Lisinopril-LF tablets 10mg №15×2

Name:
Lisinopril-lf. Forms of release Tablets. INN Lisinopril.
Description:
Tablets of white or almost white color, ploskotsilindrichesky form, with a facet (dosages of 5 mg and 10 mg). Tablets of white or almost white color, ploskotsilindrichesky form, with a facet and risk (a dosage of 20 mg). Composition Each tablet contains: active substance: lisinopril dihydrate – 5 mg, 10 mg or 20 mg; excipients: mannitol, corn starch, talc, magnesium stearate, calcium hydrogen phosphate dihydrate. Pharmacotherapeutic group Means that affect the renin-angiotensin system. ACE inhibitors. ATX Code C09AA03. Pharmacological properties Pharmacodynamics Lisinopril is a peptidyl dipeptidase inhibitor. Lisinopril inhibits the angiotensin-converting enzyme (ACE), which catalyses the conversion of angiotensin I to the vasoconstrictor peptide, angiotensin II. Also, angiotensin II stimulates the secretion of aldosterone in the adrenal cortex. Inhibition of ACE leads to a decrease in the concentration of angiotensin II in the blood plasma, which leads to a decrease in the activity of vasopressors and secretion of aldosterone, and can also lead to an increase in the concentration of potassium in the blood serum. Since the mechanism of action in hypertension is through inhibition of the renin-angiotensin-aldosterone system, lisinopril has a hypotensive effect even in hypertensive patients with low renin levels. ACE is identical to kininase II, an enzyme that breaks down bradykinin, which leads to an increase in the concentration of bradykinin while taking lisinopril. The role of elevated levels of bradykinin (which has pronounced vasodilating properties) during treatment with lisinopril has not been fully elucidated and requires further study. Pharmacokinetics Absorption Following oral administration of lisinopril, peak serum concentrations are reached after approximately 7 hours. Judging by the amount excreted in the urine, the average degree of absorption of lisinopril is approximately 25% at a dose of 5-80 mg. The variability of indicators between patients can be from 6 to 60%. The absolute bioavailability of lisinopril is reduced to approximately 16% in patients with NYHA class II-IV heart failure. Eating does not affect the absorption of lisinopril. Distribution In addition to binding to ACE, lisinopril does not bind to other serum proteins. Studies in rats show that lisinopril crosses the blood-brain barrier to a small extent. Excretion Lisinopril is not metabolized and is excreted exclusively through the kidneys unchanged. With multiple dosing, the effective half-life is 12.6 hours. The clearance of lisinopril is approximately 50 ml/min in healthy subjects. After the removal of a significant amount of free active substance, a slower removal of the fraction associated with ACE follows. Impaired liver function In patients suffering from cirrhosis of the liver, the absorption of lisinopril is slowed down by approximately 30% depending on the violation of liver function (as determined by urinary excretion). On the other hand, its excretion decreases and leads to an increase in the effectiveness of lisinopril by 50%. Impaired renal function Impaired renal function reduces the excretion of lisinopril, which is excreted through the kidneys. This decrease is of clinical significance only if the glomerular filtration rate is less than 30 ml/min. If the creatinine clearance is 30-80 ml/min, the mean area under the curve increases by only 13%. If the creatinine clearance is between 5 and 30 ml/min, despite this, the mean area under the curve increases by 4.5 times compared to the norm. Lisinopril can be removed with dialysis. Within 4 hours of hemodialysis, the plasma concentration of lisinopril decreases to a level of 60% with a dialysis clearance of 40 to 55 ml/min. Heart failure In the presence of heart failure, the exposure to lisinopril is increased compared to healthy patients (AUC increased by approximately 25%). On the other hand, the absolute bioavailability of lisinopril is reduced to approximately 16% in patients with heart failure. Pediatric population The pharmacokinetic profile of lisinopril was studied in 29 pediatric hypertensive patients aged 6 to 16 years with a glomerular filtration rate of less than 30 ml/min/1.73 m2. When taking a dose of 0.1 to 0.2 mg/kg, the steady-state plasma concentration of lisinopril achieved within 6 hours, as well as the degree of absorption, based on excretion in the urine, was approximately 28%. The values differed from the values obtained in adult patients. The