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

Component name		Amount, mg
Active substance:
Perindopril erbumine	2,0	4,0	8,0
Excipients:
Lactose Monohydrate	88,94	120,45	240,9
Microcrystalline cellulose	18,56	20,0	40,0
Corn starch	9,3	13,95	27,9
Magnesium stearate	1,2	1,6	3,2

Description:

Tablets are white or almost white in color. Light marble is allowed.

Tablets 2 mg - round, biconcave, without risks.

Tablets 4 mg - round, biconcave, with a risk.

Tablets 8 mg - round, flat-cylindrical, with a risk and a facet.

Pharmacotherapeutic group:ACE inhibitor

ATX: & nbsp

C.09.A.A.04 Perindopril

Pharmacodynamics:

Perindopril is an ACE inhibitor. ACE is an exopeptidase that ensures the conversion of angiotensin I into a vasoconstrictor substance, angiotensin II, as well as the destruction of bradykinin, which has a vasodilating action, to an inactive heptapeptide. The suppression of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which increases the activity of renin in the blood plasma and 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 antihypertensive action of ACE inhibitors, as well as the mechanism of development of some side effects of these drugs (eg, cough).

Helps restore the elasticity of large arterial vessels (reducing the formation of excessive amounts of subendothelial collagen), reduces pressure in the pulmonary capillaries, with long-term administration reduces the severity of myocardial hypertrophy of the left ventricle and interstitial fibrosis, normalizes the isozyme profile of myosin; normalizes the work of the heart. Reduces preload and afterload (reduces systolic and diastolic blood pressure (BP) in the "lying" and "standing"), the filling pressure of the left and right ventricles, reduces the overall peripheral vascular resistance increases the minute volume of blood and cardiac index, does not increase the heart rate (Heart rate) (in patients with chronic heart failure (CHF) moderately reduces heart rate), increases regional blood flow in the muscles. Increases the concentration of high-density lipoproteins in patients with hyperuricemia reduces the concentration of uric acid.Increases renal blood flow, does not change the rate of glomerular filtration.

In patients with CHF causes a significant decrease in the severity of clinical signs of heart failure increases exercise tolerance (according to the bicycle ergometric test), does not significantly reduce blood pressure.

After oral administration of the median single dose, the maximum antihypertensive effect is achieved after 4-6 hours and persists for 24 hours. Stabilization of the antihypertensive effect is observed after 1 month. therapy and persists for a long time.

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

Pharmacokinetics:

Suction

Absorption is 25%, bioavailability is 65-70%. Ingestion perindopril quickly absorbed in the gastrointestinal tract. The maximum concentration in the blood (C_mOh) is achieved after 1 hour, perindoprilata - 3-4 hours. Equilibrium concentration (Css) is created on the 4th day. The half-life (T_1/2) of perindopril from the blood plasma is 1 hour. It was shown that the relationship between the dose of perindopril and its concentration in the blood plasma is linear.

Distribution

The association of perindoprilat with plasma proteins is insignificant, with an ACE of less than 30% (depends on concentration). The volume of distribution of free perindoprilata is 0.2 l / kg.

Metabolism

Perindopril does not have pharmacological activity. Approximately 27% of the total absorbed Perindopril enters the bloodstream in the form of active metabolite - perindoprilata. In addition to perindoprilata, another 5 metabolites are formed that do not have pharmacological activity. FROM_mOh Perindoprilata in blood plasma is achieved 3-4 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.

Excretion

Perindoprilat is excreted by the kidneys, the half-life of the free fraction of the metabolite is 3-5 hours. The dissociation of perindoprilat, associated with ACE, is slow. As a consequence, the "effective" T_1/2is 25 h. Re-administration of perindopril does not lead to its cumulation, and T_1/2Perindoprilata with repeated admission corresponds to the period of its activity. The state of "effective" Css is reached by the end of 4 days.

Pharmacokinetics in selected patient groups

The excretion of perindoprilat slows down in elderly patients, and in patients with CHF and chronic renal failure (CRF) (in the latter, dose adjustment should be performed depending on the creatinine clearance (CC)). The dialytic clearance of perindopril is 70 ml / min.

In patients with cirrhosis of the liver the hepatic clearance of perindopril decreases by a factor of 2, while the total amount of perindoprilat formed does not change and correction of the dosing regimen is not required.

Indications:

- Arterial hypertension (in monotherapy and as part of combination therapy);

- chronic heart failure;

- stable ischemic heart disease (IHD): reduced risk of cardiovascular complications in patients with previous myocardial infarction and / or 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:

Hypersensitivity to perindopril or other ACE inhibitors and to the excipients included in the preparation, angioedema (Quincke's edema) in history, associated with the administration of ACE inhibitors, hereditary / idiopathic angioedema, pregnancy, the period of breastfeeding, simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or renal dysfunction (glomerular filtration rate (GFR) <60 ml / min / 1.73 m² (see the sections "Special instructions" and "Interactions with other medicines"), age under 18 years (efficacy and safety not established), lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the preparation contains lactose) .

