Tritace tablets 5mg №14×2

Name:
Tritace tab 5mg in a blister pack No. 14×2
Description:
Tritace® 2.5 is a yellow oblong tablet with a score line on both sides and engraving 2.5/stylized image of the letter h and HMR/2.5 on the other side. Tritace® 5 is a pink oblong tablet with a score line on both sides and engraved 5/stylized letter h and HMP/5 on the other side. Tritace® 10 are white oblong tablets with a score line, engraved on one side with HMO/HMO. The main active ingredient is ramipril. Release form Tablets Dosage 5 mg PharmacodynamicsPharmacodynamics Mechanism of action Ramiprilat, the active metabolite of ramipril, is a long-acting angiotensin-converting enzyme (ACE) inhibitor. In plasma and tissues, ACE catalyzes the conversion of angiotensin I to angiotensin II (an active vasoconstrictor) and the breakdown of the active vasodilator bradykinin. A decrease in the formation of angiotensin II and an increase in bradykinin activity leads to vasodilation and contributes to the cardioprotective and endothelioprotective effects of ramipril. Angiotensin II stimulates the release of aldosterone, in connection with this, ramipril causes a decrease in aldosterone secretion. The overall response to ACE inhibitor monotherapy is lower in black hypertensive patients (low renin population) than in white patients. Pharmacodynamic action Hypotensive action Taking ramipril causes a pronounced decrease in peripheral arterial resistance. Changes in renal blood flow and glomerular filtration rate are usually not observed. Reception of ramipril causes in hypertensive patients a decrease in blood pressure in the supine and standing position without a compensatory increase in heart rate. In most patients, a noticeable hypotensive effect occurs 1-2 hours after ingestion of a single dose. The maximum effect of a single dose is achieved 3-6 hours after ingestion. The hypotensive effect of a single dose usually lasts for 24 hours. The maximum hypotensive effect with continuous treatment with ramipril usually occurs after 3-4 weeks. It has been shown that the hypotensive effect of long-term therapy persists for 2 years. Abrupt discontinuation of ramipril does not cause a rapid and excessive rebound increase in blood pressure. Heart failure As with conventional therapy with diuretics and optional cardiac glycosides, ramipril has been shown to be effective in patients with NYHA functional class II-IV heart failure. The drug has favorable effects on hemodynamics (reduces the filling pressure of the left and right ventricles, reduces the total peripheral vascular resistance, increases cardiac output and cardiac index), and also reduces neuroendocrine activation. Clinical efficacy and safety Prevention of cardiovascular complications In a placebo-controlled clinical trial (HOPE), ramipril was prescribed as a prophylactic agent in addition to standard therapy in 9200 patients with increased cardiovascular risk due to vascular disorders (for example, worsening of CAD, obliterating diseases of peripheral arteries or history of stroke) or diabetes mellitus with at least 1 additional risk factor (microalbuminuria, hypertension, elevated total blood cholesterol, decreased HDL, smoking). In this study, ramipril was shown to significantly reduce the incidence of myocardial infarction, stroke, and death due to cardiovascular disease. HOPE study: main results Ramipril Placebo Relative risk (95% CI) p % % Total patients n = 4645 N = 4652 Primary combined expected clinical outcomes 14.0 17.8 0.78 (0.70-0.86 ) < 0.001 Myocardial infarction 9.9 12.3 0.80 (0.70-0.90) < 0.001 Death from cardiovascular disease 6.1 8.1 0.74 (0.64-0.87) < 0.001 Stroke 3.4 4.9 0.68 (0.56-0.84) < 0.001 Secondary expected clinical outcomes Death from any cause 10.4 12.2 0.84 (0.75-0.95) 0.005 Need in revascularization 16.0 18.3 0.85 (0.77-0.94) 0.002 Hospitalization due to unstable angina 12.1 12.3 0.98 (0.87-1.10) Not specified Hospitalization due to cardiac insufficiency 3.2 3.5 0.88 (0.70-1.10) 0.25 Complications associated with diabetes 6.4 7.6 0.84 (0.72-0.98) 0.03 Secondary prevention after acute myocardial infarction More than 2000 patients with transient/permanent clinical signs of heart failure were included in the AIRE study and after myocardial infarction. Treatment with ramipril was started 3-10 days after acute myocardial infarction. The study showed that during a follow-up period of a mean of 15 months, mortality among patients treated with ramipril was 16.9%, and in the group of patients treated with placebo - 22.6% (relative risk reduction - 27% (95% CI 11-40%) Nephroprotective properties The MICRO-HOPE study examined the effect of ramipril 