values of AUC and Cmax in children in this study are the same as those obtained in adults. Elderly Patients Elderly patients tend to have higher levels of lisinopril due to impaired renal function; AUC is approximately 60% higher than in younger patients. Indications for use Arterial hypertension: treatment of adults and children as monotherapy or in combination with other antihypertensive drugs. Heart failure: Treatment of symptomatic heart failure in adults. Acute myocardial infarction: short-term (within 6 weeks) treatment of hemodynamically stable adult patients initiated within 24 hours of acute myocardial infarction. Diabetic nephropathy: treatment of kidney disease in adult patients with arterial hypertension and type 2 diabetes mellitus with initial nephropathy. Dosage and administration The drug should be taken once a day in the morning, preferably at the same time, with plenty of water. Lisinopril-LF can be taken with or without food. The dose and course of treatment is determined by the doctor individually, depending on the severity of the disease, the state of kidney function and concomitant therapy. If it is necessary to use a dose of 2.5 mg, lisinopril-containing drugs should be prescribed in the appropriate dosage and dosage form. The notch on the 20 mg tablets is intended solely to facilitate taking one tablet (by breaking the tablet into two halves), and not to divide the tablet into two doses. Arterial hypertension Lisinopril can be used as monotherapy or in combination with other antihypertensive drugs. starting dose. The recommended starting dose is 10 mg per day. Patients with increased activity of the renin-angiotensin-aldosterone system (in particular with renovascular hypertension, increased excretion of electrolytes from the body and / or dehydration, cardiac decompensation or severe arterial hypertension) may experience an excessive decrease in blood pressure after taking the initial dose. Therefore, at the beginning of treatment, such patients should be under medical supervision, the initial recommended dose is 2.5-5 mg. maintenance dose. The usual effective maintenance dose is 20 mg once daily. If the desired therapeutic effect is not achieved when using the prescribed dose for 2-4 weeks, the dose can be increased in the future. The maximum daily dose should not exceed 80 mg. Patients taking diuretics. In patients receiving diuretic therapy, after taking the first dose of the drug, symptomatic arterial hypotension may occur. Treatment with diuretics should be discontinued 2-3 days before the start of the use of Lisinopril-LF. If it is impossible to cancel diuretics, the initial dose of Lisinopril-LF should be no more than 5 mg per day. Kidney function and serum potassium levels should be monitored. Further dosing regimen must be set in accordance with blood pressure indicators. If necessary, diuretic treatment can be resumed. Patients with renal insufficiency For patients with renal insufficiency, the initial dose is set depending on the value of creatinine clearance (see table 1). Dose adjustment in renal failure Creatinine clearance (ml / min) Initial dose (mg / day) <10 (including patients on hemodialysis) 2.5* 10-30 2.5-5 31-80 5-10* - dose and/or dosing regimen is set depending on the values of blood pressure. The dose can be increased to no more than 40 mg per day under the control of blood pressure. Treatment of hypertension in children aged 6-16 years The recommended starting dose is 2.5 mg once daily in patients weighing 20 to < 50 kg and 5 mg once daily in patients weighing > 50 kg . The dosage should be adjusted individually up to a maximum daily dose of 20 mg for children weighing 20 to < 50 kg and a maximum daily dose of 40 mg in patients weighing ≥ 50 kg. There are no data on the use in children of a dose higher than 0.61 mg / kg (or higher than 40 mg). In children with reduced renal function, a lower initial dose or an increase in the interval between doses of the drug is required. Heart failure In patients with symptomatic heart failure, lisinopril can be used as an adjunct to therapy with diuretics, digitalis preparations, or β-blockers. The initial dose, which must be taken under the supervision of a physician in order to determine the initial effect on blood pressure, is 2.5 mg per day. The dose of the drug should be increased by no more than 10 mg, with an interval of at least 2 weeks and up to a maximum dose of 35 mg per day. When adjusting the dose, it is necessary to take into account the clinical response of the individual patient. In patients at high risk of