Co-Sentor tab. p / captivity. about. 100mg/12.5mg in bl. in pack. №10х3

Name:
Co-Sentor tab. p / captivity. about. 100mg/12.5mg in bl. in pack. No. 10×3 Main active ingredient Losartan + hydrochlorothiazide Release form Tablets Composition Each film-coated tablet contains: Co-Sentor® film-coated tablets, 50/12.5 mg Active ingredients: losartan potassium – 50 mg; hydrochlorothiazide – 12.5 mg. Excipients: Core: magnesium stearate, pregelatinized starch, lactose monohydrate, microcrystalline cellulose. Film shell: Opadry II 85F23426 orange (iron oxide black E 172, sunset yellow E 110, iron oxide yellow E 172, talc, macrogol 3350, titanium dioxide E 171, polyvinyl alcohol). Co-Sentor® film-coated tablets, 100/12.5 mg Active ingredient: losartan potassium – 100 mg; hydrochlorothiazide – 12.5 mg. Excipients: Core: magnesium stearate, pregelatinized starch, lactose monohydrate, microcrystalline cellulose. Film shell: Opadry II 85F27044 yellow (iron oxide black E 172, sunset yellow E 110, iron oxide yellow E 172, talc, macrogol 3350, titanium dioxide (E 171), polyvinyl alcohol). Co-Sentor® film-coated tablets, 100/25 mg Active ingredients: losartan potassium – 100 mg; hydrochlorothiazide – 25 mg. Excipients: Core: magnesium stearate, pregelatinized starch, lactose monohydrate, microcrystalline cellulose. Film shell: Opadry II 85F23426 orange (iron oxide black E 172, sunset yellow E 110, iron oxide yellow E 172, talc, macrogol 3350, titanium dioxide E 171, polyvinyl alcohol).
Description:
Co-Sentor® film-coated tablets 50/12.5 mg Round, biconvex, orange film-coated tablets debossed with “C23” on one side. Diameter about 9 mm. Co-Sentor® film-coated tablets, 100/12.5 mg Oval, biconvex, yellow film-coated tablets debossed with “C25” on one side. Other side without engraving. Co-Sentor® film-coated tablets, 100/25 mg Oval, biconvex, orange film-coated tablets debossed with “C24” on one side. The longest diameter is about 15.5mm, the shortest is about 8mm. Dosage 50/12.5 mg and 100/12.5 mg and 100/25 mg Pharmacological properties Pharmacodynamics Combined drug, has a hypotensive effect. Contains losartan potassium – an angiotensin II receptor antagonist (ATI subtype) and hydrochlorothiazide – a diuretic. Losartan + Hydrochlorothiazide It has been proven that the combined use of losartan and hydrochlorothiazide (HCT) has an additive effect on lowering blood pressure (BP), lowering it to a greater extent than either of the components separately. This is due to the complementary action of both components. In addition, as a result of its diuretic action, HCT increases plasma renin activity and aldosterone release, as well as reduces potassium and increases plasma angiotensin II levels. Losartan blocks all physiologically significant actions of angiotensin II and, through the inhibition of aldosterone, reduces the loss of potassium ions caused by diuretics. Losartan has been shown to have a mild and transient uricosuric effect. Hydrochlorothiazide slightly increases the concentration of uric acid in the blood plasma; the combination of losartan and HHT helps to reduce diuretic-induced hyperuricemia. The antihypertensive effect of losartan and HCT lasts for 24 hours and persists with continuous treatment. Despite a significant decrease in blood pressure, they do not have a clinically significant effect on heart rate. In clinical studies, after 12 weeks of using losartan + hydrochlorothiazide 50/12.5 mg, a decrease in diastolic blood pressure in the sitting position by an average of 13.2 mm Hg was recorded. Losartan and HCT effectively reduce blood pressure in men and women, in blacks and other races, in young and elderly (≥ 65 years) patients; the drug is effective for any degree of arterial hypertension. Losartan is a specific angiotensin II receptor antagonist (ATI subtype). Losartan and its main active metabolite have greater affinity for AT1 receptors than for AT2 receptors. The active metabolite is 10-40 times more active than losartan. In vitro and in vivo, losartan and its pharmacologically active carboxylic acid metabolite E-3174 block all physiologically significant effects of angiotensin II, regardless of the source or route of its synthesis. Does not inhibit kinase II – an enzyme that destroys bradykinin. Reduces total peripheral vascular resistance (OPSS), blood concentration of epinephrine and aldosterone, blood pressure, pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure. Discontinuation of treatment with losartan did not cause a sharp increase in blood pressure in patients suffering from arterial hypertension (rebound hypertension). It was found that the incidence of cough in patients treated with losartan or HCT was similar, while in the group treated with angiotensin-converting enzyme (ACE) inhibitors, the frequency was significantly higher. Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions, enhances the excretion of potassium ions, bicarbonate and phosphates by the kidneys. Lowers blood pressure by reducing the volume of circulating blood (BCC), changes in the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictor substances. After oral administration, increased diuresis is observed within 2 hours, reaching a peak after approximately 4 hours, and lasts from 6 to 12 hours, the antihypertensive effect persists for 24 hours. Pharmacokinetics Losartan is rapidly absorbed from the gastrointestinal tract. Bioavailability – about 33%. It has the effect of “first pass” through the liver, it is metabolized by carboxylation with the formation of an active metabolite. In addition to the active metabolite, inactive metabolites are also formed, including two major metabolites formed by hydroxylation of the butyl side chain and one minor, N-2-tetrazole-glucuronide. Both losartan and its active metabolite are more than 99% bound to plasma proteins, predominantly to albumin. The volume of distribution of losartan is 34 liters. The time to reach the maximum plasma concentration of losartan is 1 hour, the active metabolite is 3-4 hours after oral administration. Regular meals do not significantly affect the plasma concentration profile of losartan. The plasma clearance of losartan and its active metabolite is about 600 ml/min and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml/min and 26 ml/min, respectively. With oral administration of losartan, about 4% of the dose is excreted unchanged in the urine and about 6% of the dose is excreted in the urine as the active metabolite. Losartan and its active metabolite have linear pharmacokinetics with oral administration of losartan potassium at doses up to 200 mg. After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a terminal elimination half-life of approximately 2 hours and 6-9 hours, respectively. When taking the drug at a dose of 100 mg 1 time per day, there is no significant accumulation in the blood plasma of either losartan or its active metabolite. Excretion of losartan and its metabolites occurs with bile and urine. After ingestion of losartan labeled with carbon 14C, about 35% of the radioactive label is found in the urine and 58% in the feces. Neither losartan nor its active metabolite can be removed by hemodialysis. Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. The half-life is 5.8-14.8 hours. It is not metabolized in the liver. About 61% is excreted by the kidneys unchanged within 24 hours. Hydrochlorothiazide crosses the placental barrier and is excreted in breast milk. Does not penetrate the blood-brain barrier. Features of use in special groups of patients Losartan + Hydrochlorothiazide Significant differences in the concentration of losartan and its active metabolite in blood plasma, as well as the absorption of hydrochlorothiazide in young and elderly patients suffering from arterial hypertension, are not observed. Losartan After taking losartan orally in patients with mild to moderate alcoholic cirrhosis, the plasma concentration of losartan was 5 times higher, and the concentration of the active metabolite was 1.7 times higher compared with healthy volunteers. Indications for use Treatment of arterial hypertension in patients who are indicated for combination therapy; To reduce the risk of cardiovascular disease and mortality in patients with arterial hypertension and left ventricular hypertrophy. Contraindications Hypersensitivity to losartan and sulfonamide derivatives (such as hydrochlorothiazide) or to any of the components of the drug; Untreated hypokalemia or hypercalcemia; severe liver failure; cholestasis or obstruction of the biliary tract; Refractory hyponatremia; Symptomatic hyperuricemia/gout; Severe renal failure (creatinine clearance < 30 ml / min.); Anuria; Severe arterial hypotension; Hypovolemia (including against the background of high doses of diuretics); Pregnancy and lactation; Age up to 18 years (efficacy and safety not established). The concomitant use of angiotensin-converting enzyme inhibitors or RTA receptor blockers with Aliskiren in patients with diabetes mellitus or moderate / severe renal insufficiency (GFR < 60 ml / min / 1.73 m2) is contraindicated. The drug contains lactose, so patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this drug. Carefully; bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, hypovolemic conditions (including diarrhea, vomiting), hyponatremia (increased risk of arterial hypotension in patients on a low-salt or salt-free diet), hypochloremic alkalosis, hypomagnesemia, hypokalemia, connective tissue diseases ( including systemic lupus erythematosus), diabetes mellitus, gout, bronchial asthma, aggravated allergic history, hyperuricemia, hypercalcemia, mild to moderate hepatic insufficiency, aortic or mitral valve stenosis, obstructive hypertrophic cardiomyopathy, concomitant use with non-steroidal anti-inflammatory drugs (NSAIDs) , including cyclooxygenase-2 inhibitors (COX-2 inhibitors). Use during pregnancy and lactation Pregnancy Use during pregnancy is contraindicated, and if pregnancy is detected during the course of Co-Sentor® therapy, the use of the drug