Prestarium 10 mg No. 30 tablet.

Pharmacological properties of the drug Bi-prestarium

Perindopril is an ACE inhibitor that converts angiotensin I into the vasoconstrictor angiotensin II, and also causes the breakdown of the vasodilator bradykinin. ACE inhibition leads to a decrease in the concentration of angiotensin II in the blood plasma, an increase in the activity of renin in the blood plasma and a decrease in the secretion of aldosterone. Also, ACE inhibition leads to an increase in bradykinin levels, the activity of the circulating and local kalikreinin system, as well as activation of the prostaglandin system. This mechanism of action determines a decrease in blood pressure. The action of perindopril is due to its active metabolite - perindoprilat. Other metabolites are inactive. Hypertension (arterial hypertension) Perindopril effectively reduces systolic and diastolic blood pressure in hypertension (arterial hypertension) of any severity: mild, moderate and severe. Perindopril reduces peripheral vascular resistance, which leads to a decrease in blood pressure. As a result, peripheral blood flow increases, but heart rate does not change. Renal blood flow increases, but the glomerular filtration rate does not change. The maximum antihypertensive effect develops 4–6 hours after taking a single dose and persists for at least 24 hours: the T/R ratio (the ratio of the residual effect to the maximum) of perindopril is 87–100%. Blood pressure decreases quickly. In patients who responded to treatment, blood pressure normalizes within a month and persists for a long time without the occurrence of tachyphylaxis. When you stop taking perindopril, there is no withdrawal effect. Perindopril reduces left ventricular hypertrophy. Perindopril has vasodilatory properties, improves the elasticity of large arteries and reduces the wall thickness to lumen ratio of small vessels. Prevention of cardiovascular complications in patients with documented stable coronary artery disease. The 4-year EUROPA study (European Trial on the Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease) with the participation of more than 12 thousand patients with coronary artery disease proved that treatment with perindopril significantly reduces probability:

development of fatal and non-fatal myocardial infarction by 24%;
development of heart failure, which requires hospitalization, by 39%.

Amlodipine Amlodipine is a calcium ion antagonist (slow calcium channel blocker), which blocks the transmembrane flow of calcium ions to myocardial and vascular smooth muscle cells. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle. The antianginal effect of amlodipine is achieved by two mechanisms:

expansion of peripheral arterioles, and, as a result, a decrease in total peripheral resistance (afterload). Since heart rate does not change, reducing the load on the heart reduces myocardial energy consumption and its oxygen demand;
expansion of the main coronary arteries and arterioles in both unchanged and ischemic areas of the myocardium. This dilation increases the supply of oxygen to the myocardium in patients with vasospastic angina (Prinzmetal's angina or variant angina).

In patients with hypertension (arterial hypertension), taking amlodipine once a day provides a clinically significant decrease in blood pressure over 24 hours. Due to the slow onset of action of amlodipine, a sharp decrease in blood pressure was not observed. In patients with angina pectoris, amlodipine prolongs the total time of physical activity, the time before the onset of an angina attack and increases the time before the onset of depression of the S-T by 1 mm during exercise, and also reduces the frequency of angina attacks and reduces the need for nitroglycerin. Amlodipine does not cause undesirable metabolic effects or changes in plasma lipid levels, so it can be used in patients with asthma, diabetes mellitus and gout. Properties common to perindopril and amlodipine The ASCOT-BLPA study (Anglo-Scandinavian Cardiac outcomes Trial - Blood Pressure Lowering Arm) involving 19,257 patients with hypertension (arterial hypertension) and cardiovascular risk factors proved the advantages of long-term therapy with amlodipine and perindopril compared with therapy with atenolol and a diuretic to reduce the incidence of cardiovascular complications. According to the results of the study, patients in the group that received amlodipine + perindopril had a significantly reduced risk of cardiovascular complications, namely, a reduced risk of:

coronary complications and interventions - by 16%;
overall mortality - by 11%;
cardiovascular mortality - by 24%;
fatal and non-fatal stroke - by 23%;
non-fatal myocardial infarction (except silent) and fatal complications of coronary artery disease - by 13%.

The rate and degree of absorption of perindopril and amlodipine, both as single drugs and as part of the drug Bi-Prestarium, do not differ significantly. Perindopril After oral administration, perindopril is rapidly absorbed, the maximum concentration in the blood plasma is reached within 1 hour. The half-life of perindopril in the blood plasma is 1 hour. Perindopril is a prodrug. 27% of the total amount of perindopril taken is determined in the blood in the form of an active metabolite - perindoprilate. In addition to the active metabolite - perindoprilate, the drug forms 5 inactive metabolites. The maximum concentration of perindoprilate in the blood plasma is achieved 3–4 hours after administration. There is a linear relationship between the dose of perindopril and its concentration in the blood plasma. Eating food slightly slows down the conversion of perindopril to perindoprilat, so perindopril should be taken before meals. The volume of distribution of unbound perindoprilate is 0.2 l/kg. The binding of perindoprilate to plasma proteins is 20%, mainly with ACE, this indicator is dose-dependent. Perindoprilat is excreted in the urine. The stage of equilibrium concentration in blood plasma occurs 4 days after the start of treatment. The kinetics of perindopril changes in patients with liver cirrhosis. The hepatic clearance of perindopril is reduced by half. However, the amount of perindoprilate formed does not decrease. Therefore, such patients do not need to adjust the dose. Dialysis clearance of perindoprilate is 70 ml/min. Amlodipine After oral administration in therapeutic doses, amlodipine is well absorbed and reaches maximum concentration in the blood 6-12 hours after administration. Absolute bioavailability is 64–80%. Volume of distribution - 21 l/kg. Food intake does not affect the bioavailability of amlodipine. in vitro study showed that 97.5% of circulating amlodipine is bound to plasma proteins. The half-life from blood plasma is 35–50 hours, which allows the drug to be administered once a day. Amlodipine is metabolized in the liver to form inactive metabolites, 10% of the drug is excreted in the urine unchanged and 60% in the form of metabolites.

Prestarium 10 mg No. 30 tablet.

