Triplixam pills 5mg+1.25mg+5mg, 30pcs

Pharmacological action

Triplixam® is a combination drug that includes three antihypertensive components, each of which complements the action of others to control blood pressure in patients with arterial hypertension. Amlodipine-slow calcium channel blocker (BMCC), dihydropyridine derivative, indapamide-sulfonamide diuretic, perindopril arginine – inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor)The pharmacological properties of Triplixam® combine the properties of each of its active ingredients. In addition, the combination of amlodipine, indapamide and perindopril arginine enhances the antihypertensive effect of each of the components. Mechanism of action Amlodipinamlodipine is a BMCC dihydropyridine derivative. Amlodipine inhibits the transmembrane transfer of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall. Indapamidindapamide belongs to the derivatives of sulfonamide with an indole ring and is similar in pharmacological properties to thiazide diuretics, which inhibit the reabsorption of sodium ions in the cortical segment of the nephron loop. At the same time, the excretion of sodium, chlorine and, to a lesser extent, potassium and magnesium ions by the kidneys increases, which is accompanied by an increase in diuresis and an antihypertensive effect. Perindopril Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (angiotensin-converting enzyme (ACE) inhibitor). kininase II, or kininase II, is an exopeptidase that converts angiotensin I to the vasoconstrictor angiotensin II. In addition, the enzyme stimulates the production of aldosterone by the adrenal cortex and the destruction of bradykinin, which has a vasodilating effect, to an inactive heptapeptide. As a result, perindopril: – reduces the secretion of aldosterone; – increases the activity of renin in the blood plasma according to the negative feedback principle; – with prolonged use, it reduces the total peripheral vascular resistance (OPSS), which is mainly due to the effect on the vessels in the muscles and kidneys. These effects are not accompanied by retention of sodium or liquid ions or the development of reflex tachycardia with prolonged use. Perindopril has an antihypertensive effect in patients with both low and normal plasma renin activity. Perindopril has a therapeutic effect due to the active metabolite perindoprilat. Other metabolites do not have pharmacological activity. Perindopril normalizes heart function, reducing preload and afterload due to: – vasodilating effect on the veins, possibly associated with the activation of the prostaglandin system; – reduction of total peripheral vascular resistance (OPSS)When studying hemodynamic parameters in patients with chronic heart failure (CHF), it was revealed: – a decrease in filling pressure in the left and right ventricles of the heart; a decrease in OPSS;- increased cardiac output and increased cardiac index; – increased muscular peripheral blood flow. Physical activity tolerance also increased. Pharmacodynamic effectsamlodipine antihypertensive effect of amlodipine is due to direct action on smooth muscle cells of the vascular wall. The detailed mechanism by which amlodipine exerts its antianginal action is not fully established, but it is known that amlodipine reduces the overall ischemic load by two actions: : – causes dilation of peripheral arterioles, reducing the total peripheral vascular resistance (afterload). This reduction in the load on the heart reduces energy consumption, and the need for oxygen in the myocardium. – causes dilation of the coronary arteries and arterioles in both ischemic and intact areas. At the same time, patients with coronary artery spasm (Prinzmetal angina) improve coronary blood flow and oxygen supply to the myocardium. In patients with arterial hypertension (AH), taking amlodipine once a day provides a clinically significant reduction in blood pressure in the “standing” and “lying” positions for 24 hours. The antihypertensive effect develops slowly, and therefore, the development of acute arterial hypotension is uncharacteristic. Amlodipine has no undesirable metabolic effects and does not affect lipid metabolism, does not cause changes in lipid-lowering blood plasma parameters, and can be used in patients with concomitant bronchial asthma, diabetes mellitus, and gout. Indapamide When indapamide was used as monotherapy, a 24-hour antihypertensive effect was demonstrated. The antihypertensive effect is manifested when the drug is used in doses that have a minimal diuretic effect. The antihypertensive activity of indapamide is associated with an improvement in the elastic properties of large arteries, a decrease in arteriolar and total peripheral vascular resistance. Indapamide reduces left ventricular hypertrophy. Thiazide and thiazide-like diuretics at a certain dose reach a plateau of therapeutic effect, while the frequency of side effects continues to increase with further increase in the dose of the drug. Therefore, do not increase the dose of the drug if the recommended dose does not achieve a therapeutic effect. In short, medium-term and long-term studies involving patients with arterial hypertension, it was shown that indapamide: does not affect the parameters of lipid metabolism, including the level of triglycerides, cholesterol, low-density lipoproteins and high-density lipoproteins; does not affect the parameters of carbohydrate metabolism, including in patients with diabetes mellitus. Perindopril Perindopril is effective in the treatment of arterial hypertension of any severity. Against the background of its use, there is a decrease in both systolic and diastolic blood pressure (BP) in the “lying” and “standing”positions. The antihypertensive effect of the drug reaches a maximum in 4-6 hours after a single oral use and persists for 24 hours. 