Perindopril-SZ - instructions for use, doses, side effects, contraindications

Perindopril is an inhibitor of the angiotensin-converting enzyme (ACE). Angiotensin converting the enzyme is an exopeptidase, which ensures the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, as well as the destruction of bradykinin, which has vasodilator action, to the inactive heptapeptide.

Suppression of ACE leads to a decrease in angiotensin content II in blood plasma, which increases the activity of renin in the blood plasma and decreases the secretion of aldosterone.

Because the ACE inactivates bradykinin, suppression of ACE is accompanied by an increase in the activity of both the circulating, hack and tissue kallikrein-kinin system, while 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, as well as the mechanism of development of some side effects of these drugs (eg, cough).

Perindopril has a therapeutic effect due to the active metabolite, perindoprilat. Other metabolites have no inhibitory effect on ACE in vitro.

Arterial hypertension

Periidopril is effective for the treatment of arterial hypertension (AH) of any severity. Against the background of its use, there is a decrease in both systolic and diastolic arterial pressure (BP) in the "lying" and "standing" positions.

Peridopril reduces overall peripheral vascular resistance, which leads to a decrease in elevated blood pressure and an improvement in peripheral blood flow without changing the heart rate (heart rate).

As a rule, the use of perindopril leads to an increase in renal blood flow, but the rate of glomerular filtration does not change. The antihypertensive effect of the drug reaches a maximum at 4-6 h after single ingestion and lasts 24 hours.

Antihypertensive effect at the end of the day after a single dose of the drug is about 87 - 100 % maximum anti-hypertein effect.

Decrease in blood pressure is achieved quickly enough. In patients with a positive response to treatment, BP normalization occurs within a month, with no "addictive" effect observed.

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. The concomitant use of thiazide diuretics increases the severity of antihypertensive action.Combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of developing hypokalemia with diuretics.

Heart failure

Perindopril normalizes the work of the heart, reducing preload and postload.

In patients with chronic heart failure, taking perindopril, It revealed:

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

- decrease in total peripheral resistance of blood vessels,

- increased cardiac output and an increase in cardiac index. It was shown that a decrease in blood pressure after the first administration of the drug perindopril in patients with chronic heart failure (CHF) I-II functional class by classification NYIIA was statistically significantly different from the change in blood pressure in the placebo group.

Ischemic heart disease (CHD)

When taking perindopril at a dose of 8 mg / day, 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 followed by successful resuscitation);Similarly, absolute risk reduction is noted in patients who have had previous myocardial infarction or coronary revascularization.

Pharmacokinetics:

Ingestion perindopril quickly absorbed in the gastrointestinal tract. The maximum concentration (C_max) in the blood plasma is achieved after 1 hour. Bioavailability is 65 - 70%.

Approximately 20% of the total amount of absorbed perindopril is converted to perindoprilat, the active metabolite. In addition to perindopril, another 5 metabolites are formed that do not show pharmacological activity.

The half-life period (T1_/2) of perindopril from blood plasma is 1 hour.

The perindoprilite stan in the blood plasma is achieved 3 to 4 hours after ingestion.

Simultaneous intake of food 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.

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

Perindoprilat is excreted by the kidneys, T1_/2 free fraction is 3 - 5 hours. "Effective" T1_/2 is 25 hours, the equilibrium state is reached within 4 days.

With long-term admission perindopril Do not cumulate.

The excretion of perindoprilat is delayed in old age, as well as in patients with cardiac and renal insufficiency. In renal failure, correction of the dose of the drug is desirable in view of the degree of impaired renal function, creatinine clearance (CC).

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 (in monotherapy and as part of combination therapy);

- chronic heart failure;

- IHD: reduced risk of cardiovascular complications in patients who had previous myocardial infarction and / or coronary revascularization;

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

Contraindications:

- hypersensitivity to perindopril or excipients included in the preparation, as well as to other ACE inhibitors;

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

- hereditary / idiopathic angioedema;

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

- simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate (GFR) <60 ml / mii / 1.73 m²) (see the sections "Special instructions" and "Interaction with other medicinal products").

