Co-Prenessa tablets 4mg/1.25mg №10×9

Name:
Co-Prenessa. Forms of release Tablets. INN Perindopril + indapamide. FTGHypotensive combined means (APF blocker + diuretic). CompositionCo-Prenessa 2 mg/0.625 mg tablets Each tablet contains perindopril erbumine 2 mg and indapamide 0.625 mg. Co-Prenessa 4 mg/1.25 mg tablets Each tablet contains perindopril erbumine 4 mg and indapamide 1.250 mg. Excipients: calcium chloride hexahydrate, lactose monohydrate, crospovidone, microcrystalline cellulose, sodium bicarbonate, hydrated colloidal silicon dioxide, magnesium stearate.
Description:
Co-Prenessa 2 mg/0.625 mg tablets White to off-white round, slightly biconvex tablets with bevelled edges and a short line engraved on one side. Co-Prenessa 4 mg/1.25 mg tablets Round, slightly biconvex, white or almost white tablets with bevelled edges and a notch on one side. Pharmacotherapeutic group Means that affect the renin – angiotensin system. ACE inhibitors in combination with diuretics. ATX code: C09BA04. Pharmacological properties Pharmacodynamics Co-Prenessa is a complex preparation containing an angiotensin-converting enzyme (ACE) inhibitor – perindopril erbumine and a chlorosulfamoyl (thiazide-like) diuretic – indapamide. The pharmacological action of the drug is due to the properties of each of these components, taken separately, as well as the additive synergistic effect of both components when combined. Pharmacodynamic properties Associated with perindopril Perindopril is an angiotensin converting enzyme inhibitor (ACE inhibitor) that converts angiotensin I to angiotensin I, belongs to the class of vasoconstrictor substances; in addition, the enzyme stimulates the secretion of aldosterone by the adrenal cortex and stimulates the breakdown of bradykinin, a vasodilator, to inactive heptapeptides. This leads to: – a decrease in aldosterone secretion, – an increase in plasma renin activity due to a decrease in the effect of aldosterone on negative feedback, – a decrease in total peripheral resistance with a predominant effect on the vascular bed in the muscles and kidneys, without concomitant water and salt retention or reflex tachycardia with chronic treatment. The antihypertensive effect of perindopril is also seen in patients with low or normal renin levels. Perindopril acts through its active metabolite, perindoprilat. Other metabolites are inactive. Perindopril reduces the load on the heart: by a vasodilating effect on the veins, possibly caused by a change in the metabolism of prostaglandins: a decrease in preload, by a decrease in total peripheral resistance: a decrease in afterload. Studies conducted on patients with heart failure have revealed: a decrease in filling pressure of the left and right ventricle, a decrease in total peripheral vascular resistance, an increase in cardiac output and an improvement in the index of heart work, an increase in regional blood flow in the muscle. The results of the exercise test also showed an improvement. Related to indapamide Indapamide is a sulfamide derivative with an indole ring, pharmacologically belonging to the group of thiazide diuretics. Indapamide inhibits sodium reabsorption in the cortical segment. It increases the excretion of sodium and chlorides in the urine and at least the excretion of potassium and magnesium, thereby increasing diuresis and has an antihypertensive effect. Characteristics of antihypertensive action Associated with Co-Preness In patients with elevated blood pressure, regardless of age, the drug has a dose-dependent antihypertensive effect on diastolic and systolic blood pressure in both the supine and standing positions. The antihypertensive effect lasts for 24 hours. Lowering of blood pressure is achieved in less than one month without tachyphylaxis. Termination of treatment does not cause a withdrawal syndrome. During clinical studies, the simultaneous administration of perindopril and indapamide caused a synergistic antihypertensive effect relative to each drug prescribed separately. Co-Prenessa 2 mg/0.625 mg tablets only The low-dose combination of Co-Prenessa 2 mg/0.625 mg tablets on cardiovascular morbidity and mortality has not yet been studied. PICXEL, a multicentre, randomized, double-blind, active-controlled study, evaluated the effects of perindopril/indapamide combination on LVH by echocardiography compared with enalapril alone. In the PICXEL study, patients with elevated blood pressure with LVH (defined as a left ventricular mass index (LVMI) >120 g/m2 in men and >100 g/m2 in women) were randomized to