Active substancePerindopril argininePerindopril arginine
Similar drugsTo uncover
Dosage form: & nbsptablets dispersible in the oral cavity
Composition:

Tablet 2.5 mg

Active substance: perindopril arginine 2.5 mg (1.698 mg in terms of perin dopryl).

Excipients:

Acesulfame potassium 0.1 mg, aspartame 0.1 mg, magnesium stearate 0.2 mg, silicon dioxide colloidal anhydrous 0.2 mg, dry mixture of lactose and starch (lactose monohydrate 85%, corn starch 15%) 36.9 mg.

Tablet 5 mg

Active substance: perindopril arginine 5 mg (3.395 mg in terms of perindopril).

Excipients:

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

Tablet 10 mg

Active substance: perindopril arginine 10 mg (6,790 mg in terms of perindopril).

Excipients:

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

Description:Round biconvex tablets of white color.
Pharmacotherapeutic group:inhibitor of angiotensin-converting enzyme (ACE)
Pharmacodynamics:

Mechanism of action

Perindopril is an inhibitor of the enzyme converting angiotensin I to angiotensin II. ACE, or kininase II, is an exopeptidase that carries out both the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, and the destruction of bradykinin, which has a vasodilating action, to an inactive heptapeptide. As a result, perindopril reduces the secretion of aldosterone.

Since the angiotensin converting enzyme inactivates bradykinin, suppression of ACE is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, and the system of prostaglandins is also activated. It is possible that this effect is part of the mechanism of antihypertensive action of ACE inhibitors, as well as the mechanism of development of some side effects of drugs of this class (for example, cough). Perindopril It has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites have no 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 (BP) in the patient's position "lying" and "standing".

Perindopril reduces the overall peripheral vascular resistance (OPSS), which leads to a decrease in blood pressure, while peripheral blood flow accelerates without changing the heart rate (heart rate).

Usually, perindopril leads to an increase in renal blood flow, the rate of glomerular filtration does not change.

Antihypertensive effect of the drug reaches a maximum after 4-6 hours after a single oral intake and remains for 24 hours. After 24 hours after ingestion, a residual (about 80%) residual ACE inhibition is observed. Decrease in blood pressure is achieved quickly enough. In patients with a positive response to treatment, BP normalization occurs within a month and persists without the development of tachycardia.

The termination of treatment is not accompanied by the development of the "withdrawal" syndrome.

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

Simultaneous administration of thiazide diuretics increases 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 with diuretics.

Heart failure:

Perindopril normalizes the heart, reducing preload and postnagruzku.

In patients with chronic heart failure who received perindopril, it was revealed: a decrease in filling pressure in the left and right ventricles of the heart; decrease in total peripheral resistance of blood vessels; of theyshcardiac output and an increase in cardiac index. Study of the drug compared with placebo showed that changes in blood pressure after the first administration of Prestarium ® A 2.5 mg in patients with chronic heart failure (II - III functional class by classification NYHA), statistically significantly did not differ from changes in blood pressure observed after taking placebo.

TseReproductive diseases

The results of the PROGRESS study, which evaluated the effect of active perindopril therapy (monotherapy or in combination with indapamide) for 4 years on the risk of recurrent stroke in patients with a history of cerebrovascular disease. After an introductory period of 2 mg perindopril of tert-butylamine (equivalent to perindopril arginine 2.5 mg) once a day for two weeks and then 4 mg (equivalent to 5 mg perindopril arginine) odionce a day for the next two weeks, 6105 patients were randomized into two groups: placebo (n = 3054) and perindopril tretbutylamine by 4 mg (corresponding to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n = 3051). Indapamide additionally assigned to patients who do not have direct indications or contraindications for the use of diuretics. This therapy was prescribed in addition to standard therapy of stroke and / or hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular disease (stroke or transient ischemic attack) during the last 5 years.The value of AD was not an inclusion criterion: 2916 patients had arterial hypertension and 3189 had normal BP. After 3.9 years of therapy, the value of AD (systolic / diastolic) decreased by an average of 9.0 / 4.0 mm Hg. There was also a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic) of about 28% (95% CI (17; 38), p <0.0001) compared with placebo (10.1% and 13.8%).

