Prestans pills 5mg + 10mg N30
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Active ingredients
Amlodipine + Perindopril
Release form
Pills
Composition
Active ingredient: Perindopril arginine. Concentration of active ingredient (mg): 10
Pharmacological effect
Perindopril Perindopril is an inhibitor of the enzyme that converts angiotensin I to angiotensin II (ACE inhibitor). ACE, or kininase II, is an exopeptidase, which carries out both the conversion of angiotensin I into angiotensin II, a vasoconstrictor, and the breakdown of bradykinin, which has a vasodilating effect, to inactive heptapeptide. kallikrein-kinin system, while also activating the prostaglandin system. Perindopril has a therapeutic effect due to its active metabolite, perindopril that Other metabolites have no inhibitory effect on ACE in vitro. Arterial hypertension Perindopril is a drug for treating arterial hypertension of any severity. Against the background of its use, a decrease in both systolic and diastolic blood pressure in the prone and standing position is noted. Perindopril reduces OPSS, which leads to a decrease in blood pressure and improvement of peripheral blood flow without changing the heart rate. As a rule, taking perindopril increases renal blood flow, the glomerular filtration rate does not change. The antihypertensive effect of the drug reaches a maximum after 4-6 hours after a single ingestion and remains within 24 hours. The antihypertensive effect 24 hours after a single dose is about 87-100% of the maximum antihypertensive effect. Reduction of blood pressure is achieved quite quickly. The therapeutic effect occurs less than 1 month after the start of therapy and is not accompanied by tachyphylaxis. Termination of treatment does not cause rebound effect. Perindopril has a vasodilating effect, helps to restore the elasticity of large arteries and the structure of the vascular wall of small arteries, and also reduces left ventricular hypertrophy. Stable coronary artery disease The effectiveness of perindopril in patients (12 218 patients over 18) with stable coronary artery disease without clinical symptoms of chronic heart failure was studied during 4 year study.90% of study participants had previously experienced acute myocardial infarction and / or revascularization. Most patients received standard therapy in addition to the study drug, including antiplatelet agents, lipid-lowering drugs and beta-blockers. As the main criterion of effectiveness, a combined end point was chosen, including cardiovascular mortality, nonfatal myocardial infarction and / or cardiac arrest with successful resuscitation. Therapy with perindopril tertbutylamine at a dose of 8 mg 1 time / day (equivalent to 10 mg of perindopril arginine) resulted in a significant the absolute risk of complications decreased by 1.9%, in patients who had previously suffered a myocardial infarction and / or revascularization procedure, the absolute risk was reduced by 2.2% compared with the placebo group. Dual RAACI blockade provides clinical trials of combination therapy using an ACE inhibitor and an angiotensin II receptor blocker (APA II). A clinical study was conducted with patients with a history of cardiovascular or cerebrovascular disease, or diabetes mellitus type 2, accompanied by confirmed lesion of the target organ, also studies involving patients with type 2 diabetes and diabetic nephropathy. These studies did not reveal a significant positive effect of combined treatment for the occurrence of renal and / or cardiovascular events and mortality rates, while the risk of hyperkalemia, acute renal failure and / or arterial hypotension increased compared with monotherapy. Taking into account the similar intragroup pharmacodynamic properties of ACE inhibitors and ARA II, These results can be expected for the interaction of any other drugs, representatives of the classes of ACE inhibitors and ARA II. Therefore, ACE inhibitors and ARA II should not be used simultaneously in patients with diabetic nephropathy. There are data from a clinical study examining the positive effects of adding aliskiren to standard therapy with an ACE inhibitor or ARA II in patients with type 2 diabetes and chronic kidney disease or cardiovascular disease, or having a combination of these diseases.The study was terminated early due to an increased risk of adverse outcomes. Cardiovascular death and stroke were observed more frequently in the group of patients receiving aliskiren, compared with the placebo group; also adverse events and serious adverse events of particular interest (hyperkalemia, hypotension, and renal dysfunction) were recorded more often in the aliskiren group than in the placebo group. Amlodipine Amlodipine is a slow calcium channel blocker derived from dihydropyridine. Amlodipine inhibits the transmembrane transition of calcium ions to cardiomyocytes and smooth muscle cells of the vascular wall. The antihypertensive effect of amlodipine is due to a direct relaxing effect on the smooth muscle cells of the vascular wall. The detailed mechanism