Analogues of lorist n medicine and instructions for its use. Method of application and dose. Description of the pharmacological action

In this article, you can read the instructions for using the drug Lorista. Reviews of site visitors - consumers of this medicine, as well as opinions of doctors of specialists on the use of Lorista in their practice are presented. We kindly ask you to actively add your reviews about the drug: the medicine helped or did not help get rid of the disease, what complications and side effects were observed, perhaps not declared by the manufacturer in the annotation. Analogues of Lorista in the presence of existing structural analogues. Use to treat high blood pressure in adults, children, and during pregnancy and lactation.

Lorista- selective angiotensin 2 type AT1 receptor antagonist of non-protein nature.

Losartan (the active ingredient of Lorista) and its biologically active carboxyl metabolite (EXP-3174) block all physiologically significant effects of angiotensin 2 on AT1 receptors, regardless of the route of its synthesis: it leads to an increase in plasma renin activity, reduces the concentration of aldosterone in blood plasma.

Losartan indirectly causes the activation of AT2 receptors by increasing the level of angiotensin 2. Losartan does not inhibit the activity of kininase 2, an enzyme that is involved in the metabolism of bradykinin.

Reduces OPSS, 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.

Taking Lorista once a day leads to a statistically significant decrease in systolic and diastolic blood pressure. During the day, losartan evenly controls blood pressure, while the antihypertensive effect corresponds to the natural circadian rhythm. The decrease in blood pressure at the end of the dose of the drug was approximately 70-80% of the effect at the peak of the drug, 5-6 hours after administration. There is no withdrawal syndrome; also, losartan does not have a clinically significant effect on heart rate.

Losartan is effective in men and women, as well as in older (≥ 65 years) and younger patients (≤ 65 years).

Hydrochlorothiazide is a thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, and water ions in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; hypotensive effect develops due to the expansion of arterioles. Virtually no effect on normal blood pressure. The diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours.

The antihypertensive effect occurs after 3-4 days, but it may take 3-4 weeks to achieve the optimal therapeutic effect.

Compound

Losartan potassium + excipients.

Losartan potassium + Hydrochlorothiazide + excipients (Lorista H and ND).

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide with simultaneous use does not differ from that with their separate use.

Losartan

Well absorbed from the gastrointestinal tract. Taking the drug with food does not have a clinically significant effect on its serum concentrations. Practically does not penetrate through the blood-brain (BBB). About 58% of the drug is excreted in the bile, 35% in the urine.

Hydrochlorothiazide

After oral administration, the absorption of hydrochlorothiazide is 60-80%. Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys.

Indications

• arterial hypertension;
• reduced risk of stroke in patients with arterial hypertension and left ventricular hypertrophy;
• chronic heart failure (as part of combination therapy, with intolerance or ineffectiveness of therapy with ACE inhibitors);
• protection of kidney function in patients with type 2 diabetes mellitus with proteinuria to reduce proteinuria, reduce the progression of kidney damage, reduce the risk of end-stage development (preventing the need for dialysis, the likelihood of an increase in serum creatinine), or death.

Release form

Tablets 12.5 mg, 25 mg, 50 mg and 100 mg.

Lorista N (additionally contains 12.5 mg of hydrochlorothiazide).

Lorista ND (additionally contains 25 mg of hydrochlorothiazide).

Instructions for use and dosage

The drug is taken orally, regardless of food intake, the frequency of administration is 1 time per day.

With arterial hypertension, the average daily dose is 50 mg. The maximum antihypertensive effect is achieved within 3-6 weeks of therapy. It is possible to achieve a more pronounced effect by increasing the dose of the drug to 100 mg per day in two doses or in one dose.

Against the background of taking diuretics in high doses, it is recommended to start therapy with Lorista with 25 mg per day in one dose.

Elderly patients, patients with impaired renal function (including patients on hemodialysis) do not require adjustment of the initial dose of the drug.

In patients with impaired liver function, the drug should be prescribed at a lower dose.

In chronic heart failure, the initial dose of the drug is 12.5 mg per day in one dose. In order to reach the usual maintenance dose of 50 mg per day, the dose must be increased gradually at intervals of 1 week (eg, 12.5 mg, 25 mg, 50 mg per day). Lorista is usually given in combination with diuretics and cardiac glycosides.

To reduce the risk of stroke in patients with arterial hypertension and left ventricular hypertrophy, the standard initial dose is 50 mg per day. In the future, low-dose hydrochlorothiazide may be added and / or the dose of Lorista may be increased to 100 mg per day.

For kidney protection in type 2 diabetic patients with proteinuria, the standard starting dose of Lorista is 50 mg daily. The dose of the drug can be increased to 100 mg per day, taking into account the decrease in blood pressure.

side

• dizziness;
• asthenia;
• headache;
• fatigue;
• insomnia;
• anxiety;
• sleep disturbance;
• drowsiness;
• memory disorders;
• peripheral neuropathy;
• paresthesia;
• hypoesthesia;
• migraine;
• tremor;
• depression;
• orthostatic hypotension (dose-dependent);
• heartbeat;
• tachycardia;
• bradycardia;
• arrhythmias;
• angina;
• nasal congestion;
• cough;
• bronchitis;
• swelling of the nasal mucosa;
• nausea, vomiting;
• diarrhea;
• abdominal pain;
• anorexia;
• dry mouth;
• toothache;
• flatulence;
• constipation;
• imperative urge to urinate;
• impaired renal function;
• decreased libido;
• impotence;
• convulsions;
• pain in the back, chest, legs;
• tinnitus;
• taste disorder;
• visual impairment;
• conjunctivitis;
• anemia;
• purpura of Shenlein-Henoch;
• dry skin;
• increased sweating;
• alopecia;
• gout;
• hives;
• skin rash;
• angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx).

Contraindications

• arterial hypotension;
• hyperkalemia;
• dehydration;
• lactose intolerance;
• galactosemia or glucose/galactose malabsorption syndrome;
• pregnancy;
• lactation period;
• age up to 18 years (efficacy and safety in children have not been established);
• hypersensitivity to losartan and / or other components of the drug.

