Diroton tablets 10mg №14×2

Name:
Diroton tabl 10mg in bl. in pack. No. 14×2
Description:
Tablets 5 mg White or almost white round, flat tablets with a bevel, engraved “5” on one side and with a notch on the other. Tablets 10 mg White or almost white, quadrangular, slightly biconvex tablets, debossed with “10” on one side and scored on the other another. The main active ingredient Lisinopril Release form Tablets Pharmacological properties Pharmacodynamics Mechanism of action Lisinopril is an inhibitor of the peptidyl dipeptidase enzyme. It inhibits the angiotensin-converting enzyme (ACE), which catalyses the conversion of angiotensin I to the vasoconstrictor peptide, angiotensin II. Angiotensin II also stimulates the secretion of aldosterone by the adrenal cortex. Inhibition of ACE leads to a decrease in angiotensin II concentrations, resulting in a decrease in vasopressor activity and a decrease in aldosterone secretion. A decrease in the latter can lead to an increase in the content of potassium in the blood serum. Pharmacodynamic effects Since the mechanism by which lisinopril lowers blood pressure is believed to be primarily inhibition of the renin-angiotensin-aldosterone system, lisinopril lowers blood pressure even in hypertensive patients with low renin levels. ACE is identical to kininase II, an enzyme that breaks down bradykinin. Whether elevated concentrations of bradykinin, a potent vasodilator peptide, play a role in the therapeutic effects of lisinopril remains to be seen. Clinical efficacy and safety The effect of lisinopril on morbidity and mortality in heart failure was studied by comparing a high dose of lisinopril (32.5 mg or 35 mg once daily) with a low dose (2.5 mg or 5 mg once daily). The study included 3164 patients with a mean follow-up period of 46 months (for survivors). The high dose of lisinopril provided a 12% risk reduction for the combined endpoint of all-cause mortality and all-cause hospitalization (p=0.002) and an 8% risk reduction for all-cause death and CVD hospitalization (p=0.036) for compared to low dose. There was a reduction in the risk of death from all causes (8%; p=0.128) and death from cardiovascular disease (10%; p=0.073). In a retrospective analysis, the number of hospitalizations due to heart failure decreased by 24% (p = 0.002) in patients who received high doses of lisinopril compared with patients who received low doses. Changes in symptoms in patients treated with high and low doses of lisinopril were the same. The results of the study showed that the overall profiles of adverse events in patients treated with high or low doses of lisinopril are similar in nature and quantitative parameters. Predicted adverse events resulting from ACE inhibition, such as arterial hypotension or impaired renal function, responded well to correction and rarely led to discontinuation of treatment. Cough was less common in patients treated with high doses of lisinopril than in patients treated with low doses. The GISSI-3 study used a 2×2 factorial design to compare the effects of lisinopril and glyceryl trinitrate (nitroglycerin) given alone or in combination for 6 weeks relative to a control group. In a study of 19,394 patients treated within 24 hours of an acute myocardial infarction, lisinopril provided a statistically significant reduction in the risk of death of 11% compared with controls (2p=0.03). The risk reduction with nitroglycerin was not statistically significant, but the combination of lisinopril and nitroglycerin resulted in a statistically significant reduction in the risk of death of 17% compared with control (2p=0.02). In subgroups of older adults (>70 years of age) and women, predefined as patients at high risk of death, a significant benefit was observed for the combined endpoint of mortality and cardiac function. The composite endpoint for all patients as well as high-risk subgroups at 6 months also improved significantly in patients treated with lisinopril or lisinopril plus nitroglycerin for 6 weeks, indicating a prophylactic effect of lisinopril. As with any vasodilator therapy, lisinopril has been associated with an increased incidence of arterial hypotension and impaired renal function, but these events have not been associated with a proportional increase in mortality. In a double-blind, randomized, multicenter study (N=335) comparing lisinopril with a calcium channel blocker in patients with hypertension and type 2 diabetes mellitus with initial nephropathy with microalbuminuria, lisinopril 10-20 mg once daily for 12 months , reduced systolic/diastolic blood pressure by 13/10 mm Hg. Art., and urinary albumin