Lorista N 100 tablets p/o 100mg/12.5mg №15×4

Name:
Lorista H 100 tab. about. 100mg/12.5mg in bl. in pack. №15×4
Description:
White, oval, biconvex film-coated tablets. The main active ingredient Losartan + hydrochlorothiazide Release form film-coated tablets Dosage 100 mg + 12.5 mg Pharmacological action Angiotensin II receptor antagonist in combination with a diuretic. PharmacodynamicsCombined drug, the action of which is due to the properties of the components that make up its composition. Losartan, an angiotensin II type AT1 receptor antagonist Angiotensin II binds to AT1 receptors in various tissues (eg, vascular smooth muscle tissue, adrenal glands, kidneys, and heart) and causes a number of important biological effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. By blocking AT1 receptors, losartan has an antihypertensive effect. Dual blockade of the darenin-angiotensin-aldosterone system (PAAS) Two large randomized controlled trials (ONTARGET (Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and VA NEPHRON-D (The Veterans Affairs Nephropathy in Diabetes) investigated the use of ACE inhibitors (ACE inhibitors). ) in combination with an angiotensin II receptor blocker (ARB II).The ONTARGET study was conducted in patients with cardiovascular disease, cerebrovascular disease, or type 2 diabetes mellitus with evidence of target organ damage.The VA NEPHRON-D study was conducted in patients with type 2 diabetes mellitus and diabetic nephropathy.These studies did not show a significant positive effect of combination therapy on kidney function and/or cardiovascular disease outcome and mortality, while there was an increased risk of hyperkalemia, acute renal failure and/or gi sweating compared to monotherapy. Given the similar pharmacodynamic properties, these results may be relevant to other ACE inhibitors and ARBs II. Therefore, ACE inhibitors and ARBs II should not be co-administered to patients with diabetic nephropathy. The ALTITUDE (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints) trial was designed to determine the benefits of adding aliskiren to standard therapy with an ACE inhibitor or ARB II in patients with type 2 diabetes mellitus, chronic renal failure, or cardiovascular disease. The study was terminated early due to an increased risk of adverse outcomes. Stroke, cardiovascular mortality and adverse reactions (hyperkalemia, hypotension, renal dysfunction) were more frequently observed in the aliskiren group than in the placebo group. Hydrochlorothiazide is a thiazide diuretic. Acts at the level of the distal renal tubules, increasing the excretion of sodium and chloride ions. At the beginning of treatment with hydrochlorothiazide, the volume of fluid in the vessels decreases as a result of increased excretion of sodium and fluid, which leads to a decrease in blood pressure and a decrease in cardiac output. Due to hyponatremia and a decrease in fluid volume, the renin-angiotensin-aldosterone system is activated. A reactive increase in the concentration of angiotensin II partially limits the decrease in blood pressure (BP). With continued therapy, the hypotensive effect of hydrochlorothiazide is based on a decrease in total peripheral vascular resistance. The simultaneous use of losartan and hydrochlorothiazide has an additional antihypertensive effect. In addition, an angiotensin II receptor antagonist prevents or attenuates the metabolic effects of diuretic therapy and favorably affects structural changes in the heart and blood vessels. The simultaneous appointment of an angiotensin II receptor antagonist and hydrochlorothiazide is used in cases where each drug alone is not effective enough, or when monotherapy is carried out using the maximum dose of the drug, which increases the incidence of adverse events. This combination improves the therapeutic effect and reduces the likelihood of adverse events. The antihypertensive effect of the combination usually persists for 24 hours. Non-melanoma skin cancer. Based on the available data from epidemiological studies, there is a cumulative dose-dependent relationship between hydrochlorothiazide and NMSC. One study included a population of 71,533 cases of basal cell carcinoma and 8,629 cases of squamous cell carcinoma corresponding to 1,430,833 and 172,462 control populations, respectively. The use of high doses of hydrochlorothiazide (cumulatively 50,000 mg) was associated with an adjusted OR of 1.29 (95% CI: 1.23–1.35) for basal cell carcinoma and 3.98 (95% CI: 3.68–4 ,31) for squamous cell carcinoma. A clear dose-response relationship has been observed for both basal cell carcinoma and squamous cell carcinoma. Another study showed a possible association between lip cancer (SCC) and HCTZ exposure: 633 cases of lip cancer were matched against 63,067 control populations using a risk-based sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted OR of 2.1 (95% CI: 1.7-2.6) increasing to an OR of 3.9 (3.0-4.9) for the high cumulative dose (~25 000 mg) and OR 7.7 (5.7-10.5) for the highest cumulative dose (~100,000 mg). Pharmacokinetics: Losartan is well absorbed from