Perindopril PLUS Indapamide pills 0.625mg + 2mg 30pcs

Composition

1 tablet contains:

Active ingredients:

Indapamide 0.625 mg;

Perindopril erbumin 2 mg.

Auxiliary substances:

Microcrystalline cellulose – 70.375 mg;

Pre-gelatinized corn starch-15 mg;

Crospovidone – 10 mg;

Magnesium stearate – 1 mg;

Colloidal silicon dioxide – 1 mg

Pharmacological action

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 that does not depend on the patient’s age and body position and is not accompanied by reflex tachycardia. It does not affect the metabolism of lipids (total cholesterol, low-density lipoproteins (LDL), very low-density lipoproteins (VLDL), high-density lipoproteins (HDL), triglycerides (TG) and carbohydrates), including in patients with diabetes mellitus. Reduces the risk of hypokalemia due to diuretic monotherapy.

The antihypertensive effect persists for 24 hours.

A stable reduction in blood pressure (BP) is achieved within 1 month with the use of Perindopril PLUS Indapamide without increasing the heart rate (HR). Discontinuation of treatment does not lead to the development of “withdrawal”syndrome.

Perindopril is an ACE inhibitor, the mechanism of action of which is associated with inhibition of ACE activity, leading to a decrease in the formation of angiotensin II, eliminates the vasoconstrictor effect of angiotensin II, reduces the secretion of aldosterone. The use of perindopril does not lead to sodium and fluid retention, does not cause reflex tachycardia during long-term treatment. The hypotensive effect of perindopril develops in patients with low or normal plasma renin activity. Perindopril acts through its main active metabolite, perindoprilate. Its other metabolites are inactive.

The effect of perindopril leads to dilation of the veins (reduced preload on the heart), due to changes in prostaglandin metabolism; a decrease in total peripheral vascular resistance (OPSS) (reduced afterload on the heart).

In patients with heart failure, perindopril reduces the filling pressure of the left and right ventricles; increases cardiac output and cardiac index; and increases regional blood flow in the muscles.

Perindopril is effective in patients with arterial hypertension of any severity: mild, moderate and severe.

The maximum hypotensive effect develops in 4-6 hours after a single oral use and persists throughout the day.

Discontinuation of therapy does not lead to the development of “withdrawal”syndrome.

It has vasodilating properties and restores the elasticity of large arteries. The addition of a thiazide-like diuretic enhances the hypotensive (additive) effect of perindopril.

Indapamide is a sulfonamide derivative and is a diuretic. It inhibits sodium reabsorption in the cortical segment of the renal tubules, increasing the excretion of sodium and chlorine by the kidneys, thus leading to increased diuresis. Increases the excretion of potassium and magnesium to a lesser extent. Having the ability to selectively block slow calcium channels, indapamide increases the elasticity of arterial walls and reduces OPSS. It has an antihypertensive effect in doses that do not have a pronounced diuretic effect. Increasing the dose of indapamide does not increase the hypotensive effect, but increases the risk of adverse events. Indapamide in patients with arterial hypertension does not affect the metabolism of lipids – TG, LDL and HDL; on the metabolism of carbohydrates, even in patients with diabetes mellitus and arterial hypertension.

Pharmacokinetics:

The combined use of perindopril and indapamide does not change their pharmacokinetic parameters, compared with separate use of these drugs.

Perindopril

Suction

After oral use, perindopril is rapidly absorbed from the gastrointestinal tract (GIT). Bioavailability is 65-70%. The maximum concentration (Cmax) in blood plasma is reached 3-4 hours after oral use.

Food intake reduces the conversion of perindopril to perindoprilate and the bioavailability of perindopril, so it should be taken 1 time / day in the morning, before breakfast. When taking perindopril 1 time/day. Equilibrium Concentration (Css) reached within 4 days.

Distribution

Binding to plasma proteins of perindoprilat is dose-dependent and amounts to 20%. Perindoprilat easily passes through histohematic barriers, excluding the blood-brain barrier (BBB). It doesn’t accumulate.

Metabolism

It is metabolized in the liver to form the active metabolite perindoprilate. In addition,5 more inactive metabolites are formed.