excretion by 40%. Compared with a calcium channel blocker, which caused the same decrease in blood pressure, patients treated with lisinopril showed a significantly greater decrease in urinary albumin excretion, indicating that the ACE-inhibiting effect of lisinopril, in addition to the antihypertensive effect, also reduced microalbuminuria by direct effect on kidney tissue. Treatment with lisinopril does not affect glycemic control, as evidenced by the absence of a significant effect on glycosylated hemoglobin (HbA1c) levels. Two large, randomized, controlled trials (ONTARGET, Ongoing to Endpoint, Telmisartan alone and with ramipril and the VA NEPHRON-D Diabetic Nephropathy Study by the Department of Veterans Affairs) studied the co-administration of an ACE inhibitor with a receptor antagonist. angiotensin II. The ONTARGET study was conducted in patients with a history of cardiovascular or cerebrovascular disease or type 2 diabetes mellitus with evidence of target organ damage. The VA NEPHRON-D study was conducted in patients with type 2 diabetes mellitus and diabetic nephropathy. These studies did not reveal a significant beneficial effect on renal and / or cardiovascular function and mortality, at the same time, an increased risk of hyperkalemia, acute kidney injury and / or arterial hypotension was noted compared with monotherapy. Given similar pharmacodynamic characteristics, these results are also relevant for other ACE inhibitors and angiotensin II receptor antagonists. In this regard, the combined use of ACE inhibitors and angiotensin II receptor antagonists in patients with diabetic nephropathy is not recommended. In addition, the ALTITUDE (aliskiren study in patients with type 2 diabetes mellitus, with changes in cardiovascular and renal function as end points) was conducted, which tested the benefits of adding aliskiren to standard therapy (ACE inhibitor or receptor antagonist). angiotensin II) in patients with type 2 diabetes mellitus and chronic kidney disease, cardiovascular disease, or both. The study was terminated prematurely due to an increased risk of adverse outcomes. Cardiovascular death and stroke were much more common in the aliskiren-supplemented group than in the placebo group, and adverse events and serious adverse events (hyperkalemia, hypotension, and renal dysfunction) were more common in the aliskiren group than in the placebo group. placebo group. Children and adolescents In a clinical study of 115 children with hypertension aged 6-16 years, patients weighing less than 50 kg received 0.625 mg, 2.5 mg or 20 mg of lisinopril once a day, and patients weighing 50 kg or more received 1 .25 mg; 5 mg or 40 mg of lisinopril once a day. After 2 weeks, once-daily lisinopril lowered blood pressure in a dose-dependent manner with sustained antihypertensive efficacy at doses above 1.25 mg. This effect was confirmed in the withdrawal phase, when diastolic blood pressure rose by about 9 mmHg. Art. more in patients who were randomized to placebo than in patients who were randomized to medium and high doses of lisinopril. The dose-dependent antihypertensive effect of lisinopril in several demographic subgroups was similar: age, Tanner stages, gender and race. Pharmacokinetics Lisinopril is an ACE inhibitor that does not contain a sulfhydryl group and is active when taken orally. Absorption After oral administration, the maximum serum concentrations of lisinopril are observed after approximately 7 hours, while there was a tendency to a slight increase in the time to reach maximum serum concentrations in patients with acute myocardial infarction. Based on urinary excretion data, the average extent of absorption of lisinopril is approximately 25%, with variability between patients ranging from 6 to 60% over the studied dose range (5 to 80 mg). In patients with heart failure, the absolute bioavailability of lisinopril is reduced to approximately 16%. Absorption of lisinopril does not depend on food intake. Distribution Lisinopril does not bind to serum proteins, with the exception of circulating angiotensin-converting enzyme (ACE). Studies in rats have shown that lisinopril practically does not penetrate the blood-brain barrier. Excretion Lisinopril is not metabolized and is excreted in the urine unchanged. With repeated use of lisinopril, the effective half-life is 12.6 hours. The clearance of lisinopril in healthy volunteers is approximately 50 ml/min. The decrease in serum concentration has a prolonged terminal phase, which does not contribute to the accumulation of the drug in the body. This terminal phase is probably saturable binding to ACE and is dose