by which amlodipine performs an antianginal effect is not fully established, but it is known that amlodipine reduces the overall ischemic load through a double action: - causes expansion of peripheral arterioles, reducing OPSS (afterload). Since the heart rate does not change, the myocardial oxygen demand decreases; it causes expansion of the coronary arteries and arterioles in both ischemic and intact zones. Their dilatation increases the oxygen supply to the myocardium in patients with vasospastic angina (Prinzmetal's angina, or variant angina). In patients with hypertension, taking amlodipine 1 time / day provides a clinically significant reduction in blood pressure while standing and lying down for 24 hours. Antihypertensive effect develops slow, and therefore the development of acute arterial hypotension is uncharacteristic. In patients with angina, taking amlodipine 1 time / day increases the total exercise time, increases time mja before development angina and before the ST segment depression of 1 mm, and also reduces the frequency of angina attacks and nitroglycerin consumption under yazyk.Amlodipin has no adverse metabolic effects and does not affect the concentration of plasma lipids. The drug can be used in patients with concomitant bronchial asthma, diabetes mellitus and gout. IBS The results of the effectiveness evaluation indicate thatthat amlodipine intake is characterized by a smaller number of hospitalizations for angina pectoris and revascularization procedures in patients with IBS. Heart failure The results of hemodynamic studies, as well as the results of clinical studies involving patients with chronic heart failure, FC II-IV, according to the NYHA classification, showed that amlodipine does not result to clinical deterioration, based on data on exercise tolerance, left ventricular ejection fraction and clinic Symptoms. Patients with chronic heart failure III-IV FC according to the NYHA classification, while receiving digoxin, diuretics, and ACE inhibitors, it was shown that taking amlodipine does not increase the risk of mortality or mortality and morbidity associated with heart failure. long-term studies in patients with chronic heart failure III and IV FC according to the NYHA classification without clinical symptoms of IHD or objective data indicating the presence of IHD, while receiving stable doses and gibitorov ACE, cardiac glycosides and diuretics showed that taking amlodipine has no effect on mortality from cardiovascular diseases. In this patient population, amlodipine was accompanied by an increase in the number of reports of pulmonary edema. Prevention of myocardial infarction The efficacy and safety of using amlodipine at a dose of 2.5-10 mg / day, an ACE inhibitor lisinopril at a dose of 10-40 mg / day and thiazide diuretic chlorthalidone at 12.5- 25 mg / day as a first-line drug was studied in patients with mild or moderate degree of hypertension and at least one of the additional risk factors for coronary complications, such as myocardial infarction or stroke, Yesenia more than 6 months prior to study entry, or other evidence of cardiovascular disease of atherosclerotic; diabetes; the concentration of HDL cholesterol is less than 35 mg / dL; left ventricular hypertrophy according to ECG or echocardiography; smoking. The main criterion for evaluating the effectiveness is a combined indicator of the frequency of deaths from IHD and the frequency of nonfatal myocardial infarction.There were no significant differences between the amlodipine and chlorthalidone groups in the main evaluation criteria. The incidence of heart failure in the amlodipine group was significantly higher than in the chlorthalidone group — 10.2% and 7.7%, respectively, and the overall death rate in the amlodipine and chlorthalidone groups did not differ significantly. Perindopril and amlodipine Effectiveness with long-term use of amlodipine in combination with perindopril and atenolol in combination with bendroflumethiazide in patients aged 40 to 79 years with hypertension and at least 3 of additional risk factors such as left ventricular hypertrophy according to an ECG or echo ardiografii; type 2 diabetes; peripheral artery atherosclerosis; previous stroke or transient ischemic attack; male; age 55 years and older; microalbuminuria or proteinuria; smoking; total cholesterol / HDL cholesterol ≥ 6; early development of coronary artery disease in next of kin, was studied in the ASCOT-BPLA study. The main criterion for evaluating the effectiveness is a combined indicator of the incidence of nonfatal myocardial infarction (including painless) and deaths of IBS. The frequency of complications provided for by the main evaluation criterion in the amlodipine group / perindopril was 10% lower than in the atenolol / bendroflumethiazide group, but this difference was not statistically significant. In the amlodipine / perindopril group, there was a significant decrease in the incidence of complications, provided by additional criteria of effectiveness (except for fatal and nonfatal heart failure).
