Prestarium A pills p/o 10mg №30

Name:
Prestarium 10 mg
Description:
Green, round, biconvex film-coated tablets, embossed on one side and on the other. The main active ingredient Perindopril Release form tablets Dosage 10 mg Special instructions Stable coronary heart disease. If an episode of unstable angina (of any severity) occurs during the first month of treatment with perindopril, the benefit / risk ratio must be carefully weighed before deciding whether to continue therapy. Arterial hypotension. Taking ACE inhibitors can cause a decrease in blood pressure. Symptomatic hypotension occurs less frequently in patients with uncomplicated hypertension and is more likely in patients with hypovolemia, those on diuretics, those on a salt-restricted diet, those on dialysis, those with diarrhea or vomiting, or those with severe renin-dependent arterial hypertension (see sections “Interaction with other drugs and other forms of interaction” and “Adverse reactions”). Symptomatic arterial hypotension is more likely in patients with symptomatic heart failure, with or without concomitant renal failure. The occurrence of symptomatic arterial hypotension is most likely in patients with more severe heart failure, who take large doses of loop diuretics, have hyponatremia, or have renal failure of a functional nature. To reduce the risk of symptomatic arterial hypotension during the initiation of therapy and at the stage of dose selection, patients should be under the supervision of a physician (see Sections “Method of application and doses” and “Adverse reactions”). The same caution applies to patients with ischemic heart disease or cerebrovascular disease, in whom an excessive reduction in blood pressure may cause myocardial infarction or stroke. If arterial hypotension occurs, the patient should be placed in a horizontal position and, if necessary, injected intravenously with 0.9% (9 mg / ml) sodium chloride solution. Transient hypotension is not a contraindication to further use of the drug, which can usually be used without any obstacles after restoration of blood volume and increase in blood pressure. In some patients with congestive heart failure with normal or low blood pressure, perindopril arginine may cause an additional decrease in systemic blood pressure. This effect is predictable and usually does not require discontinuation of the drug. If arterial hypotension is symptomatic, it may be necessary to reduce the dose or discontinue the drug. Stenosis of the aortic and mitral valves / hypertrophic cardiomyopathy. As with other ACE inhibitors, perindopril arginine should be used with caution in patients with mitral valve stenosis or left ventricular outflow obstruction (aortic stenosis or hypertrophic cardiomyopathy). Renal failure. In case of renal insufficiency (creatinine clearance <60 ml / min), the initial dose of perindopril should be prescribed in accordance with the patient's QC (see section "Dosage and Administration"), and then - depending on the patient's response to treatment. Monitoring of potassium and creatinine is the usual standard for such patients (see section "Adverse reactions"). In patients with symptomatic heart failure, arterial hypotension, which occurs at the beginning of the use of ACE inhibitors, can lead to impaired renal function, in some cases - with the onset of acute renal failure, which is usually reversible. In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, an increase in serum urea and creatinine levels was observed when using ACE inhibitors, usually returning to normal after stopping treatment. This is especially true for patients with renal insufficiency. In the presence of concomitant renovascular hypertension, the risk of severe arterial hypotension and renal failure increases. For such patients, treatment should be started under close medical supervision with small doses and with careful dose titration. Given the above, treatment with diuretics can contribute to the occurrence of arterial hypotension, so they should be canceled and monitoring of kidney function should be carried out in the first weeks of treatment with perindopril arginine. In some patients with arterial hypertension, in whom renovascular disease was not detected before the start of treatment, there was an increase in serum urea and creatinine, usually minor and temporary, especially when perindopril arginine was prescribed simultaneously with a diuretic. But this is more common in patients with pre-existing renal failure. Dose reduction and/or withdrawal of the diuretic and/or perindopril arginine may be required. Patients after kidney transplantation. There is no experience in prescribing perindopril arginine to patients after a recent kidney transplant operation. Renovascular hypertension. When prescribing ACE inhibitors to patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney, the risk of hypotension and renal failure increases (see Section "Contraindications"). A favorable factor may be treatment with diuretics. Loss of kidney function can be manifested by minimal changes in serum creatinine levels, even in patients with arterial stenosis in one of the kidneys. Hypersensitivity / angioedema. Rare cases of angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and / or larynx have been reported in patients