disproportionate. Impaired liver function Impaired liver function in patients with cirrhosis of the liver resulted in a decrease in the absorption of lisinopril (approximately 30%, according to urinary excretion), but the drug exposure was increased (approximately 50%) compared with healthy volunteers due to reduced clearance . Impaired renal function Impaired renal function reduces the excretion of lisinopril, which is excreted through the kidneys, but this decrease becomes clinically significant only when the glomerular filtration rate is less than 30 ml / min. In mild to moderate renal insufficiency (creatinine clearance 30 to 80 ml/min) the mean AUC increases by only 13%, while in severe renal insufficiency (creatinine clearance 5 to 30 ml/min) there is an increase in the mean AUC 4.5 times. Lisinopril can be removed from the body by hemodialysis. After 4 hours of hemodialysis, the concentration of lisinopril in the blood plasma decreased by an average of 60%, and the dialysis clearance ranged from 40 to 55 ml / min. Heart failure Patients with heart failure have higher plasma concentrations of lisinopril compared to healthy volunteers (average 125% increase in AUC), but based on urinary excretion data, their absorption of lisinopril is reduced by about 16% compared with healthy volunteers. Children and adolescents The pharmacokinetic profile of lisinopril was studied in 29 hypertensive patients aged 6 to 16 years with a glomerular filtration rate greater than 30 ml/min/1.73 m2. After a dose of 0.1 to 0.2 mg/kg, the maximum steady-state plasma concentration of lisinopril was reached within 6 hours, and the extent of absorption, based on urinary excretion, was approximately 28%. These values are similar to those previously obtained in adults. The values of AUC and Cmax in children in this study are comparable to those obtained for adults. Elderly Patients Elderly patients have higher plasma concentrations of lisinopril and higher values for the area under the plasma concentration-time curve (more than approximately 60%) compared with younger study participants. Indications for useArterial hypertension Treatment of arterial hypertension. Heart failure Treatment of heart failure. Acute myocardial infarction Short-term (6 weeks) treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction. Diabetic nephropathy Treatment of kidney damage in patients with arterial hypertension and type 2 diabetes mellitus and the initial stage of nephropathy (see the Pharmacodynamics section). Route of administration and doses Dosage The dose should be selected individually according to blood pressure (see section “Precautions”). The score on the tablet is intended to divide the tablet in order to simplify the process of swallowing, but not to divide into equal doses. For this reason, a dosage of 2.5 mg cannot be provided with a drug at a dosage of 5 mg. Arterial hypertension Diroton can be used in monotherapy or in combination with other classes of antihypertensive drugs (see sections “Contraindications”, “Precautions”, “Interaction with other drugs”, “Pharmacodynamics”). Initial dose In patients with arterial hypertension, the recommended initial dose is 10 mg. In patients with severe activation of the renin-angiotensin-aldosterone system (in particular, with renovascular hypertension, in patients on a salt-restricted diet and / or hypovolemia, cardiac decompensation, or severe arterial hypertension), a more pronounced decrease in blood pressure after initial doses. In such patients, the recommended initial dose is 2.5-5 mg, and the initiation of therapy should be carried out under strict medical supervision. In renal insufficiency, a lower initial dose is recommended (see table 1 below). Maintenance dose An effective maintenance dose is 20 mg once daily. Usually, if the desired therapeutic effect cannot be achieved within 2-4 weeks at a certain dose, a further dose increase is possible. The maximum dose used in long-term controlled clinical trials was 80 mg/day. Patients receiving diuretics After the start of therapy with Diroton, symptomatic hypotension may develop. The risk of developing symptomatic hypotension is higher in patients receiving diuretics. For this reason, caution should be exercised in the treatment of such patients due to the risk of electrolyte loss/hypovolaemia. If possible, diuretics should be canceled 2-3 days before the start of Diroton therapy. In hypertensive patients who cannot be treated with diuretics, treatment with Diroton should be initiated at a dose of 5 mg. At the same time, the control of kidney function and the content of potassium in the blood