- age under 18 years (effectiveness and safety not established);

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

Carefully:

Bilateral stenosis of the renal artery, stenosis of the artery of a single functioning kidney; chronic renal failure, systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, etc.), simultaneous use of immunosuppressants, allopuriola,procainamide (risk of neutropenia, agranulocytosis); reduced circulating blood volume (diuretics, salt-free diet, vomiting, diarrhea), stenocardia, atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, severe chronic heart failure IV functional class by classification NYHA, intake of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for dietary salt and lithium, hyperkalemia, surgical intervention / general anesthesia, advanced age, hemodialysis using high-flow membranes (for example, AN69®), desensitizing therapy, low-density lipoprotein apheresis (LDL), post-kidney transplant state (due to lack of clinical data), aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, use of Negroid race in patients.

Pregnancy and lactation:

The drug Perindopril-SZ is contraindicated in pregnancy (see the section "Contraindications").

Perindopril-SZ should not be used in the first trimester of pregnancy. When planning a pregnancy or diagnosing it when using Perindopril-SZ,it is necessary to stop taking the drug as soon as possible and to carry out another antihypertensive therapy with a proven safety profile during pregnancy. Appropriate controlled trials of the use of ACE inhibitors in pregnant women have not been conducted. Available limited data on the effect of the drug in the first trimester of pregnancy suggest that the use of ACE inhibitors does not lead to fetal malformations associated with fetotoxicity.

It is known that the long-term effect of ACE inhibitors on the fetus II and III trimester of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, slowing ossification of the bones of the skull) and development of complications in the newborn (such as kidney failure, arterial hypotension, hyperkalemia).

If the patient received Perindopril-SZ during II or III trimester of pregnancy, it is recommended to perform an ultrasound examination to assess the condition of the bones of the skull and the function of the kidneys of the fetus.

Breastfeeding period

The use of the drug Perindopril-SZ during breastfeeding is not recommended due to the lack of data on the possibility of its penetration into breast milk.

If taking the drug is necessary during lactation, breastfeeding must be stopped.

Dosing and Administration:

Inside.

The drug Perindopril-SZ is recommended to be taken before meals, once a day, preferably in the morning. 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

Perindopril-SZ 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 (RAAS) (especially in the case of renovascular hypertension, hypovolemia and / or a decrease in the content of plasma electrolytes, cardiac decompensation insufficiency or seriousness

arterial hypertension) after receiving the first dose of the drug, a pronounced decrease in blood pressure can develop. At the beginning of therapy, such patients should be careful medical supervision.

The recommended initial dose for such patients is 2 mg 1 time per day.

If necessary, a month after the start of therapy, you can increase the dose of the drug to 8 mg once a day.

At the beginning of therapy with the drug Perindopril-SZ, symptomatic arterial hypotension may occur. In patients simultaneously
receiving diuretics, 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 Perindopril-SZ in such patients.

It is recommended, if possible, to stop taking diuretics 2-3 days before the proposed initiation of therapy with Perindopril-SZ (see section "Special instructions").

If it is not possible to cancel diuretics, the initial dose of Perindopril-SZ should be 2 mg. It is necessary to monitor the kidney function and the potassium content in the blood serum. In the subsequent if necessary, the dose of the drug can be increased. If necessary, the reception of diuretics can be resumed.

In elderly patients, treatment should begin with a dose of 2 mg per day, and then, if necessary, 1 month after the start of therapy, the dose can be increased to 4 mg per day, and then to a maximum dose of 8 mg per day, taking into account the function state kidneys (see Table 1).

Chronic heart failure

The recommended initial dose of Perindopril-SZ is 2 mg once a day. Patients should be under close medical supervision. As a rule, the drug is used in combination with potassium-sparing diuretics and / or digoxin and / or beta-blockers. Later, depending on the tolerability and therapeutic response, 2 weeks after the start of therapy, the dose of Perindopril-C3 can be increased to 4 mg once a day.

Particular caution at the beginning of therapy should be observed in patients with severe chronic heart failure IV functional class by classification NYHA, as well as in other patients from the high-risk group (renal dysfunction and the possibility of developing water-electrolyte balance disorders, concomitant diuretics and / or vasodilating agents) (see section "Special instructions").

If possible, prior to the use of Perindopril-SZ, patients from the group at high risk of developing arterial hypotension should adjust the BCC. Such indicators as AD value, kidney function and potassium content in blood plasma should be monitored both before and during therapy with Perindopril-SZ (see below).section "Special instructions"),

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, therapy with Perindopril-S3 should be started at 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 1 time per day for one week, then 4 mg once a day for the next pedal. Then, taking into account the state of the kidney function, the dose should be increased to 8 mg once a day (see Table 1). Increase the dose of the drug only if it is well tolerated in the previously recommended dose. Prevention of recurrent stroke (in combination with nndapamid) in patients who underwent a stroke or transient cerebral circulation disorder by ischemic type

In patients with cerebrovascular disease in history, therapy with Perindopril-SZ should be started at a dose of 2 mg 1 time per day for the first 2 weeks before taking indapamide.

