Co-amlessa tablets 4mg/5mg/1.25mg 10×3

Name:
Ko-amlessa tab. 4mg5mg1.25mg in a blister. in pack. No. 10×3
Description:
Tablets 2 mg + 5 mg + 0.625 mg: white or almost white, oval, biconvex, with a score on one side of the tablet. The score line is intended solely to facilitate swallowing and does not ensure the division of the tablet into equal parts. Tablets 4 mg + 5 mg + 1.25 mg: white or almost white, round, slightly biconvex tablets with bevelled edges. Tablets 4 mg + 10 mg + 1.25 mg: white or almost white, oval, biconvex, scored on one side of the tablet. The tablet can be divided into equal parts. Tablets 8 mg + 5 mg + 2.5 mg: white or almost white, round, biconvex tablets. Tablets 8 mg + 10 mg + 2.5 mg: white or almost white, round, biconvex, scored on one side of the tablet. The tablet can be divided into equal parts. The main active ingredient Perindopril + indapamide + amlodipine Release form Tablets Dosage 4 mg + 5 mg + 1.25 mg Special warnings Lithium The concomitant use of lithium and the combination of perindopril/indapamide is generally not recommended. Double blockade of the renin-angiotensin-aldosterone system Double blockade of the renin-angiotensin-aldosterone system is associated with an increased risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Dual RAAS blockade with ACE inhibitors, angiotensin II receptor blockers (ARB II), or aliskiren cannot be recommended. In cases where concomitant use is absolutely indicated, careful observation by a specialist and mandatory monitoring of kidney function, water and electrolyte balance and blood pressure are necessary. ACE inhibitors and angiotensin II receptor blockers should not be administered simultaneously to patients with diabetic nephropathy. Potassium-sparing diuretics, potassium salts The combined use of perindopril and potassium-sparing diuretics, as well as potassium salts, is not recommended. Neutropenia/agranulocytosis Patients receiving ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia. Neutropenia is rare in patients with normal renal function in the absence of other complications. Perindopril should be used with extreme caution in patients with collagenoses receiving immunosuppressive treatment, allopurinol or procainamide treatment, especially in pre-existing renal dysfunction. These patients may develop serious infections that in some cases do not respond to intensive antibiotic therapy. In the case of the appointment of perindopril, it is recommended to periodically monitor the number of leukocytes; patients should be informed that if any signs of an infectious disease appear (sore throat, fever), they should immediately consult a doctor. Hypersensitivity/angioneurotic edema Rare cases of angioedema of the face, extremities, lips, tongue, pharynx and/or larynx have been reported in patients treated with ACE inhibitors, including perindopril. These conditions can develop at any time during therapy. In such cases, you should immediately stop taking the drug and establish appropriate monitoring of the patient’s condition until the complete disappearance of symptoms is confirmed. In cases where swelling affects only the face and lips, its manifestations usually disappear without special treatment, however, antihistamines may be used to relieve symptoms. Angioedema, accompanied by swelling of the larynx, can be fatal. If edema is detected in the region of the tongue, pharynx or larynx, which may lead to airway obstruction, appropriate therapy should be immediately prescribed, including subcutaneous administration of a 1:1000 solution of epinephrine (0.3 ml – 0.5 ml), and / or measures were taken to ensure the patency of the respiratory tract. A higher incidence of angioedema has been established in dark-skinned patients receiving ACE inhibitors. Patients with a history of angioedema that is not associated with ACE inhibitor therapy may be at an increased risk of developing angioedema while taking this group of drugs. There are rare cases of the development of intestinal vascular edema during therapy with ACE inhibitors. Patients have experienced abdominal pain (sometimes with nausea or vomiting); in some cases this was not preceded by angioedema of the face, C-1 esterase levels were normal. Angioedema has been diagnosed by procedures including abdominal computed tomography, either ultrasound or during surgery; symptoms disappeared after discontinuation of the ACE inhibitor. These phenomena should be taken into account in the differential diagnosis of patients receiving ACE inhibitors and presenting with abdominal pain. Anaphylactoid reactions during desensitization There are isolated reports of the development of a persistent, life-threatening anaphylactoid reaction in patients taking ACE inhibitors during desensitization therapy with hymenoptera (bees, wasps) venom. ACE inhibitors should be used with caution in patients prone to allergic reactions and undergoing desensitization; administration of the drug to patients undergoing antidote immunotherapy should be avoided. In cases where the patient requires both treatment with ACE inhibitors and desensitization, the onset of such reactions can be prevented by temporarily discontinuing the ACE inhibitor at least 24 