Sentor tab. p / captivity. about. 100mg in bl. in pack. №10х3

Name:
Sentor tab. p / captivity. about. 100mg in bl. in pack. No. 10×3 Main active ingredient Losartan Release form tablets Composition Each film-coated tablet contains: Active ingredient: Film-coated tablets, 50 mg: losartan potassium – 50 mg; Film-coated tablets, 100 mg: losartan potassium – 100 mg. Excipients: Core: anhydrous colloidal silicon dioxide, magnesium stearate, croscarmellose sodium, pregelatinized starch, microcrystalline cellulose. Film shell: Opadry II. 33G28523 white (glycerol triacetate, macrogol, lactose monohydrate, titanium dioxide CI 77891, E171, hypromellose).
Description:
Film-coated tablets, 50 mg: Round, biconvex, film-coated tablets, white or almost white, marked on one side and engraved “50” on the other side. Film-coated tablets, 100 mg: Oval biconvex film-coated tablets, white or almost white, on one side – engraved “100”, the other side – smooth. Dosage 50 mg; 100 mg. Pharmacological properties Pharmacodynamics Losartan is a synthetic angiotensin II receptor antagonist (type AT1) intended for oral administration. Angiotensin II, a powerful vasoconstrictor, is the main active hormone of the renin-angiotensin system and the most important factor in the pathophysiology of arterial hypertension. Angiotensin II binds to AT1 receptors found in many tissues (eg, vascular smooth muscle, adrenal glands, kidneys, and heart) and produces a number of important biological effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. Losartan selectively blocks AT1 receptors. Losartan and its pharmacologically active carboxylic acid metabolite (E-3174) in vitro and in vivo blocks all physiologically significant effects of angiotensin II, regardless of the source or route of its synthesis. Losartan does not have an agonistic effect and does not block other hormone receptors or ion channels that play an important role in the regulation of the cardiovascular system. In addition, losartan does not inhibit ACE (kinase II), an enzyme that breaks down bradykinin. Therefore, there is no increase in undesirable effects mediated by bradykinin. When using losartan, suppression of negative feedback on renin secretion is observed, which leads to an increase in plasma renin activity (ARP). An increase in ARP leads to an increase in the concentration of angiotensin II in the blood plasma. Despite this, an increase, antihypertensive activity and a decrease in the concentration of aldosterone in blood plasma persist, indicating an effective blockade of angiotensin II receptors. Within 3 days after discontinuation of treatment with losartan, the levels of ARP and angiotensin II decrease to initial levels. Both losartan and its major active metabolite have greater affinity for AT1 receptors than for AT2 receptors. In terms of weight, the active metabolite is 10-40 times more active than losartan. Hypertension Studies In controlled clinical trials in patients with mild to moderate essential hypertension who received losartan once daily, there was a statistically significant decrease in systolic and diastolic blood pressure. Measurement of blood pressure 24 hours after taking the drug and 5-6 hours after taking the drug showed a decrease in blood pressure within 24 hours; the natural circadian rhythm was preserved. The decrease in blood pressure at the end of the interval of taking the drug was 70-80% of the values observed 5-6 hours after administration. Discontinuation of treatment with losartan did not cause a sharp increase in blood pressure in patients suffering from arterial hypertension (rebound hypertension). Despite a pronounced decrease in blood pressure, the use of losartan does not have a clinically significant effect on heart rate. Losartan is equally effective for the treatment of men and women, young (under 65 years of age) and elderly patients suffering from arterial hypertension. The LIFE study The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was a triple-blind, active-controlled study that included 9193 patients aged 55 to 80 years with hypertension and left ventricular hypertrophy, confirmed by ECG data. Patients were randomized to receive losartan 50 mg once daily or atenolol 50 mg once daily. If the target blood pressure (<140/90 mmHg) could not be achieved, the treatment regimen was initially supplemented with hydrochlorothiazide (12.5 mg), and, if necessary, the dose of losartan or atenolol was increased to 100 mg once a day. Other antihypertensive drugs, with the exception of ACE inhibitors, angiotensin II antagonists or beta-blockers, were prescribed if it was necessary to achieve