Perindopril - instructions for use, dose, side effects, contraindications

ACE (kininase II) is an exopeptidase that carries out both the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, and the destruction of adikinin, which has a vasodilating action, to an inactive ztapeptide. As a result, perindopril reduces the secretion of aldosterone.

Since ACE inactivates bradykinin, ACE inhibition 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 anti-hypertensive action of ACE inhibitors,and that mechanism of development of some side effects of drugs of this class (for example, coughing).

Perindopril has a therapeutic effect due to the active metabolite - perindoprilat. Other metabolites of the drug have no inhibitory effect for ACE in vitro.

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

As a rule, psrndopril leads to an increase in renal blood flow, the rate of glomerular filtration does not change.

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

The cessation of treatment with ns is accompanied by the development of the "withdrawal" syndrome.

Psrindopril exerts 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.

The simultaneous administration of thiazide diuretics enhances the manifestation of the antihypertensive effect. In addition, the combination of an ACE inhibitor and Ti[Azide diuretic also leads to a reduction in the risk of hypokalemia with diuretics.

Heart failure afterloading.

Perindopril normalizes the heart, reducing preload and postnagruzku. In patients with chronic heart failure (CHF) who received perindopril, It revealed:

- decrease of filling pressure in the left and right ventricles of the heart;

- decrease in OPCC;

- increased cardiac output and an increase in cardiac index.

Stable ischemic heart disease (CHD)

It was found,that with the use of perindopril at a dose of 8 mg per day in patients with stable coronary heart disease there is a significant reduction in the absolute risk of complications provided by the main efficacy criterion (mortality from cardiovascular diseases, incidence of nosophalic myocardial infarction and / or cardiac arrest followed by successful resuscitation) by 1 ,9%. In patients who had previous myocardial infarction or after coronary revascularization, the absolute risk reduction was 2.2% compared with the placebo group.

Cerebrovascular diseases

When perindopril is used both in monotherapy and in combination with indapamide, simultaneously with standard therapy of stroke and / or arterial hypertension or other pathological conditions, in patients with a history of cerebrovascular disease (stroke or transient ischemic attack) over the last five years, significantly the risk of recurrent stroke (both ischemic and hemorrhagic nature) decreases. Additionally, the risk of developing lethal or disabling strokes is reduced; major cardiovascular complications,including myocardial infarction, including fatal outcome; dementia associated with stroke; serious deterioration of cognitive functions. These therapeutic advantages are observed both in patients with arterial hypertension and with "normal" BP, regardless of age, sex, the presence or absence of diabetes mellitus and the type of stroke.

Pharmacokinetics:

Suction

After oral administration perindopril quickly absorbed in the gastrointestinal tract and reaches a maximum concentration (C_max) in the blood plasma for 1 hour. The period of subtidal (T1 / 2) perindopril from the blood plasma is 1 hour.

Perindopril does not have pharmacological activity. Approximately 27% of the total absorbed perindoprnal enters the bloodstream as an active metabolite, perindoprilat. In addition to perindoprilata, another 5 metabolites that do not have pharmacological activity. FROM_max Perindoprilata is achieved in 3-4 hours.

Admission of the drug during meals is accompanied by a decrease in the conversion of perindopril to perindoprilat, respectively, the bioavailability of the drug decreases.

Distribution

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

Excretion

The half-life (T1 / 2) of perindopril from plasma is 1 hour. Perindoprilat is excreted by the kidneys. T1/2 perindoprilata (unbound fraction) is about 3-5 hours, "effective" T1 / 2 is approximately 17 hours, the equilibrium state in the blood plasma is reached within 4 days. Pharmacopeques in special groups of patients

Patients elderly increase, in patients with chronic renal disease and heart adequacy the excretion of perindoprilate is slowed down.

Perindoyrilat is removed during hemodialysis (rate 70 ml / min, 1.17 ml / sec) and peritoneal dialysis.

Patients with hepatic impairment

In patients with cirrhosis, the liver clearance of perindopril is reduced by a factor of 2, while the total amount of perindoprilat formed does not change and correction of the dosing regimen is not required (see the sections "Dosing and Administration" and "Special instructions").

Patients with impaired renal function

In patients with renal insufficiency, the dose is selected taking into account the degree of impaired renal function (creatinine clearance (CK)).

The dialytic clearance of perindopril is 70 ml / min.