24 hours after oral use, there is a pronounced (about 80%) residual ACE inhibition. In patients with a positive response to treatment, blood pressure normalizes within a month and persists without developing tachycardia. Discontinuation of treatment is not accompanied by the development of the “rebound” effect. 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. Simultaneous use of thiazide diuretics increases the severity of the antihypertensive effect. In addition, the combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of hypokalemia when taking diuretics. Perindopril / Indapamid E in hypertensive patients, regardless of age, the combination of perindopril and indapamide has a dose-dependent antihypertensive effect on both diastolic and systolic blood pressure in the “standing” and “lying” positions. Clinical studies have shown a more pronounced antihypertensive effect on the background of combined therapy with perindopril and indapamide compared to monotherapy with individual components. Clinical efficacy and safety The effect of Triplixam® on morbidity and mortality has not been studied. Amlodipine The efficacy and safety of amlodipine at a dose of 2.5–10 mg/day, the ACE inhibitor lisinopril at a dose of 10-40 mg/day as a first–line drug, and the thiazide diuretic chlortalidone at a dose of 12.5-25 mg/day were studied in a 5-year ALLHAT study (involving 33,357 patients aged 55 years and older) in patients with mild or moderate hypertension and with at least one additional risk factor coronary complications, such as: myocardial infarction or stroke more than 6 months prior to inclusion in the study, or other confirmed cardiovascular disease of atherosclerotic origin; type 2 diabetes mellitus; high-density lipoprotein cholesterol (HDL-C) concentration less than 35 mg/dl; left ventricular hypertrophy according to electrocardiography or echocardiography; smoking. The main criterion for evaluating effectiveness is a combined indicator of the frequency of deaths from CHD and the frequency of non-fatal myocardial infarction. There were no significant differences between the amlodipine and chlortalidone groups according to the main evaluation criterion. The incidence of heart failure in the amlodipine group was significantly higher than in the chlortalidone group — 10.2% and 7.7%, however, the overall mortality rate in the amlodipine and chlortalidone groups did not differ significantly. Perindopril/Indapamid E In a study involving patients with arterial hypertension and left ventricular hypertrophy (left ventricular mass index >120 g/m%^%2 in men and >>100 g/m%^%2 in women), the effectiveness of 2 mg of perindopril tertbutylamine (corresponding to 2.5 mg of perindopril arginine) in combination with 0.625 mg of indapamide compared to monotherapy with 10 mg of enalapril, taken once a day for 1 year, It was evaluated by echocardiography. If necessary, to maintain adequate blood pressure control, titration of doses of perindopril tertbutylamine up to 8 mg (corresponding to 10 mg of perindopril arginine) and indapamide up to 2.5 mg once a day or enalapril up to 40 mg once a day was performed. In the perindopril/indapamide group, no dose increase was required in 34% of patients compared to 20% in the enalapril group.At the end of treatment, left ventricular mass index values decreased more significantly in the perindopril/indapamide group (-10.1 g/m2) compared to the enalapril group (-1.1 g/m2). The best effect on left ventricular mass index values was achieved with higher doses of the combination of perindopril and indapamide. In terms of lowering blood pressure, the difference between the groups was 5.8 mmHg for systolic pressure and 2.3 mmHg for diastolic pressure, respectively, in favor of the perindopril/indapamide group. A study in patients with type 2 diabetes mellitus examined the effect of lowering blood pressure on the incidence of macrovascular events (death due to cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke) and microvascular events (the occurrence or worsening of nephropathy and eye diseases) in patients taking the combination of perindopril/indapamide compared with placebo, on the background of standard therapy, as well as taking modified-release gliclazide compared with standard therapy aimed at maintaining the level of blood glucose is normal. After 4.3 years of therapy, the relative risk of macrovascular and microvascular complications decreased by 9% in the perindopril / indapamide group. The benefit was achieved by significantly reducing the relative risk of mortality by 14%, death due to cardiovascular causes by 18%, and the development of renal complications by 21% in the group of patients receiving the perindopril/indapamide combination compared to placebo. In the subgroup of patients with arterial hypertension, a significant 9% reduction in the relative risk of combined incidence of macro – and microvascular complications was shown in the group taking the combination of perindopril/indapamide, compared with placebo. This group also significantly reduced the relative risk of death (by 16%), death due to cardiovascular causes (by 20%) and development of renal complications (by 20%) in patients receiving the perindopril/indapamide combination compared to patients receiving placebo. The benefits of antihypertensive therapy did not depend on the benefits achieved with intensive glycemic control. Double blockade of the rhein-angioteisin-aldosterone system (RAAS)There are data from clinical studies of combination therapy with an ACE inhibitor with ARA II. Clinical studies were conducted with the participation of patients