Use during pregnancy and lactation

There are no data on the use of Lorist during pregnancy. Renal perfusion of the fetus, which depends on the development of the renin-angiotensin system, begins to function in the 3rd trimester of pregnancy. The risk to the fetus increases when taking losartan in the 2nd and 3rd trimesters. When pregnancy is established, losartan therapy should be discontinued immediately.

There are no data on the allocation of losartan with breast milk. Therefore, the issue of stopping breastfeeding or discontinuing losartan therapy should be considered, taking into account its importance to the mother.

special instructions

Patients with a reduced volume of circulating blood (for example, during therapy with large doses of diuretics) may develop symptomatic arterial hypotension. Before taking losartan, it is necessary to eliminate existing disorders, or start therapy with small doses.

In patients with mild to moderate liver cirrhosis, the concentration of losartan and its active metabolite in the blood plasma after oral administration is higher than in healthy people. Therefore, in patients with a history of liver disease, therapy at lower doses is recommended.

Patients with impaired renal function, both with and without diabetes mellitus, often develop hyperkalemia, which should be borne in mind, but only in rare cases do they stop treatment as a result. During the period of treatment, the concentration of potassium in the blood should be regularly monitored, especially in elderly patients, with impaired renal function.

Drugs that act on the renin-angiotensin system may increase serum urea and creatinine in patients with bilateral renal artery stenosis or unilateral stenosis of the artery to a solitary kidney. Changes in renal function may be reversible after discontinuation of therapy. During treatment, it is necessary to regularly monitor the concentration of creatinine in the blood serum at regular intervals.

Influence on the ability to drive vehicles and control mechanisms

There are no data on the effect of Lorist on the ability to drive vehicles or other technical means.

drug interaction

There were no clinically significant drug interactions with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole and erythromycin.

During simultaneous administration with rifampicin and fluconazole, a decrease in the level of the active metabolite of losartan potassium was noted. The clinical consequences of this phenomenon are unknown.

Simultaneous use with potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride) and potassium preparations increases the risk of hyperkalemia.

The simultaneous use of non-steroidal anti-inflammatory drugs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive drugs.

When Lorista is administered concomitantly with thiazide diuretics, the reduction in blood pressure is approximately additive. Enhances (mutually) the effect of other antihypertensive drugs (diuretics, beta-blockers, sympatholytics).

Analogues of the drug Lorista

Structural analogues for the active substance:

• Blocktran;
• Brozaar;
• Vasotens;
• Vero Losartan;
• Zisacar;
• Cardomine Sanovel;
• Carsartan;
• Cozaar;
• Lakea;
• Lozap;
• Losarel;
• Losartan;
• Losartan potassium;
• Losacor;
• Lotor;
• Presartan;
• Renicard.

In the absence of analogues of the drug for the active substance, you can follow the links below to the diseases that the corresponding drug helps with and see the available analogues for the therapeutic effect.

You are on the page where the description of the drug Lorista N is presented, the instructions for it are given in full. Attention! The information is available for practitioners and pharmacists.

Producers: Krka (Slovenia)

Active ingredients

• Hydrochlorothiazide
• Losartan

• Essential [primary] hypertension
• Secondary hypertension

• Not indicated. See instructions

Pharmacological action

• Hypotensive

• Angiotensin II receptor antagonists (AT1 subtype) in combinations

Indications for use of Lorista N

arterial hypertension (for patients who are indicated for combination therapy);

Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Release form of Lorista N

Film-coated tablets 1 tab.
losartan potassium 50 mg
hydrochlorothiazide 12.5 mg
excipients: pregelatinized starch; MCC; lactose monohydrate; magnesium stearate
shell: hypromellose; macrogol 4000; quinoline yellow dye (E104); titanium dioxide (E171); talc

In blisters of 7, 10 or 14 pieces; in a cardboard pack 2, 4, 8, 12 or 14 blisters (7 pcs.); 3, 6 or 9 blisters (10 pcs.); 1, 2, 4, 6 or 7 blisters (14 pcs.).

Pharmacodynamics

Lorista® N - combination drug; has a hypotensive effect.

Losartan. Selective angiotensin II receptor antagonist (type AT1) for oral administration, non-protein nature. In vivo and in vitro, losartan and its biologically active carboxyl metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on AT1 receptors.

Losartan indirectly causes the activation of AT2 receptors by increasing the level of angiotensin II.

Losartan does not inhibit the activity of kininase II, an enzyme that is involved in the metabolism of bradykinin.

Reduces OPSS, pressure in the "small" circle of blood circulation; reduces afterload, has a diuretic effect.

Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure. Taking losartan once a day leads to a statistically significant decrease in SBP and DBP. Losartan evenly controls blood pressure throughout the day, while the antihypertensive effect corresponds to the natural circadian rhythm. The decrease in blood pressure at the end of the dose of the drug was approximately 70-80% of the effect at the peak of the drug, 5-6 hours after administration. There is no withdrawal syndrome; also, losartan has no clinically significant effect on heart rate.

Losartan is effective in men and women, as well as in older (over 65 years) and younger patients (under 65 years of age).

Hydrochlorothiazide. Thiazide diuretic, the diuretic effect of which is associated with a violation of the reabsorption of sodium, chlorine, potassium, magnesium, water ions in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties. Virtually no effect on normal blood pressure.

The diuretic effect occurs after 1-2 hours, reaches a maximum after 4 hours and lasts 6-12 hours.

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide, when taken simultaneously, does not differ from that when they are administered separately.

Losartan. Well absorbed from the gastrointestinal tract. It is extensively metabolized during the "first pass" through the liver, forming an active metabolite (EXP-3174) with carboxylic acid and other inactive metabolites. Bioavailability is approximately 33%. Taking the drug with food does not have a clinically significant effect on its serum concentrations. Tmax - 1 hour after oral administration, and its active metabolite (EXP-3174) - 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. It penetrates very poorly through the BBB.

Losartan is metabolized to form an active (EXP-3174) metabolite (14%) and inactive, including 2 major metabolites formed by hydroxylation of the butyl group of the chain, and a less significant metabolite, N-2-tetrazol glucuronide.