hours before starting a course of desensitization therapy. Anaphylactoid reactions during LDL apheresis (low-density lipoprotein apheresis) Rare cases of life-threatening anaphylactoid reactions have been noted in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. The onset of such reactions can be prevented by temporarily stopping the use of ACE inhibitors before each JI11H11 apheresis procedure. Hemodialysis Cases of anaphylactoid reactions have been reported in patients undergoing hemodialysis using high flux density membranes (eg AN 69®) and concomitantly treated with ACE inhibitors. Such patients should be treated with either another type of dialysis membrane or another class of antihypertensive drugs. Hepatic encephalopathy With impaired liver function, the use of thiazide and thiazide-like diuretics can cause hepatic encephalopathy; in this case, the use of diuretics should be immediately discontinued. Photosensitivity There are cases of manifestations of photosensitivity reactions while taking thiazide and thiazide-like diuretics; in this case, it is recommended to stop taking the drug. When diuretics are re-administered, exposed areas of the skin should be protected from direct exposure to sunlight or artificial UV radiation. Pharmacological action Co-Amlessa is a combined antihypertensive drug containing three active components, with a complementary mechanism for controlling blood pressure in patients with hypertension. Perindopril erbumine (perindopril mpem-butylamine) is an angiotensin-converting enzyme inhibitor (ACE inhibitor), indapamide is a chlorosulfamoyl diuretic, amlodipine is a calcium ion antagonist. 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 the three components when combined. Indications for use Co-Amlessa is indicated for the treatment of arterial hypertension in patients who control blood pressure using a fixed combination of perindopril / indapamide while taking amlodipine at the same dosages. Dosing and Administration Dosage Take 1 tablet 1 time per day as a single dose, preferably in the morning before meals. The fixed dose combination is not intended to initiate therapy. Patients with impaired renal function The use of the drug is contraindicated in patients with severe renal insufficiency (creatinine clearance (Clcr) below 30 ml / min). Dosages of 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg are contraindicated in patients with moderate renal impairment (creatinine clearance 30-60 ml/min). Such patients are recommended individual selection of doses of each of the components separately. Routine medical supervision should include frequent monitoring of creatinine and potassium levels. Patients with renal insufficiency (glomerular filtration rate (GFR) < 60 ml / min / 1.73 m2) are contraindicated in the simultaneous use of perindopril with drugs containing aliskiren. Patients with impaired liver function In severe liver dysfunction, the use of the drug is contraindicated. The dosage regimen for patients with mild or moderate hepatic impairment has not been established; caution should be exercised when prescribing this combination. Elderly patients Excretion of perindoprilat is slowed down in this category of patients. Treatment should be based on their renal function. Children The safety and efficacy of the drug in children and adolescents have not been established. No data available. How to use For oral administration. Take 1 tablet 1 time per day as a single dose, preferably in the morning before meals. If necessary, Co-Amlessa tablets 4 mg/10 mg/1.25 mg and Co-Amlessa tablets 8 mg/10 mg/2.5 mg can be divided into equal parts (doses). To do this, the tablet should be placed on a horizontal surface with the risk up and pressed with two fingers on both edges. Application during pregnancy and lactation Pregnancy Considering the influence of each component separately, the drug is not recommended in the first trimester of pregnancy. The drug is contraindicated in the second and third trimesters of pregnancy. The drug is contraindicated during lactation. A decision should be made either to stop breastfeeding or to suspend treatment, taking into account the need for this therapy for the mother. Perindopril The use of ACE inhibitors is not recommended during the first trimester of pregnancy. The use of ACE inhibitors is contraindicated in the second and third trimesters of pregnancy. Epidemiological data on the risk of teratogenicity when taking ACE inhibitors in the first trimester of pregnancy do not allow a final conclusion, but some increased risk is not excluded. Unless it is not possible to replace ACE inhibitors with other alternative therapy, patients planning pregnancy should be switched to therapy with drugs whose safety profile for pregnant women is well established. If pregnancy occurs, the ACE inhibitor should be discontinued immediately and, if necessary, other therapy should be prescribed. When using ACE inhibitors in the second and third trimesters of pregnancy, a manifestation of fetotoxic action (impaired kidney function, oligohydroamniosis, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia) was established. If an ACE inhibitor was taken from the second trimester of pregnancy, it