developing symptomatic hypotension (eg, with electrolyte deficiency and hyponatremia or without it, with hypovolemia, or those who received intensive diuretic therapy), the above conditions should be compensated before starting treatment. Treatment with lisinopril should be carried out under the control of kidney function and serum potassium levels. Acute myocardial infarction Patients should simultaneously take the usual standard therapy with thrombolytic drugs, acetylsalicylic acid and β-blockers. Lisinopril is compatible with nitroglycerin administered intravenously or transdermally. Therapy with lisinopril should be started within the first 24 hours from the onset of symptoms of myocardial infarction according to the scheme: the initial dose is 5 mg, the next dose (after 24 hours) - 5 mg, then (after 48 hours) - 10 mg. Further, the maintenance dose is 10 mg per day. Patients with low systolic blood pressure (120 mm Hg or below) at the beginning of treatment or the first 3 days after myocardial infarction - 2.5 mg / day. Treatment should not be started if systolic blood pressure is below 100 mm Hg. Art. In case of renal insufficiency (creatinine clearance less than 80 ml / min), the initial dose of the drug should be adjusted in accordance with the patient's creatinine clearance (see table 1). Maintenance dose The maintenance dose is 10 mg once daily. With the development of hypotension (systolic blood pressure less than or equal to 100 mm Hg. Art.) While taking a daily dose of 5 mg, a temporary dose reduction to 2.5 mg is possible. With prolonged hypotension (systolic blood pressure less than 90 mm Hg for more than 1 hour), Lisinopril-LF should be discontinued. Treatment should be continued for 6 weeks, followed by a review of the need for the drug. If the patient has symptoms of heart failure, the drug should be continued (see "Heart failure"). Diabetic nephropathy In the treatment of arterial hypertension in patients with type II diabetes mellitus and initial nephropathy, the dose of the drug is 10 mg 1 time per day. If necessary, the dose can be increased to 20 mg per day to achieve diastolic blood pressure values below 90 mm Hg. Art. in a sitting position. In renal insufficiency (creatinine clearance < 80 ml / min), the initial dose of the drug must be adjusted depending on the patient's creatinine clearance (see table 1). Elderly patients There were no differences in the efficacy or safety of the drug depending on the age of the patient. To prescribe the initial dose of lisinopril to elderly patients with reduced renal function, the data in Table 1 should be followed. After that, the dose should be changed in accordance with blood pressure indicators. Use in pediatrics Data on the efficacy and safety of lisinopril in children over 6 years of age with arterial hypertension are limited, data on the use of other indications are not available. In children, Lisinopril-LF is indicated only for the treatment of arterial hypertension. Lisinopril-LF is not recommended for use in children under 6 years of age and in children with renal insufficiency (GFR <30 ml / min / 1.73 m2). Use in patients after kidney transplantation There is no experience with the use of lisinopril in patients after kidney transplantation. The appointment of the drug in this category of patients is not recommended. Side effects Adverse reactions, information on which is given below, are classified by organs and systems and by the frequency of their occurrence: very often (≥ 10%); often (≥ 1% and < 10%); infrequently (≥ 0.1% and < 1%); rarely (≥ 0.01% and < 0.1%); very rarely (<0.01%); unknown (cannot be estimated from the available data). Blood and lymphatic system disorders: rarely - a decrease in hemoglobin, a decrease in hematocrit; very rarely - anemia, including hemolytic, bone marrow depression, leukopenia, thrombocytopenia, neutropenia, agranulocytosis, lymphadenopathy, autoimmune diseases. Immune system disorders: unknown - anaphylactic / anaphylactoid reactions. Metabolic and nutritional disorders: very rarely - hypoglycemia. Nervous system disorders: often - dizziness, headache; infrequently - paresthesia, vertigo, change in taste; rarely - impaired sense of smell; unknown - fainting. Mental disorders: infrequently - mood lability, sleep disturbances, hallucinations; rarely - confusion; unknown: depressive symptoms. Vascular disorders: often - orthostatic effects (including orthostatic hypotension); infrequently - myocardial infarction or stroke, possibly secondary to excessive arterial hypotension in patients at high