10 mg in addition to the current treatment regimen compared with placebo in 3577 normo- or hypertensive patients aged 55 years and older (no upper age limit), most of whom had type 2 diabetes (with at least one additional risk factor for cardiovascular disease).The primary analysis showed that severe nephropathy developed in 117 (6.5%) patients in the ramipril group and in 149 (8.4%) patients in the ramipril group placebo, corresponding to a relative risk reduction of 24%, 95% CI 3–40, p = 0.027 Multicenter, randomized, placebo-controlled, double-blind, parallel study group (REIN study) was aimed at evaluating the effect of ramipril treatment on the incidence of reduced glomerular filtration rate (GFR), the study included 352 normo- or hypertensive patients (aged 18 to 70 years) suffering from moderate (moderate protein excretion) urine > 1 and < 3 g/24 h) or severe proteinuria (? 3 g/24 h) caused by chronic non-diabetic nephropathy (these two subgroups were stratified at baseline). The main analysis of patients with the most severe proteinuria (the study for this subgroup was terminated prematurely due to benefit in the ramipril group) showed that the mean decrease in GFR per month was lower in the ramipril group than in the placebo group: 0.54 (0.66) compared c 0.88 (1.03) ml/min/month, p = 0.038. Thus, the difference between the groups was 0.34 0.03 - 0.65 ml/min/month and about 4 ml/min/year. A secondary composite endpoint of doubling baseline serum creatinine and/or end-stage renal disease (ESRD) (need for hemodialysis or renal transplantation) was seen in 23.1% of patients in the ramipril group compared to placebo amounted to 45.5% (p = 0.02). Pharmacokinetics Absorption After oral administration, it is rapidly absorbed in the gastrointestinal tract: the maximum content of ramipril in the blood plasma is reached within an hour and is at least 56% of the dose taken, practically does not depend on the simultaneous intake of food. The bioavailability of the active metabolite of ramiprilat after oral administration of 2.5 mg and 5 mg of ramipril is 45%. After oral administration, the maximum plasma concentration of ramiprilat is reached after 2 to 4 hours. A constant plasma concentration of ramiprilat after daily administration of usual doses of ramipril is reached approximately on the fourth day of treatment. Distribution Protein binding is about 73% for ramipril and about 56% for ramiprilat. Metabolism Ramipril is almost completely converted to ramiprilat, diketopiperazine ester, diketopiperazine acid, and ramipril and ramiprilat glucuronides. Excretion Excretion of metabolites is carried out mainly by the kidneys. Removal of ramiprilat is carried out in several phases. Due to the activity of ramiprilat, saturable binding to ACE and weak dissociation with this enzyme, the final phase of ramiprilat excretion is long at very low plasma concentrations. With multiple doses of ramipril once a day, the "effective" half-life, important in terms of dosing, was 13-17 hours for dosages of 5-10 mg/ml and longer for lower dosages of 1.25-2.5 mg/ml . This difference is due to the strong binding of ramiprilat to ACE. In breast milk after a single dose of the drug ramipril and its metabolites are not detected by quantitative methods. However, with multiple doses, the effect is unknown. Patients with impaired renal function (see Dosage and Administration) In case of impaired renal function, the excretion of ramiprilat by the kidneys is reduced, the renal clearance of ramiprilat decreases in proportion to creatinine clearance. This leads to an increase in the plasma concentration of ramiprilat, which decreases more slowly than in patients with intact kidneys. Patients with impaired liver function (see Dosage and Administration) A decrease in hepatic function leads to a slow metabolism of ramipril to ramiprilat and a slow elimination of ramiprilat, plasma levels of ramipril are increased in such patients. However, the maximum level of ramiprilat in patients with reduced liver function does not differ from the maximum level observed in patients with normal liver function. Results of preclinical safety studies In rodents and dogs, no acute toxicity has been identified with oral administration of ramipril. Chronic oral studies have been conducted in rats, dogs and monkeys. All three species showed signs of a shift in the concentrations of plasma electrolytes and changes in the hemogram. In dogs and monkeys at daily doses of 250 mg/kg/day. a pronounced increase in the juxtaglomerular apparatus was revealed, which was a consequence of the pharmacodynamic action of ramipril. Rats, dogs and monkeys tolerated daily