using ACE inhibitors, including perindopril arginine (see section "Adverse reactions"). This can happen at any time during treatment. In such cases, it is necessary to urgently cancel the drug and establish appropriate supervision of the patient's condition until the symptoms disappear completely. In those rare cases where the edema only spreads to the face and lips, the patient's condition usually improves without treatment. Prescribing antihistamines may be helpful in reducing symptoms. Angioedema associated with laryngeal edema can be fatal. In cases where swelling extends to the tongue, glottis, or larynx, causing airway obstruction, urgent emergency treatment is needed, which may include the administration of adrenaline and/or airway management. Rare cases of intestinal angioedema have been reported in patients treated with ACE inhibitors. These patients experienced abdominal pain (with or without nausea or vomiting); in some cases, no previous angioedema of the face was observed and the level of C-1 esterase was normal. The diagnosis of intestinal angioedema was established during abdominal computed tomography or ultrasound or during surgery. After discontinuation of the ACE inhibitor, the symptoms of angioedema disappeared. Intestinal angioedema should be excluded as a differential diagnosis in patients with abdominal pain taking ACE inhibitors. Patients simultaneously treated with mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) may be at increased risk of developing angioedema (eg, edema of the airways or tongue, with or without respiratory dysfunction) (see Section "Interaction with other medicinal products"). means and other types of interactions”). Anaphylactoid reactions during low-density lipoprotein (LDL) plasmapheresis. Rarely, life-threatening anaphylactoid reactions may occur in patients taking ACE inhibitors during low-density lipoprotein (LDL) plasmapheresis (LDL) using dextran sulfate. The development of anaphylactoid reactions can be avoided by temporarily stopping treatment with ACE inhibitors before each plasmapheresis. Anaphylactoid reactions during desensitizing therapy. Life-threatening anaphylactoid reactions may occur in patients taking ACE inhibitors during desensitization of bee venom containing agents. These reactions can be avoided with a temporary cessation of the use of ACE inhibitors, but the reactions can occur again with careless provocative tests. Liver failure. Cases in which jaundice has developed while taking an ACE inhibitor or an increase in the level of liver enzymes are rare. Such patients should stop taking the ACE inhibitor and receive appropriate medical examination and treatment (see section "Adverse reactions"). Neutropenia/agranulocytosis, thrombocytopenia, and anemia have been reported among patients taking ACE inhibitors. In patients with normal renal function and in the absence of other risk factors, neutropenia rarely occurs. Perindopril should be administered very cautiously to patients with collagenoses, during therapy with immunosuppressants, allopurinol or procainamide, or a combination of these aggravating factors, especially if there is impaired renal function. If perindopril is prescribed to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Also, patients should be aware that it is necessary to report any manifestation of an infectious disease (sore throat, fever). The racial factor. ACE inhibitors are more likely to cause angioedema in African American patients than in non-African American patients. This may be due to the low level of renin in the blood of patients with arterial hypertension from the African American population. Cough. Cough has been reported during therapy with ACE inhibitors. According to the characteristics of the cough is unproductive, persistent and stops after discontinuation of the drug. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. During surgery or during anesthesia with drugs that cause hypotension, perindopril can block the secondary formation of angiotensin II in response to compensatory renin release. The drug should be discontinued one day before surgery. If arterial hypotension has developed and it is considered to be caused by this mechanism, the patient's condition can be normalized by increasing the volume of circulating blood. Hyperkalemia. In some patients with risk factors while taking ACE inhibitors, including perindopril arginine, there was an increase in the concentration of potassium in the blood serum. Risk factors for hyperkalemia include renal failure, impaired renal function, age (over 70 years), diabetes mellitus, intercurrent conditions such as dehydration, acute cardiac decompensation, metabolic acidosis, and concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene, or amiloride), food supplements containing potassium, or its potassium salts; or those patients who are taking other drugs that cause an increase in the concentration of potassium in the blood serum (for example, heparin). The use of potassium supplements, potassium-sparing diuretics or salt substitutes with potassium, especially in patients with impaired renal function, can lead to a significant increase in serum potassium levels. Hyperkalemia can lead to serious, sometimes fatal arrhythmias. If the simultaneous use of perindopril and