Prilam tablets 4mg №10×3

Name:
Prilam (Perindopril Lek) tablets 4mg №30 Main active ingredientPerindopril Release formtablets CompositionPrilam 4 mg tablets Each tablet contains 4 mg of perindopril tertbutylamine. Excipients: hydroxypropyl betadex, microcrystalline cellulose, silicified microcrystalline cellulose, potassium polacrilin, silicon dioxide, colloidal anhydrous silicon dioxide, magnesium stearate.
Description:
4 mg: White, round, biconvex tablet, scored on one side and embossed with “4” on the other side. The tablet is divided into two equal parts. Dosage 4 mg Pharmacological properties Pharmacodynamics Perindopril is an inhibitor of the angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II. A converting enzyme, or kinase, is an exopeptidase that converts angiotensin I to the vasoconstrictor angiotensin II and also causes the breakdown of the bradykinin vasodilator to an inactive heptapeptide. Inhibition of ACE leads to a decrease in the content of angiotensin II in plasma, which leads to increased renin activity (by suppressing the negative feedback of renin release) and a decrease in aldosterone secretion. Since ACE inactivates bradykinin, ACE inhibition also results in increased activity of the circulating and local kallikrein-kinin systems (as well as activation of the prostaglandin system). It is possible that this mechanism contributes to the hypotensive effect of ACE inhibitors (ACE inhibitors) and is partially responsible for a number of their side effects (eg, cough). Perindopril acts through its active metabolite, perindoprilat. Other metabolites did not show suppression of ACE activity in vitro. Arterial hypertension Perindopril works with arterial hypertension of any degree: mild, moderate, severe; there is a decrease in systolic and diastolic blood pressure, both in the supine position and in the upright position. Perindopril reduces peripheral vascular resistance, leading to a decrease in blood pressure. As a result, peripheral blood flow improves without affecting the heart rate. As a rule, renal blood flow increases, while the glomerular filtration rate (GFR) usually remains unchanged. After taking a single dose, antihypertensive activity is maximal between 4 and 6 hours and persists for at least 24 hours: a plateau of action is approximately 87-100% of peak. The decrease in blood pressure occurs quickly. In responding patients, normalization of blood pressure is achieved within a month and is maintained without the occurrence of tachyphylaxis. Termination of treatment does not lead to a withdrawal effect. Perindopril reduces left ventricular hypertrophy. In humans, the vasodilating properties of perindopril have been confirmed. It improves the elasticity of large arteries and reduces the ratio of vessel wall thickness to vessel lumen diameter in small arteries. Additional therapy with a thiazide diuretic leads to drug synergism. The combination of an ACE inhibitor and a thiazide also reduces the risk of diuretic-induced hypokalemia. Heart failure Perindopril tertbutylamine facilitates the work of the heart by reducing pre- and afterload. Studies in patients with heart failure have demonstrated: – a decrease in the filling pressure of the left and right ventricles; – decrease in total peripheral vascular resistance; – increased cardiac output and improved cardiac index. In comparative studies, the first appointment of 2 mg of perindopril tertbutylamine in patients with mild or moderate heart failure was not associated with any significant reduction in blood pressure compared with placebo. Pharmacokinetics After oral administration, perindopril is rapidly absorbed, its peak concentration is reached within 1 hour. Bioavailability is 65-70%. About 20% of the total amount of absorbed perindopril is converted into its active metabolite, perindoprilat. In addition to the active perindoprilat, perindopril has five more inactive metabolites. The half-life of perindopril from plasma is 1 hour. Peak plasma concentration of perindoprilat is reached within 3-4 hours. Since ingestion with food reduces the conversion to perindoprilat (and therefore bioavailability), perindopril tertbutylamine should be administered orally once a day in the morning, before meals. The volume of distribution is approximately 0.2 L/kg for unbound perindoprilat. Protein binding is weak (binding of perindoprilat to angiotensin-converting enzyme is less than 30%), but is concentration dependent. Perindoprilat is excreted in the urine, and the half-life of the unbound fraction is approximately 3-5 