Instructions for medical use of the drug PrestariumÒ 5 mg PrestariumÒ 10 mg Trade name PrestariumÒ 5 mg PrestariumÒ 10 mg International nonproprietary name Perindopril Dosage form Film-coated tablets 5 mg or 10 mg Composition One tablet contains the active substance - perindopril arginine 5 mg or 10 mg, respectively (equivalent to the content of perindopril 3.395 mg or 6.790 mg), excipients: lactose monohydrate, magnesium stearate, maltodextrin, colloidal silicon dioxide anhydrous, sodium starch glycolate (type A) shell: glycerin, hypromellose, copper chlorophyllin (E141ii), macrogol 6000, magnesium stearate, titanium dioxide (E171). Description PrestariumÒ 5 mg: elongated, light green film-coated tablets, marked “ ” on one side and scored on both sides. PrestariumÒ 10 mg: round tablets, with a biconvex surface, green film-coated tablets, marked “ ” on one side and “ ” on the other side. Pharmacotherapeutic group Drugs affecting the renin-angiotensin system. Angiotensin converting enzyme (ACE) inhibitors. ACE inhibitors. Perindopril ATC code C09AA04 Pharmacological properties Pharmacokinetics Absorption After oral administration, perindopril is rapidly absorbed from the gastrointestinal tract (GIT). Cmax is reached after 1 hour. The bioavailability of the drug is 65-70%. Distribution and metabolism During metabolism, perindopril is biotransformed to form an active metabolite - perindoprilate (about 27%) and 5 inactive compounds. Cmax of perindoprilate in plasma is achieved between 3 and 5 hours after taking Prestarium. The binding of perindoprilate to plasma proteins (mainly ACE) is 20% and depends on the concentration of the drug. Vd of free perindoprilate is close to 0.2 l/kg. The drug does not accumulate in the body. Repeated administration does not lead to accumulation and T1/2 corresponds to the period of its activity. When taking the drug with food, the metabolism of perindopril slows down. The elimination T1/2 of perindopril is 1 hour. Perindoprilat is excreted from the body through the kidneys; T1/2 of its free fraction is about 17 hours, which allows it to reach a steady state in 4 days. Pharmacokinetics in special clinical situations: In elderly patients, as well as in patients with renal and heart failure, the elimination of perindoprilate is slowed down. In patients with cirrhosis, the hepatic clearance of the parent molecule perindopril is slowed by half. However, the amount of perindoprilate formed does not decrease, so no dose adjustment is required. Pharmacodynamics Perindopril is an angiotensin-converting enzyme (ACE) inhibitor. ACE catalyzes the conversion of angiotensin I to angiotensin II, which has vasoconstrictor properties. In addition, ACE stimulates the secretion of aldosterone and accelerates the breakdown of the vasodilator compound bradykinin to an inactive heptapeptide. The mechanism of the antihypertensive effect of perindoprilat is associated with inhibition of ACE activity, which leads to a decrease in the rate of conversion of angiotensin I to angiotensin II. As a result of a decrease in the concentration of angiotensin II, there is a secondary increase in plasma renin activity (due to the elimination of negative feedback during the release of renin) and a direct decrease in aldosterone secretion. In addition, perindoprilat affects the kinin-kallikrein system, preventing the breakdown of bradykinin. It is a prodrug from which the active metabolite perindoprilat is formed in the body. Hypertension Prestarium is effective for mild, moderate and severe arterial hypertension. The drug reduces systolic and diastolic blood pressure both in the supine and standing positions. Thanks to its vasodilating effect, the drug reduces total peripheral vascular resistance (TPVR) and reduces pathologically elevated blood pressure (BP), thereby improving the rheological properties of the blood without affecting the heart rate. The drug, as a rule, increases renal blood flow, while the level of glomerular filtration does not change. After oral administration in an average single dose, the maximum hypotensive effect is achieved after 4-6 hours and persists for 24 hours. If the patient responds adequately to the drug, blood pressure normalizes within 1 month and remains stable without the development of tachyphylaxis. Interruption of treatment is not accompanied by withdrawal syndrome. With long-term use, Prestarium helps restore the elasticity of large arterial vessels, corrects histomorphological changes in resistant arteries and causes regression of left ventricular hypertrophy of the heart. Chronic heart failure Prestarium® normalizes heart function, reducing preload and afterload. When using the drug, a decrease in filling pressure of the left and right ventricles and a decrease in peripheral vascular resistance were noted. When Prestarium is used for the treatment of heart failure in recommended doses, no significant changes in blood pressure are observed after the first dose of the drug and after long-term use. Indications for use: arterial hypertension, chronic heart failure, coronary heart disease: reduction in the frequency of cardiac events in patients with a history of myocardial infarction and/or condition after revascularization. Method of administration and dosage The drug is recommended to be taken in the morning, 1 time per day, before meals. In the treatment of arterial hypertension, Prestarium can be used as monotherapy or in combination with antihypertensive drugs of other groups. The recommended initial dose is 5 mg once a day (in the morning), if necessary, the dose can be gradually increased to 2 tablets (10 mg) per day. If there is significant activation of the renin-angiotensin-aldosterone system (particularly in patients with renovascular hypertension, electrolyte disturbances and/or reduced circulating blood volume (BCV), cardiac decompensation or severe hypertension), a sharp drop may occur after taking the initial dose blood pressure. Treatment of such patients is recommended to begin with a dose of 2.5 mg under strict supervision. After 1 month of therapy, the dose can be increased to 10 mg once a day. Treatment of elderly patients with arterial hypertension should begin with a dosage of 2.5 mg, gradually increasing it: up to 5 mg one month after the start of treatment, then up to 10 mg, depending on the functional state of the kidneys (see table below). When treating chronic heart failure, the recommended dose is half a tablet (2.5 mg) per day. The use of the drug with non-potassium sparing diuretics and/or digoxin and/or beta-blockers should be initiated under close medical supervision, the recommended initial dose is 2.5 mg in the morning. If well tolerated, the dose is gradually increased by 2.5 mg to reach a dose of 5 mg once a day, maintaining an interval of at least 2 weeks. The basis for such correction should be the clinical response of each individual patient. When treating coronary heart disease, the drug should be started with a dose of 5 mg once a day for 2 weeks, then increased to 10 mg once a day, depending on the condition of the kidneys and provided that the dose of 5 mg is well tolerated. In elderly patients, therapy should begin with a dose of 2.5 mg 1 time per day for 1 week, then for 1 week - 5 mg 1 time per day, then increase the daily dose to 10 mg depending on renal function ( see table below). The dose is increased only if the lower previous dose is well tolerated. Dose adjustment for renal impairment Creatinine clearance (ClCr), ml/min Recommended dose of ClCr≥ 60 5 mg per day 30 2.5 mg per day 15 2.5 mg per day every other day Patients on hemodialysis* ClCr<30 2 .5 mg per day of dialysis * Dialysis clearance of perindoprilate is 70 ml/min. Patients on hemodialysis should take the drug after the dialysis session. No dose adjustment is required for liver dysfunction. Side effects The frequency of adverse reactions that may occur during therapy is given in the following gradation: very often (>1/10); often (>1/100, <1/10); uncommon (>1/1000, <1/100); rare (>1/10,000, <1/1000); very rare (<1/10,000); frequency not established (frequency cannot be calculated from available data). Often cough (often described as dry or irritating), shortness of breath - headache, asthenia, dizziness, convulsions, paresthesia, taste disturbances, visual disturbances, tinnitus, vertigo, - arterial hypotension - nausea, vomiting, abdominal pain, dysgeusia, diarrhea or constipation, dyspepsia - rash, pruritus