / day (1 tablet of the drug Prestarium 5 mg), preferably in the morning. After 2 weeks, subject to good tolerance, the dose is increased to 10 mg and switched to long-term use of the drug Prestarium 10 mg.
Prestarium 10 mg at a dose of 1 tablet per day is prescribed for long-term therapy in patients with proven stable coronary artery disease, regardless of comorbidity, age and additional therapy.
In elderly patients with proven stable coronary artery disease, treatment begins with a dose of 2.5 mg 1 time per day before meals, preferably in the morning; after 1 week of treatment, the dose is increased to 5 mg (Prestarium 5 mg), after 2 weeks of treatment, if well tolerated, the dose is increased to 10 mg (Prestarium 10 mg), in which the drug continues to be taken for a long time.

Contraindications to the use of the drug Prestarium

Hypersensitivity to perindopril and other components of the drug; angioedema in history, including after the use of ACE inhibitors, pregnancy (especially II-III trimester) and breastfeeding.

Side effects of Prestarium

During the use of perindopril, the following side effects may be noted.
From the blood system: decrease in hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, anemia, agranulocytosis, pancytopenia. In patients with congenital deficiency of the enzyme glucose-6-phosphate dehydrogenase (G-6PDH), isolated cases of hemolytic anemia were noted.
From the side of the central nervous system and peripheral nervous system: headache, asthenia, dizziness, paresthesia; very rarely - mood disorders, sleep.
From the side of the organ of vision: visual impairment.
From the organ of hearing: noise in ears .
From the side of the cardiovascular system: arterial hypotension (especially after taking the first dose); very rarely - due to a sudden decrease in blood pressure in high-risk patients, arrhythmia, stable angina, myocardial infarction, stroke may occur (see).
From the respiratory system: dry cough, shortness of breath; infrequently - bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.
From the digestive system: nausea, vomiting, abdominal pain, diarrhea, constipation, feeling of dry mouth; very rarely - pancreatitis.
From the hepatobiliary system: very rarely - hepatitis, jaundice (see).
From the side urinary system: infrequently - aggravation of chronic renal failure; very rarely - OPN.
Allergic and skin reactions: skin rashes, erythema; infrequently - angioedema; very rarely - erythema multiforme.
Other manifestations: asthenia, muscle cramps, rarely - impotence, sweating.
Laboratory indicators: a possible increase in the concentration of potassium, creatinine and urea in the blood serum, especially in patients with severe heart failure and renovascular hypertension. Rarely - an increase in the activity of hepatic transaminases and the level of bilirubin in the blood plasma.