Deduction

The half-life (T 1/2) of perindopril from blood plasma is 1 h. T 1/2 of perindoprilat is about 17 h. It is excreted by the kidneys.

Pharmacokinetics in special patient groups

In elderly patients, in patients with renal and heart failure, the elimination of perindoprilat is slowed down.

The dialysis clearance of perindoprilat is 70 ml/min.

The kinetics of perindopril was altered in patients with cirrhosis of the liver: hepatic clearance was reduced by half. However, the amount of perindoprilate produced does not decrease, which does not require dose adjustment.

Indapamide

Suction

After oral use, it is rapidly and almost completely absorbed from the gastrointestinal tract. Food intake slightly slows down absorption, but does not significantly affect the amount of indapamide absorbed. After oral use in a single dose, Cmax in blood plasma is reached in 1 h.

Distribution

Binding to plasma proteins is 79%. It doesn’t accumulate.

Metabolism

It is metabolized in the liver.

Elimination

of T 1/2 is from 14 to 24 hours (on average,18 hours). It is excreted by the kidneys (70%) mainly in the form of metabolites (the fraction of unchanged drug is about 5%) and by the intestines with bile in the form of inactive metabolites (22%).

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, the pharmacokinetic parameters of indapamide do not change significantly.

Indications

Arterial hypertension.

Contraindications

• Hypersensitivity to excipients that are part of the drug;

• Severe renal insufficiency (creatinine clearance <30 ml / min);

• Concomitant 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 undergoing hemodialysis, as well as in patients with untreated heart failure in the decompensation stage;

• Age up to 18 years (efficacy and safety have not been established).

With caution:

• The drug should be used for systemic connective tissue diseases (including systemic lupus erythematosus, scleroderma);

• Against the background of immunosuppressant therapy (risk of neutropenia, agranulocytosis); with inhibition of bone marrow hematopoiesis;

• Reduced circulating blood volume (BCC) (due to taking diuretics, a diet with a restriction of table salt, vomiting, diarrhea);

• Coronary heart disease (CHD);

• Cerebrovascular diseases;

• Renovascular hypertension;

• Chronic heart failure (NYHA functional Class IV);

• With hyperuricemia (especially accompanied by gout and urate nsfrolithiasis);

• Blood pressure lability.

• Hemodialysis with high-flow polyacrylonitrile membranes (risk of anaphylactoid reactions);

• Before the procedure of LDL apheresis with dextrin sulfate;wbr>Simultaneously with desensitizing allergen therapy (for example, hymenopteran insect venom);

• In the condition after kidney transplantation;

• Aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy;

• In elderly patients.

• Patients who have a history of angioedema that is not associated with ACE inhibitors may have an increased risk of developing angioedema when taking this group of drugs.

Patients of the black race develop angioedema more often than patients of other races.

Side effects

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

From the hematopoietic system:  infrequently – eosinophilia, hyponatremia, very rarely – thrombocytopenia, leukopeia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia. In certain clinical situations (patients after kidney transplantation, patients on hemodialysis), ACE inhibitors can cause anemia.

From 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 visual organ: often-visual impairment.

From the side of the hearing organ: often-tinnitus.

From the cardiovascular system: rarely, marked reduction in blood pressure (including orthostatic hypotension), palpitations; very rarely, arrhythmias (including bradycardia, ventricular tachycardia, atrial fibrillation), angina and myocardial infarction, possibly due to excessive blood pressure lowering in patients at high risk; the frequency is unknown – arrhythmia type “pirouette” (possibly fatal), an increase of the QT interval on the ECG.

Respiratory system disorders: often-against the background of the use of ACE inhibitors, a dry cough may occur, which persists for a long time during taking drugs of this group and disappears after their withdrawal, shortness of breath; infrequently – bronchospasm; very rarely – eoshiophilic 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 hepatic insufficiency, increased activity of “liver” transaminases.

From the side of the skin: often-skin rash, pruritus, maculopapular rash; infrequently-angioedema of the face, lips, limbs, tongue mucosa, vocal folds and / or larynx, urticaria, hypersensitivity reactions in patients predisposed to bronchial and allergic reactions, hemorrhagic vasculitis. Patients with acute systemic lupus erythematosus may worsen the course of the disease; very rarely – erythema multiforme, toxic epidermal necrolysis. Stevens-Johnson syndrome. Cases of photosensitivity reactions have been reported.