Therapy should be started at any time (from 2 weeks to several years) after a stroke or cerebral circulation. Renal insufficiency

In patients with renal insufficiency, the dose of the drug should be selected with allowance for QC.

Table. The dose of preparation PeRindoprnl-SZ with renal failure

CK (ml / min)	Recommended dose
Greater than or equal to 60	4 mg / day
Less than 60, but more than 30	2 mg / day
Less than 30, but more than 15	2 mg every other day
Patients on hemodialysis * less than 15	2 mg per day of dialysis

* dialysal clearance perindoprilata - 70 ml / min. The drug should be taken after a dialysis session.

Liver failure

When using Perindopril-SZ in patients with impaired liver function, dose adjustment is not required (see the sections "Pharmacokinetics" and "Special instructions").

Age under 18 years old

Perindopril-SZ should not be used in children and adolescents under 18 years due to lack of data on efficacy and safety in patients of this age group.

Side effects:

The frequency of adverse reactions that may occur during perindopril therapy is given in 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), including individual messages (classification World Health Organization).

From the nervous system

Often: paresthesia, headache, dizziness, vergigo.

Infrequently: sleep disorders, mood lability, drowsiness, fainting. Rarely: confusion.

From the side of the organ of vision Often: impaired vision.

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

From the side of the cardiovascular system

Often: excessive reduction in blood pressure, including orthostatic hypotension. Infrequently: vasculitis, tachycardia, palpitation.

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

On the part of the respiratory system Often: cough, shortness of breath.

Infrequently: bronchospasm, pain in the chest.

Rarely: eosinophilic pneumonia, rhinitis.

From the digestive system

Often: nausea, vomiting, abdominal pain, taste disorder, indigestion, diarrhea, constipation.

Infrequently: dryness of the oral mucosa.

Rarely: pancreatitis, hepatitis (cholestatic or cytological), angioedema of the intestine (see section "Special instructions").

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

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

Rarely: erythema multiforme.

From the musculoskeletal system and connective tissue

Often: muscle spasms.

Infrequently: arthralgia, myalgia.

From the urinary system Infrequently: impaired renal function.

Rarely: acute renal failure.

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

General disorders and symptoms

Often: asthenia.

Infrequently: increased sweating, peripheral edema, weakness, fever, falls.

From the side of the blood and lymphatic system

Infrequently: hypoglycaemia, hyperkalemia, reversible after discontinuation of the drug, hyponatremia, eosinophilia.

Rarely: reduction of hemoglobin and hematocrit, thrombocytopenia, leukopenia / neutropenia, pancytopenia, agranulocytosis.

In patients with congenital deficiency of glucose-6-phosphate dehydrogenase, hemolytic anemia occurs in very rare cases (see section "Special instructions").

Laboratory indicators

Infrequently: increase in urea and creatinine in the blood plasma, reversible after discontinuation of the drug, more often in patients with renal insufficiency, severe chronic heart failure and renovascular hypertension.

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

Overdose:

Symptoms: marked decrease in blood pressure, shock, water disturbances

electrolyte balance, kidney failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety and 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 reduction in blood pressure, the patient should be transferred to the "lying" position on the back with raised legs and immediately replenished with BCC, a 0.9% solution of sodium chloride should be administered intravenously. Perindoprilat, an active metabolite of perindopril, can be removed from the body by dialysis. When developing a bradycardia-resistant therapy, it may be necessary to set up an artificial pacemaker.The basic vital functions of the body, the content of electrolytes of blood serum and QA should be under constant control.

Interaction:

Medicines that cause gynercalemia

Some medicines or preparations of other pharmacologistsClasses can increase the risk of hyperkalemia: aliskiren and aliskiren containing preparations, potassium salts, potassium-sparing diuretics, AG1F inhibitors, 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 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,may increase the risk of hyperkalemia, worsening kidney function and increasing the incidence of cardiovascular morbidity and mortality. Double blockade of RALS

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 arterial hypotension, syncope, hyperkalemia and impaired renal function (including acute renal failure) compared with using 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.