The plasma clearance of losartan and its active metabolite is approximately 10 ml/s (600 ml/min) and 0.83 ml/s (50 ml/min), respectively. The renal clearance of losartan and its active metabolite is about 1.23 ml/s (74 ml/min) and 0.43 ml/s (26 ml/min). T1 / 2 of losartan and the active metabolite is 2 hours and 6-9 hours, respectively. It is excreted mainly with bile - 58%, kidneys - 35%.

Hydrochlorothiazide. After oral administration, the absorption of hydrochlorothiazide is 60-80%. Cmax of hydrochlorothiazide in the blood is achieved 1-5 hours after ingestion.

Plasma protein binding of hydrochlorothiazide is 64%.

Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. T1 / 2 is 5-15 hours.

Use of Lorista N during pregnancy

There are no data on the use of losartan during pregnancy.

Renal perfusion of the fetus, which depends on the development of the renin-angiotensin system, begins to function in the third trimester of pregnancy. The risk to the fetus increases when taking losartan in the II and III trimesters. When pregnancy is established, Lorista® N therapy should be discontinued immediately.

If necessary, the appointment of the drug during lactation, it is necessary to stop breastfeeding.

Contraindications for use

Hypersensitivity to losartan, to drugs that are derivatives of sulfonamides and other components of the drug, anuria, severe renal dysfunction (Cl creatinine<30 мл/мин), гиперкалиемия, дегидратация (в т.ч. на фоне приема высоких доз диуретиков), выраженные нарушения функции печени, рефрактерная гипокалиемия, беременность, период лактации, артериальная гипотензия, возраст до 18 лет (эффективность и безопасность не установлены), дефицит лактазы, галактоземия или синдром мальабсорбции глюкозы/галактозы.

With caution: violations of the water and electrolyte balance of the blood (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, diabetes mellitus, hypercalcemia, hyperuricemia and / or gout, aggravated allergic history (development of angioedema earlier with taking other drugs, including ACE inhibitors) and bronchial asthma, systemic blood diseases (including systemic lupus erythematosus), simultaneous administration of NSAIDs, incl. COX-2 inhibitors.

Side effects

On the part of the blood and lymphatic system: infrequently - anemia, Shenlein-Genoch disease.

From the immune system: rarely - anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx).

From the side of the central nervous system and peripheral nervous system: often - headache, systemic and non-systemic dizziness, insomnia, fatigue; infrequently - migraine.

From the side of the cardiovascular system: often - orthostatic hypotension (dose-dependent), palpitations, tachycardia; rarely - vasculitis.

From the respiratory system: often - cough, infections of the upper respiratory tract, pharyngitis, swelling of the nasal mucosa.

From the digestive tract: often - diarrhea, dyspepsia, nausea, vomiting, abdominal pain.

From the hepatobiliary system: rarely - hepatitis, impaired liver function.

On the part of the skin and subcutaneous fat: infrequently - urticaria, pruritus.

From the musculoskeletal system and connective tissue: often - myalgia, back pain; infrequently - arthralgia.

Other: often - asthenia, weakness, peripheral edema, chest pain.

Laboratory indicators: often - hyperkalemia, an increase in the concentration of hemoglobin and hematocrit (clinically not significant); sometimes - a moderate increase in the level of urea and creatinine in the blood serum; very rarely - increased activity of liver enzymes and bilirubin.

Dosage and administration

Inside, regardless of the meal.

Lorista® N can be combined with other antihypertensive agents.

Arterial hypertension. Initial and maintenance dose - 1 tab. Lorista® N (50/12.5 mg) 1 time per day. The maximum antihypertensive effect is achieved within 3 weeks of therapy. To achieve a more pronounced effect, it is possible to increase the dose of the drug to 2 tablets. Lorista® N (50/12.5 mg) 1 time per day. The maximum daily dose is 2 tablets. Lorista® N.

In patients with reduced BCC (for example, while taking high doses of diuretics), the recommended initial dose of losartan in patients with hypovolemia is 25 mg 1 time per day. In this regard, therapy with Lorista® N should be started after discontinuation of diuretics and correction of hypovolemia.

In elderly patients and patients with moderate renal insufficiency, including those on dialysis, no initial dose adjustment is required.

Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy. The standard starting dose of losartan is 50 mg once daily.

Patients who fail to achieve target blood pressure levels while taking losartan 50 mg / day require selection of therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg); if necessary, you need to increase the dose of losartan to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg / day, in the future - up to 2 tablets. Lorista® N 50 / 12.5 mg (total - 100 mg of losartan and 25 mg of hydrochlorothiazide 1 time per day).

Overdose

Symptoms: pronounced decrease in blood pressure, tachycardia; bradycardia due to parasympathetic (vagal) stimulation.

Treatment: forced diuresis, symptomatic therapy; hemodialysis is ineffective.

Hydrochlorothiazide

Symptoms: The most common symptoms are due to electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.

Treatment: symptomatic.

Interaction with other drugs

Losartan

In clinical studies, there were no clinically significant pharmacokinetic interactions of the drug with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin.

Rifampicin and fluconazole reduce the level of the active metabolite (this interaction has not been clinically studied).

The combination of losartan with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-sparing supplements or potassium salts can lead to hyperkalemia.

NSAIDs, incl. selective COX-2 inhibitors may reduce the effect of diuretics and other antihypertensive drugs, including losartan.

In patients with impaired renal function treated with NSAIDs (including COX-2 inhibitors), angiotensin II receptor antagonist therapy may lead to further deterioration of renal function, including acute renal failure, which is usually reversible.

The hypotensive effect of losartan, like other antihypertensive drugs, can be reduced when taking indomethacin.

Hydrochlorothiazide

In combination with thiazide diuretics, drugs such as ethanol, barbiturates and narcotic drugs can potentiate the risk of developing orthostatic hypotension.

Hypoglycemic agents (oral and insulin) - dose adjustment of hypoglycemic agents may be required.

Other antihypertensives - additive effect.

Colestyramine and colestipol - in the presence of anionic exchange resins, the absorption of hydrochlorothiazide is impaired.