Musculoskeletal disorders: often-muscle spasms.

From the urinary system: infrequently – renal failure; very rarely-acute renal failure, frequency unknown-hepatitis.

From the side of the reproductive system: infrequently – erectile dysfunction.

Laboratory parameters: rarely – hypercalcemia; frequency unknown – hypokatiemia, especially significant for patients at risk; hyponatremia and gynovolemia, leading to dehydration and orthostatic hypotension; increased uric acid and glucose concentrations in the blood during drug use: a slight increase in creatinine concentrations in the urine and in the blood plasma, passing after discontinuation of therapy, more often in patients with renal artery stenosis, in the treatment of arterial hypertension with diuretics and in the case of renal failure hyperkalemia, often transient.

Other services: often-asthenia; infrequently-increased sweating.

When using ACE inhibitors, the syndrome of impaired aitidiuretic hormone secretion was rarely observed.

Interaction

Simultaneous use is not recommended

Lithium preparations: Reversible increases in serum lithium concentrations have been reported. The risk of its toxic effect increases when taking an ACE inhibitor.

Concomitant use of a combination of perindopril and indapamide with lithium preparations is not recommended.

In the case of therapy, it is necessary to monitor the concentration of lithium in the blood plasma.

Special care should be taken when using the drug at the same time

Baclofen: potentiates the antihypertensive effect (requires monitoring of blood pressure, renal function and, if necessary, dose adjustment Perindopril PLUS Indapamide).

Combination of ACE inhibitors with non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-2) inhibitors and non-selective NSAIDs, acetylsalicylic acid in doses that have an anti-inflammatory effect) reduces the antihypertensive effect of ACE inhibitors; increases the risk of impaired renal function, up to the development of acute renal failure; increases the content of potassium in the blood serum in patients with pre-existing renal dysfunction.

This combination is recommended to be used with caution, especially in elderly patients.

Patients should be compensated for BCC, as well as monitor renal function before and after treatment. Perindoprilom PLUS Indapamide.

Caution should be exercised when used concomitantly

Tricyclic antidepressants, antipsychotics (neuroleptics) enhance the antihypertensive effect and increase the risk of orthostatic hypotension (additive effect).

Glucocorticosteroids (corticosteroids), tetracosactide reduce the antihypertensive effect (fluid retention).

When used concomitantly with other antihypertensive agents, the antihypertensive effect of the drug may increase.

Perindopril

Simultaneous use is not recommended

ACE inhibitors reduce the diuretic-induced loss of potassium in the kidneys.

With the combined use of potassium-sparing diuretics (spironolactone, triamterene. amiloride. eplerenone), potassium preparations or potassium-containing salt substitutes with ACE inhibitors may increase the content of potassium in the blood serum up to a fatal outcome.

If the combined use of an ACE inhibitor and the above drugs is necessary (in the case of confirmed hypokalemia), caution should be exercised and regular monitoring of the potassium content in the blood plasma and ECG parameters should be carried out.

Concomitant use of ACE inhibitors and angiotensin II receptor antagonists with aliskiren is contraindicated in patients with diabetes mellitus and patients with moderate renal insufficiency (creatinine clearance less than 60 ml / min).

Concomitant use with estramustine increases the risk of angioedema.

Special care should be taken when using the drug at the same time

The use of ACE inhibitors may increase the hypoglycemic effect of oral hypoglycemic agents (sulfonylurea derivatives) and insulin in patients with diabetes mellitus; when they are used together, glucose tolerance may increase, which may require dose adjustment of oral hypoglycemic agents and insulin.

Baclofen enhances the antihypertensive effect of ACE inhibitors.

With the simultaneous use of potassium-sparing diuretics, gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin) – the risk of angioedema due to the suppression of dipeptidyl peptidase IV activity by gliptin.

When used concomitantly with sympathomimetics, it enhances the antihypertensive effect of ACE inhibitors.

