Lisoretic pills 10mg/12.5mg №14×2

Name:
Lisoretic. Forms of release Tablets. INN Lisinopril + hydrochlorothiazide. FTGHypotensive combined means (APF blocker + diuretic). Composition Each 10 mg/12.5 mg tablet contains: Active ingredients: lisinopril (as lisinopril dihydrate) 10.00 mg and hydrochlorothiazide 12.50 mg Excipients: calcium hydrogen phosphate 38.01 mg, mannitol 22.00 mg, corn starch 22 40 mg, pregelatinized starch 3.00 mg, iron dye red oxide (E172) 0.05 mg, iron dye yellow oxide (E172) 0.05 mg, magnesium stearate 1.10 mg. Each 20 mg/12.5 mg tablet contains: Active ingredients: lisinopril (as lisinopril dihydrate) 20.00 mg and hydrochlorothiazide 12.50 mg Excipients: calcium hydrogen phosphate 88.72 mg, mannitol 44.00 mg, corn starch 44 .80 mg, pregelatinized starch 6.00 mg, magnesium stearate 2.20 mg.
Description:
Dosage 10mg/12.5mg: beige-pink, round, biconvex, with a dividing line on one side. Dosage 20 mg / 12.5 mg: white to almost white, round, biconvex. Pharmacotherapeutic group Means that affect the renin-angiotensin system. ACE inhibitors and diuretics. ATX code C09BA03. Pharmacological action Pharmacodynamics The drug Lisoretic is a combination of fixed doses of lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, and hydrochlorothiazide (thiazide diuretic), which have a complementary effect and complement each other’s antihypertensive effect. Lisinopril Lisinopril is an angiotensin-converting enzyme (ACE) inhibitor that catalyzes 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 the concentration of angiotensin II, which leads to a decrease in vasopressor activity and a decrease in aldosterone secretion. Suppression of the activity of the renin-angiotensin-aldosterone system is considered the main mechanism by which lisinopril lowers blood pressure. Lisinopril exhibits an antihypertensive effect even in patients with low renin levels. ACE inhibitors reduce the concentration of the vasoconstrictor angiotensin II, but increase the level of bradykinin. This explains the presence of dry cough in patients taking ACE inhibitors. Hydrochlorothiazide Hydrochlorothiazide is a diuretic and antihypertensive agent. Hydrochlorothiazide inhibits the transport protein that provides the transfer of sodium and chlorine to the cells of the tubular epithelium, resulting in a decrease in the reabsorption of these ions in the distal tubules. An increase in the sodium concentration in the collecting duct system stimulates its exchange for potassium, which leads to an increase in potassium loss. The mechanism of the antihypertensive action of thiazides is unknown. Thiazides usually do not affect normal blood pressure. Pharmacokinetics The combination tablet is bioequivalent to the administration of each of the active substances separately. Absorption of Lisinopril Approximately 25% with inter-patient variability (6-60%) at all doses tested (5-80 mg). Eating does not affect the absorption of lisinopril. The maximum serum concentration is reached in 6-8 hours. The effect on blood pressure is observed after 1-2 hours. The effect is maximum after 6 hours and lasts at least 24 hours. Hydrochlorothiazide The diuretic effect is observed within 2 hours. The maximum effect is achieved after 4 hours. Clinically adequate diuretic effects last for 6-12 hours. Distribution Protein binding Lisinopril does not bind to any other plasma proteins other than ACE. In the elderly, a reduced volume of distribution may result in higher plasma concentrations. Metabolism/elimination Both active substances are not metabolized and are almost completely excreted by the kidneys unchanged. The half-life for lisinopril with repeated use averages 12 hours, for hydrochlorothiazide – 5-15 hours. Approximately 61% of the hydrochlorothiazide taken is eliminated within 24 hours. Hydrochlorothiazide crosses the placental barrier. Liver failure In patients with cirrhosis of the liver, the bioavailability of lisinopril is reduced by 30%, and clearance by 50% compared with patients with normal liver function. Renal failure With impaired renal function, the elimination of lisinopril is reduced, but this decrease becomes clinically significant only when the glomerular filtration rate is less than 30 ml / min. Pharmacokinetic parameters of lisinopril in various groups of patients with renal insufficiency after taking a dose multiple of 5 mg Creatinine clearance n Cmax (ng / ml) Tmax (h) AUC (0-24h) (ng / h / ml) t1 / 2 (h) >80 ml /min 6 40.3 6492+/-172 6.0+/-1.1 30-80 ml/min 6 36.6 8555+/-364 11.8+/-1.9 5-30 ml/min min 6 106.7 8 2228+/-938 19.5+/-5.2 In patients with creatinine clearance 30-80 ml/min, the average AUC increases only by 13%, and in patients with creatinine clearance 5-30 ml/min min there is an increase in the average AUC by 4-5 times. Lisinopril can be removed by dialysis. For 4 hours of hemodialysis, the plasma concentration of lisinopril decreased by an average of 60%, with a dialysis clearance of 40 to 55 ml / min. Heart failure In patients with heart failure, the systemic exposure to lisinopril is increased (average increase in AUC by 125%), and there is a decrease in the absorption of lisinopril by 16% compared with healthy people. Elderly patients In elderly patients, the concentration of the drug in blood plasma and the area under the concentration-time curve is greater than in young patients. The concentration of lisinopril in the blood is increased, on average, by 60%. Indications for use Lysoretic is used to treat mild to moderate hypertension in patients who are amenable to therapy with individual components (lisinopril hydrochlorothiazide) at the same dosages. Contraindications Hypersensitivity to the drug, other ACE inhibitors and sulfonamide derivatives, anuria, severe renal failure (creatinine clearance less than 30 ml / min.), angioedema (including a history of the use of ACE inhibitors), hemodialysis using high-flow membranes, hypercalcemia , hyponatremia, porphyria, severe liver failure, diabetes mellitus (severe forms), hereditary or idiopathic angioedema, pregnancy, breastfeeding period, age up to 18 years (efficacy and safety have not been established). The simultaneous use of angiotensin-converting enzyme inhibitors or ATP receptor blockers with Aliskiren in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2) is contraindicated. With caution: aortic stenosis / hypertrophic cardiomyopathy, bilateral renal artery stenosis, stenosis of the artery of a single kidney with progressive azotemia, condition after kidney transplantation, renal failure (creatinine clearance more than 30 ml / min.), Primary hyperaldosteronism, arterial hypotension, bone marrow hypoplasia, hyponatremia (increased risk of arterial hypotension in patients on a low-salt or salt-free diet), conditions accompanied by a decrease in circulating blood volume (including diarrhea, vomiting), connective tissue diseases (systemic lupus erythematosus, scleroderma), diabetes mellitus, gout, hyperuricemia, hyperkalemia, ischemic heart disease, cerebrovascular insufficiency, severe chronic heart failure, liver failure, old age. Dosage and administration Take orally, once a day. The appointment of a fixed combination of lisinopril and hydrochlorothiazide is usually recommended after selecting the dose of the individual components. In certain clinical conditions, direct replacement of monotherapy with a fixed combination may be considered. In arterial hypertension It is usually recommended to take Lysoretic one tablet (10 mg / 12.5 mg or 20 mg / 12.5 mg) once a day, preferably at the same time. If the desired therapeutic effect cannot be achieved within a period of 2 to 4 weeks, then in this case the dose of Lysoretic can be increased to two tablets (10 mg / 12.5 mg or 20 mg / 12.5 mg) once a day. Prior Diuretic Therapy Symptomatic hypotension may occur after the initial dose of Lysoretic and is more likely to occur in patients who are deficient in fluid and/or salt volume as a result of prior diuretic therapy. Treatment with diuretics should be discontinued 2-3 days before the start of therapy with Lysoretic. If this is not possible, treatment should be initiated with 5 mg lisinopril alone. Doses in Renal Insufficiency The lisinopril/hydrochlorothiazide combination is contraindicated in patients with severe renal impairment (creatinine clearance < 30 ml/min). In patients with creatinine clearance from 30 to 80 ml / min, it can only be used after selecting the dose of the individual components. In such patients, the recommended initial dose of lisinopril given as monotherapy is 5-10 mg (see Precautions section). Elderly patients Clinical studies of the combination of lisinopril and hydrochlorothiazide did not reveal an age relationship with any changes in efficacy and tolerability. See section "Doses in Renal Insufficiency" above. Children and adolescents (<18 years of age) The safety and efficacy of Lysoretic in children