with a history of cardiovascular or cerebrovascular disease, or type 2 diabetes mellitus, accompanied by confirmed damage to the target organ, as well as studies with the participation of patients with type 2 diabetes mellitus and diabetic nephropathy. These studies did not show a significant positive effect on the occurrence of renal and/or cardiovascular complications and mortality rates in patients receiving combination therapy, while the risk of hyperkalemia, acute renal failure and/or arterial hypotension increased compared to patients receiving monotherapy. Taking into account the similar intragroup pharmacodynamic properties of ACE inhibitors and ARA II, these results can be expected for the interaction of any other drugs, representatives of the classes of ACE inhibitors and ARA II. Therefore, ACE inhibitors and ARA II inhibitors should not be used simultaneously in patients with diabetic nephropathy. There is evidence from a clinical trial investigating the beneficial effects of adding aliskiren to standard therapy with an ACE inhibitor or ARA II in patients with type 2 diabetes mellitus and chronic kidney disease or cardiovascular disease, or who have a combination of these diseases. The study was terminated prematurely due to an increased risk of adverse outcomes. Cardiovascular death and stroke occurred more frequently in the aliskiren-treated group compared to the placebo group. Also, adverse events and serious adverse events of special interest (hyperkalemia, hypotension, and renal dysfunction) were reported more frequently in the aliskiren group than in the placebo group. Pharmacokineticsatriplixam®The combined use of perindopril / indapamide and amlodipine does not change their pharmacokinetic characteristics compared to separate use of these drugs. Amlodipine resorption After oral use, amlodipine is well absorbed from the gastrointestinal tract. The maximum concentration of amlodipine in blood plasma is reached 6-12 hours after oral use. Distributionabsolute bioavailability is about 64-80%, volume of distribution is about 21 l / kg. In vitro studies have shown that about 97.5% of circulating amlodipine is bound to plasma proteins. Simultaneous food intake does not affect the bioavailability of amlodipine. Metabolismamlodipine is metabolized in the liver to form inactive metabolites; the kidneys eliminate 10% of the dose of amlodipine unchanged and 60% in the form of metabolites. The elimination half-life (half-life) of amlodipine from blood plasma is 35-50 hours, which allows you to take the drug once a day. Special patient groups In elderly patients, there is a slowdown in the clearance of amlodipine, which leads to an increase in the area under the concentration-time curve (AUC) and Half-life. The increase in AUC and half-life in patients with chronic heart failure (CHF) corresponds to the expected value for this age group. Data on the use of amlodipine in patients with hepatic insufficiency are limited. In patients with hepatic insufficiency, there is a decrease in the clearance of amlodipine, which leads to an increase in Half-life and AUC by approximately 40-60%. Indapamide Absorption Indapamide is rapidly and completely absorbed in the gastrointestinal tract. The maximum concentration of indapamide in blood plasma is observed 1 hour after oral use. Distribution of binding to plasma proteins — 79%. Metabolism and excretionthe elimination half-life is 14-24 hours (average,18 hours). With repeated use of the drug, its accumulation is not observed. Indapamide is excreted as inactive metabolites, mainly by the kidneys (70% of the administered dose) and through the intestine (22%). Special patient groups In patients with renal insufficiency, the pharmacokinetics of indapamide do not change. Perindoprilabsorption When taken orally, perindopril is rapidly absorbed in the gastrointestinal tract, the maximum concentration (Cmax) in blood plasma is reached after 1 h (the active metabolite of perindopril is perindoprilat). The plasma half-life of perindopril is 1 h. Food intake slows down the conversion of perindopril to perindoprilate, thus affecting bioavailability. Therefore, the drug should be taken once a day, in the morning, before meals. Distributionthe volume of distribution of free perindoprilate is approximately 0.2 l / kg. Association of perindoprilat with plasma proteins, mainly with ACE. it is about 20% and is dose-dependent. Metabolism Perindopril has no pharmacological activity. Approximately 27% of the total amount of oral perindopril enters the bloodstream as the active metabolite of perindoprilat. In addition to perindoprilat,5 more metabolites are formed that do not have pharmacological activity. The maximum concentration of perindoprilat in blood plasma is reached 3-4 hours after oral use. Excretion Perindoprilat is eliminated from the body by the kidneys. The final half-life of the free fraction is about 17 hours, so the equilibrium state is reached within 4 days. There is a linear dependence of the concentration of perindopril in blood plasma on its dose. Special groups of patients with long-term age, the elimination of perindoprilat is slowed in the elderly, as well as in patients with heart and kidney failure. Renal insufficiency Dose selection should be carried out taking into account the severity of renal insufficiency (plasma creatinine clearance). The dialysis clearance of perindoprilat is 70 ml/min. Cirrhosis of the liverthe pharmacokinetics of perindopril are impaired in patients with cirrhosis of the liver: its hepatic clearance decreases by 2 times. However, the amount of perindoprilat produced does not decrease, which does not require dose adjustment (see sections” Dosage and use “and”Special instructions”).