Corticosteroids, ACTH - a pronounced decrease in the level of electrolytes, in particular hypokalemia.

Pressor amines (for example, epinephrine, norepinephrine) - a decrease in the severity of the response to pressor amines.

Muscle relaxants of a non-depolarizing type of action (for example, tubocurarine) - enhancing the effect of muscle relaxants.

Lithium - diuretics reduce the renal clearance of lithium and increase the risk of developing the toxic effects of lithium; simultaneous use is not recommended.

NSAIDs (including COX-2 inhibitors) - may reduce the diuretic, natriuretic and hypotensive effect of diuretics. Due to the effect on calcium metabolism, their intake may distort the results of the study of the function of the parathyroid glands.

Special instructions for taking the drug Lorista N

Can be administered together with other antihypertensive drugs.

There is no need for a special selection of the initial dose for elderly patients. The drug may increase the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney.

Hydrochlorothiazide can increase arterial hypotension and disturbances in water and electrolyte balance (decrease in BCC, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce urinary calcium excretion and cause a transient, slight increase in plasma calcium concentration, increase cholesterol concentration and triglycerides, provoke the occurrence of hyperuricemia and / or gout. Taking drugs that directly affect the renin-angiotensin system during the II and III trimesters of pregnancy can lead to fetal death. If pregnancy occurs, drug withdrawal is indicated.

For pregnant women, the use of diuretics is usually not recommended due to the risk of fetal and neonatal jaundice and maternal thrombocytopenia. Therapy with diuretics does not prevent the development of toxicosis of pregnancy.

Special warnings regarding excipients Lorista® N contains lactose and therefore cannot be administered in the following conditions: lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome.

Influence on the ability to drive a car and other mechanisms. Almost all patients during therapy with Lorista® N can perform tasks that require increased attention (for example, driving a car). In some individuals, at the beginning of therapy, the drug can cause a decrease in blood pressure and dizziness and thus indirectly affect their psycho-emotional state. For safety reasons, before starting activities that require increased attention, patients should first evaluate their response to the treatment being carried out.

Storage conditions

List B.: In a dry place, at a temperature not exceeding 30 ° C.

Best before date

ATH classification:

C Cardiovascular system

C09 Drugs affecting the renin-angiotensin system

C09D Angiotensin II antagonists, combinations

C09DA Angiotensin II antagonists and diuretics

Information source portal: www.eurolab.ua

Instructions for use Lorista

Buy at the pharmacy Lorista N tab. 50mg+12.5mg №60

Dosage forms
tablets 12.5mg+50mg

Synonyms
Blocktran GT
Vazotens N
Gizaar
Gizaar forte
Lozap plus
Losarel Plus
Losartan-N Richter
Losartan/Hydrochlorothiazide-Teva
Lorista N
Lorista ND

Group
Combination of angiotensin II receptor antagonists and diuretics

International non-proprietary name
Losartan + Hydrochlorothiazide

Compound
Active substances: losartan potassium 50 mg, hydrochlorothiazide 12.5 mg.

Manufacturers
Krka d.d., Novo Mesto (Slovenia)

pharmachologic effect
Pharmacodynamics. Lorista H is a combination drug; has a hypotensive effect. Losartan is a selective angiotensin II receptor (type AT1) antagonist for oral administration, non-protein nature. In vivo and in vitro, losartan and its biologically active carboxyl metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on AT1 receptors, regardless of the route of its synthesis: it leads to an increase in plasma renin activity, reduces the concentration of aldosterone in blood plasma, etc. Losartan indirectly causes the activation of AT2 receptors by increasing the level of angiotensin II. Losartan does not inhibit the activity of kininase II, an enzyme that is involved in the metabolism of bradykinin. Reduces total peripheral vascular resistance (OPSS), pressure in the "small" circle of blood circulation; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure (CHF). Taking losartan once a day leads to a statistically significant decrease in systolic and diastolic blood pressure (BP). Losartan evenly controls blood pressure throughout the day, while the antihypertensive effect corresponds to the natural circadian rhythm. The decrease in blood pressure (BP) at the end of the dose of the drug was approximately 70-80% of the effect at the peak of the drug, 5-6 hours after administration. The syndrome of "cancellation" is not observed; also, losartan does not have a clinically significant effect on heart rate (HR). Losartan is effective in men and women, and in older (> 65 years) and younger patients (< 65 лет). Гидрохлоротиазид. Тиазидный диуретик, диуретический эффект которого связан с нарушением реабсорбции ионов натрия, хлора, калия, магния, воды в дистальном отделе нефрона; задерживает выведение ионов кальция, мочевой кислоты. Обладает антигипертензивными свойствами; гипотензивное действие развивается за счет расширения артериол. Практически не оказывает влияния на нормальное артериальное давление (АД). Диуретический эффект наступает через 1-2 часа, достигает максимума через 4 часа и продолжается 6-12 часов. Антигипертензивное действие наступает через 3-4 дня, но для достижения оптимального терапевтического эффекта может потребоваться 3-4 недели. Фармакокинетика. Фармакокинетика лозартана и гидрохлоротиазида при одновременном приеме не отличается от таковой при их раздельном назначении. Лозартан. Лозартан хорошо всасывается из желудочно-кишечного тракта. Подвергается значительному метаболизму при «первом прохождении» через печень, образуя активный метаболит (ЕХР-3174) с карбоксиловой кислотой и другие неактивные метаболиты. Биодоступность составляет примерно 33%. Прием препарата с пищей не оказывает клинически значимого влияния на его сывороточные концентрации. Время максимальной концентрации - 1 час после приема внутрь, а его активного метаболита (ЕХР-3174) - 3-4 часа. Более 99% лозартана и ЕХР-3174 связывается с белками плазмы крови, преимущественно, с альбумином. Объем распределения лозартана равен 34 л. Очень плохо проникает через гематоэнцефалический барьер. Лозартан метаболизируется с образованием активного (ЕХР-3174) метаболита (14%) и неактивных, включая два основных метаболита, образующихся путем гидроксилирования бутильной группы цепи и менее значимый метаболит, N-2-тетразол глюкуронид. Плазменный клиренс лозартана и его активного метаболита составляет приблизительно 10 мл/сек. (600 мл/мин.) и 0,83 мл/сек. (50 мл/мин.) соответственно. Почечный клиренс лозартана и его активного метаболита составляет около 1,23 мл/сек. (74 мл/мин.) и 0,43 мл/сек. (26 мл/мин.). Период полувыведения лозартана и активного метаболита составляет 2 часа и 6-9 часов, соответственно. Выводится преимущественно с желчью - 58%, почками -35%. Гидрохлоротиазид. После приема внутрь всасывание гидрохлоротиазида составляет 60-80%. Максимальная концентрация гидрохлоротиазида в крови достигается через 1-5 часов после приема внутрь. Связь с белками плазмы крови гидрохлоротиазида - 64%. Гидрохлоротиазид не метаболизируется и быстро выводится через почки. Период полувыведения составляет 5-15 часов.