either perindopril 2 mg/indapamide 0.625 mg or enalapril 10 mg once daily for one year. The dosage was adjusted according to blood pressure control up to 8 mg of perindopril and 2.5 mg of indapamide or up to 40 mg of enalapril once a day. Only 34% of patients continued treatment with perindopril 2 mg/indapamide 0.625 mg (versus 20% with enalapril 10 mg). At the end of treatment, LVMI decreased significantly more in the perindopril/indapamide group (-10.1 g/m2) than in the enalapril group (-1.1 g/m2) in all randomized groups of patients. The difference in LVMI change between groups was -8.3 (95% CI (-11.5-5.0), p<0.0001). The best effect on LVMI was achieved with the higher dose of perindopril 8 mg/indapamide 2.5 mg. With respect to blood pressure, the estimated mean intergroup differences in the randomized groups were 5.8 mm. rt. Art. (95% CI (-7.9, - 3.7), p < 0.0001) for systolic blood pressure and - 2.3 mm. rt. Art. (95% CI (-3.6, -0.9), p = 0.0004) for diastolic blood pressure, respectively, with a benefit in the perindopril/indapamide group. Associated with perindopril Perindopril is active in all stages of hypertension: mild, moderate, or severe. A decrease in systolic and diastolic blood pressure is observed both in the supine position and in the sitting position. Antihypertensive activity after a single dose reaches a maximum of 4 to 6 hours and persists for 24 hours. A high degree of residual blocking of the angiotensin-converting enzyme persists for 24 hours and is approximately 80%. In sensitive patients, normalization of blood pressure is achieved after a month of treatment and is maintained without the development of tachyphylaxis. Stopping the drug does not cause a withdrawal syndrome. Perindopril has vasodilating properties and restores the elasticity of the main arterial vessels, corrects histomorphometric changes in resistant arteries and causes a decrease in left ventricular hypertrophy. If necessary, the addition of a thiazide diuretic results in additional synergism. The combination of an angiotensin-converting enzyme inhibitor with a thiazide diuretic reduces the risk of hypokalemia associated with taking the diuretic alone. Two large randomized controlled trials (ONTARGET (Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes) examined the use of ACE inhibitors in combination with angiotensin II receptor blockers. patients suffering from cardiovascular disease and cerebrovascular disease, or type 2 diabetes mellitus, accompanied by signs of target organ damage.VA NEPHRON-D study was conducted in patients suffering from type 2 diabetes mellitus and diabetic nephropathy.Compared with monotherapy these studies did not show a significant positive effect on renal function and / or cardiovascular disease outcome and mortality, while an increased risk of hyperkalemia, acute renal failure and / or hypotension was observed.Due to similar pharmacodynamic properties, these results they are also related to other ACE inhibitors and angiotensin II receptor blockers. Therefore, ACE inhibitors and angiotensin II receptor blockers should not be used simultaneously in patients with diabetic nephropathy. The ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) study was designed to determine the benefits of adding aliskiren to standard ACE inhibitor therapy or to angiotensin II receptor blockers in patients with type 2 diabetes mellitus, chronic renal failure, cardiovascular disease. The study was terminated early due to an increased risk of adverse outcomes. Stroke and cardiovascular mortality were more common in the aliskiren group than in the placebo group. Also, in the aliskiren group, adverse reactions (hyperkalemia, hypotension, renal dysfunction) were more often observed. Associated with indapamide Indapamide in the form of monotherapy has an antihypertensive effect that lasts for 24 hours. This effect is manifested at a dose at which diuretic activity is minimal. The antihypertensive effect is proportional to the improvement in arterial elasticity and the decrease in total peripheral vascular resistance and arteriole resistance. Indapamide reduces left ventricular hypertrophy. When the dosage of a thiazide or thiazide-like diuretic is exceeded, the antihypertensive effect reaches a plateau, while the side effects of the drug continue to increase. If treatment is not effective, the dosage should not be increased. In addition, it has been shown that in short, moderate and long-term treatment, indapamide has no effect on lipid metabolism: triglycerides, LDL cholesterol and HDL cholesterol, has no effect on carbohydrate metabolism, even in patients with hypertension and diabetes mellitus. Pharmacokinetics Associated with Co-Preness The pharmacokinetic properties of the combination of perindopril and indapamide do not change compared to their separate use. Associated with perindopril After oral administration, perindopril is rapidly absorbed and reaches peak concentrations within 1 hour. The half-life is 1 hour. Perindopril is a prodrug. 