In addition, a significant reduction in risk was shown:

- Fatal or incapacitating strokes;

- Major cardiovascular complications, including myocardial infarction, incl. with lethal outcome;

- dementia associated with stroke;

- serious impairment of cognitive functions.

This was noted both in patients with arterial hypertension and at normal BP, regardless of age, sex, the presence or absence of diabetes mellitus and the type of stroke.

Stable ischemic heart disease (CHD)

It has been shown that, when taking 8 mg per day of perindopril at a dosage of 8 mg / day (equivalent to 10 mg perindopril arginine) in patients with stable coronary artery disease, there is a significant reduction in the absolute risk of complications provided by the main efficacy criterion (mortality from cardiovascular diseases,the incidence of nonfatal myocardial infarction and / or cardiac arrest with subsequent successful resuscitation) by 1.9%. Patients previously who underwent myocardial infarction or coronary revascularization, the absolute risk reduction was 2.2% compared to the placebo group.

Pharmacokinetics:

Suction

Ingestion perindopril quickly absorbed in the gastrointestinal tract, the maximum concentration (Cmax) in the blood plasma is achieved after 1 h. The half-life period (T1/2) of perindopril from blood plasma is 1 hour.

Perindopril does not have pharmacological activity. Approximately 27% of the total amount of absorbed perindopril enters the bloodstream as an active metabolite of perindoprilate. In addition to perindoprilata, another 5 metabolites are formed that do not have pharmacological activity. The perindoprilite stan in the blood plasma is achieved 3-4 hours after ingestion.

Eating slows the conversion of perindopril to perindoprilat, thus affecting bioavailability. Therefore, the drug should be taken orally 1 time per day, in the morning, before eating.

Distribution

The volume of distribution of free perindoprilata is approximately 0.2 l / kg. The association of perindoprilata with blood plasma proteins, mainly with ACE, is insignificant and is dose-dependent.

Excretion

Perindoprilat is excreted by the kidneys. The free fraction is 3-5 hours. "Effective" T1/2 is approximately 17 hours, the equilibrium state is reached within 4 days.

Special patient groups

The excretion of perindoprilat is delayed in old age, as well as in patients with cardiac and renal insufficiency.

The dialytic clearance of perindoprilat is 70 ml / min.

In patients with cirrhosis, the liver clearance of perindopril is reduced by a factor of 2. Nevertheless, the amount of perindoprilat formed does not decrease, and dose adjustment is not required (see the "Dosage and Administration" and "Specific Guidelines" sections).

Indications:

arterial hypertension; chronic heart failure;

prevention of recurrent stroke (combination therapy with indapamide) in patients who underwent a stroke or transient cerebral circulation disorder by ischemic type;

stable ischemic heart disease: reduction in the risk of cardiovascular complications in patients with stable ischemic heart disease.

Contraindications:

- hypersensitivity to active substance, other ACE inhibitors and excipients (see section "Composition"), included in the preparation;

- angioedema (angioedema) in the anamnesis associated with the administration of an ACE inhibitor;

- hereditary / idiopathic angioedema;

- pregnancy (see section "Application during pregnancy and during breast-feeding");

- the period of breastfeeding (see section "Application during pregnancy and during breast-feeding");

- simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) ml / min / 1.73 m2) (see the sections "Special instructions" and "Interaction with other medicinal products").

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

- age to 18 years (efficacy and safety not established).

Carefully:

(see also the sections "Special instructions" and "Interaction with other medicinal products")

Two-sided stenosis of the renal arteries or the presence of only one functioning kidney, renal failure, systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.), immunosuppressor therapy, allopurinol, procainamide (risk of neutropenia, agranulocytosis), decreased circulating blood volume (diuretics , salt-free diet, vomiting, diarrhea), angina pectoris, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure IV function class by classification NYHA, simultaneous application of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for dietary salt and lithium, hyperkalemia, surgical intervention / general anesthesia, hemodialysis using high-flux membranes, desensitizing therapy, low density lipoprotein apheresis (LDL), condition after kidney transplantation, aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, the use of Negroid race in patients.