hours. Dissociation of angiotensin-converting enzyme-bound perindoprilat results in an “effective” half-life of 25 hours, which maintains an equilibrium state for 4 days. After re-appointment, the accumulation of perindopril is not observed. Removal of perindoprilat is reduced in the elderly, as well as in patients with heart or kidney failure. In renal insufficiency, it is desirable to select a dose depending on the degree of deterioration in the functional state of the kidneys (creatinine clearance). The clearance of perindoprilat during dialysis is 70 ml / min. The kinetics of perindopril changes in patients with cirrhosis of the liver: the hepatic clearance of the parent molecule is reduced by half. However, the amount of perindoprilat formed does not decrease, and therefore dose adjustment is not required. Indications for use Treatment of arterial hypertension. Treatment of heart failure with clinical manifestations. Stable coronary artery disease: reduced risk of cardiac events in patients with a history of myocardial infarction and/or revascularization. Contraindications Hypersensitivity to perindopril, drug excipients or other ACE inhibitors; angioedema associated with the appointment of an ACE inhibitor in history; hereditary or idiopathic angioedema (HAE); pregnancy; breast-feeding; concomitant use of ACE inhibitors or angiotensin II receptor blockers with aliskiren in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2). Use during pregnancy and lactation The drug is contraindicated for use during pregnancy. If necessary, the appointment of the drug during lactation should decide on the termination of breastfeeding. Dosage and administration The drug is recommended to be taken once a day in the morning, before meals with a sufficient amount of liquid (eg water). The dose is selected individually depending on the profile of the patient and the response of blood pressure to treatment. Arterial hypertension Perindopril tertbutylamine can be used as monotherapy or in combination with other classes of antihypertensive drugs. The recommended starting dose is 4 mg once daily in the morning. In patients with significant activity of the renin-angiotensin-aldosterone system (in particular, with renovascular hypertension, deficiency of salt and / or circulating blood volume, cardiac decompensation or severe arterial hypertension), an excessive drop in blood pressure may occur after taking the first dose of the drug. For such patients, the recommended starting dose is 2 mg and medical supervision is required at the start of treatment. After a month, the dose can be increased to 8 mg once a day. At the beginning of perindopril therapy with tertbutylamine, symptomatic hypotension may occur; it is more likely to develop in patients receiving concomitant diuretics. Therefore, such patients are advised to exercise caution due to the possible deficiency of salt and fluid volume. If possible, diuretics should be canceled 2-3 days before the start of treatment with perindopril tertbutylamine. In hypertensive patients who cannot be discontinued diuretics, perindopril treatment with tertbutylamine should be initiated at a dose of 2 mg. It is necessary to monitor the state of kidney function and serum potassium levels. The subsequent dosage of perindopril tertbutylamine should be adjusted depending on the response of blood pressure levels to treatment. If necessary, diuretic therapy can be resumed. In elderly patients, treatment should begin with a dose of 2 mg, which after a month can be gradually increased to 4 mg, and then, if necessary, up to 8 mg, depending on the functional state of the kidneys (see table below). Symptomatic heart failure It is recommended that the administration of perindopril tertbutylamine (usually in combination with a non-potassium-sparing diuretic and/or digoxin and/or a beta-blocker) be accompanied by close medical supervision at an initial dose of 2 mg in the morning. If well tolerated, after at least 2 weeks, this dose may be increased to 4 mg once daily. Dose selection should be based on the clinical response of the patient. The initiation of treatment in patients with severe heart failure and patients at high risk (impaired renal function and a tendency to electrolyte disturbances, concomitant use of diuretics and / or vasodilators) should be carried out under the supervision of medical staff. In patients at high risk of symptomatic hypotension, such as salt-deficient patients, regardless of the presence of hyponatremia, patients with symptomatic hypovolemia, or patients receiving