Side effect
On the part of the blood and lymphatic system: infrequently: anemia, Henoch-Schonlein purpura. From the immune system: rarely: anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx). From the side of the central nervous system and peripheral nervous system: often: headache, systemic and non-systemic dizziness, insomnia, fatigue; infrequently: migraine. From the side of the cardiovascular system: often: orthostatic hypotension (dose-dependent), palpitations, tachycardia; rarely: vasculitis. From the respiratory system: often: cough, infections of the upper respiratory tract, pharyngitis, swelling of the nasal mucosa. From the gastrointestinal tract: often: diarrhea, dyspepsia, nausea, vomiting, abdominal pain. From the hepatobiliary system: rarely - hepatitis, liver dysfunction. On the part of the skin and subcutaneous fat: infrequently: urticaria, pruritus. From the musculoskeletal system and connective tissue: often: myalgia, back pain; infrequently: arthralgia. Other: often: asthenia, weakness, peripheral edema, chest pain. Laboratory indicators: often: hyperkalemia, increased hemoglobin and hematocrit concentrations (clinically not significant); infrequently: a moderate increase in the level of urea and creatinine in the blood serum; very rarely: increased activity of liver enzymes and bilirubin.

Indications for use
Arterial hypertension (for patients who are indicated for combination therapy). Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Contraindications
Hypersensitivity to losartan, to drugs that are derivatives of sulfonamides and other components of the drug, anuria, severe renal dysfunction (creatinine clearance (CC) less than 30 ml / min.), Hyperkalemia, dehydration (including against the background of taking high doses of diuretics) , severe liver dysfunction, refractory hypokalemia, pregnancy, lactation, arterial hypotension, age under 18 years (efficacy and safety have not been established), lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome. With caution: violations of the water and electrolyte balance of the blood (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, diabetes mellitus, hypercalcemia, hyperuricemia and / or gout, aggravated allergic history (in some patients, angioedema developed earlier when taking other drugs, including ACE inhibitors) and bronchial asthma, systemic blood diseases (including systemic lupus erythematosus), simultaneous prescription of non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-II inhibitors (COX- 2 inhibitors). Use during pregnancy and lactation. There are no data on the use of losartan during pregnancy. Fetal renal perfusion, which depends on the development of the renin-angiotensin system, begins to function in the third trimester of pregnancy. The risk to the fetus increases when taking losartan in the second and third trimesters. When pregnancy is established, therapy should be discontinued immediately. If necessary, the appointment of the drug during lactation, it is necessary to stop breastfeeding.

Method of application and dosage
Inside, regardless of the meal. The drug can be combined with other antihypertensive agents. Arterial hypertension. The initial and maintenance dose is 1 tablet of the drug (50/12.5 mg) 1 time per day. The maximum antihypertensive effect is achieved within three weeks of therapy. To achieve a more pronounced effect, it is possible to increase the dose of the drug up to 2 tablets (50/12.5 mg) 1 time per day. The maximum daily dose is 2 tablets of the drug. In patients with a reduced volume of circulating blood (for example, while taking high doses of diuretics), the recommended initial dose of losartan in patients with hypovolemia is 25 mg once a day. In this regard, therapy should be started after the abolition of diuretics and correction of hypovolemia. In elderly patients and patients with moderate renal insufficiency, including those on dialysis, no initial dose adjustment is required. Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy. The standard starting dose of losartan is 50 mg once daily. Patients who fail to achieve target blood pressure levels while taking losartan 50 mg / day require selection of therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg), and, if necessary, increase the dose of losartan to 100 mg per day. in combination with hydrochlorothiazide at a dose of 12.5 mg / day, in the future - increase to 2 tablets of the drug 50 / 12.5 mg in total (100 mg of losartan and 25 mg of hydrochlorothiazide once a day).

Overdose
Losartan. Symptoms: pronounced decrease in blood pressure, tachycardia; bradycardia due to parasympathetic (vagal) stimulation. Treatment: forced diuresis, symptomatic therapy, hemodialysis is ineffective. Hydrochlorothiazide. Symptoms: The most common symptoms are due to electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias. Treatment: symptomatic.

Interaction
Losartan. In clinical studies of pharmacokinetic interactions, no clinically significant interactions of the drug with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin were detected. Rifampicin and fluconazole reduce the level of the active metabolite (this interaction has not been clinically studied). The combination of losartan with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium-sparing supplements or potassium salts can lead to hyperkalemia. NSAIDs, including selective cyclooxygenase-2 inhibitors, may reduce the effect of diuretics and other antihypertensive drugs, including losartan. In patients with impaired renal function treated with NSAIDs (including cyclooxygenase-2 inhibitors), therapy with angiotensin II receptor antagonists may lead to further deterioration of renal function, including acute renal failure, which is usually reversible. The hypotensive effect of losartan, like other antihypertensive drugs, can be reduced when taking indomethacin. Hydrochlorothiazide. With thiazide diuretics, drugs such as ethanol, barbiturates and narcotic drugs may potentiate the risk of developing orthostatic hypotension. Hypoglycemic agents (oral and insulin) - dose adjustment of hypoglycemic agents may be required. Other antihypertensives - additive effect. Colestyramine and colestipol - in the presence of anionic exchange resins, the absorption of hydrochlorothiazide is impaired. Corticosteroids, ACTH (adrenocorticotropic hormone) - a pronounced decrease in electrolyte levels, in particular hypokalemia. Pressor amines (for example, epinephrine, norepinephrine) - a decrease in the severity of the response to taking pressor amines. Muscle relaxants of a non-depolarizing type of action (for example, tubocurarine) - enhancing the effect of muscle relaxants. Lithium - diuretics reduce the renal clearance of lithium and increase the risk of developing the toxic effects of lithium; simultaneous use is not recommended. NSAIDs (including cyclooxygenase-2 inhibitors) - may reduce the diuretic, natriuretic and hypotensive effect of diuretics. Due to the effect on calcium metabolism, their intake may distort the results of the study of the function of the parathyroid glands.