serum is shown. Subsequently, the dose of Diroton can be adjusted depending on the level of blood pressure. If necessary, it is possible to resume treatment with diuretics (see sections “Precautions” and “Interaction with other drugs”). Dose adjustment in renal insufficiency The dose in patients with impaired renal function should be selected taking into account creatinine clearance (CC) (see table 1). Table 1. Dose adjustment in renal failure Creatinine clearance (ml / min) Initial dose (mg / day) Less than 10 ml / min (including patients on dialysis) 2.5 mg * 10-30 ml / min 2.5- 5 mg 31-80 ml/min 5-10 mg *Dose and/or frequency of administration should be adjusted according to blood pressure levels. The dose can be gradually increased until the desired values of blood pressure are reached, or up to a maximum of 40 mg / day. Application in children with arterial hypertension aged 6-16 years The recommended initial dose is 2.5 mg 1 time per day in children weighing 20-50 kg and 5 mg 1 time per day in children weighing more than 50 kg. The dose should be selected individually up to a maximum of 20 mg / day in children weighing 20-50 kg and 40 mg in children weighing more than 50 kg. In studies involving children, doses higher than 0.61 mg / kg (or higher than 40 mg) have not been studied (see the Pharmacodynamics section). In children with reduced renal function, it is necessary to prescribe a lower initial dose or increase the intervals between dose increases. Heart failure In patients with heart failure, Diroton should be used as an additional therapy to diuretics and, if necessary, digitalis preparations or beta-blockers (see sections “Contraindications”, “Precautions”, “Interaction with other drugs”, ” Pharmacodynamics”), the initial dose may be 2.5 mg 1 time per day, while treatment should be initiated under close medical supervision to evaluate the effect on blood pressure. When increasing the dose, the following should be taken into account: the step of increasing the dose should not exceed 10 mg; the interval between dose increases should not be less than 2 weeks; the dose should be increased to the maximum tolerated (35 mg 1 time per day). Dose adjustment is carried out individually, depending on the clinical effect. In patients at high risk of symptomatic hypotension, for example, in patients with electrolyte deficiency and / or hyponatremia, in patients with hypovolemia or in patients receiving strong diuretics, if possible, correction of such factors should be carried out before prescribing Diroton. Monitoring of kidney function and serum potassium is shown (see section “Precautions”). Acute myocardial infarction Patients should receive standard recommended drugs, as needed, such as thrombolytics, acetylsalicylic acid, and beta-blockers. Nitroglycerin intravenously or transdermally can be used in combination with Diroton (see sections “Contraindications”, “Precautions”, “Interaction with other drugs”, “Pharmacodynamics”), Initial dose (first 3 days after myocardial infarction) Treatment with Diroton may be started within 24 hours of symptom onset. Therapy should not be started at systolic blood pressure less than 100 mm Hg. Art. The first dose of the drug Diroton – 5 mg orally, then 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg 1 time per day. In patients with low systolic blood pressure (120 mm Hg or below), if treatment is started or continued during the first 3 days after myocardial infarction, the dose should be lower – 2.5 mg orally (see section “Precautions” ). In the presence of renal insufficiency (creatinine clearance <80 ml / min), the initial dose of Diroton should be selected depending on the CC (see table 1). Maintenance dose The maintenance dose is 10 mg once daily. In the event of hypotension (systolic blood pressure less than or equal to 100 mm Hg), the daily maintenance dose may be 5 mg with a temporary reduction to 2.5 mg if necessary. With the development of prolonged arterial hypotension (systolic blood pressure less than 90 mm Hg for more than 1 hour), Diroton must be canceled. Treatment should be continued for 6 weeks and then the patient's condition should be reassessed. Patients who develop symptoms of heart failure should continue treatment with Diroton (see section "Method of application and doses"). Diabetic nephropathy In patients with arterial hypertension, type 2 diabetes mellitus and the initial stage of nephropathy, the dose is 10 mg 1 time per day; the dose may be increased, if necessary, to 20 mg 1 time per day to achieve diastolic blood pressure below 90 mm Hg. Art. when measured in a sitting position. In the