potent diuretic therapy, these conditions should be corrected, if possible, before prescribing perindopril tertbutylamine. Both before and during the treatment of perindopril with tertbutylamine, blood pressure, renal function and serum potassium levels should be carefully monitored. Stable ischemic heart disease Perindopril tertbutylamine 4 mg once daily for the first two weeks, after which the dose is increased to 8 mg once daily, provided renal function is normal and the 4 mg dose is well tolerated. Elderly patients are given 2 mg once a day for the first week, then 4 mg once a day for the next week, and only then increase the dose to 8 mg per day if renal function allows (see Table 1: dosage adjustment for impaired renal function). The dose can only be increased if lower doses are well tolerated. Dose Adjustment for Renal Impairment Dose for patients with impaired renal function is calculated from creatinine clearance as shown in Table 1. Table 1: Dose Adjustment for Renal Impairment Creatinine Clearance (mL/min) Recommended Dose ClCR ? 60 4 mg per day 30 < ClCR < 60 2 mg per day 15 < ClCR < 30 2 mg every other day Patients on hemodialysis*, ClCR < 15 2 mg per day of dialysis* The dialysis clearance of perindoprilat is 70 ml/min. Patients on hemodialysis treatment should take the drug after a dialysis session. Dose adjustment in hepatic impairment Patients with hepatic impairment do not require dose adjustment. Children and adolescents Perindopril tertbutylamine is not indicated in children and adolescents due to a lack of data on safety and efficacy. Side effectsThe frequency of the following adverse reactions is defined as follows: very common (?1/10), frequent (?1/100, <1/10), infrequent (?1/1000, <1/100), rare (?1/10 10000, <1/1000), very rare (<1/10000), unknown (cannot be calculated from available data) Psychiatric disorders: infrequent: mood or sleep disturbances Nervous system disorders: common: headache, dizziness, paresthesia infrequent: drowsiness, syncope very rare: confusion Visual disturbances: common: blurred vision Hearing and balance disorders: common: ringing in the ears Cardiovascular disorders: common: hypotension and effects associated with hypotension infrequent: palpitations, tachycardia, vasculitis very rare: arrhythmia, angina pectoris, myocardial infarction and stroke, possibly associated with excessive hypotension in patients at high risk Respiratory, chest and mediastinal disorders: common: cough, dyspnea infrequent: bronchospasm very rare: eosin nophilic pneumonia, rhinitis Gastrointestinal disorders: common: nausea, vomiting, abdominal pain, dysgeusia, dyspepsia, diarrhea, constipation infrequent: dry mouth very rare: pancreatitis Hepato-biliary disorders: very rare: hepatitis, cytolytic or cholestatic Skin and subcutaneous tissue disorders: common: rash, pruritus infrequent: angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx, urticaria, photosensitivity reactions, hyperhidrosis, non-acantholytic pemphigus rare: exacerbation of psoriasis very rare: multiforme erythema Musculoskeletal, connective and bone disorders: common: muscle cramps uncommon: arthralgia, myalgia Renal and urinary tract disorders: infrequent: renal failure very rare: acute renal failure Reproductive system and mammary gland disorders: infrequent: impotence General disorders: common: asthenia infrequent: chest pain , malaise, peripheral edema, fever, sweating Blood and lymphatic system disorders: infrequent: eosinophilia very rare: decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, agranulocytosis or pancytopenia. In patients with congenital deficiency of glucose-6-phosphate dehydrogenase, cases of hemolytic anemia have been described. Metabolic disorders: infrequently: hypoglycemia, hyperkalemia (reversible after discontinuation of treatment), hyponatremia Laboratory investigations infrequently: increased blood urea and plasma creatinine, rare: increased liver enzymes and serum bilirubin Injury, poisoning and procedural complications infrequently: fall Clinical trials During the procedure EUROPA studies only selected severe adverse events. They were observed in 16 (0.3%) of 6122 patients taking perindopril, and 12 (0.2%) of 6107 patients taking placebo. Six of the perindopril-treated patients experienced hypotension, three angioedema, and one sudden cardiac arrest. The number of patients taking perindopril and requiring discontinuation of the drug due to cough, hypotension or intolerance to perindopril for another reason was higher compared with the number of patients taking placebo: 