Special instructions for the use of the drug Prestarium

The use of the drug in the first trimester of pregnancy is not recommended. With a planned or established pregnancy, the drug should be discontinued. The use of the drug in the II-III trimester of pregnancy is contraindicated.
The use of perindopril during lactation is not recommended due to the lack of data on the excretion of perindopril in breast milk.
Perindopril is not recommended for children and adolescents due to the lack of relevant studies in such groups of patients.
Before starting the use of the drug and during its administration, it is necessary to monitor blood pressure, kidney function and the level of potassium in the blood plasma.
Influence on the level of potassium in the blood
There may be fluctuations in the level of potassium in the blood plasma in patients who take ACE inhibitors. In patients at risk of hyperkalemia, namely in patients with renal insufficiency, uncontrolled diabetes mellitus, hyperkalemia may occur.
First dose hypotension
When using ACE inhibitors after taking the first dose, a sudden decrease in blood pressure (hypotension of the first dose) is possible. Hypotension usually occurs in patients with concomitant disorders - hypovolemia, sodium deficiency caused by the use of diuretics, salt-free diet, vomiting, diarrhea, in patients with severe renin-dependent hypertension (arterial hypertension) and with symptoms of heart failure with or without concomitant renal failure), especially in patients with severe heart failure, taking loop diuretics in high doses, having an electrolyte imbalance or impaired renal function of a functional origin. Patients with impaired water and electrolyte balance are recommended to correct them before starting treatment with perindopril.
In patients at risk of developing arterial hypotension, initial therapy and further increase in dose should be carried out under medical supervision.
Use in patients with ischemic heart disease and cerebrovascular disease.
The above recommendations regarding the initiation of treatment should be followed in order to avoid a possible sudden decrease in blood pressure, which in such patients can lead to the development of myocardial infarction or stroke.
In the presence of severe heart failure and in other patients at risk, treatment should be started under the supervision of a physician. If hypotension of the first dose occurs in the patient while taking perindopril, the patient should be given a horizontal position with a low headboard and restore the BCC with an infusion of isotonic sodium chloride solution. Transient hypotension after the first dose is not a contraindication for further dose escalation if there is a need for further reduction in blood pressure after restoration of fluid and electrolyte balance and normalization of the patient's condition.
In order to reduce the risk of developing symptomatic arterial hypotension, patients who take diuretics are advised to stop taking them 2-3 days before starting treatment with perindopril; if this is not possible, treatment should be started with a minimum dose of 2.5 mg (Prestarium 2.5 mg). It is necessary to monitor kidney function and the level of potassium in the blood plasma. Further increase in the dose is carried out under the control of the level of blood pressure. If necessary, resume the use of diuretics.
Stenosis of the aortic or mitral valves, hypertrophic cardiomyopathy
All ACE inhibitors should be used with caution in patients with mitral valve stenosis or obstruction of the outflow tract from the left ventricle (aortic stenosis, hypertrophic cardiomyopathy).
Use in patients with renal insufficiency
In patients with renal insufficiency (creatinine clearance ≤60 ml / min), the dose should be adjusted taking into account creatinine clearance and the patient's response to treatment. It is also recommended to periodically monitor the level of potassium and creatinine in the blood serum.

Dialysis clearance of perindoprilat is 70 ml/min. Perindopril is not prescribed to patients on hemodialysis using high-flow polyacrylic membranes due to the possibility of an anaphylactoid reaction.
In some patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney, an increase in the level of urea and creatinine in the blood plasma may be noted, especially in the presence of renal insufficiency. Changes in indicators are reversible and normalize after stopping treatment. In the presence of renovascular hypertension in such patients, the risk of developing symptomatic hypotension and renal failure is increased. Treatment in such patients is recommended to begin under the supervision of a physician with a low dose and subject to good tolerance, with further titration of the dose upwards.
In some patients who did not have kidney disease before the start of treatment, an increase in the level of urea and creatinine in the blood plasma when using perindopril, especially in combination with diuretics, may indicate that the patient had impaired renal function before starting treatment. In this case, it may be necessary to reduce the dose, cancel the diuretic or ACE inhibitor.
In patients with heart failure, the occurrence of arterial hypotension at the beginning of treatment with an ACE inhibitor may lead to further impairment of renal function.
Use in patients with diabetes
Patients using insulin or oral hypoglycemic agents, while taking ACE inhibitors, need to control their blood glucose levels, especially during the first month of use (see also) .
Use in patients with hepatic insufficiency
Dose adjustment is not required. If the patient develops jaundice while using an ACE inhibitor, or if a significant increase in liver enzymes is noted, the ACE inhibitor should be discontinued and the patient should be carefully monitored.
Application in patients with collagenosis and in those taking allopurinol, immunosuppressants, procainamide
It should be used with caution, especially in the presence of impaired renal function.
Cough
Since the drug contains an ACE inhibitor, during its use, a dry cough may occur, which disappears after the drug is discontinued. If necessary, treatment can be continued.
Surgical interventions and anesthesia
The anesthesiologist should be informed about the use of any ACE inhibitor if the patient is scheduled for anesthesia or surgery. Treatment with an ACE inhibitor should be discontinued the day before surgery (see).
lactose intolerance
The composition of the drug includes lactose, so patients with congenital galactose intolerance, malabsorption syndrome of glucose and galactose, Lapp lactase deficiency are not recommended to prescribe the drug.
Plasmapheresis
Patients with elevated LDL levels during plasmapheresis with dextran sulfate while using an ACE inhibitor may experience life-threatening anaphylactoid reactions. The development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor before starting plasmapheresis.
Carrying out desensitization
Anaphylactoid reactions may occur in patients taking ACE inhibitors during specific desensitization to bee venom. These reactions can be prevented by temporarily stopping the ACE inhibitor. These reactions may appear during provocative tests.
Influence on psychomotor reactions
When driving vehicles or when working with mechanisms, the possibility of developing dizziness or weakness due to a sharp decrease in blood pressure should be taken into account.