should be immediately discontinued and, if necessary, switched to alternative treatment. It is known that the use of ARAP during the second and third trimesters of pregnancy induces fetotoxicity (impaired renal function, oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If ARAP was used during the second trimester of pregnancy, an ultrasound examination is recommended to check kidney function and the condition of the bones of the skull. The condition of newborns whose mothers used ARAP should be checked frequently for the occurrence of arterial hypotension. Hydrochlorothiazide can reduce BCC and, accordingly, uteroplacental blood flow. Thiazides cross the placental barrier and have been found in cord blood. They can cause electrolyte disturbances in the fetus and possibly other reactions that have been observed in adults. Cases of neonatal thrombocytopenia and fetal or neonatal jaundice have been reported following maternal treatment with thiazides. Breast-feeding There is no data on whether losartan passes into breast milk. If necessary, the use of the drug during lactation, it is recommended to stop breastfeeding. Use in children The efficacy and safety of losartan for the treatment of arterial hypertension in children and adolescents have not been established. Dosage and administration Inside, regardless of the meal, with a glass of water. Co-Sentor® is not intended for use at the initial stage of therapy, the drug is intended for the treatment of patients whose blood pressure is not sufficiently controlled by losartan alone or hydrochlorothiazide alone. Usually the initial and maintenance dose of the drug is 50 mg of losartan + 12.5 mg of hydrochlorothiazide (1 tablet of Co-Sentor®) per day. For those patients who fail to achieve adequate blood pressure control at this dose, the dose may be increased to 1 tablet 100 mg / 12.5 mg or up to 1 tablet 100 mg / 25 mg 1 time per day of Co-Sentor®. The maximum dose is one tablet of Co-Sentor® 100 mg/25 mg once a day. In general, the antihypertensive effect is achieved within 3-4 weeks after the start of therapy. Co-Sentor® can be used with other antihypertensive drugs. Use in patients with impaired renal function or in patients on hemodialysis In patients with moderate renal impairment (creatinine clearance 30-50 ml / min), no initial dose adjustment is required. Patients on hemodialysis are not recommended to prescribe the drug. The use of the drug is contraindicated in patients with severe renal insufficiency (creatinine clearance < 30 ml / min). Use in patients with reduced circulating blood volume Decrease in circulating blood volume and / or a decrease in sodium content must be corrected before using Co-Sentor®. Use in patients with hepatic impairment Co-Sentor® is contraindicated in patients with severe hepatic impairment. Use in Elderly Patients In general, dose adjustment is not required for elderly patients. Side effects Side effects are limited to those observed previously with the use of losartan and / or hydrochlorothiazide. Dizziness is one of the most common side effects in the treatment of essential hypertension. The undesirable adverse reactions listed below are classified by system organ class and frequency: Very common: ? 1/10 Often: ? 1/100, <1/10 Uncommon: ? 1/1000, <1/100 Rare: ? 1/10,000, < 1/1,000 Very rare: < 1/10,000 Not known: cannot be estimated from the available data. Losartan Blood and lymphatic system disorders: Uncommon: anemia, Henoch-Schonlein disease, ecchymosis, hemolysis. Immune system disorders: Rare: anaphylactic reactions, angioedema, urticaria. Nutritional and metabolic disorders: Uncommon: anorexia, gout. Mental disorders: Often: insomnia. Infrequently: anxiety, anxiety disorder, panic disorder, confusion, depression, unusual dreams, sleep disturbances, drowsiness, memory impairment. Nervous system disorders: Often: headache, dizziness. Uncommon: irritability, paresthesia, peripheral neuropathy, tremor, migraine, syncope. On the part of the organ of vision: Infrequently: blurred vision, burning sensation / tingling in the eye, conjunctivitis, decreased visual acuity. Hearing and balance disorders: Uncommon: vertigo, tinnitus. Cardiac disorders: Uncommon: hypotension, orthostatic hypotension, sternalgia (chest pain), angina pectoris, 2nd degree AV block, cerebrovascular disorders, myocardial infarction, palpitations, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation ). Vascular disorders: Uncommon: vasculitis. Respiratory, thoracic and mediastinal disorders: Common: cough, upper respiratory infections, nasal congestion, sinusitis, sinus disease. Uncommon: throat discomfort, pharyngitis, laryngitis, dyspnea, bronchitis, epistaxis, rhinitis, airway congestion. Gastrointestinal disorders: Common: Abdominal pain, nausea, diarrhea, dyspepsia. Infrequently: constipation, toothache, dryness of the oral mucosa, flatulence, gastritis, vomiting. Hepatobiliary system disorders: Not known: liver dysfunction. Skin and subcutaneous tissue disorders: Uncommon: alopecia, dermatitis, dry