There are reports that patients with established atherosclerotic disease, heart failure or diabetes mellitus, with a lesion of target organs, concomitant therapy with ACE inhibitor and AR is associated with a higher frequency of hypotension, syncope, hyperkalemia and deterioration of renal function (including acute renal failure) as compared with using only one drug that affect the RAAS.

Double blockade (for example, when an ACE inhibitor is combined with ARAII) should be limited to individual cases with careful monitoring of renal function, potassium content and blood pressure.

Caution should be exercised when used concomitantly

Concomitant use of allopurinol, cytostatics, immunosuppressants, corticosteroids (for systemic use), procainamide with ACE inhibitors may increase the risk of leukopenia.

In patients whose condition requires extensive surgery or general anesthesia with drugs that cause hypotension, ACE inhibitors, including perindopril, can block the formation of angiotensin II with compensatory renin release.

The day before surgery or ACE inhibitor therapy should be discontinued.

If the ACE inhibitor cannot be discontinued, then hypotension, which develops according to the described mechanism, can be corrected by increasing the BCC.

When using diuretics in high doses, hypovolemia is possible (due to a decrease in BCC), and the addition of perindopril to therapy leads to a pronounced decrease in blood pressure.

When prescribing ACE inhibitors, including perindopril. patients receiving the gold preparation (sodium aurothiomalate) intravenously experienced nitrate-like reactions (nausea, vomiting, marked decrease in blood pressure, hyperemia of the facial skin).

Indapamide

Special care should be taken when using the drug at the same time

Due to the risk of hypokalemia, indapamide should be used with caution in combination with drugs that cause ventricular arrhythmia of the “pirouette” type, such as antiarrhythmics (quinidine, hydroquinidine, disopyramide, amiodarone, dofetilide, ibutilide, bretilia tosilate, sotalol), some neuroleptics (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenone (droperidol, haloperidol), other neuroleptics (pimozide); other substances such as bepridil, cisapride, difemanyl methylsulfate, erythromycin (iv), halofantrin, mizolastine, moxifloxacin, pentamidine, sparfloxacin, vincamine for intravenous use, methadone, astemizole, terfenadine.

It is necessary to monitor the potassium content in order to avoid hypokalemia, with the development of which it is necessary to correct it, monitor the QT interval on the ECG.

With simultaneous use of indapamide with amphotericin (IV), gluco-and mineralocorticoids (with systemic use), tetracosactide. laxatives that stimulate the motility of the gastrointestinal tract increase the risk of hypokalemia (additive effect).

It is necessary to monitor the content of potassium in the blood plasma, if necessary – its correction.

Special attention should be paid to patients receiving concomitant cardiac glycosides.

Laxatives that do not stimulate the motility of the gastrointestinal tract should be used.

Hypokalemia increases the toxic effect of cardiac glycosides.

With simultaneous use of indapamide and cardiac glycosides, the content of potassium in the blood plasma, ECG indicators should be monitored and, if necessary, the dose of cardiac glycosides should be adjusted.

Caution should be exercised when used concomitantly

When using metformin with diuretics, renal failure may develop.

Concomitant use with metformin increases the risk of lactic acidosis.

Do not use metformin if the serum creatinine concentration exceeds 15 mg / l in men and 12 mg/l in women.

Against the background of taking diuretics, BCC decreases, and the risk of acute renal failure increases, especially when using high-dose iodine-containing contrast agents.

Before using iodine-containing contrast media, it is necessary to compensate for BCC.

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

Concomitant use with cyclosporine increases the risk of developing impaired renal function (hypercreatininemia).

How to take, course of use and dosage

Assign inside 1 time/day. preferably in the morning hours before breakfast, with a sufficient amount 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 insufficiency (creatinine clearance 60 ml / min or more) no dose adjustment is required. For patients with creatinine clearance 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 the selection of doses of perindopril and indapamide in the monotherapy mode. When creatinine clearance is less than 30 ml / min, the use of Perindopril plus Indapamide is contraindicated (see the section “Contraindications”).

No dose adjustment is required in patients with moderate hepatic impairment. Perindopril plus Indapamide is contraindicated in patients with severe hepatic impairment.

