Perindopril PLUS Indapamide tab.pp.p.o.2.5mg+8mg No. 30

Instructions:

Clinical and pharmacological group

01.024 (ACE inhibitor)

Release form, composition and packaging

White film-coated tablets, round, biconvex.

Excipients: lactose monohydrate, magnesium stearate, maltodextrin, hydrophobic colloidal silicon dioxide, sodium carboxymethyl starch, glycerol, hypromellose, macrogol 6000, titanium dioxide.

30 pcs. — polypropylene bottles (1) — cardboard packs with first opening control.

Light green film-coated tablets, oblong, rounded on both sides, notched on both sides and engraved with the company logo on one of the front sides.

Excipients: lactose monohydrate, magnesium stearate, maltodextrin, hydrophobic colloidal silicon dioxide, sodium carboxymethyl starch, glycerol, hypromellose, macrogol 6000, titanium dioxide, copper chlorophyllin dye (E141ii).

14 pcs. — polypropylene bottles (1) — cardboard packs with first opening control. 30 pcs. — polypropylene bottles (1) — cardboard packs with first opening control.

Green film-coated tablets, round, biconvex, engraved with a heart on one side and the company logo on the other.

Excipients: lactose monohydrate, magnesium stearate, maltodextrin, hydrophobic colloidal silicon dioxide, sodium carboxymethyl starch, glycerol, hypromellose, macrogol 6000, titanium dioxide, copper chlorophyllin dye (E141ii).

30 pcs. — polypropylene bottles (1) — cardboard packs with first opening control.

pharmachologic effect

Antihypertensive drug, ACE inhibitor. ACE, or kininase, is an exopeptidase that carries out both the conversion of angiotensin I into the vasoconstrictor substance angiotensin II, and the destruction of bradykinin, which has a vasodilator effect, into an inactive heptapeptide.

Suppression of ACE leads to a decrease in the content of angiotensin II in the blood plasma, as a result of which plasma renin activity increases (due to inhibition of negative feedback, which prevents the release of renin) and aldosterone secretion decreases. Since ACE inactivates bradykinin, suppression of ACE is accompanied by an increase in the activity of both the circulating and tissue kallikrein-kinin system, while the prostaglandin system is activated. Perindopril reduces peripheral vascular resistance, which leads to a decrease in blood pressure. In this case, peripheral blood flow accelerates, but heart rate does not increase.

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

Arterial hypertension

In case of arterial hypertension with the use of the drug, there is a decrease in both systolic and diastolic blood pressure in the supine and standing positions. A decrease in blood pressure is achieved quite quickly. In patients with a positive response to treatment, normalization of blood pressure occurs within a month. In this case, no addiction effect is observed.

Discontinuation of treatment is not accompanied by the development of 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. Concomitant administration of thiazide diuretics enhances the hypotensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia while taking diuretics.

Heart failure

Perindopril normalizes heart function by reducing preload and afterload. In patients with chronic heart failure receiving perindopril, a decrease in filling pressure in the left and right ventricles of the heart was detected; decrease in OPSS; increased cardiac output and increased cardiac index. A study of the drug compared with placebo showed that changes in blood pressure after the first dose of Prestarium® A at a dose of 2.5 mg in patients with mild to moderate heart failure were not statistically significantly different from changes in blood pressure observed after taking placebo.

Cerebrovascular diseases

An international multicenter study (PROGRESS) assessed the effect of active therapy with perindopril (monotherapy or in combination with indapamide) for 4 years on the risk of recurrent stroke in patients with a history of cerebrovascular disease. After a run-in period of perindopril tert-butylamine 2 mg (equivalent to perindopril arginine 2.5 mg) once a day for 2 weeks and then 4 mg (equivalent to perindopril arginine 5 mg) once a day for the next two weeks, 6105 patients were randomized into two groups: placebo (n=3054) and perindopril tertbutylamine 4 mg (corresponding to 5 mg perindopril arginine) (monotherapy) or in combination with indapamide (n=3051). Indapamide was additionally prescribed to patients who did not have direct indications or contraindications for the use of diuretics. This therapy was prescribed in addition to standard therapy for stroke and/or arterial hypertension or other pathological conditions. All randomized patients had a history of cerebrovascular disease (stroke or transient ischemic attack) within the past 5 years. Blood pressure was not an inclusion criterion: 2916 patients had arterial hypertension and 3189 had normal blood pressure. After 3.9 years of therapy, blood pressure (systolic/diastolic) decreased by an average of 9/4 mm Hg. It also showed a significant reduction in the risk of recurrent stroke (both ischemic and hemorrhagic in nature) of about 28% (95% CI (17; 38), p < 0.0001) compared with placebo (10.1% vs 13.8%). Additionally, a significant reduction in the risk of fatal or disabling strokes was shown; major cardiovascular complications, including myocardial infarction, incl. with fatal outcome; stroke-related dementia; serious deterioration of cognitive functions.

These therapeutic benefits are observed in both patients with arterial hypertension and normal blood pressure, regardless of age, gender, presence or absence of diabetes mellitus and type of stroke.

Stable ischemic heart disease

During the international multicenter randomized, double-blind, placebo-controlled EUROPA study lasting 4 years, the effectiveness of perindopril was studied in patients with stable coronary artery disease. The clinical trial involved 12,218 patients over 18 years of age: 6,110 patients received perindopril tert-butylamine 8 mg (equivalent to 10 mg of perindopril arginine) and 6,108 patients received placebo.

The main outcome measures were cardiovascular mortality, non-fatal myocardial infarction and/or cardiac arrest followed by successful resuscitation. Patients with coronary artery disease with known myocardial infarction at least 3 months before screening, coronary revascularization at least 6 months before screening, angiographically detected stenosis (at least 70% narrowing of one or more major coronary arteries) or positive stress test if there is a history of chest pain. The drug was prescribed in addition to standard therapy used for hyperlipidemia, arterial hypertension and diabetes mellitus.

Most patients took antiplatelet agents, lipid-lowering agents, and beta-blockers. At the end of the study, the ratio of the number of patients taking these groups of drugs was 91%, 69% and 63%, respectively. After 4.2 years, the result of treatment with perindopril tertbutylamine at a dose of 8 mg 1 time / day was a significant reduction in the relative risk by 20% (95% CI) of developing prespecified complications: in 488 (8%) patients in the group taking perindopril tertbutylamine, and in 603 (9.9%) patients in the placebo group (p=0.0003).