the gastrointestinal tract. It undergoes significant metabolism during the “first pass” through the liver, forming an active metabolite (EXP-3174) and a number of inactive metabolites. Bioavailability is about 33%. Taking the drug with food does not have a clinically significant effect on its serum concentrations. The maximum concentration of losartan in the blood plasma is reached 1 hour after ingestion, and the maximum concentration of EXP-3174 – after 3-4 hours. More than 99% of losartan and EXP-3174 binds to plasma proteins, mainly to albumin. The volume of distribution of losartan is 34 liters. Practically does not get through a blood-brain barrier. Losartan is metabolized to form the active metabolite EXP-3174 (14%) and a number of inactive ones. The plasma clearance of losartan and EXP-3174 is approximately 10 ml/s (600 ml/min) and 0.83 ml/s (50 ml/min), respectively. The renal clearance of losartan and EXP-3174 is about 1.23 ml/s (74 ml/min) and 0.43 ml/s (26 ml/min). The half-lives of losartan and EXP-3174 are 2 hours and 6 to 9 hours, respectively. About 58% of the drug is excreted in the bile, 35% – by the kidneys. Hydrochlorothiazide is absorbed mainly in the duodenum and in the proximal small intestine. Absorption is 70% and increases by 10% when taken with food. The maximum concentration in blood serum is reached in 1.5-5 hours. The volume of distribution is about 3 l/kg. It binds to plasma proteins by 40%, accumulates in erythrocytes. It is not metabolized in the liver, 95% of the drug is excreted unchanged mainly by the kidneys. The renal clearance of hydrochlorothiazide in healthy volunteers and in patients with arterial hypertension is approximately 5.58 ml / s (335 ml / min). Hydrochlorothiazide has a biphasic elimination profile. The half-life in the initial phase is 2 hours, in the final phase (10-12 hours after administration) – about 10 hours. Penetrates through the placental barrier and accumulates in the amniotic fluid. The serum concentration of hydrochlorothiazide in the blood of the umbilical vein is almost the same as in the maternal blood. The concentration in the amniotic fluid exceeds that in the blood serum from the umbilical vein by 19 times. The level of hydrochlorothiazide in breast milk is very low. Hydrochlorothiazide has not been detected in the serum of infants whose mothers took it during breastfeeding. Indications for use The drug is indicated for the treatment of primary arterial hypertension in cases where adequate control of blood pressure cannot be achieved using losartan and hydrochlorothiazide used separately. Dosing and Administration The drug can be taken together with other antihypertensive drugs. The drug is taken regardless of the meal, with a glass of water. Arterial hypertension The combination of losartan and hydrochlorothiazide is not intended for initial therapy; the use is recommended in cases of lack of adequate control of blood pressure with the help of losartan and hydrochlorothiazide used separately. Titration of doses by components is recommended. When clinically necessary, it is advisable to consider switching from monotherapy to the use of a combination with a fixed dose. The usual maintenance dose is 1 tablet of Lorista N (losartan 50 mg / hydrochlorothiazide 12.5 mg) once a day. In case of insufficient therapeutic response, the dose may be increased to 1 tablet of Lorista ND (losartan 100 mg / hydrochlorothiazide 25 mg) 1 time per day. The maximum dose is 1 tablet of Lorista ND per day. As a rule, the hypotensive effect is achieved within 3-4 weeks after the start of therapy. Lorista H 100 (losartan 100 mg / hydrochlorothiazide 12.5 mg) is indicated for patients who are titrated to 100 mg losartan and require additional blood pressure control. Application for impaired renal function and in patients on hemodialysis Patients with moderate renal insufficiency (creatinine clearance 30-50 ml / min) do not need to adjust the initial dose. It is not recommended to prescribe this combination to patients on hemodialysis and with severe renal impairment (creatinine clearance < 30 ml / min) (section "Contraindications"). Conditions accompanied by depletion of intravascular volume Before using the combination of losartan / hydrochlorothiazide, correction of intravascular volume deficiency and / or sodium deficiency is required. Use in hepatic insufficiency Use is contraindicated in patients with severe hepatic insufficiency (section "Contraindications"), Elderly patients Dose adjustment in elderly patients is usually not required. Use in children and adolescents (< 18 years) There is no experience of use in children and adolescents, therefore, the appointment of this combination in this category of patients is not recommended. Use during pregnancy and lactation Pregnancy The use of ARA-II is not recommended in the first trimester of pregnancy (section "Precautions"). The use of ARA-II is contraindicated in the second and third trimesters of pregnancy (sections "Contraindications", "Precautions"). Epidemiological data on the risk of teratogenicity when taking ACE inhibitors in the