Active substanceHydrochlorothiazide + LosartanHydrochlorothiazide + Losartan Similar drugsTo uncover Blocktran® GT pills inwards PHARMSTANDART-FORESTRY, OJSC Russia Hydrochlorothiazide + Losartan pills inwards BIOKOM, CJSC Russia Hydrochlorothiazide + Losartan TAD pills inwards TAD Pharma GmbH Germany Hydrochlorothiazide + Losartan-Akrihin pills inwards AKRIKHIN HFK, JSC Russia Gizaar® pills inwards Merck Sharp and Doum B.V. Netherlands GISAAR® Forte pills inwards Merck Sharp and Doum B.V. Netherlands Lopaz plus pills inwards Zentiva c.s. Czech Republic Lozarel® Plus pills inwards Sandoz d. Slovenia Losartan H pills inwards ATOLL, LLC Russia Losartan-N Canon pills inwards CANONFARMA PRODUCTION, CJSC Russia Losartan / Hydrochlorothiazide-Teva pills inwards Teva Pharmaceutical Enterprises Co., Ltd. Israel Lorista® H pills inwards KRKA, dd, Novo mesto, AO Lorista® N 100 pills inwards KRKA, dd, Novo mesto, AO Lorista® ND pills inwards KRKA, dd, Novo mesto, AO Prezartan® H pills inwards Ipka Laboratories Ltd. India Simartan-N pills inwards Simpex Pharma Pvt Ltd. India Dosage form: & nbspFilm-coated tablets. Composition:1 tablet, film-coated, contains:Active substances: Losartan potassium - 50 mg, hydrochlorothiazide - 12.5 mg Excipients: Kernel: mannitol - 89.0 mg, microcrystalline cellulose - 210.0 mg, croscarmellose sodium - 18.0 mg, povidone - 7.0 mg, magnesium stearate - 3.5 mg.Film Sheath: hypromellose 2910/5 - 6.8597 mg, macrogol 6000 - 0.8 mg, talc - 1.9 mg, emetic simethicone - 0.3 mg, titanium dioxide - 0.1288 mg, dye Quinolin Yellow (E 104) 0.011 mg, Crimson Crude [Ponso 4R] (Pounceau 4R) (E 124) -0,0005 mg. Description:The oblong tablets are pale yellow, film-coated, with a half-and-half risk on both sides. Pharmacotherapeutic group:HYPOTHENNE COMBINED MEANS (angiotensin II receptor antagonist + diuretic) ATX: & nbspC.09.D.A.01 Losartan in combination with diuretics Pharmacodynamics:The combined drug has an antihypertensive effect. Contains losartan potassium - blocker (antagonist) of angiotensin II receptors (subtype AT1 ) (BRA) and hydrochlorothiazide -thiazide diuretic.Losartan / giduochlorothiazideLosartan and hydrochlorothiazide demonstrate a synergistic hypotensive effect, reducing blood pressure (BP) more than each of the components individually.It is assumed that this effect is the result of additive action of both components. In addition, as a result of diuretic action hydrochlorothiazide increases the activity of renin in plasma, the secretion of aldosterone, reduces the concentration of potassium in the blood plasma and increases the content of angiotensin II. The use of losartan blocks all physiologically significant actions of angiotensin II and reduces potassium losses associated with the use of a diuretic by inhibiting aldosterone.Losartan has an easy and short-term uricosuric effect. Hydrochlorothiazide leads to a moderate increase in uric acid in the plasma; The combination of losartan and hydrochlorothiazide contributes to the weakening of diuretic-induced hyperuricemia.The hypotensive effect of losartan / hydrochlorothiazide persists for 24 hours. Despite a significant reduction in blood pressure, the administration of losartan / hydrochlorothiazide does not significantly affect the heart rate (HR). In clinical studies, it was shown that after a 12-week therapy with losartan 50 mg / hydrochlorothiazide 12.5 mg, minimal diastolic blood pressure (measurement in the sitting position) decreased, on average, by 13.2 mm Hg. Art.Lozartan / hydrochlorothiazide effectively reduces blood pressure in men and women, negroid patients, as well as in other races, in young (<65 years) and elderly (≥ 65 years) patients and at any degree of arterial hypertension.LosartanLozartan is a synthetic blocker of angiotensin II receptors (type AT1). Angiotensin II, a potent vasoconstrictor, is the main active hormone of the renin-angiotensin-aldosterone system (RAAS) and the most important factor in the pathophysiology of hypertension. Angiotensin-II binds to AT1receptors found in many tissues (in smooth muscle vessels, in the adrenal gland, kidneys and heart) and causes a number of biologically important effects, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. Losartan selectively blocks AT1-receptors. Losartan and its pharmacologically active carboxyl metabolite E-3174 block all physiologically significant effects of angiotensin II in vitro and in vivo, regardless of the source and route of synthesis of the latter. Losartan does not have an agonistic effect and does not block the receptors of other hormones or ion channels, which play an important role in regulating the function of the cardiovascular system. Besides, losartan does not inhibit angiotensin-converting enzyme (ACE) (kininase-II), an enzyme that cleaves bradykinin. Consequently, there is no potentiation of undesirable effects mediated by bradykinin.With the use of losartan, the elimination of the negative reverse reaction of angiotensin II to renin secretion leads to an increase in the activity of the latter in the blood plasma. Increased renin activity leads to an increase in angiotensin-II concentration in the blood plasma. Despite such an increase, hypotensive activity and a decrease in plasma aldosterone concentration persist, indicating an effective blockade of angiotensin II receptors. After stopping the use of losartan, the renin activity in the plasma and the angiotensin II content return to the initial values within 3 days.AND losartan, and its main active metabolite possess a greater affinity