is recommended to conduct an ultrasound of the function of the kidneys and bones of the skull. In newborns whose mothers have taken ACE inhibitors, blood pressure should be carefully monitored to prevent the possible development of hypotension. Indapamide Long-term use of thiazide diuretics in the third trimester of pregnancy can lead to a decrease in maternal plasma volume, as well as a decrease in uteroplacental blood flow, which can cause fetoplacental ischemia and fetal growth retardation. In addition, there are rare cases of the development of hypoglycemia and thrombocytopenia in newborns while taking diuretics shortly before childbirth. Amlodipine The safety of amlodipine in pregnant women has not been established. In animal studies, reproductive toxicity has been identified at high doses. Lactation The drug is contraindicated during lactation. A decision should be made either to stop breastfeeding or to suspend treatment, taking into account the need for this therapy for the mother. Perindopril there are no data on the use of perindopril during lactation, the drug is not recommended for this category of patients. Alternative treatment with an established safety profile should be considered, especially when feeding neonates or premature infants. Indapamide Excreted in breast milk. In terms of pharmacological properties, indapamide is close to thiazide diuretics, which, in turn, when taken during breastfeeding, can lead to a decrease in the amount of breast milk or suppress lactation. Possible hypersensitivity reactions to sulfonamide derivatives, hypokalemia and "nuclear" jaundice. Amlodipine It is not known whether amlodipine is excreted in breast milk. Effects on the reproductive system Perindopril and indapamide Reproductive toxicity studies have shown no effect on the reproductive function of female and male rats. Impact on human reproductive function is not expected. Amlodipine Reversible biochemical changes in the head of spermatozoa have been reported in some patients treated with calcium channel blockers. Clinical data regarding the potential effect of amlodipine on reproductive function are insufficient. In one study, adverse effects on the reproductive system of male rats were reported. PrecautionsImpaired renal function The use of the drug is contraindicated in patients with severely impaired renal function (creatinine clearance < 30 ml / min). Dosages containing 8 mg/2.5 mg perindopril/indapamide (eg, 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg tablets) are contraindicated in patients with moderate renal impairment (creatinine clearance lower 60 ml/min). Treatment should also be discontinued if functional renal failure is detected in a patient with arterial hypertension without previous severe renal dysfunction during laboratory blood tests. Therapy may be resumed either at a lower dosage or with only one of the components. The usual medical examination of such patients should include frequent monitoring of potassium and creatinine levels according to the scheme: the first time - after two weeks of treatment, then every two months during the period of therapeutic stability. Renal failure has been observed mainly in patients with severe heart failure or previous renal failure, including renal artery stenosis. This drug is generally not recommended for patients with bilateral renal artery stenosis or patients with one functioning kidney. Risk of arterial hypotension and / or renal failure (in case of heart failure, water-salt imbalance, etc.) With a significant loss of water and electrolytes (strict salt-free diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with stenosis renal artery, chronic heart failure or cirrhosis of the liver, accompanied by edema and ascites, there is a pronounced stimulation of the renin-angiotensin-aldosterone system. Therefore, inhibition of this system when taking ACE inhibitors can cause (most likely at the first dose of the drug or during the first two weeks of treatment) a sharp drop in blood pressure and / or an increase in plasma creatinine, which indicates functional renal failure. In rare cases, these symptoms can develop acutely and with varying time before their onset. In such cases, treatment can be resumed at a lower dose, with a gradual increase. In patients with ischemic heart disease or cerebrovascular disease, an excessive decrease in blood pressure can lead to myocardial infarction or cerebrovascular complications. Thiazide and thiazide-like diuretics are most effective in cases where renal function is normal or slightly impaired (for adult patients, creatinine levels are below ~ 25 mg / l, i.e. 220 μmol / l). In elderly patients, plasma creatinine levels should be adjusted for age, body weight and sex of the patient using the Cockcroft formula: clcr = (140 - age in years) ? body weight in kg / 0.814 ? plasma creatine level in µmol/l, which is derived for men and can be adapted for women by multiplying the result by 0.85. At the beginning of treatment, hypovolemia caused by the loss of water and sodium while taking diuretics can lead to a decrease in the glomerular filtration rate and be accompanied by an increase in the concentration of creatinine and urea in the blood