target blood pressure. The mean length of medical follow-up was 4.8 years. The primary endpoint was the combined endpoint of cardiovascular deaths and the reduction in cumulative mortality from cardiovascular causes, stroke, and myocardial infarction. Blood pressure was reduced to a large extent to similar levels in both groups. Treatment with losartan resulted in a 13.0% reduction in the risk of reaching the endpoint (p = 0.021, 95% confidence interval 0.77-0.98) compared with patients treated with atenolol. Mainly, this result was achieved by reducing the number of strokes. Treatment with losartan reduced the risk of stroke by 25% compared with atenolol (p = 0.001, 95% confidence interval 0.63-0.89). Mortality rates from myocardial infarction and cardiovascular causes did not differ significantly between the two groups. Race In the LIFE study, black patients treated with losartan had a higher risk of achieving the primary composite endpoint, ie. cardiovascular event (eg, heart attack or death from cardiovascular causes) and, in particular, stroke than black patients treated with atenolol. Therefore, the results obtained in the LIFE study regarding losartan versus anenolol in relation to cardiovascular morbidity/mortality are not applicable to black patients with arterial hypertension and left ventricular hypertrophy. The RENAAL study The RENAAL study, a risk reduction endpoint in patients with non-insulin dependent diabetes mellitus (NIDDM) treated with losartan, an angiotensin II receptor antagonist, was a controlled clinical study conducted worldwide with 1513 patients, patients with type II diabetes mellitus with proteinuria with or without arterial hypertension. 751 patients were treated with losartan. The aim of the study was to demonstrate that, in addition to lowering blood pressure, losartan potassium has a protective effect on the kidneys. Patients with proteinuria and a serum creatinine concentration in the range of 1.3-3.0 mg/dl were randomized into groups, one group received 50 mg of losartan once a day, (dose titrated if necessary), and the other placebo. Treatment was carried out against the background of conventional antihypertensive therapy, with the exception of the use of ACE inhibitors and angiotensin II receptor antagonists. Investigators were instructed to increase the dose to 100 mg if necessary; 72% of patients took 100 mg once daily most of the time. Other antihypertensive drugs (diuretics, calcium channel blockers, alpha- and beta-blockers, and centrally acting antihypertensives) were allowed as add-on therapy on demand in both groups. Follow-up medical follow-up of patients lasted up to 4.6 years (mean 3.4 years). The primary endpoint was the combined serum creatinine doubling point and end-stage renal disease (needing dialysis or kidney transplantation) or death. The results showed that treatment with losartan (327 cases) compared with placebo (359 cases) resulted in a 16.1% reduction (p=0.022) in the number of patients reaching the primary endpoint. The results also demonstrated a significant reduction in risk for the following components of the primary composite endpoint: 25.3% reduction in risk of doubling serum creatinine (p=0.006); 28.6% reduction in the risk of developing end-stage renal disease (p=0.002); 19.9% reduction in the risk of developing end-stage renal disease or death (p=0.009); 21.0% reduction in the risk of doubling serum creatinine or developing end-stage renal disease (p=0.01). There were no statistically significant differences in mortality from any cause between the two groups. In this study, losartan was generally well tolerated, with the percentage of patients discontinuing therapy due to adverse reactions comparable to that reported in the placebo group. The HEAAL study The HEAAL study, an endpoint risk assessment in patients with heart failure treated with an angiotensin II receptor antagonist losartan, was a controlled clinical trial conducted worldwide in 3834 patients aged 18 to 98 years with heart failure ( class II-IV according to the NYHA classification) and intolerance to ACE inhibitors. Patients were randomized to receive 50 mg or 150 mg of losartan once daily while receiving conventional antihypertensive therapy, except for the use of ACE inhibitors. Medical follow-up of patients lasted over 4 years (average 4.7 years). The primary end point was the composite point of death from any cause or hospitalization for heart failure. The results showed that treatment with losartan 150 mg (828 cases) compared with 50 mg (889 cases) resulted in a 10.1% risk reduction (p = 0.027, 95% CI 0.82-0.99) in relation to