Pregnancy and lactation:

Pregnancy

Prestarium ® A is contraindicated for use in pregnancy (see p.section "Contraindications").

Prestarium® A should not be used in the first trimester of pregnancy. When planning a pregnancy or when it comes during Prestarium ® A, stop taking the medication immediately and, if necessary, prescribe another antihypertensive therapy with a proven safety profile during pregnancy.

It is known that the effect of ACE inhibitors on the fetus in the II and III trimester of gestation may lead to disruption of its development (reduction of renal function, oligohydramnios, slowing ossification of bones of the skull) and the development of complications in the newborn (renal failure, hypotension, hyperkalaemia).

If the patient received ACE inhibitors during the second or third trimester of pregnancy, an ultrasound examination of the newborn is recommended to assess the condition of the skull bones and kidney function.

Breastfeeding period

It is not known whether the perindopril in breast milk. In this connection, the use of Prestarium ® A during breast-feeding is not recommended.

If the use of the drug is necessary during lactation, then breastfeeding should be abolished.

Fertility

In preclinical studies, the absence of perindopril has been shown to affect reproductive function in rats of both sexes.

Dosing and Administration:

Inside, 1 tablet 1 time per day, preferably in the morning, before eating.

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, it is necessary to take into account the peculiarities of the clinical situation (see the section "Special instructions") and the degree of BP reduction on the background of the therapy. Arterial hypertension Prestarium ® A can be used both in monotherapy and in combination therapy.

The recommended initial dose is 5 mg once a day.

In patients with severe renin-angiotensin-aldosterone (RAAS) activity (especially with renal vascular hypertension, hypovolemia and / or reduced plasma electrolytes, decompensation of chronic heart failure or severe arterial hypertension), after a first dose of the drug, a marked decrease in blood pressure . At the beginning of therapy, such patients should be under close medical supervision.The recommended initial dose for such patients is 2.5 mg 1 time per day.

If necessary, a month after the start of therapy, you can increase the dose of the drug to 10 mg once a day.

At the beginning of therapy with Prestarium ® A, symptomatic arterial hypotension may occur. In patients receiving diuretics concomitantly, the risk of developing arterial hypotension is higher due to possible hypovolemia and a decrease in the content of plasma electrolytes. Care should be taken when using Prestarium ® A in this group of patients. It is recommended, if possible, to stop taking diuretics 2-3 days before the proposed start of therapy with Prestarium ® A (see section "Special instructions").

If it is not possible to abolish diuretics, the initial dose of Presarium A should be 2.5 mg. It is necessary to monitor the kidney function and the potassium content in the blood serum. In the future, if necessary, the dose of the drug may be increased. If necessary, the reception of diuretics can be resumed.

In elderly patients, treatment should begin with a dose of 2.5 mg per day.If necessary, a month after the start of therapy, the dose can be increased to 5 mg per day, and then to the maximum dose of 10 mg per day, taking into account the state of kidney function (see Table 1).

The maximum daily dose is 10 mg.

CeCardiac insufficiency

Treatment of patients with chronic heart failure with Prestarium ® A in combination with non-potassium-sparing diuretics and / or digoxin and / or beta-blockers is recommended to begin under close medical supervision, prescribing the drug at an initial dose of 2.5 mg once a day in the morning. After two weeks of treatment, the dose of the drug can be increased to 5 mg once a day, provided a good dose tolerance of 2.5 mg and a satisfactory response to ongoing therapy.

In patients with a high risk of developing symptomatic arterial hypotension, for example, with a reduced electrolyte content with or without hyponatremia, hypovolemia, or taking diuretics, before the start of Prestarium ® A, if possible, the listed conditions should be adjusted. Such indicators as blood pressure, renal function and potassium content in blood plasma should be monitored both before and during therapy.

Prevention of recurrent stroke (combination therapy with indapamide)

In patients with previous history of cerebrovascular disease, Prestarium® A therapy should be started at a dose of 2.5 mg during the first two weeks, then increasing the dose to 5 mg over the next two weeks before using the indapamide.