doses of 2, 2.5 and 8 mg/kg/day without adverse effects. respectively. Reproductive toxicity studies in mice, rabbits and monkeys have not shown teratogenic properties. There was no decrease in fertility in male and female rats. The introduction of ramipril to female rats during fetal development and lactation caused irreversible kidney damage (dilatation of the renal pelvis) in offspring at daily doses of 50 mg/kg of body weight and above. Extensive mutagenic studies using several test systems have not revealed evidence that ramipril has mutagenic or genotoxic properties. Indications for use Treatment of arterial hypertension: to lower blood pressure both in monotherapy and in combination with other antihypertensive drugs. Prevention of potentially lethal cardiovascular complications (see also Dosage and Administration): reduction in the number of cardiovascular complications (myocardial infarction, stroke and death) in patients with: manifestations of atherothrombotic cardiovascular diseases (presence of coronary heart disease or stroke in anamnesis) obliterating diseases of the arteries of the lower extremities) or diabetes mellitus and with at least one cardiovascular risk factor (see Pharmacological properties). Secondary prevention in patients with acute myocardial infarction: reduction in the risk of death, starting from the acute stage of myocardial infarction, in patients with clinical signs of heart failure when administered 48 hours after the onset of the disease. Treatment of glomerular kidney disease: the initial stage of diabetic nephropathy, manifested by the presence of microalbuminuria; severe diabetic nephropathy with the presence of macroproteinuria in patients with at least one risk factor for cardiovascular disease (see Pharmacological properties); severe non-diabetic nephropathy with macroproteinuria? 3 g/day (see Pharmacological properties). Treatment of symptomatic heart failure. Dosage and administration Inside. It is recommended to take Tritace every day at the same time of the day. Tritace is taken with plenty of liquid and with or without food. Eating does not significantly affect the absorption of the active component of ramipril (see Pharmacokinetics). Tablets should be swallowed whole (not chewed). Adults Patients treated with diuretics The initiation of Tritace may be associated with hypotension; this is more common in patients treated with diuretics. The lack of salts and fluids in the body is subject to preliminary correction before starting treatment with Tritace, diuretics should be previously limited or canceled, no later than 2-3 days (see Special instructions and precautions for use). Treatment of patients who have not canceled the intake of diuretics should begin with the smallest single dose of 1.25 mg of ramipril. It is necessary to monitor kidney function and the content of potassium in the blood serum. The subsequent dosage of Tritace should be adjusted according to the target blood pressure level. Treatment of arterial hypertension The dosage is calculated depending on the expected therapeutic effect and the tolerance of the drug to patients in each case (see Special instructions and precautions for use). Tritace can be used alone or in combination with other classes of antihypertensive drugs. Initial Dose Treatment with Tritace should be initiated gradually at the recommended initial dose of 2.5 mg per day. In patients with a highly activated renin-angiotensin-aldesterone system, a significant decrease in blood pressure may follow the initial dose. For such patients, the recommended initial dose is 1.25 mg, and the start of treatment should be carried out under medical supervision (see Special Instructions and Precautions for Use). Individual maintenance dose titration The dose may be doubled at 2 to 4 week intervals to achieve the target blood pressure level. The maximum daily dose is 10 mg. The daily dose is taken once a day. Prevention of Potentially Fatal Cardiovascular Complications Starting Dose The recommended starting dose is 2.5 mg Tritace once daily. Titration of an individual maintenance dose The dose is gradually increased depending on the patient's tolerance of the active substance. It is recommended to double the dose after 1-2 weeks of treatment, and after the next 2-3 weeks, increase the maintenance dose to 10 mg Tritace daily. See also dosing in patients previously treated with diuretics. Secondary prophylaxis in patients with acute myocardial infarction with clinical signs of heart failure Initial dose After 48 hours following myocardial infarction in clinically and hemodynamically stable patients, the recommended initial dose is 2.5 