Indications

As therapy in patients with arterial hypertension with a decrease in blood pressure against the background of taking amlodipine, indapamide and perindopril in the same doses.

Contraindications

Hypersensitivity to active and auxiliary substances that are part of the drug, sulfonamide derivatives, dihydropyridine derivatives, other ACE inhibitors, any other substances that are part of the drug;Patients on hemodialysis;Untreated heart failure in the decompensation stage;Severe renal failure (creatinine clearance (CC) less than 30 ml/min);Moderate renal failure (creatinine clearance (CC) less than 60 ml perindopril/indapamide 10 mg/2.5 mg combination dosage (i. e. Triplixam® 5 mg + mg + 10 mg and Triplixam® 10 mg + 2.5 mg + 10 mg); Angioedema (angioedema) with a history of ACE inhibitors (see section “Special instructions”); Hereditary/idiopathic angioedema;Pregnancy (see section “Use during pregnancy and lactation”); Breast-feeding period breast-feeding disorders (see the section “Use during pregnancy and lactation”); Hepatic encephalopathy:Severe hepatic insufficiency; Hypokalemia;Severe arterial hypotension (systolic blood pressure less than 90 mm Hg).Left ventricular outflow tract obstruction (for example, clinically significant aortic stenosis); Hemodynamically unstable heart failure after acute myocardial infarction; Concomitant use with aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate (GFR) Use caution (see also sections “Special instructions” and “Interactions with other medicinal products”). The presence of only one functioning kidney, impaired water and electrolyte balance, systemic connective tissue diseases, therapy with immunosuppressants, allopurinol, procainamide (risk of neutropenia, agranulocytosis), acute myocardial infarction (and within 1 month after myocardial infarction), sinus node weakness syndrome (pronounced tachy-and bradycardia), when prescribed simultaneously with inhibitors or inducers of the CYP3A4 isoenzyme, hepatic mild to moderate insufficiency, inhibition of bone marrow hematopoiesis, reduced circulating blood volume (taking diuretics, a diet with restriction of table salt, vomiting, diarrhea, hemodialysis), hyperuricemia (especially accompanied by gout and urate nephrolithiasis), simultaneous use of dantrolene, estramustin, lability of blood pressure, before the procedure of low – density lipoprotein (LDL) apheresis with dextran post-kidney transplant conditions, black patients, coronary heart disease, cerebrovascular diseases, renovascular hypertension, diabetes mellitus, chronic heart failure (NYHA functional class III and IV), concomitant use of potassium-sparing diuretics, potassium preparations, potassium-containing dietary salt and lithium substitutes, surgery/general anesthesia, hemodialysis using high-flow membranes (for example, AN69®), concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing dietary salt and lithium substitutes, surgery/general anesthesia, hemodialysis using high-flow membranes (for example, AN69®), concomitant use of desensitizing therapy with allergens (e. g. hymenopteran venom), aortic stenosis/mitral stenosis / hypertrophic obstructive cardiomyopathy, elderly.

Side effects

The most common adverse reactions reported with perindopril, indapamide, and amlodipine as monotherapy were: dizziness, headache, paresthesia, vertigo, drowsiness, visual disturbances, tinnitus, palpitations, flushes of blood to the skin of the face, decreased blood pressure (and effects associated with hypotension), cough, shortness of breath, gastrointestinal disorders (abdominal pain, constipation, diarrhea, taste distortion, etc. ). nausea, dyspepsia, vomiting), itching of the skin, rash, maculopapular rash, muscle spasms, swelling of the ankles, asthenia, swelling and fatigue.