risk, palpitations, tachycardia, Raynaud's syndrome. Respiratory, thoracic and mediastinal disorders: often - cough; infrequently - rhinitis; very rarely - bronchospasm, sinusitis, allergic alveolitis / eosinophilic pneumonia. Gastrointestinal disorders: often - diarrhea, vomiting; infrequently - nausea, abdominal pain, dyspepsia; rarely - dry mouth; very rarely - pancreatitis, intestinal angioedema. Liver and biliary tract disorders: very rarely - hepatitis, hepatocellular or cholestatic jaundice, liver failure. Skin and subcutaneous tissue disorders: infrequently - rash, itching; rarely - urticaria, alopecia, psoriasis, hypersensitivity reactions / angioedema: angioedema of the face, extremities, lips, tongue, glottis and / or larynx; very rarely - increased sweating, pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, cutaneous pseudolymphoma. A symptom complex has been reported that may include one or more of the following: fever, vasculitis, myalgia, arthralgia/arthritis, positive antinuclear antibody (ANA) test, elevated ESR, eosinophilia and leukocytosis, rash, photosensitivity, or other skin manifestations. Renal and urinary tract disorders: often - renal dysfunction; rarely - uremia; acute renal failure; oliguria/anuria. Endocrine disorders: rarely - inadequate secretion of antidiuretic hormone. Reproductive system and mammary gland disorders: infrequently - decreased potency / impotence; rarely - gynecomastia. General disorders and reactions at the injection site: infrequently - asthenia, fatigue. Laboratory and instrumental data: infrequently - an increase in the level of urea and creatinine in the blood plasma, an increase in the activity of liver enzymes, hyperkalemia; rarely - hyponatremia, hyperbilirubinemia. Contraindications Hypersensitivity to lisinopril, any other ACE inhibitor or excipients that make up the drug. History of angioedema associated with previous treatment with other ACE inhibitors. Hereditary or idiopathic angioedema. Second or third trimester of pregnancy. In combination with drugs containing aliskiren in patients with diabetes mellitus (type I or II) or with moderate / severe renal insufficiency (glomerular filtration rate less than 60 ml / min / 1.73 m2). Overdose Symptoms: arterial hypotension, shock, water and electrolyte imbalance, renal failure, hyperventilation, tachycardia, palpitation, bradycardia, dizziness, anxiety and cough. Treatment: symptomatic treatment, intravenous saline is recommended. In case of arterial hypotension, the patient should be placed on the bed (the legs must be raised). Possible infusion of angiotensin II and / or intravenous administration of catecholamines. If the drug has been taken recently, then gastric lavage, enterosorbents and sodium sulfate are recommended to remove it. Lisinopril can be removed from the body by hemodialysis. For the treatment of persistent bradycardia, the use of a pacemaker is indicated. It is necessary to constantly monitor vital signs, serum electrolytes and creatinine concentrations. With the development of angioedema, adequate emergency therapy is necessary (administration of adrenaline, glucocorticosteroids, antihistamines). Precautions Symptomatic arterial hypotension. Symptomatic arterial hypotension is rarely found. In patients with arterial hypertension who take lisinopril, hypotension often develops due to hypovolemia during diuretic therapy, salt restriction in food, dialysis, diarrhea or vomiting, or severe forms of renin-dependent hypertension. Cases of symptomatic hypotension have been observed in patients with heart failure and concomitant renal failure or without it. It has been found more frequently in patients with severe heart failure who are required to take high doses of loop diuretics and who have hyponatremia or functional renal failure. Patients with an increased risk of symptomatic hypotension should begin treatment with the drug under the supervision of a physician, when changing the dose of the drug, monitoring should be especially careful. Similar control is necessary for patients with coronary heart disease or cerebrovascular disease, in which a significant decrease in pressure can lead to myocardial infarction or stroke. In case of arterial hypotension, the patient should be placed on his back and, if necessary, an intravenous infusion of sodium chloride solution should be given. Transient arterial hypotension when taking the drug is not a contraindication for treatment, which can be continued after normalization of blood pressure and restoration of fluid volume. In some patients with heart failure