6.0% (n=366) and 2.1% (n= 129) respectively. Overdose Data on overdose in humans are limited. Symptoms of an ACE inhibitor overdose are hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, restlessness, and cough. Overdose is recommended to be treated with intravenous administration of physiological saline. If hypotensive, the patient should be placed horizontally. Angiotensin II infusions and/or intravenous catecholamines may be given if available. Perindopril can be removed from the general circulation by hemodialysis. With therapy-resistant bradycardia, the installation of an artificial pacemaker is indicated. Vital signs, serum electrolytes and creatinine concentrations should be continuously monitored. Interactions with other drugs Diuretics At the beginning of treatment with ACE inhibitors in patients treated with diuretics (especially with a deficiency of volume and / or salt), there may be an excessive decrease in blood pressure. The likelihood of hypotensive effects can be reduced by discontinuing diuretics, increasing fluid volume or salt intake before starting therapy with low and gradually increasing doses of perindopril. Against the background of the treatment of heart failure with diuretics, the appointment of ACE inhibitors should be started with very small doses, possibly after reducing the dose of loop diuretics. In all cases, renal function (creatinine levels) should be monitored during the first few weeks of ACE inhibitor treatment. Potassium-sparing diuretics (eplerenone, spironolactone) There is a risk of potentially lethal hyperkalemia when low-dose ACE inhibitors are co-administered with eplerenone or spironolactone at doses of 12.5 mg to 50 mg per day, especially if this combination is uncontrolled in combination with previous therapy with ACE inhibitors and loop class II-IV heart failure diuretics (NYHA) with ejection volume <40%. Before starting combination therapy, it is necessary to make sure that there is no hyperkalemia and renal failure. Careful monitoring of serum potassium and creatinine levels is recommended weekly during the first month of treatment and monthly thereafter. Drugs that cause hyperkalemia Some drugs or therapeutic classes increase the incidence of hyperkalemia: aliskiren, potassium salts, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, NSAIDs, heparins, immunosuppressants such as cyclosporine or tacrolimus, trimethoprim. When used together with perindopril, these drugs increase the risk of hyperkalemia. Racecadotril ACE inhibitors (eg, perindopril) are known to cause angioedema. This risk may be increased when used concomitantly with racecadotril (a drug used to treat acute diarrhea). mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) Patients taking concomitant therapy with mTOR inhibitors may be at increased risk of angioedema. Co-trimoxazole (trimethoprim/sulfamethoxazole) Patients taking concomitant co-trimoxazole (trimethoprim/sulfamethoxazole) may be at an increased risk of hyperkalemia (see Precautions section). Estramustine There is an increased risk of angioedema (angioedema) with the combined use of estramustine and perindopril. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes When co-administered with perindopril, hyperkalemia (potentially fatal) may occur, especially in combination with impaired renal function. Although serum potassium usually remains within normal limits, some patients treated with perindopril may develop hyperkalemia. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes can lead to a significant increase in serum potassium, so the combination of perindopril with the above drugs is not recommended. If concomitant use is indicated, then treatment with these drugs should be carried out with caution and accompanied by frequent monitoring of serum potassium. Lithium preparations With the concomitant administration of lithium preparations and ACE inhibitors, a reversible increase in serum lithium concentration and its toxicity has been described. Co-administration of thiazide diuretics may increase lithium toxicity and increase the existing risk of lithium toxicity when taken with an ACE inhibitor. The use of perindopril with lithium preparations is not recommended, but if the need for this combination is proven, serum lithium levels should be carefully monitored. Non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin 3 g/day The appointment of NSAIDs may reduce the antihypertensive effect of ACE inhibitors. In addition, NSAIDs and ACE inhibitors have an additive effect on increasing serum potassium