any of the above substances is considered appropriate, they should be used with caution and with frequent monitoring of serum potassium levels (see Section "Interaction with other medicinal products and other forms of interaction"). Patients with diabetes taking oral hypoglycemic agents or receiving insulin should carefully monitor the level of glycemia during the first month of therapy with ACE inhibitors (see Section "Interaction with other drugs and other forms of interaction"). Lithium. The simultaneous use of lithium and perindopril is usually not recommended (see section "Interaction with other medicinal products and other types of interactions"). Simultaneous use of perindopril with potassium-sparing drugs, food supplements containing potassium or salt substitutes with potassium is not recommended (see Section "Interaction with other medicinal products and other types of interactions"). Double blockade of renin-angiotensin-(RAAS). There is evidence that the simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by concomitant administration of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see Section "Interaction with other medicinal products and other types of interactions"). If treatment with simultaneous use of two RAAS blockers is considered absolutely necessary, it can only occur under the supervision of a specialist and with frequent close monitoring of kidney function, electrolyte levels and blood pressure. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy. primary aldosteronism. Patients with primary hyperaldosteronism usually do not respond to treatment with antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, the appointment of this drug is not recommended. Excipients. The composition of the drug includes lactose, so patients with rare hereditary galactose intolerance, glucose-galactose malabsorption syndrome, Lapp lactase deficiency are not recommended to take perindopril arginine. Pharmacological properties Pharmacodynamics Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE ACE). The conversion enzyme, or kinase, is an exopeptidase that allows the conversion of angiotensin I to the vasoconstrictor angiotensin II, and also causes the breakdown of the vasodilator bradykinin to an inactive heptapeptide. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which increases the activity of renin in the blood plasma (by inhibiting the negative feedback on renin release) and reduces the secretion of aldosterone. Since ACE inactivates bradykinin, ACE inhibition also leads to increased activity of the circulating and local kalikreinkin system (and thus also leads to activation of the prostaglandin system). This mechanism of action results in the lowering of blood pressure by ACE inhibitors and is partly responsible for some of the side effects (eg, cough). Perindopril arginine acts through its active metabolite, perindoprilat. Other metabolites do not show activity in ACE suppression under experimental conditions. Arterial hypertension. Perindopril effectively lowers blood pressure in all degrees of mild, moderate and severe arterial hypertension; a decrease in systolic and diastolic blood pressure is observed both in the supine position and in the standing position. Perindopril reduces the resistance of peripheral vessels, which leads to a decrease in blood pressure. As a result, peripheral blood flow increases without affecting the heart rate. As a rule, renal blood flow also increases, while the glomerular filtration rate (GFR) usually does not change. The maximum antihypertensive effect develops 4-6 hours after a single dose and persists for at least 24 hours: the T / P ratio (trough / peak - minimum efficiency / maximum efficiency during the day) of perindopril is 87-100%. Blood pressure drops quickly. In patients who responded to treatment, normalization of blood pressure occurs within a month and is maintained without the occurrence of tachyphylaxis. In the case of the abolition of perindopril arginine, the withdrawal effect does not occur. Perindopril reduces left ventricular hypertrophy. Clinical studies have proven that perindopril has vasodilating properties. It improves the elasticity of large arteries and reduces the wall thickness to vessel lumen ratio for small arteries. Additional therapy with a thiazide diuretic has a synergistic effect. The combination of an ACE inhibitor and a thiazide diuretic also reduces the risk of diuretic-induced hypokalemia. Heart failure. Perindopril arginine reduces the work of the heart by reducing pre- and afterload on the heart. A study in patients with heart failure demonstrated a decrease in right and left ventricular filling pressure, a decrease in systemic peripheral resistance, an increase in cardiac index, and an improvement in cardiac output. In comparative studies, the first administration of perindopril arginine 2.5 mg to patients with mild to moderate heart failure was not associated with any significant reduction in blood pressure compared with placebo. Patients with a history of cerebrovascular disease. The multicenter, international, double-blind, randomized, placebo-controlled PROGRESS study determined the benefits of 4-year treatment with perindopril (alone or in combination with indapamide) in preventing recurrent stroke in patients with a