number of patients reaching the primary composite endpoint. This result was mainly achieved by reducing the number of hospitalizations due to heart failure. Treatment with losartan 150 mg reduced the risk of hospitalization for heart failure by 13.5% compared with losartan 50 mg (p = 0.025, 95% confidence interval 0.76-0.98). There were no significant differences in mortality from any cause between the two groups. Impaired renal function, arterial hypotension and hyperkalemia were more frequently observed in the losartan 150 mg group, however, these adverse reactions did not lead to a significantly higher percentage of patients who interrupted treatment in the 150 mg group. The ELITE I and ELITE II studies In the ELITE I study, which lasted over 48 weeks and included 722 patients with heart failure (NYHA class II-IV), there were no differences between patients treated with losartan and those treated with captopril, with respect to the primary endpoint, i.e. changes in renal function with long-term use, was not observed. The study found that treatment with losartan compared with treatment with captopril showed an unexpected reduction in mortality, however, the ELITE II study described below did not confirm this difference. In the ELITE II study, losartan 50 mg once daily (starting at 12.5 mg once daily, then increased to 25 mg and subsequently to 50 mg once daily) was compared with captopril 50 mg taken three times a day (initial dose was 12.5 mg three times a day, then the dose was increased to 25 mg and subsequently to 50 mg three times a day). The primary endpoint of this prospective study was all-cause mortality. In this study, medical follow-up of almost two years (mean 1.5 years) was established for 3125 patients with heart failure (class II-IV according to the NYHA classification), in order to determine whether the use of losartan leads to a decrease in mortality from any cause, compared with captopril. The endpoint did not confirm a statistically significant difference between losartan and captopril in terms of reduction in all-cause mortality. In both comparator-controlled (not placebo-controlled) clinical trials in patients with heart failure, losartan was better tolerated than captopril, as evidenced by a significantly lower percentage of patients who discontinued treatment due to adverse reactions and a lower incidence cough. During the ELITE II study, an increased mortality rate was observed in a small subset of patients (22% of all patients with heart failure) who initially received beta-blockers. Pediatric patients Arterial hypertension in children The purpose of the clinical study, which included 177 children aged 6 to 16 years, weighing ≥20 kg and glomerular filtration rate ≥30 ml / min / 1.73 m2, was to establish the antihypertensive effect losartan in children. Patients weighing ≥20 kg to <50 kg received 2.5, 25, or 50 mg of losartan per day, and patients weighing ≥50 kg received 5, 50, or 100 mg of losartan per day. Three weeks later, once daily lozaratan was found to cause a dose-dependent reduction in blood pressure. Overall, the response to treatment was dose-dependent. The dose-response relationship is particularly evident when comparing the lowest dose group and the middle dose group (period I: -6.2 mmHg vs. -11.65 mmHg), the relationship weakens when comparing the middle dose group and the highest dose group (period I: -11.65 mmHg vs. -12.21 mmHg). The lowest doses studied, 2.5 and 5 mg, corresponding to an average daily dose of 0.07 mg/kg, did not produce a sustained antihypertensive effect. These results were confirmed in the II period of the study, when after three weeks of treatment, patients were randomized to receive losartan or placebo. Differences in blood pressure elevation increased compared to the placebo group and were largest in the middle dose group (6.70 mmHg for the middle dose vs. 5.38 mmHg for the highest dose) . The minimum increase in diastolic pressure in patients treated with placebo and patients treated with losartan at the lowest dose was the same, which again confirmed the assumption that the lowest dose of losartan does not have a significant antihypertensive effect. The effect of long-term use of losartan on growth, puberty and overall development has not been studied. Also, the effectiveness of long-term treatment of pediatric patients with losartan, carried out in order to reduce cardiovascular morbidity and mortality, has not been established. The effect of losartan on proteinuria was evaluated in a placebo-controlled and active (amlodipine) controlled clinical trial lasting 12 weeks and including children with