for ATA receptors than to AT2receptors. The specified metabolite is 10-40 times more active than losartan.The incidence of cough is comparable in patients who took losartan or hydrochlorothiazide and significantly lower than with the use of an ACE inhibitor.In patients with arterial hypertension, proteinuria without the presence of diabetes and taking losartan, there was a significant decrease in proteinuria, fractional isolation of proteins and immunoglobulin G. Losartan stabilizes the glomerular filtration rate and reduces the filtration fraction. Generally, losartan causes a decrease in serum uric acid, which persists during prolonged therapy.Losartan does not affect vegetative reflexes and does not have a lasting effect on the content of noradrenaline in the blood plasma. In patients with left ventricular failure, 25 mg and 50 mg of losartan have positive hemodynamic and neurohumoral effects, characterized by an increase in the cardiac index and a decrease in pulmonary capillary wedge pressure, systemic vascular resistance, mean systemic blood pressure and heart rate, as well as concentrations of aldosterone and norepinephrine in plasma blood, respectively. The development of hypotension in these patients with heart failure was dose-dependent.Guiduochlorooctiazide - Thiazide diuretic.The mechanism of antihypertensive action of this group of drugs is not fully known. Thiazide diuretics affect the mechanisms of reabsorption of electrolytes in the tubules of the kidneys, directly increasing the excretion of sodium and chlorides in approximately equivalent amounts. The diuretic action of hydrochlorothiazide reduces the plasma volume, increases the renin activity in plasma and increases the secretion of aldosterone, followed by an increase in the concentration of potassium in the urine and loss of bicarbonates and a decrease in the potassium concentration in the blood plasma. The association of renin with aldosterone is mediated by angiotensin-P, and therefore the concomitant use of ARBs generally stops potassium loss due to thiazide diuretics.When administered, the diuretic effect of hydrochlorothiazide begins after 2 hours, reaches a maximum, on average, after 4 hours and lasts from 6 to 12 hours, the hypotensive effect persists for 24 hours. Pharmacokinetics:SuctionLosartanLosartan is well absorbed after ingestion and is subjected to a systemic metabolism with the formation of an active metabolite of carboxylic acid, as well as other inactive metabolites.Systemic bioavailability of losartan in the form of tablets is approximately 33%. The average maximum concentrations of losartan and its active metabolite are reached after 1 and 3-4 hours, respectively. When losartan was used concomitantly with standardized food, there was no clinically significant effect on the plasma concentration profile of the drug.Hydrochlorothiazide quickly absorbed from the gastrointestinal tract.DistributionLosartanhow losartan, and its active metabolite, more than 99% bind to plasma proteins, mainly with albumins. The volume of distribution of losartan is 34 liters. Studies have shown that losartan poorly penetrates or does not penetrate the blood-brain barrier.HydrochlorothiazideHydrochlorothiazide penetrates the placental, but does not penetrate the blood-brain barrier and is not secreted into breast milk.MetabolismLosartanAbout 14% of the dose of losartan, injected intravenously orally, is converted into its active metabolite. After intravenous or oral administration of 14C-labeled potassium losartan, the radioactivity of the circulating blood plasma is mainly due to losartan and its active metabolite.The minimum conversion of losartan to its active metabolite was observed in approximately 1% of study participants. In addition to the active metabolite, inactive metabolites are formed, including the 2 main metabolites that are formed by the hydroxylation of the butyl side chain, and the non-essential metabolite is N-2 tetrazol glucuronide.ExcretionLosartanThe plasma clearance of losartan and its active metabolite is approximately 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. When ingesting about 4% of the dose, losartan is excreted unchanged in the urine and about 6% of the dose is excreted in the urine as an active metabolite. The pharmacokinetics of losartan and its active metabolite is linear when administered in doses up to 200 mg of losartan per day.After oral administration, the concentrations of losartan and its active metabolite in the blood plasma decrease polyexponentially with a finite half-life of about 2 and 6-9 hours, respectively. When applying a dose of 100 mg once a day losartan and its active metabolite does not accumulate to a large extent in blood plasma.Lozartan and its active metabolite are excreted with bile and urine.In humans, after oral administration of 14C-labeled losartan, approximately 35% of radioactivity is excreted in the urine and 58% through the intestine.HydrochlorothiazideHydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. About 61% of the drug is excreted unchanged. According to the 24-hour determination of the hydrochlorothiazide concentration in plasma, its half-life is 5.8 -14.8 hours.Pharmacokinetics in special patient groups Losartan-hydrochlorothiazideThe concentration of losartan and its active metabolite in the blood plasma, as well as the absorption of hydrochlorothiazide in elderly patients with hypertension is significantdo not differ from the indices observed in patients of young age with arterial hypertension.LosartanIn patients