The result did not depend on gender, age, blood pressure, or a history of myocardial infarction.

Pharmacokinetics

Suction

After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract, Cmax in blood plasma is reached after 1 hour. Approximately 27% of the total amount of absorbed perindopril is converted into perindoprilat, the active metabolite. In addition to perindoprilate, 5 more metabolites are formed during metabolism - all of them are inactive substances.

T1/2 of perindopril from plasma is 1 hour. Cmax of perindoprilate in blood plasma is achieved after 3-4 hours.

Taking the drug with food is accompanied by a decrease in the conversion of perindopril to perindoprilat, accordingly reducing the bioavailability of the drug.

Distribution

The binding of perindoprilate to plasma proteins is 20%, mainly with ACE, and is dose-dependent. The Vd of free perindoprilate is approximately 0.2 l/kg.

Removal

Perindoprilat is excreted by the kidneys and the total T1/2 of the unbound fraction is 17 hours, which ensures an equilibrium state for 4 days.

Pharmacokinetics in special clinical situations

The elimination of perindoprilate is slowed down in old age, as well as in patients with heart and renal failure. In case of renal failure, it is advisable to adjust the dose of the drug taking into account the degree of renal dysfunction.

The dialysis clearance of perindoprilate is 70 ml/min.

In patients with liver cirrhosis, the hepatic clearance of perindopril is reduced by half. However, the amount of perindoprilate formed does not decrease and no changes in the dose of the drug are required.

Dosage

The drug is prescribed orally 1 time/day in the morning, before meals.

Arterial hypertension

The recommended starting dose is 5 mg 1 time/day, in the morning. If therapy is ineffective within a month, the dose can be increased to 10 mg 1 time / day.

When prescribing ACE inhibitors to patients with severely activated RAAS (with renovascular arterial hypertension, water-salt imbalance, diuretic therapy, severe arterial hypertension, cardiac decompensation), an unpredictable sharp decrease in blood pressure may be observed, for the prevention of which it is recommended to stop taking diuretics for 2-3 days before the intended start of therapy with Prestarium® A.

If it is impossible to cancel diuretics, the initial dose of Prestarium® A is 2.5 mg. In this case, it is necessary to monitor kidney function and potassium levels in the blood serum. Subsequently, if necessary, the dose can be increased.

In elderly patients, treatment should begin with a dose of 2.5 mg/day, and then, if necessary, gradually increase it up to a maximum dose of 10 mg/day.

Heart failure

Treatment with Prestarium® A in combination with non-potassium-sparing diuretics and/or digoxin and/or beta-blockers is recommended to begin under close medical supervision, prescribing the drug at an initial dose of 2.5 mg 1 time/day, in the morning. Subsequently, depending on tolerability and response to therapy, after 2 weeks of treatment, the dose of the drug can be increased to 5 mg 1 time / day.

In patients at high risk of developing symptomatic arterial hypotension, for example, with a reduced salt intake with or without hyponatremia, hypovolemia or taking diuretics, these conditions should, if possible, be corrected before starting Prestarium® A. Indicators such as blood pressure, renal function and potassium levels in the blood plasma should be monitored both before and during therapy.

Prevention of recurrent stroke

In patients with a history of cerebrovascular disease, therapy with Prestarium® A should begin with a dose of 2.5 mg during the first 2 weeks before the administration of indapamide.

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

Reducing the risk of cardiovascular complications

In case of stable coronary artery disease, therapy with Prestarium® A should be started with a dose of 5 mg 1 time/day for 2 weeks. Then the daily dose should be increased to 10 mg 1 time / day (depending on renal function).

Elderly patients should begin therapy with a dose of 2.5 mg 1 time/day for one week, then 5 mg 1 time/day for the next week before increasing the dose to 10 mg 1 time/day (depending on renal function).

If renal function is impaired, the dose of Prestarium® A should be selected taking into account the degree of renal failure and under regular monitoring of potassium and QC levels.

* dialysis clearance of perindoprilate: 70 ml/min

When prescribing the drug to patients with impaired liver function, no dose changes are required.

Overdose

Symptoms: marked decrease in blood pressure, shock, electrolyte imbalance (such as increased concentration of potassium ions, decreased sodium); renal failure, hyperventilation, tachycardia, dizziness, bradycardia, restlessness and cough.

Treatment: with a significant decrease in blood pressure, the patient should be placed in a supine position and the blood volume should be immediately restored, if possible, an infusion of angiotensin II and/or intravenous catecholamines should be administered. If persistent severe bradycardia develops, the use of an artificial pacemaker may be required. Constant monitoring of vital body functions, serum electrolytes and CK is required. Perindopril can be removed from the systemic circulation by hemodialysis. During dialysis, the use of high-flow polyacrylonitrile membranes should be avoided.

Drug interactions

During the initial period of treatment, some patients during diuretic therapy, especially with excessive excretion of fluid and/or salts, may experience an excessive decrease in blood pressure, the risk of which can be reduced by discontinuing the diuretic, administering increased amounts of water and/or sodium chloride, and also prescribing ACE inhibitor at lower doses. Further increases in the dose of perindopril should be carried out with caution.

During therapy with ACE inhibitors, as a rule, the potassium content in the blood serum remains within normal limits, but hyperkalemia can sometimes develop. The combined use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene and amiloride) and potassium preparations, potassium-containing products and nutritional supplements can lead to a significant increase in serum potassium concentrations. In this regard, their combined use with ACE inhibitors is not recommended. These combinations should be used only in case of hypokalemia, taking precautions and constantly monitoring serum potassium levels.

Co-administration of ACE inhibitors and lithium preparations can lead to a reversible increase in the concentration of lithium in the blood serum and the development of lithium toxicity. Additional administration of thiazide diuretics against the background of the combined use of lithium and ACE inhibitors increases the already existing risk of developing lithium toxicity. Concomitant use of ACE inhibitors and lithium is not recommended. If this combination cannot be avoided, then it is necessary to regularly monitor the lithium content in the blood serum.

The administration of NSAIDs may be accompanied by a weakening of the antihypertensive effect of ACE inhibitors. Moreover, NSAIDs and ACE inhibitors have been shown to have an additive effect on increasing serum potassium levels, which may also worsen renal function. As a rule, these effects are reversible. In rare cases, acute renal failure may develop, which usually occurs with pre-existing renal dysfunction in elderly patients or due to dehydration.