arterial hypertension (N=60) and normal blood pressure (N=246) in combination with proteinuria. Proteinuria was defined as a condition in which the protein/creatinine ratio was 0.3. Hypertensive patients (aged 6 to 18 years) were randomized to receive either losartan (n=30) or amlodipine (n=30). Patients with normal blood pressure (aged 1 to 18 years) were randomized to receive either losartan (n=122) or placebo (n=124). Losartan has been used at dosages ranging from 0.7 mg/kg to 1.4 mg/kg (up to a maximum dose of 100 mg per day). Amlodipine has been used at dosages ranging from 0.05 mg/kg to 0.2 mg/kg (up to a maximum dose of 5 mg per day). Overall, after 12 weeks of treatment, patients treated with losartan showed a statistically significant reduction in proteinuria of 36% from baseline versus a 1% increase in the placebo/amlodipine groups (p = 0.001). In hypertensive patients treated with losartan, the reduction in proteinuria from baseline was -41.5% (95% CI -29.9; -51.1) versus +2.4% (95% CI -22.2; 14 ,1) in the amlodipine group. The decrease in diastolic and systolic blood pressure was greater in the losartan group (-5.5/-3.8 mmHg) than in the amlodipine group (-0.1/+0.8 mmHg) . In children with normal blood pressure, there was also a slight decrease in blood pressure when taking losartan (-3.7 / -3.4 mm Hg) compared with the placebo group. There was no significant correlation between the decrease in proteinuria and blood pressure, but it is possible that the decrease in proteinuria in the losartan group was partly due to the decrease in blood pressure. The long-term effect of reducing proteinuria in children has not been studied. Pharmacokinetics Absorption After oral administration, losartan is well absorbed and undergoes primary metabolism in the liver (the "first pass" effect), which forms the active carboxylic acid metabolite and other inactive metabolites. The systemic bioavailability of losartan is approximately 33%. The average maximum concentrations of losartan and its active metabolite are reached after 1 hour and 3-4 hours after ingestion, respectively. Distribution Both losartan and its active metabolite are more than 99% bound to plasma proteins, predominantly to albumin. The volume of distribution of losartan is 34 liters. Biotransformation About 14% of an orally or intravenously administered dose of losartan is converted to the active metabolite. After oral or intravenous administration of radioactive carbon (14C) labeled potassium losartan, the radioactivity of circulating blood plasma is mainly due to losartan and its active metabolite. Losartan is minimally converted to the active metabolite in approximately 1% of the examined individuals. In addition to the active metabolite, inactive metabolites are also formed. Withdrawal Plasma clearance of losartan and its active metabolite is about 600 ml/min and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml/min and 26 ml/min, respectively. When losartan is taken orally, about 4% of the dose is excreted unchanged in the urine and about 6% of the dose is excreted in the urine as the active metabolite. Losartan and its active metabolite have linear pharmacokinetics when losartan potassium is taken orally at doses up to 200 mg. After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a terminal elimination half-life of approximately 2 hours and 6-9 hours, respectively. When taking the drug at a dose of 100 mg 1 time per day, there is no significant accumulation in the blood plasma of either losartan or its active metabolite. Excretion of losartan and its metabolites occurs with bile and urine. After oral/intravenous administration of losartan labeled with carbon 14C, about 35%/43% of the radioactive label is found in the urine and 58%/50% in the feces. Application in special groups of patients Significant differences in the concentration of losartan and its active metabolite in plasma in young and elderly patients suffering from arterial hypertension are not observed. In women with arterial hypertension, plasma concentrations of losartan were almost twice as high as in men with arterial hypertension, while plasma concentrations of the active metabolite in men and women did not differ significantly. After taking losartan orally in patients with mild to moderate alcoholic cirrhosis, the plasma concentration of losartan was 5 times higher, and the concentration of the active metabolite was 1.7 times higher compared with young male volunteers (see sections "Method of administration and dosage" and "Precautions for use"). The plasma concentration of losartan does not change in patients with creatinine