27% of the administered dose of perindopril reaches the bloodstream as the active metabolite of perindoprilat. In addition to the active perindoprilat, perindopril forms five inactive metabolites. The peak plasma concentration of perindoprilat is reached after 3-4 hours. Since food intake reduces the conversion of perindopril to perindoprilat, and, consequently, its bioavailability, perindopril tert-butylamine is recommended to be taken orally once a day in the morning before meals. It has been shown that the relationship between the dose of perindopril and its content in blood plasma is a linear function. The volume of distribution of unbound perindoprilat is about 0.2 l/kg. The binding of perindoprilat to plasma protein is 20%, mainly binding occurs with the angiotensin converting enzyme and depends on the concentration of the drug. Perindoprilat is excreted in the urine. The terminal half-life of the unbound fraction is approximately 17 hours. The state of equilibrium is reached within 4 days. Excretion of perindoprilat is reduced in the elderly, as well as in patients with heart or kidney failure. Dose selection in patients with renal insufficiency depends on the degree of impaired renal function (creatinine clearance). The dialysis clearance of perindoprilat is 70 ml/min. The kinetics of perindopril changes in patients with cirrhosis: the hepatic clearance of the parent molecule is reduced by half. However, the amount of perindoprilat formed is not reduced and therefore no dose adjustment is required. Associated with indapamide, indapamide is rapidly and completely absorbed from the digestive tract. Peak plasma concentration in humans is reached approximately one hour after oral administration. Plasma protein binding is 79%. The elimination half-life includes from 14 to 24 hours (average 18 hours). Repeated administration of the drug does not lead to its accumulation in the body. It is excreted mainly in the urine (70% of the dose) and faeces (22%) in the form of inactive metabolites. Pharmacokinetics does not change in patients with renal insufficiency. Indications for use Co-Prenessa 2 mg / 0.625 mg and 4 mg / 1.25 mg Primary arterial hypertension. Co-Prenessa 4 mg/1.25 mg Co-Prenessa tablets 4 mg/1.25 mg are indicated in patients when blood pressure is not adequately controlled with perindopril monotherapy. Contraindications Associated with perindopril Hypersensitivity to perindopril or any other ACE inhibitor. Angioedema (Quincke's edema) in history associated with the use of ACE inhibitors. Hereditary or idiopathic angioedema. Second and third trimesters of pregnancy. Co-administration of Co-Prenessa and aliskiren-containing medicinal products is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR < 60 ml/min/1.73 m2). Indapamide related Hypersensitivity to indapamide or any other sulfonamides. Severe impairment of renal function (creatinine clearance below 30 ml / min). Hepatic encephalopathy. Severe hepatic impairment. Hypokalemia. Simultaneous use with antiarrhythmic drugs that cause prolongation of the QT interval due to an increased risk of developing ventricular tachycardia of the "pirouette" type. lactation period. Associated with Co-Prenessa Hypersensitivity to any component of the drug. Due to insufficient clinical experience, Co-Preness tablets should not be used: - in patients on dialysis; - in patients with untreated decompensated heart failure. Method of administration and doses For oral administration. Co-Prenessa 2 mg/0.625 mg The usual dose is 1 tablet 1 time per day, preferably in the morning before meals. If, after one month of treatment, blood pressure is not controlled, the dosage may be doubled. Co-Prenessa 4 mg/1.25 mg Co-Prenessa tablets 4 mg/1.25 mg are indicated when blood pressure control cannot be achieved with Co-Prenessa 2 mg/0.625 mg tablets. The usual dose is 1 tablet 1 time per day, preferably in the morning before meals. Individual dose selection is carried out, if possible, by each component separately. In case of clinical need, it is possible to prescribe Co-Preness