How to take, course of use and dosage

Inside,1 tablet 1 time a day, preferably in the morning before meals. The dose of Triplixam® is selected after previously titrated doses of individual components. The maximum daily dose is 1 tablet in a dosage of 10.0 mg +2.5 mg + 10.0 mg. Special patient groups Patients with renal insufficiency (see sections “Pharmacokinetics”, “Contraindications” and “Special instructions”)Triplixam® is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) (see section “Contraindications”). In patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min), Triplixam® is contraindicated in the dosage of 5.0 mg + 2.5 mg + 10.0 mg and 10.0 mg + 2.5 mg + 10.0 mg. It is recommended to start therapy with the selection of doses of monocomponents. Constant medical monitoring should include regular monitoring of the concentration of creatinine and potassium in the blood plasma. Concomitant use with aliskiren is contraindicated in patients with impaired renal function (GFRPatients with hepatic insufficiency (see sections “Pharmacokinetics”, “Contraindications” and “Special instructions”)Triplixam is contraindicated in patients with severe hepatic insufficiency. For patients with mild or moderate hepatic insufficiency, dose selection should be carried out with caution, since there are no unambiguous recommendations on the dosage of amlodipine for this group of patients. Elderly patients (see section “Special instructions”)The elimination of perindoprilat in elderly patients is slowed (See section “Pharmacokinetics”). Therapy should be carried out taking into account the function of the kidneys. Paediatric patients Currently, there are no data on the safety and efficacy of Triplixam® in children and adolescents.

Overdose

There is no information on overdose of Triplixam®. Amlodipine overdose information is limited. Symptoms. There is evidence of excessive peripheral vasodilation with the possible development of reflex tachycardia. The risk of severe and persistent hypotension, including shock and death, has been reported. Methods of providing medical care. If clinically significant hypotension occurs due to an overdose of amlodipine, it is necessary to take measures aimed at maintaining the function of the cardiovascular system, including placing the limbs in an elevated position, monitoring BCC and diuresis, monitoring heart and respiratory activity. Vasoconstrictor drugs can be used to normalize vascular tone and blood pressure, provided that there are no contraindications to their use. To eliminate the consequences of calcium channel blockage, intravenous use of calcium gluconate is possible. In some cases, gastric lavage may be effective. In healthy volunteers, it was demonstrated that the use of activated charcoal for 2 hours after taking 10 mg of amlodipine reduces the rate of absorption of amlodipine. Since amlodipine binds to proteins, hemodialysis is ineffective. Combination of perindopril / indapamidsymptomfor the combination of perindopril/indapamide, the most likely symptom of overdose is hypotension, sometimes in combination with nausea, vomiting, convulsions, dizziness, drowsiness, confusion and oliguria, which can turn into anuria (as a result of hypovolemia). Electrolyte disturbances (hyponatremia, hypokalemia) may also occur. Methods of providing medical assistance in emergency situations are reduced to removing the drug from the body: gastric lavage and / or taking activated carbon, followed by restoring the water-electrolyte balance. With a significant decrease in blood pressure, the patient should be transferred to the supine position with raised legs, if necessary, correction of hypovolemia (for example, an intravenous infusion of 0.9% sodium chloride solution). Perindoprilate, the active metabolite of perindopril, can be removed from the body by dialysis (see section “Pharmacokinetics”)

Description

1 tablet 5 mg + 1.25 mg + 5 mg: contains active ingredients amlodipine bezylate 6.935 mg, corresponds to 5.0 mg of amlodipine,1.25 mg of indapamide and perindopril arginine 5 mg.