with alcoholic cirrhosis of the liver of mild and moderate severity, the concentration of losartan and its active metabolite in the blood plasma was respectively 5 and 1.7 times higher than in young male volunteers.Lozartan and its active metabolite are not excreted during hemodialysis. Indications:- Arterial hypertension (in patients for whom combination therapy is optimal);- Reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy. Contraindications:- Hypersensitivity to any of the components of the drug or to other drugs that are derivatives of the sulfonamide;- refractory hypokalemia or hypercalcemia;severe liver dysfunction;- Obturation diseases of the biliary tract; cholestasis;- refractory hypoatria; symptomatic hyperuricemia and / or gout;- severe renal dysfunction (creatinine clearance (CK) less than 30 ml / min);- simultaneous use with preparations containing aliskiren, in patients with diabetes mellitus and patients with moderate and severe degree of renal failure (glomerular filtration rate [GFR] less than 60 ml / min / 1.73 m2 body surface area) (see the sections "Interaction with other drugs" and "Special instructions"); simultaneous use with angiotensin converting enzyme inhibitors (ACE inhibitors) in patients with diabetic nephropathy (see the sections "Interaction with other drugs" and "Special instructions"); anuria;- pregnancy and the period of breastfeeding;- age under 18 years (efficiency and safety not established). Carefully:With the following diseases / conditions: bilateral stenosis of the renal arteries or stenosis of the single kidney artery, hypovolemic conditions (including diarrhea, vomiting), hyponatremia (increased risk of hypotension in patients on a low-salt or salt-free diet), hypochloraemic alkalosis, hypomagnesemia. connective tissue diseases (including systemic lupus erythematosus); impaired liver function or progressive liver disease, diabetes mellitus, bronchial asthma (including history), a history of allergic anamnesis, an angioedema in history; simultaneous use with non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 inhibitors (COX-2 inhibitors); representatives of the Negroid race; heart failure and with concomitant renal failure of severe severity, severe chronic heart failure IV functional class according to the NYIIA classification,heart failure, accompanied by life-threatening arrhythmias, ischemic heart disease, hypertrophic obstructive cardiomyopathy; cerebrovascular diseases, hyperkalemia, patients over the age of 75 years, condition after kidney transplantation (no experience), aortic and mitral stenosis, primary hyperaldosteronism, acute myopia and / or angle-closure glaucoma. Pregnancy and lactation:Application in pregnancy Angiotensin II receptor blockersThe use of angiotensin II blockers during pregnancy is contraindicated. Patients planning a pregnancy should switch to alternative forms of antihypertensive therapy with an established safety profile. In the case of pregnancy diagnosis during treatment with LOZAP® PLUS should immediately stop and begin alternative treatment.It is known that the treatment of ARB during the second and third trimesters leads to fetotoxic effects (decreased kidney function, low blood pressure, ossification of the skull), as well as toxicity to the newborn (kidney failure, arterial hypotension, hyperkalemia).In the case of the drug LOZAP® PLUS in the second or third trimester of pregnancy, it is recommended to perform an ultrasound examination of the kidneys and the skull of the fetus.Children whose mothers during pregnancy took the drug LOZAP® PLUS, should be carefully monitored for the development of arterial hypotension. HydrochlorothiazideThe experience with hydrochlorothiazide during pregnancy, especially during the first trimester, is limited. Studies on animals are inadequate. Hydrochlorothiazide penetrates the placental barrier and is determined in the blood of the umbilical cord. Proceeding from the pharmacological mechanism of action of hydrochlorothiazide, its use during pregnancy can worsen fetoplacental blood flow and lead to violations from the fetus and newborn such as jaundice, electrolyte balance disorder and thrombocytopenia.Application of the drug LOZAP® PLUS is contraindicated during pregnancy. Application in the period of breastfeeding Angiotensin II receptor blockersIn connection with the lack of information on the use of the drug LOZAP® PLUS during the period of breastfeeding the appointment of the drug in this period is contraindicated.In the period of breastfeeding, alternative treatment with a more studied safety profile is preferred.HydrochlorothiazideHydrochlorothiazide is excreted in breast milk. Thiazides can cause intense diuresis and can inhibit the production of milk. Therefore, the use of the drug LOZAP® PLUS during the period of breastfeeding is contraindicated. Dosing and Administration:Inside, regardless of food intake. Arterial hypertension The drug LOZAP® PLUS is not used as an initial therapy in patients with arterial hypertension. The drug is designed to treat patients who do not manage to achieve adequate control of blood pressure when using only losartan or hydrochlorothiazide in monotherapy. Before prescribing the drug LOZAP® PLUS it is recommended to pre-titrate the doses of individual components (losartan and hydrochlorothiazide).Usually the initial and maintenance dose of the drug LOZAP® PLUS is 1 tablet per day. For those patients who do not manage to achieve adequate blood pressure control at this dosage, the dose of the drug LOZAP® PLUS