clearance above 10 ml/minute. Compared with patients with normal renal function, in patients on hemodialysis, the AUC of losartan is approximately 2 times higher. The concentration of the active metabolite in plasma does not change in patients with impaired renal function, as well as in patients on hemodialysis. Neither losartan nor its active metabolite is removed from the body by hemodialysis. Pharmacokinetics in Pediatric Patients The pharmacokinetics of losartan was studied in 50 pediatric hypertensive patients aged > 1 month to < 16 years following a once-daily dose of approximately 0.54 to 0.77 mg/day. kg (medium doses). The results obtained showed that the formation of the active metabolite of losartan occurs in all age groups. According to the results obtained, the pharmacokinetic parameters of losartan after oral administration are approximately the same in infants, children under 3 years of age, preschool children, school-age children and adolescents. The pharmacokinetic parameters of the metabolite in age groups differed to a greater extent. When comparing preschool children and adolescents, this difference became statistically significant. The concentration in infants/children under 3 years of age was relatively high. Preclinical safety data According to the data of preclinical safety studies obtained in the course of standard studies that considered general pharmacology, genotoxicity and carcinogenic potential, the drug does not pose a particular danger to humans. In multiple dose toxicity studies, losartan caused a decrease in red blood cell parameters (erythrocytes, hemoglobin, hematocrit), an increase in plasma urea-N concentration, an occasional increase in serum creatinine, a decrease in heart weight (not correlated with histology), and changes in the gastrointestinal tract. -intestinal tract (mucosal lesions, ulcers, erosion, hemorrhages). Like other drugs that have a direct effect on the renin-angiotensin system, losartan has a negative effect on the development of the fetus, leads to the death or pathology of the fetus. Indications for use Treatment of primary arterial hypertension in adults, as well as in children and adolescents aged 6 to 18 years. Treatment of kidney disease in adult patients with arterial hypertension and type II diabetes mellitus in combination with proteinuria ?0.5 g / day, as part of antihypertensive therapy. Treatment of chronic heart failure in adult patients when treatment with angiotensin-converting enzyme (ACE) inhibitors is not possible due to drug intolerance, especially if cough occurs or there are contraindications. If the condition of a patient with heart failure has stabilized during treatment with ACE inhibitors, it should not be transferred to treatment with losartan. Patients should receive chronic heart failure treatment according to the established regimen, their condition should be stable, and the left ventricular ejection fraction in patients should be ≥40%. Reducing the risk of stroke in adult patients with arterial hypertension in combination with left ventricular hypertrophy, confirmed by ECG data (see Pharmacodynamics, LIFE Study, Race). Contraindications Hypersensitivity to the active substance or any of the excipients listed in the "Composition" section. 2nd and 3rd trimesters of pregnancy (see sections "Precautions for use" and "Use during pregnancy and lactation"). Severe liver failure. The concomitant use of ATP receptor blockers with Aliskiren in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2 is contraindicated. Use during pregnancy and lactation Pregnancy Losartan is not recommended during the first trimester of pregnancy (see Use of losartan is contraindicated during the 2nd and 3rd trimesters of pregnancy (see Sections "Contraindications" and "Precautions for use") Convincing epidemiological evidence of the risk of teratogenicity when using ACE inhibitors no pregnancy during the first trimester, but a slight increase cannot be ruled out.Until there are data from controlled epidemiological studies regarding the risk of using angiotensin II receptor antagonists (Angiotensin II Receptor Inhibitors-AIIRAs), it should be considered that for this class of drugs such risks may exist. ovate. In cases where treatment with angiotensin II receptor antagonists is not mandatory, patients planning pregnancy should be switched to alternative antihypertensive drugs that have proven safety data for use during pregnancy. If pregnancy is confirmed, treatment with losartan should be stopped immediately and, if necessary, switched to alternative treatment. It is known that therapy with angiotensin II receptor