first trimester of pregnancy do not allow a final conclusion, but some increased risk is not excluded. Although there are no controlled epidemiological data on the teratogenicity of ARA-II, similar risks cannot be excluded in this group of drugs. Unless it is not possible to replace ARA-II with another alternative therapy, patients planning pregnancy should be switched to therapy with drugs whose safety profile for pregnant women is well established. If pregnancy occurs, ARA-II should be discontinued immediately and other therapy prescribed if necessary. When using ARA-II in the second and third trimesters of pregnancy, a manifestation of fetotoxic action (impaired renal function, oligohydroamniosis, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia) was established. If ARA-II was taken from the second trimester of pregnancy, it is recommended to conduct an ultrasound scan to determine the condition of the kidneys and bones of the skull. In newborns whose mothers took ARA-II, it is necessary to carefully monitor blood pressure to prevent the possible development of hypotension (sections "Contraindications", "Precautions"). Hydrochlorothiazide Information on the use of hydrochlorothiazide during pregnancy is limited, especially in the first trimester. Data from animal studies are not sufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action, it can be argued that its use in the second and third trimesters of pregnancy can disrupt fetoplacental perfusion and cause such disorders in the fetus and newborn as jaundice, electrolyte imbalance and thrombocytopenia. Hydrochlorothiazide should not be used in gestational edema, gestational hypertension, or pregnancy toxicity due to the risk of decreased plasma volume and development of placental hypoperfusion in the absence of a positive effect on the course of the disease. Hydrochlorothiazide should not be used to treat primary hypertension in pregnant women, except in those rare cases when alternative therapy is not possible. Lactation There are no data on the use of the drug during breastfeeding, so its use during breastfeeding is not recommended. Alternative therapy should be prescribed using drugs that have proven themselves in terms of safety during lactation, especially when feeding newborns or premature babies. Hydrochlorothiazide Hydrochlorothiazide is excreted in breast milk in small amounts. Thiazide drugs in high doses, causing intense diuresis, can suppress lactation. The use of the drug during breastfeeding is not recommended. If necessary, the minimum dose of the drug should be prescribed. Precautions Losartan Angioedema Patients with a history of angioedema (swelling of the face, lips, throat and / or tongue) should be under strict medical supervision (section "Side Effects"). Hypotension and intravascular volume depletion Hypotension may occur in patients with hypovolemia and/or hyponatremia (due to intensive diuretic therapy, sodium-reduced diet, diarrhea or vomiting), especially after the first dose. These conditions require correction before starting treatment (sections "Method of application and doses", "Contraindications"). Electrolyte disorders Electrolyte disorders are common in patients with renal insufficiency, especially those with diabetes. Thus, during treatment, the concentration of potassium in the blood plasma and creatinine clearance should be monitored, in particular in patients with heart failure and creatinine clearance of 30-50 ml / min. The concomitant use of potassium-sparing diuretics, potassium supplements and salt substitutes containing potassium with losartan / hydrochlorothiazide is not recommended (section "Interaction with other medicinal products"). Impaired liver function Based on pharmacokinetic data demonstrating a significant increase in plasma concentrations of losartan in patients with liver cirrhosis, the drug should be administered with caution to patients with a history of mild or moderate hepatic dysfunction. Since there are no data on the therapeutic use of losartan in patients with severe hepatic insufficiency, the drug is contraindicated in this category of patients (sections "Dosage and administration", "Contraindications"). Impaired renal function As a result of suppression of the renin-angiotensin-aldosterone system, changes in kidney function, including renal failure, have been noted (in particular, in patients with dependence of renal function on the renin-angiotensin-aldosterone system: patients with severe heart failure or with chronic renal dysfunction) How and in the case of other drugs that act on the renin-angiotensin-aldosterone system, in patients with bilateral renal artery stenosis or stenosis of the artery to a single kidney, an increase in urea and creatinine levels was noted; these changes are reversible upon discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or arterial stenosis of a single kidney. Kidney transplantation There are no data on the use of the drug in patients undergoing kidney transplantation. Primary hyperaldosteronism In patients with primary hyperaldosteronism, as a rule, there is no