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 evaluated 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 BCC and with chronic heart failure (NYHA functional class IV). The risk of arterial hypotension

exists in all patients, but special care should be taken when using the drug Perindopril plus Indapamide in patients with coronary heart disease and cerebral circulatory 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 initiated in a hospital setting with a dose of 0.625 mg / 2 mg under the control of renal function and blood potassium content. Some patients may develop acute renal failure, which is reversible after discontinuation of the drug.

In patients with chronic heart failure (NYHA functional Class IV), treatment with Perindopril plus Indapamide should begin with an initial dose of 0.625 mg / 2 mg under medical supervision.

Special instructions

It is not recommended to use the drug simultaneously with lithium preparations.

Therapy Perindoprilom PLUS Indapamide is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min).

In some patients with arterial hypertension without previous renal impairment, symptoms of acute renal failure may occur during therapy with the drug. In this case, treatment with this drug should be discontinued. In the future, you can resume combination therapy using low doses. Perindopril PLUS Indapamide, or use perindopril and indapamide in monotherapy. Such patients should be regularly monitored for potassium and serum creatinine levels every 2 weeks after starting therapy and every subsequent 2 months of therapy Perindoprilom PLUS Indapamide.

Acute renal failure is more likely to occur in patients with severe chronic heart failure or underlying renal dysfunction, including bilateral renal artery stenosis or artery stenosis of a single functioning kidney.

The drug is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney. Hyponatremia is associated with the risk of a sudden decrease in blood pressure (especially in patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney). Therefore, during dynamic monitoring of patients, attention should be paid to possible symptoms of dehydration and a decrease in the content of electrolytes in the blood plasma, for example, after prolonged diarrhea or vomiting. Such patients need regular monitoring of electrolytes in the blood plasma.

With a marked decrease in blood pressure, an intravenous injection of 0.9% sodium chloride solution may be required.

Transient arterial hypotension is not a contraindication for further continuation of therapy. After BCC and BP are restored, Perindopril therapy can be resumed 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 insufficiency. As with the combined use of antihypertensive agents and diuretics, regular monitoring of the potassium content in the blood plasma is necessary.

Perindopril

Patients taking ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia.

In patients with normal renal function in the absence of other complications, neutropenia rarely develops and resolves independently after the withdrawal of ACE inhibitors.

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

When taking ACE inhibitors, including perindopril, in rare cases, angioedema of the face, lips, tongue, uvula of the upper palate, and/or larynx may develop. If these symptoms occur, the drug should be discontinued immediately. The patient’s condition should be monitored until the signs of edema disappear completely.

If angioedema affects only the face and lips, then its manifestations usually go away on their own or antihistamines can be used to treat the symptoms. Angioedema, accompanied by swelling of the tongue or larynx, can lead to airway obstruction and death.

If symptoms of angioedema appear, epinephrine (epinephrine) should be immediately administered subcutaneously at a dilution of 1: 1000 (0.3 or 0.5 ml) and / or airway patency should be ensured. Patients who have a history of angioedema that is not associated with ACE inhibitors may have an increased risk of developing angioedema when taking this group of drugs.

Patients of the black race develop angioedema more often than patients of other races. In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. At the same time, patients have 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 levels of C-1 esterase.

The diagnosis is established by computed tomography of the abdominal cavity, ultrasound, or at the time of surgery. Symptoms disappear after discontinuation of ACE inhibitors. In patients with abdominal pain treated with ACE inhibitors, the differential diagnosis should take into account the possibility of developing angioedema of the intestine.There are isolated reports of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in patients prone to allergic reactions, undergoing desensitization procedures.

Avoid prescribing an ACE inhibitor to patients receiving hymenopteran venom immunotherapy. However, the development of anaphylactoid reactions can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure.

In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis with dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be discontinued before each LDL apheresis procedure using high-flow membranes.

Anaphylactoid reactions have been reported in patients receiving ACE inhibitors during hemodialysis using high-flow membranes (for example, AN69R). Therefore, it is advisable to use a different type of membrane or use a hypotensive drug of a different pharmacotherapeutic group.

