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Active ingredients
Ramipril
Release form
Pills
Composition
1 tablet contains: Active substance: ramipril 10 mg. Auxiliary substances: hypromellose, pregelatinized starch, microcrystalline cellulose, sodium fumarate.
Pharmacological effect
An antihypertensive drug, an ACE inhibitor. The active metabolite of ramipril, ramiprilat, which is influenced by hepatic enzymes, is a long-acting ACE inhibitor, which is a peptidyl dipeptidase. ACE in plasma and tissues catalyzes the conversion of angiotensin I to angiotensin II and the breakdown of bradykinin. Therefore, when taking ramipril inside, the formation of angiotensin II decreases and there is an accumulation of bradykinin, which leads to the expansion of blood vessels and a decrease in blood pressure. An increase in the activity of the kallikrein-kinin system in the blood and tissues causes the cardioprotective and endothelioprotective effect of ramipril due to the activation of the prostaglandin system and, accordingly, an increase in the synthesis of prostaglandins that stimulate the formation of nitric oxide (NO) in endothelial cells. a decrease in the secretion of aldosterone and an increase in the serum concentrations of potassium ions. When the concentration of angiotensin II is reduced, its blood is eliminated inhibitory effect on the secretion of renin by the type of negative feedback, which leads to an increase in plasma renin activity. It is assumed that the development of some undesirable reactions (in particular dry cough) is also associated with an increase in bradykinin activity. In patients with arterial hypertension, ramipril reduces Blood pressure in the supine position and standing, without a compensatory increase in heart rate. Ramipril significantly reduces OPSS, almost without causing changes in the renal blood flow and glomerular filtration rate. The hypotensive effect begins to manifest after 1-2 hours after ingesting a single dose of the drug, reaching its highest value after 3-9 hours, and persists for 24 hours. When taking a course dose, the hypotensive effect can gradually increase, stabilizing usually by 3-4 weeks of regular use drug and then persisting for a long time.Sudden discontinuation of the drug does not lead to a rapid and significant increase in blood pressure (no withdrawal syndrome). In patients with arterial hypertension, ramipril slows down the development and progression of myocardial hypertrophy and vascular wall. In patients with chronic heart failure, ramipril reduces OPSS (decrease in heart load), increases the capacity of the venous bed and reduces the filling pressure of the left ventricle, which, respectively, leads to a decrease in the preload on the heart. In these patients, when receiving ramipril, there is an increase in cardiac output, ejection fraction and improved exercise tolerance. In diabetic and non-diabetic nephropathy, ramipril intake slows down the rate of progression of renal failure and the onset of end-stage renal failure, and thereby reduces the need for hemodialysis or transplantation procedures the kidneys. In the initial stages of diabetic or non-diabetic nephropathy, ramipril reduces albuminuria. In patients with a high risk of developing cardiovascular diseases due to either vascular lesions (diagnosed with coronary artery disease, obliterating diseases of the peripheral arteries in history, stroke in history, or diabetes mellitus with no less than one additional risk factor (microalbuminuria, arterial hypertension, an increase in total cholesterol concentrations, a decrease in HDL cholesterol concentrations P, smoking) the addition of ramipril to standard therapy significantly reduces the incidence of myocardial infarction, stroke and mortality from cardiovascular causes. In addition, ramipril reduces overall mortality, as well as the need for revascularization procedures, and slows the onset or progression of chronic heart failure. In patients with heart failure that developed in the first days of acute myocardial infarction (2-9 days), while taking ramipril, starting from 3 to 10 days of acute myocardial infarction, the risk of mortality decreases (by 27%), the risk of sudden death (by 30%), the risk of progression of chronic heart failure to severe (III-IV functional class a classification NYNA) / resistant to therapy (27%)the likelihood of subsequent hospitalization due to the development of heart failure (by 26%). In the general population of patients, as well as in patients with diabetes mellitus, with both hypertension and normal blood pressure, ramipril significantly reduces the risk of nephropathy and microalbuminuria.