Uncommon - eosinophilia - hyponatremia - hyperkalemia, transient increase in serum urea and creatinine - hypoglycemia, - drowsiness, - syncope, malaise, chest pain - tachycardia, palpitations - vasculitis , peripheral edema, increased body temperature - eczema, photosensitivity - arthralgia, myalgia - accidental injuries due to a fall Rarely - bronchospasm - dry mouth, increased activity of liver enzymes and serum bilirubin levels - renal failure, impotence - angioedema of the face, limbs, lips , mucous membranes, tongue, larynx, glottis and/or larynx, urticaria - increased sweating - mood and sleep disturbances Very rare - arrhythmia, angina pectoris, myocardial infarction and stroke (possibly caused by severe hypotension in high-risk patients) - eosinophilic pneumonia , rhinitis - pancreatitis, cytolytic or cholestatic hepatitis - erythema (various types) - decreased hemoglobin and hematocrit, thrombocytopenia, leukopenia/neutropenia, agranulocytosis or pancytopenia, hemolytic anemia (in patients with congenital deficiency of the enzyme glucose-6-phosphate dehydrogenase (G-6PDH) )). - confusion - acute renal failure Contraindications - hypersensitivity to perindopril and other components of the drug or any other ACE inhibitor - angioedema (hereditary or idiopathic) due to previous therapy with ACE inhibitors in history - pregnancy and lactation - combined use with Aliskiren in patients, suffering from diabetes mellitus or renal failure (GFR <60 ml/min/1.73 m²) - children and adolescents under 18 years of age (efficacy and safety have not been established). Drug interactions ACE inhibitors reduce potassium loss caused by diuretics. Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may cause significant increases in serum potassium levels. Potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes should be used with caution and frequent monitoring of serum potassium is necessary. In patients taking diuretic drugs, especially in patients with decreased blood volume and/or electrolyte disturbances, a marked decrease in blood pressure may be observed after initiation of ACE inhibitor therapy. Discontinuation of the diuretic, replenishment of blood volume or correction of electrolyte balance before starting treatment, as well as the administration of low initial doses of perindopril and their gradual increase reduce the risk of hypotension. When taking lithium and ACE inhibitors in combination, there have been cases of reversible increases in serum lithium concentrations and the development of lithium toxicity. Concomitant use of thiazide diuretics may increase the existing risk of toxicity and increase the toxicity of lithium. The combined use of perindopril and lithium preparations is not recommended, but if necessary, lithium levels in the blood serum should be carefully monitored. Nonsteroidal anti-inflammatory drugs (NSAIDs), including acetylsalicylic acid at a dose of ≥3 g/day, reduce the hypotensive effect of ACE inhibitors. In addition, it has been noted that NSAIDs and ACE inhibitors have an additive effect on increasing plasma potassium levels, leading to a deterioration in renal function. This effect is reversible, but in rare cases, acute renal failure may develop, especially in patients with impaired renal function, for example, in elderly patients or in cases of dehydration. The combined use of antihypertensive and vasodilator drugs can lead to an increase in the hypotensive effect of perindopril. Concomitant use of nitroglycerin and other nitrates or vasodilators may lead to a further decrease in blood pressure. Co-administration of ACE inhibitors and antidiabetic drugs (insulins, oral hypoglycemic drugs) can lead to increased hypoglycemic effect, especially in the first weeks of therapy and in patients with impaired renal function. Perindopril can be prescribed simultaneously with acetylsalicylic acid, thrombolytic drugs, β-blockers and/or nitrates. The combined use of tricyclic antidepressants, antipsychotic drugs and antipsychotics with ACE inhibitors can lead to a further decrease in blood pressure. Sympathomimetic agents may reduce the hypotensive effect of ACE inhibitors. When combined with perindopril and gold preparations (sodium aurothiomalate injection), some patients experienced reactions (including facial flushing, nausea, vomiting and hypotension). Special instructions Aortic and mitral stenosis/hypertrophic cardiomyopathy Prestarium, like other ACE inhibitors, should be prescribed with extreme caution to patients with mitral valve stenosis, aortic stenosis or hypertrophic cardiomyopathy. Coronary heart disease If an episode of unstable angina occurs during the first month of perindopril therapy, a careful assessment of the therapeutic benefit-risk ratio should be performed before continuing treatment. Hypotension ACE inhibitors may cause a decrease in blood pressure. Hypotension with clinical manifestations rarely develops in hypertensive patients without concomitant diseases, but more often occurs in patients with reduced blood volume (taking diuretics, on a diet with limited salt intake, patients on dialysis, patients suffering from diarrhea or vomiting) or in patients with severe renin -dependent hypertension. Symptomatic hypotension has been reported in patients with severe symptomatic heart failure, with or without concomitant renal failure. It is most likely to occur in patients with more severe heart failure, as a result of taking high doses of loop diuretics, hyponatremia or impaired renal function. Patients at increased risk for symptomatic hypotension should be closely monitored during initiation of therapy and during dose adjustment. A similar approach should also be followed when treating patients suffering from ischemia or cerebrovascular disease, in whom acute hypotension can lead to myocardial infarction or stroke. In some patients with congestive heart failure with normal or low blood pressure, taking Prestarium® may lead to an additional decrease in systemic blood pressure. This is an expected effect and usually does not require discontinuation of treatment. In some cases, with the onset of severe clinical manifestations of hypotension, it may be necessary to reduce the dose or discontinue the drug. Renal failure In case of impaired renal function (creatinine clearance < 60 ml/min), the initial dose should be adjusted according to the patient's creatinine clearance and then according to the patient's response to treatment. For these patients, regular monitoring of potassium and creatinine levels is common practice. Hypotension that occurs early in ACE inhibitor therapy in patients with symptomatic heart failure may lead to further deterioration of renal function. There are reports of acute renal failure occurring in this situation, which is usually reversible. Reversible increases in serum urea and creatinine levels have been reported in some patients with bilateral renal artery stenosis or solitary renal artery stenosis (especially those with renal failure) taking ACE inhibitors. In some patients with hypertension without visible renal vascular impairment, an increase in the concentration of urea in the blood and creatinine in the serum was observed, usually it was minor and transient, especially with the combined use of Prestarium and a diuretic. This is most likely in patients who already have impaired renal function. In this case, it may be necessary to reduce the dosage and/or stop taking the diuretic and/or Prestarium. Hemodialysis in patients receiving AKF inhibitors, during hemodialysis using high -flow membranes (for example, AN69®), anaphylactoid reactions were noted. Therefore, it is advisable to use a membrane of a different type or use a hypotensive agent of another pharmacotherapeutic group. Increased sensitivity/ anaphylactic swelling of the Angioneurotic edema of the face, limbs, lips, mucous membranes, tongue, voice gap and/ or larynx in patients undergoing AEF inhibitors, including the preserium, were rare. These reactions can occur at any time during therapy. In such cases, the reception of the Preminum should be immediately terminated and appropriate monitoring until the symptoms completely disappear. Usually, in cases where the edema affected only his face and lips, it took place without any treatment, although antihistamine drugs helped alleviate the symptoms. With the edema of the tongue, the voice gap or larynx, in which the obstruction of the respiratory tract is likely, the appropriate