Carefully:

Cerebro- and cardiovascular diseases (including cerebral circulatory insufficiency, coronary heart disease, coronary insufficiency - the risk of excessive blood pressure lowering and concomitant ischemia), angina pectoris, chronic cardiac insufficiency IV functional class by classification NYHA, aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, renovascular hypertension.

Severe autoimmune systemic connective tissue diseases (including systemic lupus erythematosus (SLE), scleroderma), oppression of bone marrow hematopoiesis with immunosuppressant, allopurinol or procainamide - the risk of agranulocytosis and neutropenia.

Diabetes mellitus (possibly increasing the effect of hypoglycemic drugs).

Two-sided stenosis of the renal arteries, stenosis of the artery of a single kidney, condition after kidney transplantation (risk of kidney and agranulocytosis), CRF (especially accompanied by hyperkalemia), hyperkalemia, diet with restriction of table salt, conditions accompanied by a decrease in the volume of circulating blood (BCC) ( including diarrhea, vomiting), hemodialysis using high-flow membranes (for example, AN69®), desensitizing therapy, low density lipoprotein apheresis (LDL), simultaneous use of potassium-sparing diuretics, potassium preparations, potassium-containing substitutes for edible salt and lithium,surgical intervention / general anesthesia, advanced age, the use of Negroid in patients, congenital deficiency of glucose-6-phosphate dehydrogenase - single cases of hemolytic anemia.

Pregnancy and lactation:

Pregnancy

Perindopril is contraindicated in pregnancy (see "Contraindications"). At the moment, there is no conclusive epidemiological evidence of teratogenic risk when taking ACE inhibitors in the first trimester of pregnancy. However, a small increase in the risk of fetal development disorders can not be ruled out. When planning a pregnancy or when it occurs during the use of the drug Perindopril, you should immediately stop taking the drug 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 during the II and III trimester of pregnancy can lead to disruption of its development (decreased kidney function, oligohydramnion, slowing ossification of the skull bones) and development of complications in the newborn (kidney failure, arterial hypotension, hyperkalemia).If the patient received ACE inhibitors in the II and III trimesters of pregnancy, an ultrasound examination is recommended to assess the condition of the skull bones and kidney function. Newborns whose mothers received ACE inhibitors during pregnancy should be monitored because of the risk of developing arterial hypotension.

Breastfeeding period

Due to the lack of information on the use of perindopril during breastfeeding, it is not recommended.

It is preferable to use other drugs with a more studied safety profile during breastfeeding, especially when feeding newborns or premature babies.

Fertility

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

Dosing and Administration:

The dose of the drug is selected individually for each patient, depending on the severity of the disease and individual response to ongoing therapy.

Inside, preferably in the morning, before meals, the initial dose is 4 mg / day, if necessary (after 1 month) - increase to 8 mg / day. in one step.

Arterial hypertension

Perindopril can be used both in monotherapy and in combination therapy. The recommended initial dose is 4 mg / day.

In patients with a pronounced activation of the renin-angiotensin-aldosterone system (RAAS) (especially with renovascular hypertension, hypovolemia and / or a decrease in plasma electrolytes, decompensation of chronic heart failure or severe hypertension), after a first dose of the drug, . At the beginning of therapy, such patients should be under close medical supervision. The recommended initial dose for such patients is 2 mg / day.

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

At the beginning of drug therapy Perindopril 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 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 (see section "Special instructions"). If it is not possible to cancel diuretics, the initial dose of the drug should be 2 mg. It is necessary to monitor the kidney function and the potassium content in the blood serum. In the future, it is necessary to monitor the kidney function and the potassium content in the blood serum. In the future, 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 / day, and then 1 month after the start of therapy, the dose can be increased to 4 mg / day, and then to a maximum dose of 8 mg / day, taking into account the state of kidney function (see. Table 1).

Chronic heart failure

The recommended initial dose is 2 mg / day. (for 1 reception). Patients should be under close medical supervision. Typically, 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 the drug can be increased to 4 mg / 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 therapy with diuretics and / or vasodilators) (see section "Special instructions").

In patients with a high risk of developing clinically significant arterial hypotension (for example, taking high doses of diuretics), if possible, before the drug is taken Perindopril it is necessary to eliminate hypovolemia and water-electrolyte disturbances. It is recommended to carefully monitor blood pressure, the state of kidney function and the content of potassium in the blood serum before and during therapy.

Stable ischemic heart disease

In patients with stable course of ischemic heart disease, the recommended initial dose of the drug Perindopril is 4 mg per day. After 2 weeks, the dose is increased to 8 mg per day, provided that the dose is well tolerated at 4 mg per day and that the kidney function is monitored.