history of cerebrovascular disease. The primary end point was stroke. After 2 weeks (run-in period) of perindopril tertbutylamine 2 mg (equivalent to perindopril arginine 2.5 mg) once daily and 2 weeks of 4 mg (equivalent to perindopril arginine 5 mg) once daily , 6105 patients were randomized into two groups: in one group, patients received placebo (n = 3054), and in the other, perindopril tertbutylamine 4 mg (equivalent to perindopril arginine 5 mg) as monotherapy or in combination with indapamide (n = 3051). Indapamide was added to patients who had indications for the appointment of a diuretic and had no contraindications to its appointment. This therapy was prescribed in addition to the traditional treatment of stroke and/or hypertension or any other pathological conditions. All patients who participated in the study had a history of cerebrovascular disease (stroke or transient ischemic attack) within the last 5 years. Blood pressure was not a criterion for inclusion in the study: 2916 patients were with arterial hypertension, 3189 patients were with normal blood pressure. After 3.9 years (average) follow-up, systolic/diastolic blood pressure decreased by an average of 9.0/4.0 mmHg. Art. and the risk of recurrent strokes (both ischemic and hemorrhagic) was significantly reduced by 28% (95% CI 17.38, p < 0.0001) compared with patients who took placebo (10.1% compared with 13.8% ). There was also a significant reduction in the risk of: fatal or disabling stroke (4% compared to 5.9%, corresponding to a risk reduction of 33%); the total number of significant cardiovascular events, which consist of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (15% compared to 19.8%, corresponding to a risk reduction of 26%); dementia due to stroke (1.4% vs. 2.1%, corresponding to a 34% risk reduction) and severe cognitive impairment due to stroke (1.6% vs. 2.8%, corresponding to risk reduction by 45%); significant coronary events, including non-fatal myocardial infarction or death due to coronary heart disease (3.8% compared to 5%, corresponding to a risk reduction of 26%). These therapeutic benefits were observed in patients regardless of the presence/absence of hypertension, regardless of age, gender, type of stroke, or presence of diabetes mellitus. The results of the PROGRESS study showed that after 5 years of treatment, one stroke in every 23 patients and one serious cardiovascular event in every 18 patients can be avoided. Patients with stable CAD. EUROPA is an international, multicenter, randomized, double-blind, placebo-controlled clinical trial that lasted 4 years. 12218 patients aged 18 years and over were randomized into groups: 6110 patients received perindopril tertbutylamine 8 mg (equivalent to perindopril arginine 10 mg) and 6108 patients received placebo. The study included patients with confirmed coronary heart disease and without clinical symptoms of heart failure. Overall, 90% of patients had a history of myocardial infarction and/or revascularization surgery. Most patients in the study received perindopril in addition to standard therapy: antiplatelet agents, lipid-lowering drugs, and β-blockers. The main efficacy end point was the cumulative assessment of the occurrence of cardiovascular mortality, non-fatal myocardial infarction and/or cardiac arrest followed by a successful start. Treatment with perindopril 8 mg (equivalent to perindopril arginine 10 mg) once daily resulted in a significant absolute reduction in the primary endpoint of the study by 1.9% (20% relative risk reduction, 95% CI 9.4; 28, 6 - p<0.001). Patients with a history of myocardial infarction and/or revascularization had an absolute reduction of 2.2% in the primary endpoint, corresponding to a relative risk reduction of 22.4% (95% CI 12.0; 31.6 - p < 0.001) compared to placebo. Application for children. The safety and efficacy of perindopril in children and adolescents under 18 years of age have not been established. In an open clinical study without comparison groups, 62 children aged 2 to 15 years, whose glomerular filtration rate was> 30 ml / min / 1.73 m 2, were prescribed perindopril at an average dose of 0.07 mg / kg. The dose was adjusted individually, increasing to a maximum of 0.135 mg/kg/day depending on the patient’s profile and blood pressure responses to treatment. 59 patients participated in the study for 3 months, 36 patients continued treatment for at least 24 months (mean study duration 44 months). Systolic and diastolic blood pressure remained stable (from entry into the study to the last visit) in patients previously treated with other antihypertensive drugs and decreased in patients not previously treated. More than 75% of the children had systolic and diastolic blood pressures below the 95th percentile at their last study visit. The safety profile of use in children was consistent with the known safety profile of perindopril. PharmacokineticsAbsorption. After administration, perindopril is rapidly absorbed, the maximum plasma concentration is reached within 1:00. The half-life of perindopril in plasma is 1:00. Perindopril is a prodrug. 