measures should be immediately taken. Emergency assistance may include the purpose of adrenaline and/or maintaining the patency of the respiratory tract. The patient should be under close medical supervision until symptoms disappear completely and completely. An increased risk of the onset of angioedema when taking the AKF inhibitor exists for patients who have undergone angioedema, not associated with the receipt of AKF inhibitors. There are rare reports of angioedema, affecting the gastrointestinal tract, in patients taking AKF inhibitors. These patients complained about abdominal pain (accompanied or not vomiting and nausea); In some cases, the Angiootects of the face did not precede this, and the level of C-1 esterase was normal. Diagnostics of the angiooteite was carried out using the procedures that included computed tomography of the abdomen, or during an ultrasound examination, or during a surgical operation; The symptoms took place after the termination of the reception of the AKF inhibitor. In patients taking AKF inhibitor, with complaints of abdominal pain, angioteum affecting the gastrointestinal tract should be included in the differential diagnosis. Anaphylactoid reactions during the procedures of low -density lipoprotein procedures (LDL) and during desensitization in rare cases in patients receiving LDSP anti -sulfate absorption, when prescribing AKF inhibitors, cases of development of anaphylactoid reactions were noted. It was possible to avoid these reactions by temporary cancellation of the AKF inhibitor every time before the apel. Anaphylactoid reaction occurred in some patients who received AKF inhibitors during desensitizing therapy (for example, hymenoperic poison). In some patients, these reactions were able to avoid by temporary abolition of the AKF inhibitor, but they again occurred in case of careless administration of the drug. Violation of the liver function, patients receiving AKF inhibitors who develop jaundice or the level of liver enzymes develops noticeably should stop taking the AKF inhibitor and undergo a thorough medical examination. Neutropenia/agranulocytosis/thrombocytopenia/anemia in patients with normal liver function and the absence of other complicating factors, neutropenia rarely occurs. Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressive drugs, allopurinol or procainamide and when used together, especially in patients with underlying renal impairment. Some patients developed severe infectious diseases, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the number of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their doctor. The race of angioedemic edema in the treatment of AKF inhibitors is more often occurs in patients of a non -graid race than in patients of other races. Like other AKF inhibitors, the hypotensive efficiency of perindopril in patients of a non -graid race can be lower than in patients of other races. Perhaps the reason for this is that hypertension in such patients very often occurs against a background of low renin content. Cough during treatment with ACE inhibitors in the patient may occur dry unproductive cough, which stops after the cancellation of the drug. Surgical intervention/General anesthesia. The use of AKF inhibitors in patients undergoing surgical intervention using general anesthesia can lead to a pronounced decrease in blood pressure, especially when using general anesthesia that have an antihypertensive effect. It is recommended to stop taking long -acting AKF inhibitors, including perindopril, 12 hours before surgery. Hyperkalemia hyperkalemia can develop during treatment with AKF inhibitors, including and perindopril. Hyperkalemia risk factors are renal failure, impaired renal function, elderly *over 70 years), diabetes mellitus, some concomitant conditions (dehydration, acute decompensation of chronic heart failure, metabolic acidosis), simultaneous intake of potassium -saving diuretics (such as spironolactone, eplerenon, triamateren , amyloride), as well as potassium and potassium -containing food substitutes, as well as the use of other products that help increase the content of potassium ions in blood plasma (for example, heparin) (especially in patients with reduced renal function). Hyperkalemia can lead to serious, sometimes fatal, heart rhythm disturbances. If you need a combined technique of the above funds, treatment should be carried out with caution, amid regular control of potassium ions in blood serum. Potassium -saving diuretics and potassium preparations are usually the joint use of perindopril and potassium -saving diuretics, as well as potassium preparations and potassium -containing food substitutes, is not recommended. The double blockade of the renin-angiotensin-aldosterone system in susceptible patients, especially with combined administration of drugs affecting this system, there were cases of hypotension, syncopes, strokes, hypercalemia and changes in renal function (including acute renal failure). In this regard, the dual blockade of the renin-angiotensin-aldosterone system by combined receiving an angiotensin-I-transforming enzyme and a receptor of angiotensin II or aliskirene receptors is not recommended. Patients with diabetes for patients with diabetes taking oral antidiabetic drugs or insulin, during the first month of treatment with AKF inhibitors, careful monitoring should be performed. Excipients with planned surgical intervention with anesthesia should stop treatment with the presetarium 1 day before surgery. The drug contains lactose, so it should not be used for congenital galactosemia, glucose-galactose malabsorption syndrome, as well as with lactase deficiency. The use of the effectiveness and safety of the use of the drug in children and adolescents in pediatrics is not established, and therefore the prescription of the drug to these categories of patients is not recommended. Pregnancy and lactation, if the pregnancy is planned or the fact of pregnancy has been confirmed, you should switch to an alternative type of treatment as soon as possible. The use of the drug in the II - III trimesters of pregnancy and during lactation is contraindicated. Features of the effect of the drug on the ability to drive a car and potentially dangerous mechanisms in some patients in response to a decrease in blood pressure can develop various individual reactions, especially at the beginning of therapy or when other hypotensive drugs are added to the therapy. Caution should be observed when driving vehicles and working with potentially dangerous mechanisms in connection with the possible development of dizziness. Overdose symptoms: acute hypotension, bradycardia, dizziness, anxiety, coughing, electrolyte disorders, renal failure, shock, tachycardia, rhythm disturbance, hyperpine (lung hyperventilation). Treatment: intravenous administration of sodium chloride solution of 9 mg/ml (0.9%), giving horizontal position, intravenous administration of solutions to replenish the fluid deficiency, angiotensin II and/or catecholamines, atropine. The patient should be under close attention, preferably in the intensive care unit. The content of electrolytes and creatinine in the patient serum should be constantly monitored. If necessary, pacemanism (to eliminate bradycardia). Hemodialysis (the use of polyacrylonitril high -flow membranes should be avoided). The production form and packaging of 30 tablets are placed in a polypropylene container. 1 container (for a dosage of 5 mg and 10 mg) or 3 containers (for a dosage of 10 mg) along with instructions for medical use in the state and Russian languages are placed in a cardboard box. Storage conditions are stored in a tightly cooled container at a temperature of not higher than 30 ° C. Keep out of the reach of children! Shelf life 3 years Do not use after the expiration date indicated on the package. Conditions of the vacation from pharmacies according to the recipe manufacturer Les Laboratoires Servier Industrie (Le Laboratory Servier Industri), France or Servier (Ireland) Industries Ltd (Servia (Ireland) Industry LTD), Ireland Owner Laboratoires Servier registration certificate Boratoire Servier), France address organizations receiving in the territory of the Republic of Kazakhstan claims from consumers for products: Representative Office in the Republic of Kazakhstan 050020, Almaty, Prospect of Dostyk 310 g, business center, 3rd floor of tel., 386 76 63, 386 76 64, 386 76 70, 386 76 71 fax e -mail