has not been established. Side effects In clinical studies, the same undesirable effects have been described that were previously observed with the separate appointment of lisinopril and hydrochlorothiazide. Lisinopril: The frequency of adverse reactions listed below was defined as follows: very common (≥ 10%), frequent (≥ 1%, < 10%), infrequent (≥ 0.1, < 1%), rare (≥ 0.01, < 0.1% ), very rare (< 0.01%), including isolated cases Blood and lymphatic system disorders Rare Decrease in hemoglobin, decrease in hematocrit. Very rare Bone marrow depression, anemia, thrombocytopenia, leukopenia, neutropenia, agranulocytosis, enlarged lymph nodes. Endocrine disorders Rare Antidiuretic hormone secretion disorders. Metabolic and nutritional disorders Very rare Hypoglycemia. Psychiatric disorders Uncommon Mood changes, depressive symptoms. Rare mental confusion. Nervous system disorders Common Dizziness, headache, fainting. Infrequent Paresthesia, dizziness, taste disturbance, sleep disturbance. Rare olfactory disorders. Cardiac disorders Uncommon Myocardial infarction or cerebrovascular accident, palpitations, tachycardia. Vascular disorders Common Orthostatic hypotension. Infrequent Raynaud's syndrome. Respiratory, mediastinal disorders Frequent Cough. Infrequent Rhinitis. Rare Bronchospasm, sinusitis, allergic alveolitis/eosinophilic pneumonia. Gastrointestinal disorders Frequent Diarrhea, vomiting. Infrequent Nausea, abdominal pain, dyspepsia. Rare Dry mouth. Very rare Pancreatitis. Hepatobiliary disorders Uncommon Elevated liver enzymes and bilirubin. Very rare Hepatitis - or hepatocellular sludge, cholestatic, liver failure. Skin and subcutaneous fat disorders Uncommon Rare Hypersensitivity, angioedema of the face, extremities, lips, tongue, glottis and/or larynx, urticaria, alopecia, psoriasis. Very rare Sweating, pemphigus, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme. Renal and urinary disorders Common Renal impairment. Rare Uremia, acute renal failure. Very rare Oliguria/anuria. Reproductive system and mammary gland disorders Uncommon Impotence. Rare Gynecomastia. General disorders Uncommon General malaise, asthenia. Laboratory findings Infrequent Increase in serum urea, creatinine, hyperkalemia. Rare Hyponatremia. Hydrochlorothiazide (frequency of side effects unknown) Infections or infestations: sialadenitis. Blood and lymphatic system disorders: leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anemia, hemolytic anemia, bone marrow depression. Metabolic and nutritional disorders: anorexia, hyperglycemia, glucosuria, hyperuricemia, electrolyte imbalance (including hyponatremia and hypokalemia), increased cholesterol, triglycerides, gout. Mental disorders: anxiety, depression, sleep disturbance. Nervous system disorders: loss of appetite, paresthesia, dizziness. Visual disturbances: xanthopsia, transient decrease in visual acuity, acute glaucoma. Hearing and balance disorders: labyrinth disorders, dizziness. Cardiovascular disorders: orthostatic hypotension, cardiac arrhythmias. Vascular disorders: necrotizing vasculitis. Respiratory and mediastinal disorders: respiratory distress syndrome (including pneumonia, pulmonary edema). Gastrointestinal disorders: dyspepsia, diarrhea, constipation, pancreatitis. Hepatobiliary system disorders: cholestatic jaundice. Skin and subcutaneous fat disorders: photosensitivity reactions, rash, discoid lupus erythematosus, urticaria, anaphylactic reactions, toxic epidermal necrolysis. Musculoskeletal disorders: muscle cramps, muscle weakness. Renal and urinary disorders: renal dysfunction, interstitial nephritis. General disorders: fever, weakness. OverdoseSymptoms: In case of an overdose of the combination of lisinopril / hydrochlorothiazide, the following symptoms are possible: a pronounced decrease in blood pressure, collapse, tachycardia, rapid breathing, palpitations, bradycardia, cough, dizziness, dryness of the oral mucosa, urinary retention, constipation, anxiety, impaired water and electrolyte balance, renal failure. Treatment: gastric lavage and / or administration of activated charcoal, restoration of water and electrolyte balance in a hospital setting. With a pronounced decrease in blood pressure, it is necessary to transfer the patient to the “lying” position on his back, with his legs raised up; further, measures should be taken to increase the BCC (administering a 0.9% solution of sodium chloride intravenously). If necessary, it is