special instructions
Can be administered together with other antihypertensive drugs. There is no need for a special selection of the initial dose for elderly patients. The drug may increase the concentration of urea and creatinine in the blood plasma in patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney. Hydrochlorothiazide can increase arterial hypotension and disturbances in water and electrolyte balance (decrease in circulating blood volume, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce urinary calcium excretion and cause a transient, slight increase in plasma calcium concentration, increase concentration of cholesterol and triglycerides, provoke the occurrence of hyperuricemia and / or gout. Taking drugs that directly affect the renin-angiotensin system during the II and III trimesters of pregnancy can lead to fetal death. If pregnancy occurs, drug withdrawal is indicated. Diuretics are generally not recommended for pregnant women due to the risk of fetal and neonatal jaundice and maternal platelet count. Therapy with diuretics does not prevent the development of toxicosis of pregnancy. Special warnings regarding excipients. The drug contains lactose, therefore, it cannot be prescribed in the following conditions: lactase deficiency, galactosemia or glucose / galactose malabsorption syndrome. Influence on the ability to drive a car and other mechanisms. Almost all patients during therapy can perform tasks that require increased attention (for example, driving a car). In some individuals, at the beginning of therapy, the drug can cause a decrease in blood pressure and dizziness, thus indirectly affecting their psycho-emotional state. For safety reasons, before starting activities requiring increased attention, patients should first evaluate their response to the treatment being carried out.

Storage conditions
Store in a dry place, out of the reach of children, at a temperature not exceeding 30 C.

Composition and form of release

Active substances:
hydrochlorothiazide 12.5 mg
losartan potassium 50 mg
excipients: pregelatinized starch - 34.92 mg; MCC - 87.7 mg; lactose monohydrate - 63.13 mg; magnesium stearate - 1.75 mg
film shell: hypromellose - 5 mg; macrogol 4000 - 0.5 mg; quinoline yellow dye (E104) - 0.11 mg; titanium dioxide (E171) - 1.39 mg; talc - 0.5 mg

Description of the dosage form

Oval, slightly biconvex film-coated tablets from yellow to yellow with a greenish tint, scored on one side.
Type of tablet in cross section: white core.

pharmachologic effect

Hypotensive

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide, when taken simultaneously, does not differ from that when they are used separately.
Suction. Losartan: After oral administration, losartan is well absorbed and metabolized during the primary passage through the liver with the formation of an active carboxyl metabolite (EXP-3174) and inactive metabolites. Systemic bioavailability is approximately 33%. Cmax in plasma of losartan and its active metabolite are reached after 1 hour and 3-4 hours, respectively. Hydrochlorothiazide: after oral administration, the absorption of hydrochlorothiazide is 60-80%. Cmax of hydrochlorothiazide in blood plasma is reached 1-5 hours after ingestion.
Distribution. Losartan: more than 99% of losartan and EXP-3174 bind to plasma proteins, mainly albumin. Vd of losartan is 34 liters. It penetrates very poorly through the BBB. Hydrochlorothiazide: the relationship with plasma proteins is 64%; crosses the placenta, but not through the BBB and is excreted in breast milk.
Biotransformation. Losartan: Approximately 14% of an intravenous or oral dose of losartan is metabolized to form the active metabolite. Following oral and/or intravenous administration of 14C-losartan potassium, circulating plasma radioactivity was mainly determined by losartan and its active metabolite.
In addition to the active metabolite, inactive metabolites are formed, including two main metabolites formed by hydroxylation of the butyl group of the chain, and a minor metabolite, N-2-tetrazole glucuronide.
Taking the drug with food does not have a clinically significant effect on its serum concentrations.
Hydrochlorothiazide: Not metabolized.
Withdrawal. Losartan: The plasma clearance of losartan and its active metabolite is 600 and 50 ml/min, respectively; renal clearance of losartan and its active metabolite is 74 and 26 ml/min, respectively. After oral administration, only about 4% of the dose taken is excreted unchanged by the kidneys and about 6% as the active metabolite. The pharmacokinetic parameters of losartan and its active metabolite when taken orally (in doses up to 200 mg) are linear.
T1 / 2 in the terminal phase of losartan and the active metabolite is 2 hours and 6-9 hours, respectively. There is no accumulation of losartan and its active metabolite when used at a dose of 100 mg once a day.
It is excreted mainly by the intestines with bile - 58%, by the kidneys - 35%.
Hydrochlorothiazide: Rapidly excreted via the kidneys. T1 / 2 is 5.6-14.8 hours. About 61% of the ingested dose is excreted unchanged.
Separate groups of patients
Hydrochlorothiazide/losartan. Plasma concentrations of losartan and its active metabolite and hydrochlorothiazide in elderly patients with arterial hypertension did not significantly differ from those in young patients.
Losartan. In patients with mild and moderate alcoholic cirrhosis of the liver after ingestion of losartan, plasma concentrations of losartan and the active metabolite were 5 and 1.7 times higher than in young male volunteers, respectively.
Losartan and its active metabolite are not removed by hemodialysis.