Indications:

arterial hypertension (in monotherapy and as part of combination therapy); chronic heart failure;

stable coronary heart disease: reduced risk of developing cardiovascular complications in patients who had had previous myocardial infarction and / or after coronary revascularization;

prevention of recurrent stroke (in the complex therapy with indapamide) in patients with a history of cerebrovascular disease (stroke or transient cerebral ischemic attack).

Contraindications:

increased sensitivity to perindopril or excipients included in the preparation, as well as other ACE inhibitors; angioedema in history, associated with the administration of ACE inhibitors; hereditary or idiopathic angioedema; pregnancy; the period of breastfeeding;

age under 18 years (effectiveness and safety not established); severe renal dysfunction (CK less than 30 ml / min);

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

simultaneous use with aliskiren and aniserene-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate <60 ml / min / 1.73 m2).

Carefully:

aortic stenosis / mitral stenosis / gipsertrophic obstructive cardiomyopathy;

angina pectoris;

atherosclerosis;

cerebrovascular diseases (the risk of excessive reduction of blood pressure and the development of concomitant ischemia);

chronic heart failure in the stage of decompensation;

systemic connective tissue diseases (systemic lupus erythematosus,

scleroderma and others);

simultaneous use of immunosuppressants, allopurinol, procainamide (risk development of neutropenia, agranulocytosis);

Renovascular hypertension;

bilateral stenosis of the renal arteries;

stenosis of the artery of a single functioning night;

state after kidney transplantation (in the absence of clinical data); hemodialysis using high-density membranes;

chronic renal failure (especially accompanied by

gynecology);

hyperkalemia;

reception of potassium-sparing diuretics, potassium preparations, potassium-containing

substitutes for edible salt and lithium, diet with sodium restriction;

reduced volume of circulating blood (BCC) (diuretics, salt-free diet,

vomiting, diarrhea);

diabetes;

elderly age;

surgical intervention (general anesthesia);

desensitizing therapy;

apheresis of low-density lipoproteins (LMPA);

congenital deficiency of glucose-6-phosphate dehydrogenase (single cases of development hemolytic anemia);

the use of Negroid race in patients.

Pregnancy and lactation:

Pregnancy

During pregnancy, the drug Perindopril it is contraindicated. ACE inhibitors are able to penetrate the placenta and lead to an increase in the incidence and mortality of the fetus and newborn. The effect of ACE inhibitors on the fetus in the II and III trimesters of pregnancy can lead to fetal development of arterial hypotension, renal insufficiency, deformities of the bones of the skull and face, and even fatal. There are reports of the development of the mother oligohydramnion (a pronounced decrease in the volume of amniotic fluid), which is due to impaired renal function in the fetus.Olngogidramnion may be accompanied by the appearance of contractures of the upper and lower extremities, deformities of the bones of the skull and face, gynoplastic development of the lungs and retardation of intrauterine development. In case of pregnancy during treatment with the drug Perindopril should immediately stop therapy and, if necessary, prescribe an alternative treatment. If drug therapy Perindopril was performed in the II and / or III trimesters of pregnancy, it is necessary to perform ultrasound examination of the skull and the function of the kidneys of the fetus.

In newborns exposed to an ACE inhibitor in utero, a thorough examination should be performed to exclude arterial hypotension, oliguria and hyperkalemia.

Breastfeeding period

Currently, there are no data on the release of perindopril in breast milk. Women receiving the drug should be advised to stop feeding the pile.

Fertility

In pre-clinical studies, the absence of perindopril has been shown to affect the reproductive function of rats of both sexes.

Dosing and Administration:

The drug is administered orally 1 time per day, preferably in the morning, before meals.

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. To ensure the dosing regimen in a dose of 2 mg, it is recommended to use perindopril preparations with a different dosage: tablets of 2 mg or 1/2 tablets of 4 mg with a risk.

Arterial hypertension

Perindopril can be used both in monotherapy and in combination therapy.

The recommended initial dose is 4 mg once a day.

In patients with a pronounced activation of the renin-angiotensin-aldosterone system AAS) (especially with renovascular hypertension, hypovolemia and / or a decrease in the content of plasma electrolytes, decompensation of heart failure or severe hypertension), a marked decrease in blood pressure may occur after the first dose. At the beginning of therapy, such patients should be kept in a fashion by careful medical supervision. The recommended initial dose is d; I have such patients 2 mg once a day.If the therapy is ineffective, the dose of the month can be increased to 8 mg once a day, with good tolerability of the previous dose.