possible to use angiotensin II, with bradycardia - atropine or setting an artificial pacemaker. It is necessary to control diuresis, the concentration of urea, creatinine and electrolytes in the blood serum. Hemodialysis is effective, but high-flow polyacrylic dialysis membranes should be avoided. The appointment of digitalis preparations against the background of hypokalemia can lead to cardiac arrhythmias. Interaction with other medicinal products Potassium-sparing diuretics, potassium supplements and salt substitutes The potassium-sparing effect of thiazide diuretics is usually attenuated by the potassium-sparing effect of lisinopril. The use of potassium-sparing diuretics, potassium supplements, or potassium-containing salt substitutes can lead to a significant increase in serum potassium. If necessary, the concomitant use of Lysoretic and any of these drugs should be used with caution and frequent monitoring of serum potassium levels. Lithium Reversible increases in serum lithium concentrations and toxicity have been reported when lithium was co-administered with ACE inhibitors. Concomitant use of thiazide diuretics may increase the risk of lithium toxicity and exacerbate the already existing increased risk of lithium toxicity caused by ACE inhibitors. For this reason, the combination of lisinopril and hydrochlorothiazide with lithium is not recommended, and if combined administration is nevertheless necessary, careful monitoring of serum lithium levels should be carried out. Antidiabetic agents Co-administration of ACE inhibitors with antidiabetic drugs may enhance the effect of lowering blood sugar and lead to an increased risk of hypoglycemia. This phenomenon most often occurs during the first weeks of treatment and in patients with impaired renal function. NSAIDs (non-steroidal anti-inflammatory drugs) Simultaneous use with NSAIDs (i.e. selective COX-2 inhibitors, acetylsalicylic acid (> 3 g / day) and non-selective NSAIDs) may reduce the antihypertensive and diuretic effects of ACE inhibitors and thiazide diuretics. In patients with renal dysfunction treated with NSAIDs, the concomitant use of lisinopril may lead to further deterioration of renal function, including the possibility of developing acute renal failure and an increase in serum potassium levels. This combination should be used with caution, especially in the elderly. Patients should be adequately hydrated and have their kidney function monitored at the start of concomitant therapy (and regularly thereafter). Allopurinol The simultaneous administration of ACE inhibitors and allopurinol increases the risk of renal failure. Cyclosporine The simultaneous use of ACE inhibitors and cyclosporine increases the risk of renal failure and hyperkalemia. Lovastatin The simultaneous use of ACE inhibitors and lovastatin increases the risk of hyperkalemia. Trimethoprim Co-administration of ACE inhibitors and thiazides with trimethoprim increases the risk of hyperkalemia. Sotalol Hypokalemia caused by thiazide treatment may increase the risk of arrhythmias caused by sotalol. Cholestyramine, cholestipol Concomitant use of cholestyramine or cholestipol reduces the excretion of thiazide by 85% and 43%, respectively. If the concomitant administration of these drugs and a combination drug is indicated, the administration should be carried out separately with an interval of several hours. Tricyclic antidepressants / antipsychotics May enhance the hypotensive effect of ACE inhibitors. Drugs that cause pirouette-type heart rhythm disturbances Hypokalemia caused by thiazide treatment is a factor contributing to the development of pirouette-type tachycardia. Periodic serum potassium measurements and electrocardiogram recordings are recommended if hydrochlorothiazide is used concomitantly with drugs that are affected by changes in serum potassium concentration (for example, digitalis glycosides and antiarrhythmic drugs), as well as drugs that cause torsades de pointes. Corticosteroids, amphotericin B (parenteral), carbenoxolone, corticotropin (ACTH), or stimulant laxatives Hydrochlorothiazide may exacerbate electrolyte imbalances, particularly hypokalemia. Other antihypertensive agents Additive effects may occur. Sympathomimetics May reduce the antihypertensive effect of ACE inhibitors. The achievement of the desired effects should be monitored during careful monitoring of the patient’s condition. Allopurinol, procainamide, cytotoxic or immunosuppressive