plasma. This transient functional renal failure has no adverse consequences in patients with normal renal function, but may worsen pre-existing renal failure. The usual medical examination of such patients should include frequent monitoring of potassium and creatinine levels according to the scheme: the first time - after two weeks of treatment, then every two months during the period of therapeutic stability. Changes in the concentration of amlodipine in plasma do not correlate with the degree of impaired renal function. Amlodipine can be used in usual doses for the treatment of such patients. The effect of Co-Amlessa has not been studied in patients with impaired renal function. The properties of each individual component of this combination should be taken into account. Hypotension and electrolyte disturbances With low sodium levels, especially in patients with initially low blood pressure, renal artery stenosis, congestive heart failure, or cirrhosis with edema and ascites, there is a risk of sudden hypotension. Systematic monitoring should be carried out to detect clinical signs of deficiency in the body of water or electrolytes, for example, after diarrhea or vomiting. In such patients, it is necessary to regularly determine the content of electrolytes in the plasma. In the case of severe hypotension, intravenous isotonic saline may be necessary. Transient hypotension is not a contraindication for continued treatment. After restoration of a satisfactory blood volume and blood pressure, treatment can be resumed either with a lower dosage of the drug, or with only one of its components. Taking any diuretic drugs can lead to a decrease in the sodium content in the blood plasma, which, in turn, contributes to the development of a number of serious complications. Initially, a decrease in sodium levels may be asymptomatic, which is why regular monitoring is necessary. In elderly patients and in patients with cirrhosis, monitoring should be carried out even more frequently. Potassium content The combination of indapamide, perindopril and amlodipine does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or in patients with renal insufficiency. As in the case of the use of any other antihypertensive drug in combination with a diuretic, regular monitoring of the content of potassium in the blood plasma should be carried out. In some patients treated with ACE inhibitors, including perindopril, there have been cases of an increase in the content of potassium in the blood serum. Risk factors for hyperkalemia include renal insufficiency, worsening renal function, age > 70 years, diabetes mellitus, certain comorbid conditions (decreased CBV, acute heart failure, metabolic acidosis, concomitant use of potassium-sparing diuretics, such as spironolactone, eplerenone, triamterene, or amiloride), and also potassium preparations or potassium-containing salt substitutes. The risk group also includes patients taking other drugs that increase the content of potassium in the blood serum (for example, heparin). Hyperkalemia can lead to serious heart rhythm disturbances, sometimes fatal. If the concomitant administration of the above-mentioned agents is considered necessary, then their administration should be carried out with regular monitoring of the level of potassium in the blood serum. The greatest risk when taking thiazide and thiazide-like diuretics is hypokalemia. Particular attention in order to prevent hypokalemia (< 3.4 mmol / l) should be given to persons at increased risk: elderly patients and / or patients with malnutrition, regardless of whether they are taking other drugs; patients with cirrhosis of the liver, which is accompanied by edema and ascites; patients with ischemic heart disease and heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of developing arrhythmias. The high-risk group also includes patients with an extended QT interval on the ECG, regardless of the etiology of the disease. Hypokalemia, as well as bradycardia, is a predisposing factor in the development of serious cardiac arrhythmias, especially torsades de pointes, which can be fatal. In all the cases described, more frequent monitoring of the concentration of potassium in the blood plasma is required - the first measurement of this indicator should be carried out during the first week of treatment. If a low potassium level is detected, correction is required. Calcium content Thiazide and thiazide-like diuretics can reduce the excretion of calcium in the urine, leading to a slight and temporary increase in the content of calcium in the blood plasma. A significant increase in calcium levels may be due to latent hyperparathyroidism. In this case, treatment should be discontinued until the function of the parathyroid glands has been investigated. Renovascular hypertension Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension who are awaiting surgery or in whom such surgery is not possible. When prescribing the drug to patients with established or suspected renal artery stenosis, treatment should be started with low doses in a hospital setting, while monitoring renal function and potassium levels is necessary, since some patients developed functional renal failure, reversible after