27% of the total amount of perindopril taken is determined in the blood as an active metabolite – perindoprilat. In addition to the active metabolite, perindoprilat, the drug forms 5 metabolites that are inactive. The maximum concentration of perindoprilat in plasma is reached 3-4 hours after ingestion. Food intake reduces the conversion of perindopril to perindoprilat, therefore, its bioavailability decreases, therefore the daily dose of perindopril arginine is recommended to be taken once in the morning before meals. Distribution. There is a linear relationship between the dose of perindopril and its concentration in blood plasma. The volume of distribution of unbound perindoprilat is approximately 0.2 l/kg. The binding of perindoprilat to plasma proteins is 20%, mainly from ACE, but this figure is dose-dependent. Conclusion. Perindoprilat is excreted in the urine. The terminal half-life of the unbound fraction is approximately 17 hours. The stage of equilibrium concentration in blood plasma is reached after 4 days from the start of treatment. Special groups of patients. The output of perindoprilat slows down in elderly patients, as well as in patients with heart or kidney failure. It is recommended to select a dose for patients with renal insufficiency, taking into account the degree of insufficiency (QC). Dialysis clearance of perindoprilat – 70 ml / min. The kinetics of perindopril changes in patients with cirrhosis of the liver, the hepatic clearance of perindopril is halved. However, the amount of perindoprilat formed does not decrease. Therefore, such patients do not need to adjust the dose. Indications for use Arterial hypertension. Heart failure. Prevention of recurrent stroke in patients with cerebrovascular disease. Prevention of cardiovascular complications in patients with documented stable ischemic heart disease. Long-term treatment reduces the risk of myocardial infarction and heart failure (according to the results of the EUROPA study). Method of administration and doses For oral administration. Tablets of 2.5 mg (Prestarium ® 2.5 mg) and 10 mg (Prestarium ® 10 mg) are not subject to distribution. Tablets of 5 mg (Prestarium ® 5 mg) are to be divided into two equal parts. Tablets are recommended to be taken 1 time per day in the morning before meals. The dose should be selected individually, depending on the patient’s profile, blood pressure indicators and response to treatment (see section “Peculiarities of use”). Arterial hypertension. Perindopril arginine can be given alone or in combination with other classes of antihypertensive drugs. The recommended starting dose is 5 mg once daily in the morning. Patients with high renin-angiotensin activity (especially patients with renovascular hypertension, fluid and electrolyte imbalance, cardiac decompensation or severe hypertension) may experience an excessive decrease in blood pressure after taking the first dose. It is recommended that such patients start treatment with a dose of 2.5 mg and start therapy under the supervision of a physician. The dose can be increased to 10 mg 1 time per day after 1 month of treatment. At the beginning of the use of perindopril arginine, symptomatic arterial hypotension may occur; this is more likely in patients who are taking diuretics concomitantly. In such patients, treatment with perindopril should be initiated with caution, as they may be deficient in water and/or salt. If possible, you should stop taking diuretics 2-3 days before the start of therapy with perindopril arginine (see section “Peculiarities of use”). In patients with arterial hypertension who cannot be discontinued from diuretics, treatment should be started with a dose of 2.5 mg. In such patients, renal function and serum potassium levels should be monitored. Further increase in the dose of perindopril arginine should be carried out depending on the indicators of blood pressure. If necessary, diuretic therapy can be restored. Elderly patients should begin treatment with a dose of 2.5 mg, which can be increased to 5 mg after 1 month of treatment, and then, if necessary, up to 10 mg, taking into account renal function (see Table provided below). Symptomatic heart failure. Patients with heart failure in whom perindopril arginine should usually be administered concomitantly with a diuretic that removes potassium and / or digoxin and / or a β-blocker, treatment is recommended to be started under close supervision and with an initial dose of 2.5 mg, should be taken in the morning. After 2 weeks, subject to good tolerance, increase the dose to 5 mg 1 time per day. In the future, the dose should be selected individually, depending on the clinical response of the patient to treatment. Patients with severe heart failure and other patients at high risk (patients with impaired renal function and a tendency to electrolyte disturbances, patients who receive concomitant therapy with diuretics and / or vasodilators) treatment should be started under close supervision (see section “Peculiarities of use “). In patients at high risk of symptomatic arterial hypotension, namely, patients with electrolyte deficiency with or without hyponatremia, patients with hypovolemia or those who received intensive diuretic therapy, the above conditions should be corrected, if possible, before prescribing the drug. Blood pressure, kidney function and serum potassium levels should be carefully monitored both before and during treatment (see section “Peculiarities of use”). Prevention of