and normal or low blood pressure, the drug may further lower blood pressure. This expected effect is usually not a reason to stop treatment. If symptomatic hypotension occurs, it may be necessary to reduce the dose or stop the use of lisinopril. Arterial hypotension in acute myocardial infarction. In patients with acute myocardial infarction, treatment with lisinopril should not be started if there is a risk of further serious hemodynamic disturbances after vasodilator therapy. This applies to patients with a systolic pressure of 100 mmHg. or lower, or patients who are in cardiogenic shock. If the systolic pressure is 120 mm Hg. or lower, then during the first three days after a heart attack, the dose of the drug should be reduced. If the systolic pressure is 100 mm Hg or lower, then the maintenance dose of the drug should be reduced to 5 mg or temporarily to 2.5 mg. In case of prolonged arterial hypotension (systolic pressure less than 90 mm Hg for more than 1 hour), the use of lisinopril should be discontinued. Stenosis of the aortic and / or mitral valve / hypertrophic cardiomyopathy. As with other ACE inhibitors, lisinopril should be used with caution in patients with mitral valve stenosis and left ventricular outflow obstruction (eg, aortic stenosis or hypertrophic cardiomyopathy). Impaired kidney function. In patients with renal insufficiency (creatinine clearance <80 ml / min), the initial dose of lisinopril should be selected in accordance with the level of creatinine clearance (see table 1), and then - in accordance with the level of blood pressure. Such patients need to periodically monitor the level of potassium and creatinine. In patients with heart failure, arterial hypotension caused by the use of ACE inhibitors can lead to a decrease in kidney function with subsequent development of reversible (after discontinuation of the drug) acute renal failure. A reversible increase in blood urea and serum creatinine levels can be observed in patients with bilateral renal artery stenosis or renal artery stenosis in a solitary kidney. This is more common in patients with pre-existing renal impairment. In the presence of renovascular hypertension, there is an increased risk of developing severe hypotension and renal failure. In such patients, treatment should be initiated under close medical supervision, at low doses and with careful dose adjustments. Since diuretics may be a contributing factor to the above, their use should be discontinued and renal function monitored during the first weeks of treatment with lisinopril. In some patients with arterial hypertension without obvious signs of damage to the blood vessels of the kidneys, a slight temporary increase in the level of urea in the blood and serum creatinine may be observed, especially when lisinopril is used simultaneously with diuretics. This is more common in patients with pre-existing renal impairment. This condition requires dose reduction and/or discontinuation of the diuretic and/or lisinopril. Treatment of acute myocardial infarction with lisinopril is not indicated in patients with signs of kidney dysfunction (creatinine concentration (CC) exceeds 177 μmol / l and / or proteinuria exceeds 500 mg / day). If during therapy with lisinopril, renal dysfunction develops (CC exceeds 265 µmol / l or this figure is twice that before treatment), the drug should be discontinued. Hypersensitivity/angioedema. Angioedema of the face, extremities, lips, tongue, vocal cords and/or larynx has occasionally been observed in patients treated with ACE inhibitors, including lisinopril. During the treatment period, angioedema can develop at any time. In this case, the use of lisinopril should be stopped immediately, appropriate treatment should be carried out and the patient monitored until the symptoms disappear completely. Even in cases where the edema is limited to the tongue, there are no signs of respiratory failure, patients may need long-term observation, since treatment with antihistamines and corticosteroids may not be sufficient. Very rarely, deaths have been reported as a result of angioedema of the larynx or tongue. If swelling extends to the tongue, vocal cords, or larynx, airway obstruction may occur, especially in patients who have previously undergone respiratory surgery. In such cases, it is necessary to take emergency measures (administration of adrenaline (epinephrine) and / or maintenance of airway patency). The patient should be under close medical supervision until the symptoms disappear completely and permanently. Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at an increased risk of developing it when using ACE inhibitors. ACE inhibitors are more likely to cause angioedema in black patients than in non-black patients. Patients concomitantly taking mTOR inhibitors (eg, sirolimus, everolimus, temsirolimus) may be at increased risk of developing angioedema (eg, swelling of the airways or tongue with or without respiratory distress). Anaphylactoid reactions during hemodialysis. Patients on dialysis using high permeability membranes (eg AN 69) and concomitant treatment with ACE inhibitors are at risk of developing anaphylactoid reactions. For the treatment of this group of patients, it is recommended to use a different type of membrane or other antihypertensive drug for dialysis. Anaphylactoid reactions in low-density lipoprotein (LDL) apheresis. Rarely, life-threatening anaphylactoid reactions can occur during LDL apheresis with dextran sulfate in patients taking ACE inhibitors. These reactions can be avoided by temporarily discontinuing ACE inhibitor therapy before each apheresis. Anaphylactoid reactions during desensitizing therapy. Anaphylactoid reactions have developed in patients treated with ACE inhibitors during desensitization with an allergen from hymenoptera venom (for example, bee venom). If such patients abstained from taking ACE inhibitors for the duration of desensitization, no reactions were observed, however, accidental administration of inhibitors provoked an anaphylactoid reaction. Impaired liver function. Very rarely, with the use of ACE inhibitors, a syndrome is associated that begins with cholestatic jaundice or hepatitis and progresses to liver necrosis, sometimes with a fatal outcome. The mechanism of this syndrome is unknown. If jaundice develops in patients taking ACE inhibitors or liver enzymes are significantly increased, the drug should be discontinued and the patient should be kept under medical supervision until symptoms disappear. Neutropenia/agranulocytosis. Patients taking ACE inhibitors may develop neutropenia/agranulocytosis, thrombocytopenia, and anemia. With normal renal function and in the absence of complications, neutropenia rarely develops. Neutropenia and agranulocytosis are reversible and resolve after discontinuation of ACE inhibitors. Lisinopril should be used with particular caution in patients with connective tissue disease with vascular manifestations, when treated with immunosuppressants, allopurinol or procainamide, or a combination of these factors, especially in the presence of pre-existing renal impairment. Some of these patients develop severe infections that sometimes do not respond to intensive antibiotic therapy. When using lisinopril in this group of patients, periodic monitoring of leukocytes is recommended, and the patient should also be warned about the need to inform the doctor about any signs of infection. Ethnic features. Blacks who used ACE inhibitors were more likely to experience angioedema compared with patients of other races. As with other ACE inhibitors, the antihypertensive effect of lisinopril is less pronounced in patients of the Negroid race than in patients of another race, which may be due to the low level of renin in the blood of these patients. Cough. When treated with ACE inhibitors, an unproductive persistent cough may occur, which stops after the drug is discontinued. Cough caused by ACE inhibitors must be differentiated from cough in other diseases. Surgery/anesthesia. During major surgery or anesthesia with drugs that cause arterial hypotension, lisinopril may re-block the formation of angiotensin II due to compensatory renin release. If at the same time arterial hypotension develops, which can be explained by this mechanism, then it should be corrected by increasing the volume of fluid. Hyperkalemia. In some patients, when taking ACE inhibitors, including lisinopril, there was an increase in the concentration of potassium in the blood serum. Risk factors for hyperkalemia include renal insufficiency, diabetes mellitus, concomitant use of potassium-sparing diuretics, dietary supplements that contain potassium or salt substitutes with potassium, or other drugs that cause an increase in serum potassium (eg, heparin). If the intake of the above drugs against the background of treatment with ACE inhibitors is recognized as necessary, regular monitoring of the level of potassium in the blood serum is recommended. Diabetes. Patients taking oral antidiabetic drugs or insulin require careful glycemic control, especially during the first month of treatment with ACE