At the beginning of drug therapy Perindopril symptomatic arterial hypotension may occur. In patients taking diuretics at the same time, 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 the drug Perindopril in such patients.

It is recommended, if possible, to stop taking diuretics 2-3 days before the expected start of therapy with the drug Perindopril. If it is not possible to cancel diuretics, the initial dose of the drug Perindopril should be 2 mg. It is necessary to monitor the kidney function and the content of potassium in the blood plasma. In the following, if necessary, the dose of the drug can be increased. If necessary, the reception of diuretics can be resumed.

CHF

The recommended initial dose of the drug Perindopril is 2 mg once a day. Patients should be under medical supervision in the treatment.Cg, as a rule, the drug is used in combination with non-potassium-sparing diuretics, run-adrenoblockers and / or digoxin. In the future, depending on the tolerability and therapeutic response, 2 weeks after the start of therapy, the dose of the drug Perindopril can be increased to 4 mg once a day.

IHD: reduced risk of cardiovascular events in patients who had had previous myocardial infarction and / or after coronary revascularization patients with stable course of IHD therapy with the drug Perindopril should be started with a dose of 4 mg once a day for 2 weeks. Then the daily dose can be increased to 8 mg once a day.

Elderly patients should begin therapy with a dose of 2 mg once daily for 1 weeks, then 4 mg once a day for the next week. Then, taking into account the state of the function of the nights, the dose should be increased to 8 mg once a day. Increase the dose of drugs can be only if it is well tolerated in the previously recommended dose. Prevention of recurrent stroke (as part of complex therapy with indapamide) in patients with cerebrovascular diseases in history (stroke or transient cerebral ischemic attack)

In patients with cerebrovascular disease in history, perindopril therapy should be started at a dose of 2 mg once daily for the first two weeks, then increasing the dose to 4 mg for the next two weeks before using indapamide. Therapy should be started at any time (from two weeks to several years after a stroke or transient cerebrovascular accident.

Elderly age

In elderly patients, treatment should be started at a dose of 2 mg per day and further, if necessary, 1 month after the start of therapy, the dose can be reduced to 4 mg per day, and then to a maximum dose of 8 mg per day, taking into account the state of kidney function . The maximum daily dose is 8 mg.

Patients with impaired renal function

In patients with renal insufficiency, the dose of the drug should be selected with regard to QC, and the daily dose should not exceed 8 mg. With CC> 60 ml / min, the recommended dose of perindoprml is 4 mg once a day; with KK 30-59 ml / min - 2 mg once a day; with SC 15-29 ml / min - 2 mg every other day; patients on hemodialysis (QC less than 15 ml / min) - 2 mg per day of dialysis. Dialyz clearance of perindolil - 70 ml / min, the drug should be taken after a dialysis session.

Patients with hepatic impairment

In patients with impaired liver function, dose adjustment perindopril is not required (see the section "Pharmacokinetics").

Age under 18 years old

Perindopril should not be used in children and adolescents under 18 due to lack of data on the efficacy and safety of perindopril in this age group.

Side effects:

Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO): very often> 1/10; often from> 1/100 to <1/10; infrequently from> 1/1000 to <1/100; rarely from> 1/10000 to <1/1000; ochenrarely <1/10000, including individual messages; frequentlyIt is not known - according to the available data, it is not possible to establish the frequency of occurrence.

From the nervous system.

Often - Headache, increased fatigue, dizziness, paresthesia, vertigo, decreased appetite, convulsions;

Rarely - lability of mood, insomnia, drowsiness *, fainting *; very rarely confusion.

From the sense organs: often - noise in the ears, impaired vision.

From the cardiovascular system: hourthen - excessive reduction of blood pressure and associated symptoms of vasodilation; infrequently - vasculitis *, tachycardia, palpitation; very rarely - arrhythmia, angina pectoris, myocardial infarction, stroke (possibly a secondary mechanism of development as a result of a sharp decrease in blood pressure).

From the respiratory system.

often - a "dry" cough, difficulty breathing; infrequently bronchospasm; very rarely - eosinophilic pneumonia, rhinitis.

From the digestive system: often - nausea, vomiting, abdominal pain, taste disorder, diarrhea or constipation, dyspepsia; infrequently - intestinal angioedema; rarely dryness of the oral mucosa; very rarely - pancreatitis, cholestatic jaundice, cytolygic or cholestatic hepatitis.