Pharmacokinetics
The amount of absorption of perindopril and amlodipine when using Prestanta is not significantly different from that when using monopreparations. Perindopril Absorption When taken perindopril is rapidly absorbed, Cmax in the blood plasma is reached within 1 hour. T1 / 2 of perindopril from the blood plasma is 1 hour. Perindopril does not have pharmacological activity. Approximately 27% of the total amount of perindopril ingested enters the bloodstream as an active metabolite of perindoprilat. In addition to perindoprilat, 5 more metabolites are formed that do not possess pharmacological activity. Cmax of perindoprilat in plasma is reached 3-4 h after ingestion.Eating slows down the conversion of perindopril to perindoprilat, thereby affecting bioavailability. Therefore, the drug should be taken 1 time / day, in the morning, before eating. Distribution There is a linear dependence of the concentration of perindopril in the blood plasma from its dose. Vd of free perindoprilat is approximately 0.2 l / kg. The binding of perindoprilat with plasma proteins, mainly with ACE, is about 20% and is dose-dependent in nature. ExcretionPerindoprilat is excreted by the kidneys. The final T1 / 2 of the free fraction is about 17 hours, so an equilibrium state is reached within 4 days. Pharmacokinetics in special clinical situations. Perinoprilat release is slowed down in old age, as well as in patients with heart and kidney failure (see Dosage regimen). Therefore, in these groups of patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. The dialysis clearance of perindoprilat is 70 ml / min. The pharmacokinetics of perindopril is impaired in patients with cirrhosis of the liver: its hepatic clearance decreases by 2 times. However, the amount of perindoprilat formed does not decrease, which does not require dose adjustment (see section Dosage regimen and Special Instructions). Amlodipine Absorption After oral administration, amlodipine is slowly absorbed from the gastrointestinal tract. Eating does not affect the bioavailability of amlodipine. Cmax of amlodipine in the blood plasma is achieved 6-12 hours after ingestion. Absolute bioavailability is about 64-80%. The distribution of Vd is about 21 l / kg. In vitro studies have shown that about 97.5% of circulating amlodipine is associated with plasma proteins. Metabolism and elimination The final T1 / 2 of amlodipine from plasma is 35-50 h, which allows you to take the drug 1 time / day. Amlodipine is metabolized in the liver to form inactive metabolites, with 10% of the dose taken out unchanged and 60% by the kidneys as metabolites. Pharmacokinetics in special clinical situations. The time from taking the drug to reaching Cmax of amlodipine does not differ in elderly and younger patients. In elderly patients, amlodipine clearance slows down, which leads to an increase in AUC. The increase in AUC and T1 / 2 in patients with CHF corresponds to the expected value for this age group. In patients with impaired renal function, changes in plasma concentration of amlodipine do not correlate with the degree of renal failure.A slight increase in T1 / 2 is possible. Data on the use of amlodipine in patients with hepatic insufficiency are limited. In patients with liver failure, there is a decrease in the clearance of amlodipine, which leads to an increase in T1 / 2 and AUC of approximately 40-60%. Amlodipine is not excreted from the body through dialysis.
Indications
Arterial hypertension. IBS: stable exertional angina in patients who require perindopril and amlodipine.
Contraindications
Perindopril: - Angioedema (Quincke's edema) in history (including against the background of taking other ACE inhibitors) .- Hereditary / idiopathic angioedema .- Age up to 18 years (efficacy and safety have not been established) .- Hypersensitivity to perindopril or other ACE inhibitors. Amlodipine: - Severe arterial hypotension (systolic blood pressure less than 90 mm Hg). - Obstruction of the left ventricular output tract (for example, severe aortic stenosis) .- Unstable stenocardia (except for Prinzmetal angina) .- t to 18 years (efficacy and safety have not been established) .- Hypersensitivity to amlodipine or other dihydropyridine derivatives. Suspension: - Renal failure (CC less than 60 ml / min) .- Age 18 years (efficacy and safety not established) .- Hereditary lactose intolerance, lactase deficiency and glucose / galactose malabsorption syndrome. - Hypersensitivity to excipients that make up the drug. With caution: Renal artery stenosis (including bilateral) .- The only functioning kidney. - Hepatic failure. - Renal failure. - Systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma). - Immunosuppressant therapy, allopurinol, procainamide (risk of developing neutropenia, agranulocytosis) .- Reduced bcc (diuretic intake, salt-free diet, vomiting, diarrhea) .- Atherosclerosis .- Cerebrovascular diseases.- Renovascular hypertension.- Diabetes mellitus.- Chronic heart failure.- Use of dantrolene, estramus ina, potassium-sparing diuretics, potassium preparations, potassium-based salt substitutes and food preparations litiya.- Giperkaliemiya.- Surgery / total anesteziya.- Elder vozrast.- hemodialysis using vysokoprotochnyh membranes (e.g.AN69) .- Desensitizing therapy. - Apheresis, LDL. - Aortic stenosis / mitral stenosis / hypertrophic cardiomyopathy. - Patients of the negroid race.
