Losartan plus tablets p/o 50mg/12.5mg №10×3

Name:
Losartan plus tablet coated p/o 50mg/12.5mg in blister pack No. 10*3
Description:
Tablets 50 mg + 12.5 mg: round tablets, white film-coated, biconvex shape. The main active ingredient Losartan + hydrochlorothiazide Release form Film-coated tablets Dosage 50 mg / 12.5 mg Pharmacological properties Pharmacodynamics Losartan plus is a combination of losartan and hydrochlorothiazide. The components of Losartan plus have an additive hypotensive effect, lowering the level of blood pressure (BP) to a greater extent than each of the components separately. It is believed that this effect is due to the complementary action of both components. Due to the diuretic effect, hydrochlorothiazide increases the activity of plasma renin (ARP), stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the content of potassium in the blood serum. Taking losartan blocks all physiologically significant effects of angiotensin II and, due to the suppression of the effects of aldosterone, may help reduce the loss of potassium associated with taking a diuretic. Losartan has a moderate and transient uricosuric effect. Hydrochlorothiazide causes a slight increase in the concentration of uric acid in the blood. The combination of losartan and hydrochlorothiazide helps to reduce the severity of hyperuricemia caused by taking a diuretic. The antihypertensive effect of losartan and hydrochlorothiazide 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. Losartan and hydrochlorothiazide 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 Losartan is a selective angiotensin II AT1 receptor antagonist (ARAII). Losartan and its active metabolite have greater affinity for AT1 receptors than for AT2 receptors. In terms of weight, the main metabolite is 10-40 times more active than losartan. In in vitro and in vivo studies, losartan and its pharmacologically active metabolite, carboxylic acid (E-3174), block all physiological effects of angiotensin II, regardless of its source or route of synthesis. Losartan does not inhibit angiotensin-converting enzyme (ACE, kininase II), which is responsible for the destruction of 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). Hydrochlorothiazide Hydrochlorothiazide is a thiazide diuretic. It affects the reabsorption of electrolytes in the distal tubules of the kidneys. Hydrochlorothiazide approximately equally increases the excretion of sodium and chloride ions. 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. When taken orally, the diuretic effect develops within 2 hours, reaches a peak after an average of 4 hours and lasts from 6 to 12 hours. Pharmacokinetics Losartan 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 ingestion. 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. Losartan and its active metabolite are not excreted from the body during hemodialysis. Hydrochlorothiazide Rapidly absorbed from the gastrointestinal tract. The half-life is 5.8-14.8 hours. 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. Pharmacokinetics in selected groups of patients Losartan – hydrochlorothiazide Elderly patients Plasma concentrations of losartan and its active metabolite and the rate of absorption of hydrochlorothiazide in elderly patients with arterial hypertension do not significantly differ from those in young patients with arterial hypertension. Losartan Gender In women with arterial hypertension, plasma concentrations of losartan are 2 times higher than in men with arterial hypertension. The concentrations of the active metabolite in men and women did not differ. Patients with impaired liver function In patients with mild to moderate alcoholic cirrhosis, plasma concentrations of losartan and its active metabolite were 5 and 1.7 times higher, respectively, than in healthy male volunteers. Patients with impaired renal function Plasma concentrations of losartan in patients with creatinine clearance above 10 ml/min did not differ from those in patients with unchanged renal function. The area under the concentration-time curve (AUC) of losartan in patients on hemodialysis was approximately 2 times higher than in patients with normal renal function. Plasma concentrations of the active metabolite in patients with impaired renal function or patients on hemodialysis. Losartan and its active metabolite are not excreted from the body during hemodialysis. Indications for use 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. Dosage and administration Losartan plus is taken orally, without chewing, with a glass of water. Eating does not affect the bioavailability of the drug. Losartan plus is not intended for use at the initial stage of therapy, this drug is intended for the treatment of patients whose blood pressure is not adequately controlled by losartan alone or hydrochlorothiazide alone. Dose titration of the individual components (losartan and hydrochlorothiazide) is recommended. In the presence of clinical feasibility, a direct transition from monotherapy to a fixed combination is possible. The usual initial and maintenance dose of Losartan Plus is 50 mg/12.5 mg. For those patients who fail to achieve adequate blood pressure control at this dose, the dose may be increased to 100 mg / 12.5 mg or up to 100 mg / 25 mg 1 time per day. The maximum dose is 100 mg/25 mg once a day. The antihypertensive effect is achieved within 3-4 weeks after the start of therapy. Losartan plus can be used with other antihypertensive drugs. Losartan plus tablets are indivisible and cannot be used to obtain a lower dosage. If it is necessary to use the drug at a dose of less than 50 mg / 12.5 mg, it is recommended to consider the possibility of using drugs containing losartan and hydrochlorothiazide in the appropriate dosage. It is recommended to follow the regimen prescribed by the doctor for taking the drug. If you miss a daily dose, you should simply continue taking it as usual. Do not take a double dose to make up for a forgotten one. Special patient populations The usual maintenance dose is 1 tablet of Losartan plus 50 mg/12.5 mg (Losartan 50 mg/Hydrochlorothiazide 12.5 mg). In case of insufficient therapeutic response, the dose may be increased to 1 tablet of the drug Losartan plus (Losartan 100 mg / Hydrochlorothiazide 25 mg) per day. The maximum daily dose is 1 tablet of Losartan plus 100 mg/25 mg. As a rule, the hypotensive effect is achieved within 3-4 weeks after the start of therapy. For patients titrated to 100 mg losartan and those requiring additional blood pressure control, Losartan Plus 100 mg/12.5 mg (Losartan 100 mg/Hydrochlorothiazide 12.5 mg) is indicated. 