Special instructions

All precautions associated with the use of individual components of the drug should be taken into account when using their fixed combination as part of Triplixam®. Amlodipynchronous heart failure Treatment of patients with chronic heart failure should be performed with caution. When using amlodipine in patients with chronic heart failure of NYHA class III and functional class, pulmonary edema may develop. Slow calcium channel blockers, including amlodipine, should be used with caution in patients with chronic heart failure, due to the possible increase in the risk of adverse events from the cardiovascular system and mortality. In patients with severe chronic heart failure (NYHA Functional Class IV), treatment should be initiated at lower doses and under close medical supervision. Patients with arterial hypertension and coronary heart disease should not stop taking beta-blockers: an ACE inhibitor should be used in conjunction with beta-blockers. Hypertensive crisis The efficacy and safety of amlodipine in hypertensive crisis has not been established. Indapamide hepatic encephalopath Yin the presence of impaired liver function, taking thiazide and thiazide-like diuretics can lead to the development of hepatic encephalopathy. In this case, you should immediately stop taking the diuretic. Photosensitivity Cases of photosensitivity reactions have been reported with thiazide and thiazide-like diuretics (see section “Side effects”). If a photosensitivity reaction develops while taking the drug, treatment should be discontinued. If it is necessary to continue diuretic therapy, it is recommended to protect the skin from exposure to sunlight or artificial ultraviolet rays. Plasma calcium ion content Blood-based diuretics and thiazide-like diuretics can reduce the excretion of calcium ions by the kidneys and lead to a slight and temporary increase in the content of calcium ions in the blood plasma. Severe hypercalcemia may be a consequence of previously undiagnosed hyperparathyroidism. In such cases, you should stop taking diuretics and conduct a study of the function of the parathyroid glands (seesection “Side effects”). Uric acid patients with elevated plasma uric acid concentrations may experience an increased incidence of gout attacks during therapy. Perindopril potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes, and food additives Simultaneous use of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing salt substitutes, and food additives is not recommended (see the section “Interaction with other medicinal products”). Double blockade of the renin-angiotensin-aldosterone system (RAAS)There is evidence of an increased risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure) when ACE inhibitors are co-administered with ARA II or aliskiren. Therefore, double blockade of the RAAS as a result of the combination of an ACE inhibitor with ARA II or aliskiren is not recommended (see sections “Interaction with other drugs” and “Pharmacodynamics”). If a double blockade is necessary, it should be performed under the strict supervision of a specialist with regular monitoring of kidney function, blood plasma electrolyte levels and blood pressure. ACE inhibitors should not be used concomitantly with ARA II in patients with diabetic nephropathy. Neutropenia / agranulocytosis / thrombocytopenia/anemia Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported with ACE inhibitors. Neutropenia is rare in patients with normal renal function and in the absence of other aggravating factors. Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or when they are combined, especially in patients with impaired renal function. Some of these patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor their white blood cells, and patients should inform the doctor about any signs of infectious diseases (for example, sore throat, fever) (see the section “Side effects”). Hypersensitivity/angioedema When taking ACE inhibitors, including perindopril, in rare cases, angioedema of the face, limbs, lips, tongue, glottis and/or larynx may develop. This can happen during any period of therapy. If symptoms appear, the drug should be stopped immediately and the patient should be monitored until the signs of edema disappear completely. If the swelling affects only the face and lips, then its manifestations usually go away on their own, although antihistamines can be used to treat the symptoms. Angioedema accompanied by laryngeal edema can be fatal. Swelling of the tongue, glottis, or larynx can lead to airway obstruction, in which case intensive care should be given immediately. If such symptoms occur, a solution of epinephrine (epinephrine)should be administered immediately 1: 1000 (0.3-0.5 ml) and / or provide airway patency. The patient should be under medical supervision until complete and persistent disappearance of symptoms. Patients of the black race had a higher incidence of angioedema when taking ACE inhibitors compared to other races. In patients with a history of angioedema not associated with ACE inhibitor use. the risk of its development may be increased when taking the drug (see the section “Contraindications”). There are reports of rare cases of intestinal angioedema during therapy with ACE inhibitors. At the same time, patients experienced 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 C1-esterase. The diagnosis was made using computed tomography of the abdominal region, ultrasound, or at the time of surgery. Symptoms resolved after discontinuation of ACE inhibitors. Therefore, in patients with abdominal pain treated with ACE inhibitors, the possibility of developing angioedema of the intestine should be taken into account during differential diagnosis. Anaphylactoid reactions during desensitization, there have been isolated reports of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitization therapy with hymenopteran venom (bees, wasps). ACE inhibitors should be used with caution in patients with a history of allergy or a tendency to allergic reactions, undergoing desensitization procedures, and the use of an ACE inhibitor in patients receiving immunotherapy with hymenopteran venom should be avoided. However, an anaphylactoid reaction can be avoided by temporarily stopping the ACE inhibitor at least 24 hours before the start of the desensitization procedure. Anaphylactoid reactions during LDL apheresis In rare cases, patients receiving ACE inhibitors may develop life-threatening anaphylactoid reactions during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure. Hemodialysis patients