agents Concomitant use with ACE inhibitors may increase the risk of leukopenia. Calcium salts With simultaneous use with thiazide diuretics, there may be an increase in serum calcium levels due to a decrease in its excretion. Other agents Thiazides may increase the response to tubocurarine. Dual blockade of the renin-angiotensin-aldosterone system Based on available data, dual blockade of the RAAS with an ACE inhibitor, ARB II, 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 concomitant use of Aliskiren with an ACE inhibitor or ARB II is contraindicated. In some cases, when the combined use of an ACE inhibitor and ARB II is absolutely indicated, careful observation by a specialist and mandatory monitoring of kidney function, water and electrolyte balance, and blood pressure are necessary. Hemodialysis Since there are reports of a high frequency of anaphylactoid reactions in patients receiving dialysis using high-flow membranes and concomitant treatment with an ACE inhibitor, Lysoretic is not indicated in this group of patients. This combination should be avoided. Precautions Symptomatic hypotension may occur after the initial dose; this applies more to patients with fluid and/or salt deficiency due to diuretic therapy. Diuretics should be canceled 2-3 days before the start of Lisoretic. If this is not possible, treatment should be initiated with lisinopril 5 mg alone. After taking the first dose of Lysoretic, these patients should be closely monitored for objective and subjective symptoms of hypotension. Hypotension and electrolyte/water imbalance Symptomatic hypotension is rare in uncomplicated hypertension, but more likely in the presence of fluid or electrolyte imbalances, such as salt deficiency, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia, which may result from diuretic therapy, salt restriction , dialysis, vomiting, diarrhea. In such patients, regular monitoring of serum electrolytes should be carried out. Particular care is required when prescribing treatment to patients with coronary heart disease or cerebrovascular disease, since an excessive drop in blood pressure can lead to myocardial infarction or stroke. If hypotension occurs, the patient should be placed on their back and given an intravenous infusion of saline if necessary. A transient hypotensive response is usually not a contraindication to continuing therapy. After the restoration of plasma volume and blood pressure levels, it is possible to resume therapy or use the medicinal components separately. As with other vasodilators, Lysoretic should be used with caution in patients with aortic stenosis, mitral stenosis, or hypertrophic cardiomyopathy. Impaired renal function Thiazides are ineffective in patients with creatinine clearance < 30 ml / min (i.e., with moderate to severe renal insufficiency). Lysoretic should not be administered to patients with a creatinine clearance of 30-80 ml/minute until the doses of the combination tablet have been determined to be necessary during the selection of doses of the individual components. In some patients without a clear presence of renovascular disease, while the appointment of lisinopril and a diuretic, usually slight and transient increases in blood urea and serum creatinine developed. If this occurs during therapy with Lysoretic, treatment should be discontinued. It is possible to resume therapy at a reduced dosage or use any of the components separately. In some patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney treated with ACE inhibitors, increases in blood urea and serum creatinine were observed, which were usually reversible upon discontinuation of treatment. This is most likely to occur in patients with renal insufficiency. If renovascular hypertension is also present, there is an increased risk of severe hypotension and renal failure. Treatment in these patients should begin with low doses and their individual selection under close medical supervision. Since treatment with diuretics may exacerbate these conditions, renal function should be monitored during the first few weeks of treatment. There is no experience with the use of lisinopril in patients after kidney transplantation, therefore, the appointment of the drug Lizoretic in such patients is not recommended. Prior Diuretic Therapy Diuretic therapy should be discontinued 2-3 days prior to initiation of treatment with Lysoretic. If this is not possible, treatment should be started with