Pharmacokinetics
Absorption, distribution and metabolism. After ingestion is rapidly absorbed from the gastrointestinal tract (50-60%). Food does not affect the completeness of absorption, but slows down absorption. Ramipril undergoes intensive presystemic metabolism / activation (mainly in the liver by hydrolysis), which results in its only active metabolite, ramiprilat, which is 6 times more active in inhibiting ACE ramipril activity. In addition, as a result of ramipril metabolism, diketopiperazine does not possess pharmacological activity, which is then conjugated with glucuronic acid, ramiprilat is also glucuronic and metabolized to diketopiperazine acid. The bioavailability of ramipril after ingestion ranges from 15% (for a dose of 2.5 mg) to 15 mg (for a dose of 2.5 mg) for a dose of 5 mg). The bioavailability of the active metabolite - ramiprilat - after oral administration of 2.5 mg and 5 mg of ramipril is approximately 45% (compared to its bioavailability after i / v administration in the same doses). Cmax of ramipril and ramiprilat is reached in blood plasma after 1 and 2-4 h, respectively. The binding of ramipril to plasma proteins is 73%, ramiprilat - 56%. InjectionThe decrease in plasma concentration of ramiprilat occurs in several stages: the initial distribution and elimination phase with T1 / 2 ramiprilat, which is approximately 3 hours, then the intermediate phase with a period T1 / 2 ramiprilat, component of approximately 15 hours and the final phase with a very low concentration of ramiprilat in the blood plasma and T1 / 2 ramiprilat of approximately 4-5 days. This final phase is associated with the slow dissociation of ramiprilat from the association with the ACE receptors. Despite the prolonged final phase, taking ramipril once a day for a dose of 2.5 mg or more of Css, the concentration of ramiprilat in plasma is reached after approximately 4 days of treatment. For the course of treatment, the T1 / 2 preparation takes 13-17 hours. After ingestion of the labeledwith ramipril radioisotope (10 mg), 39% of radioactivity is excreted through the intestines and about 60% by the kidneys. After ingestion of 5 mg of ramipril in patients with bile duct drainage, almost the same amount of ramipril and its metabolites are excreted by the kidneys and through the intestine during the first 24 hours approximately 80-90% of metabolites in urine and bile were identified as ramiprilat and ramiprilat metabolites. Ramipril glucuronide and ramipril diketopiperazin account for approximately 10–20% of the total amount, and unmetabolized ramipril in the urine is approximately 2%. This leads to an increase in the plasma concentration of ramiprilat, which decreases more slowly than in patients with normal renal function. When receiving ramipril in high doses (10 mg), impaired liver function slows down the systemic metabolism of ramipril to active ramiprilat and slower elimination of ramiprilat. In healthy volunteers and in patients with arterial hypertension after two weeks of ramipril treatment in a daily dose of 5 mg, there is no clinically significant accumulation of ramipril and ramiprilat. In patients with x After two weeks of ramipril treatment with a daily dose of 5 mg, a cardiac heart failure shows a 1.5–1.8-fold increase in plasma concentrations of ramiprilat and AUC. In healthy elderly volunteers (65–76 years), the pharmacokinetics of ramipril and ramiprilat are not significantly different from those in young healthy volunteers In experimental animal studies, ramipril has been shown to be excreted in breast milk.
Indications
- Essential hypertension; - Chronic heart failure (as part of combination therapy, in particular in combination with diuretics); - Diabetic or non-diabetic nephropathy, preclinical and clinically expressed stages, including with severe proteinuria, especially when combined with arterial hypertension - reducing the risk of myocardial infarction, stroke or cardiovascular mortality in patients with high cardiovascular risk: in patients with confirmed coronary artery disease,history of myocardial infarction, with or without history, including patients undergoing percutaneous transluminal coronary angioplasty, coronary artery bypass surgery; in patients with a history of stroke; in patients with occlusive lesions of peripheral arteries; in patients with diabetes mellitus with at least one additional risk factor (microalbuminuria, arterial hypertension, increased plasma concentrations of total cholesterol, decreased plasma concentrations of HDL cholesterol, smoking) .- heart failure that developed during the first few days (from 2 to 9 day) after acute myocardial infarction.