The antihypertensive effect of drugs may be enhanced when combined with ACE inhibitors. The use of nitroglycerin and/or other vasodilators may lead to an additional hypotensive effect.

When used simultaneously with ACE inhibitors, allopurinol, immunosuppressants, incl. cytostatic agents and systemic corticosteroids, procainamide may increase the risk of developing leukopenia.

The administration of ACE inhibitors can enhance the hypoglycemic effect of insulin and oral hypoglycemic agents, up to the development of hypoglycemia. As a rule, this phenomenon is observed in the first weeks of combined use of these drugs and in patients with renal failure.

Co-prescription of tricyclic antidepressants, antipsychotics (neuroleptics), and general anesthesia with ACE inhibitors can lead to an increased hypotensive effect.

Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. When prescribing such a combination, the effectiveness of ACE inhibitors should be regularly assessed.

Antacids reduce the bioavailability of ACE inhibitors.

Perindopril can be prescribed together with acetylsalicylic acid (as a thrombolytic), thrombolytic agents, beta-blockers and/or nitrates.

Ethanol enhances the hypotensive effect of ACE inhibitors.

Use during pregnancy and lactation

The use of Prestarium® A in the first trimester of pregnancy is not recommended. When planning or confirming pregnancy, it is necessary to switch to alternative therapy. Adequate strictly controlled clinical studies have not been conducted to study the effect of ACE inhibitors in the first trimester of pregnancy. In a limited number of cases of use of ACE inhibitors in the first trimester of pregnancy, no malformations associated with fetotoxicity were observed.

Perindopril is contraindicated in the second and third trimesters of pregnancy, because There is evidence of fetotoxicity (decreased renal function, oligohydramnios (pronounced decrease in the volume of amniotic fluid), delayed formation of skull bones) and neonatal toxicity (impaired renal function, hypotension, hyperkalemia). If perindopril therapy was carried out in the second and/or third trimesters of pregnancy, it is necessary to conduct an ultrasound examination of the function of the fetus's kidneys and skull.

It is unknown whether perindopril is excreted in breast milk in humans, therefore the use of the drug during lactation (breastfeeding) is not recommended.

Side effects

From the cardiovascular system: excessive decrease in blood pressure and associated symptoms; extremely rarely - arrhythmia, angina pectoris, myocardial infarction and stroke; in patients at risk, secondary severe arterial hypotension may develop.

From laboratory parameters: extremely rarely - decreased hemoglobin concentration and hematocrit, thrombocytopenia, leukopenia/neutropenia, isolated cases of agranulocytosis or pancytopenia; the likelihood of developing hemolytic anemia due to glucose-6-phosphate dehydrogenase deficiency; rarely - increased levels of urea and creatinine in blood plasma, transient hyperkalemia, especially against the background of renal failure, increased activity of liver enzymes and liver bilirubin.

Storage conditions and periods

The drug should be stored out of the reach of children. No special conditions are required for storing the drug. Shelf life: 3 years.

Indications

- arterial hypertension;

— chronic heart failure;

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

- stable coronary artery disease: to reduce the risk of cardiovascular complications.

Contraindications

- history of angioedema (congenital/idiopathic or reaction associated with previous treatment with an ACE inhibitor);

- pregnancy;

- lactation period (breastfeeding);

- hypersensitivity to the components of the drug;

- hypersensitivity to other ACE inhibitors;

- lactase deficiency, galactosemia, glucose/galactose malabsorption syndrome (due to the fact that the excipients of the drug include lactose monohydrate).

Use with caution when there is a decrease in blood volume (taking diuretics, a salt-free diet, vomiting, diarrhea, hemodialysis), hyponatremia, cerebrovascular diseases, angina pectoris - the risk of a sharp decrease in blood pressure; with renovascular hypertension, bilateral renal artery stenosis or the presence of only one functioning kidney - the risk of developing severe arterial hypotension and renal failure; with chronic renal failure; with systemic connective tissue diseases (SLE, scleroderma) and therapy with immunosuppressants - the risk of developing agranulocytosis and neutropenia; with hyperkalemia; with aortic valve stenosis, hypertrophic obstructive cardiomyopathy; during the hemodialysis procedure using high-flow polyacrylonitrile membranes; before the LDL apheresis procedure; in patients after kidney transplantation (no experience of clinical use); simultaneously with desensitizing therapy with allergens; surgical intervention (general anesthesia); in patients with diabetes mellitus receiving hypoglycemic agents or insulin (it is recommended to monitor blood glucose levels); in patients under the age of 18 years (the effectiveness and safety of use have not been studied).

special instructions

In patients with stable coronary artery disease, if an episode of unstable angina (significant or not) occurs during the first month of therapy with Prestarium A, the benefits and risks should be assessed before continuing treatment.

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic arterial hypotension rarely develops in patients without concomitant diseases. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during therapy with diuretics, while following a strict salt-free diet, hemodialysis, as well as with vomiting and diarrhea. In most cases, episodes of pronounced decrease in blood pressure are observed in patients with severe heart failure, both in the presence of concomitant renal failure and in its absence. This side effect is most often observed in patients receiving loop diuretics in high doses, as well as against the background of hyponatremia or impaired renal function. In such patients, treatment should begin under close medical supervision, preferably in a hospital setting. In this case, the drug is prescribed in small doses, followed by careful titration of the dose. If possible, diuretic therapy should be temporarily discontinued. A similar approach is also used in patients with angina pectoris or cerebrovascular disease, in whom severe hypotension can lead to the development of myocardial infarction or cerebrovascular complications.

Before prescribing Prestarium® A, as well as other ACE inhibitors, and during its use, blood pressure levels, kidney function indicators and the concentration of potassium ions in the blood serum should be carefully monitored.

In order to reduce the likelihood of developing symptomatic arterial hypotension in patients receiving diuretic therapy in high doses, the dose of diuretics should, if possible, be reduced several days before starting use of the drug Prestarium® A.

If arterial hypotension develops, the patient should be placed in the supine position. If necessary, the volume of blood volume should be replenished using intravenous administration of saline solution. A pronounced decrease in blood pressure when taking the drug for the first time is not an obstacle to further prescription of the drug. After restoration of blood volume and blood pressure, treatment can be continued subject to careful selection of the dose of the drug.