recurrent stroke in patients with cerebrovascular disease. The recommended starting dose is 2.5 mg (½ Prestarium ® 5 mg tablets) once a day in the morning. After 2 weeks of treatment, increase the dose to 5 mg (1 tablet Prestarium ® 5 mg) 1 time per day in the morning. If, after 2 weeks of treatment with Prestarium® 5 mg, the patient needs additional control of blood pressure, indapamide can be prescribed at a dose of 1 tablet per day. Treatment can begin at any time from 2 weeks to several years after the initial stroke. Prevention of cardiovascular events in patients with documented stable ischemic heart disease. Long-term treatment with Prestarium ® 10 mg (1 tablet per day) reduces the risk of myocardial infarction and heart failure (according to the results of a 4-year EUROPA study). Treatment should begin with the drug Prestarium ® 5 mg (1 tablet per day in the morning). After 2 weeks, subject to good tolerance, increase the dose to 10 mg for long-term use of the drug Prestarium ® 10 mg 1 tablet per day in the morning. Elderly patients with documented coronary heart disease should start treatment with a dose of 2.5 mg (? Prestarium ® 5 mg tablets) once a day in the morning, after a week the dose should be increased to 5 mg (1 tablet Prestarium ® 5 mg ) after 2 weeks, subject to good tolerance and depending on kidney function, increase the dose to 10 mg (Prestarium ® 10 mg 1 tablet per day) and start long-term treatment. Dose selection in renal failure. Use during pregnancy and lactation Pregnancy The drug is contraindicated for pregnant women or women planning pregnancy. If pregnancy is confirmed during treatment with the drug, its use must be immediately discontinued and replaced with another drug approved for use by pregnant women. If a woman took an ACE inhibitor during the second trimester of pregnancy, the child is recommended to have an ultrasound examination of the function of the kidneys and bones of the skull. Newborns whose mothers took ACE inhibitors during pregnancy should be carefully monitored because of the possibility of arterial hypotension. breast-feeding The use of perindopril arginine during lactation is not recommended due to the lack of data on its penetration into breast milk. During breastfeeding, it is desirable to prescribe an alternative treatment with a more researched safety profile, especially during the feeding of a newborn or premature infant. fertility No effects on fertility or fertility have been identified. Interactions with other drugs Data from clinical studies suggest that dual blockade of the renin-angiotensin-(RAAS) by concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse reactions such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared with the use of a single drug that affects the RAAS (see sections “Contraindications” and “Peculiarities of use”). Drugs that cause hyperkalemia. Some drugs or therapeutic classes of drugs can cause hyperkalemia, namely: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory drugs (NSAIDs), heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim. The simultaneous use of these drugs increases the risk of hyperkalemia. Simultaneous use is contraindicated (see “Contraindications”). Aliskiren: In diabetic patients or patients with impaired renal function, the risk of hyperkalemia, deterioration of renal function and cardiovascular morbidity and mortality is increased. Extracorporeal treatment leads to blood contact with negatively charged surfaces, such as high-flow dialysis or hemofiltration membranes (for example, polyacrylic membranes) and low-density lipoprotein apheresis with dextran sulfate, which can lead to an increased risk of severe anaphylactic reactions (see Section “Contraindications”) “). If such treatment is necessary, consideration should be given to using different types of dialysis membranes or different classes of antihypertensive drugs. Simultaneous use is not recommended (see section “Peculiarities of use”). Aliskiren: In all other patients, as in patients with diabetes mellitus or patients with impaired renal function, the risk of hyperkalemia, deterioration of renal function and cardiovascular morbidity and mortality is increased. According to the literature, it is known that in patients with established atherosclerosis, heart failure or diabetes mellitus with target organ damage, the simultaneous use of ACE inhibitors and angiotensin receptor blockers was accompanied by an increase in the incidence of arterial hypotension, syncope, hyperkalemia and deterioration of kidney function (including acute renal insufficiency) compared with monotherapy with drugs that affect the renin-angiotensin-aldosterone system. Dual blockade (i.e., a combination of an ACE inhibitor with an angiotensin II receptor antagonist) may be used in individual cases with close monitoring of renal function, potassium levels, and blood pressure. Estramustine: increased risk of adverse reactions such as angioedema (angioedema). Potassium-sparing diuretics (for example, triamterene, amiloride and others), potassium salts: the occurrence of hyperkalemia (possibly fatal), especially in patients with renal insufficiency (additive hyperkalemic effect). These drugs are not recommended for simultaneous use with perindopril (see section “Peculiarities of use”