Pharmacodynamics

Hydrochlorothiazide/losartan
Lorista® N is a combined drug, the components of which have an additive hypotensive effect and cause a more pronounced decrease in blood pressure compared to their separate use. Due to the diuretic action, hydrochlorothiazide increases plasma renin activity, aldosterone secretion, reduces serum potassium and increases the level of angiotensin II in blood plasma. Losartan blocks the physiological effects of angiotensin II and, by inhibiting aldosterone secretion, can reverse the loss of potassium ions caused by the diuretic.
Losartan has a uricosuric effect. Hydrochlorothiazide causes a moderate increase in the concentration of uric acid; when using losartan simultaneously with hydrochlorothiazide, diuretic-induced hyperuricemia decreases.
The hypotensive effect of the hydrochlorothiazide / losartan combination persists for 24 hours. Despite a significant decrease in blood pressure, the use of the hydrochlorothiazide / losartan combination does not have a clinically significant effect on heart rate.
The hydrochlorothiazide/losartan combination is effective in men and women, as well as in younger (under 65 years of age) and elderly (65 years of age and older) patients.
Losartan
Losartan is an angiotensin II receptor antagonist for oral administration of a non-protein nature. Angiotensin II is a potent vasoconstrictor and the main RAAS hormone. Angiotensin II binds to AT1 receptors found in many tissues (eg, vascular smooth muscle, adrenal glands, kidneys, and myocardium) and mediates various biological effects of angiotensin II, including vasoconstriction and aldosterone release. In addition, angiotensin II stimulates the proliferation of smooth muscle cells.
Losartan selectively blocks AT1 receptors. In vivo and in vitro, losartan and its biologically active carboxyl metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on AT1 receptors, regardless of the route of its synthesis. Losartan does not have agonism and does not block other hormone receptors or ion channels that are important in the regulation of CVS. Losartan does not inhibit the activity of ACE (kininase II), an enzyme that is involved in the metabolism of bradykinin. Accordingly, it does not cause an increase in the frequency of undesirable effects mediated by bradykinin.
Losartan indirectly causes the activation of AT2 receptors by increasing the level of angiotensin II in the blood plasma.
Suppression of the regulation of renin secretion under the action of angiotensin II by the mechanism of negative feedback in the treatment of losartan causes an increase in plasma renin activity, which leads to an increase in the concentration of angiotensin II in the blood plasma. However, the hypotensive effect and suppression of aldosterone secretion persist, indicating effective blockade of angiotensin II receptors. After discontinuation of losartan, plasma renin activity and angiotensin II concentration decrease to baseline values ​​within 3 days.
Losartan and its major active metabolite have a significantly higher affinity for the AT1 receptor than for the AT2 receptor. The active metabolite is 10-40 times more active than losartan.
The incidence of cough is comparable with losartan or hydrochlorothiazide and significantly lower than with an ACE inhibitor.
In non-diabetic patients with arterial hypertension and proteinuria, treatment with losartan significantly reduces proteinuria, albumin and IgG excretion. Losartan supports glomerular filtration and reduces the filtration fraction. Losartan reduces serum uric acid levels (usually less than 0.4 mg/dl) throughout therapy. Losartan has no effect on autonomic reflexes and does not affect the concentration of noradrenaline in blood plasma.
In patients with left ventricular failure, losartan at doses of 25 and 50 mg has positive hemodynamic and neurohumoral effects, characterized by an increase in cardiac index and a decrease in pulmonary capillary wedge pressure, peripheral vascular resistance, mean blood pressure and heart rate, and a decrease in plasma concentrations of aldosterone and norepinephrine. The risk of arterial hypotension in patients with heart failure depends on the dose of losartan.
The use of losartan once a day in patients with mild to moderate essential hypertension causes a significant decrease in SBP and diastolic blood pressure. The hypotensive effect lasts for 24 hours while maintaining the natural circadian rhythm of blood pressure. The degree of blood pressure reduction at the end of the dosing interval is 70-80% compared with the hypotensive effect 5-6 hours after taking losartan.
Losartan is effective in men and women, as well as in elderly patients (65 years of age and older) and younger patients (under 65 years of age). Cancellation of losartan in patients with arterial hypertension does not lead to a sharp increase in blood pressure (there is no drug withdrawal syndrome). Losartan has no clinically significant effect on heart rate.
Hydrochlorothiazide
Thiazide diuretic, the mechanism of hypotensive action of which has not been fully established. Thiazides change the reabsorption of electrolytes in the distal nephron and increase the excretion of sodium and chlorine ions approximately equally. The diuretic effect of hydrochlorothiazide leads to a decrease in BCC, an increase in plasma renin activity and secretion of aldosterone, which leads to an increase in the excretion of potassium ions and bicarbonates by the kidneys and a decrease in serum potassium. The relationship between renin and aldosterone is mediated by angiotensin II, so the simultaneous use of ARA II suppresses the loss of potassium ions during treatment with thiazide diuretics.
After oral administration, the diuretic effect occurs after 2 hours, reaches a maximum after about 4 hours and persists for 6-12 hours; the hypotensive effect persists for 24 hours.

Indications for use

Arterial hypertension (patients who are indicated for combination therapy);
reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Contraindications for use

Hypersensitivity to losartan, sulfonamide derivatives and other excipients;
anuria, severe renal failure (Cl creatinine less than 30 ml / min);
severe liver failure (more than 9 points on the Child-Pugh scale), cholestasis and obstructive biliary tract disease;
simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml / min);
age up to 18 years (efficacy and safety of use have not been established);
hypokalemia or hypercalcemia resistant to therapy;
refractory hyponatremia;
symptomatic hyperuricemia/gout;
lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, tk. Lorista® N contains lactose;
pregnancy;
breastfeeding period.

With caution: severe hyponatremia and / or conditions accompanied by a decrease in BCC (including a diet with limited salt, diarrhea, vomiting, therapy with high doses of diuretics); violations of the water and electrolyte balance of the blood, diabetes mellitus, renal failure (Cl creatinine 30-50 ml / min); liver dysfunction of mild to moderate severity (more than 9 points on the Child-Pugh scale) without a history of cholestasis; chronic heart failure III-IV functional class according to the NYHA classification and other conditions accompanied by activation of the RAAS; bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; condition after kidney transplantation; primary hyperaldosteronism; coronary heart disease and cerebrovascular diseases, tk. an excessive decrease in blood pressure can lead to the development of myocardial infarction and stroke; stenosis of the aortic and / or mitral valve; hypertrophic obstructive cardiomyopathy (GOKMP); aggravated allergic history (the patient has a history of angioedema when using drugs, including ACE inhibitors and ARA II) and bronchial asthma; systemic lupus erythematosus; acute myopia and secondary acute angle-closure glaucoma; symptomatic hyperuricemia/gout.