Contraindications to the use of the drug Bi-prestarium

Hypersensitivity to perindopril (or any other ACE inhibitors), amlodipine (or other dihydropyridines) or to any excipient; history of angioedema associated with previous treatment with ACE inhibitors; congenital or idiopathic angioedema; During pregnancy and breastfeeding; severe arterial hypotension; shock, including cardiogenic; obstruction of the exit from the left ventricle (for example, clinically significant aortic stenosis); unstable angina (with the exception of Prinzmetal angina); heart failure after acute myocardial infarction (during the first 28 days).

Side effects of the drug Bi-prestarium

May be caused by any of the components of the drug. Both when using amlodipine and when using perindopril, headache, dizziness, abdominal pain, nausea, vomiting, dry mouth, dyspeptic symptoms, dysgeusia, shortness of breath, blurred vision, and ringing in the ears may occur more often. Mood changes, rhinitis, urticaria, angioedema, impotence, increased sweating, itching, and rashes may occur much less frequently. Rarely - chest pain. Very rarely - pancreatitis, erythema multiforme, vasculitis, cholestatic jaundice, hepatitis (with cytolytic or cholestatic syndrome), acute renal failure, arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation), myocardial infarction due to excessive arterial hypotension in patients who belong to high risk group. When using amlodipine, the most common adverse reactions are hot flashes, peripheral edema, palpitations, fatigue, and drowsiness. Much less frequently, arterial hypotension, asthenia, weight gain or loss, insomnia, hypoesthesia, paresthesia, tremor, loss of consciousness, alopecia, purpura, skin discoloration, arthralgia, myalgia, back pain, muscle cramps, dysuria, nocturia, pollakiuria may occur. , gynecomastia, malaise. Very rare: Stevens-Johnson syndrome, gingival hyperplasia, leukopenia, neutropenia, thrombocytopenia, peripheral neuropathy, hyperglycemia, gastritis. When using perindopril, the most common adverse reactions are cough, hypotension (and associated symptoms), asthenia, muscle cramps, paresthesia, diarrhea, constipation. Sleep disturbance, bronchospasm, and renal failure are noted much less frequently. Very rarely, leukopenia, neutropenia, thrombocytopenia, agranulocytosis or pancytopenia, decreased hemoglobin and hematocrit levels, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency, loss of orientation, eosinophilic pneumonia, stroke due to the development of severe arterial hypotension in patients who belong to to a high-risk group. From the laboratory parameters When taking amlodipine, an increase in the level of liver enzymes is very rarely noted: ALT, AST (mainly in the presence of cholestasis). When using perindopril, an increase in the level of bilirubin in the blood serum and liver enzymes rarely occurs, and with an unknown frequency - an increase in the level of urea in the blood and creatinine in the blood plasma, hyperkalemia.

Special instructions for the use of the drug Bi-prestarium

All warnings associated with each of the components of the drug apply to the drug Bi-Prestarium. For perindopril Arterial hypotension. ACE inhibitors can cause a sharp decrease in blood pressure, which occurs more often in patients with hypovolemia or in patients with severe renin-dependent hypertension. In patients at high risk of symptomatic hypotension, as well as patients with coronary artery disease or cerebrovascular disease in whom an excessive decrease in blood pressure may cause the development of myocardial infarction or stroke, blood pressure, renal function, and serum potassium concentrations should be carefully monitored. Aortic and mitral valve stenosis/hypertrophic cardiomyopathy ACE inhibitors should be prescribed with caution to patients with mitral valve stenosis and/or left ventricular outflow tract obstruction (aortic stenosis, hypertrophic cardiomyopathy). Neutropenia/agranulocytosis/thrombocytopenia/anemia. Perindopril should be prescribed with caution to patients with collagen diseases, during therapy with immunosuppressants, allopurinol or procainamide, especially in the presence of renal impairment, due to the risk of neutropenia/agranulocytosis, thrombocytopenia and anemia. In patients with impaired renal function and in elderly patients, the excretion of perindoprilate is reduced. Therefore, frequent monitoring of creatinine and potassium levels is necessary during treatment. While taking ACE inhibitors, some patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney may experience a reversible increase in blood urea and serum creatinine concentrations. The presence of renovascular hypertension increases the risk of severe arterial hypotension and renal failure. Liver dysfunction . If a patient develops jaundice or significantly elevated liver enzyme levels while taking an ACE inhibitor, the ACE inhibitor should be discontinued and the patient should be monitored closely medically. Anaphylactoid reactions during LDL apheresis. Rarely, life-threatening anaphylactoid reactions may occur in patients taking ACE inhibitors during LDL apheresis with dextran sulfate. The development of anaphylactoid reactions can be avoided by temporarily stopping the use of ACE inhibitors before starting plasmapheresis. Anaphylactoid reactions during desensitizing therapy. Patients who take ACE inhibitors during desensitization treatment with drugs containing bee venom may experience anaphylactoid reactions. These reactions can be avoided by temporarily stopping the use of ACE inhibitors. If the patient is about to undergo surgery or requires anesthesia , treatment with the ACE inhibitor should be discontinued the day before surgery (see INTERACTIONS WITH OTHER MEDICINES). Hyperkalemia may occur in patients taking ACE inhibitors. Risk factors for hyperkalemia include renal failure or deterioration of renal function, age (over 70 years), diabetes mellitus, intercurrent conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. For amlodipine Patients with impaired liver function. As with other calcium antagonists, the half-life of amlodipine is prolonged in patients with impaired liver function. Therefore, amlodipine should be prescribed to such patients with caution, with careful monitoring of liver enzyme levels. Amlodipine should be prescribed with caution in patients with heart failure For elderly patients, the recommended dosage is the same as for other patients, but dose increases should be done with caution. For Bi-Prestarium, Bi-Prestarium can be prescribed to patients with creatinine clearance ≥60 ml/min. For patients with creatinine clearance ≤60 ml/min, individual dose selection is recommended for each of the components of the drug separately. The drug contains lactose , therefore patients with congenital galactose intolerance, glucose and galactose malabsorption syndrome, Lapp lactase deficiency are not recommended to prescribe the drug. Children Bi-Prestarium is not recommended for use in children under 18 years of age due to the lack of studies in this group of patients. Pregnancy and breastfeeding The drug Bi-Prestarium is not recommended for use in the first trimester of pregnancy. If pregnancy is established, alternative therapy should be started as soon as possible. Bi-Prestarium is contraindicated in the second and third trimester of pregnancy. It is not recommended to take Bi-Prestarium while breastfeeding. The ability to influence the reaction rate when driving vehicles or other mechanisms When driving a car or when working with various mechanisms, the possibility of developing such adverse drug reactions as dizziness or weakness should be taken into account.