Against the background of therapy with an ACE inhibitor, a dry cough may occur, which disappears after the withdrawal of drugs of this group. If a dry cough occurs, you should be aware of the possible association of this symptom with taking an ACE inhibitor. If the doctor believes that therapy with an ACE inhibitor is necessary for the patient, the following procedure is recommended: Perindopril PLUS Indapamide can be continued.

With cirrhosis of the liver, accompanied by edema and ascites, arterial hypotension, and chronic heart failure, significant activation of the renin-angiotensin-aldosterone system (RAAS) is possible, especially with severe hypovolemia and a decrease in the content of electrolytes in 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 may occur, indicating the development of acute renal failure, which is more often observed with the first dose. Perindopril PLUS Indapamide or during the first 2 weeks of therapy.

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral use or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood. Perindopril (like other ACE inhibitors) has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races.

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

It is recommended to stop taking ACE inhibitors, including 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 exit tract obstruction and in patients with aortic and / or mitral stenosis and HOCMP (hypertrophic obstructive cardiomyopathy). In rare cases, cholestatic jaundice occurs while taking ACE inhibitors, with the progression of which fulminant liver necrosis develops, sometimes with a fatal outcome. If jaundice or a significant increase in the activity of “hepatic” transaminases occurs while taking ACE inhibitors, take Perindopril PLUSIndapamide should be discontinued.

Post-kidney transplant patients or patients undergoing hemodialysis may develop anemia. Hyperkalemia may occur during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, advanced age, diabetes mellitus, certain concomitant conditions (decreased BCC, acute heart failure in the decompensation stage, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), as well as potassium preparations or potassium-containing salt substitutes, and the use of other drugs that increase the potassium content in blood plasma (for example, heparin). Hyperkalemia can lead to serious cardiac arrhythmias, sometimes fatal. The combined use of the above drugs is not recommended, and if necessary, their use should be carried out with extreme caution.

Indapamide

Increased photosensitivity has been reported with thiazide and thiazide-like diuretics. With the development of a photosensitivity reaction against the background of taking Perindopril PLUS Indapamide treatment should be discontinued. If it is necessary to resume the use of the drug, protect the exposed areas of the skin from direct exposure to solar and artificial ultraviolet rays and avoid exposure to the sun.

Before starting treatment Perindoprilom PLUS With indapamide, it is necessary to determine the sodium content in the blood plasma and, while taking the drug, regularly monitor the electrolytes in the blood plasma (especially in elderly patients). All diuretics can cause hyponatremia, leading to serious complications. Treatment with thiazide and thiazide-like diuretics is associated with a risk of hypokalemia (less than 3.4 mmol/k) in elderly patients, emaciated patients, patients with cirrhosis of the liver, patients with peripheral edema, ascites, CHD, chronic heart failure.

Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia. The increased risk group includes patients with an extended QT interval on the ECG. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, especially ventricular arrhythmia of the “pirouette” type, which can be fatal. In all these cases, regular monitoring of the potassium content in the blood plasma is necessary. The first determination of the potassium content in the blood plasma should be carried out within the first week after the start of therapy with the drug.

Thiazide and thiazide-like diuretics reduce the excretion of calcium by the kidneys, leading to a slight and temporary increase in the content of calcium in the blood plasma. Severe hypercalcemia may be a consequence of latent hyperparathyroidism. Before studying the function of the parathyroid glands, you should cancel the reception Perindopril PLUS Indapamide. Glucose concentrations should be monitored in patients with diabetes mellitus.

In patients with an increased concentration of uric acid in the blood plasma against the background of drug therapy, an increase in the frequency of exacerbation of the course of gout is possible.

Hypovolemia due to a decrease in BCC or hyponatremia caused by taking diuretics at the beginning of treatment with the drug may lead to a decrease in the glomerular filtration rate and be accompanied by an increase in the content of creatinine and urea in blood plasma.

Indapamide may give a false positive reaction during doping control.

Application 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.

Influence on the ability to drive motor vehicles and manage mechanisms

Caution should be exercised when driving vehicles and other technical devices that require increased attention and speed of psychomotor reactions (risk of dizziness, fainting).

Active ingredient

Indapamide, Perindopril

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Angina, Heart failure, Hypertension, Prevention of heart attacks and strokes