Allergic reactions: Often - skin rashes, itching; infrequently - hives, angioedema, swelling of the face, extremities, lips, mucous membranes, tongue, epiglottis and / or larynx, photosensitivity, pemphigus; very rarely - multiforme exudative erythema.

From the urinary system:

infrequently - decreased kidney function; very rarely acute renal failure.

From the musculoskeletal system: often - muscle spasms; infrequently - arthralgia, myalgia.

From the hematopoiesis: infrequently - eosionophilia *; very rarely - a decrease in hemoglobin and hematocrit, thrombocytopenia, leukopsy / neutropenia, agranulocytosis, pancytopenia, hemolytic anemia (against a background of glucose-6-phosphate dehydrogenase deficiency).

Laboratory indicators: often - proteinuria; infrequently - hypoglycemia, hyperkalemia, reversible after drug discontinuation, hyponatremia, increased urea and creatinine concentrations in blood plasma; retsko - increased activity of "hepatic" transaminases, hyperbilirubinemia.

Other: often - asthenia; infrequently - erectile dysfunction, chest pain *, peripheral edema *, weakness *, fever *, falls *; sharply increased sweating.

* An estimate of the incidence of adverse reactions identified by spontaneous reports was made on the basis of clinical trial results.

Overdose:

Simpts

Great depression of blood pressure, shock, stupor, bradycardia, water-electrolyte tower disturbances (hyperkalemia, hyponatremia), renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, agitation, cough.

Treatment

Gastric lavage and / or reception of activated charcoal, followed by restoration of the water-electrolyte balance, replenishment of reduced BCC. With a pronounced decrease in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs. If necessary, the BCC should be filled with intravenous 0.9% sodium chloride solution. Effective hemodialysis (not use high permeability polyacrylonitrile membranes). Intravenous administration of catecholamines may be required. With the development of bradycardia requires the introduction of atropine, it may be necessary to install an artificial pacemaker. It is necessary to constantly monitor the indicators of vital functions and indicators of water-electrolyte balance of blood.

Interaction:

Medicines that cause hyperkalemia

Some drugs or preparations of other pharmacological classes may increase the risk of developing hyperkalemia: aliskirsen and alpskirenosoderzhashchie drugs, potassium salts, potassium-sparing diuretics, AG1F inhibitors, angiotensin II receptor antagonists (ARA II), nonsteroidal anti-inflammatory drugs (NSAIDs), heparin, immunosuppressants (such as ciclosporin or tacrolimus), there is an example.The combination of these drugs increases the risk of hyperkalemia. Simultaneous use is contraindicated (see section "Contraindications")

Aliskiren

In patients with diabetes or impaired renal function (glomerular filtration rate 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").

ARA II

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, fainting, hyperkalemia, and worsening of ps (including acute renal function insufficiency) compared with the use of only one drug that affects RAAS. Double blockade of RAAS (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 enerenone), potassium salts

Simultaneous application can lead to hyperkalemia (with a possible lethal course), especially if the kidney function is impaired (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 indicated, they should be used, observing precautions and regularly monitoring the potassium content in the blood plasma.

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

Preparing lithium

With the simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in the concentration of lithium in the blood plasma can be noted and the associated toxic effects. Simultaneous use of perindopril and lithium preparations is not recommended. If this therapy is necessary, a regular monitoring of the concentration of lithium in the blood plasma should be carried out.

Aliskiren

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

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

The use of AIIF inhibitors can enhance the hypoglycemic effect of insulin and poiglycemic agents for oral administration until the development of hypoglycemia. As a rule, this is observed in the first weeks of simultaneous therapy and 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, reduce the dose of antihypertensive drugs.

Non-Safer Diuretics

With arterial hypertension, diuretics should be either withdrawn before initiating the use of an ACE inhibitor in patients receiving diuretics, especially those taking out fluid and / or salts (with a non-potent diuretic later being reassigned)or an ACE inhibitor should be prescribed in a low dose with a further gradual increase.