Treatment elderly patients should begin with a dose of 2 mg, which after a week can be increased to 4 mg per day. In the future, if necessary, after a week, you can increase the dose to 8 mg per day with mandatory pre-control of kidney function. In elderly patients, the dose of the drug can be increased only if the previous, lower dose is well tolerated.

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

In patients with cerebrovascular disease in history, drug therapy Perindopril should start with a dose of 2 mg 1 time per day for the first two 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 1. The dose of the drug Perindopril with renal insufficiency

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 hemodialysis¹ less than 15	2 mg per day of dialysis

¹The dialysed clearance of perindoprilat is 70 ml / min. The drug should be taken after a dialysis session.

Liver failure

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

Age under 18 years old

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

Side effects:

To describe the frequency of undesirable reactions, the following frequency grading was used: very often -> 10%, often -> 1% and <10%, infrequently -> 0.1% and <1%, rarely -> 0.01% and <0.1%, very rarely - <0.01%, including individual messages, the frequency is unknown - can not be calculated on the basis of available data.

The incidence of adverse reactions is given in accordance with the classification of the World Health Organization.

From the side of the cardiovascular system (SSS)

Often - excessive reduction in blood pressure and related symptoms, including orthostatic hypotension; infrequently - vasculitis, tachycardia,a feeling of palpitations; very rarely - heart rhythm disturbances, angina pectoris, myocardial infarction and stroke, possibly due to excessive blood pressure lowering in high-risk patients (see section "Special instructions").

From the musculoskeletal system and connective tissue

Often - muscle spasms; infrequently - arthralgia, myalgia.

From the urinary system

Infringement of function of kidneys infrequently; rarely - aggravation or development of renal failure.

From the side of the reproductive system

Infrequent - erectile dysfunction.

On the part of the respiratory system

Often - a "dry" cough, difficulty breathing, shortness of breath; infrequently - bronchospasm, pain in the chest; very rarely - eosinophilic pneumonia, rhinitis.

From the digestive system

Often - nausea, vomiting, abdominal pain, taste change, diarrhea or constipation, dyspepsia; infrequent - dryness of the oral mucosa; very rarely - pancreatitis, hepatitis (cholestatic or cytolytic), angioedema, intestinal edema (see section "Special instructions").

From the nervous system

Often - headache, excessive fatigue, dizziness, decreased appetite,noise in the ears, visual impairment, convulsions, paresthesia, vertigo; infrequently - lability of mood, insomnia, drowsiness, fainting; very rarely confusion.

Allergic reactions

Often - skin rashes, itching; infrequently - hives, angioedema, swelling of the face, lips, upper and lower extremities, mucous membranes, tongue, vocal cords and / or larynx, photosensitivity, pemphigus, urticaria (see section "Special instructions"); very rarely - multiforme exudative erythema.

General disorders and symptoms

Often - asthenia; infrequently - increased sweating, peripheral edema, weakness, fever, falls.

Laboratory indicators

Often - hypercreatininaemia, proteinuria, hyperkalemia; hyperuricemia; rarely (with prolonged use in high doses) - neutropenia, leukopenia, hypohemoglobinaemia, thrombocytopenia, a decrease in hematocrit; very rarely - agranulocytosis, pancytopenia, increased activity of "hepatic" transaminases, hyperbilirubinemia, hemolytic anemia (against a background of deficiency of glucose-6-phosphate dehydrogenase).

There are spontaneous reports of the following adverse reactions: infrequently - eosinophilia, hyponatremia.

Overdose:

Symptoms

Pronounced decrease in blood pressure, shock, disturbance of water-electrolyte balance (hyperkalemia, hyponatremia), renal 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 restoration of the water-electrolyte balance.

With a significant decrease in blood pressure, the patient should be put in the "lying down" position, the legs should be raised and the volume of the bcc should be filled, 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 (drugs) that cause hyperkalemia

Some drugs or preparations of other pharmacological classes may increase the risk of hyperkalemia: aliskiren and aliskin-containing preparations, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists (APA II), 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 / 1.73 m² surface area of the body ") causes the risk of hyperkalemia, impaired renal function and increased incidence of cardiovascular morbidity and mortality.

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 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, fainting,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 simultaneous use 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 when excess fluid and / or electrolytes are removed, 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 (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

Against the background of perindopril therapy, the serum potassium content, as a rule, remains within the normal range. 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)), potassium and potassium-sparing products and food additives can lead to a significant increase in potassium 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.

Potassium-containing diuretics (eplerenone, spironolactone)

Spironolactone and eplerenone in doses of 12.5 mg to 50 mg per day for CHF and low doses of ACE inhibitors: in patients with CHF II-IV functional class by classification NYHA with left ventricular ejection fraction less than 40; and previously used ACE inhibitors and "loop" diuretics, there is a risk of hyperkalemia (possibly fatal), especially in case of non-compliance with recommendations for this combination of 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 and every month thereafter.