reaction to antihypertensive drugs that suppress the renin-angiotensin system. Therefore, the combination of losartan/hydrochlorothiazide is not recommended. Coronary heart disease and cerebrovascular disorders As with the use of any other antihypertensive drugs, a significant decrease in blood pressure in patients with coronary heart disease and cerebrovascular disease can lead to myocardial infarction or stroke. Heart failure In patients with heart failure (with or without renal failure), there is an increased risk of severe hypotension and renal failure (often acute). Mitral or aortic valve stenosis, obstructive hypertrophic cardiomyopathy As with other vasodilators, special care should be taken when prescribing the drug to patients with aortic stenosis, mitral valve stenosis or obstructive hypertrophic cardiomyopathy. Ethnic features Angiotensin-converting enzyme inhibitors, losartan and other angiotensin antagonists have been shown to have a significantly lower hypotensive effect when used in dark-skinned patients, possibly due to the greater incidence of low renin activity in this population. Pregnancy Angiotensin II receptor inhibitors (ARA-II) should not be started during pregnancy. If possible, patients planning pregnancy should be given alternative antihypertensive therapies that have been shown to be safe during pregnancy. After establishing pregnancy, you should immediately stop using ARA-II and, if necessary, prescribe alternative therapy (sections "Contraindications" and "Pregnancy and lactation"). 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 in any patient, especially in patients with diabetic nephropathy (sections "Interaction with other drugs", "Pharmacological properties"). 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. Hydrochlorothiazide Hypotension and fluid and electrolyte imbalance As with other antihypertensive therapy, some patients may experience symptomatic hypotension. Therefore, a systematic analysis should be carried out to identify clinical signs of fluid and electrolyte imbalance (hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia), for example, after diarrhea or vomiting. In such patients, it is necessary to regularly monitor the content of electrolytes in the plasma. In hot weather, patients suffering from edema may experience dilutional hyponatremia. Influence on metabolism and endocrine system Therapy with thiazides can lead to a deterioration in glucose tolerance. You may need to adjust the dose of antidiabetic drugs, incl. insulin (section "Interaction with other drugs"). When using thiazide therapy, latent diabetes mellitus can manifest. Thiazides can reduce the excretion of calcium in the urine and thus lead to a short-term slight increase in its concentration in the blood plasma. Severe hypercalcemia may indicate latent hyperparathyroidism. Before the study of the function of the parathyroid glands, the use of thiazide diuretics should be discontinued. An increase in cholesterol and triglyceride levels may be associated with the use of thiazide diuretics. In some patients, thiazide therapy may precipitate hyperuricemia and/or an attack of gout. Since losartan reduces the concentration of uric acid, its combination with hydrochlorothiazide reduces the likelihood of hyperuricemia associated with the use of diuretics. Impaired liver function In patients with impaired liver function or progressive liver disease, thiazides should be used with caution, as they can cause intrahepatic cholestasis, and minor changes in fluid and electrolyte balance can provoke hepatic coma. The drug is contraindicated in patients with severe hepatic impairment (section "Contraindications"). Other features In patients taking thiazides, hypersensitivity reactions may occur, regardless of the presence of a history of allergies or bronchial asthma. There are reports of exacerbation or recurrence of systemic lupus erythematosus with the use of thiazide drugs. Non-melanoma skin cancer In two epidemiological studies based on data from the Danish National Cancer Registry, an increased risk of developing non-melanoma skin cancer (NMSC) (basal cell carcinoma (BCC) and squamous cell carcinoma (PSC)) was found after the use of higher total doses of hydrochlorothiazide. The photosensitizing effect of hydrochortiazid can be regarded as a possible mechanism for the development of NMSC. Patients taking hydrochlorothiazide should be informed of the risk of developing NMSC, the need for regular skin checks for new lesions, and the need to promptly report any suspicious skin growths. To reduce the risk of developing skin cancer, patients should be informed about possible preventive measures, such as limiting exposure to sunlight and UV rays, and in case of exposure, adequate skin protection should be applied. It is necessary to examine suspicious skin lesions as soon as possible, including histological examination of biopsy material. Patients with prior NMSC may also need to reconsider the need for hydrochlorothiazide. Excipients The drug contains lactose, therefore it is not recommended for patients with rare congenital