In patients with symptomatic heart failure, arterial hypotension that develops during the initial period of therapy with ACE inhibitors can lead to deterioration of renal function. Sometimes acute renal failure that develops is, as a rule, reversible.

In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), serum urea and creatinine concentrations may increase during therapy with ACE inhibitors.

The use of ACE inhibitors in patients with renovascular arterial hypertension is accompanied by an increased risk of developing severe arterial hypotension and renal failure. Treatment of such patients begins under close medical supervision with the administration of the drug in small doses and further adequate dose selection. During the first few weeks of therapy, diuretic treatment should be temporarily discontinued and renal function monitored.

In some patients suffering from arterial hypertension, in the presence of previously undetected renal failure, especially with concomitant administration of diuretics, the concentration of urea and creatinine in the blood serum may increase. These changes are usually mild and reversible. In this case, it is recommended to reduce the dose of Prestarium® A and/or discontinue the diuretic.

In patients undergoing hemodialysis using high-flow membranes, several cases of persistent, life-threatening anaphylactic reactions have been observed. Prescription of ACE inhibitors should be avoided when using this type of membrane.

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

Angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx may develop in patients receiving ACE inhibitors, especially during the first few weeks of therapy. In rare cases, severe angioedema may occur during prolonged use of an ACE inhibitor. In such cases, treatment with an ACE inhibitor should be stopped immediately, and drugs of another pharmacotherapeutic group should be prescribed as a replacement.

Angioedema of the tongue, glottis, or larynx can be fatal. When it develops, emergency therapy includes, among other prescriptions, immediate subcutaneous administration of a solution of epinephrine (adrenaline) 1:1000 (1 mg/ml) 0.3-0.5 ml or slow intravenous administration (in accordance with the preparation instructions infusion solution) under ECG and blood pressure control. The patient should be hospitalized for treatment and observation for at least 12-24 hours until the symptoms of this reaction completely disappear.

When performing LDL apheresis using dextran sulfate absorption, patients may develop anaphylactic reactions when ACE inhibitors are prescribed.

There are isolated 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. Avoid prescribing ACE inhibitors to patients receiving bee venom immunotherapy. However, this reaction can be avoided by temporarily stopping the ACE inhibitor before the procedure.

Taking ACE inhibitors is sometimes associated with a syndrome starting with the development of cholestatic jaundice, progressing to fulminant hepatic necrosis, and (sometimes) death. The mechanism of development of this syndrome is not clear. If symptoms of jaundice or increased liver enzyme activity occur in patients taking ACE inhibitors, discontinue drug therapy and conduct appropriate evaluation.

Neutropenia, agranulocytosis, thrombocytopenia, and anemia can develop during therapy with ACE inhibitors. With normal renal function and the absence of other complications, neutropenia rarely occurs. ACE inhibitors are prescribed only in emergency cases in the presence of systemic vasculitis, immunosuppressive therapy, taking allopurinol or procainamide, as well as when combining all of these factors, especially against the background of previous renal failure. There is a risk of developing severe infectious diseases that are resistant to intensive antibiotic therapy. When carrying out perindopril therapy in patients with the above factors, it is necessary to regularly monitor the number of leukocytes and warn the patient about the need to inform the attending physician about the appearance of any symptoms of infection.

It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, perindopril is less effective as an antihypertensive agent in black patients. This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

During therapy with an ACE inhibitor, a dry, non-productive cough may occur, which stops after discontinuation of the drug.

The use of ACE inhibitors in patients whose condition requires surgery and/or general anesthesia may lead to the development of arterial hypotension or collapse, due to a sharp increase in the antihypertensive effect. Perindopril should be stopped the day before surgery. If arterial hypotension develops, it is necessary to maintain blood pressure by replenishing blood volume.

During therapy with ACE inhibitors, hyperkalemia may develop, especially if the patient has renal and/or heart failure or uncontrolled diabetes mellitus. It is generally not recommended to prescribe potassium supplements, potassium-sparing diuretics, and other drugs associated with a risk of potassium elevation (eg, heparin) due to the potential for severe hyperkalemia. If the combined use of these drugs is necessary, then therapy should be accompanied by regular monitoring of potassium levels in the blood serum.

In patients taking oral hypoglycemic agents or insulin, blood glucose levels should be carefully monitored during the first month of ACE inhibitor therapy.

It is not recommended to use lithium preparations, potassium-sparing diuretics, potassium preparations, potassium-containing products and nutritional supplements simultaneously with perindopril.

Due to the fact that the excipients of the drug include lactose monohydrate, Prestarium® A is contraindicated in patients with lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome. Prestarium® A tablets of 2.5 mg, 5 mg and 10 mg contain 36.29 mg, 72.58 mg and 145.16 mg of lactose monohydrate, respectively.

Impact on the ability to drive vehicles and operate machinery

ACE inhibitors should be prescribed with caution to patients driving vehicles and engaging in activities that require increased concentration and speed of psychomotor reactions, due to the risk of developing arterial hypotension and dizziness.

Use for renal impairment

Use the drug with caution in bilateral renal artery stenosis or the presence of only one functioning kidney - the risk of developing severe arterial hypotension and renal failure; with chronic renal failure; during the hemodialysis procedure using high-flow polyacrylonitrile membranes.

Use for liver dysfunction

In patients with liver cirrhosis, the hepatic clearance of perindopril is reduced by half. However, the amount of perindoprilate formed does not decrease and no changes in the dose of the drug are required.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Perindopril-Teva tablets 5 mg 30 pcs. in Moscow

Inside,

1 table each 1 time per day, preferably in the morning, before meals.

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

When choosing a dose, one should take into account the characteristics of the clinical situation and the degree of reduction in blood pressure during therapy.

Arterial hypertension

Can be used both in monotherapy and as part of combination therapy.

The recommended starting dose is 5 mg once daily.

In patients with severe activation of the RAAS system (especially with renovascular hypertension, hypovolemia and/or decreased plasma electrolytes, decompensated chronic heart failure or severe arterial hypertension), a marked decrease in blood pressure may develop after taking the first dose of the drug. At the beginning of therapy, such patients should be under close medical supervision. The recommended starting dose for such patients is 2.5 mg once daily. If necessary, a month after the start of therapy, you can increase the dose of the drug to 10 mg 1 time per day.