Diuretics

In patients receiving diuretics, especially with excessive excretion of fluid and / or electrolytes, 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,replenishment of fluid loss (intravenous infusion of 0.9% sodium chloride solution), and also applying perindopril in lower doses.

Potassium-sparing diuretics, potassium preparations and potassium-containing foods and nutritional supplements

On the background of perindopril therapy, the serum potassium content, as the rule remains within normal limits, but some patients may develop hyperkalemia. The combined use of ACE inhibitors and potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride, eplerenone (a derivative of spironolactone)), preparations of potassium and potassium-containing products and food additives can lead to a significant increase in the potassium content in the blood serum. Therefore, the combined use of perindopril and the above drugs is not recommended (see section "Special instructions"). Apply these combinations only in the case of hypokalemia, observing the precautionary measures, and to conduct regular monitoring of the potassium content in the serum. Spironolactone and eplerenone in doses of 12.5 mg to 50 mg / day for CHF and low doses of ACE inhibitors: in the treatment of CHF II-IV functional class by classification NYHA with left ventricular ejection fraction less than 40; and the previously used ACE inhibitors and loop diuretics, there is a risk of hyperkalemia (possibly fatal), especially in case of non-compliance with the recommendations of the relative combination of the drugs. Before using this combination of drugs, you need to make sure that there is no hyperkalemia and renal dysfunction, it is recommended to monitor the concentration of creatinine and potassium in the blood serum: weekly in the first month of therapy and monthly thereafter.

In patients receiving diuretics that remove fluid and / or salts, at the beginning of perindoprine therapy, a marked decrease in blood pressure can be observed, the risk of which can be reduced by eliminating the diuretic, replacing fluid loss or salt before initiating perindopril therapy, and prescribing low dose perindo from further gradually increase it

Lithium preparations

The combined use of lithium drugs and ACE inhibitors can lead to a reversible increase in lithium in the blood plasma and the development of lithium intoxication.The additional use of thiazide diuretics against the background of combined use of lithium preparations and ACE inhibitors increases the already existing risk of developing lithium intoxication. Simultaneous use of perindopril and lithium preparations is not recommended. If this therapy is necessary, regular monitoring of the lithium content in serum should be carried out (see section "Special instructions"),

Non-steroidal anti-inflammatory drugs (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, inhibitors
cyclooxygenase-2 (COX-2) and nonselective NSAIDs) may lead to a decrease in the antihypertensive effect of ACE inhibitors.

It has been established that NSAIDs and ACE inhibitors have an additive effect on the increase in potassium in the blood serum, and kidney dysfunction is also possible. As a rule, these effects are reversible. In some cases, acute renal failure may develop, especially with a decrease in BCC, in elderly patients and in renal impairment.

Hypotensive and vasodilating agents

The antihypertensive effect of perindopril may be intensified when combined with other antihypertensive drugs, vasodilators, nitrates of short and prolonged action.

Gynoglycemic agents

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

Acetylsalicylic acid, thrombolytic agents, beta-blockers, nitrates

Perindopril can be used in conjunction with acetylsalicylic acid (as an antiaggregant agent), thrombolytic agents, beta-blockers and / or nitrates.

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

Co-administration with ACE inhibitors can lead to an increase in the antihypertensive effect (see section "Special instructions").

Sympathomimetics

May weaken the antihypertensive effect of ACE inhibitors.

Baclofen

Strengthens the antihypertensive effect of ACE inhibitors, requires control of blood pressure and, if necessary, correction of doses of antihypertensive drugs.

The glyptypes (lipagliptin, saxagliptin, sitagliptype, vildagliptype) Simultaneous use with ACE inhibitors may increase the risk of angioedema due to suppression of the activity of dipeptidyl peptidase IV with glyptin.

Preparations of gold

With the use of ACE inhibitors, including perindopril, patients receiving an intravenous drug of gold (sodium aurotomy malate), was
describes a 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 the drug Perindopril-SZ 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 noted against diuretic therapy, with strict salt-free diet, hemodialysis, vomiting and diarrhea, as well as in patients with severe hypertension with high renin activity (see "Interaction with other medicinal products"). In most cases, episodes of marked decrease in blood pressure are observed in patients with severe chronic heart failure, both in the presence of concomitant renal failure and in its absence. Most often, this side effect is observed in patients receiving "loop" diuretics in high doses, as well as in patients with hyponatremia or with renal dysfunction. At the beginning of therapy and with an increase in the dose of Perindopril-SZ, patients should be under careful medical supervision (see the sections "Dosage and Administration" and "Side-Effects"). This approach should be used in patients with angina and cerebrovascular diseases, in which severe arterial hypotension can lead to myocardial infarction or cerebrovascular complications.