presence of renal insufficiency (creatinine clearance <80 ml / min), the initial dose of Diroton should be selected depending on the CC (see table 1). Use in children Data on the efficacy and safety of the drug in children over 6 years of age with arterial hypertension are limited, but there is no experience with other indications (see the section "Pharmacodynamics"). Lisinopril should only be used in children for the treatment of hypertension (and is not recommended for other indications). Lisinopril should not be used in children under 6 years of age or in children with severe renal insufficiency (glomerular filtration rate (GFR) <30 ml / min / 1.73 m2 of body surface area) (see section "Pharmacokinetics"). Use in Elderly Patients In clinical studies, there were no age-related changes in the efficacy or safety of the drug. If renal function is reduced in elderly patients, then the initial dose should be selected taking into account QC (table 1). Subsequently, the dose must be adjusted depending on changes in blood pressure. Use in patients with kidney transplantation There is no experience with the use of the drug Diroton in patients with recent kidney transplantation. For this reason, the use of Diroton in such patients is not recommended. Method of application Diroton is taken orally 1 time per day. As with other once-daily medications, lisinopril should be taken at the same time each day. Absorption of the drug Diroton does not depend on food intake. Use during pregnancy and lactation Do not start treatment with ACE inhibitors during pregnancy. If continued treatment with an ACE inhibitor is considered necessary, patients planning pregnancy should be switched to alternative antihypertensive drugs with a known safety profile for use during pregnancy. When pregnancy is confirmed, treatment with ACE inhibitors should be stopped immediately and, if necessary, alternative treatment should be prescribed (see sections "Contraindications" and "Use during pregnancy and during breastfeeding"). The use of lisinopril during breastfeeding is not recommended. Precautions Symptomatic hypotension Symptomatic hypotension rarely occurs in patients with uncomplicated hypertension. In patients with arterial hypertension while using lisinopril, arterial hypotension is more likely to occur against the background of hypovolemia, for example, with the use of diuretics, salt restriction in the diet, during dialysis, diarrhea or vomiting, or the presence of severe renin-dependent hypertension (see sections " Interaction with other drugs" and "Side effects"). In patients with heart failure, regardless of the presence of concomitant renal failure, the development of symptomatic hypotension was observed. Symptomatic hypotension is most likely to develop in patients with more severe heart failure, in which higher doses of loop diuretics are used, hyponatremia, or functional renal failure. In patients with an increased risk of symptomatic hypotension, careful monitoring of the condition is necessary when starting therapy or adjusting the dose. The same applies to patients with ischemic heart disease or cerebrovascular disease, in whom too much reduction in blood pressure can lead to myocardial infarction or cerebrovascular accident. If arterial hypotension occurs, the patient should be given a horizontal position, if necessary, an intravenous infusion of 0.9% sodium chloride solution is recommended. Transient arterial hypotension, as a rule, is not a contraindication for further treatment; further treatment usually passes without complications after restoration of blood pressure as a result of correction of hypovolemia. In some patients with heart failure and normal or low blood pressure, an additional decrease in systemic arterial pressure may be possible with the use of lisinopril. This effect is expected and is not a reason to stop treatment. If hypotension results in clinical manifestations, dose reduction or discontinuation of lisinopril may be indicated. Arterial hypotension in acute myocardial infarction In the event of an acute myocardial infarction, if treatment with vasodilator drugs can seriously worsen the hemodynamic state (for example, if systolic blood pressure is 100 mm Hg or lower, or in case of cardiogenic shock), lisinopril is contraindicated. During the first 3 days after myocardial infarction, it is necessary to reduce the dose if the systolic blood pressure is 120 mm Hg. Art. or below. Maintenance doses should be reduced to 5 mg or temporarily to 2.5 mg if systolic blood pressure is 100 mm Hg. Art. or below. With sustained arterial hypotension (systolic blood pressure below 