galactose intolerance, lactase deficiency or glucose-galactose malabsorption. Interaction with other drugs Losartan Rifampicin and fluconazole reduce the concentration of the active metabolite. The clinical implications of this interaction have not been studied. As with other drugs that block angiotensin II or reduce its effect, the concomitant use of potassium-sparing diuretics (spironolactone, triamterene, amiloride), as well as supplements or salt substitutes containing potassium, can lead to an increase in the concentration of potassium in the blood plasma. The simultaneous use of these drugs is not recommended. As with other drugs that affect the excretion of sodium, it is possible to reduce the excretion of lithium from the body. Therefore, with the simultaneous use of ARA-II and lithium salts, the level of the latter in the blood plasma should be carefully monitored. With the combined use of ARA-II and non-steroidal anti-inflammatory drugs (NSAIDs) (for example, selective inhibitors of cyclooxygenase-2 (COX-2), acetylsalicylic acid in anti-inflammatory doses and non-selective NSAIDs), a weakening of the hypotensive effect may be observed. Concomitant use of ARA-II or diuretics with NSAIDs may increase the risk of impaired renal function, including acute renal failure, and lead to an increase in plasma potassium concentration (especially in patients with chronic impaired renal function). This combination should be used with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring renal function after initiation of concomitant therapy and periodically during treatment. In some patients with impaired renal function receiving NSAIDs, including COX-2 inhibitors, the concomitant use of ARA-II may lead to a further deterioration in renal function. However, this effect is usually reversible. Dual blockade of the renin-angiotensin-aldosterone system Clinical trials have shown that dual blockade of the renin-angiotensin-aldosterone system through the combined use of an ACE inhibitor, ARB II, or aliskiren is associated with a higher incidence of side effects such as hypotension, hyperkalemia, and impaired renal function ( including acute renal failure), compared with monotherapy (sections "Contraindications", "Precautions", "Pharmacological properties"). Based on the available data, dual blockade of the RAAS with an ACE inhibitor, ARB II, or aliskiren cannot be recommended for any patient, especially those with diabetic nephropathy. In patients with diabetes mellitus or moderate/severe renal impairment (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 observation by a specialist and mandatory monitoring of kidney function, water and electrolyte balance, and blood pressure are necessary. Other antihypertensive drugs include tricyclic antidepressants, antipsychotics, baclofen and amifostine. Combined use with these drugs increases the risk of hypotension. Hydrochlorothiazide Interactions may occur when thiazide diuretics and the following drugs are co-administered. Ethanol, barbiturates, narcotics and antidepressants Orthostatic hypotension may worsen. Antidiabetic drugs (oral and insulin) The use of thiazides may affect glucose tolerance, which may require dose adjustment of the antidiabetic drug. Metformin should be used with caution due to the risk of lactic acidosis caused by possible functional renal failure associated with the use of hydrochlorothiazide. Other antihypertensive drugs Additive effect. Cholestyramine and colestipol resins The absorption of hydrochlorothiazide is reduced in the presence of anion exchange resins. A single dose of cholestyramine or colestipol resins binds hydrochlorothiazide, reducing its absorption in the gastrointestinal tract by 85% and 43%, respectively. Corticosteroids, adrenocorticotropic hormone (ACTH) Pronounced decrease in the concentration of electrolytes (in particular, hypokalemia). Pressor amines (eg epinephrine) Possibly reduced response to pressor amines, but not sufficient to preclude their use. Skeletal muscle relaxants, non-depolarizing agents (eg, tubocurarine) Increased susceptibility to muscle relaxants is possible. Lithium Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity. Co-administration is not recommended. Medicines used to treat gout (probenecid, sulfinpyrazone, and allopurinol) Dosage adjustment of the uric acid excretion drug may be necessary because hydrochlorothiazide may increase plasma uric acid levels. You may need to increase the dose of probenecid or sulfinpyrazone. Thiazide preparations may increase the likelihood of hypersensitivity to allopurinol. Anticholinergics (eg, atropine, biperiden) Due to the deterioration of gastrointestinal motility and gastric emptying, the bioavailability of thiazide diuretics is increased. Cytotoxic agents (eg, cyclophosphamide, methotrexate) Thiazides may reduce urinary excretion of cytotoxic drugs and potentiate their bone marrow-suppressing effects. Salicylates When high doses of salicylates are used, hydrochlorothiazide may increase their toxic effects on the central nervous system. Methyldopa There have been isolated cases