skin, erythema, skin flushing, photosensitivity, pruritus, rash, urticaria, increased sweating. Musculoskeletal and connective tissue disorders: Common: muscle cramps, back pain, leg pain, myalgia. Uncommon: arm pain, joint swelling, knee pain, muscle and bone pain, shoulder pain, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness. Urinary system disorders: Uncommon: nocturia, frequent urination, urinary tract infections. Reproductive system and mammary gland disorders: Uncommon: decreased libido, impotence. Systemic disorders and complications at the injection site: Often: asthenia, fatigue, chest pain. Infrequently: swelling of the face, fever. Laboratory indicators: Often: hyperkalemia, a slight decrease in hematocrit and hemoglobin. Infrequently: a slight increase in the concentration of urea and creatinine in the blood serum. Very rarely: increased activity of "liver" enzymes and the concentration of bilirubin. Hydrochlorothiazide Blood and lymphatic system disorders: Uncommon: agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia. Immune system disorders: Rare: anaphylactic reactions. Nutritional and metabolic disorders: Uncommon: anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia. Psychiatric disorders: Uncommon: insomnia. Nervous system disorders: Often: headache. On the part of the organ of vision: Infrequently: blurred vision (transient), xanthopsia. Vascular disorders: Uncommon: necrotizing angiitis (vasculitis, cutaneous vasculitis). Respiratory, thoracic and mediastinal disorders: Infrequently: respiratory distress syndrome, including pneumonia and pulmonary edema. Gastrointestinal disorders: Uncommon: inflammation of the salivary glands, spasms, stomach irritation, nausea, vomiting, diarrhea, constipation. Hepatobiliary system disorders: Uncommon: jaundice (intrahepatic cholestasis), pancreatitis. Skin and subcutaneous tissue disorders: Uncommon: photosensitivity, urticaria, toxic epidermal necrolysis. Musculoskeletal and connective tissue disorders: Uncommon: muscle cramps. From the urinary system: infrequently: glucosuria, interstitial nephritis, impaired renal function, renal failure. Systemic disorders and complications at the injection site: Infrequently: fever, dizziness. In addition to these side effects, the following adverse reactions have been reported since the market launch of the drug: Hepatobiliary disorders: Rare: Hepatitis Laboratory findings: Rare: Hyperkalemia, elevated alanine aminotransferase (ALT). Overdose Symptoms: losartan - a pronounced decrease in blood pressure, tachycardia, bradycardia (as a result of vagal stimulation). Hydrochlorothiazide - loss of electrolytes (hypokalemia, hypochloremia, hyponatremia), as well as dehydration resulting from excessive diuresis. Treatment: symptomatic and supportive therapy. If the drug has been recently taken, gastric lavage should be performed; if necessary, correct water and electrolyte disturbances. Losartan and its active metabolites are not removed by hemodialysis. Interaction with other drugsLosartan The combined use of losartan with drugs whose main or side effect is to lower blood pressure, for example, tricyclic antidepressants, antipsychotics, baclofen, amifostine, may increase the risk of arterial hypotension. There was no clinically significant interaction with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole, erythromycin. There are reports that rifampicin and fluconazole reduce the concentration of the active metabolite. The clinical significance of these interactions has not been studied. As with other drugs that block angiotensin II or its action, concomitant use of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium preparations, or salt substitutes containing potassium can lead to hyperkalemia. The combined use of these drugs is not recommended. lithium preparations. Like other drugs that affect the excretion of sodium, losartan can reduce the excretion of lithium, so it is necessary to control the concentration of lithium in the blood serum when co-administered with angiotensin II receptor antagonists. Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), acetylsalicylic acid in anti-inflammatory doses can reduce the antihypertensive effect of losartan. In some patients with impaired renal function treated with NSAIDs (including selective COX-2 inhibitors), treatment with angiotensin II receptor antagonists may cause further deterioration of renal function, including the development of acute renal failure, which is usually reversible. The combined use of angiotensin II receptor antagonists or diuretics and NSAIDs may also lead to an increase in serum potassium. This combination of drugs should be used with caution, especially in elderly patients. Patients should drink sufficient fluids, and after the start of combination therapy, it is necessary to monitor kidney function and then carry it out regularly. 