Co-Prenessa tablets 8mg/2.5mg №10×3

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Co-Prenessa tablets 8mg2.5mg in a blister. in pack. No. 10×3
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Tablets 8 mg: round, slightly biconvex tablets from white to almost white with bevelled edges and a notch on one side. The main active ingredient Perindopril + indapamide Release form tablets Dosage 8 mg + 2.5 mg Special instructions General for perindopril and indapamide did not have. If a patient simultaneously starts taking two new antihypertensive drugs for him, then an increase in the frequency of idiosyncratic reactions cannot be ruled out. To minimize this risk, careful monitoring of the patient’s condition should be carried out. In general, a combination of lithium preparations and a combination of perindopril and indapamide is not recommended. Neutropenia/Agranulocytosis Associated with Perindopril Neutropenia/agranulocytosis, thrombocytopenia and anemia may develop in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function in the absence of other complications. Perindopril should be administered with extreme caution to patients with collagenoses receiving immunosuppressive treatment, treatment with allopurinol or procainamide, especially with pre-existing impaired renal function. 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 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 reactions 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, but antihistamines can be used to relieve symptoms. Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, pharynx, or larynx can lead to airway obstruction. In this case, appropriate therapy should be immediately prescribed, which may include s / c administration of a solution of epinephrine 1: 1000 (0.3-0.5 ml) and / or measures to ensure airway patency. A higher incidence of angioedema has been established in black 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. Rare cases of the development of angioedema of the intestine during therapy with ACE inhibitors are known, which should be taken into account when conducting differential diagnosis of patients receiving ACE inhibitors and presenting with abdominal pain. Patients experienced abdominal pain (with or without nausea or vomiting); in some cases, this was not preceded by angioedema of the face, the activity of C1-esterase was within normal limits. Angioedema has been diagnosed through procedures including abdominal CT or ultrasound or during surgery; resolution of symptoms occurred after discontinuation of the ACE inhibitor. Concomitant use of mTOR inhibitors Patients receiving mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) concomitantly with Co-Prenessa® are at a higher risk of developing angioedema. 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 immunotherapy with hymenoptera venom 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 the start of desensitization therapy. Anaphylactoid reactions during LDL apheresis Rare cases of life-threatening anaphylactoid reactions have been reported 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 LDL apheresis procedure. Hemodialysis Anaphylactoid reactions have been reported in patients undergoing hemodialysis using high flux density membranes (eg AN69®) and concomitantly treated with ACE inhibitors. Such patients should be treated with either another type of dialysis membrane or another class of antihypertensive drugs. Potassium-sparing diuretics, potassium salts The combined use of perindopril and potassium-sparing diuretics, as well as potassium salts, is not recommended. Associated with indapamide In case of impaired liver function, the use of thiazide and thiazide-like diuretics can cause encephalopathy. In this case, the drug should be stopped immediately. Photosensitivity There are cases of manifestations of photosensitivity reactions while taking thiazide and thiazide-like diuretics. With the development of such reactions, it is recommended to stop taking the drug. When diuretics are re-administered, exposed skin should be protected from direct exposure to sunlight or artificial UV radiation. Precautions for use General for perindopril and indapamide Impaired renal function Treatment with the drug at doses of 2 mg / 0.625 mg and 4 mg / 1.25 mg is contraindicated in patients with severe renal insufficiency (CC <30 ml / min), at a dose of 8 mg / 2.5 mg - with CC <60 ml / min. Treatment should also be discontinued if functional renal failure is detected in a patient with arterial hypertension without a previous severe impairment of kidney function during a blood test. Therapy may be restarted either at a lower dose or with only one of the components. The usual medical examination of such patients should include frequent monitoring of potassium and creatinine according to the scheme: the first time - after 2 weeks of treatment, then every 2 months during the period of therapeutic stability. Renal failure has been observed mainly in patients with acute heart failure or occult 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. Hypotension and disturbance of water and electrolyte balance With a low sodium content, especially in patients with renal artery stenosis, there is a risk of a sudden drop in blood pressure. Therefore, a systematic analysis should be carried out to detect clinical signs of a deficiency in the body of water and electrolytes, for example, after diarrhea or vomiting. In such patients, it is necessary to regularly monitor the content of electrolytes in the plasma. In case of severe arterial hypotension, it may be necessary to inject an isotonic solution intravenously. 