Contraindications
- angioedema (hereditary or idiopathic, as well as after taking ACE inhibitors) in history - risk of rapid development of angioedema; - hemodynamically significant stenosis of the renal arteries (bilateral or unilateral in the case of a single kidney); - arterial hypotension (systolic BP less than 90 mm Hg) Art.) or conditions with unstable hemodynamic parameters; - hemodynamically significant stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy; - primary hyperaldosum ronism; - severe renal insufficiency (QA less than 20 ml / min with a body surface of 1.73 m2) (clinical experience is insufficient); hemodialysis (clinical experience is insufficient); pregnancy; lactation; nephropathy treated by SCS, NSAIDs, immunomodulators and / or other cytotoxic drugs (clinical experience is not enough); - chronic heart failure in the decompensation stage (clinical experience is insufficient); - age up to 18 years (clinical experience; hemodialysis or hemofiltration using some membranes with a negatively charged surface, such as high-flow polyacrylonitrile membranes (risk of hypersensitivity reactions); low-density lipoprotein apheresis using dextran sulfate (risk of hypersensitivity reactions); - hyposensitization therapy in case of hypersensitivity reactions to insect poisons such as bees, wasps; - hypersensitivity to ramipril and other inhibitors A PF,or any of the components of the drug. Additional contraindications for using Tritace in the acute stage of myocardial infarction: - severe heart failure (functional class IV according to the NYHA classification); - unstable angina; - life-threatening ventricular arrhythmias; - pulmonary heart.
Precautionary measures
Do not exceed the recommended doses. With caution, conditions in which an excessive decrease in blood pressure is especially dangerous (in case of atherosclerotic lesions of the coronary and cerebral arteries); conditions accompanied by an increase in the activity of the renin-angiotensin-aldosterone system (RAAS), in which there is the risk of a sharp decrease in blood pressure with deterioration of renal function (severe arterial hypertension, especially malignant arterial hypertension; chronic heart failure, especially severe or about which other medicines are taken with hypotensive action, hemodynamically significant unilateral stenosis of the renal artery (if both kidneys are present), prior diuretic intake, disturbance of water and electrolyte balance as a result of insufficient fluid and salt, diarrhea, vomiting, profuse sweating); - dysfunction of the liver (lack of experience in the application: it is possible both to strengthen and weaken the effects of ramipril; - if patients have cirrhosis of the liver with ascites and edema in significant activation of the RAAS is possible, see above. Conditions associated with an increase in the activity of the RAAS; kidney dysfunction (CC more than 20 ml / min with a body surface of 1.73 m2) due to the risk of hyperkalemia and leukopenia); state after kidney transplantation; Systemic diseases of the connective tissue, incl. systemic lupus erythematosus, scleroderma, concomitant therapy with drugs that can cause changes in the pattern of peripheral blood (possibly inhibition of bone marrow hematopoiesis, development of neutropenia or agranulocytosis); diabetes mellitus (risk of developing hyperkalemia); old age (risk of hypotensive effect); hyperkalemia .
Use during pregnancy and lactation
Ramipril is contraindicated during pregnancy, becausecan have an adverse effect on the fetus: impaired fetal kidney development, lowering fetal and newborn blood pressure, impaired kidney function, hyperkalemia, cranial bone hypoplasia, oligohydramnios, limb contracture, cranial bones deformation, pulmonary hypoplasia. Therefore, before starting the drug in women of childbearing age exclude pregnancy. If a woman is planning a pregnancy, the treatment with ACE inhibitors should be discontinued. If pregnancy occurs during the treatment with Tritace, follow ie, as soon as possible, stop taking it and move the patient to the treatment with other drugs, the application of which the risk to the child is naimenshim.Esli Tritace drug treatment is necessary during lactation, the breast-feeding should be discontinued.