Interactions of the drug Prestarium

Diuretics. In patients with impaired water and electrolyte balance taking diuretics, when prescribing an ACE inhibitor, a sharp decrease in blood pressure is possible. To reduce the risk of arterial hypotension in such patients, it is recommended to stop treatment with diuretics and restore water and electrolyte balance before starting treatment with perindopril.
Simultaneous administration with potassium-sparing diuretics (spironolactone, amiloride, triamterene) or potassium salts can cause hyperkalemia. The above drugs are not recommended for concomitant use with perindopril. If these funds are prescribed, they should be used with caution. It is necessary to regularly monitor the level of potassium in the blood plasma.
NSAIDs, including acetylsalicylic acid at a dose of ≥3 g/day, reduce the antihypertensive effect of ACE inhibitors, while providing a synergistic effect on increasing the level of potassium in the blood plasma, and can also cause impaired renal function. This effect is reversible. In rare cases, renal failure may occur in patients with a history of impaired renal function (the elderly, patients with impaired water and electrolyte balance).
When using ACE inhibitors with drugs lithium perhaps a reversible increase in the concentration of lithium in the blood plasma and, accordingly, an increase in the risk of its toxic effect. The use of thiazide diuretics increases the likelihood of lithium toxicity when used with ACE inhibitors. It is not recommended to use perindopril simultaneously with lithium preparations. If it is necessary to prescribe such a combination, it is necessary to control the level of lithium in the blood plasma.
Antihypertensives and vasodilators. The simultaneous use of antihypertensive agents, nitroglycerin, other nitrates and vasodilators may enhance the antihypertensive effect of perindopril.
Antidiabetic agents. The simultaneous use of ACE inhibitors and drugs that lower blood glucose levels (insulin, oral hypoglycemic agents) may cause a further decrease in blood glucose levels and the risk of hypoglycemia, especially in the first weeks of treatment and in patients with renal insufficiency.
Tricyclic antidepressants/antipsychotics/anesthetics. The simultaneous use of certain anesthetics, tricyclic antidepressants or antipsychotics with ACE inhibitors can lead to a further decrease in blood pressure.
Sympathomimetics: possible weakening of the antihypertensive effect of ACE inhibitors.

Overdose of the drug Prestarium, symptoms and treatment

Symptoms of an overdose of any ACE inhibitors are severe arterial hypotension, circulatory shock, tachycardia, bradycardia, electrolyte imbalance, renal failure, hyperventilation, dizziness, anxiety. In case of an overdose, the patient should be hospitalized and under medical supervision. Plasma electrolytes and creatinine should be monitored. Treatment depends on the nature and severity of the symptoms. It is necessary to reduce the absorption of the ACE inhibitor by gastric lavage and the appointment of enterosorbents. In case of severe arterial hypotension, the patient should be placed in a horizontal position with the head down and the BCC restored by infusion of isotonic sodium chloride solution. If necessary, angiotensin II and/or catecholamines are administered intravenously. In severe cases, temporary implantation of a pacemaker is indicated. It is necessary to control and correct the vital functions of the body.
Perindopril can be removed from the body by hemodialysis. The use of high flow membranes is not recommended.

Storage conditions of the drug Prestarium

In a tightly closed container under normal conditions.

List of pharmacies where you can buy Prestarium:

• St. Petersburg