mg twice a day for three days. If the initial dose of 2.5 mg is not tolerated by the patient, 1.25 mg twice daily for 2 days should be given before increasing the dose to 2.5 mg and 5 mg twice daily. If the dose cannot be increased to 2.5 mg twice daily, treatment should be discontinued. See also dosing in patients previously treated with diuretics. Titration and individual maintenance dose The daily dose is sequentially increased by doubling it at intervals of 1-3 days until a maintenance dose of 5 mg twice a day is reached. The maintenance daily dose is recommended to be divided into 2 doses. The maximum daily dose is 10 mg. If it is decided to treat Tritace in a patient with severe (NYHA grade IV) chronic heart failure after myocardial infarction, it is recommended to start with a dose of 1.25 mg 1 time per day. The dose should be increased with extreme caution. Treatment of kidney disease In patients with diabetes and microalbuminuria Initial dose The recommended initial dose is Tritace 1.25 mg once daily. Titration of an individual maintenance dose The dose is sequentially increased depending on the patient's tolerance of the active substance. It is recommended to double the daily dose to 2.5 mg after 2 weeks of treatment, and then to 5 mg after the next 2 weeks. In patients with diabetes and at least one cardiovascular risk factor Starting dose The recommended starting dose is Tritace 2.5 mg once daily. Titration of an individual maintenance dose The dose is sequentially increased depending on the patient's tolerance of the active substance. It is recommended to double the daily dose to 5 mg after 2 weeks of treatment, and then to 10 mg after the next 2-3 weeks. The maximum daily dose is 10 mg. In patients with non-diabetic nephropathy with macroproteinuria? 3 g/day Starting Dose The recommended starting dose is 1.25 mg Tritace once daily. Titration of an individual maintenance dose The dose is sequentially increased depending on the patient's tolerance of the active substance. It is recommended to double the daily dose to 2.5 mg after 2 weeks of treatment, and then to 5 mg after the next 2 weeks. Treatment of Symptomatic Heart Failure Starting Dose For patients receiving diuretic therapy, the recommended starting dose is Tritace 1.25 mg once daily. Individual maintenance dose titration It is recommended that the dose of Tritace be doubled every two weeks up to a maximum daily dose of 10 mg. It is preferable to divide the daily dose into 2 doses. Special categories of patients Treatment of patients with impaired renal function The daily dose for patients with impaired renal function is prescribed taking into account creatinine clearance (see Pharmacokinetics): if creatinine clearance ? 60 ml / min, no need to adjust the initial dose (2.5 mg daily), the maximum daily dose is 10 mg; if creatinine clearance is in the range of 30 - 60 ml / min, there is no need to adjust the initial dose (2.5 mg daily), the maximum daily dose is 5 mg; if creatinine clearance is in the range of 10 - 30 ml / min, the initial dose is 1.25 mg daily, and the maximum daily dose is 5 mg; in patients with hypertension undergoing hemodialysis: ramipril is poorly dialyzed; the initial dose is 1.25 mg daily, and the maximum daily dose is 5 mg; the drug must be taken a few hours after hemodialysis. Patients with impaired liver function (see Pharmacokinetics) Treatment of such patients should be carried out with extreme caution and only under medical supervision. The maximum allowable daily dose in such cases is 2.5 mg Tritace. Elderly patients Initial doses should be lower and their administration should be more gradual due to the increased risk of adverse reactions, especially in elderly and debilitated patients. The recommended starting daily dose is 1.25 mg Tritace. Pediatric population Tritace is not recommended for use in children and adolescents under 18 years of age due to insufficient relevant data on the safety and efficacy of the drug. Use during pregnancy and lactation Tritace is not recommended during the first trimester of pregnancy (see Precautions and Precautions) and is contraindicated in the second and third trimesters of pregnancy (see Contraindications). There are no conclusive epidemiological data on the risk of teratogenicity due to the use of ACE inhibitors during the first trimester of pregnancy; however, a small risk cannot be ruled out. If the patient is planning pregnancy, treatment with ACE inhibitors should be discontinued and replaced with another treatment for hypertension with a safer pregnancy profile. Therapy with ACE inhibitors / ARA II in the second and third trimesters of pregnancy can