Precautionary measures
Do not exceed the recommended dose. With cautionStenosis of the renal artery (including bilateral), the only functioning kidney, liver failure, renal failure, systemic diseases of the connective tissue (including systemic lupus erythematosus, scleroderma), therapy with immunosuppressants, allopurinol, procainamide (risk of developing neutropenia, agranulocytosis), reduced BCC (diuretic intake, salt-free diet, vomiting, diarrhea), atherosclerosis, cerebrovascular diseases, renovascular hypertension, diabetes mellitus , Chronic heart failure, the simultaneous use of dantrolene, estramustine, potassium-sparing diuretics, potassium preparations, potassium-containing substitutes salt and lithium preparations, hyperkalemia, surgery / general anesthesia, elderly, hemodialysis using vysokoprotochnyh membranes (e.g., AN69), desensitizing therapy , apheresis LDL, aortic stenosis / mitral stenosis / hypertrophic obstructive cardiomyopathy, use of the Negroid race in patients, chronic heart failure of non-ischemic etiology of III-IV FC according to NYHA classification.
Use during pregnancy and lactation
The drug is contraindicated in pregnancy. The drug is not recommended for use during breastfeeding. It is necessary to assess the significance of therapy for the mother in order to decide whether to stop breastfeeding or discontinue the drug. Pregnancy Perindopril The use of ACE inhibitors is not recommended for use in the first trimester of pregnancy (see the section on Special Instructions). The use of ACE inhibitors is contraindicated in the II and III trimesters of pregnancy (see sections Contraindications and Special Instructions). At the moment there are no conclusive epidemiological data on the teratogenic risk when taking ACE inhibitors in the I trimester of pregnancy. However, a slight increase in the risk of fetal developmental disorders cannot be excluded. When planning a pregnancy, you should cancel the drug and prescribe other antihypertensive drugs allowed for use during pregnancy.When pregnancy occurs, you should immediately stop therapy with ACE inhibitors and, if necessary, prescribe another therapy. It is known that the effect of ACE inhibitors on the fetus in the second and third trimesters of pregnancy can lead to a violation of its development (reduced kidney function, oligohydramnion, slowing ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia). If the patient received ACE inhibitors in the second and third trimesters of pregnancy, it is recommended ZI for assessing the state of the skull and kidney / fetal kidney function. Newborns whose mothers received ACE inhibitors during pregnancy should be under close medical supervision due to the risk of arterial hypotension (see the Contraindications and Special Instructions sections). Amlodipine during pregnancy not established. In experimental animal studies, the fetotoxic and embryotoxic effects of the drug were established when used in high doses. Use during pregnancy is possible only in the absence of a safer alternative and when the disease carries a greater risk for the mother and fetus. Breastfeeding Period Perindopril Due to the lack of information regarding the use of perindopril during breastfeeding, perindopril is not recommended, it is preferable to adhere to alternative treatment with breastfeeding during breastfeeding more studied safety profile, especially when feeding newborns or premature babies. There are no data on the excretion of perindopril with breast milk. Amlodipine There are no data on the excretion of amlodipine in breast milk. The decision to continue / discontinue therapy or breastfeeding should be made taking into account the benefits of breastfeeding for the child and the benefits of taking amlodipine for the mother. Impact on fertility Perindopril There were no effects of perindopril on reproductive function or fertility. biochemical changes were found in the sperm head.However, there are currently insufficient clinical data regarding the potential effect of amlodipine on fertility. A study on rats revealed undesirable effects on fertility in males.