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 dose of the drug, or with only one of its components. Potassium content The combination of perindopril and indapamide does not prevent the development of hypokalemia, especially in patients with diabetes mellitus or with renal insufficiency. As with other antihypertensive drugs containing a diuretic, regular monitoring of plasma potassium levels should be carried out. Excipients The drug contains lactose, so it should not be prescribed to patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome. Preclinical safety data The combination of perindopril and indapamide slightly increased toxicity compared to the individual components. In rats, no increase in renal toxicity was observed, but the combination caused gastrointestinal toxicity in dogs. Maternal toxicity appears to be increased in rats (compared to perindopril alone). However, these adverse effects appeared at doses with a very high margin of safety compared to the therapeutic doses used. Associated with perindopril. In chronic toxicity studies conducted in rats and monkeys, the kidney was the target organ with reversible damage when administered orally. Mutagenicity was not observed in in vitro or in vivo studies. Reproductive toxicity studies in rats, mice, rabbits and monkeys showed no signs of embryotoxicity or teratogenicity. However, ACE inhibitors, as a class, cause side effects late in fetal development. In rodents and rabbits, such effects resulted in fetal death or congenital anomalies: kidney damage was observed, as well as increased peri- and postnatal mortality. In long-term studies conducted in rats and mice, carcinogenicity has not been reported. Associated with indapamide. The highest doses administered orally in various animal species (from 40 to 8000 therapeutic doses) have been shown to increase the diuretic properties of indapamide. The main symptoms of intoxication in acute toxicity studies with indapamide administered intravenously or intraperitoneally were associated with the pharmacological action of indapamide, i.e. bradypnea and peripheral vasodilation. No mutagenic or carcinogenic effects were observed during studies. Perindopril-associated Cough Taking ACE inhibitors may cause a dry cough that is persistent and disappears when the drug is discontinued. This symptom may have an iatrogenic etiology. If an ACE inhibitor is preferred, then continued treatment should be considered. Children and adolescents The efficacy and tolerability of perindopril and its combinations in children and adolescents has not been established. Dual blockade of the RAAS There is evidence that the simultaneous use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by the combined use of ACE inhibitors, angiotensin II receptor antagonists, or aliskiren is not recommended. If dual blockade therapy is considered absolutely necessary, it should only be given under close supervision and with frequent monitoring of renal function, electrolytes, and blood pressure. ACE inhibitors and angiotensin II receptor antagonists should not be used simultaneously in patients with diabetic nephropathy. Risk of arterial hypotension and / or renal failure (in case of heart failure, water and electrolyte imbalance) With a significant loss of water and electrolytes (salt diet or long-term treatment with diuretics), especially in patients with initially low blood pressure, with renal artery stenosis, congestive heart insufficiency or cirrhosis of the liver, accompanied by edema and ascites, there is a pronounced stimulation of the RAAS. 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 or an increase in plasma creatinine, which indicates functional renal failure. In some, although rare cases, these symptoms can develop acutely and with a variable time before their onset. In such cases, treatment can be resumed at a lower dose, gradually increasing it. Elderly patients Before starting treatment, kidney function and potassium concentration should be assessed. In order to avoid a sharp decrease in blood pressure, the initial dose of the drug is selected depending on the degree of reduction in blood pressure, especially in the event of a violation of the water and electrolyte balance. Patients with established atherosclerosis The risk of hypotension exists in all patients, but special care must be taken in patients with CAD or cerebrovascular insufficiency. Treatment should begin with low doses. Renovascular hypertension Renovascular hypertension is treated by revascularization. However, the use of ACE inhibitors may be beneficial in patients with renovascular hypertension awaiting surgery, or in the absence of such treatment. When prescribing Co-Prenessa® to patients with established or suspected renal artery stenosis, treatment should be started in a hospital setting at a low dose, and monitoring of kidney function and potassium levels is necessary, because. some patients developed functional renal failure, reversible when the drug is discontinued. The drug Co-Prenessa® 8 mg / 2.5 mg is not prescribed to patients with established or suspected renal artery stenosis, because. in this case, treatment should be started in a hospital with lower doses. Patients with diabetes mellitus When prescribing ACE inhibitors to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood. Other risk groups In patients with severe heart failure (grade IV) or in patients with insulin-dependent diabetes mellitus (danger of spontaneous increase in potassium concentration), treatment should be started at low doses and under medical supervision, therefore Co-Prenessa® 8 mg / 2.5 mg should not suitable for initiation of therapy. Patients with arterial hypertension and coronary insufficiency should not stop treatment with beta-blockers: an ACE inhibitor should be taken in conjunction with beta-blockers. Surgery/Anesthesia ACE inhibitors can cause a fall 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. Aortic or mitral valve stenosis/hypertrophic cardiomyopathy Caution should be exercised when using ACE inhibitors in patients with left ventricular outflow tract obstruction. 