cause fetotoxicity (decreased renal function, oligohydramnios, severe skull hypoplasia) and neonatal intoxication (renal failure, hypotension, hyperkalemia). Patients who have had cases of taking ACE inhibitors since the second trimester of pregnancy are advised to check the function of the kidneys and skull using ultrasound. Newborns whose mothers have taken ACE inhibitors should be evaluated for hypotension, oliguria, and hypokalemia (see Contraindications and Precautions for Use). Since it is not known for certain whether ramipril passes into human milk and causes undesirable effects in breastfed children, the use of Tritace during breastfeeding is contraindicated. It is recommended to choose an alternative treatment that has a better safety profile during breastfeeding. Precautions Dual blockade of the renin-angiotensin-aldosterone system Dual blockade of the renin-angiotensin-aldosterone system is associated with an increased risk of hypotension, hyperkalemia and impaired renal function (including acute renal failure) compared with monotherapy. Double blockade of the RAAS with the use of an ACE inhibitor, ARA II or aliskiren cannot be recommended for any patient, especially patients with diabetic nephropathy. pressure. This applies to the use of candesartan or valsartan as add-on therapy to ACE inhibitors in patients with chronic heart failure. Conducting a double blockade of the RAAS under the close supervision of a specialist and mandatory monitoring of kidney function, water and electrolyte balance and blood pressure is possible in patients with chronic heart failure with intolerance to aldosterone antagonists (spironolactone), who have persistent symptoms of chronic heart failure, despite other adequate therapy. The use of Tritace in combination with angiotensin II receptor antagonists is contraindicated in patients with diabetic nephropathy. Special Patients Pregnancy ACE inhibitors such as ramipril or angiotensin II receptor antagonists (ARAII) should not be used during pregnancy. If the patient is planning a pregnancy, before continuing therapy with ACE/ARA II inhibitors, it is necessary to select another treatment for hypertension with a more reliable safety profile for pregnancy. If pregnancy is detected during treatment with ACE/ARA II inhibitors, you should immediately stop taking the medication and start therapy with other classes of drugs (see Contraindications and Adverse Reactions). Patients at risk of hypotension - Patients with increased activity of the renin-angiotensin-aldosterone system Patients with increased activity of the renin-angiotensin-aldosterone system are at risk of a sharp drop in blood pressure and deterioration of renal function during ACE inhibition, especially at the beginning of treatment or when the dose of inhibitors is first increased ACE inhibitors or co-administered diuretics. Possible manifestations of increased activity of the renin-angiotensin-aldosterone system must be taken into account, carrying out constant medical supervision, including monitoring of blood pressure, in cases, for example: patients with severe hypertension; patients with decompensated congestive heart failure; patients with clinically significant hemodynamic disorders (inflow or outflow) in the left ventricle (for example, aortic stenosis, mitral stenosis); patients with unilateral renal artery stenosis with a second functional kidney; patients with a deficiency of electrolytes and (or) fluid (including patients previously treated with diuretics); patients with liver cirrhosis and/or ascites; patients undergoing major surgery or during anesthesia with hypotensive agents. Correction of dehydration, hypovolemia, or electrolyte deficiency is recommended prior to initiation of treatment (in patients with heart failure, such corrective actions should be assessed against the risk of overvolume). Transient or permanent heart failure after myocardial infarction. Patients at risk of cardiac or cerebral ischemia due to acute hypotension. The initial stages of treatment require special medical supervision. Elderly patients See Dosage and Administration. Surgery It is recommended to stop treatment with ACE inhibitors (including ramipril) if possible the day before surgery. Monitoring of renal function Renal function should be monitored prior to the administration of Tritace. Monitoring of renal function is recommended, in particular, in the first weeks of treatment, especially in patients with renal insufficiency (see Dosage and Administration). Possible risk of impaired renal function, especially in patients with congestive heart failure or after kidney transplantation. Angioedema Cases