Therapy should be started at any time (from two weeks to several years) after a stroke.

IHD: a reduction in the risk of cardiovascular complications in patients who have had previous myocardial infarction and / or coronary revascularization In patients with stable course of IHD, treatment with Prestarium A should be started with a dose of 5 mg once a 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 once a day.

Elderly patients should begin therapy with a dose of 2.5 mg once a day for one week, then 5 mg once a day for the next week. Then, taking into account the state of kidney function, the dose can be increased to 10 mg once a day (see Table 1). Increase the dose of the drug only if it is well tolerated in the previously recommended dose.

Special patient groups Renal insufficiency

In patients with renal insufficiency, the dose of the drug should be selected taking into account the clearance of creatinine (CC).

Table 1. Dosage of Prestarium ® A in renal failure

CK (ml / min.)

Recommended dose

greater than or equal to 60

5 mg / day

more than 30 and less than 60

2.5 mg / day

more than 15 and less than 30

2.5 mg every other day

Patients on hemodialysis[1]

2.5 mg per day of dialysis

less than 15



[1] dialysed clearance of perindoprilat - 70 ml / min. The drug should be taken after the dialysis procedure.

Liver failure

Patients with a violation of the function of the liver dose adjustment is not required (see the sections "Pharmacokinetics" and "Special instructions").

Age under 18 years old

Prestarium® A should not be given to children and adolescents under 18 years of age because of lack of data on the efficacy and safety of the drug in patients of this age group.

Side effects:

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

The most frequent adverse events reported in clinical trials and that have been observed with perindopril are: dizziness, headache, paresthesia, vertigo,visual impairment, tinnitus, excessive blood pressure lowering, cough, shortness of breath, abdominal pain, constipation, diarrhea, taste disorder, dyspepsia, nausea, vomiting, itching, skin rash, muscle spasms and asthenia.

Frequency of adverse reactions that were noted during clinical trials and / or post-marketing use of perindopril, is given in the form of the following gradation: very often (> 1/10); often (> 1/100, <1/10); infrequently (> 1/1000, <1/100); rarely (> 1/10000, <1/1000); very rarely (<1/10000); frequency (frequency can not be calculated from available data). Classification of frequency indicators is recommended by the World Health Organization (WHO).

On the part of the blood and lymphatic system Infrequently*: eosinophilia.

Rarely: reduction of hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, agranulocytosis, pancytopenia, hemolytic anemia in patients with congenital deficiency of glucose-6-phosphate dehydrogenase (see section "Specific guidance").

Metabolic disorders

Infrequently*: hypoglycemia (see the sections "Special instructions" and "Interaction with other medicinal products"), hyperkalaemia reversible after drug withdrawal (see section "Special instructions"), hyponatremia.

From the central nervous system

Often: paresthesia, headache, dizziness, Vertigo.

Infrequently: violations sleep, lability mood, drowsiness *, fainting *.

Rarely: confusion.

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

From the side of the hearing organ Often: noise in the ears.

From the side of the cardiovascular system

Often: excessive blood pressure lowering and the associated symptoms.

Infrequently*: vasculitis, tachycardia, palpitation.

Rarely: heart rhythm disturbances, angina pectoris, myocardial infarction and stroke, possibly due to excessive blood pressure lowering in patients at high risk (see section "Special instructions").

From the respiratory system Often: cough, dyspnea.

Infrequently: bronchospasm.

Rarely: eosinophilic pneumonia, rhinitis.

From the digestive system

Often: constipation, nausea, vomiting, abdominal pain, taste disorder, dyspepsia, diarrhea. Infrequently: dryness the mucous membrane of the mouth.

Rarely: pancreatitis.

From the liver and biliary tract

Rarely: hepatitis (cholestatic or cytolytic) (see section "Special instructions").

From the skin and subcutaneous fat Often: cutaneous itching, rash.

Infrequently: angioedema, edema of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal cords and / or larynx; hives (see section "Special instructions").

Rarely: erythema multiforme.

Infrequently*: photosensitivity, pemphigus, increased sweating.

From the musculoskeletal system and connective tissue

Often: muscle spasms. Infrequently*: arthralgia, myalgia.