and may lead to deterioration of renal function. These effects are usually reversible. Rarely, acute renal failure is noted, especially in patients with impaired renal function, for example, in the elderly or patients with dehydration. It is necessary to adequately replenish the water volume in the body and, after the initiation of such combination therapy, as well as against the background of its implementation, the possibility of monitoring renal function should be considered. Antihypertensive agents and vasodilators The combined use of these drugs may increase the hypotensive effect of perindopril. The simultaneous use of nitroglycerin, other nitrates and vasodilators can further reduce blood pressure. Gliptins (linagliptin, saxagliptin, sitagliptin, vildagliptin) Combined use with an ACE inhibitor increases the risk of angioedema due to a decrease in dipeptidyl peptidase IV (DPP-IV) activity by gliptin. Antidiabetic agents According to epidemiological studies, the concomitant use of ACE inhibitors and antidiabetic drugs (insulins, oral hyperglycemic agents) may enhance the effect of lowering blood glucose with the risk of hypoglycemia. This phenomenon is more likely in the first weeks of combined treatment in patients with impaired renal function. Bakloven Increased antihypertensive effect. It is necessary to control blood pressure and kidney function, and if necessary, adjust the dose of the antihypertensive agent. Acetylsalicylic acid, thrombolytics, beta-blockers, nitrates Perindopril may be given in conjunction with acetylsalicylic acid (used as a thrombolytic agent), thrombolytics, beta-blockers and/or nitrates. Tricyclic antidepressants / antipsychotics / anesthetics Concomitant use of a number of drugs for anesthesia, tricyclic antidepressants and antipsychotics with ACE inhibitors may lead to an additional decrease in blood pressure. Sympathomimetics Sympathomimetics may reduce the antihypertensive effect of ACE inhibitors. Antacids Antacids may reduce the bioavailability of perindopril. Dual blockade of the renin-angiotensin-aldosterone system Based on available data, dual blockade of the RAAS with an ACE inhibitor, ARB II, or aliskiren cannot be recommended in any patient, especially in patients with diabetic nephropathy. In patients with diabetes mellitus or moderate/severe renal impairment (GFR < 60 ml/min/1.73 m2), concomitant use of aliskiren with an ACE inhibitor or ARB II is contraindicated. In some cases, when the combined use of an ACE inhibitor and ARB II is absolutely indicated, careful observation by a specialist and mandatory monitoring of kidney function, water and electrolyte balance, and blood pressure are necessary. Gold: Rarely, nitritoid reactions (symptoms including flushing, nausea, vomiting, and hypotension) have been reported with concomitant use of ACE inhibitors, including perindopril, with injections of gold (sodium aurothiomalate). Precautions Stable coronary heart disease If an attack of unstable angina pectoris occurs during the first month of treatment with perindopril, then a thorough assessment of the benefit / risk ratio should be made before continuing treatment. Hypotension and ACE inhibitors can cause a drop in blood pressure. Symptomatic hypotension rarely occurs in patients with arterial hypertension in the absence of complications. It is more likely to occur in patients with hypovolemia, for example, due to diuretic therapy, dietary salt restriction, dialysis, diarrhea or vomiting, or in patients with severe renin-dependent hypertension. Symptomatic hypotension has been observed in patients with symptomatic heart failure, regardless of the presence of renal failure. It was more common in patients with more severe heart failure, which is associated with the use of high doses of loop diuretics, hyponatremia, or impaired renal function. Patients with an increased risk of symptomatic hypotension should carefully select the dose and at the beginning of therapy appoint medical observation. The same applies to patients with ischemic heart disease or cerebrovascular disease, in whom an excessive drop in blood pressure can lead to myocardial infarction or cerebrovascular accident. With the development of hypotension, the patient should be laid on his back and, if necessary, prescribe intravenous saline. A transient hypotensive response is not a contraindication to subsequent doses, which can be taken after an increase in blood pressure due to volume replacement. In some patients with congestive heart failure with normal or low blood pressure, perindopril