90 mm Hg for more than 1 hour), lisinopril should be discontinued. Aortic and mitral valve stenosis/hypertrophic cardiomyopathy As with other ACE inhibitors, lisinopril should be used with caution in patients with mitral valve stenosis and left ventricular outflow tract obstruction, such as aortic valve stenosis or hypertrophic cardiomyopathy. Impaired renal function In case of impaired renal function (CC <80 ml / min), the initial dose of lisinopril should be selected depending on the CC (see Table 1 in the section "Method of administration and dose"), and then on the patient's clinical response to therapy. Routine monitoring of potassium levels and serum creatinine concentrations is part of standard medical practice in the treatment of these patients. In patients with heart failure, arterial hypotension after the appointment of ACE inhibitors can lead to a further deterioration in renal function. Acute renal failure, usually reversible, has been reported in this situation. In some patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney treated with ACE inhibitors, an increase in blood urea and serum creatinine has been noted, usually reversible after discontinuation of therapy. This effect is more likely to be observed in patients with renal insufficiency. In the presence of concomitant renovascular hypertension, the risk of severe arterial hypotension and renal failure increases. In such patients, treatment should be started under close medical supervision, using low doses and carefully titrating the dose. Since diuretics can exacerbate this condition, during the first weeks of therapy with lisinopril, they should be discontinued and renal function monitored. In some patients with arterial hypertension, who do not have any concomitant vascular diseases of the kidneys, there was an increase in the concentration of urea and creatinine in the blood serum, usually insignificant and short-term, especially with the simultaneous use of lisinopril and a diuretic. This effect is more likely to be observed in patients with renal insufficiency. Dose reduction and/or withdrawal of the diuretic and/or lisinopril may be required. Treatment with lisinopril should not be started in acute myocardial infarction in patients with impaired renal function, defined as a serum creatinine concentration of more than 177 μmol / l and / or proteinuria greater than 500 mg / 24 hours. in serum above 265 µmol / l or twice as high as the initial level), the doctor should consider the possibility of discontinuing lisinopril. Hypersensitivity/angioneurotic edema (Quincke's edema) In rare cases, angioedema of the face, extremities, lips, tongue, glottis and/or larynx has been reported with the use of angiotensin-converting enzyme inhibitors, including lisinopril. Edema may develop at any time during treatment. In this case, it is necessary to immediately cancel lisinopril, the patient should receive appropriate treatment and be under medical supervision in a hospital until the symptoms are completely resolved. Even if edema occurs only in the tongue area, without concomitant respiratory impairment, the patient may require long-term observation, since treatment with antihistamines and corticosteroids may not be enough. In very rare cases, death has been reported due to the development of angioedema of the larynx or tongue. Patients with involvement of the tongue, glottis, or larynx are at higher risk of airway obstruction, especially if airway surgery is present. In such cases, emergency therapy is indicated, which may include the administration of adrenaline and / or maintenance of airway patency. The patient should be under strict medical supervision until complete and sustained resolution of symptoms. Angiotensin-converting enzyme inhibitors are more likely to cause angioedema in patients of the Black race than in patients of other races. Patients who have previously experienced angioedema unrelated to ACE inhibitor treatment may be at greater risk of developing angioedema while taking an ACE inhibitor (see section "Contraindications"). Anaphylactoid reactions in patients on hemodialysis Anaphylactoid reactions have been reported in patients on hemodialysis using high-flux dialysis membranes with high permeability (eg, AN69) and concomitantly receiving an ACE inhibitor. In such patients, consideration should be given to the use of a different type of dialysis membrane or a different class of antihypertensive drug. Anaphylactoid reactions during low-density lipoprotein (LDL) apheresis Rarely, life-threatening anaphylactoid reactions may occur in patients receiving ACE inhibitors during LDL