From the side of the kidneys and urinary tract Infrequently: renal insufficiency.

Rarely: acute renal failure.

From the side of the reproductive system Infrequently: erectile disfunction.

General disorders and symptoms Often: asthenia.

Infrequently: chest pain *, peripheral edema *, weakness *, fever *, falls *.

Laboratory indicators

Rarely: increased activity of "liver" transaminases and bilirubin in the blood serum.

Infrequently*: increase in the concentration of urea and creatinine in the blood plasma. * An estimate of the incidence of adverse reactions identified by spontaneous reports was made on the basis of clinical trial results.

Undesirable effects noted in clinical studies In the study EUROPA only serious adverse events were recorded. Serious adverse events were noted in 16 (0.3%) patients in the perindopril group and in 12 (0.2%) patients in the placebo group. In the group of perindopril, a marked decrease in blood pressure was noted in 6 patients, angioedema in 3 patients, and sudden cardiac arrest in 1 patient. The frequency of withdrawal of the drug due to cough, marked 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: marked decrease in blood pressure, shock, disturbance of water-electrolyte balance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough.

Treatment

Emergency measures are reduced to removing the drug from the body: washing the stomach and / or taking activated charcoal, followed by the restoration of the water-electrolyte balance.

With a significant decrease in blood pressure, the patient should be transferred to the "prone" position on the back from the pripodnywith your feet. If necessary, intravenously 0.9% solution of sodium chloride. If necessary, you can enter intravenously a solution of catecholamines. Perindoprilat, an active metabolite of perindopril, can be removed from the body by dialysis. With the development of a bradycardia-resistant therapy, it may be necessary installation an artificial pacemaker. It is necessary to constantly monitor indicators of the basic vital functions of the body, concentration creatinine and electrolytes in serum.

Interaction:

Medicines that cause hyperkalemia

Some drugs or preparations of other pharmacological classes may increase the risk of hyperkalemia: aliskiren and aliskiren containing preparations, potassium salts, potassium-sparing diuretics, inhibitors of AIF, angiotensin II receptor antagonists (ARA II), non-steroidal anti-inflammatory drugs (NSAIDs), heparin, immunosuppressants such as ciclosporin or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalemia. Simultaneous use is contraindicated (see the section "Contraindications") Aliskiren

In patients with diabetes mellitus or renal dysfunction (GFR less than 60 mL / min), the risk of hyperkalemia, impaired renal function, and increased incidence of cardiovascular morbidity and mortality increases. Simultaneous use is not recommended (see section "Special instructions") Aliskiren

In patients without diabetes mellitus or renal dysfunction, there may be an increased risk of hyperkalemia, impaired renal function, and an increased incidence of cardiovascular morbidity and mortality.

Double blockade of RAAS

In the literature it was reported that in patients with established atherosclerotic disease, heart failure or diabetes with target organ damage, simultaneous therapy with an ACE inhibitor and ARA II is associated with a higher incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure ) compared with the use of only one drug that affects RAAS. Double blockade (for example, with the combination of an ACE inhibitor with APA II) should be limited to individual cases with careful monitoring of kidney function, potassium and blood pressure.

Estramustine

Simultaneous application can lead to an increased risk of side effects, such as angioedema.

Potassium-sparing diuretics (such as triamterene, amiloride, spironolactone and its derivative eplerenone), potassium salts

Hyperkalemia (with a possible fatal outcome), especially in cases of impaired renal function (additional effects associated with hyperkalemia). The combination of perindopril with the above medicines is not recommended (see section "Special instructions"). If, however, simultaneous application is shown, they should be used, observing safety precautions and regularly monitoring the potassium content in serum.

Features of the use of spironolactone in heart failure are described further in the text.

Lithium preparations

With simultaneous use of lithium drugs and ACE inhibitors, celebrate reversible increase concentrations lithium in serum blood and related toxic effects. Simultaneous use of perindopril and lithium preparations is not recommended. If this therapy is necessary, regular monitoring should be carried out concentrations lithium in blood plasma (see section "Special instructions").