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, 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 monitoring is necessary. specialist and mandatory monitoring of kidney function, water and electrolyte balance, blood pressure Hydrochlorothiazide The following drugs can interact with thiazide diuretics when administered simultaneously: Barbiturates, narcotic drugs, antidepressants, ethanol - potentiation of the antihypertensive effect.Hypoglycemic agents (for oral administration and insulin) - dose adjustment of hypoglycemic agents may be required. Metformin should be used with caution due to the risk of lactic acidosis, due to possible renal failure associated with taking hydrochlorothiazide. Other antihypertensive drugs - an additive effect is possible. amine and colestipol reduces the absorption of hydrochlorothiazide by 85% and 43%, respectively. Pressor amines - perhaps a slight decrease in the effect of pressor amines, which does not prevent their use. Non-depolarizing muscle relaxants (for example, tubocurarine chloride) - it is possible to increase the effect of muscle relaxants. Lithium preparations - diuretics reduce the renal clearance of lithium and increase the risk of lithium intoxication, so simultaneous use is not recommended. Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol) Dose adjustments of medicines that promote the excretion of uric acid may be required, since hydrochlorothiazide can increase the concentration of uric acid in the blood serum. It may be necessary to increase the doses of probenecid or sulfinpyrazone. Co-administration of thiazides may increase the incidence of hypersensitivity to allopurinol. Anticholinergics (eg, atropine, biperiden) Increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate. Cytotoxic agents (eg, cyclophosphamide, methotrexate) Thiazides may decrease the renal excretion of cytotoxic drugs and increase their myelosuppressive effect. Salicylates In the case of high doses of salicylates, hydrochlorothiazide may increase their toxic effect on the central nervous system. Methyldopa There are separate reports of the occurrence of hemolytic anemia with the combined use of hydrochlorothiazide and methyldopa. Cyclosporine Co-administration with cyclosporine may increase the risk of hyperuricemia and gout-like complications. Digitalis preparations Hypokalemia or hypomagnesemia induced by thiazides may lead to the development of digitalis-induced cardiac arrhythmias. Drugs affected by changes in serum potassium Periodic monitoring of serum potassium and ECG is recommended when losartan + hydrochlorothiazide is co-administered with drugs that are affected by changes in serum potassium (eg, digitalis and antiarrhythmic drugs). drugs), as well as with the following drugs (including antiarrhythmics) that cause pirouette tachycardia, while hypokalemia is a predisposing factor for pirouette tachycardia (ventricular tachycardia): Class Ia antiarrhythmic drugs (for example, quinidine, hydroquinidine , disopyramide). Class III antiarrhythmic drugs (eg, amiodarone, sotalol, dofetilide, ibutilide). Certain antipsychotics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol). Other drugs (eg, bepridil, cisapride, diphemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, intravenous vincamine). Calcium salts Thiazide diuretics can increase the content of calcium in the blood serum due to a decrease in its excretion. If necessary, the appointment of calcium preparations, the dose is selected under the control of calcium in the blood serum. Effects on laboratory results Due to their effects on calcium excretion, thiazides may interfere with parathyroid function tests. Carbamazepine There is a risk of symptomatic hyponatremia. Clinical and biological monitoring is required. Iodine-contrast agents In the case of dehydration caused by taking diuretics, the risk of developing acute renal failure increases, especially with the introduction of high doses of iodine-containing drugs. Before the introduction of such funds, patients should be rehydrated. Amphotericin B (parenteral), corticosteroids, adrenocorticotropic hormone (ACTH), and laxatives Hydrochlorothiazide may exacerbate electrolyte disturbances, particularly hypokalemia. Precautions Losartan Angioedema Patients with a history of angioedema (swelling of the face, lips, larynx and/or tongue) should be closely monitored. Arterial hypotension and decrease in circulating blood volume In patients with reduced circulating blood volume or hyponatremia caused by intensive use of diuretics, salt restriction, diarrhea or vomiting, symptomatic hypotension may develop, especially after taking the first dose of the drug. These conditions must be corrected before taking Co-Sentor®. Electrolyte disorders Electrolyte disorders are quite common in patients with renal insufficiency and concomitant diabetes, or without it. Therefore, serum potassium and creatinine clearance should be closely monitored, especially in patients with heart failure and creatinine clearance of 30 to 50 ml/min. It is not recommended to take losartan + hydrochlorothiazide together with potassium-sparing