can be increased to 2 tablets 1 time per day.The maximum dose is 2 tablets once a day. In general, the maximum hypotensive effect is achieved within 3-4 weeks after the start of treatment. Reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.Usually, the initial dose of losartan is 50 mg once a day. Patients who can not achieve target BP values when taking losartan 50 mg / day require treatment by a combination of losartan with low doses of hydrochlorothiazide (12.5 mg). If necessary, increase the dose of losartan to 100 mg / day in combination with hydrochlorothiazide at a dose of 12.5 mg / day (one tablet of the drug, the hypotensive effect is achieved within 3-4 weeks after the start of treatment. Reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.Usually, the initial dose of losartan is 50 mg once a day. Patients who can not achieve target BP values when taking losartan 50 mg / day require treatment by a combination of losartan with low doses of hydrochlorothiazide (12.5 mg).If necessary, increase the dose of losartan to 100 mg / day in combination with hydrochlorothiazide at a dose of 12.5 mg / day (one tablet of the drug LOZAP® PLUS once a day), in the future - to increase the dose to 2 tablets of the drug LOZAP® PLUS (50 mg + 12.5 mg) (total 100 mg of losartan and 25 mg hydrochlorothiazide) once a day. Patients with impaired renal function For patients with moderate renal dysfunction (CK 30-50 ml / min), initial dose adjustment is not required. The drug hypotensive effect is achieved within 3-4 weeks after the start of treatment. Reducing the risk of cardiovascular disease and mortality in patients with hypertension and left ventricular hypertrophy.Usually, the initial dose of losartan is 50 mg once a day. Patients who can not achieve target BP values when taking losartan 50 mg / day require treatment by a combination of losartan with low doses of hydrochlorothiazide (12.5 mg). If necessary, increase the dose of losartan to 100 mg / day in combination with hydrochlorothiazide at a dose of 12.5 mg / day (one tablet of the drug LOZAP® PLUS once a day), in the future - to increase the dose to 2 tablets of the drug LOZAP® PLUS (50 mg + 12.5 mg) (total 100 mg of losartan and 25 mg hydrochlorothiazide) once a day. Patients with impaired renal function For patients with moderate renal dysfunction (CK 30-50 ml / min), initial dose adjustment is not required. The drug LOZAP® PLUS is not recommended for patients on hemodialysis. Application of the drug LOZAP® PLUS in patients with severe impairment of kidney function (QC less than 30 ml / min) is contraindicated (see section "Contraindications"). Patients with reduced circulating blood volume (BCC)It is necessary to correct the BCC and / or the sodium content in the plasma prior to the use of the drug LOZAP® A PLUS.Patients with impaired hepatic function The drug LOZAP® PLUS is contraindicated for use in patients with severe impairment of liver function (see section "Contraindications").Patients of advanced age (over 65 years)There is no need for a special dose adjustment for elderly patients.Children and teensThe drug LOZAP® PLUS is contraindicated for use in children and adolescents under the age of 18 due to lack of data on efficacy and safety. Side effects:The incidence of adverse reactions was determined in accordance with the classification of the World Health Organization: very often (> 1/10); often (> 1/100 and up to <1/10); infrequently (> 1/1000 and up to <1/100); rarely (> 1/10000 and up to <1/1000); very rarely (<1/10000), the frequency is unknown (can not be calculated on the basis of available data).In clinical studies with losaran / hydrochlorothiazide. adverse reactions associated with a combination of drugs were not observed. Adverse reactions are limited to those previously observed with losartan and / or hydrochlorothiazide alone.In controlled clinical trials of the treatment of essential hypertension in patients who received losartan and hydrochlorothiazide, the only side effect, manifested with a frequency of 1% or more in comparison with placebo, was dizziness. In addition, there are other adverse reactions reported during the use of the combination of losartan / hydrochlorothiazide.Impaired nervous system: frequency is unknown - dysgeusia.Vascular disorders: frequency is unknown - dose-dependent orthostatic effect.Disturbances from the skin and subcutaneous tissues: frequency unknown - cutaneous form of systemic lupus erythematosus.Disorders from the liver and bile ducts: rarely - hepatitis. Impact on laboratory and instrumental research results: rarely, hyperkalemia, increased activity of "liver" transaminases.In addition, with the use of losartan / hydrochlorothiazide,the following adverse reactions observed with each of the components were observed.LosartanViolations from the blood and lymphatic system: infrequently -anemia, Shenlaine-Henoch disease, ecchymosis, hemolysis; frequency unknown - thrombocytopenia.Immune system disorders: rarely - hypersensitivity reactions (anaphylactic reactions, angioedema, including swelling of the larynx and vocal cords with the development of airway obstruction and / or swelling of the face, lips, pharynx, and / or tongue); some of these patients had an angioedema development in the anamnesis with other drugs, including ACE inhibitors.Disorders from the metabolism and nutrition: infrequently - anorexia, gout.Disorders of the psyche: often - insomnia; infrequent anxiety, anxiety disorder, panic disorder, confusiondepression, unusual dreams, sleep