Dosage and administration
Tablets must be swallowed whole (do not chew), and drink plenty of water (1/2 cup) of water, regardless of the meal (that is, pills can be taken both before and during or after meals). The dose is selected depending on the therapeutic effect and the patient's tolerance to the drug. Treatment with Tritace is usually long and its duration is determined by the doctor in each case. If not otherwise prescribed, the following dosing regimens are recommended for normal kidney and liver function. For essential hypertension, Usually The initial dose is 2.5 mg 1 time per day in the morning (in this case, Tritace 2.5 mg pills or 1/2 tablet of 5 mg can be used with a risk). If, when taking the drug in this dose for 3 weeks or more, it is not possible to normalize blood pressure, the dose may be increased to 5 mg / day. With insufficient effectiveness of the dose of 5 mg in 2-3 weeks, it can be doubled to the maximum recommended daily dose of 10 mg / day. As an alternative to increasing the dose to 10 mg per day with insufficient hypotensive effectiveness of the daily dose of 5 mg, it may be added to treatment of other antihypertensive drugs, in particular diuretics or slow calcium channel blockers. In chronic heart failure, the recommended initial dose is 1.25 mg 1 time / day (in this case 1/2 pills of Tritace 2.5 mg can be used with Coy).Depending on the response to the patient's therapy, the dose may increase. It is recommended to double the dose at intervals of 1-2 weeks. If a daily dose of 2.5 mg and higher is required, it can be given once a day or divided into 2 doses. The maximum recommended daily dose is 10 mg. In diabetic or non-diabetic nephropathy, the recommended initial dose is 1.25 mg 1 time / day (in this case You can use 1/2 tablet Tritace 2.5 mg with risk). The dose may be increased to 5 mg 1 time / day. In these conditions, doses higher than 5 mg 1 time / day have not been studied enough in controlled clinical studies. To reduce the risk of myocardial infarction, stroke or cardiovascular mortality in patients with high cardiovascular risk, the recommended initial dose is 2.5 mg 1 time / day (in In this case, you can use Tritace pills 2.5 mg or 1/2 tablet 5 mg with a risk). Depending on the patient's tolerance of the drug, the dose can be gradually increased. It is recommended to double the dose after 1 week of treatment, and in the next 3 weeks of treatment to increase it to the usual maintenance dose of 10 mg 1 time / day. Doses exceeding 10 mg have not been studied enough in controlled clinical studies. The use of the drug in patients with QA less than 0.6 ml / sec has not been studied enough. In case of heart failure that developed during the first few days (from 2 to 9 days) after acute myocardial infarction. The recommended initial dose is 5 mg / day, divided into two single doses of 2.5 mg, which I take One in the morning and the other in the evening (in this case, Tritace 2.5 mg pills or 1/2 pills of 5 mg can be used with risks). If the patient does not tolerate this initial dose (there is an excessive decrease in blood pressure), then it is recommended that he give 1.25 mg 2 times a day for two days (in this case, you can use 1/2 pills of Tritatz 2.5 mg with a risk). Then, from the patient's response, the dose may be increased. It is recommended that the dose with its increase doubled with an interval of 1-3 days. Later, the total daily dose, which was initially divided into two doses, may be given once. The maximum recommended dose is 10 mg. Currently, the experience of treating patients with severe heart failure (III-IV functional class according to NYHA classification) that arose immediately after an acute myocardial infarction. , is insufficient.If such patients decide to administer treatment with Tritace, it is recommended that treatment should be started with the lowest possible dose - 1.25 mg 1 time / day (in this case 1/2 pills of Tritace 2.5 mg can be used with risk) and special care should be taken when each dose increase. Use in individual groups of patients. Patients with impaired renal function. When using CK from 50 to 20 ml / min, the initial daily dose is usually 1.25 mg (in this case, you can use 1/2 pills of Tritace 2.5 mg with a risk). The maximum allowable daily dose is 5 mgPatients with incompletely corrected fluid and electrolyte loss, patients with severe arterial hypertension, as well as patients for whom excessive blood pressure reduction presents a certain risk (for example, with severe atherosclerotic lesions of the coronary and cerebral arteries). The initial dose is reduced to 1.25 mg / day (in this case, you can use 1/2 pills of Tritace 2.5 mg with a risk). Patients with prior diuretic therapyIt is necessary, if possible, to cancel diuretics in 2-3 days ( depending on the duration of the action of diuretics) before starting treatment with Tritace, or at least reduce the dose of diuretics taken. The treatment of such patients should be started with the lowest dose, equal to 1.25 mg of ramipril (in this case 1/2 pills of Tritace 2.5 mg with a risk can be used), taken 1 time / day in the morning. After taking the first dose and every time after increasing the dose of ramipril and (or) loop diuretics, patients should be under medical supervision for at least 8 hours to avoid an uncontrolled antihypertensive reaction. Elderly patients (over 65) The initial dose is reduced to 1.25 mg / day ( in this case, you can use 1/2 pills of Tritace 2.5 mg with a risk). Patients with impaired liver functionReaction of blood pressure to receive the drug Tritace can either increase (by slowing out the removal of ramiprilat) or decrease (by slowing down conversion of low-level ramipril into active ramiprilat). Therefore, at the beginning of treatment requires careful medical observation. The maximum permissible daily dose is 2.5 mg (in this case, Tritace pills 2.5 mg or 1/2 tablet of 5 mg can be used with the risk).