Simultaneous application, which requires special care Hypoglycemic agents (insulin, hypoglycemic agents for oral administration)

The use of ACE inhibitors can enhance the hypoglycemic effect of insulin and hypoglycemic means for admission Inside up to the development of hypoglycemia. As a rule, this is observed in the first weeks of the simultaneous therapy and in patients with impaired renal function.

Baclofen

Strengthens the antihypertensive effect of ACE inhibitors. It is necessary to carefully monitor the level of blood pressure and, if necessary, the dosage of antihypertensive drugs.

Potassium-sparing diuretics

In patients receiving diuretics, especially deducing liquid and / or salt, at the beginning of perindopril therapy, there may be an excessive decrease in blood pressure, the risk of which can be reduced by eliminating the diuretic, replenishing fluid loss or salts before starting therapy with perindopril, and appointment perindopril in low dose with its further gradual increase.

With arterial hypertension in patients receiving diuretics, especially those that remove fluid and / or salts, diuretics should be either withdrawn before the use of an ACE inhibitor (with a potassium-sparing diuretic may be re-assigned later), or an ACE inhibitor should be prescribed at a low dose with a further gradual increase.

When using diuretics in the case of chronic heart failure the ACE inhibitor should be administered at a low dose, possibly after a reduction in the dose of the simultaneously used potassium-sparing diuretic. In all cases, renal function (creatinine concentration) should be monitored in the first weeks of the use of ACE inhibitors. 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:
When treating heart failure II-IV functional class by classification NYHA with a left ventricular ejection fraction <40% and previous ACE inhibitors and loop diuretics, there is a risk of hyperkalemia (possibly fatal), especially in the case of non-compliance with recommendations for this combination of drugs.

Before using this combination of drugs, you need to make sure there is no hyperkalemia and renal dysfunction. It is recommended to regularly monitor the concentration of creatinine and potassium in the blood: weekly in the first month of treatment and every month thereafter. NSAIDs, including high doses of acetylsalicylic acid (more than 3 g / day) Simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE inhibitors. Simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced renal function. Care should be taken when prescribing this combination, especially in elderly patients. Patients must receive an adequate amount liquid, and recommended carefully monitor the kidney function, both at the beginning and during the treatment.

A simultaneous application that requires some caution

Hypotensive drugs and vasodilators

The antihypertensive effect of perindopril may be enhanced by simultaneous use with other antihypertensive, vasodilating agents, including nitrates of short and prolonged action.

Glyptins (linaglyptin, saxagliptin, sitagliptin, vitagliptin)

Co-administration with ACE inhibitors may increase the risk of developing angioedema due to inhibition of dipeptidyl peptidase IV (DAP-IV) glyptin.

Tricyclic antidepressants, antipsychotics (antipsychotics) and means for general anesthesia

Simultaneous use with ACE inhibitors can lead to an increase in antihypertensive action (see section "Special instructions").

Sympathomimetics

May weaken the antihypertensive effect of ACE inhibitors.

Preparations of gold

With the use of ACE inhibitors, including perindopril, patients receiving an intravenous preparation of gold (sodium aurotomy malate), was described symptom-complex, which includes flushing of the facial skin, nausea, vomiting, arterial hypotension.

Special instructions:

IHD: a reduction in the risk of cardiovascular complications in patients who have had previous myocardial infarction and / or coronary revascularization

With the development of unstable angina during the first month of therapy with Prestarium ® A, 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 course of arterial hypertension. The risk of excessive reduction in blood pressure is increased in patients with reduced BCC, which can be observed against diuretic therapy, with strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe hypertension with high renin activity (see "Interactions with other medicinal products "and" Side effect "). Patients with an increased risk of developing symptomatic arterial hypotension should carefully monitor blood pressure, kidney function and potassium content in the blood serum during therapy with Prestarium ® A.

A similar approach is also used in patients with ischemic heart disease and cerebrovascular diseases in which severe arterial hypotension can lead to myocardial infarction or impaired cerebral circulation.

In the case of development of arterial hypotension the patient should be transferred to the "lying" position on the back with raised legs. If necessary, replenish the volume of circulating blood by intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle for further administration of the drug. After restoration BCC and AD treatment can be continued.