receiving ACE inhibitors have experienced anaphylactoid reactions during hemodialysis using high-flow membranes (for example, AN69®). Therefore, it is desirable to use a different type of membrane or use an antihypertensive agent of a different pharmacotherapeutic group. Pregnancy ACE inhibitors are contraindicated during pregnancy. If it is necessary to continue therapy with ACE inhibitors, patients should switch to other types of antihypertensive therapy with an established safety profile when taken during pregnancy. If pregnancy occurs, ACE inhibitors should be discontinued immediately and, if necessary, alternative antihypertensive therapy should be initiated (see sections “Contraindications” and “Use during pregnancy and lactation”). Cough During ACE inhibitor therapy, a dry cough may occur. Cough persists for a long time against the background of taking drugs of this group and disappears after their cancellation. If a patient has a dry cough, you should be aware of the possible iatrogenic nature of this symptom. If the doctor believes that ACE inhibitor therapy is necessary for the patient, the possibility of continuing the drug may be considered. Mitral stenosis/aortic stenosis/hypertrophic obstructive cardiomyopathy ACE inhibitors should be used with caution in patients with left ventricular outflow tract obstruction. Ethnic Differencesperindopril, like other ACE inhibitors, apparently has a less pronounced hypotensive effect in patients of the black race compared to representatives of other races. Perhaps this difference is due to the fact that patients with arterial hypertension of the black race often have low renin activity. Surgical intervention/General anaesthetisthe use of ACE inhibitors in patients undergoing surgery with general anaesthesia can lead to a marked decrease in blood pressure, especially when using general anaesthetic agents that have an antihypertensive effect. If possible, it is recommended to stop taking long-acting ACE inhibitors, including perindopril, one day before surgery. Patients with renovascular hypertension The treatment method for renovascular hypertension is revascularization. However, the use of ACE inhibitors has a beneficial effect in patients who are waiting for surgery, and in the case when surgical intervention is not possible. When using Triplixam® in patients with existing or suspected renal artery stenosis, treatment should be started in a hospital setting with low doses and constant monitoring of kidney condition and blood potassium levels, since such patients may develop functional renal failure, which disappears when therapy is discontinued. Arterioscler Osis risk of hypotension exists in all patients, but special care should be taken when using the drug in patients with coronary heart disease and cerebral circulatory insufficiency. In such patients, treatment should begin with low doses of the drug. Perindopril / indapamide. Lithium preparations Simultaneous use of a combination of perindopril and indapamide with lithium preparations is not recommended (see the section “Interaction with other drugs”). Arterial hypotension and impaired water-electrolyte Balancethe presence of initial hyponatremia is associated with the risk of sudden development of arterial hypotension (especially in patients with renal artery stenosis). Therefore, when monitoring patients, you should pay attention to possible symptoms of dehydration and a decrease in the content of electrolytes in the blood plasma, for example, after diarrhea or vomiting. Such patients need regular monitoring of blood plasma electrolyte levels. Severe hypotension may require intravenous use of 0.9% sodium chloride solution. Transient arterial hypotension is not a contraindication for continuing therapy. After recovery of BCC and BP, you can resume therapy using a low-dose combination, or use the components of the drug in a monotherapy mode. All diuretics can cause hyponatremia. which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary.More frequent monitoring of sodium ions is indicated in elderly patients and patients with cirrhosis of the liver (see sections “Side effects” and “Overdose”). Patients with diabetes Mellitus For patients with type 1 diabetes mellitus (risk of spontaneous increase in potassium ions), treatment should begin with lower doses and under close medical supervision. When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral use or insulin, regular monitoring of blood glucose concentration is necessary during the first month of therapy. It is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia. Amlodipine/perindoprilhepatic insufficiency In rare cases, cholestatic jaundice occurs while taking ACE inhibitors. With the progression of this syndrome, fulminant liver necrosis develops, sometimes with a fatal outcome. The mechanism of development of this syndrome is unclear. If jaundice or a significant increase in the activity of “liver” enzymes occurs in patients taking ACE inhibitors, you should stop taking an ACE inhibitor and consult a doctor (see the section “Side effects”). In patients with impaired liver function, the half-life and AUC of amlodipine increases. Amlodipine should be started at the lowest possible dose and precautions should be taken both at the beginning of treatment and when increasing the dose. Patients with severe hepatic insufficiency should increase the dose gradually, ensuring careful monitoring of the clinical condition. Triplixam® has not been studied in patients with hepatic insufficiency. Taking into account the effect of each component included in the drug, separately, Triplixam® is contraindicated in patients with severe hepatic insufficiency, and also requires special caution when prescribing to patients with moderate and mild hepatic insufficiency. Amlodipine / indapamide/Perindopril Impaired renal Functionthe drug is contraindicated in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) (see section “Contraindications”). In patients with moderate renal insufficiency (creatinine clearance 30-60 ml/min), the use of Triplixam® in dosages containing 10 mg of perindopril and 2.5 mg of indapamide is contraindicated (i. e., Triplixam® dosages of 5 mg + 2.5 mg + 10 mg and 10 mg + 2.5 mg + 10 mg). Some patients with arterial hypertension without previous obvious renal impairment may develop laboratory signs of functional renal failure during therapy. In this case, treatment with the drug should be discontinued with the further possibility of resuming combination therapy using low doses of the drug, or using the components of the