antagonists during the second and third trimesters of pregnancy has a toxic effect on the embryo (decreased kidney function, polyhydramnios, slowing the formation of bone tissue of the skull) and on the body of a newborn child (renal failure, arterial hypotension, hyperkalemia) (see also . section "Preclinical safety data"). If losartan therapy was started from the second trimester of pregnancy, an ultrasound examination of renal function and the structure of the skull of the newborn is recommended. For newborns whose mothers took losartan, medical supervision should be established in order to timely detect and correct arterial hypotension (see also sections "Contraindications" and "Precautions for use"). Breastfeeding Since there is no information on the use of losartan during breastfeeding, treatment with losartan is not recommended, the patient should be switched to alternative drugs that have confirmed data on the safety of use during breastfeeding, especially if the patient is breastfeeding a newborn or a child born prematurely. Use in children Data on the efficacy and safety of the use of losartan for the treatment of arterial hypertension in children and adolescents aged 6-18 years are limited (see the section "Pharmacodynamics"), Limited pharmacokinetic data are available for children with arterial hypertension over the age of one month ( see section "Pharmacokinetics"). For patients who can swallow tablets and whose body weight is > 20 to < 50 kg, the recommended dose is 25 mg once daily. (In exceptional cases, this dose may be increased to a maximum of 50 mg once daily). The dosage should be adjusted depending on the blood pressure indicators. For patients whose body weight is > 50 kg, the usual dose is 50 mg once daily. In exceptional cases, this dose may be increased to a maximum of 100 mg once daily. Doses greater than 1.4 mg/kg (or greater than 100 mg) per day have not been studied in children. It is not recommended to use losartan for the treatment of children under the age of 6 years, since data on the experience of use in this age group is limited. It is not recommended to use the drug for the treatment of children with a glomerular filtration rate < 30 ml / min / 1.73 m2, since there are no data on the experience of use in this group of patients (see section "Precautions for use"). Losartan is not recommended for the treatment of children with impaired liver function (see section "Precautions for use"). Influence on the ability to drive vehicles and work with mechanisms Studies on the effect of the drug on the ability to drive a car and work with mechanisms have not been conducted. However, when driving a vehicle or working with mechanisms, it must be taken into account that when taking antihypertensive drugs, a sudden onset of dizziness or drowsiness may occur, especially at the beginning of treatment or when the dose is increased. Method of administration and doses Film-coated tablets are indivisible and cannot be used at a lower dosage. If it is necessary to use losartan in doses less than 50 mg, it is recommended to consider the possibility of using drugs containing losartan from other manufacturers in the appropriate dosage. Dosage Hypertension As a rule, the initial and maintenance dose for most patients is 50 mg once a day. The maximum antihypertensive effect is achieved 3-6 weeks after the start of treatment. In some patients, a better effect can be achieved by increasing the dose to 100 mg once a day (in the morning). Losartan can be used in combination with other antihypertensive drugs, especially diuretics (eg, hydrochlorothiazide). Arterial hypertension in patients with type II diabetes mellitus in combination with proteinuria ? 0.5 g / day As a rule, the initial dose is 50 mg once a day. This dose may be increased to 100 mg per day, depending on blood pressure readings, approximately one month after the start of treatment. Losartan can be used with other antihypertensive agents (eg, diuretics, calcium channel blockers, alpha- or beta-blockers, and centrally acting drugs), as well as with insulin and other commonly used hypoglycemic agents (eg, sulfonylurea drugs, glitazones, and glucosidase inhibitors). Heart failure The usual starting dose of losartan for the treatment of patients with heart failure is 12.5 mg once daily. As a rule, the dose is increased at weekly intervals (for example, 12.5 mg per day, 25 mg per day, 50 mg per day, 100 mg per day and up to a maximum dose of 150 mg once a day), taking into account individual tolerability of the drug. Reducing the risk of stroke in patients with arterial hypertension and left ventricular