disturbance, drowsiness, memory impairment.Impaired nervous system: often - headache, dizziness; infrequent - increased excitability, paresthesia, peripheral neuropathy, tremor, migraine, synconal states.Disorders from the side of the organ of vision: infrequent - blurred vision, burning sensation in the eyes, conjunctivitis, decreased visual acuity.Hearing disorders and labyrinthine disturbances: infrequently - vertigo, ringing in the ears.Heart Disease: infrequent decrease in blood pressure, orthostatic hypotension, pain in the sternum, stenocardia, atrioventricular blockade of the 2nd degree, cerebral blood flow disorder, myocardial infarction, palpitations, arrhythmias (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation).Vascular disorders: infrequently - vasculitis.Disturbances from the respiratory system, chest and mediastinal organs: often - cough, upper respiratory tract infections, nasal congestion, sinusitis; infrequently - a feeling of discomfort in the pharynx, pharyngitis, laryngitis, dyspnoea, bronchitis, nosebleeds, rhinitis, obstruction of the respiratory tract.Disorders from the gastrointestinal tract: often - abdominal pain, nausea, diarrhea, indigestion; infrequently, the pain, toothache, dry mouth, flatulence, gastritis, vomiting, intestinal obstruction.Disorders from the liver and bile ducts: frequency unknown - impaired liver function. Disturbance from the skin and subcutaneous tissues: infrequently - alopecia, dermatitis, dry skin, erythema, hyperemia, photosensitivity, skin itching, urticaria, skin rash, increased sweating.Disturbances from the musculoskeletal and connective tissue: often - muscle cramps, back pain, pain in the lower extremities, myalgia; infrequently - pain in the upper extremities, swelling of the joints, pain in the knee joint area, pain in the shoulder region, pain in the muscles and bones, joint stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness; frequency is unknown rhabdomyolysis.Disorders from the kidneys and urinary tract: often - renal dysfunction, kidney failure; infrequently - nocturia, frequent urination, urinary tract infections.Violations of the genitals and breast: infrequently - decreased libido, erectile dysfunction.General disorders and disorders at the site of administration: often - asthenia, fatigue, chest pain; infrequently - puffiness of the face, peripheral edema, fever; frequency unknown - hrippopodobnye symptoms, weakness. Laboratory and instrumental data: often - hyperkalemia, a slight decrease in hematocrit and hemoglobin, hypoglycemia; infrequently, a slight increase in the concentration of urea and creatinine in the blood plasma; very rarely - increased activity of "liver" transaminases and bilirubin; frequency is unknown - hyponatremia. HydrochlorothiazideViolations from the blood and lymphatic system: infrequently - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopaia.Immune system disorders: rarely anaphylactic reactions.Disorders from the metabolism and nutrition: infrequently - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia.Disorders of the psyche: infrequently - insomnia. Impaired nervous system: often a headache.Disorders from the side of the organ of vision: infrequently - a temporary decrease in visual acuity, xantopsy.Vascular disorders: infrequently, necrotic vasculitis, cutaneous vasculitis.Disturbances from the respiratory system, chest and mediastinal organs: infrequently - a respiratory distress syndrome, including pneumoiitis and non-cardiogenic pulmonary edema.Disorders from the gastrointestinal tract: infrequently - sialadenitis, spasms, gastritis, nausea, vomiting, diarrhea, constipation.Disorders from the liver and bile ducts: infrequently - cholestatic jaundice, cholecystitis, pancreatitis.Disturbance from the skin and subcutaneous tissues: infrequently photosensitivity, hives, toxic epidermal necrolysis. Disturbances from the musculoskeletal and connective tissue: infrequently - muscle cramps.Disorders from the kidneys and urinary tract: infrequently - glucosuria, interstitial nephritis, impaired renal function, renal failure.General disorders and disorders at the site of administration: infrequently - fever, dizziness. Overdose:There is no data on the specific treatment of overdose with LOZAP® A PLUS. Administration of the drug LOZAP® PLUS must be discontinued, and the patient must be monitored. Overdose shows symptomatic therapy: gastric lavage in case the drug is taken recently, as well as eliminating dehydration, electrolyte disorders and lowering blood pressure by standard methods (recovery of bcc and water-electrolyte balance).LosartanThe most frequent manifestations of overdose are a marked decrease in blood pressure and tachycardia; Bradycardia can be a consequence of parasympathetic (vagal) stimulation. In the case of symptomatic arterial hypotension, supportive infusion therapy is indicated. Losartan and its active metabolite are not excreted by hemodialysis.HydrochlorothiazideThe most frequent symptoms of overdose are a consequence of deficiency of electrolytes (hypokalemia, hypochloraemia, hyponatremia) and dehydration due to excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.There is no specific antidote for hydrochlorothiazide overdose. It is not established to what extent hydrochlorothiazide can be removed from the body by hemodialysis. Interaction:Cases of a decrease in the concentration of the active metabolite in the combined use of rifampicin and fluconazole have been described. Assessment of the clinical data of such interactions was