lisinopril monotherapy at a dose of 5 mg. Liver disease Thiazides should be used with caution in patients with impaired liver function or progressive disease of this organ, since small changes in fluid and electrolyte balance can cause the development of hepatic coma. Rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is unclear. Patients receiving ACE inhibitors who develop jaundice or a significant increase in liver enzymes in the blood should stop taking the ACE inhibitor and be under appropriate medical supervision. Surgery / anesthesia When using drugs that reduce blood pressure in patients with major surgery or during general anesthesia, lisinopril may block the formation of angiotensin II. A pronounced decrease in blood pressure, which is considered a consequence of this mechanism, can be eliminated by increasing the volume of circulating blood. Before surgery (including dentistry), it is necessary to warn the anesthesiologist about the use of ACE inhibitors and exclude the use of ACE inhibitors 12 hours before the start of surgery. Metabolic and endocrine effects Thiazide diuretics may affect glucose tolerance. When using the drug Lysoretic in patients with diabetes mellitus receiving oral hypoglycemic agents or insulin, during the first month of therapy, it is necessary to regularly monitor the concentration of glucose in the blood. Against the background of therapy with thiazide diuretics, the concentration of cholesterol and triglycerides may increase. In some patients, thiazide diuretic therapy may exacerbate hyperuricemia and/or exacerbate gout. However, lisinopril enhances the excretion of uric acid by the kidneys, thereby counteracting the hyperuricemic effect of hydrochlorothiazide. Electrolyte imbalance In every patient receiving diuretics, it is necessary to periodically monitor the concentration of electrolytes in the blood serum. Hydrochlorothiazide can cause changes in circulating blood volume and electrolyte imbalance (hypokalemia, hyponatremia and hypochloremia). Signs of lack of fluid in the body and electrolyte imbalance are as follows: dry mouth, thirst, fatigue, lethargy, drowsiness, muscle pain or cramps, muscle fatigue, arterial hypotension, oliguria, tachycardia, gastrointestinal disorders (nausea or vomiting). Caution should be exercised when exercising, hot weather (risk of dehydration and an excessive decrease in blood pressure due to a decrease in circulating blood volume). Thiazides lead to increased excretion of magnesium, which can lead to hypomagnesemia. Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a temporary moderate increase in serum calcium. Severe hypercalcemia may be a manifestation of undiagnosed hyperparathyroidism. Before conducting a study of the function of the parathyroid glands, thiazide diuretics must be discontinued. Hypersensitivity/angioneurotic edema Angioedema of the face, extremities, lips, tongue, epiglottis and/or larynx has been reported rarely in patients treated with ACE inhibitors, including lisinopril, which may occur at any time during treatment. In this case, treatment with lisinopril should be discontinued as soon as possible and the patient should be observed until complete regression of symptoms. Even in cases where the edema covers only the tongue, without compromising the airway, the patient may require long-term monitoring, since therapy with antihistamines and glucocorticosteroids may not be sufficient. Angioedema with laryngeal edema can be fatal. When the tongue, epiglottis, or larynx are involved, airway obstruction may occur, so appropriate therapy (0.3-0.5 ml of 1:1,000 epinephrine (adrenaline) solution subcutaneously) and/or airway management should be initiated immediately. Patients with a history of angioedema unrelated to previous treatment with ACE inhibitors may be at an increased risk of developing it during treatment with an ACE inhibitor. In patients receiving thiazide diuretics, hypersensitivity reactions may occur with or without a history of allergies and asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides. Anaphylactoid reactions during desensitization procedures There are separate reports of the development of long-term, life-threatening anaphylactoid reactions in patients receiving ACE inhibitors during desensitizing therapy with hymenoptera venom (bees, wasps). ACE inhibitors should be used with caution in allergic patients undergoing desensitization procedures. The development of