In some patients with chronic heart failure (CHF) and normal or reduced BP Prestarium ® A can cause an additional reduction in blood pressure. This effect is predictable and usually does not require discontinuation of therapy. If symptoms of a marked decrease in blood pressure appear, reduce the dose or stop taking it.

Mitral stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

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

Impaired renal function

For patients with renal insufficiency (KC less than 60 ml / min), the initial dose of Prestarium ® A is selected depending on the value of the CC (see the "Method of administration and dose" section) and then depending on the therapeutic effect. For such patients, regular monitoring is necessary concentrations of creatinine and potassium at serum blood (see section "Side effect").

Arterial hypotension, which sometimes develops early in the administration of ACE inhibitors in patients with symptomatic CHF, can lead to impaired renal function. It is possible to develop acute renal failure, as a rule, reversible. In patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney (especially in the presence of kidney failure) against the background of therapy with ACE inhibitors, an increase in the concentration of urea and creatinine in the blood serum, usually taking place with the withdrawal of therapy, is possible. The additional presence of reninvascular hypertension causes an increased risk of severe arterial hypotension and kidney failure in these patients.

Treatment of such patients begins under careful medical supervision with the use of low doses of the drug and further adequate selection of doses. Diuretic treatment should be temporarily discontinued and regular monitoring of potassium and creatinine in the blood plasma during the first few weeks of therapy.

In some patients with hypertension Without indicating the presence of a previous disease of the kidneys can increase the concentration urea and creatinine in the blood serum, especially with the simultaneous use of diuretics. These changes are usually not very pronounced and are reversible. The probability of these disorders is higher in patients with a history of renal insufficiency. 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-permeability membranes (for example, AN69®), cases of development of anaphylactic reactions on the background of therapy with ACE inhibitors. The use of ACE inhibitors should be avoided when using this type of membrane.

Kidney Transplantation

Data on the use of Prestarium ® A in patients after kidney transplantation are not available.

Hypersensitivity / angioedema

When taking ACE inhibitors, including perindopril, in rare cases and in any period of therapy may develop angioedema, edema of the face, upper and lower limbs, lips, mucous membranes, tongue, vocal cords and / or larynx (see section "Side effect"). When symptoms appear, taking the drug should be stopped immediately, and the patient should be observed until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually pass on their own, although antihistamines can be used to treat the symptoms.

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

Patients with a history of Quinck's edema who are not associated with taking ACE inhibitors may be at increased risk of developing this drug when taking this drug (see "Contraindications").

In rare cases, against the background of therapy with ACE inhibitors, angioedema develops in the intestine. Thus, patients have a pain in the abdomen as an isolated symptom or in combination with nausea and vomiting in some cases without prior angioneurotic edema of the face and at normal levels of C1-esterase. The diagnosis was established using computed tomography of the abdominal region, ultrasound examination or surgical intervention. Symptoms disappeared after discontinuation of ACE inhibitors. Therefore, patients with abdominal pain receiving ACE inhibitors should take into account the possibility of angioedema edema development during differential diagnosis (see section "Side effect").

Anaphylactoid reactions during apheresis of low density lipoproteins (LDL)

In rare cases in patients receiving ACE inhibitors, during the procedure of apheresis of LDL with the use of dextran sulfate may develop life threatening anaphylactoid reactions. To prevent anaphylactoid reaction, therapy with an ACE inhibitor should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There are some reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy, for example, by the venom of Hymenoptera. ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors should be avoided for patients receiving immunotherapy with bee venom. However, this reaction can be avoided by the temporary withdrawal of the ACE inhibitor before the desensitization procedure begins.

Impaired liver function

In rare cases, when taking ACE inhibitors there was a syndrome of development cholestatic jaundice with the transition to fulminant liver necrosis, sometimes fatal.The mechanism of development of this syndrome is unclear. When there is jaundice or a significant increase in the activity of "hepatic" Enzymes on the background of taking ACE inhibitors should stop taking the drug (see the section "Side effect"), the patient should be under appropriate medical supervision.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Against the background of taking ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia can occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With extreme caution follow the apply Prestarium® A in patients with systemic connective tissue diseases, with immunosuppressant, allopurinol or procainamide, especially in patients with impaired renal function.