Prestarium A tab disperg 5mg N30 (Servier)

Stable ischemic heart disease

If any episode of unstable angina develops during the first month of perindopril therapy, the benefits and risks should be assessed before continuing therapy.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of excessive reduction in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, dialysis, diarrhea and vomiting, as well as in patients with severe renin-dependent hypertension.

Symptomatic hypotension may occur in patients with clinical manifestations of heart failure, regardless of the presence of renal failure. This is more likely in patients with severe heart failure, as a reaction to high-dose loop diuretics, hyponatremia, or functional renal failure.

In patients at increased risk of developing symptomatic arterial hypotension, blood pressure, renal function and serum potassium levels should be carefully monitored when initiating therapy with Prestarium® A and during dose adjustment.

A similar approach is used in patients with coronary artery disease and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.

If arterial hypotension develops, the patient should be transferred to the supine position with legs elevated. If necessary, the volume of circulating blood should be replenished with intravenous administration of 0.9% sodium chloride solution. Transient arterial hypotension is not an obstacle to further taking the drug. After restoration of blood volume and blood pressure, treatment can be continued.

In some patients with chronic heart failure (CHF) and normal or low blood pressure, the drug Prestarium® A may cause an additional decrease in blood pressure. This effect is predictable and does not usually require discontinuation of therapy. If symptoms of a pronounced decrease in blood pressure appear, the dose of the drug should be reduced or discontinued.

Mitral valve stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

The drug Prestarium® A, like other ACE inhibitors, should be prescribed with caution to patients with obstruction of the left ventricular outflow tract (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as to patients with mitral valve stenosis.

Renal dysfunction

For patients with renal failure (creatinine clearance less than 60 ml/min), the initial dose of perindopril is selected depending on the clearance value and then depending on the therapeutic effect. For such patients, regular monitoring of serum creatinine and potassium concentrations is necessary.

Hypotension, which sometimes develops when starting ACE inhibitors in patients with symptomatic CHF, can lead to deterioration of renal function. Acute renal failure may develop, usually reversible. In patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney (especially in the presence of renal failure), during therapy with ACE inhibitors, there may be an increase in the concentration of urea and creatinine in the blood serum, which usually resolves when therapy is discontinued. The additional presence of renovascular hypertension causes an increased risk of severe hypotension and renal failure in such patients.

Treatment of such patients begins under close medical supervision using low doses of the drug and further adequate selection of doses. Treatment with diuretics should be temporarily discontinued and plasma potassium and creatinine levels should be regularly monitored during the first few weeks of therapy.

In some patients with arterial hypertension without indication of pre-existing renal vascular disease, serum urea and creatinine concentrations may increase, especially with simultaneous use of diuretics. These changes are usually mild and reversible. The likelihood of developing these disorders is higher in patients with a history of renal failure. In such cases, it may be necessary to discontinue or reduce the dose of Prestarium® A and/or the diuretic.

Hemodialysis

In patients undergoing hemodialysis using high-flow membranes, cases of anaphylactic reactions have been reported during therapy with ACE inhibitors. In such situations, consideration should be given to prescribing a different class of antihypertensive drug or using a different type of dialysis membrane.

Kidney transplant

There are no data on the use of the drug Prestarium® A in patients after kidney transplantation.

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, the risk of developing arterial hypotension and renal failure increases during therapy with ACE inhibitors. Taking diuretics may be an additional risk factor. Deterioration of renal function can be observed with even a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis.

Hypersensitivity/angioedema

When taking ACE inhibitors, including perindopril, in rare cases and during any period of therapy, the development of angioedema of the face, upper and lower extremities, lips, mucous membranes, tongue, vocal folds and/or larynx may be observed (see section “Side effects”). action"). If symptoms appear, the drug should be stopped immediately and the patient should be observed until signs of edema completely disappear. If the swelling affects only the face and lips, it usually resolves on its own, although antihistamines may be used to treat symptoms.

Angioedema, accompanied by swelling of the larynx, can be fatal. Swelling of the tongue, vocal folds, or larynx can lead to airway obstruction. When such symptoms appear, emergency treatment is required, including subcutaneous administration of epinephrine (adrenaline) and/or ensuring airway patency. The patient should be under close medical supervision until symptoms disappear completely and permanently.

In patients with a history of angioedema not associated with taking ACE inhibitors, the risk of its development may be increased when taking drugs of this group (see section "Contraindications").

In rare cases, angioedema of the intestine develops during therapy with ACE inhibitors. In this case, patients experience abdominal pain as an isolated symptom or in combination with nausea and vomiting, in some cases without previous angioedema of the face and with normal levels of C1-esterase. The diagnosis was made using abdominal computed tomography, ultrasound, or surgery. Symptoms disappeared after stopping the ACE inhibitors. Therefore, in patients with abdominal pain receiving ACE inhibitors, when carrying out differential diagnosis, it is necessary to take into account the possibility of developing angioedema of the intestine.