of hemolytic anemia with the combined use of hydrochlorothiazide and methyldopa. Cyclosporine Concomitant use of cyclosporine may increase the risk of hyperuricemia and gouty complications. Digitalis glycosides Hypokalemia or hypomagnesaemia caused by thiazide diuretics can lead to an attack of digitalis-induced cardiac arrhythmias. Drugs whose effect changes with changes in the level of potassium in the blood It is recommended to periodically determine the level of potassium and monitor the ECG in cases of combined use of the combination of losartan / hydrochlorothiazide and drugs whose effect depends on the concentration of potassium in the blood plasma (for example, digitalis glycosides and antiarrhythmic drugs), as well as drugs that cause "torsades de pointes" (ventricular tachycardia), including some antiarrhythmic drugs (hypokalemia is a predisposing factor for ventricular tachycardia): class Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide); class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide); certain antipsychotics (thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol); others (bepridil, cisapride, difemanil, erythromycin (for intravenous administration), halofantrine, mizolastine, pentamidine, terfenadine, vincamine (for intravenous administration). Calcium salts Thiazide diuretics can increase the concentration of calcium in the blood plasma by reducing its excretion. If necessary, prescribe these Calcium concentrations should be monitored and dose adjustments should be made according to the results Interference with laboratory results Thiazide diuretics may interfere with parathyroid function tests (see Precautions) Carbamazepine There is a risk of symptomatic hyponatremia Required clinical and biological observation of the patient. x the patient should be rehydrated. Amphotericin B (for parenteral administration), corticosteroids, ACTH, stimulant laxatives, or glycyrrhizin (from licorice root) Hydrochlorothiazide may exacerbate electrolyte imbalances, especially hypokalemia. Contraindications Hypersensitivity to losartan, sulfonamide derivatives (eg hydrochlorothiazide) or any of the excipients Pregnancy (sections "Precautions", "Pregnancy and lactation") Severe renal failure (creatinine clearance < 30 ml/min) Anuria Severe liver failure Resistant to Hypokalemia or hypercalcemia Refractory hyponatremia Symptomatic hyperuricemia/gout Hereditary angioedema or a history of angioedema after previous treatment with an ACE inhibitor or ARB < 60 ml / min / 1.73 m2) (sections "Pharmacological properties", "Interaction with other drugs") Composition One film-coated tablet contains Active substances: losartan potassium 100 mg, hydrochlor orthiazide 12.5 mg. Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate. Shell: hypromellose, macrogol 4000, titanium dioxide, talc. Overdose There is no specific information on overdose of the combination of losartan 100 mg / hydrochlorothiazide 12.5 mg. Treatment: symptomatic and supportive. In case of overdose, therapy with the drug should be discontinued, and the patient should be transferred under strict supervision. If the drug has been taken recently, it is recommended to induce vomiting, and also, using known methods, take preventive measures aimed at eliminating dehydration, electrolyte imbalance, hepatic coma and hypotension. Losartan Overdose data are limited. Possible, most likely signs: hypotension, tachycardia, bradycardia (due to parasympathetic (due to vagus) stimulation). If symptomatic hypotension occurs, supportive treatment should be given. Neither losartan nor its active metabolite can be removed from the body by hemodialysis. Hydrochlorothiazide The most common signs and symptoms are hypokalemia, hypochloremia, hyponatremia (due to low electrolyte levels) and dehydration (due to excessive diuresis). If digitalis was administered at the same time, hypokalemia can lead to an exacerbation of cardiac arrhythmias. How much hydrochlorothiazide is excreted during hemodialysis is unknown. Side effects Classification of the incidence of side effects according to the World Health Organization: very common (? 1/10); frequent (? 1/100 to < 1/10); infrequent (? 1/1000 to < 1/100); rare (? 1/10,000 to < 1/1,000); very rare (< 1/10000), frequency not known (cannot be estimated from the available data). The frequency of side effects is listed for individual organ systems. In the course of clinical studies of losartan potassium and hydrochlorothiazide, adverse events characteristic of this combination were not identified. The noted side effects were established earlier in the study of losartan potassium and / or hydrochlorothiazide. In controlled clinical trials for primary hypertension, dizziness was the only side effect associated with the use of the drug and was observed in 1% or more of patients. The following undesirable effects have been noted since the product was released to the market. Adverse reaction Frequency Hepatobiliary system disorders hepatitis Rare Laboratory findings hyperkalemia, elevated alanine aminotransferase rare , Henoch-Schonlein disease, ekhi