Some patients had severe infections, in some cases, resistant to intensive antibiotic therapy. When appointing Prestarium® A such patients are advised to periodically monitor content leukocytes in the blood. Patients should inform the doctor of any signs of infectious diseases (eg, sore throat, fever).

Ethnic differences

It should be borne in mind that in patients of the Negroid race the risk of angioedema development is higher. Like other ACE inhibitors, Prestarium ® A is less effective in reducing blood pressure in patients of the Negroid race.

This effect is probably associated with a marked predominance of low-grade status in patients of the Negroid race with arterial hypertension.

Cough

On the background of therapy with an inhibitor ACE may arise persistent dry cough, which stops after the drug is discontinued. This should be taken into account in the differential diagnosis of cough.

Surgery / general anesthesia

The use of ACE inhibitors in patients who undergo surgery with general anesthesia can lead to a marked decrease in blood pressure, especially when using drugs for general anesthesia that have an antihypertensive effect. Prestarium ® A should be discontinued one day before surgery. With the development of arterial hypotension, blood pressure should be maintained by replenishing the BCC. It is necessary to alert the surgeon / anesthesiologist that the patient is taking ACE inhibitors.

Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, including, and perindopril. Risk factors for hyperkalemia are renal failure, decreased kidney function, age over 70 years, diabetes mellitus, some concomitant conditions (dehydration, acute heart failure, metabolic acidosis), simultaneous reception of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), food additives / potassium preparations or potassium-containing substitutes for edible salt, as well as the use of other drugs that increase the potassium content in the blood (for example, heparin). Application food additives / potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal heart rhythm disturbances. If simultaneous reception is required Prestarium® A and the above drugs, treatment should be carried out with caution in the background of regular monitoring of potassium content in serumblood (see the section "Interaction with other medicinal products").

Patients with diabetes mellitus

When prescribing a drug for patients with diabetes mellitus receiving hypoglycemic agents for ingestion or insulin, during the first month of therapy it is necessary to regularly monitor concentration glucose in the blood (see section "Interaction with other medicinal products"). Lithium preparations

The simultaneous use of Prestarium ® A and lithium preparations is not recommended (see the section "Interaction with Other Drugs"),

Potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for edible salt and food additives

It is not recommended the simultaneous administration of Prestarium A and potassium-sparing diuretics, as well as preparations of potassium, potassium-containing substitutes for edible salt and food additives (see the section "Interaction with other medicinal products").

Double blockade of RAAS

Arterial hypotension, fainting, stroke, hyperkalemia and renal dysfunction (including acute renal failure) have been reported in susceptible patients, especially when used with medications that affect this system.Therefore, the double blockade of RAAS due to a combination of an ACE inhibitor with ARAP or aliskiren is not recommended.

The combination with aliskiren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR <60 mL / min / 1.73 m2) (see the sections "Contraindications" and "Interaction with other medicinal products").

Effect on the ability to drive transp. cf. and fur:

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

Form release / dosage:

Tablets are dispersible in the oral cavity 2.5 mg, 5 mg and 10 mg.

For 30 tablets in a polypropylene bottle, equipped with a dispenser and a stopper containing a moisture absorbing gel.

For 1 bottle of 30 tablets with instructions for medical use in a pack of cardboard with the control of the first autopsy.

Packaging:(30) - polypropylene bottles with a dispenser (1) - packs cardboard
Storage conditions:

Special storage conditions are not required.

Keep out of the reach of children.

Shelf life:

2 years.

DO NOT USE AT THE EXPIRY OF THE YEAR OF LIFE, INDICATED ON PACKAGING.

Terms of leave from pharmacies:On prescription
Registration number:LP-001805
Date of registration:17.08.2012
The owner of the registration certificate:Servier LaboratoriesServier Laboratories France
Manufacturer: & nbsp
Representation: & nbspServier Laboratories Servier Laboratories France
Information update date: & nbsp28.08.2015
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