tablets 4 mg / 1.25 mg with the ineffectiveness of perindopril monotherapy. Elderly patients Co-Prenessa 2 mg / 0.625 mg Initial dose - 1 tablet 1 time per day. Co-Prenessa 4 mg/1.25 mg Treatment should be started after assessment of blood pressure response and renal function. Patients with impaired renal function Co-Preness 2 mg / 0.625 mg and 4 mg / 1.25 mg In severe renal impairment (creatinine clearance below 30 ml / min), treatment is contraindicated. For patients with moderate renal impairment (creatinine clearance 30-60 ml / min), the maximum dose of Co-Prenessa 2 mg / 0.625 mg is 1 tablet 1 time per day. Co-Prenessa 4 mg/1.25 mg Patients with moderate renal impairment (creatinine clearance 30-60 ml/min) are advised to start treatment with an adequate dose of the free combination. Patients with a creatinine clearance greater than or equal to 60 ml/min do not require dose modification. Routine medical supervision should include frequent monitoring of creatinine and potassium. Patients with hepatic impairment In severe hepatic impairment, treatment is contraindicated. Dose modification is not required in patients with moderate hepatic impairment. Children and adolescents Co-Preness tablets 2 mg / 0.625 mg and tablets 4 mg / 1.25 mg should not be administered to children and adolescents, since the efficacy and tolerability of perindopril with mono- or combination therapy in this category of patients has not been established. Co-Preness tablets should be taken regularly, every day. If the drug was missed, the patient should continue treatment according to the prescribed regimen, without doubling the dose. Side effects Taking perindopril inhibits the renin-angiotensin-aldosterone system and reduces the loss of potassium caused by indapamide. In 2% of patients receiving a combination of perindopril and indapamide at a dose of 2 mg / 0.625 mg, hypokalemia was observed (potassium level < 3.4 mmol / l). In 4% of patients receiving a combination of perindopril and indapamide at a dose of 4 mg / 1.25 mg, hypokalemia was observed (potassium level < 3.4 mmol / l). Classification of the incidence of side effects according to the World Health Organization: very frequent (≥ 1/10); frequent (≥ 1/100, < 1/10); infrequent (≥ 1/1.000, < 1/100); rare (≥ 1/10.000, < 1/1.000); very rare (< 1/10.000), unknown (cannot be estimated from the available data). The frequency of side effects is listed for individual organ systems. Blood and lymphatic system disorders are very rare: thrombocytopenia, leukopenia/neutropenia, agranulocytosis, aplastic anemia, hemolytic anemia; when prescribing ACE inhibitors in special groups (in patients who underwent kidney transplantation, in patients on hemodialysis), anemia was observed. Psychiatric disorders: rare: mood and sleep disorders. Violations from the central and peripheral nervous system are frequent: paresthesia, headache, asthenia, dizziness; very rare: confusion; unknown: fainting. Violations of the organ of vision are frequent: visual disturbances. Frequent hearing impairments: ringing in the ears. Vascular disorders are common: orthostatic or non-orthostatic hypotension; Cardiac disorders are very rare: arrhythmia, including bradycardia, ventricular tachycardia, atrial fibrillation, angina pectoris and myocardial infarction, against the background of excessive hypotension in high-risk patients; unknown: flutter-flicker (potentially fatal). Respiratory, thoracic and mediastinal disorders are common: shortness of breath; angiotensin-converting enzyme inhibitors may cause a dry cough. The cough is persistent, but disappears after discontinuation of the drug. When this symptom appears, the possibility of iatrogenic etiology should be considered. infrequent: bronchospasm; very rare: eosinophilic pneumonia, rhinitis. Gastrointestinal disorders common: constipation, dry mouth, nausea, abdominal pain, taste disturbance, vomiting, taste change, dyspepsia, diarrhea; very rare: pancreatitis. Hepatobiliary disorders are very rare: cytolytic hepatitis or cholestatic hepatitis; unknown: in case of liver failure, hepatic encephalopathy is likely to develop. Skin and subcutaneous tissue disorders are common: rash, itching, maculopapular rashes; infrequent: angioedema of the face, extremities, lips, mucous membranes, tongue, pharynx and / or larynx, urticaria; hypersensitivity reaction, mainly dermatological, in persons with a predisposition to allergic and asthmatic reactions; purpura; possible worsening of pre-existing systemic lupus erythematosus; very rare: erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome; photosensitivity reactions have been reported. Violations of the musculoskeletal, connective and bone tissues are frequent: muscle cramps; Renal and urinary tract disorders infrequent: renal failure; very rare: acute renal failure. Violations of the genital organs and mammary glands infrequent: impotence. Complications of a general nature and reactions at the injection site are infrequent: sweating. Laboratory indicators Prolongation of the QT-interval on the electrocardiogram. Increased levels of liver enzymes. Increase in uric acid levels and blood glucose levels during treatment. A slight increase in urea and plasma creatinine levels, reversible upon discontinuation of treatment. This increase is more common in renal artery stenosis, diuretic treatment of arterial hypertension, and renal failure. Metabolic and nutritional disorders Rare: hypercalcemia Not known: Decreased potassium with hypokalemia present, especially in populations at risk Increased potassium levels, usually transient. - Hyponatremia with hypovolemia leading to dehydration and orthostatic hypotension. If the listed adverse reactions occur, as well as reactions not listed in the instructions for use, the patient should consult a doctor. Overdose Symptoms. The most likely adverse reaction in case of overdose is hypotension, sometimes accompanied by nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria, which may worsen to anuria (due to hypovolemia). Violations of the water and electrolyte balance are possible (low sodium and potassium). Treatment. The first urgent measure is the elimination of the drug taken by gastric lavage and / or activated charcoal, and then the restoration of water and electrolyte balance in a specialized center until the indicators return to normal. In the event of apparent hypotension, the patient should be given the position of "lying on his back with his head down." If necessary, isotonic saline is given intravenously, or another method of volume restoration may be used. Perindoprilat, the active form of perindopril, can be removed from the body by dialysis. Interaction with other drugs, as well as other forms of interaction General for perindopril and indapamide Simultaneous use is not recommended Lithium: there have been cases of reversible elevated serum lithium concentrations and cases of toxicity with the combined appointment of lithium and ACE inhibitors. Concomitant use of thiazide diuretics may increase the level of lithium and increase the risk of lithium toxicity developed while taking ACE inhibitors. The simultaneous use of perindopril in combination with indapamide and lithium is not recommended, but if the drug is proven necessary, then careful monitoring of the content of lithium in the blood serum should be carried out. Simultaneous use requiring special care Baclofen: potentiation of the antihypertensive effect. Blood pressure and renal function should be monitored, and, if necessary, the dose of the antihypertensive agent should be adjusted. - Non-steroidal anti-inflammatory drugs: the simultaneous use of ACE inhibitors with non-steroidal anti-inflammatory drugs (acetylsalicylic acid in doses that have an anti-inflammatory effect, COX-2 inhibitors and non-selective H11BC) may cause a decrease in the hypotensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs also increases the risk of impaired renal function, up to the development of acute renal failure, and an increase in serum potassium, especially in patients with pre-existing impaired renal function. This combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function is recommended before and after initiation of co-treatment. Simultaneous use requiring caution Imipramine-like antidepressants (tricyclic), antipsychotics: increased hypotensive effect and increased risk of orthostatic hypotension (additive effect). Corticosteroids, tetracosactide: reduction of the hypotensive effect (water and salt retention caused by the action of corticosteroids). Other antihypertensive drugs: an additional decrease in blood pressure is possible. Associated with perindopril Clinical trials have shown that, compared with the use of a single RAAS-active agent, dual blockade of the renin-angiotensin-aldosterone system (RAAS), through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren, is associated with a higher incidence of these side effects. as arterial hypotension, hyperkalemia and impaired renal function (including acute renal failure). Simultaneous use is not recommended Potassium-sparing diuretics (spironolactone, triamterene, mono- or combination therapy) and potassium preparations: ACE inhibitors reduce the loss of potassium caused by diuretics. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes can cause a significant (potentially fatal) increase in serum potassium levels. If co-administration is indicated due to proven hypokalemia, care must be taken and frequent monitoring of serum potassium and ECG should be carried out. Simultaneous use requiring special care - Antidiabetic agents (insulin, hypoglycemic sulfonamides). Validated for captopril and enalapril. Taking ACE inhibitors may increase the hypoglycemic effect in diabetic patients receiving insulin or sulfonylurea derivatives. Cases of the onset of hypoglycemia are extremely rare (improvement in glucose tolerance leads to a decrease in the need for insulin). Concomitant use requiring caution Allopurinol, cytotoxic or immunosuppressive substances, systemic corticosteroids or procainamide: Concomitant use of these drugs with ACE inhibitors may increase the risk of leukopenia. Anesthetics: ACE inhibitors may enhance the hypotensive effect of some anesthetics. Diuretics (thiazide or "loop" diuretics): Prior treatment with high doses of diuretics may lead to hypovolemia and the risk of hypotension at the beginning of treatment with perindopril. Gold preparations: in rare cases, nitritoid reactions (symptoms: facial flushing, nausea, vomiting and hypotension) have been observed in patients receiving injectable gold preparations (sodium aurothiomalate) and ACE inhibitors, including enalapril. Related to indapamide Concomitant use requiring special caution Drugs that cause torsades de pointes. Due to the risk of hypokalemia, caution should be exercised when indapamide is coadministered with drugs that cause torsades de pointes, such as: class IA antiarrhythmics (quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (amiodarone, dofetilide, ibutilide, bretylium, 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, diphemanil, IV erythromycin, halofantrine, mizolastine, moxifloxacin, pentamidine, sparfloxacin, IV vincamine, methadone, astemizole, terfenadine. Prevention of hypokalemia should be carried out, if necessary, correct and monitor the QT interval on the ECG. Means leading to hypokalemia - amphotericin B (in / in the route of administration), gluco- and mineralocorticoids (systemic route of administration), tetracosactide, stimulant laxatives: increase the risk of a decrease in potassium levels (additive effect). It is necessary to control the content of potassium, if necessary - to carry out a correction. Particular attention should be paid to patients simultaneously receiving cardiac glycosides. Stimulant laxatives should not be prescribed. Cardiac glycosides: Low potassium levels may increase the toxic effects of cardiac glycosides. It is necessary to control the content of potassium and ECG indicators; if necessary, treatment should be reviewed. Concomitant use requiring caution Metformin: lactic acidosis due to the use of metformin, caused by possible functional renal failure, is associated with the use of diuretics and, in particular, "loop" diuretics. Metformin should not be used if plasma creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women. Iodine-containing contrast agents: in case of dehydration caused by taking diuretics, the risk of developing acute renal failure increases, especially when high doses of iodine-containing contrast agent are used. Before the appointment of iodine-containing drugs, rehydration should be carried out. Calcium preparations: the risk of increasing the content of calcium due to a decrease in its excretion in the urine. Cyclosporine: The risk of an increase in plasma creatinine without changing the level of circulating cyclosporine, even in the absence of a decrease in water and electrolytes. Precautions Symptoms. The most likely adverse reaction in case of overdose is hypotension, sometimes accompanied by nausea, vomiting, muscle cramps, dizziness, drowsiness, confusion, oliguria, which may worsen to anuria (due to hypovolemia). Violations of the water and electrolyte balance are possible (low sodium and potassium). Treatment. The first urgent measure is the elimination of the drug taken by gastric lavage and / or activated charcoal, and then the restoration of water and electrolyte balance in a specialized center until the indicators return to normal. In the event of apparent hypotension, the patient should be given the