Potassium-sparing diuretics

In patients receiving diuretics that remove liquid and / or salts, at the beginning of Perindopril therapy, a marked decrease in blood pressure can be observed, the risk of which can be reduced by eliminating diuretics, replenishing fluid loss or salts before starting therapy with Perindopril, and using Perindopril in a low dose with further gradual increase.

In patients who receive diuretics, especially those who take out fluid and / or salts, diuretics should be either abolished prior to the use of an ACE inhibitor in patients receiving diuretics (with a potassium-sparing diuretic may be administered later), or an ACE inhibitor should be prescribed at a low dose with its further gradual increase.

When using diuretics in the case of CHF, the ACE inhibitor should be prescribed 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.

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, cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs) can 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.

Hypoglycemic 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-adrenoblockers, nitrates

Perindopril can be used in conjunction with acetylsalicylic acid (as an antiplatelet 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 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.

Glyptins (linaglyptin, saxagliptin, sitagliptin, vildagliptin)

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), a symptom complex including facial flushing, nausea, vomiting, and arterial hypotension was described.

Special instructions:

Stable IHD: reduced risk of cardiovascular complications in patients who had previous myocardial infarction and / or 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 decrease in blood pressure is increased in patients with reduced BCC, which can be observed against diuretic therapy, with strict salt-free diet, hemodialysis, vomiting and diarrhea, as well as in patients with severe hypertension with high renin plasma activity (see section "Interaction with other drugs").

In most cases, episodes of severe BP decrease are observed in patients with severe CHF, 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 the drug Perindopril patients should be under close medical supervision (see p.sections "Method of administration and dose" and "Side effect"). 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 decrease in blood pressure, the patient should be transferred to the "lying down" position, the legs should be raised, BCC replenishment (for example, intravenous infusion 0.9% solution of sodium chloride). The pronounced decrease in blood pressure at the first intake of the drug is 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 the drug Perindopril.

In some patients with CHF and normal or low blood pressure 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

Perindopril, 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

Patients with renal insufficiency (KC less than 60 ml / min.) Initial dose of the drug Perindopril are selected depending on the value of the CC (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, it may be necessary to cancel or reduce the dose of the drug Perindopril 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.

Kidney Transplantation

Data on the use of the drug Perindopril after transplantation, the kidneys are absent.

Hypersensitivity / angioedema

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

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 epinephrine (adrenaline) 1: 1000 (1 mg / ml) 0.3-0.5 ml solution or slow intravenous administration (according to the instructions for preparing the infusion solution) under the control of the electrocardiogram 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 pain in the abdomen,receiving ACE inhibitors, when making a differential diagnosis, it is necessary to consider the possibility of developing angioedema 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.Nevertheless, this reaction can be avoided by temporary discontinuation of ACE inhibitor prior to the desensitization treatment.

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 the drug is administered Perindopril in patients with the above factors it is necessary to regularly monitor the number of leukocytes.

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, Perindopril It 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

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 who are undergoing surgery with general anesthesia can lead to a marked decrease in blood pressure, especially with the use of general anesthetic agents that have antihypertensive effects. Reception of the drug Perindopril must be discontinued one day before surgery. With the development of arterial hypotension, BP should be maintained by replenishing the ODC.

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, a latent diabetes mellitus. 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 agents for oral administration or insulin, during the first month of therapy with ACE inhibitors, the concentration of glucose in the blood plasma should be monitored regularly (see section "Interaction with other drugs").

Not recommended for use in conjunction with ACE inhibitors ARAII antagonists in patients with diabetic nephropathy.

Lithium preparations

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

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

Not recommended combined use of ACE inhibitor (see. The 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 ARAII or aliskiren is not recommended.

The combination with aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR <60 ml / min / 1.73 m²body surface area) (see the sections "Contraindications" and "Interaction with other medicinal products").

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

There is no data on the effect of perindopril on the ability to drive vehicles and manage the mechanisms used in therapeutic doses, but it must be borne in mind that dizziness may occur, therefore, care must be taken.

Form release / dosage:

Tablets, 2 mg, 4 mg and 8 mg.

Packaging:

7 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil. 2, 3, 4 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

10 tablets per contour cell packaging made of polyvinylchloride and aluminum foil. 1, 2, 3, 4, 5 contour cell packs along with the instruction for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003712

Date of registration:29.06.2016

Expiration Date:29.06.2021

The owner of the registration certificate:PRANAFARM, LLC PRANAFARM, LLC Russia

Manufacturer: & nbsp

PRANAFARM, LLC Russia

Information update date: & nbsp15.08.2016

Illustrated instructions

Instructions

Perindopril (Perindopril)