not conducted.As with other drugs blocking angiotensin II or its effects, the simultaneous use of potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations or potassium-containing salt substitutes can lead to an increase in potassium levels in the blood plasma. Joint use of these drugs is not recommended.As with other drugs that affect the excretion of sodium, the drug may slow the excretion of lithium. Therefore, with the simultaneous administration of lithium salts and ARAII, the concentration of lithium salts in the blood plasma must be carefully monitored.With simultaneous use of ARAII and NSAIDs, for example, selective inhibitors of cyclooxygenase-2 (COX-2), acetylsalicylic acid in doses,used for anti-inflammatory effect, and nonselective NSAIDs, there may be a weakening of the antihypertensive effect of the drug LOZAP® A PLUS.The simultaneous use of ARAII or diuretics and NSAIDs may be the cause of an increased risk of impaired renal function, including acute renal failure and an increase in potassium levels in the blood plasma, especially in patients with initial renal impairment. Combination treatment should be administered with caution, especially in elderly patients. It is necessary to ensure adequate hydration of patients and monitor kidney function after the initiation of combined treatment and periodically during the treatment.In some patients with impaired renal function receiving NSAID treatment, including selective COX-2 inhibitors, the simultaneous use of ARAII can exacerbate renal dysfunction. These effects are usually reversible. There is evidence of that. that the simultaneous use of ACE inhibitors, ARAII or aliskiren increases the risk of arterial hypotension, hyperkalysis, and and impaired kidney function (including acute renal failure) when compared with the use of a single drug that affects RAAS. Application of the drug LOZAP® PLUS in conjunction with aliskiren is contraindicated in patients with diabetes mellitus or in patients with moderate to severe renal failure (GFR less than 60 mL / min / 1.73 m2 surface area of the body) and ns recommended to other patients (see section "Contraindications").Application of the drug LOZAP® PLUS in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and ns is recommended to other patients (see the section "Contraindications"),Other drugs that cause a decrease in blood pressure, such as tricyclic antidepressants, antipsychotics, baclofen, amifostine: simultaneous application of the drug LOZAP® PLUS with these drugs can increase the risk of developing arterial hypotension.HydrochlorothiazideWith simultaneous administration with thiazide diuretics, interaction with the following substances can be observed:Ethanol, barbiturates, drugs or antidepressants The risk of orthostatic hypotension may increase. Hypoglycemic agents (insulin and preparations for oral administration)Treatment with thiazide diuretics can affect glucose tolerance.It may be necessary to adjust the dose of irrotiviabetic drugs.Metformin should be used with caution because of the risk of developing lactic acidosis caused by a possible functional renal failure associated with the use of hydrochlorothiazide.Other antihypertensive drugs Additive effect.Kolestyramine and colestipol In the presence of ion-exchange resins, hydrochlorothiazide absorption is impaired. Taking a single dose of colestyramine or colestipol leads to the binding of hydrochlorothiazide and a decrease in its absorption from the gastrointestinal tract by 85% and 43%, respectively.Corticosteroids, adrenocorticotropic hormone (ACTT) It is possible to aggravate the deficiency of electrolytes, especially hypokalemia.Pressor amines (eg, epinephrine) Possible reduction of the effect of pressor amines, however, does not exclude their use.Non-depolarizing muscle relaxants (eg, tubocurarine chloride) It is possible to increase the effect of muscle relaxants.Lithium preparationsDiuretics reduce renal clearance of lithium and significantly increase the risk of its toxic effects. It is advisable to avoid the simultaneous use of hydrochlorothiazide withlithium preparations. Medicines used to treat gout (probenecid, sulfypyrazone and allopurinol)It may be necessary to adjust the dose of antidotal drugs, since hydrochlorothiazide can increase the concentration of uric acid in the blood plasma. Co-administration with thiazides can increase the incidence of hypersensitivity reactions by allopurinol. Anticholieergic drugs (for example, atropine, piperidine)It is possible to increase the bioavailability of thiazide diuretics by reducing the motility of the gastrointestinal tract and the rate of gastric emptying. Cytotoxic drugs (eg, cyclophosphamide, methotrexate)Thiazide diuretics can inhibitthe excretion of cytotoxic drugs through the kidneys and to enhance their migratory effect.SalicylatesIn the case of high doses of salicylates hydrochlorothiazide can enhance their toxic effects on the central nervous system.MethyldopaSingle cases of development of hemolytic anemia in patients simultaneously receiving hydrochlorothiazide and methyldopa. CyclosporinConcomitant treatment with cyclosporine may increase the risk of hyperuricemia and complications of gout.Cardiac glycosidesHypokalemia or hypomagnesemia caused by thiazide diuretics can contribute to the development of arrhythmias induced by cardiac glycosides.Drugs, the effect of which is influenced by changes in the potassium content in the blood plasmaWith the simultaneous administration of the drug LOZAP® PLUS with medicines, the effect of which