inhibitors. Patients after kidney transplantation. There is no experience of using the drug for the treatment of patients with a recently transplanted kidney, so the drug is not used for this group of patients. Lithium. The concomitant use of lithium and lisinopril is generally not recommended. Double blockade of the renin-angiotensin-aldosterone system Double blockade of the renin-angiotensin-aldosterone system is associated with an increased risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Dual RAAS blockade with ACE inhibitors, angiotensin II receptor blockers, or aliskiren cannot be recommended for any patient, especially those with diabetic nephropathy. In some cases, when the combined use of ACE inhibitors and ARB II is absolutely indicated, careful observation of a specialist and mandatory monitoring of kidney function, water and electrolyte balance, and blood pressure are necessary. This refers 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. Pregnancy ACE inhibitors should not be initiated during pregnancy. If continuation of ACE inhibitor therapy is not considered necessary, patients planning pregnancy should be switched to therapy with alternative antihypertensive drugs that have an established safety profile for use during pregnancy. When pregnancy is diagnosed, treatment with ACE inhibitors should be stopped immediately and, if necessary, alternative therapy initiated. Use during pregnancy and lactation Pregnancy It is not recommended to take ACE inhibitors during the first trimester of pregnancy. ACE inhibitors are contraindicated during the second and third trimesters of pregnancy. Epidemiological data on the risk of teratogenic effects of ACE inhibitors during the first trimester of pregnancy are not conclusive, however, a small increase in risk cannot be ruled out. If continuation of ACE inhibitor therapy is not considered necessary, patients planning pregnancy should be switched to therapy with alternative antihypertensive drugs that have an established safety profile for use during pregnancy. If pregnancy is established, treatment with ACE inhibitors should be stopped immediately and, if necessary, alternative treatment should be started. Treatment with ACE inhibitors during the second and third trimester has toxic effects on the human fetus (renal failure, oligohydramnios, skull hypoplasia) and neonates (renal failure, hypotension, hyperkalemia). If exposure to ACE inhibitors is observed in the second trimester of pregnancy, it is recommended to conduct an ultrasound examination of the function of the kidneys and the fetal skull. It is necessary to conduct a thorough examination for the presence of hypotension in infants whose mothers take ACE inhibitors. Breastfeeding period Since there is no information on the use of lisinopril during the lactation period, it is not recommended to take lisinopril, it is preferable to prescribe an alternative treatment with a better safety profile during the lactation period, in particular, newborns and premature babies. Influence on the ability to drive vehicles and work with mechanisms When driving vehicles and / or working with mechanisms, it is necessary to take into account the possible occurrence of dizziness or fatigue while taking lisinopril. Interaction with other drugs Dual blockade of the renin-angiotensin-aldosterone system Based on the available data, dual blockade of the RAAS with ACE inhibitors, angiotensin II receptor blockers or aliskiren cannot be recommended in any patient, especially in patients with diabetic nephropathy. In patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2), the simultaneous use of Aliskiren with ACE inhibitors or angiotensin II receptor blockers is contraindicated. In some cases, when the combined use of ACE inhibitors and angiotensin II receptor blockers is absolutely indicated, careful observation of a specialist and mandatory monitoring of kidney function, water and electrolyte balance, and blood pressure are necessary. With the simultaneous use of Lisinopril-LF with: - diuretics, the summation of the antihypertensive effect is noted. In patients already taking diuretics, especially those who have recently been prescribed diuretics, the use of lisinopril can sometimes cause an excessive decrease in blood pressure. The risk of symptomatic arterial hypotension can be reduced if the diuretic is discontinued before starting treatment with lisinopril; - Potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium preparations or table salt substitutes that contain potassium increase the risk of developing hyperka