diuretics, potassium supplements and salt substitutes. Impaired liver function According to pharmacokinetic data, in patients with cirrhosis of the liver, a significant increase in the concentration of losartan in the blood plasma was detected, therefore Co-Sentor® should be used with caution in patients with a history of mild to moderate hepatic insufficiency. There is no experience with the use of losartan in patients with severe hepatic insufficiency, therefore Co-Sentor® is contraindicated in this category of patients. Renal impairment Due to inhibition of the renin-angiotensin-aldosterone system, renal impairment, including renal failure, has been observed (particularly in patients whose renal function is dependent on the activity of the renin-angiotensin-aldosterone system, such as in patients with severe heart failure or patients with existing renal impairment). As with the use of other drugs that affect the renin-angiotensin-aldosterone system, with the use of losartan, an increase in the concentration of urea and creatinine in the blood serum was reported in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney; these changes were reversible after discontinuation of therapy. Care must be taken when prescribing losartan to patients with bilateral renal artery stenosis or arterial stenosis of a single kidney. 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. Kidney transplantation There is no experience with the use of the drug in patients who have recently undergone kidney transplantation. Primary hyperaldosteronism Patients with primary hyperaldosteronism usually do not respond to therapy with antihypertensive drugs that act through inhibition of the renin-angiotensin-aldosterone system, so the use of Co-Sentor® is not recommended. Ischemic heart disease (CHD) and cerebrovascular disease Like any antihypertensive drug, losartan can cause a significant decrease in blood pressure in patients with coronary artery disease and cerebrovascular disease, which can lead to myocardial infarction or stroke. Heart failure In patients with heart failure with or without concomitant renal failure, as with other drugs that act on the renin-angiotensin-aldosterone system, there is a risk of developing severe arterial hypotension and renal failure (often acute). Stenosis of the aortic and mitral valves, obstructive hypertrophic cardiomyopathy As with the use of other vasodilators, special care is required when prescribing the drug to patients suffering from stenosis of the aortic or mitral valve or obstructive hypertrophic cardiomyopathy. Ethnic differences ACE inhibitors, losartan, and other angiotensin antagonists have been observed to be less effective at lowering blood pressure in blacks than in non-blacks; perhaps this is due to the fact that among the representatives of the Negroid race suffering from arterial hypertension, persons with low renin activity predominate. Hydrochlorothiazide Hypotension and Fluid and Electrolyte Disturbances As with any antihypertensive drug, symptomatic hypotension may occur in some patients. It is necessary to monitor patients in order to timely detect clinical symptoms of fluid and electrolyte disorders, such as dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which can develop with intercurrent diarrhea or vomiting. In these patients, it is necessary to regularly monitor the content of electrolytes in the blood serum. In hot weather, patients suffering from edema may experience dilutional hyponatremia. Metabolic and endocrine effects Thiazide therapy may reduce glucose tolerance. In some cases, dose adjustment of hypoglycemic agents, including insulin, may be required. During treatment with thiazides, latent diabetes mellitus may manifest. Thiazides can reduce the excretion of calcium in the urine and cause an occasional and slight increase in serum calcium. Severe hypercalcemia may indicate the presence of latent hyperparathyroidism. Before examining the function of the parathyroid glands, thiazides should be discontinued. An increase in plasma cholesterol and triglyceride levels may also be associated with thiazide diuretic therapy. In some patients, treatment with thiazides may lead to hyperuricemia and/or the development of gout. Since losartan reduces the concentration of uric acid, its combination with hydrochlorothiazide reduces the severity of diuretic-induced hyperuricemia. Hepatic insufficiency Thiazides should be used with caution in patients with impaired liver function or progressive liver disease, as they can cause intrahepatic cholestasis, which, with minimal disturbance of water and electrolyte balance, can progress to hepatic coma. Co-Sentor® is contraindicated in patients with severe hepatic impairment. Other In patients taking thiazide diuretics, hypersensitivity reactions may occur even in the absence of symptoms of allergy or bronchial asthma in history. There is evidence of exacerbation or progression of systemic lupus erythematosus while taking thiazides. Excipients The preparation contains a dye "suns