anaphylactoid reactions can be avoided by temporarily discontinuing the ACE inhibitor at least 24 hours before the start of the desensitization procedure. Anaphylactoid reactions during high-flow dialysis/membrane exposure during lipoprotein apheresis. Anaphylactoid reactions have been described in patients undergoing dialysis using high-flow membranes or low-density lipoprotein apheresis with dextran sulfate absorption. In these patients, a decision should be made to use a different type of dialysis membrane or a different class of drugs. Serum Potassium The effect of potassium excretion by thiazide diuretics is usually attenuated by the potassium-sparing effect of lisinopril. During treatment with ACE inhibitors, patients with kidney dysfunction, diabetes mellitus, patients taking potassium-sparing diuretics, potassium supplements and / or potassium-containing salt substitutes have an increased risk of hyperkalemia. Frequent monitoring of serum potassium is recommended (see section "Interaction with other medicinal products"). The use of a combination of an ACE inhibitor with a thiazide diuretic does not exclude the occurrence of hypokalemia. Regular monitoring of potassium should be carried out. Cough Cough has been reported with the use of an ACE inhibitor. Cough dry, prolonged, which disappears after discontinuation of treatment with an ACE inhibitor. In the differential diagnosis of cough, it is necessary to take into account the cough caused by the use of an ACE inhibitor. Neutropenia/agranulocytosis Neutropenia/agranulocytosis, thrombocytopenia, and anemia have been described in patients receiving ACE inhibitors. Neutropenia is rarely observed in patients with normal renal function and in the absence of other complicating factors. Lisinopril should be used with extreme caution in patients with vascular collagen disease, immunosuppressive therapy, treatment with allopurinol or procainamide, or a combination of these complicating factors, especially in patients with pre-existing impaired renal function. Some of these patients developed severe infections, in some cases not responding to intensive antibiotic therapy. Lysoretic is used in such patients, it is recommended to check the number of leukocytes in the blood and the blood formula before starting therapy, and then monitor every 2 weeks during the first 3 months of treatment and periodically thereafter. Inform patients that they should report any signs of infection before determining the WBC count. The combination of fixed doses of lisinopril and hydrochlorothiazide should be discontinued if neutropenia (neutrophil count less than 1000/mm3) is identified or suspected. Proteinuria Proteinuria may be more common in patients with impaired renal function or on relatively high doses of ACE inhibitors. Anti-doping test Please note that hydrochlorothiazide may cause a positive result in anti-doping tests. Ethnic differences ACE inhibitors are more likely to cause angioedema in black patients than in patients of other skin colors. When prescribing lisinopril as a component of a fixed dose combination in Afro-Caribbean patients, the therapeutic effect may be reduced. 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 an ACE inhibitor, ARB II, or Aliskiren cannot be recommended for any patient, especially those with diabetic nephropathy. In some cases, when the combined use of an ACE inhibitor and ARB II is absolutely indicated, careful observation by 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 and lactation Pregnancy Lisoretic is contraindicated during pregnancy. Taking the drug can cause disease and death of the fetus and newborn. ACE inhibitors When using ACE inhibitors in the second and third trimesters of pregnancy, toxic effects on the fetus and newborns have been established, including hypotension, hypoplasia of the skull of the newborn, anuria, reversible and irreversible renal failure, and death. Cases of oligohydroamnios, presumably caused by fetal renal failure, have also been reported. Oligohydroamnion in these cases was associated with contracture of the fetal limbs, craniofacial deformities, and the development of pulmonary hypoplasia. Cases of preterm birth, intrauterine growth retardation, and non-closure of the ductus arteriosus have also been reported, although it is not clear whether these were caused by ACE inhibitors. In addition, the use of ACE inhibitors during the first trimester of pregnancy has been associ