At the beginning of drug therapy, 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 plasma electrolytes. Caution should be exercised when using the drug in this group of patients.

It is recommended, if possible, to stop taking diuretics 2-3 days before the intended start of drug therapy.

If it is impossible to cancel diuretics, the initial dose of the drug should be 2.5 mg. In this case, it is necessary to monitor kidney function and potassium levels in the blood serum. In the future, if necessary, the dose of the drug can be increased. If necessary, diuretics can be resumed.

In elderly patients

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

The maximum daily dose is 10 mg.

Heart failure

Treatment of patients with chronic heart failure with the drug in combination with non-potassium-sparing diuretics and/or digoxin and/or beta-blockers is recommended to begin under close medical supervision, prescribing the drug at an initial dose of 2.5 mg 1 time per day, in the morning. After 2 weeks of treatment, the dose of the drug can be increased to 5 mg 1 time per day, provided that the dose of 2.5 mg is well tolerated and the response to therapy is satisfactory.

In patients at high risk of developing symptomatic arterial hypotension, for example, with reduced electrolyte levels with or without hyponatremia, hypovolemia, or taking diuretics, these conditions should, if possible, be corrected before starting the drug.

Indicators such as blood pressure, renal function and potassium levels in the blood plasma should be monitored both before and during therapy.

Prevention of recurrent stroke (combination therapy with indapamide)

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

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

IHD: reducing the risk of cardiovascular complications in patients who have previously had myocardial infarction and/or coronary revascularization

In patients with stable ischemic heart disease, drug therapy should be started with a dose of 5 mg once a day.

After 2 weeks, if the drug is well tolerated and taking into account the state of renal function, the dose can be increased to 10 mg 1 time per day.

Elderly patients

Therapy should be started with a dose of 2.5 mg 1 time per day for 1 week, then 5 mg 1 time per day over the next week. Then, taking into account the state of renal function, the dose can be increased to 10 mg 1 time per day (see Table 1). The dose of the drug can be increased only if it is well tolerated at the previously recommended dose.

Special patient groups:

Kidney failure

In patients with renal failure, the dose of the drug should be adjusted taking into account creatinine Cl.

Table 1

Dosage of the drug for renal failure

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

Liver failure

In patients with impaired liver function, no dose adjustment is required.

Age up to 18 years

It should not be prescribed to children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of the drug in patients in this age group.

Perindopril PLUS Indapamide tab.pp.p.o.2.5mg+8mg No. 30

Indications

• arterial hypertension.

pharmachologic effect

A combined antihypertensive drug containing an angiotensin-converting enzyme (ACE) inhibitor - perindopril and a thiazide-like diuretic - indapamide. The drug has antihypertensive, diuretic and vasodilating effects.

Perindopril plus Indapamide

has a pronounced dose-dependent antihypertensive effect, independent of the age and body position of the patient and not accompanied by reflex tachycardia. Does not affect lipid metabolism (total cholesterol, low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), high-density lipoproteins (HDL), triglycerides (TG) and carbohydrates), incl. in patients with diabetes mellitus. Reduces the risk of hypokalemia caused by diuretic monotherapy. The hypotensive effect lasts for 24 hours.

A stable reduction in blood pressure (BP) is achieved within 1 month with the use of the drug Perindopril plus Indapamide without an increase in heart rate (HR). Discontinuation of treatment does not lead to the development of “oopiruet” syndrome, such as antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, amiodarone, dofstilide, ibutilide, bretylium tosylate, sotalol), some antipsychotics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides ( amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol), other antipsychotics (pimozide); other substances such as bepridil, cisapride, difemanil methyl sulfate, erythromycin (iv), halofantrine, mizolastine, moxifloxacin. pentamidine, sparfloxacin. vincamine for intravenous use, methadone, astemizole. terfenadine It is necessary to control the content of the execution in order to avoid hypocaemia, the development of which requires its correction, and to monitor the QT interval on the ECG.

With simultaneous use of indapamide with amphotericin B (iv), gluco- and mineralocorticoids (if administered systemically), tstracosactide. laxatives that stimulate intestinal motility increase the risk of hypokatemia (additive effect). It is necessary to monitor the content of casium in the blood plasma and, if necessary, correct it. Particular attention should be paid to patients simultaneously receiving cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used.

Hypokalemia enhances the toxic effect of cardiac glycosides. With the simultaneous use of indapamide and cardiac glycosides, the potassium content in the blood plasma, ECG parameters should be monitored and, if necessary, the dose of cardiac glycosides should be correlated.

Caution is required during simultaneous use

When using metformin with diuretics, renal failure may develop.

When used simultaneously with metformin, the risk of developing lactic acidosis increases. Metformin should not be used if serum creatipine levels exceed 15 mg/l (135 µmol/l) in men and 12 mg/l (110 µmol/l) in women.

While taking diuretics, there is a decrease in blood volume, and the risk of developing acute renal failure increases, especially when using iodine-containing contrast agents in high doses. Before using iodine-containing contrast agents, it is necessary to compensate for the volumetric volume.

When used simultaneously with calcium supplements, hypercalcemia may develop due to a decrease in calcium excretion by the kidneys.

When used simultaneously with cyclosporine, the risk of developing renal dysfunction (hypercreatininemia) increases.

Dosage regimen

Prescribed orally 1 time/day. preferably in the morning before breakfast, with plenty of liquid.

Doses are given for the perindopril/indapamide ratio.

The initial dose of Perindopril plus Indapamide is 0.625 mg/2 mg (1 tablet) 1 time/day. If after 1 month of taking the drug it is not possible to achieve adequate blood pressure control. then the dose of the drug should be increased to 1.25 mg/4 mg (1 tablet) 1 time/day.

Patients with renal failure

(CrCl 60 ml/min or more) no dose adjustment is required. For patients with CC 30-60 ml/min, the maximum dose of Perindopril plus Indapamide is 0.625 mg/2 mg (1 tablet) 1 time/day; treatment should begin with selection of doses of perindopril and indapamide in monotherapy. When CC is less than 30 ml/min, the use of Perindopril plus Indapamide is contraindicated (see section “Contraindications”).

Patients with moderate liver dysfunction

no dose adjustment is required. In patients with severe liver dysfunction, the use of Perindopril plus Indapamide is contraindicated.