When using diuretics in the case of CHF, an ACE inhibitor should be prescribed in ndose, possibly after a reduction in the dose of the simultaneous, kocaly-effective 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 per day to 50 mg per day and low doses of ACE inhibitors: when treating heart failure II-IV functional class by classification NYHA with a fraction of left ventricular ejection of less than 40% and previously used ACE inhibitors and loop diuretics, there is a risk of hyperkalemia (with a possible fatal outcome), in case of non-compliance with recommendations for this combination of drugs. Before using this combination of drugs, it is necessary to make sure that 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 grams per day) Simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has an anti-inflammatory effect, COX-2 inhibitors and nonselective NSAIDs) can lead to a decrease in the antihypertensive effect of ACE-GIFT. Simultaneous use of ACE inhibitors and NSAIDs can lead to impaired renal function, including the development of acute renal sufficiency, and an increase in potassium in the blood plasma, especially in patients with reduced renal function. Care should be taken when prescribing this combination, especially in elderly patients. Patients should receive an adequate amount of fluid, and it is recommended that the kidney function be carefully monitored, 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 antihypertensive action.

Sympathomimetics

May attenuate the antihypertensive effect of ACE inhibitors).

Preparations of gold

When using inhibitors of PSA, including perindopril, receiving intravenously a gold preparation (sodium aurotomy malate), was described simtotmocomplex, which includes thermal hypotension.

Special instructions:

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

With the development of unstable angina during the first month of therapy with the drug perindopril should evaluate the benefits and risks 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 with diuretic therapy, with strict salt-free diet, hemodialysis, diarrhea and vomiting, as well as in patients with severe hypertension with high renin activity. In patients with an increased incidence of symptomatic arterial hypotension, blood pressure, renal function, and potassium levels in the blood plasma should be carefully contoured during pediatric therapy Perindopril.

This approach is also used in patients with IHD and cerebrovascular disease, 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, BCC should be filled with intravenous 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle for further administration of the drug.After the recovery of bcc and blood pressure treatment can be continued, some patients with CHF and normal or low blood pressure medication Perindopril may cause an additional decrease 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

A drug Perindopril, like other ACE inhibitors, should be administered with caution to patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), and also to patients with mitral stenosis.

Impaired renal function

Patients with renal insufficiency (KC less than 60 ml / min) the initial dose of the drug Perindopril are selected depending on the value of the CC (see the section "Method of rhyme and dosage") and then depending on the therapeutic effect. For such patients, regular monitoring of QC and potassium in blood plasma is necessary. Arterial hypotension, which sometimes develops early in the administration of ACE inhibitors in patients with symptomatic CHF,can lead to impaired renal function, the possibility of developing acute renal failure, as a rule, reversible.

In patients with bilateral stenosis of the renal artery or stenosis of the artery of a single kidney (especially in the presence of kidney failure) against the background of therapy with PSA inhibitors, an increase in the concentration of urea and creatinine in the blood plasma, which usually occurs when the therapy is withdrawn. 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. It is necessary to temporarily stop diuretic treatment and to conduct regular monitoring of the content of KG 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, the concentration of urea and creatinine in the blood plasma can increase, 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 the drug Perindopril and / or diuretic.

Demodialysis

In patients on hemodialysis using high-permeability membranes (for example, AN69^®), cases of development of anaphylactic reactions against the background of therapy with ACE inhibitors were noted. The use of ACE inhibitors should be avoided when using this type of membrane.

Trancerenal plantation

Data on the use of the drug Perindopril in patients after kidney transplantation there are no kidneys.

Increased susceptibility / angioedema

When taking ACE inhibitors, including perindopril, in rare cases and in any period of therapy, development of angioedema of the upper and lower extremities, face, lips, mucous membranes, tongue, vocal folds and / or larynx can be observed (see "Side act"). If symptoms appear, taking the drug should be stopped immediately, and the patient should be monitored until signs of edema disappear completely. If the swelling affects only the face and g.then its manifestations usually pass independently, although antihistamines can be used to treat the symptoms.

Angioneurotic edema, laryngeal edema accompanied may lead to legal outcome. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. When these symptoms occur, emergency therapy is required, including subcutaneous injection of e.g. efspsin (adrenaline) and / or airway patency. The patient should be under medical supervision until the symptoms disappear completely and persistently.

Patients with a history of angioneurotic edema, non-reception of the ACE inhibitors, the risk of its development when receiving the drugs in this group (see. The section "Contra ') can be raised,

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

Anaphylactoid reactions during apheresis of LDL

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during an LDL-apheresis procedure using dextran sulfate. 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 temporarily lifting the ACE inhibitor before the desensitization procedure begins.