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 less than 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 the use of losartan plus. Use in patients with hepatic impairment Losartan plus is contraindicated in patients with severe hepatic impairment. Use in Elderly Patients In general, dose adjustment is not required for elderly patients. Use in children and adolescents under the age of 18 The efficacy and safety of Losartan plus in children and adolescents have not been established. Application during pregnancy and lactation Pregnancy The use of losartan, as well as other angiotensin II AT1 receptor antagonists, in the first trimester of pregnancy is not recommended and is contraindicated during the second and third trimesters of pregnancy. Epidemiological data do not allow clear conclusions about the risk of teratogenic effects from exposure to ACE inhibitors during the first trimester of pregnancy. However, a small increase in risk cannot be ruled out. Although there are no epidemiological data on the teratogenicity of ARAII, similar risks for this group of drugs cannot be ruled out. Unless the need for angiotensin II AT1 receptor antagonists has been established, patients planning pregnancy should be switched to alternative antihypertensive therapy with a known safety profile during pregnancy. If pregnancy occurs, ARAII should be stopped immediately and, if necessary, other therapy should be prescribed. It is known that the use of ARAII 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 ARAIIs were 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 ARA II should be checked frequently for the occurrence of arterial hypotension. Hydrochlorothiazide can reduce the volume of circulating blood and, accordingly, uteroplacental blood flow. Thiazides cross the placental barrier and are 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. Lactation There is no data on the excretion of losartan into breast milk. In this regard, it is not recommended to use Losartan plus during breastfeeding. Alternative treatment with medicinal products with a known safety profile during lactation is preferred, especially when feeding newborns and premature infants. Hydrochlorothiazide is excreted in small amounts into breast milk. High doses of thiazides, leading to a significant increase in urine output, may interfere with milk production. The use of the drug Losartan plus during breastfeeding is not recommended. If necessary, low doses should be prescribed. Influence on the ability to drive vehicles or potentially dangerous mechanisms No studies have been conducted on the effect of the drug on the ability to drive vehicles and mechanisms. However, when driving vehicles and other mechanisms, one should be aware of the possibility of developing adverse reactions such as dizziness and drowsiness, especially at the beginning of treatment and with an increase in the dose of the drug. 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 therapy with 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 the drug Losartan plus. 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 carefully monitored, especially in patients with heart failure and creatinine clearance between 30 ml/min and 50 ml/min. It is not recommended to take Losartan Plus concomitantly with potassium-sparing diuretics, potassium-containing 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 blood plasma was detected, therefore Losartan plus 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 the drug Losartan plus is contraindicated in this category of patients. Renal impairment As a result of inhibition of the renin-angiotensin-aldosterone system, impairment of renal function, including renal failure, has been noted (in particular in patients whose renal function depends on the activity of the renin-angiotensin-aldosterone system, for example, 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 arterial stenosis 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 Losartan plus 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 the drug Losartan plus is not recommended. Ischemic heart disease (CHD) and cerebrovascular disease As with any antihypertensive drug, Losartan plus 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 Arterial hypotension and disturbances in water and electrolyte balance. As with any antihypertensive drug, symptomatic hypotension may occur in some patients. Patients should be monitored for the timely detection of clinical symptoms of fluid and electrolyte imbalance (eg, dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia) that may 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. 