With a significant reduction in blood pressure, the patient should be placed in the "lying" position on the back with elevated legs and immediate replacement of the BCC (for example, intravenous infusion of 0.9% sodium chloride solution). The pronounced decrease in blood pressure at the first intake of the drug is not an obstacle for the further use of the drug. After the recovery of bcc and blood pressure, treatment can be continued with careful selection of the doses of Perindopril-SZ.

In some patients with chronic heart failure and normal or low blood pressure Perindopril-SZ may cause an additional reduction in blood pressure. This effect is predictable and usually not

requires discontinuation of therapy. If symptoms of a marked decrease in blood pressure appear, reduce the dose or stop taking it. Mitral stethosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

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

Impaired renal function

For patients with renal insufficiency (KC less than 60 ml / min.), The initial dose of Perindopril-SZ is selected depending on the value of the CK (see the section "Dosing and Administration") and then depending on the therapeutic effect. For such patients, a regular control of the concentration of creatinine and the content of potassium in the blood plasma (see section "Side effect").

Arterial hypotension, which sometimes develops early in the administration of ACE inhibitors in patients with symptomatic chronic heart failure, 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 artery 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 plasma, usually taking place when the therapy is withdrawn. The additional presence of reninvascular hypertension causes an increased risk of severe arterial hypotension and kidney failure. Treatment of such patients begins under careful medical supervision with the use of low doses of the drug and further adequate selection of doses.Diuretics should be discontinued and regular monitoring of serum potassium and creatinine levels during the first few weeks of therapy.

In some patients with arterial hypertension, in the presence of previously unrecognized renal failure, especially with the simultaneous use of diuretics, the concentration of urea and creatinine in serum can increase. These changes are usually not very pronounced and are reversible. In such cases, you may need to cancel or reduce the dose of Perindopril-C3 and / or diuretic.

The probability of these disorders is higher in patients with a history of renal dysfunction.

Hemodialysis

In patients on hemodialysis using high-permeability membranes (for example, AN69®), Several cases of development of persistent, life-threatening anaphylactic reactions were noted. The use of ACE inhibitors should be avoided when using this type of membrane.

Night transplantation

Data on the use of the drug Perindopril-SZ after kidney transplantation are absent.

Increased susceptibility / angioedema

In patients taking ACE inhibitors, in rare cases, especially during the first few weeks of therapy, may develop angioedema, swelling of the face, extremities, lips, tongue, vocal folds and / or larynx. In rare cases, severe angioedema may occur with prolonged use of an ACE inhibitor. If these symptoms appear, the use of Perindopril-S3 should be stopped immediately, as a substitute, drugs of another pharmacotherapeutic group should be used.

Angioedema, accompanied by swelling of the larynx, can lead to death. Swelling of the tongue, vocal cords, or larynx can lead to airway obstruction. In its development, emergency therapy includes, in addition to other prescriptions, immediate subcutaneous injection of an epinephrine (adrenaline) 1: 1000 (1 mg / ml) solution of 0.3-0.5 ml or slow intravenous administration (according to the instructions for preparation infusion solution) under the control of ECG and blood pressure. The patient should be hospitalized for treatment and follow-up for at least 12-24 hours and until the symptoms regress completely.

Patients with a history of observed angioedema not associated with 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. 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 enzyme activity C-1 esterase. The diagnosis is established using computed tomography of the abdominal region, ultrasound or at the time of surgery. Symptoms disappear after stopping the intake of ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, in the differential diagnosis should be considered the possibility of angioedema edema development of the intestine.

Anaphylactic reactions in the apheresis of low-density lipoproteins (LDL)

In rare cases in patients receiving ACE inhibitors, during the procedure of apheresis of low density lipoproteins with the help of dextran sulfate may develop life-threatening anaphylactic reactions. To prevent an anaphylactic reaction, therapy with an ACE inhibitor should be temporarily discontinued before each procedure for LDL apheresis using dextran sulfate. Anaphylactic reactions during desensitization There are some reports of the development of life-threatening anaphylactic reactions in patients receiving ACE inhibitors during desensitizing therapy with bee venom (bees, wasps). ACE inhibitors should be used with caution in patients with a predisposition to allergic reactions undergoing desensitization procedures. The use of ACE inhibitors in patients receiving immunotherapy with bee venom should be avoided. However, this reaction can be avoided by the temporary withdrawal of the ACE inhibitor before the desensitization procedure begins.