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 unknown. Patients receiving ACE inhibitors who develop jaundice or have a significant increase in liver enzymes should stop taking ACE inhibitors and undergo a thorough medical examination. Hyperkalemia In some patients treated with ACE inhibitors, including perindopril, there have been cases of increased serum potassium levels. Risk factors for hyperkalemia include renal insufficiency, age over 70 years, diabetes mellitus, certain comorbid conditions (decrease in BCC, acute heart failure in the stage of decompensation, metabolic acidosis), concomitant use of potassium-sparing diuretics (eg, spironolactone, eplerenone, triamterene, or amiloride), and also potassium preparations or potassium-containing salt substitutes. Patients at risk also include 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 concentration of potassium in the blood serum. 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. Related to indapamide Sodium content Before starting treatment, sodium content should be assessed; in the future, such a survey should be carried out regularly. 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 concentration may be asymptomatic, which is why regular monitoring is necessary. In elderly patients and patients with cirrhosis, monitoring should be carried out even more frequently. Potassium content Therapy with thiazide and thiazide-like diuretics is associated with the risk of hypokalemia. It is necessary to take into account the risk of reducing the potassium content below the acceptable level (<3.4 mmol / l) in people who are at high 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 coronary heart disease and heart failure. In such cases, hypokalemia increases the toxicity of cardiac glycosides and increases the risk of developing arrhythmias. Patients with an extended QT interval are also at increased risk. Hypokalemia, like bradycardia, is a risk factor for the development of serious cardiac arrhythmias, especially torsades de pointes, which can be fatal. In all the cases described, the concentration of potassium should be regularly monitored. The first determination of the content of potassium in plasma should be carried out within the first week after the start of treatment. In the event of a decrease in the concentration of potassium, a correction is necessary. 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 may be the result of latent hyperparathyroidism. In this case, treatment should be discontinued until the function of the parathyroid glands has been investigated. The content of glucose in the blood In patients with diabetes, it is necessary to constantly monitor the concentration of glucose in the blood, especially in cases where the potassium content is simultaneously reduced. Uric acid In patients with hyperuricemia during therapy with the drug, the frequency of exacerbation of gout attacks may increase. Renal function and diuretics 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 values should be adjusted according to the age, body weight and sex of the patient using the Cockcroft formula: For men: img_f-KK- For women: the result of the calculation should be multiplied by 0.85. At the beginning of treatment, hypovolemia caused by the loss of water and sodium while taking diuretics may lead to a decrease in GFR and be accompanied by an increase in the concentration of creatinine and urea in the blood plasma. This transient functional renal insufficiency does not lead to undesirable consequences in patients with unchanged renal function, but in patients with renal insufficiency it can cause a worsening of the condition. Visual impairment Sulfonamide-based preparations can cause an idiosyncratic reaction leading to short-term myopia and acute angle-closure glaucoma. Acute glaucoma can cause permanent vision loss. The first step is to stop treatment as soon as possible. If intraocular pressure remains uncontrolled, appropriate drug therapy or surgery may be required. A risk factor for the development of acute closed glaucoma is a history of hypersensitivity to sulfonamides or penicillins. Athletes The product contains an active substance that may give a positive reaction during doping control. Influence on the ability to drive vehicles and control mechanisms None of the active substances, either individually or in combination as part of Co-Prenessa®, has a direct effect on the ability to drive a car and work with potentially dangerous mechanisms. However, in some patients, especially at the beginning of treatment or when combined with other antihypertensive drugs, the drug may cause individual reactions associated with a decrease in blood pressure, and thus