of angioedema have been reported in patients treated with ACE inhibitors, including ramipril (see Adverse Reactions). The risk of angioedema may be increased in patients taking concomitant medications such as vildagliptin or mTOR inhibitors (target of rapamycin in cells) eg temsirolimus, everolimus, sirolimus. If angioedema occurs during treatment, Tritace should be discontinued immediately. Emergency treatment must be started immediately. The patient should be observed for at least 12-24 hours and discharged only after the disappearance of all symptoms. A case of angioedema of the intestine has been reported in patients treated with ACE inhibitors, including Tritace (see Adverse Reactions). Patients had abdominal pain (sometimes accompanied by nausea and vomiting). Anaphylactic reactions during sensitization The likelihood and severity of anaphylactic and anaphylactoid reactions to insect venom increases with the use of ACE inhibitors. It is assumed that a similar effect may also occur when interacting with other allergens. Temporary discontinuation of Tritace should be considered prior to the onset of sensitization. Hyperkalemia Hyperkalemia has been observed in some patients treated with ACE inhibitors, including Tritace. Patients at risk of developing hyperkalemia include patients with renal insufficiency; aged > 70 years; with uncontrolled diabetes; using potassium salts, potassium-sparing diuretics or other substances that increase the content of potassium in the plasma; as well as conditions such as dehydration, acute cardiac decompensation, metabolic acidosis. During simultaneous treatment with these drugs, strict monitoring of serum potassium concentration is necessary (see Interaction with other medicinal products and other forms of interaction). Hyponatremia In some patients treated with ramipril, a syndrome of inappropriate ADH secretion was observed with the subsequent development of hyponatremia. It is recommended to regularly monitor serum sodium levels in the elderly and in other patients who are at risk of developing hyponatremia. Neutropenia/agranulocytosis Neutropenia/agranulocytosis, as well as thrombocytopenia and anemia, are rare, and bone marrow depression has also been reported. It is recommended to monitor the number of leukocytes to prevent possible leukopenia. More detailed monitoring is recommended at the initial stages of treatment and in patients with impaired renal function, with concomitant collagenosis (lupus erythematosus or scleroderma), treated with other drugs that may affect the blood picture (see Interaction with other medicinal products and other forms of interaction and adverse reactions). Ethnic differences The risk of angioedema when taking ACE inhibitors is more likely in black patients than in white patients. The overall response to ACE inhibitor monotherapy is lower in black (Afro-Caribbean) patients with hypertension (low renin population) than in white patients. Cough Cough has been reported during treatment with ACE inhibitors. The cough is unproductive, persistent and disappears after discontinuation of therapy. When making a differential diagnosis of cough in a patient, the possibility of its association with the use of ACE inhibitors should be taken into account. Pregnancy and lactation Tritace is not recommended during the first trimester of pregnancy (see Warnings and Precautions) and is contraindicated in the second and third trimesters of pregnancy (see Contraindications). There are no conclusive epidemiological data on the risk of teratogenicity due to the use of ACE inhibitors during the first trimester of pregnancy; however, a small risk cannot be ruled out. If the patient is planning pregnancy, treatment with ACE inhibitors should be discontinued and replaced with another treatment for hypertension with a safer pregnancy profile. Therapy with ACE inhibitors / ARA II in the second and third trimesters of pregnancy can cause fetotoxicity (decreased renal function, oligohydramnios, severe skull hypoplasia) and neonatal intoxication (renal failure, hypotension, hyperkalemia). Patients who have had cases of taking ACE inhibitors since the second trimester of pregnancy are advised to check the function of the kidneys and skull using ultrasound. Newborns whose mothers have taken ACE inhibitors should be evaluated for hypotension, oliguria, and hypokalemia (see Contraindications and Precautions for Use). Since it is not known for certain whether ramipril passes into human milk and causes undesirable effects in breastfed children, the use of Tritace during breastfeeding is contraindicated. It is recommended to choose an alternative treatment that