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. Losartan plus 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. The medicinal product contains sodium in an amount of less than 1 mmol (23 mg) per dose, i.e. practically does not contain sodium. The medicinal product contains lactose and therefore should not be used in patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency, glucose-galactose malabsorption. Interaction with other drugsLosartan The combined use of losartan with drugs, the main or side effect of which 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 enough 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), 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 supervision of a specialist is necessary and mandatory monitoring of renal function, water and electrolyte balance, blood pressure Hydrochlorothiazide The following drugs may interact with thiazide diuretics when administered simultaneously. Barbiturates, narcotic drugs, antidepressants, ethanol - potentiation of antihypertensive action. Hypoglycemic agents (oral 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 hydrochlorothiazide. Other antihypertensive drugs - an additive effect is possible. Colestyramine and colestipol reduce 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-polarizing 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. Medicines affected by changes in serum potassium Periodic monitoring of serum potassium and ECG is recommended when Losartan Plus is co-administered with medicines that are affected by changes in serum potassium (e.g., digitalis and antiarrhythmic drugs), as well as with the following drugs (including antiarrhythmic drugs) that cause torsades de pointes, while hypokalemia is a predisposing factor for torsades de pointes (ventricular tachycardia): class Ia antiarrhythmic drugs quinidine, hydroquinidine , disopyramide); class III antiarrhythmic drugs (eg amiodarone, sotalol, dofetilide, ibutilide); certain antipsychotic drugs (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 it is necessary to prescribe 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. Contraindications Hypersensitivity to losartan, sulfonamide derivatives (such as hydrochlorothiazide) or any of the excipients that make up the medicinal product. Anuria. Severe renal dysfunction (creatinine clearance less than 30 ml / min). Severe liver dysfunction: severe liver failure, cholestasis or biliary obstruction. Refractory hyponatremia. Symptomatic hyperuricemia/gout. Untreated hypokalemia or hypercalcemia. Hypovolemia, including against the background of high doses of diuretics. Pregnancy and lactation (see section "Use during pregnancy and lactation"). The simultaneous use of Losartan plus with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR less than 60 ml / min / 1.73 m2). The drug is contraindicated in patients with angioedema and in patients who have developed angioedema during previous treatment with ACE inhibitors or angiotensin II receptor antagonists. Composition Each tablet 50 mg +12.5 mg contains: active substance: losartan potassium - 50 mg; hydrochlorothiazide - 12.5 mg; excipients: magnesium stearate, sodium stearyl fumarate, sodium starch glycolate (type A), lactose monohydrate, anhydrous colloidal silicon dioxide, microcrystalline cellulose; shell composition: Opadray II 85F18422 white (polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol, talc). OverdoseSymptoms of intoxication Losartan. The most likely manifestations of an overdose may be arterial hypotension and tachycardia. Bradycardia may occur due to parasympathetic (vagal) stimulation. Hydrochlorothiazide. Loss of electrolytes (hypokalemia, hypochloremia, hyponatremia), dehydration resulting from excessive diuresis. Treatment of intoxication. Symptomatic and supportive therapy. In case of overdose, stop taking the drug, transfer the patient under strict supervision. If the drug has been taken recently, it is recommended to induce vomiting, and to correct dehydration, electrolyte imbalance, hepatic coma and hypotension using known methods. Neither losartan nor its active metabolite is excreted from the body by hemodialysis. The degree of excretion of hydrochlorothiazide during hemodialysis has not been established. Side effects Side effects are limited to those previously observed with the use of losartan and / or hydrochlorothiazide. Dizziness is one of the most common side effects in the treatment of essential hypertension. The following undesirable effects are noted for one of the components of the drug and can potentially be applied to the losartan/hydrochlorothiazide combination. The frequency of adverse reactions is defined as follows: very often (> 1/10), often (> 1/100 – < 1/10), infrequently (> 1/1,000 – < 1/100), rarely (> 1/10,000 – < 1/1 000), very rare (< 1/10 000), unknown (cannot be determined from the available data). Losartan Blood and lymphatic system disorders: infrequently - anemia, Henoch-Schonlein disease, ecchymosis, hemolysis; unknown - thrombocytopenia. Immune system disorders: rarely - hypersensitivity: anaphylactic reactions, angioedema, including swelling of the larynx and glottis, with possible further obstruction of the airways, and / or swelling of the face, lips, pharynx and / or tongue, some patients have angioedema in history associated with taking other drugs, including ACE inhibitors, urticaria. Nutritional and metabolic disorders: infrequently - 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; infrequently - irritability, paresthesia, peripheral neuropathy, tremor, migraine, fainting. 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: infrequently - vertigo, tinnitus. Cardiac disorders: infrequently - arterial 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: infrequently - vasculitis. Respiratory, chest and mediastinal disorders: often - cough, upper respiratory tract infections, nasal congestion, sinusitis, sinus disease; infrequently - a feeling of discomfort in the throat, pharyngitis, laryngitis, dyspnea, bronchitis, epistaxis, rhinitis, airway congestion. Gastrointestinal disorders: often - abdominal pain, nausea, diarrhea, indigestion; infrequently - constipation, toothache, dryness of the oral mucosa, flatulence, gastritis, vomiting, intestinal obstruction; unknown - pancreatitis. Hepatobiliary system disorders: unknown - liver dysfunction. Skin and subcutaneous tissue