discontinuation of the drug. Dosages of 8 mg/5 mg/2.5 mg and 8 mg/10 mg/2.5 mg are not recommended for this category of patients. Atherosclerosis The risk of hypotension exists in all patients, but special care must be taken in patients with ischemic heart disease or cerebrovascular insufficiency. Treatment should begin with low doses. Hypertensive crisis The safety and efficacy of amlodipine in hypertensive crisis have not been established. Heart failure The drug should be used with caution in patients with heart failure. In patients with severe heart failure (class IV), treatment should be initiated under medical supervision and at lower doses. Beta-blockers should not be discontinued in patients with hypertension and coronary insufficiency: ACE inhibitors should be added to the beta-blocker regimen. In a long-term placebo-controlled study in patients with severe heart failure (NYHA functional classes III and IV), the incidence of pulmonary edema in the amlodipine group was higher than in the placebo group. Calcium channel blockers, including amlodipine, should be used with caution in patients with congestive heart failure, as the risk of cardiovascular events and mortality may be increased. Aortic or mitral valve stenosis/hypertrophic cardiomyopathy Caution should be exercised when using ACE inhibitors in patients with left ventricular outflow tract obstruction. Patients with diabetes mellitus In patients with insulin-dependent diabetes mellitus (danger of spontaneous increase in potassium levels), treatment should be started at low doses and under medical supervision. In patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, during the first month of therapy with an ACE inhibitor, it is necessary to regularly monitor the concentration of glucose in the blood. Cough During therapy with ACE inhibitors, a dry cough may develop, which is persistent and disappears after discontinuation of the drug. This symptom may have an iatrogenic etiology. If an ACE inhibitor is preferred, then continued treatment should be considered. Ethnic characteristics Perindopril (like other ACE inhibitors) has a less pronounced hypotensive effect in patients of the black race compared to representatives of other races, possibly due to the higher prevalence of low renin conditions in this category of patients suffering from hypertension. Surgery / Anesthesia ACE inhibitors can cause a drop in blood pressure during anesthesia, especially if the anesthetic used has a hypotensive effect. Therefore, treatment with long-acting ACE inhibitors such as perindopril is recommended, if possible, to stop one day before surgery. Liver failure In rare cases, therapy with ACE inhibitors was accompanied by a syndrome that began with cholestatic jaundice, progressed to fulminant hepatic necrosis and (sometimes) ended in death. The mechanism of this syndrome is not known. Patients receiving ACE inhibitors who develop jaundice or significantly elevated liver enzymes should stop taking ACE inhibitors and undergo medical evaluation. In patients with impaired liver function, the half-life of amlodipine is prolonged and AUC values are increased; dosing recommendations not validated. However, it is recommended to start treatment with low doses of amlodipine, and caution should be exercised at the beginning of therapy and when increasing doses. When using the drug in patients with severe hepatic insufficiency, slow dose titration and careful medical supervision may be required. The effect of Co-Amlessa has not been studied in patients with hepatic impairment. Given the properties of each individual component of this combination, the drug is contraindicated in patients with severe hepatic impairment, with mild to moderate hepatic insufficiency, caution should be exercised. Uric acid In patients with hyperuricemia, the frequency of exacerbation of gout attacks may increase. Elderly patients Renal function and potassium levels should be assessed before starting treatment. In order to avoid a sharp decrease in blood pressure, the initial dose of the drug is selected depending on the hypotensive effect, especially in cases of sodium deficiency. Caution should be exercised when increasing the dose of amlodipine in this category of patients. Children The efficacy and tolerability of the drug in children and adolescents have not been established. Interactions with other drugs Drug-induced hyperkalemia Some drugs may increase the likelihood of developing hyperkalemia: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, HHAC, heparin, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim. The combination of these drugs increases the risk of hyperkalemia. Simultaneous administration of Aliskiren is contraindicated In patients with diabetes mellitus or renal insufficiency, the risk of hyperkalemia, deterioration of renal function, cardiovascular morbidity and mortality is increased. Simultaneous administration is not recommended Perindopril / indapamide Lithium With the simultaneous use of lithium and ACE inhibitors, cases of a reversible increase in serum lithium concentration and toxicity have been reported. Concomitant use of thiazide diuretics against the background of ACE inhibitors may increase the level of lithium and increase the risk of lithium toxicity. The use of perindopril in combination with indapamide and lithium is not recommended, but if it is still necessary, then careful monitoring of the content of lithium in the blood serum should be carried out. Perindopril Aliskiren In patients, incl. without a history of diabetes mellitus or renal insufficiency, there is a risk of hyperkalemia, deterioration of renal function, cardiovascular morbidity and mortality. Concomitant use of ACE inhibitors and angiotensin II receptor blockers Clinical trials have shown that 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 side effects such as hypotension , hyperkalemia and impaired renal function (including acute renal failure), compared with monotherapy. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes Hyperkalemia (potentially fatal) possible, particularly in patients with renal insufficiency (additive hyperkalemic effect). Combinations of perindopril with the drugs listed above are not recommended. If co-administration is indicated, then care must be taken and frequent monitoring of the content of potassium in the blood serum is necessary. For the case of the use of spironolactone in patients with heart failure, see the subsection "Concomitant use requiring special care". Estramustine Risk of increased adverse effects such as angioedema (angioedema). Amlodipine Dantrolene (infusion) In animals after the introduction of verapamil and dantrolene intravenously, cardiovascular failure and ventricular fibrillation with a fatal outcome were noted, accompanied by hyperkalemia. In view of possible hyperkalemia, it is recommended to avoid the concomitant administration of calcium channel blockers such as amlodipine in patients at risk of developing malignant hyperthermia or in the treatment of malignant hyperthermia. Grapefruit juice It is not recommended to take amlodipine concomitantly with grapefruit juice or grapefruit, as the effect of lowering blood pressure may be enhanced due to increased bioavailability. Simultaneous reception requiring special care Perindopril / indapamide 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 (NSAIDs), including high doses of acetylsalicylic acid 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 NSAIDs) can cause a decrease in the hypotensive effect of ACE inhibitors. The simultaneous use of these drugs also increases the risk of impaired renal function up to the development of acute renal failure and an increase in the content of potassium in the blood serum, especially in patients with pre-existing impaired renal function. This combination should be used with caution, especially in the elderly. Patients should receive adequate fluids, and it is recommended to monitor kidney function before and periodically after the start of treatment. Perindopril Antidiabetic drugs (insulin, oral hypoglycemic agents) Epidemiological studies suggest that the combined use of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic agents) may cause or increase the hypoglycemic effect with the risk of hypoglycemia, which is most likely in patients with renal insufficiency and in the first weeks of therapy. Potassium-sparing diuretics Patients taking diuretics, especially those with hypovolemia and/or salt deficiency, may develop an excessive decrease in blood pressure at the beginning of taking ACE inhibitors. The risk of hypotension can be reduced by discontinuing the diuretic, increasing fluid or salt intake before starting treatment, and starting with low initial doses of perindopril followed by increases. In arterial hypertension, when hypovolemia and / or salt deficiency due to diuretic use are possible, consideration should be given to either discontinuing the diuretic before starting the ACE inhibitor and then re-administering it, or starting ACE inhibitor therapy from lower doses with subsequent increase. In patients with chronic heart failure receiving diuretic therapy, the ACE inhibitor should be prescribed at a very low dose, if possible after reducing the dose of the diuretic. In all cases, renal function (creatinine levels) should be monitored during the first weeks of therapy with an ACE inhibitor. Potassium-sparing diuretics (eplerenone, spironolactone) Eplerenone or spironolactone at doses of 12.5 mg - 50 mg / day and an ACE inhibitor at low doses: in patients with heart failure (NYHA functional classes II-IV) with an ejection fraction < 40%, previously treated with ACE inhibitors and "loop" diuretics, in cases of non-compliance with the recommendations for the use of this combination, there is a risk of developing hyperkalemia, potentially fatal. Before starting this combination, hyperkalemia and renal failure should be excluded. The content of potassium and creatinine in the blood plasma should be monitored weekly during the first month of treatment and then once a month. Indapamide Drugs that cause ventricular tachycardia type "pirouette" Due to the risk of developing hypokalemia, care should be taken when prescribing indapamide and drugs that cause ventricular tachycardia type "pirouette", such as: antiarrhythmic substances of class IA (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), oth