hypertrophy, confirmed by ECG data. The usual initial dose is 50 mg of losartan once a day. The treatment should then be supplemented with a low dose of hydrochlorothiazide and/or the dose of losartan should be increased to 100 mg once daily, depending on the blood pressure. Special patient groups Use in the treatment of patients with reduced circulating blood volume (CBV) For patients with reduced circulating blood volume (eg, treated with high doses of diuretics), a dose of 25 mg once daily should be considered as an initial dose (see section "Precautions for use"). Application for the treatment of patients with impaired renal function and patients on hemodialysis For patients with impaired renal function and patients on hemodialysis, no initial dose adjustment is required. Application for the treatment of patients with impaired liver function Patients with a history of impaired liver function should be prescribed lower doses of the drug. There is no experience of using the drug for the treatment of patients with severe hepatic impairment, therefore, losartan is contraindicated in patients with severe hepatic impairment (see sections "Contraindications" and "Precautions for use"). Use in Elderly Patients: Although an initial dose of 25 mg should be considered for the treatment of patients over 75 years of age, no dose adjustment is generally required in elderly patients. Method of administration Losartan tablets should be swallowed with a glass of water. The drug can be taken regardless of food intake. Side effects Losartan has been studied in the following clinical trials: Controlled clinical trial involving> 3000 adult patients aged 18 years and older with essential arterial hypertension. Controlled clinical study in 177 children and adolescents aged 6 to 16 years with hypertension. Controlled clinical study involving > 9000 patients aged 55 to 80 years with arterial hypertension in combination with left ventricular hypertrophy. Controlled clinical study in > 7700 adult patients with chronic heart failure. Controlled clinical study involving > 1500 patients aged 31 years and older with type II diabetes mellitus in combination with proteinuria. The most frequently observed adverse reaction in these studies was dizziness. The adverse reactions listed in the table below, identified in clinical and post-marketing studies, are classified by frequency in accordance with generally accepted evaluation criteria: very often (? 1/10); often (?1/100 and <1/10); infrequently (?1/1000 and <1/100); rarely (?1/10000 and <1/1000); very rare (< 1/10000), not known (cannot be estimated from the available data). Undesirable adverse reaction Frequency of adverse reactions when prescribed according to indications Other Arterial hypertension Patients with arterial hypertension in combination with left ventricular hypertrophy Chronic heart failure Arterial hypertension and type II diabetes mellitus in combination with kidney disease Post-marketing studies Nervous system disorders dizziness, vertigo often Often often often drowsiness, sleep disturbances infrequently headache infrequently paresthesia rarely migraine unknown Cardiac disorders palpitations, angina pectoris infrequently syncope, atrial fibrillation, stroke rarely syncope, palpitations unknown Vascular disorders symptomatic arterial hypotension, orthostatic hypotension infrequently often arterial hypotension often orthostatic hypotension unknown Gastrointestinal disorders abdominal pain, constipation uncommon nausea, vomiting uncommon pancreatitis unknown diarrhea infrequently unknown unknown Blood and lymphatic system disorders anemia often unknown unknown thrombocytopenia unknown Hearing organ and vertigo labyrinth disorders Often tinnitus unknown Systemic disorders and injection site complications edema infrequently asthenia, fatigue infrequently Often infrequently often malaise unknown influenza-like symptoms unknown Immune system disorders hypersensitivity: anaphylactic reactions, angioedema, including laryngeal and pharyngeal edema causing airway obstruction and/or swelling of the face, lips, pharynx and/or tongue; some of these patients have previously experienced angioedema while taking other drugs, including ACE inhibitors; Vasculitis, including Henoch-Schonlein purpura Rare Laboratory findings Hypokalemia Common Common* Increased alanine aminotransferase (ALT) (usually reversible after treatment is stopped) Rarely Increased blood urea, creatinine, and serum potassium often Hypoglycemia Often hyponatremia Unknown respiratory, thoracic, and mediastinal dyspnea infrequently cough infrequently unknown Skin disorders