is influenced by changes in the potassium content in the blood plasma (for example, cardiac glycosides and antiarrhythmic drugs),it is recommended to conduct regular monitoring of potassium content in blood plasma and ECG monitoring. These measures are also recommended when using the drug LOZAP® PLUSO with the following medicines that can cause pyruvic (ventricular) tachycardia (including antiarrhythmic), as hypokalemia is a factor predisposing to the development of pirouette tachycardia:- antiarrhythmic drugs of class 1A (for example, quinidine, hydroquinidine, disopyramide);- antiarrhythmic drugs of class III (for example, amiodarone, dofetilide, ibutilide); sotalol;- some neuroleptics (for example, thioridazine, chlorpromazine, levomepromazine, trifluonerazine, cyamemazine, sulpride. sulphoprid. amisulpride, tiapride, imimoside, haloperidol, droperidol);- other (for example, bepridil., cisapride, difemanyl, erythromycin intravenous, halofantrine, misolastine, pentamidine, terfenadia, wincamine intravenously). Salts of calciumThiazide diuretics can increase the calcium content in the blood plasma by reducing the excretion of calcium by the kidneys. If a patient takes calcium preparations, it is necessary to monitor the calcium content in the blood plasma and, accordingly, adjust the dosage of calcium preparations.Influence on the results of laboratory studiesIn connection with the effect on calcium metabolism, thiazides can distort the results of tests to assess the function of parathyroid glands.CarbamazepineThere is a risk of symptomatic hyponatremia.It is necessary to conduct clinical observation and laboratory monitoring of sodium in blood plasma in patients taking carbamazepine. Iodine-containing contrast agents In the case of dehydration caused by the use of diuretics, the risk of developing acute renal failure increases, especially when taking high doses of iodine preparations. Before their introduction, patients should be rehydrated.Amphotericip B (for parenteral administration), corticosteroids, adrenocorticotropic hormone, stimulating laxatives or glycyrrhizin (found in licorice)Hydrochlorothiazide can cause the development of a deficiency of electrolytes, especially hypo-potassium. Special instructions:LosartanAngioedemaPatients with cases of angioedema in the anamnesis (swelling of the face, lips, throat and / or tongue) should be closely monitored. Arterial hypotension and decreased circulating blood volume In patients with hypovolemia and / or a reduced content of sodium in the blood plasma, resulting from the intensive use of diuretics, restriction of consumption of table salt from beggars, diarrhea or vomiting may develop symptomatic arterialhypotension (especially after taking the first dose). It is necessary to correct such conditions beforeof the drug LOZAP® A PLUS.Violations of the water-electrolyte balanceViolations of the water-electrolyte balance often occur in patients with impaired renal function, so the potassium content in the blood plasma and QC are subject to close monitoring,especially carefully monitor the condition of patients with heart failure and CC in the range of 30-50 ml / min. It is not recommended to use the joint drug LOZAP® PLUS with potassium-sparing diuretics, potassium preparations and potassium-containing salt substitutes.Impaired liver functionThese pharmacokinetics indicate a marked increase in losartan concentrations in plasma in patients with cirrhosis of the liver.Based on these data, the drug LOZAP® PLUS should be used with caution in patients with a history of mild to moderate mild liver failure. Experience with losartan in patients with severe liver dysfunction is absent. Therefore, the drug LOZAP® PLUS is contraindicated in patients with severe impairment of liver function. Impaired renal function Reported a violation of kidney function due to oppression of the RAAS, including kidney failure (in particular, in patients,the function of the kidneys in which it depends on RAAS, for example, with severe heart failure or existing renal dysfunction). As with the use of other drugs that affect RAAS, cases of increased urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or with renal artery stenosis of a single kidney have been described. These changes in kidney function may be reversible and decrease after the treatment is withdrawn. The drug LOZAP® PLUS should be used with caution in patients with bilateral stenosis of the renal arteries or with stenosis of the renal artery of a single kidney.Kidney Transplantation The experience of using the drug in patients who have recently undergone kidney transplantation is absent.Primary hyperaldosteronism In patients with primary hyperaldosteronism, as a rule, there is no response to treatment with antihypertensive agents that inhibit RAAS. For this reason, the use of the drug LOZAP® PLUS is not recommended.Ischemic heart disease and cerebrovascular disease As with any other antihypertensive drugs,excessive BP reduction in patients with coronary heart disease or cerebrovascular disease can lead to the development of myocardial infarction or stroke. Heart failure As with other drugs that affect RAAS, patients with heart failure (accompanied or not accompanied by impaired renal function) are at risk of developing severe arterial hypotension, as well as impaired renal function (often acute).Stenosis of the aortic and mitral valve, hypertrophicь obstructive cardiomyopathy As with other vasodilagators, special care should be taken when treating patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.Differences