For elderly patients

The initial dose of Perindopril plus Indapamide is 0.625 mg/2 mg (1 tablet) 1 time/day.

In elderly patients, renal function and plasma potassium levels should be assessed before starting Perindopril plus Indapamide. The initial dose of Perindopril plus Indapamide is selected depending on the degree of reduction in blood pressure, especially with a decrease in blood volume and in chronic heart failure (functional class IV according to the NYHA classification). Such measures help to avoid a sharp decrease in blood pressure.

The risk of arterial hypotension exists in all patients, however, special caution should be observed when using the drug Perindopril plus Indapamide in patients with coronary artery disease and cerebrovascular insufficiency. In such patients, treatment with the drug should begin with a dose of 0.625 mg/2 mg (initial dose). In patients with diagnosed or suspected renal artery stenosis, treatment with Perindopril plus Indapamide should be started in a hospital setting with a dose of 0.625 mg/2 mg under monitoring of renal function and potassium levels in the blood plasma. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.

In patients with chronic heart failure

(IV functional class according to the NYHA classification), treatment with Perindopril plus Indapamide should be started with an initial dose of 0.625 mg/2 mg under medical supervision.

Overdose

Symptoms:

marked decrease in blood pressure, nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria up to anuria (due to a decrease in blood volume); disturbances in water and electrolyte balance are possible (low sodium and potassium levels in the blood plasma).

Treatment:

gastric lavage and/or administration of activated carbon, restoration of water and electrolyte balance in a hospital setting. If there is a pronounced decrease in blood pressure, it is necessary to transfer the patient to a position lying on his back with the yoga legs raised up; then measures should be taken aimed at increasing the volume of blood volume (administration of 0.9% sodium chloride solution intravenously). Perindoprilat. active metabolite of perindopril, can be removed from the body by dialysis.

Contraindications for use

Perindopril

• hypersensitivity to perindopril and other ACE inhibitors;
• history of angioedema (Quincke's edema) associated with taking an ACE inhibitor;
• hereditary/idiopathic angioedema;
• bilateral renal artery stenosis or stenosis of the artery of a single kidney;
• simultaneous use of ACE inhibitors with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and renal failure (creatinine clearance (CC) less than 60 ml/min);
• pregnancy;
• breastfeeding period;
• age under 18 years (efficacy and safety have not been established).

Indapamide

• hypersensitivity to indapamide and other sulfonamide derivatives;
• severe liver failure (including encephalopathy);
• hypokalemia;
• simultaneous use with drugs that can cause ari;
• pregnancy and breastfeeding;
• age under 18 years (efficacy and safety have not been established).

Perindopril plus Indapamide

• hypersensitivity to the excipients included in the drug;
• severe renal failure (CK
• simultaneous use with potassium-sparing diuretics, potassium and lithium preparations, and in patients with hyperkalemia;
• simultaneous use of drugs that prolong the QT interval;
• due to the lack of sufficient clinical experience, Perindopril plus Indapamide should not be used in patients on hemodialysis, as well as in patients with untreated heart failure in the stage of decompensation;
• age under 18 years (efficacy and safety have not been established).

Carefully:

the drug should be used for systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma); during therapy with immunosuppressants (risk of developing neutropenia, agranulocytosis); with suppression of bone marrow hematopoiesis; a decrease in circulating blood volume (CBV) (due to taking diuretics, a diet with limited salt, vomiting, diarrhea); with coronary heart disease (CHD); cerebrovascular diseases; renovascular hypertension; chronic heart failure (IV functional class according to the NYHA classification); with hyperuricemia (especially accompanied by gout and urate nsphrolithiasis); blood pressure lability; during hemodialysis using high-flow polyacrylonitrile membranes (risk of developing anaphylactoid reactions); before the LDL apheresis procedure using dextrin sulfate; simultaneously with desensitizing therapy with allergens (for example, hymenoptera venom); in a condition after kidney transplantation; stenosis of the aortic and/or mitral valve, hypertrophic obstructive cardiomyopathy; in elderly patients. Patients with a history of angioedema not associated with taking ACE inhibitors may have an increased risk of developing it when taking drugs of this group. In patients of the Negroid race, angioedema develops more often than in patients of other races.

Use in children

Perindopril plus Indapamide is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of its use.

Restrictions for children

Contraindicated

Use in elderly patients

For elderly patients, the initial dose of Perindopril plus Indapamide is 0.625 mg/2 mg (1 tablet) 1 time/day.

In elderly patients, renal function and plasma potassium levels should be assessed before starting Perindopril plus Indapamide. The initial dose of Perindopril plus Indapamide is selected depending on the degree of reduction in blood pressure, especially with a decrease in blood volume and in chronic heart failure (functional class IV according to the NYHA classification). Such measures help to avoid a sharp decrease in blood pressure.

Restrictions for elderly patients

Use with caution

Use for liver dysfunction

In patients with moderate liver dysfunction, no dose adjustment is required. In patients with severe liver dysfunction, the use of Perindopril plus Indapamide is contraindicated.

Restrictions for liver dysfunction

Use with caution

Use during pregnancy and breastfeeding

Perindopril plus Indapamide is contraindicated during pregnancy.

If you are planning pregnancy or if it occurs while taking the drug, you should immediately stop taking the drug and prescribe other antihypertensive therapy. There have been no adequate controlled studies of ACE inhibitors in pregnant women. The limited available data on the effects of the drug in the first trimester of pregnancy indicate that the drug did not lead to malformations associated with fetotoxicity.

It is not recommended to use the drug Perindopril plus Indapamide in the first trimester of pregnancy. Perindopril plus Indapamide is contraindicated in the second and third trimesters of pregnancy.

It is known that long-term exposure of the fetus to ACE inhibitors in the second and third trimesters of pregnancy can lead to disruption of its development (decreased renal function, oligohydramnios, delayed ossification of the skull bones) and the development of complications in the newborn (such as renal failure, arterial hypotension, hyperkalemia).

Long-term use of thiazide diuretics in the third trimester of pregnancy can cause hypovolemia in the mother and a decrease in uteroplacental blood flow, which leads to fetoplacental ischemia and fetal growth retardation. In rare cases, while taking diuretics shortly before birth, newborns develop hypoglycemia and thrombocytopenia.