Combined use with combination drugs containing valsartan + sacubitril

The combined use of perindopril with combination drugs containing valsartan + sacubitril is contraindicated, as the risk of developing angioedema is increased (see section "Contraindications").

The use of a combination drug containing valsartan + sacubitril is possible no earlier than 36 hours after the last dose of perindopril. The use of perindopril is possible no earlier than 36 hours after stopping the combination drug containing valsartan + sacubitril.

When taking ACE inhibitors concomitantly with other neprilysin inhibitors (for example, racecadotril), the risk of developing angioedema may be increased (see section "Interaction with other drugs"). In patients receiving perindopril, a careful risk/benefit assessment should be performed before initiating treatment with enkephalinase inhibitors (eg, racecadotril).

Concomitant use with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus)

When used together with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus), the risk of developing angioedema (for example, swelling of the airways or tongue, with or without impaired respiratory function) increases.

Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis

In rare cases, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. To prevent an anaphylactoid reaction, ACE inhibitor therapy should be temporarily discontinued before each apheresis procedure.

Anaphylactoid reactions during desensitization

There are isolated reports of the development of anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy, for example, with hymenoptera venom. In these patients, such reactions were prevented by temporary discontinuation of ACE inhibitors, but with accidental or careless resumption of treatment, the reactions could develop again.

Liver dysfunction

In rare cases, while taking ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, the drug should be stopped and the patient should be under appropriate medical supervision.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

While taking ACE inhibitors, neutropenia/agranulocytosis, thrombocytopenia and anemia may occur. In patients with normal renal function and in the absence of other aggravating factors, neutropenia rarely develops. Perindopril should be used with extreme caution in patients with systemic connective tissue diseases, while taking immunosuppressants, allopurinol or procainamide, or a combination of these risk factors, especially in the presence of underlying renal impairment.

Some patients developed severe infections, in some cases resistant to intensive antibiotic therapy. When prescribing perindopril to such patients, it is recommended to periodically monitor the content of leukocytes in the blood. Patients should report any signs of infectious diseases (eg, sore throat, fever) to their healthcare provider.

Ethnic differences

It should be taken into account that patients of the Negroid race have a higher risk of developing angioedema. Like other ACE inhibitors, the drug Prestarium® A is less effective in lowering blood pressure in black patients.

This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Cough

During therapy with an ACE inhibitor, a persistent dry cough may occur, which stops after discontinuation of the drug. This should be taken into account when carrying out the differential diagnosis of cough.

Surgery/general anesthesia

In patients who are planning to undergo major surgery or use anesthetic agents that cause arterial hypotension, the use of perindopril may block the formation of angiotensin II against the background of compensatory release of renin. Treatment should be stopped one day before surgery. If arterial hypotension develops according to this mechanism, blood pressure should be maintained by replenishing blood volume.

Hyperkalemia

Hyperkalemia may develop during treatment with ACE inhibitors, including perindopril. Risk factors for hyperkalemia include renal failure, decreased renal function, age over 70 years, diabetes mellitus, certain concomitant conditions, in particular dehydration, acute heart failure, metabolic acidosis, and concomitant use of potassium-sparing diuretics (such as spironolactone and its derivatives eplerenone, triamterene, amiloride), food supplements/potassium preparations or potassium-containing table salt substitutes, as well as the use of other drugs that increase potassium levels in the blood (for example, heparin, co-trimoxazole (a fixed combination of sulfamethoxazole and trimethoprim).

The use of potassium supplements/preparations, potassium-sparing diuretics, and potassium-containing table salt substitutes can lead to a significant increase in potassium levels in the blood, especially in patients with reduced renal function.

Hyperkalemia can cause serious, sometimes fatal, abnormal heart rhythms. If simultaneous use of the drug Prestarium® A and the above drugs is necessary, treatment should be carried out with caution against the background of regular monitoring of potassium levels in the blood serum.

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, blood glucose concentrations should be regularly monitored during the first month of therapy with an ACE inhibitor.

Lithium preparations

Concomitant use of perindopril and lithium preparations is not recommended

Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements

The combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended.

Double blockade of the RAAS

There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Thus, dual blockade of the RAAS by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended. If dual block therapy is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, blood electrolytes and blood pressure.

The use of ACE inhibitors in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually not susceptible to antihypertensive drugs that act by inhibiting the RAAS. Therefore, taking the drug is not recommended.

Interactions of the drug Bi-prestarium

All warnings associated with each of the components of the drug apply to the drug Bi-Prestarium. For perindopril, simultaneous use with:

potassium-sparing diuretics, potassium supplements, or potassium salt substitutes, as these may significantly increase serum potassium levels. Their simultaneous use with Bi-Prestarium is not recommended. If concomitant use is indicated due to the presence of documented hypokalemia, they should be used with caution. It is necessary to monitor blood plasma potassium levels;
lithium Concomitant use of lithium and ACE inhibitors is not recommended due to the possible occurrence of a reverse increase in the concentration of lithium in the blood serum and, accordingly, an increase in its toxicity (severe neurotoxicity). However, if this is truly necessary, serum lithium concentrations should be carefully monitored;
estramustine - increased risk of angioedema.