drug in a monotherapy mode. Such patients need regular monitoring of the content of potassium and creatinine ions in the blood serum-2 weeks after the start of therapy and thereafter every 2 months. Renal failure occurs more frequently in patients with severe chronic heart failure or underlying renal dysfunction, including renal artery stenosis. Triplixam® is not recommended for patients with bilateral renal artery stenosis or stenosis of the artery of a single functioning kidney. There is a risk of hypotension and/or renal failure (in the presence of chronic heart failure, dehydration, and decreased plasma electrolytes, etc. ): in some pathological conditions, significant activation of RAAS may occur, especially with severe hypovolemia and a decrease in plasma electrolytes (against the background of a salt-free diet or prolonged use of diuretics), in patients with initially low blood pressure, renal artery stenosis (including bilateral), chronic heart failure, or cirrhosis of the liver with edema and ascites. Blockade of RAAS with ACE inhibitors may be accompanied by a sharp decrease in blood pressure and / or an increase in the concentration of creatinine in blood plasma, indicating the development of functional renal failure. These phenomena are more often observed when taking the first dose of the drug or during the first two weeks of therapy. Sometimes these conditions develop acutely and the time of their onset may vary. In such cases, it is recommended to resume therapy starting with lower doses, gradually increasing them. In patients with CHD and cerebrovascular diseases, a sharp decrease in blood pressure can lead to myocardial infarction or impaired cerebral circulation. Thiazide and thiazide-like diuretics are fully effective only in patients with normal or slightly impaired renal function (plasma creatinine concentrations in adult patients below 25 mg / l or 220 mmol/l). In elderly patients, creatinine levels should be assessed based on age, body weight, and gender. At the beginning of diuretic treatment, patients may experience a temporary decrease in glomerular filtration rate and an increase in plasma urea and creatinine concentrations due to hypovolemia and hyponatremia. This transient functional renal insufficiency is not dangerous for patients with unchanged renal function, but in patients with initial renal insufficiency, its severity may increase. Patients with renal insufficiency can take amlodipine in standard doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal failure. Special studies on the use of Triplixam® in renal insufficiency have not been conducted. When using Triplixam® in patients with renal insufficiency, the effects observed when taking individual components of the drug should be taken into account. Plasma potassium ion content Blood-based therapy with indapamide, perindopril and amlodipine does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or renal insufficiency. As with the use of other antihypertensive agents in combination with a diuretic, regular monitoring of the content of potassium ions in the blood plasma is necessary. Hyperkalemia may develop in some patients during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, impaired renal function, advanced age (>70 years), diabetes mellitus, certain concomitant conditions (dehydration, acute decompensation of cardiac activity, metabolic acidosis), concomitant use of potassium-sparing diuretics (such as spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing salt substitutes, as well as the use of other agents that increase the content of potassium ions in blood plasma (for example, heparin). The use of potassium supplements/preparations, potassium-sparing diuretics, potassium-containing salt substitutes can lead to a significant increase in the blood potassium content, especially in patients with reduced renal function. Hyperkalemia can lead to serious, sometimes fatal cardiac arrhythmias. If combined use of the above drugs is necessary, treatment should be carried out with caution, against the background of regular monitoring of the content of potassium ions in the blood serum (see the section “Interaction with other drugs”). Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia. Hypokalemia (less than 3.4 mmol) should be avoided. /k) in the following categories of patients from the high-risk group: elderly patients and / or emaciated patients (even if they do not receive concomitant drug therapy), patients with cirrhosis of the liver with edema and ascites, patients with coronary heart disease, chronic heart failure. Hypokalemia in these patients increases the toxic effect of cardiac glycosides and increases the risk of arrhythmia. The risk group also includes patients with an extended QT interval, and it does not matter whether this increase is caused by congenital causes or the action of medications. Hypokalemia, like bradycardia, contributes to the development of severe cardiac arrhythmias, in particular, polymorphic ventricular tachycardia of the “pirouette” type, which can be fatal. In all the cases described above, regular monitoring of the content of potassium ions in the blood plasma is necessary. The first measurement of the potassium ion content should be carried out within the first week after the start of therapy. If hypokalemia is detected, appropriate treatment should be prescribed. Elderly patients Before taking the drug, it is necessary to assess the functional activity of the kidneys and the content of potassium ions in the blood plasma. At the beginning of therapy, the dose of the drug is selected taking into account the degree of reduction in blood pressure, especially in the case of a decrease in the volume of circulating blood (BCC) and loss of electrolytes. Such measures can avoid a sharp decrease in blood pressure. In elderly patients, dose increases should be carried out with caution (see sections “Dosage and use” and “Pharmacokinetics”). Influence on the ability to drive vehicles, mechanisms due to the possibility of weakness, dizziness during the use of Triplixam®, care should be taken when driving vehicles and working with other technical devices that require increased concentration of attention and speed of psychomotor reactions.

Form of production

Film-coated tablets

Storage conditions

At a temperature not exceeding 25°C. Keep out of reach of children.

Shelf

life is 2 years.

Active ingredient

Amlodipine, Indapamide, Perindopril

Conditions of release from pharmacies

By prescription

Purpose

For adults as directed by your doctor

Indications

Hypertension