Dosage and administration
The drug is administered orally, 1 tablet 1 time / day, preferably in the morning before a meal. The dose of Prestans is adjusted after the previous titration of doses of individual components of the drug: perindopril and amlodipine in patients with arterial hypertension and stable angina pectoris. When therapeutic, the dose of Prestans can be changed based on individual selection of doses of individual components: 5 mg of perindopril + 5 mg amlodipine or 5 mg of perindopril + 10 mg of amlodipine or 10 mg of perindopril + 5 mg of amlodipine or 10 mg of perindopril + 10 mg of amlodipine. Permanently in doses of 10 mg of perindopril + 10 mg of amlodipi on is the maximum daily dose of the drug, which is not recommended to exceed. The release of perindoprilat in elderly patients and patients with renal insufficiency is slow. Therefore, in such patients, it is necessary to regularly monitor the concentration of creatinine and potassium in the blood plasma. Can Prestans be prescribed to patients with QA? 60 ml / min. Prestanc is contraindicated in patients with CC <60 ml / min. Such patients are recommended individual selection of doses of perindopril and amlodipine. Changes in the concentration of amlodipine in the blood plasma do not correlate with the severity of renal failure. Care should be taken when prescribing Prestan to patients with hepatic insufficiency due to the lack of recommendations for dosing the drug in these patients. Prestans should not be given to children and adolescents under 18 years of age due to lack of data on the efficacy and safety of perindopril and amlodipine in these groups of patients, both as monotherapy and as a combination therapy.
Side effects
On the part of the hemopoietic system: very rarely - leukopenia, neutropenia, agranulocytosis, pancytopenia, thrombocytopenia, hemolytic anemia in patients with congenital glucose-6-phosphate dehydrogenase deficiency, decreased hemoglobin and hematocrit concentrations. Allergic reactions: infrequently, a nopartist, and a nopartistone nopropagate, an np parashy; body weight, weight loss.Very rarely - hyperglycemia. From the side of the central nervous system: often - drowsiness, dizziness, headache, paresthesia; infrequently - insomnia, mood lability, sleep disturbance, tremor, hypoesthesia; very rarely - peripheral neuropathy, confusion of consciousness. On the part of the organ of vision: often - visual disturbances. On the side of the organ of hearing: often - tinnitus. On the part of the cardiovascular system: often - palpitations, flushing of the face . Infrequently - fainting. Rarely - pain behind the sternum. Very rarely, angina pectoris, myocardial infarction, possibly due to an excessive decrease in blood pressure in patients from the high risk group, arrhythmias (including bradycardia, ventricular tachycardia and atrial fibrillation), stroke, possibly due to an excessive decrease in blood pressure in patients from the high risk, vasculitis. On the part of the respiratory system: often - shortness of breath, cough; infrequently - rhinitis, bronchospasm; very rarely - eosinophilic pneumonia. From the digestive system: often - abdominal pain, nausea, vomiting, dyspepsia, a violation of taste perception, diarrhea, constipation; infrequently - constipation, dryness of the oral mucosa; rarely, increased bilirubin levels; very rarely - pancreatitis, gingival hyperplasia, gastritis, hepatitis, cholestatic jaundice, cytolytic or cholestatic hepatitis, increased activity of liver enzymes ACT, ALT (most often in combination with cholestasis). From the skin: often - itchy skin, rash; infrequently - angioedema of the face, extremities, lips, mucous membranes, tongue, glottis and / or larynx, alopecia, hemorrhagic rash, photosensitization, increased sweating; very rarely - angioedema, erythema multiforme, Stevens-Johnson syndrome. On the part of the musculoskeletal system: often - muscle spasms; infrequently - arthralgia, myalgia, back pain. On the part of the kidneys and urinary tract: infrequently - urination disorder, nocturia, frequent urination, renal failure; very rarely - severe renal failure. From the reproductive system: infrequently - impotence, gynecomastia. On the whole body: often - peripheral edema, asthenia, increased fatigue. Infrequently - chest pain, malaise. Laboratory parameters: unspecified frequency - increased concentration of urea and creatinine in blood serum, hyperkalemia.