If the patient received Perindopril plus Indapamide in the second or third trimesters of pregnancy, it is recommended to conduct an ultrasound examination of the fetus to assess the condition of the skull bones and kidney function.

In newborns whose mothers received therapy with ACE inhibitors, arterial hypotension may be observed, and therefore newborns should be under close medical supervision.

Perindopril plus Indapamide is contraindicated during breastfeeding. It is unknown whether perindopril is excreted into breast milk.

Indapamide is excreted in breast milk. Taking thiazide diuretics causes a decrease in the amount of breast milk or suppression of lactation. In this case, the newborn may develop increased sensitivity to sulfonamide derivatives, hypokalemia and nuclear jaundice.

If it is necessary to use the drug Perindopril plus Indapamide during breastfeeding, breastfeeding should be discontinued.

Restrictions when breastfeeding

Contraindicated

Restrictions during pregnancy

Contraindicated

Use for renal impairment

Patients with renal failure (creatinine clearance 60 ml/min or more) do not require dose adjustment. For patients with CC 30-60 ml/min, the maximum dose of Perindopril plus Indapamide is 0.625 mg/2 mg (1 tablet) 1 time/day; treatment should begin with selection of doses of perindopril and indapamide in monotherapy. When CC is less than 30 ml/min, the use of Perindopril plus Indapamide is contraindicated (see section “Contraindications”).

Restrictions for impaired renal function

Use with caution

Storage conditions

In a place protected from light at a temperature not exceeding 25°C. Keep out of the reach of children.

Terms of sale

On prescription.

special instructions

Perindopril plus Indapamide

The simultaneous use of Perindopril plus Indapamide with lithium preparations is not recommended.

Therapy with Perindopril plus Indapamide is contraindicated in patients with severe renal failure (creatinine clearance less than 30 ml/min). In some patients with arterial hypertension without previous renal impairment, symptoms of acute renal failure may appear during therapy with Perindopril plus Indapamide. In this case, treatment with Perindopril plus Indapamide should be discontinued. In the future, you can resume combination therapy using low doses of Perindopril plus Indapamide, or use Perindopril and Indapamide in monotherapy. Such patients require regular monitoring of potassium levels and serum creatinine concentrations every 2 weeks after the start of therapy and every subsequent 2 months of therapy with Perindopril plus Indapamide. Acute renal failure often develops in patients with severe chronic heart failure or underlying renal impairment, incl. with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney. Perindopril plus Indapamide is not recommended for patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney.

Hyponatremia is associated with a risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in plasma electrolytes, for example, after prolonged diarrhea or vomiting. Such patients require regular monitoring of plasma electrolytes.

With a pronounced decrease in blood pressure, intravenous administration of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After restoration of blood volume and blood pressure, you can resume therapy with Perindopril plus Indapamide, using low doses of the drug, or using perindopril and indapamide in monotherapy.

The combined use of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal failure. As in the case of the combined use of antihypertensive drugs and a diuretic, regular monitoring of potassium levels in the blood plasma is necessary.

Perindopril

In patients taking ACE inhibitors, cases of neutropenia/agranulocytosis, thrombocytopenia and anemia may develop. In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves spontaneously after discontinuation of ACE inhibitors.

Perindopril should be used with extreme caution in patients with connective tissue diseases and concomitantly receiving immunosuppressive therapy, allopurinol or procainamide, especially with existing renal impairment. Such patients may develop a severe infection that does not respond to intensive antibiotic therapy. If perindopril is prescribed, it is recommended to periodically monitor the number of leukocytes in the blood. The patient should be warned that if any signs of an infectious disease appear (sore throat, fever), consult a doctor immediately.

When taking ACE inhibitors, incl. perindopril, in rare cases, the development of angioedema of the face, lips, tongue, uvula, and/or larynx may occur. If these symptoms appear, the drug should be stopped immediately. The patient's condition should be monitored until signs of edema completely disappear.

If angioedema affects only the face and lips, its symptoms usually resolve on their own, or antihistamines can be used to treat symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death. If symptoms of angioedema appear, you should immediately administer subcutaneous epinephrine (adrenaline) at a dilution of 1:1000 (0.3 or 0.5 ml) and/or ensure airway patency.

In patients with a history of angioedema not associated with taking ACE inhibitors. The risk of its development may be increased when taking drugs from this group. In patients of the Negroid race, angioedema develops more often than in patients of other races.

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal C-1-esterase levels. The diagnosis is made using computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after stopping ACE inhibitors. In patients with abdominal pain receiving ACE inhibitors, the possibility of developing angioedema of the intestine must be taken into account when making a differential diagnosis. There are isolated reports of the development of prolonged, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions undergoing desensitization procedures. Prescription of an ACE inhibitor should be avoided in patients receiving immunotherapy with hymenoptera venom. However, the development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before starting the desensitization procedure.

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LINI apheresis using dskstran sulfate. To prevent an apaphenlactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flux membranes.

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flux membranes (eg, AN69®). Therefore, it is advisable to use a different type of membrane or use an antihypertensive drug of a different pharmacotherapeutic group. During therapy with an ACE inhibitor, a dry cough may occur, which disappears after discontinuation of drugs in this group. If a dry cough appears, you should be aware of the possible connection of this symptom with taking an ACE inhibitor. If the physician believes that ACE inhibitor therapy is necessary for the patient, Perindopril plus Indapamide may be continued.

With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension. Chronic heart failure may significantly activate the renin-angiotensin-aldosterone system (RAAS), especially with severe hypovolemia and a decrease in the content of electrolytes in the blood plasma (against the background of a salt-free diet or long-term use of diuretics).

The use of an ACE inhibitor causes blockade of the RAAS, and therefore a sharp decrease in blood pressure and/or an increase in serum creatinine is possible, indicating the development of acute renal failure, which is more often observed when taking the first dose of Perindopril plus Indapamide or during the first 2 weeks of therapy.

When prescribing Perindopril plus Indapamide to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy.

Perindopril (like other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the Negroid race compared to representatives of other races.

The use of ACE inhibitors in patients undergoing surgery under general anesthesia can lead to a significant decrease in blood pressure, especially when using general anesthetic agents that have an antihypertensive effect.

It is recommended to stop taking ACE inhibitors, incl. perindopril, 12 hours before surgery, warning the anesthesiologist about the use of ACE inhibitors.

ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction and with aortic and/or mitral stenosis and HOCM (hypertrophic obstructive cardiomyopathy).

In rare cases, while taking ACE inhibitors, cholestatic jaundice occurs, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice or a significant increase in the activity of liver transaminases occurs while taking ACE inhibitors, Perindopril plus Indapamide should be discontinued.

In patients after kidney transplantation or in patients on hemodialysis, anemia may develop.

During treatment with ACE inhibitors, incl. and perindopril may develop hyperkalemia. Risk factors for hyperkalemia are renal failure, old age, diabetes mellitus, some concomitant conditions (decrease in blood volume, acute heart failure in the stage of decompensation, metabolic acidosis), simultaneous use of potassium-sparing diuretics (such as spironolactone, zplerenone, triamterene, amiloride), as well as drugs potassium or potassium-containing substitutes for table salt and the use of other drugs that increase the content of potassium in the blood plasma (for example, heparin). Hyperkalemia can cause serious heart rhythm problems, sometimes fatal. The combined use of the drugs listed above is not recommended; if their use is necessary, therapy should be carried out with extreme caution.

Indapamide

There are reports of cases of increased photosensitivity while taking thiazide and thiazide-like diuretics. If a photosensitivity reaction develops while taking Perindopril plus Indapamide, treatment should be discontinued. If it is necessary to resume the use of Perindopril plus Indapamide, exposed skin should be protected from direct exposure to sunlight and artificial ultraviolet rays.

Before starting treatment with Perindopril plus Indapamide, it is necessary to determine the sodium content in the blood plasma and, while taking the drug, regularly monitor electrolytes in the blood plasma (especially in elderly patients). All diuretics can cause hyponatremia, leading to serious complications.

Therapy with thiazide and thiazide-like diuretics is associated with a risk of developing hypokalemia (less than 3.4 mmol/l) in elderly patients, malnourished patients, patients with liver cirrhosis, patients with peripheral edema, ascites, coronary artery disease, and chronic heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of developing arrhythmia. The high-risk group includes patients with an increased QT interval on the ECG. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially ventricular arrhythmias, which can be fatal. In all the described cases, regular monitoring of potassium levels in the blood plasma is necessary. The first determination of potassium in the blood plasma should be carried out within the first week of starting therapy with Perindopril plus Indapamide,

Hyazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in plasma calcium. Severe hypercalcemia may be a consequence of latent hyperparathyroidism. Before studying the function of the parathyroid glands, you should stop taking the drug I crindopril plus Indapamide.

Glucose concentrations should be monitored in patients with diabetes mellitus. In patients with increased concentrations of uric acid in the blood plasma during therapy with Perindopril plus Indapamide, an increase in the frequency of exacerbations of podapha may occur.

Hypovolemia as a result of decreased blood volume or hyponatremia. caused by taking diuretics, at the beginning of treatment with Perindopril plus Indapamide can lead to a decrease in glomerular filtration rate and be accompanied by an increase in the content of creaginine and urea in the blood plasma.

Indapamide may give a false-positive reaction during doping control.

Use in pediatrics

Perindopril plus Indapamide is contraindicated in children and adolescents under 18 years of age due to the lack of data on the effectiveness and safety of its use.

Impact on the ability to drive vehicles and machinery

Care must be taken when driving vehicles and other technical devices that require increased attention and speed of psychomotor reactions.

Side effect

Classification of the frequency of side effects (WHO): very common (>1/10). often (from >1/100 to 1/1000 to 1/10,000 to

From the hematopoietic system:

infrequently - eosinophilia, hyponatremia, very rarely - thrombocytopenia, leukopeia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (kidney transplant patients, hemodialysis patients), ACE inhibitors may cause anemia.

From the side of the central nervous system:

often - paresthesia, headache, dizziness, vertigo; infrequently - sleep disturbance, mood lability; very rarely - confusion; frequency unknown - fainting.

From the side of the organ of vision:

often - visual impairment.

On the part of the hearing organ:

often - tinnitus.

From the cardiovascular system:

uncommon - marked decrease in blood pressure (including orthostatic hypotension), palpitations; very rarely - cardiac arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation), angina pectoris and myocardial infarction, possibly due to an excessive decrease in blood pressure in high-risk patients; frequency unknown - ari (possibly fatal), increased QT interval on the ECG.

From the respiratory system:

often - during the use of ACE inhibitors, a dry cough may occur, which persists for a long time while taking drugs of this group and disappears after their withdrawal, shortness of breath; uncommon - bronchospasm; very rarely - eosiophilic pneumonia, rhinitis.

From the digestive system:

often - dryness of the oral mucosa, nausea, vomiting, abdominal pain, epigastric pain, impaired taste perception, decreased appetite, dyspepsia, constipation, diarrhea: very rarely - pancreatitis, angioedema of the intestine, cholestatic jaundice; frequency unknown - hepatic encephalopathy in patients with liver failure, increased activity of liver transaminases.

From the skin:

often - skin rash, itching, maculopapular rash; uncommon - angioedema of the face, lips, extremities, mucous membrane of the tongue, vocal folds and/or larynx, urticaria, hypersensitivity reactions in patients predisposed to broncho-obstructive and allergic reactions, hemorrhagic vasculitis. In patients with acute form of systemic lupus erythematosus, the course of the disease may worsen; very rarely - erythema multiforme, toxic epidermal necrolysis. Stevens-Johnson syndrome. Cases of photosensitivity reactions have been reported.

From the musculoskeletal system:

often - muscle spasms.

From the urinary system:

uncommon - renal failure; very rarely - acute renal failure, frequency unknown - hepatitis.

From the reproductive system:

infrequently - erectile dysfunction.

Laboratory indicators:

rarely - hypercalcemia; frequency unknown - hypokatemia, especially significant for patients at risk; hyponatremia and gyvolemia, leading to dehydration and orthostatic hypotension; increase in the concentration of uric acid and glucose in the blood while taking the drug: a slight increase in the concentration of creatinine in the urine and in the blood plasma, which occurs after discontinuation of therapy, more often in patients with renal artery stenosis, when treating hypertension with diuretics and in the case of renal failure; hyperkalemia, often transient.

Other:

often - asthenia; infrequently - increased sweating.

When using ACE inhibitors, a syndrome of impaired secretion of antidiuretic hormone was rarely observed.