position of "lying on his back with his head down." If necessary, isotonic saline is given intravenously, or another method of volume restoration may be used. Perindoprilat, the active form of perindopril, can be removed from the body by dialysis. Interaction with other drugs, as well as other forms of interaction General for perindopril and indapamide Simultaneous use is not recommended Lithium: there have been cases of reversible elevated serum lithium concentrations and cases of toxicity with the combined appointment of lithium and ACE inhibitors. Concomitant use of thiazide diuretics may increase the level of lithium and increase the risk of lithium toxicity developed while taking ACE inhibitors. The simultaneous use of perindopril in combination with indapamide and lithium is not recommended, but if the drug is proven necessary, then careful monitoring of the content of lithium in the blood serum should be carried out. Simultaneous use requiring special care Baclofen: potentiation of the antihypertensive effect. Blood pressure and renal function should be monitored, and, if necessary, the dose of the antihypertensive agent should be adjusted. - Non-steroidal anti-inflammatory drugs: the simultaneous use of ACE inhibitors with non-steroidal anti-inflammatory drugs (acetylsalicylic acid in doses that have an anti-inflammatory effect, COX-2 inhibitors and non-selective H11BC) may cause a decrease in the hypotensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs also increases the risk of impaired renal function, up to the development of acute renal failure, and an increase in serum potassium, especially in patients with pre-existing impaired renal function. This combination should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and monitoring of renal function is recommended before and after initiation of co-treatment. Simultaneous use requiring caution Imipramine-like antidepressants (tricyclic), antipsychotics: increased hypotensive effect and increased risk of orthostatic hypotension (additive effect). Corticosteroids, tetracosactide: reduction of the hypotensive effect (water and salt retention caused by the action of corticosteroids). Other antihypertensive drugs: an additional decrease in blood pressure is possible. Associated with perindopril Clinical trials have shown that, compared with the use of a single RAAS-active agent, dual blockade of the renin-angiotensin-aldosterone system (RAAS), through the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren, is associated with a higher incidence of these side effects. as arterial hypotension, hyperkalemia and impaired renal function (including acute renal failure). Simultaneous use is not recommended Potassium-sparing diuretics (spironolactone, triamterene, mono- or combination therapy) and potassium preparations: ACE inhibitors reduce the loss of potassium caused by diuretics. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes can cause a significant (potentially fatal) increase in serum potassium levels. If co-administration is indicated due to proven hypokalemia, care must be taken and frequent monitoring of serum potassium and ECG should be carried out. Simultaneous use requiring special care - Antidiabetic agents (insulin, hypoglycemic sulfonamides). Validated for captopril and enalapril. Taking ACE inhibitors may increase the hypoglycemic effect in diabetic patients receiving insulin or sulfonylurea derivatives. Cases of the onset of hypoglycemia are extremely rare (improvement in glucose tolerance leads to a decrease in the need for insulin). Concomitant use requiring caution Allopurinol, cytotoxic or immunosuppressive substances, systemic corticosteroids or procainamide: Concomitant use of these drugs with ACE inhibitors may increase the risk of leukopenia. Anesthetics: ACE inhibitors may enhance the hypotensive effect of some anesthetics. Diuretics (thiazide or "loop" diuretics): Prior treatment with high doses of diuretics may lead to hypovolemia and the risk of hypotension at the beginning of treatment with perindopril. Gold preparations: in rare cases, nitritoid reactions (symptoms: facial flushing, nausea, vomiting and hypotension) have been observed in patients receiving injectable gold preparations (sodium aurothiomalate) and ACE inhibitors, including enalapril. Related to indapamide Concomitant use requiring special caution Drugs that cause torsades de pointes. Due to the risk of hypokalemia, caution should be exercised when indapamide is coadministered with drugs that cause torsades de point