Overdose
Information on overdose of Prestan is not available. Amlodipine Information on overdose of amlodipine is limited. Symptoms: excessive peripheral vasodilation, leading to reflex tachycardia, pronounced and persistent decrease in blood pressure, including with the development of shock and death. Treatment: a pronounced decrease in blood pressure caused by an overdose of amlodipine, requires active measures aimed at maintaining the function of the cardiovascular system, including monitoring the performance of the heart and lungs, elevated limbs, control of bcc and diuresis. To restore vascular tone and blood pressure, it may be useful to use a vasoconstrictor drug, if there are no contraindications to its use, to eliminate the effects of calcium channel blockade - on / in the administration of calcium gluconate. In some cases, gastric lavage may be effective. Acceptance of activated carbon during the first 2 hours after taking amlodipine at a dose of 10 mg leads to a delay in the absorption of the drug. Since amlodipine is actively associated with plasma proteins, hemodialysis is ineffective. Perindopril Perindopril overdose is limited. Symptoms: overdose with ACE, there can be a marked decrease in blood pressure, shock, impaired water and electrolyte balance, renal insufficiency, hyperventilation, tachycardia, heartbeat, impaired hydrofluence, renal failure, hyperventilation, tachycardia, heartbeat, disturbances, hyperventilation, heart rate, tachycardia, heartbeat, disturbances, hyperventilation, tachycardia, heartbeat, disturbances in water and electrolyte balance, renal insufficiency, hyperventilation, tachycardia, heartbeat, impaired hydrofluence , cough. Treatment: with a significant decrease in blood pressure should transfer the patient to the supine position with raised legs. In / in infusion of 0.9% sodium chloride solution. If necessary, it is possible to introduce catecholamine solution on / in. With dialysis, perindopril can be removed from the systemic circulation (see Special Instructions section). With the development of treatment-resistant bradycardia, it may be necessary to install an artificial pacemaker. It is necessary to constantly monitor the indicators of the main vital functions of the body, the concentration of creatinine and electrolytes in the serum.
Interaction with other drugs
Perindopril Clinical studies show that double blockade of RAAS as a result of the simultaneous use of ACE inhibitors, ARA II or aliskiren leads to an increase in the incidence of adverse events such as arterial hypotension,hyperkalemia and renal dysfunction (including acute renal failure), compared with situations where only one drug is used that affects the RAAS (see sections Contraindications, Special instructions and Pharmacological action). Recommended drug combinations edible salt: although the serum potassium content remains within the normal range, some patients may experience it with perindopril. hyperkalemia. Potassium-sparing diuretics (for example, spironolactone, eplerenone (a derivative of spironolactone), triamterene, amiloride), potassium supplements, and potassium-containing salt substitutes can lead to a significant increase in serum potassium. Therefore, the simultaneous use of an ACE inhibitor and the above funds is not recommended (see section Special instructions). If simultaneous use is necessary (in the case of confirmed hypokalemia), care should be taken to regularly monitor plasma potassium levels and ECG parameters. Lithium preparations: while using lithium preparations and ACE inhibitors, a reversible increase in plasma lithium may occur and associated with this toxic effects. The simultaneous use of perindopril and lithium preparations is not recommended. If necessary, such therapy requires regular monitoring of the lithium content in the blood plasma (see section Specific Instructions). Estramustin: simultaneous use of estramustine with ACE inhibitors is accompanied by an increased risk of developing angioedema. ≥ 3 g / day): simultaneous use of ACE inhibitors with NSAIDs (acetylsalicylic acid in a dose that has anti-inflammatory effect, inhibitor oors COX-2 and non-selective NSAIDs), can lead to a decrease in the antihypertensive effect of ACE inhibitors. The simultaneous use of ACE inhibitors and NSAIDs can lead to a deterioration in renal function, including the development of acute renal failure, and an increase in serum potassium, especially in patients with reduced kidney function. Care should be taken in the appointment of this combination, especially in elderly patients.Patients need to compensate for fluid loss and carefully monitor kidney function both at the beginning of treatment and during treatment. Hypoglycemic agents (insulin, sulfonylurea derivatives): ACE inhibitors can enhance the hypoglycemic effect of insulin and sulfonylurea derivatives in patients with diabetes. The development of hypoglycemia is observed very rarely (probably due to an increase in glucose tolerance and a decrease in insulin requirements). Drug combinations that require attention Diuretics (thiazide and loop): in patients receiving diuretics, especially with excessive fluid and / or electrolytes, At the beginning of therapy with an ACE inhibitor, a significant decrease in blood pressure can be observed, the risk of developing which can be reduced by canceling the diuretic, administering an increased amount of liquid and / or salt, and also prescribing rindopril at a low dose with a gradual further uvelicheniem.Simpatomimetiki it can weaken the antihypertensive effect APF.Preparaty gold inhibitors: The use of ACE inhibitors, including perindopril, in patients receiving IV gold medications (sodium aurothiomalate), a symptom complex was described, including facial flushing, nausea, vomiting, arterial hypotension. Simultaneous use with ACP inhibitors allopurinol, immunosuppressive drugs, corticosteroids (for systemic use and protopia), and protopia) may be associated with an increased risk of leukopenia, especially in patients with existing impaired renal function. A joint