has a better safety profile during breastfeeding. Influence on the ability to drive vehicles or other mechanisms Some adverse reactions (such symptoms of lowering blood pressure as heaviness, dizziness) can reduce the reaction and concentration of the patient, which may affect his ability to drive a car and mechanisms. This is most likely at the start of treatment, during dose increases, drug changes, and interactions with alcohol. It is not recommended to drive a car or operate machinery within a few hours after taking the first dose or increasing the dose. Adverse reactions In case of symptoms similar to those described below, please contact your doctor immediately! During therapy with ramipril, side effects such as persistent dry cough and hypotensive reactions may occur. Serious adverse reactions include angioedema, hyperkalemia, deterioration of kidney and liver function, pancreatitis, some skin reactions, and neutropenia/agranulocytosis. The frequency of occurrence of adverse reactions is determined as follows: very frequent (> 1/10), frequent (> 1/100, < 1/10), infrequent (> 1/1000, < 1/100), rare (> 1/10000, < 1/1000), very rare (< 1/10000) and unknown (cannot be estimated from the available data). Within each group of defined frequency criteria, adverse reactions are presented in descending order of their severity. Blood and lymphatic system disorders Uncommon: eosinophilia. Rarely: a decrease in the number of leukocytes (including neutropenia and agranulocytosis), a decrease in the number of red blood cells, a decrease in hemoglobin, a decrease in the number of platelets. Frequency unknown: bone marrow depression, pancytopenia, hemolytic anemia. Immune system disorders Frequency unknown: anaphylactic or anaphylactoid reactions (some anaphylactic and anaphylactoid reactions from insect venom are aggravated by ACE inhibitors), increased levels of antinuclear antibodies. Disorders of the endocrine system Frequency unknown: syndrome of inadequate production of antidiuretic hormone. Metabolic and nutritional disorders Common: increased potassium content. Uncommon: anorexia (loss of appetite), loss of appetite. Frequency unknown: Decreased sodium levels. Mental disorders Uncommon: depressed mood, anxiety, nervousness, agitation, sleep disturbance, including drowsiness (hypersomnia). Rare: confusion. Frequency unknown: Attention disorder. Nervous system disorders Common: headache, dizziness. Uncommon: vestibular vertigo, paresthesia, ageusia (loss of taste), dysgeusia (taste disturbance). Rare: tremor, imbalance. Frequency unknown: cerebral ischemia, including ischemic stroke and transient ischemic cerebrovascular accident, impaired psychomotor functions (impaired reaction), burning sensation, impaired sense of smell. On the part of the organ of vision Infrequently: visual disturbances, including blurred vision. Rare: conjunctivitis. Hearing disorders and labyrinth disorders Rare: hearing impairment, tinnitus. Cardiac disorders Uncommon: myocardial ischemia, including angina pectoris or myocardial infarction, tachycardia, arrhythmia, palpitations, peripheral edema. Vascular disorders Common: hypotension, decreased orthostatic blood pressure, syncope. Uncommon: hyperemia. Rare: vascular stenosis, insufficient perfusion, vasculitis. Respiratory, thoracic and mediastinal disorders Common: dry, nonproductive cough, bronchitis, sinusitis, dyspnea. Infrequently: bronchospasm, including exacerbation of asthma, runny nose. Gastrointestinal disorders Common: inflammatory reactions of the gastrointestinal tract, indigestion, gastrointestinal discomfort, dyspepsia, diarrhea, nausea, vomiting. Infrequently: pancreatitis (rare cases of death have been described when taking ACE inhibitors), increased pancreatic enzymes, angioedema of the small intestine, pain in the gastrointestinal tract, including gastritis, intestinal obstruction, dry mouth. Rare: glossitis. Frequency unknown: aphthous stomatitis (inflammatory reactions of the oral cavity). Liver and biliary tract disorders Uncommon: increased levels of liver enzymes and/or bilirubin. Rare: cholestatic jaundice, hepatocellular disorder. Frequency unknown: liver dysfunction, cholestatic or cytolytic hepatitis (there was a single case of fatal outcome). Skin and subcutaneous tissue disorders Common: Rash, including maculopapular rash. Infrequently: angioedema (possibly in rare cases, fatal upper respiratory tract obstruction), pruritus, hyperhidrosis (excessive sweating). Rare: exfoliative dermatitis, urticaria, onycholysis. Very rare: photosensitive reactions. Frequency unknown: toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, pemphigus, worsenin