Impaired liver function

Acceptance of ACE inhibitors is sometimes associated with a syndrome that begins with the development of cholestatic jaundice, progressing to fulminant liver necrosis, and (sometimes) fatal. The mechanism of development of this syndrome is unclear.If symptoms of jaundice appear or the activity of liver enzymes increases in patients taking ACE inhibitors, drug therapy should be discontinued and an appropriate examination performed (see "Side effect" section). Neutropenia / agranulocytosis / thrombocytopenia / anemia Against the background of therapy with ACE inhibitors, neutropenia / agranulocytosis, thrombocytopenia and anemia can develop. With normal kidney function and no other complications, neutropenia occurs rarely. ACE inhibitors are used only in emergency cases in the presence of systemic vasculitis, immunosuppressive therapy, reception of allopurinol or procainamide, as well as when combining all these factors, especially against the background of previous renal failure. There is a risk of developing severe infectious diseases resistant to intensive antibiotic therapy. When carrying out therapy with Perindopril-SZ in patients with the above factors, it is necessary to regularly monitor the content of leukocytes.

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, Perindopril-C3 is less effective in reducing blood pressure in patients of the Negroid race.

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

Cough

Against the background of therapy with an ACE inhibitor, a dry, nonproductive cough may occur, which ceases after the drug has been discontinued, this should be taken into account in the differential diagnosis of cough.

Surgery / general anesthesia

The use of ACE inhibitors in patients undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetic agents that have an antihypertensive effect. The drug Perindopril-SZ should be stopped one day before surgery. With the development of arterial hypotension, blood pressure should be maintained by replenishing the BCC.

It is necessary to warn the anesthesia doctor that the patient is taking ACE inhibitors.

Hyperkalemia

Hyperkalemia can develop during treatment with ACE inhibitors, especially if the patient has renal and / or heart failure, latent diabetes.It is usually not recommended to use potassium preparations, potassium-sparing diuretics and other drugs associated with the risk of increasing the potassium content (eg, heparin), because of the possibility of pronounced hyperkalemia. If joint intake of these drugs is necessary, then therapy should be accompanied by regular monitoring of potassium in the blood serum.

Diabetes

In patients taking hypoglycemic drugs for ingestion or insulin, during the first month of therapy with ACE inhibitors should regularly monitor the concentration of glucose in the blood plasma (see section "Interaction with other drugs"). The drug is used

Joint use of the drug Perindopril-SZ and lithium preparations is not recommended (see the section "Interaction with other medicinal products").

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

It is not recommended joint use with ACE inhibitors (see section "Interaction with other drugs").

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, a double blockade of RAAS due to a combination of an ACE inhibitor with ARA II 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 m 2) (see the sections "Contraindications" and "Interaction with other medicinal products").

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

Perindopril-SZ should be used with caution in patients who manage motor vehicles and engage in activities that require increased concentration of attention and quick response, due to the danger of developing arterial hypotension and dizziness.

Form release / dosage:

Tablets of 2 mg and 4 mg.

For 10 or 30 tablets in a planar cell package.

For 30 tablets in a plastic can or in a polymer bottle.

Each bank, vial, 3, 5 contour cell packs of 10 tablets or 1.2 outline packs of 30 tablets together with instructions for use in a cardboard bundle.

Tablets of 8 mg.

For 10 or 30 tablets in a planar cell package.

For 30 tablets in a plastic can or in a polymer bottle.

Each bank, vial, 3, 6, 9 contour cell packs of 10 tablets or 1, 2, 3 contourcell packs of 30 tablets together with instructions for use in a cardboard bundle.

Packaging:(10) - packings, cellular, outline (3) - packs, cardboard
(10) - packings, cell planimetric (6) - packs cardboard
(10) - packings, cellular planimetric (9) - packs cardboard
(30) - polymer cans (1) - packs of cardboard
(30) - packings cellular planimetric (1) - packs cardboard
(30) - packings cellular planimetric (2) - packs cardboard
(30) - packings, cellular planimetric (3) - packs cardboard
(30) - polymer bottles (1) - packs cardboard

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003060

Date of registration:25.06.2015

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Information update date: & nbsp28.08.2015

Illustrated instructions

Instructions

Perindopril-SZ (Perindopril-SZ)