Dysfunction of the liver

In rare cases, with the administration of ACE inhibitors, there was a syndrome of cholestagic jaundice development with the transition to fulminant liver necrosis, sometimes with a lethal outcome. The mechanism of development of this syndrome is unclear. When jaundice occurs, or a significant increase in the activity of "liver" enzymes against the background of taking ACE inhibitors should stop taking the drug, the patient should be under appropriate medical supervision. Neutropenia / agranulocytosis / thrombocytopenia / anemia

Against the background of taking ACE inhibitors may occur neutropenia, agranulocytosis, thrombocytopenia and anemia. In patients with normal renal function and in the absence of other aggravating factors, neutropenia develops rarely. With extreme caution, use the drug Peripodopril in patients with systemic connective tissue diseases, when taking immunosuppressants, allopuripol, or procainamide, especially in patients with impaired renal function.

Infectious diseases

Some patients developed severe infections, in some cases resistant to intense antibiotic treatment. When prescribing the drug Peripodopril, it is recommended that such patients periodically check the white blood cell count. Patients should inform the doctor about any signs of infectious diseases (i For example, 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, peripedopril is less effective in reducing blood pressure in patients of the Negroid race. This effect, perhaps, is associated with a marked predominance of low-grade status in patients of the Negroid race with arterial hypertension.

Cough

Against the background of therapy with an ACE inhibitor, a persistent "dry" cough may occur, which stops after the drug is discontinued. This should be taken into account when conducting dififferential diagnosis of cough.

Surgical intervention / 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.Taking the drug Peripodopril should be discontinued one day before surgery. With the development of arterial hypotension byhold BP by replenishment BCC. It is necessary to warn The surgeon / anesthesiologist that the patient is taking ACE inhibitors.

Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia are renal failure, decreased kidney function, age over 70 years, diabetes mellitus, some concomitant state (dehydration, acute heart failure, metabolic acidosis), simultaneous administration of potassium-sparing diuretics (such as spironolactone and its derivative eplerenone, triamterene, amiloride), food additives / potassium potassium or potassium-containing substitutes for edible salt, as well as the use of other drugs that increase the content of potassium in the blood Mr.for example, heparin). The use of dietary supplements / potassium preparations, potassium-sparing diuretics, potassium-containing substitutes for edible salt can lead to a significant increase in potassium in the blood, especially in patients with reduced renal function.Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If simultaneous reception of a preparation is necessary Perindopril and the above drugs, treatment should be conducted with caution in the context of regular monitoring of potassium content in blood plasma (see section "Interaction with other drugs").

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 the concentration of glucose in the blood (see section "Interaction with other drugs").

Lithium preparations

Simultaneous use of the drug Perindopril 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

Not riversSimultaneous administration of the drug Perindopril and potassium-sparing diuretics, as well as preparations of potassium, potassium-containing substitutes for salt and food additives.

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 medicines, which affect RAAS. Therefore, a double blockade of RAAS due to a combination of an ACE inhibitor with ARA II or aliskiren is not recommended.

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

During the treatment period, care must be taken when driving a car and engaging in potentially dangerous activities requiring concentration of attention and speed of psychomotor reactions, especially at the beginning of treatment, due to the danger of developing arterial hypotension and dizziness.

Form release / dosage:

Tablets 4 mg.

10, 15 or 30 tablets in a planar cell packaging made of a polyvinylchloride film and aluminum foil.

10 or 30 tablets in a can of high-density polyethylene.

1 or 3 contour packs of 10 tablets, 2 contiguous packs of I about 15 tablets, 1 circuit pack of 30 tablets, or one bank along with instructions for medical use in a pack of cardboard.

For hospitals: 8 outline cell packs of 30 tablets together with instructions for medical use in a pack of cardboard.

Packaging:10) - polyethylene cans (1) - packs cardboard
(10) - packings, cellular, outline (1) - packs, cardboard
(10) - packings, cellular, outline (3) - packs, cardboard
(15) - packings, cellular, outline (2) - packs, cardboard
(30) - polyethylene cans (1) - packs of cardboard
(30) - packings cellular planimetric (1) - packs cardboard
(30) - packings cellular planimetric (8) - packs cardboard

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use but expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002246/09

Date of registration:23.03.2009

The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia

Manufacturer: & nbsp

VERTEKS, AO Russia

Information update date: & nbsp29.08.2015

Illustrated instructions

Instructions

Perindopril (Perindopril)