indirectly affect their psychophysical state. As a result, the ability to drive and use machines may be impaired. Pharmacodynamics Pharmacodynamic properties Perindopril is an angiotensin-converting enzyme (ACE) inhibitor that converts angiotensin I to angiotensin II (angiotensin-converting enzyme - ACE). A converting enzyme or kininase is an exopeptidase that allows the conversion of angiotensin I to the vasoconstrictor angiotensin II and also degrades the vasodilator bradykinin to an inactive hectapeptide. Inhibition of ACE leads to a decrease in the content of angiotensin II in blood plasma, which entails an increase in plasma renin activity (through inhibition of negative feedback on renin release), and to a decrease in aldosterone secretion. Since ACE inactivates bradykinin, ACE inhibition also leads to an increase in the activity of the circulation and local kallikrein-kinin systems (which activates the prostaglandin system). It is possible that this mechanism contributes to the blood pressure-lowering action of ACE inhibitors and partly explains some of their side effects (eg, cough). Perindopril acts through its active metabolite, perindoprilat. Other metabolites do not show activity against ACE inhibition in vitro. Hypertension Perindopril acts on arterial hypertension of any degree: mild, moderate and severe, reduces systolic and diastolic blood pressure in the supine and standing position. Perindopril reduces peripheral vascular resistance, which leads to a decrease in systemic blood pressure. As a result, peripheral blood flow increases without any effect on heart rate. Typically, renal blood flow increases while glomerular filtration rate (GFR) usually remains unchanged. The antihypertensive effect reaches a maximum 4-6 hours after taking a single dose and persists for at least 24 hours; the minimum effect is about 87%-100% of the maximum effect. Reducing the decrease in blood pressure occurs quickly. In treated patients, blood pressure normalizes within one month and persists without tachyphylaxis. Termination of therapy does not lead to a withdrawal syndrome. Perindopril reduces left ventricular hypertrophy. It has been confirmed that perindopril has vasodilating properties. Perindopril helps to restore the elasticity of large arterial vessels and reduces the duct/lumen ratio in small arterial vessels. Combination therapy with a thiazide diuretic results in additive synergism. The combined use of an ACE inhibitor and thiazide drugs also reduces the risk of diuretic-induced hypokalemia. Heart failure Perindopril reduces the work of the heart, reducing pre- and afterload. Studies in patients with heart failure have shown the following: decreased left and right ventricular filling pressure, reduced total peripheral vascular resistance, increased cardiac output, and improved cardiac index. In comparative studies, the first use of the initial dose of perindopril 2 mg in patients with mild to moderate heart failure did not cause a significant decrease in blood pressure compared with placebo. Patients with stable coronary heart disease The EUROPA study was a 4-year multicentre, international, randomized, double-blind, placebo-controlled clinical trial. Twelve thousand two hundred and eighteen (12218) patients over 18 years of age were randomized to receive perindopril 8 mg (n=6110) or placebo (n=6108). There was evidence of coronary heart disease in the study population. Evidence of clinical signs of heart failure was not obtained. Overall, 90% of patients had a previous myocardial infarction and/or coronary artery revascularization. Most patients received the study drug in addition to conventional therapy, which included platelet inhibitors, lipid-lowering agents, and beta-blockers. The primary end point was the composite of cardiovascular death, non-fatal myocardial infarction, and/or cardiac arrest with successful resuscitation. Treatment with perindopril 8 mg once daily resulted in a significant absolute reduction in the primary endpoint of 1.9% (relative risk reduction 20%, 95% CI 9.4; 28.6 - p<0.001). Patients who underwent myocardial infarction and/or revascularization experienced an absolute decrease of 2.2%, corresponding to an RRR of 22.4%, 95% CI 12.0; 31.6 - p<0.001), in the primary endpoint compared to placebo. Pharmacokinetics Absorption After oral administration, the absorption of perindopril is rapid and reaches a maximum concentration within 1 hour. The plasma half-life of perindopril is 1 hour. Perindopril is a prodrug. Bioavailability from 65 to 70%. Metabolism Approximately 20% of the administered dose of perindopril reaches the bloodstream as the active metabolite of perindoprilat. In addition to the active perindoprilat, 5 inactive metabolites are formed in the body. The highest concentration of perindoprilat in plasma is reached within 2-6 hours. Food intake reduces the conversion of perindopril to perindoprilat and, therefore, its bioavailability, therefore perindopril tertbutylamine is recommended to be taken once a day, orally, in the morning before meals. A linear relationship was shown between the dose of perindopril and its plasma exposure. Distribution The volume of distribution is approximately 0.2 L/kg for unbound perindoprilat. The binding of perindoprilat to plasma proteins is less than 30%, mainly with the angiotensin-converting enzyme, but the binding is concentration dependent. Withdrawal Approximately 70% of perindoprilat is excreted from the body by the kidneys. The elimination