apheresis using dextran sulfate. Such reactions could be avoided if, before each apheresis, the ACE inhibitor was temporarily stopped. Desensitization With desensitization (eg, insect venom) in patients receiving ACE inhibitors, sustained anaphylactoid reactions are observed. In the same patients, it was possible to avoid the occurrence of such reactions with a temporary suspension of therapy with ACE inhibitors, but they reappeared when these drugs were accidentally taken. Liver failure In very rare cases, during therapy with ACE inhibitors, a syndrome developed that began with cholestatic jaundice and progressed to fulminant necrosis and (sometimes) led to death. The mechanism of development of this syndrome has not been studied. If signs of jaundice appear or if there is a significant increase in the activity of "liver" enzymes, treatment with lisinopril should be discontinued and be under appropriate medical supervision. Neutropenia/agranulocytosis Neutropenia/agranulocytosis, thrombocytopenia and anemia have been reported in patients receiving ACE inhibitors. Neutropenia rarely develops in patients with normal renal function without other aggravating factors. Neutropenia and agranulocytosis disappeared after discontinuation of treatment with ACE inhibitors. Lisinopril should be used with extreme caution in patients with vascular collagenosis, as well as in patients receiving immunosuppressive therapy, allopurinol or procainamide, or a combination of these complicating factors, especially if there is also impaired renal function. Some of these patients developed serious infections, which in some cases did not respond to intensive antibiotic therapy. If lisinopril is used in such patients, then periodic monitoring of the number of leukocytes is recommended; in addition, patients should be advised to report any signs of infection. Dual blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence that the concomitant use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and decreased renal function (including acute renal failure). Double blockade of the RAAS due to the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended for this reason (see sections "Interaction with other drugs" and "Pharmacodynamics"), If a double blockade is absolutely necessary, then such treatment should be carried out under medical supervision with frequent close monitoring of kidney function, electrolytes and blood pressure. In patients with diabetic nephropathy, combination therapy with ACE inhibitors and angiotensin II receptor blockers should not be used. Race In black patients, angiotensin-converting enzyme inhibitors are more likely to cause angioedema than in patients of other races. As with other ACE inhibitors, in Black patients, lisinopril may be less effective in lowering blood pressure than in patients of other races, which is likely due to the higher incidence of low renin conditions in Black patients suffering from arterial hypertension. Cough Cough has been reported during treatment with ACE inhibitors. The cough is usually dry. Stable, and stopped after discontinuation of the drug. In the differential diagnosis of cough, the possibility of cough induced by ACE inhibitors should be considered. Surgery/Anesthesia In patients undergoing major surgery or during general anesthesia with drugs that cause arterial hypotension, lisinopril may block the formation of angiotensin II after a compensatory release of renin. If arterial hypotension develops, probably as a result of the above mechanism, a correction can be made by increasing the volume of circulating blood. Hyperkalemia In some patients treated with ACE inhibitors, including lisinopril, an increase in serum potassium was observed. The risk of developing hyperkalemia is higher in patients with renal insufficiency, diabetes mellitus, with the concomitant use of potassium-sparing diuretics, dietary supplements or salt substitutes containing potassium, and in patients taking drugs that can increase serum potassium (for example, heparin). If the simultaneous administration of the above drugs is mandatory, regular monitoring of the content of potassium in the blood serum is recommended (see section "Interaction with other drugs"). Patients with diabetes mellitus Patients with diabetes require more careful monitoring of glucose concentration in the first month of treatment with an ACE inhibitor in addition to previous treatment with insulin or hypoglycemic drugs for oral administration (see the section "Interaction with other drugs"). Lithium preparations Usually not concomitant administration of lithium and lysinop is recommended