related to ethnicityBy analogy with other ACE inhibitors, losartan and other ARAII are significantly less effective in lowering arterial blood pressure in representatives of the Negroid race than in patients of other races. Perhaps this is due to the more frequent cases of low renin content in the population of representatives of the Negroid race with hypertension.Double blockade of the renin-angiotensin-aldosterone system There is evidence that simultaneous use of ACE inhibitors, ARAII or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure).Application of the drug LOZAP® PLUS, together with an aliskirep, is contraindicated in patients with diabetes mellitus or patients with moderate to severe renal failure (GFR less than 60 mL / min / 1.73 m2 body surface area) and is not recommended in other patients (see section "Contraindications").Application of the drug LOZAP® PLUS in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see section "Contraindications"). HydrochlorothiazideArterial hypotension and disturbances of water-electrolyte balanceAs with any other antihypertensive drugs, symptomatic arterial hypotension may develop in some patients. It should monitor the appearance in patients of clinical signs of disturbance of the water-electrolyte balance, such as hypovolemia, hyponatremia,hypochloraemic alkalosis, hypomagnesemia or hypokalemia, which can develop against the background of concomitant diarrhea or vomiting. Such patients should periodically (at appropriate intervals) monitor the content of electrolytes in the blood plasma. In patients with edema in hot weather, hypervolemic hyponatremia may develop.Endocrine and metabolic effects Treatment with thiazides can lead to a violation of glucose tolerance. It may be necessary to correct the dose of hypoglycemic agents, including insulin. During treatment with thiazides in patients with impaired glucose tolerance, manifestation of diabetes mellitus is possible.Thiazides can reduce the excretion of calcium by the kidneys and cause a slight periodic increase in the concentration of calcium in the blood plasma. Expressed hypercalcemia may be a sign of latent hyperparathyroidism. Before the study of parathyroid function, treatment with thiazides should be discontinued.Treatment with thiazide diuretics can be accompanied by an increase in the concentration of cholesterol and triglycerides in the blood plasma.In some patients, treatment with thiazides can provoke hyperuricemia and / or gout. Because the losartan reduces the concentration of uric acid, the use of losartan in combination with hydrochlorothiazide can slow the development of hyperuricemia caused by the action of the diuretic.Impaired liver function Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease due to the risk of intrahepatic cholestasis, as well as the fact that minor disturbances in the water-electrolyte balance can be a prerequisite for the development of hepatic coma.The drug LOZAP® PLUS is contraindicated in patients with severe impairment of liver function (see "Contraindications"),OtherAgainst the background of the use of hydrochlorothiazide there were cases of transient myopia and acute attack of closed-angle glaucoma. Risk factors for the development of an acute attack of closed-angle glaucoma may be anamnestic data on allergic reactions to sulfonamide and penicillin derivatives. Symptoms: sudden onset, sharp reduction in visual acuity or pain in the eye,usually occurring in the period from a few hours to a week after the start of therapy. A non-curable attack of angle-closure glaucoma can lead to persistent loss of vision. The first step is to stop taking hydrochlorothiazide. If intraocular pressure does not decrease after hydrochlorothiazide cancellation, medical or surgical treatment may be required.Against the background of thiazides, hypersensitivity reactions may develop in patients with a history of asthma, as well as in patients with a history of allergic anamnesis. There have been described cases of occurrence or exacerbation of systemic lupus erythematosus on the background of treatment with thiazides.Excipient The drug contains a dye Crimson [Ponso 4R], which can cause allergic reactions. Effect on the ability to drive transp. cf. and fur:Studies on the effect of the drug LOZAP® PLUS for the ability to manage vehicles or work with mechanisms have not been conducted. However, it must be borne in mind that against the background of treatment with antihypertensive drugs when driving or working with mechanisms, dizziness or drowsiness may occur,especially during the start of treatment or with increasing dosage of the drug. Form release / dosage:Tablets, film-coated, 50 mg / 12.5 mg. Packaging:For 10, 14 or 15 tablets in a blister of A1 / PVC. For 1, 3, 6 or 9 blisters (10 tablets) or 2 blisters (14 tablets) or 2, 4 or 6 blisters (15 tablets), together with the instructions, they are placed in a cardboard box. Storage conditions:At temperatures up to 30 ° C in a dry place.Keep out of the reach of children! Shelf life:3 years.Do not use after the expiration date printed on the package. Terms of leave from pharmacies:On prescription Registration number:LSR-000084 Date of registration:29.05.2007 / 29.09.2015 Expiration Date:Unlimited The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic Manufacturer: & nbspZENTIVA, k.s. Czech Republic Representation: & nbspSanofi Aventis GroupSanofi Aventis Group Information update date: & nbsp2016-08-22 Illustrated instructions × Illustrated instructions Instructions