tertbutylamine may cause an additional decrease in systemic blood pressure. This effect is expected and is not usually a reason to stop treatment. If hypotension becomes symptomatic, dose reduction or withdrawal of perindopril tertbutylamine may be necessary. Aortic and mitral valve stenosis/hypertrophic cardiomyopathy As with other ACE inhibitors, perindopril tertbutylamine should be used with caution in patients with mitral valve stenosis and left ventricular outflow tract obstruction, such as aortic stenosis or hypertrophic cardiomyopathy. Violation of the functional state of the kidneys In renal failure (creatinine clearance <60 ml / min), the initial dose of perindopril is selected depending on the creatinine clearance, and then depending on the response of the patient's kidneys to treatment. Such patients are shown to constantly monitor the levels of potassium and creatinine. In patients with clinical manifestations of heart failure, hypotension after initiation of ACE inhibitor therapy may lead to some further deterioration in renal function. In such a situation, the development of acute renal failure is described, which, as a rule, is reversible. In some patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney, an increase in blood urea and serum creatinine was observed during the treatment with ACE inhibitors, usually reversible upon discontinuation of therapy. This is most likely in patients with renal insufficiency. An increased risk of severe hypotension and renal failure is also present in renovascular hypertension. In these patients, treatment should be started with low doses and careful dose titration under close medical supervision. Since treatment with diuretics can aggravate the situation, it should be canceled, and in the first weeks of perindopril therapy with tertbutylamine, the functional state of the kidneys should be monitored. In some hypertensive patients without overt renal vascular disease, elevated blood urea and serum creatinine, usually slight and transient, have been observed, especially when perindopril tertbutylamine and a diuretic are coadministered. This occurs more frequently in patients with pre-existing renal impairment. Dose reduction and/or withdrawal of the diuretic and/or perindopril tertbutylamine may be required. The co-administration of an ACE inhibitor, including perindopril, or an ARB II with aliskiren should be avoided in patients with severe renal impairment (GFR < 60 mL/min). Hemodialysis Patients Anaphylactoid reactions have been described in patients undergoing dialysis using high-flow dialysis membranes and concomitantly receiving ACE inhibitors. In such patients, a different type of dialysis membrane or a different class of antihypertensive agents is needed. Kidney transplantation There is no experience with the use of perindopril tertbutylamine in patients who have recently undergone kidney transplantation. Hypersensitivity/angioedema In patients treated with ACE inhibitors, including perindopril tertbutylamine, there have been rare reports of angioedema (angioedema) of the face, extremities, lips, mucous membranes, tongue, glottis and/or larynx. Angioedema can develop at any time during therapy and requires immediate discontinuation of perindopril tertbutylamine, as well as observation of the patient until the symptoms have completely resolved. If the swelling is limited to the face and lips, the general condition usually improves without treatment, although antihistamines may be useful to relieve symptoms. Angioedema associated with laryngeal edema can be fatal. Involvement of the tongue, glottis, or larynx may cause airway obstruction and require emergency care. This may include administration of epinephrine and/or maintenance of airway patency. The patient should be under close medical supervision until the symptoms are completely and permanently resolved. ACE inhibitors are more likely to cause the development of angioedema in patients with black skin. Patients with a history of angioedema unrelated to ACE inhibitors have an increased risk of developing angioedema when receiving an ACE inhibitor. Concomitant use of mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) Patients taking concomitant mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) may be at increased risk of angioedema (eg, swelling of the airways or tongue, with or without respiratory violations). Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis Rarely, patients receiving ACE inhibitors during LDL apheresis using dextran sulfate have experienced life-threatening anaphylactoid reactions. These reactions were avoided by temporarily canceling the ACE inhibitor before each apheresis session. Anaphylactoid reactions during desensitization Anaphylactoid reactions have been observed in patients receiving ACE inhibitors during desensitization therapy (eg, hymenoptera venom). In these patients, anaphylactoid reactions were avoided by temporary withdrawal of ACE inhibitors, but they reappeared with arbitrary re-provocation. Liver failure Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is unclear. Patients receiving ACE inhibitors who develop jaundice or have significantly elevated liver enzymes should stop taking ACE inhibitors and be under appropriate medical supervision. Neutropenia/agranulocytosis/thrombocytopenia/anemia Neutropenia/agranulocytosis, thrombocytopenia, and anemia have been reported in patients receiving ACE inhibitors. Neutropenia is rare in patients with normal renal function and no other complicating factors. Sporadic hemolytic anemia has been reported in patients with congenital glucose-6-phosphate dehydrogenase (G-6-PDH) deficiency. Perindopril should be used with extreme caution in patients with collagen vascular disease, with concomitant immunosuppressive therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially in pre-existing impaired renal function. Some of them developed serious infections, in some cases not responding to intensive antibiotic therapy. When using perindopril in such patients, periodic monitoring of the number of leukocytes in the blood is recommended, and patients should be instructed to inform about any sign of infection. Race ACE inhibitors are more likely to cause angioedema in patients with black skin. Like other ACE inhibitors, perindopril may be less effective in lowering blood pressure in blacks, possibly due to the higher prevalence of low renin in hypertensive blacks. Cough Cough has been described with ACE inhibitors. Characteristically, the cough is unproductive, persistent, and disappears after treatment is stopped. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough. Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with hypotensive agents, perindopril tertbutylamine may block secondary angiotensin II formation due to compensatory renin release. Treatment should be canceled the day before surgery. If hypotension develops and is suspected to be related to this mechanism, it can be corrected by volume replacement. Hyperkalemia In some patients treated with ACE inhibitors (including perindopril), there is an increase in serum potassium levels. Patients at risk of developing hyperkalemia include patients with renal insufficiency, impaired renal function, age over 70 years, uncontrolled diabetes mellitus, intercurrent diseases, in particular dehydration, acute cardiac decompensation, metabolic acidosis, and patients who are simultaneously using potassium-sparing diuretics (eg, spironolactone). , eplerenone, triamterene, or amiloride), potassium supplements or salt substitutes containing potassium, or patients taking other drugs associated with an increase in serum potassium (eg, heparin, co-trimoxazole, also known as trimethoprim/sulfamethoxazole). In patients taking potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes, especially in the presence of impaired renal function, serum potassium may increase significantly. Hyperkalemia can cause serious and sometimes fatal arrhythmias. With the concomitant use of the above-mentioned agents, care must be taken and serum potassium levels should be monitored frequently. Intestinal edema Intestinal angioedema has been reported in rare cases in patients treated with ACE inhibitors. These patients experienced abdominal pain (with or without nausea and vomiting); in a few cases there was no previous facial edema and C-1 inhibitor levels were normal. Angioedema was diagnosed on an abdominal CT scan or ultrasound examination, or during surgery. The symptoms stopped after the ACE inhibitor was discontinued. Intestinal angioedema should be included in the differential diagnosis in patients taking ACE inhibitors and experiencing abdominal pain. Dual blockade of the renin-angiotensin-aldosterone system (RAAS) Dual blockade of the RAAS system is associated with an increased risk of hypotension, hyperkalemia, and renal dysfunction (including acute renal failure) compared with monotherapy. Dual RAAS blockade with an ACE inhibitor, ARB II, or aliskiren cannot be recommended for any patient, especially those with diabetic nephropathy. Conducting a double blockade of