Side effects
The following undesirable effects are given in accordance with the following gradations of the frequency of their occurrence: very often (≥10%), often (≥1%, but <10%), sometimes (≥0.1%, but <1%), rarely (≥0.01 %, but <0.1%), very rarely (<0.01%, including isolated cases), the frequency is unknown (according to the available data it is impossible to establish the frequency of occurrence). From the cardiovascular system: often - excessive reduction of blood pressure, orthostatic regulation vascular tone (orthostatic hypotension), syncopal states; sometimes - myocardial ischemia, including the development of an attack of stenocardia or myocardial infarction, tachycardia, arrhythmias (appearance or intensification), heartbeat, peripheral edema, flushing of blood to the skin of the face; rarely - the occurrence or enhancement of circulatory disorders on the background of stenotic vascular lesions, vasculitis; frequency is unknown - Raynaud's syndrome. From the side of the CNS: often - headache, feeling of lightness in the head; sometimes - dizziness, agevziya (loss of taste sensitivity), dysgeusia (violation of taste sensitivity), depressed mood, anxiety, nervousness, restlessness, sleep disorders, including drowsiness; rarely - tremor, imbalance, confusion; frequency is unknown - cerebral ischemia, including ischemic stroke and transient cerebral circulation disturbance, impaired psychomotor reactions, paresthesia (burning sensation), parosmia (impaired sense of smell), impaired attention. Eyesight: sometimes visual disturbances, including blurred images; rarely - conjunctivitis. From the side of the organ of hearing: rarely - hearing loss, ringing in the ears. From the side of the respiratory system: often - dry cough (aggravated at night and when lying down), bronchitis, sinusitis, shortness of breath; sometimes bronchospasm, including worsening of asthma, nasal congestion. On the digestive system: often - inflammatory reactions in the stomach and intestines, digestive disorders, discomfort in the abdomen, dyspepsia, diarrhea, nausea, vomiting; sometimes - pancreatitis, incl. fatal (cases of pancreatitis with a fatal outcome when taking ACE inhibitors were extremely rare), an increase in the activity of pancreatic enzymes in the blood plasma,intestinal angioedema, abdominal pain, gastritis, constipation, dryness of the oral mucosa; rarely - glossitis; frequency unknown - aphthous stomatitis (inflammatory reaction of the mucous membrane of the oral cavity). On the part of the hepatobiliary system: sometimes - increased activity of liver enzymes and concentration of conjugated bilirubin in the blood plasma; rarely - cholestatic jaundice, hepatocellular lesions; frequency unknown - acute liver failure, cholestatic or cytolytic hepatitis (death was extremely rare). From the kidneys and urinary tract: sometimes - impaired kidney function, including the development of acute renal failure, increased urine output, increased pre-existing proteinuria, increased concentration urea and creatinine in the blood. From the reproductive system and mammary glands: sometimes - transient impotence due to erectile dysfunction, decreased libido; frequency is unknown: gynecomastia. From the hematopoietic system: sometimes - eosinophilia; rarely - leukopenia, including neutropenia and agranulocytosis, a decrease in the number of erythrocytes in peripheral blood, a decrease in the concentration of hemoglobin, thrombocytopenia; frequency is unknown - oppression of bone marrow hematopoiesis, pancytopenia, hemolytic anemia. From the skin and mucous membranes: often - skin rash (in particular maculopapular rash); sometimes - angioedema, incl. fatal (laryngeal edema can cause airway obstruction, resulting in death), pruritus, hyperhidrosis; rarely - exfoliative dermatitis, urticaria, oniholysis; very rarely - photosensitivity reactions; frequency is unknown - toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsening of the course of psoriasis, psoriasis-like dermatitis, pemphigoid or lichenoid (desiccous) exanthema or enanthema, alopecia. sometimes - arthralgia. Disorders of metabolism, nutrition and laboratory parameters: often - an increase in the concentration of potassium in the blood; sometimes anorexiadecreased appetite; frequency unknown - decrease in sodium concentration in the blood. From the immune system: frequency unknown - anaphylactic or anaphylactoid reactions (with inhibition of ACE, anaphylactic or anaphylactoid reactions to insect poisons increase), increasing the concentration of antinuclear antibodies. General disorders: often - chest pain, feeling tired; sometimes - fever; rarely - asthenia (weakness).