half-life of perindopril is 1-2 hours. The elimination profile of perindoprilat is biphasic with a short T1 / 2 and its free fraction of 3-5 hours, and a longer final elimination phase (24 hours) with the dissociation of perindopril associated with ACE, which allows reaching an equilibrium state in 4 days. After repeated administration of perindopril cumulation is not observed. Pharmacokinetics in special clinical situations Excretion of perindoprilat is reduced in elderly patients, as well as in patients with heart or kidney failure. In renal insufficiency, it is desirable to adjust the dosage based on the degree of damage (creatinine clearance). During dialysis, the clearance of perindoprilat is 70 ml / min. There is a change in the kinetics of perindopril in patients suffering from cirrhosis: the hepatic clearance of the original molecule slows down by half. However, the amount of perindoprilat formed does not decrease and therefore no dosage adjustment is required. Indications for use Hypertension: Treatment of hypertension. Heart failure: Treatment of symptomatic heart failure. Ischemic heart disease, stable course. Reducing the risk of cardiovascular complications in patients who have had myocardial infarction and / or revascularization. Dosage and Administration The usual dose is 1 tablet once a day. Your doctor may change your dosing regimen if you have kidney problems. It is advisable to take the tablet in the morning and before meals. If you have the impression that the effect of the drug is too strong or weak, tell your doctor about it. The drug is taken orally, preferably in the morning before meals. The recommended dose is 1 tab. (2 mg / 0.625 mg, 4 mg / 1.25 mg, 8 mg / 2.5 mg) 1 time / day. If, after one month of treatment with the drug at a dose of 2 mg / 0.625 mg, blood pressure is not controlled, then the dose may be doubled. Tablets 4 mg / 1.25 mg should be prescribed in cases where blood pressure is not adequately controlled by Co-Prenessa® 2 mg / 0.625 mg. An individual selection of individual components of the drug is recommended. In case of clinical need, a direct transition from perindopril monotherapy to therapy with Co-Prenessa® at a dose of 4 mg / 1.25 mg can be considered. In case of missing the drug, the patient should continue treatment according to the prescribed regimen, without doubling the dose. Elderly patients Treatment should begin with 1 tab. Co-Prenessa® 2 mg / 0.625 mg 1 time / day. Treatment with the drug at a dose of 4 mg / 1.25 mg and 8 mg / 2.5 mg should be started after assessing the response of blood pressure and renal function. Plasma creatinine concentration should be adjusted for age, body weight and sex of the patient. Patients with impaired renal function Tablets 2 mg / 0.625 mg and 4 mg / 1.25 mg: in severe renal impairment (CC<30 ml / min), treatment is contraindicated. For patients with moderate renal impairment (CC 30-60 ml / min), the maximum dose of Co-Prenessa® 2 mg / 0.625 mg - 1 tab. 1 time / day Tablets 4 mg / 1.25 mg: in patients with moderate renal impairment (CC 30-60 ml / min), it is recommended to start treatment with an adequate dose of the combination. Patients with CC ?60 ml / min dose adjustment is not required. Tablets 8 mg / 2.5 mg: in severe and moderate renal failure (CC below 60 ml / min), treatment is contraindicated. Patients with CC ?60 ml / min dose adjustment is not required. It is necessary to conduct medical supervision, which should include frequent monitoring of creatinine and potassium in the blood serum. Patients with hepatic impairment In severe hepatic impairment, treatment is contraindicated. Patients with moderate hepatic impairment do not require dose adjustment. Children and adolescents The drug should not be prescribed to children and adolescents, because. the efficacy and tolerability of perindopril in monotherapy or combination therapy in this category of patients have not been established. Use during pregnancy and lactation Co-Prenessa® is contraindicated during pregnancy and lactation. Pregnancy Perindopril The use of ACE inhibitors is not recommended in the first trimester of pregnancy and 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 increase in 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 II and III trimesters of pregnancy, a manifestation of a fetotoxic effect (impaired kidney function, oligohydramnios, 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 took ACE inhibitors, blood pressure should be carefully monitored to prevent the possible development of arterial 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. As a precaution, it is recommended to avoid the use of indapamide during pregnancy. Lactation period The use of the drug is contraindicated during breastfeeding. Perindopril Due to the lack of information on the use of perindopril during lactation, the appointment of the drug is not recommended; alternative treatments with an established safety profile for use during breastfeeding, especially neonates or premature infants, are preferred. Indapamide Indapamide is 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. In this case, the development of hypersensitivity to sulfonamide derivatives, hypokalemia and kernicterus is possible. Indapamide is contraindicated during breastfeeding. Precautions Coronary heart disease, stable course: If episodes of unstable angina (severe or not) occur, which may occur during the first month of treatment with perindopril, the benefit / risk ratio should be care