Drugs that require monitoring when co-administered: NSAIDs, including acetylsalicylic acid at a dose of ≥3 g/day, may increase the risk of renal impairment, including acute renal failure, and increased serum potassium levels, especially in patients with existing impairment kidney function. Prescribe with caution, especially for elderly patients. Periodic monitoring of renal function is necessary. Antidiabetic agents (insulin, hypoglycemic sulfonamides): when used simultaneously with ACE inhibitors, the hypoglycemic effect may be enhanced (possibly due to increased glucose tolerance). Diuretics: to reduce the risk of arterial hypotension, it is recommended to stop taking diuretics and restore water and electrolyte balance before starting treatment with ACE inhibitors. Sympathomimetics may reduce the antihypertensive effects of ACE inhibitors. Gold : with the simultaneous use of ACE inhibitors, including perindopril, and injectable gold preparations (sodium aurothiomalate), reactions similar to those with the use of nitrates (facial redness, hot flushes, nausea, vomiting and hypotension) may rarely occur. For amlodipine, simultaneous administration of: Dantrolene (infusion): simultaneous administration of dantrolene and calcium antagonists is not recommended due to the risk of ventricular fibrillation. Drugs for which simultaneous use requires caution Inducers of CYP 3A4 (rifampicin, hypericum perforatum, anticonvulsants such as carbamazepine, phenobarbital, fosphenytoin, phenytoin, primidone): simultaneous use may lead to a decrease in the concentration of amlodipine in the blood plasma. Amlodipine should be prescribed in combination with CYP3A4 inducers with caution; if necessary, the dose of amlodipine can be adjusted. CYP3A4 inhibitors (itraconazole, ketoconazole): simultaneous use may increase the plasma concentration of amlodipine and the incidence of its side effects. Amlodipine should be prescribed in combination with these drugs with caution; if necessary, the dosage of amlodipine can be changed. β-receptor blockers used for heart failure (bisoprolol, carvedilol, metoprolol): risk of arterial hypotension, cardiac weakness in patients with heart failure (both latent and uncontrolled). Co-administration of amlodipine is safe with thiazide diuretics, ACE inhibitors, β-receptor blockers, long-acting nitrates, sublingual nitroglycerin, digoxin, warfarin, atorvastatin, sildenafil, drugs to reduce gastric acidity (aluminum hydroxide gel, magnesium hydroxide, simethicone), cimetidine, NSAIDs , antibiotics and oral hypoglycemic drugs. Consuming grapefruit juice does not significantly affect the pharmacokinetics of amlodipine. General properties of perindopril and amlodipine Drugs whose simultaneous administration requires monitoring: baclofen - may enhance the antihypertensive effect; antihypertensive drugs (such as beta-receptor blockers) and vasodilators : the simultaneous use of these drugs may enhance the hypotensive effect of perindopril and amlodipine; α-receptor blockers (prazosin, alfuzosin, doxazosin, tamsulosin, terazosin): enhance the antihypertensive effect and increase the risk of orthostatic hypotension; GCS, tetracosactide : weakening of the antihypertensive effect (through the retention of water and salts of GCS); amifostine : may enhance the hypotensive effect; tricyclic antidepressants/antipsychotics/anesthetics : increased antihypertensive effect and increased risk of orthostatic hypotension.

Prestarium® A

Stable ischemic heart disease

If any episode of unstable angina develops during the first month of perindopril therapy, the benefits and risks should be assessed before continuing therapy.

Arterial hypotension

ACE inhibitors can cause a sharp decrease in blood pressure. Symptomatic hypotension rarely develops in patients with uncomplicated arterial hypertension. The risk of an excessive decrease in blood pressure is increased in patients with reduced blood volume, which can be observed during diuretic therapy, while following a strict salt-free diet, dialysis, diarrhea and vomiting, as well as in patients with severe renin-dependent hypertension (see sections “Interaction with others”). drugs" and "Side effects").

In patients with an increased risk of developing symptomatic arterial hypotension, it is necessary to carefully monitor blood pressure, renal function and potassium levels in the blood serum during the initiation of therapy with the drug Prestarium® A and during the selection of its dose (see sections "Dosage and Administration" and "Adverse action").

A similar approach is used in patients with coronary artery disease and cerebrovascular diseases, in whom severe arterial hypotension can lead to myocardial infarction or cerebrovascular accident.

Mitral valve stenosis / aortic stenosis / hypertrophic obstructive cardiomyopathy

Renal dysfunction

For patients with renal failure (creatinine clearance less than 60 ml/min), the initial dose of perindopril is selected depending on the clearance value (see section "Method of administration and dosage") and then depending on the therapeutic effect. For such patients, regular monitoring of serum creatinine and potassium concentrations is necessary (see section “Side Effects”).

Hemodialysis

Kidney transplant

There are no data on the use of the drug Prestarium® A in patients after kidney transplantation.

Renovascular hypertension

In patients with bilateral renal artery stenosis or arterial stenosis of a single functioning kidney, the risk of arterial hypotension and renal failure increases during therapy with ACE inhibitors (see section “Contraindications”). Taking diuretics may be an additional risk factor. Deterioration of renal function can be observed with even a slight change in serum creatinine concentration, even in patients with unilateral renal artery stenosis.

Hypersensitivity/angioedema

In patients with a history of angioedema not associated with taking ACE inhibitors, the risk of its development may be increased when taking drugs of this group (see section "Contraindications").

Combined use with combination drugs containing valsartan + sacubitril

The combined use of perindopril with combination drugs containing valsartan + sacubitril is contraindicated, as the risk of developing angioedema is increased (see section "Contraindications").

Concomitant use with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus)

When used together with mTOR inhibitors (for example, sirolimus, everolimus, temsirolimus), the risk of developing angioedema (for example, swelling of the airways or tongue, accompanied or not accompanied by impaired respiratory function) increases (see section "Interaction with other drugs"). .

Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis

Anaphylactoid reactions during desensitization

Liver dysfunction

In rare cases, while taking ACE inhibitors, a syndrome of development of cholestatic jaundice with transition to fulminant liver necrosis, sometimes with death, was observed. The mechanism of development of this syndrome is unclear. If jaundice appears or a significant increase in the activity of liver enzymes while taking ACE inhibitors, you should stop taking the drug (see section “Side Effects”), the patient should be under appropriate medical supervision.

Neutropenia / agranulocytosis / thrombocytopenia / anemia

Ethnic differences

This effect may be associated with a pronounced predominance of low-renin status in black patients with arterial hypertension.

Cough

Surgery/general anesthesia

Hyperkalemia

Patients with diabetes mellitus

When prescribing the drug to patients with diabetes mellitus receiving hypoglycemic agents for oral administration 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 (see section “Interaction with other drugs”).

Lithium preparations

The combined use of perindopril and lithium preparations is not recommended (see section “Interaction with other drugs”).

Potassium-sparing diuretics, potassium supplements, potassium-containing table salt substitutes and food supplements

The combined use of perindopril and potassium-sparing diuretics, as well as potassium preparations, potassium-containing table salt substitutes and food additives is not recommended (see section “Interaction with other drugs”).

Double blockade of the RAAS

There is evidence that concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Thus, double blockade of the RAAS by combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see sections “Interaction with other drugs” and “Pharmacodynamics”). If dual block therapy is considered absolutely necessary, it should only be carried out under strict medical supervision and with regular monitoring of renal function, blood electrolytes and blood pressure.

The use of ACE inhibitors in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications").

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually not susceptible to antihypertensive drugs that act by inhibiting the RAAS. Therefore, taking the drug is not recommended.

Overdose of the drug Bi-prestarium

No cases have been reported. Overdose of amlodipine can lead to excessive peripheral vasodilation and, as a result, significant and possibly prolonged systemic hypotension. Amlodipine is not excreted during hemodialysis. Information on perindopril is limited. An overdose of ACE inhibitors may cause arterial hypotension, circulatory shock, electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitations, bradycardia, dizziness, anxiety, cough, etc. Perindopril can be removed from the systemic circulation using hemodialysis.