Overdose
Symptoms: excessive peripheral vasodilation with the development of a pronounced decrease in blood pressure, shock; bradycardia, water and electrolyte disorders, acute renal failure, stupor. Treatment: gastric lavage, taking adsorbents, sodium sulfate (if possible during the first 30 minutes). In the case of a pronounced decrease in blood pressure, the introduction of alpha1-adrenergic agonists (norepinephrine, dopamine) and angiotensin II (angiotensinamide) can be added to therapy for replenishing the blood volume rate and restoring electrolyte balance. In the case of bradycardia refractory to a drug treatment, it may be necessary to install a temporary artificial pacemaker. In case of overdose, it is necessary to monitor serum concentrations of creatinine and electrolytes.
Interaction with other drugs
Contraindicated combinations Using certain high-flow membranes with a negatively charged surface (for example, polyacrylonitrile membranes) when performing hemodialysis or hemofiltration and using dextran sulfate when apheresis of low-density lipoproteins increases the risk of developing severe anaphylactic reactions. , spironolactone) perhaps a more pronounced increase in the concentration of potassium in serum e blood (while the application requires careful control of the concentration of potassium in blood serum) .Kombinatsii to be applied with ostorozhnostyuS antihypertensives (especially diuretics) and other drugs that lower blood pressure (nitrates, tricyclic antidepressants) marked potentiation of the antihypertensive effect; when combined with diuretics should be monitored the level of sodium in the serum. With hypnotics,narcotic and anesthetics are possible a more pronounced decrease in blood pressure. With vasopressor sympathomimetics (epinephrine), a decrease in the hypotensive effect of ramipril is noted, careful control of blood pressure is required. risk of developing leukopenia. With lithium salts, an increase in the serum concentration of lithium and an increase in the cardio-and neurotoxic effects With lithium. With hypoglycemic agents for oral administration (sulfonylurea derivatives, biguanides), insulin: due to a decrease in insulin resistance under the influence of ramipril, the hypoglycemic effect of these drugs can be enhanced up to the development of hypoglycemia. ) may weaken the action of ramipril, increase the risk of renal dysfunction and increase the concentration of potassium in the blood serum. With heparin may increase potassium ontsentratsii krovi.S serum sodium chloride may weaken the hypotensive action of ramipril and less effective treatment of the symptoms of chronic heart ethanol nedostatochnosti.S noted increased vasodilation. Ramipril may increase the adverse effect of ethanol on the body. With estrogen, a weakening of the hypotensive effect of ramipril (fluid retention) is noted. When desensitizing therapy is used, if you are hypersensitive to insect poisons, ACE inhibitors, including ramipril, increase the likelihood of severe anaphylactic or anaphylactoid reactions of insects.
special instructions
Before starting treatment with Tritace, it is necessary to eliminate hyponatremia and hypovolemia. In patients who have previously taken diuretics, it is necessary to cancel them or, at least, reduce their dose 2-3 days before starting taking the drug Tritace (in this case, the condition of patients with chronic heart failure should be carefully monitored, due to the possibility of their developing decompensation due to an increase in the BCC). After taking the first dose of the drug,as well as increasing the dose and / or dose of diuretics (especially loop ones), it is necessary to ensure careful medical observation of the patient for at least 8 hours in order to take appropriate measures in the event of an excessive decrease in blood pressure. If Tritace is used for the first time or in a high dose of patients with increased activity of the RAAS, they should be carefully monitored for blood pressure, especially at the beginning of treatment, as these patients have an increased risk of an excessive decrease in blood pressure. In malignant arterial hypertension and heart failure, especially in the acute stage of myocardial infarction, treatment with Tritace should be started only in a hospital setting. In patients with chronic heart failure, taking the drug can lead to the development of a pronounced decrease in blood pressure, which in some cases is accompanied by oliguria or azotemia and rarely development of acute renal failure. Care should be taken when treating older patients, since they may be particularly sensitive to ACE inhibitors; in the initial phase of treatment, it is recommended to monitor renal function indicators. In patients for whom a decrease in blood pressure may present a certain risk (for example, in patients with atherosclerotic narrowing of the coronary or cerebral arteries), treatment should begin under strict medical supervision. Caution should be exercised during physical exertion and / or hot weather due to the risk of sweating and dehydration with the development of arterial hypotension, due to the mind nsheniya bcc and reduction in the sodium concentration krovi.Vo time of treatment is not recommended to use Tritace alkogol.Prehodyaschaya hypotension is not a contraindication to continue treatment after stabilization of blood pressure. In case of recurrence