Use in pregnancy and children

The use of ARA II in the first trimester of pregnancy is not recommended.
Lorista® N should not be used during pregnancy or in women planning a pregnancy. When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile. If pregnancy is confirmed, Lorista® N should be discontinued and, if necessary, the patient should be transferred to alternative antihypertensive therapy.
Lorista® N, as well as other drugs that have a direct effect on the RAAS, can cause adverse effects in the fetus (impaired renal function, slowing the ossification of the bones of the fetal skull, oligohydramnios) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If, however, the drug Lorista® N was used in the II-III trimesters of pregnancy, then it is necessary to conduct an ultrasound scan of the kidneys and bones of the fetal skull.
Hydrochlorothiazide crosses the placenta. When using thiazide diuretics in the II-III trimester of pregnancy, a decrease in uteroplacental blood flow, the development of thrombocytopenia, jaundice, and water and electrolyte imbalance in the fetus or newborn may occur.
Hydrochlorothiazide should not be used to treat preeclampsia in the second half of pregnancy (edema, arterial hypertension or preeclampsia (nephropathy)) due to the risk of a decrease in BCC and a decrease in uteroplacental blood flow in the absence of a beneficial effect on the course of the disease. Hydrochlorothiazide should not be used to treat essential hypertension in pregnancy, except in rare cases where alternative agents cannot be used.
Newborns whose mothers took Lorista® N during pregnancy should be monitored, because. possible development of arterial hypotension in the newborn.
The drug Lorista® N is not recommended during breastfeeding, because. no application experience. The use of other antihypertensive drugs is recommended, taking into account the safety profile.
It is not known whether losartan is excreted in breast milk.
Hydrochlorothiazide passes into the mother's breast milk in small amounts. Thiazide diuretics in high doses cause intense diuresis, thereby suppressing lactation.

Side effects

WHO classification of the incidence of side effects:
very often ≥1/10; often ≥1/100 to<1/10; нечасто от ≥1/1000 до <1/100; редко от ≥1/10000 до <1/1000; очень редко <1/10000; частота неизвестна — не может быть оценена на основе имеющихся данных.
Adverse reactions with the use of a combination of hydrochlorothiazide / losartan have been observed previously with the use of losartan and / or hydrochlorothiazide.
Post-marketing use of hydrochlorothiazide/losartan combination
Additional adverse reactions
From the digestive system: rarely - hepatitis.
Laboratory data: rarely - hyperkalemia, increased activity of ALT.
Adverse reactions that occurred when used in monotherapy with losartan or hydrochlorothiazide may be when using a combination of hydrochlorothiazide / losartan:
Losartan
On the part of the hematopoietic organs: infrequently - anemia, Shenlein-Genoch purpura, ecchymosis, hemolysis; frequency unknown - thrombocytopenia.
From the side of the cardiovascular system: infrequently - a pronounced decrease in blood pressure, orthostatic hypotension, chest pain, angina pectoris, AV block II degree, cerebrovascular accident, myocardial infarction (with an excessive decrease in blood pressure), palpitations, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, ventricular fibrillation), vasculitis.
From the senses: infrequently - vertigo, tinnitus, blurred vision, burning sensation / tingling in the eyes, conjunctivitis, decreased visual acuity.
From the digestive system: often - abdominal pain, nausea, diarrhea, dyspepsia; infrequently - constipation, toothache, dryness of the oral mucosa, bloating, gastritis, vomiting, intestinal obstruction; frequency unknown - pancreatitis, impaired liver function.
Allergic reactions: rarely - hypersensitivity, anaphylactic reactions, angioedema, including edema of the larynx and pharynx, causing airway obstruction, and / or swelling of the face, lips, pharynx and / or tongue; in some patients, angioedema was also noted in the history of treatment with other drugs, including ACE inhibitors.
From the musculoskeletal system: often - muscle cramps, back pain, pain in the legs, myalgia; infrequently - pain in the hands, swelling of the joints, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness; frequency unknown - rhabdomyolysis.
From the nervous system: often - headache, dizziness, insomnia; infrequently - nervousness, paresthesia, peripheral neuropathy, tremor, migraine, fainting, anxiety, anxiety disorder (excessive, uncontrollable and often irrational worry about everyday events), panic disorder (recurring panic attacks), confusion, depression, nightmares, sleep disturbances , drowsiness, memory impairment.
From the genitourinary system: often - impaired renal function, renal failure; infrequently - nocturia, frequent urination, urinary tract infections.
From the reproductive system: infrequently - decreased libido, erectile dysfunction / impotence.
On the part of the respiratory system: often - cough, upper respiratory tract infections, nasal congestion, sinusitis, upper respiratory tract obstruction; infrequently - a feeling of discomfort in the throat, pharyngitis, laryngitis, shortness of breath, bronchitis, epistaxis, rhinitis, congestion in the respiratory tract.
On the part of the skin: infrequently - alopecia, dermatitis, dry skin, erythema, feeling of flushing to the skin of the face, photosensitivity, skin itching, skin rash, urticaria, increased sweating.
Others: often - asthenia, fatigue, anorexia; infrequently - swelling of the face, edema, fever; frequency unknown - flu-like symptoms, malaise.
Laboratory indicators: often - hyperkalemia, a slight decrease in Hb and hematocrit, hypoglycemia; infrequently - a slight increase in serum concentrations of urea and creatinine; very rarely - an increase in the activity of liver enzymes and the concentration of bilirubin in the blood plasma; frequency unknown - hyponatremia.
Hydrochlorothiazide
On the part of the hematopoietic organs: infrequently - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.
Allergic reactions: rarely - an anaphylactic reaction.
From the side of metabolism: infrequently - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia.
From the nervous system: often - headache; infrequently - insomnia.
From the senses: infrequently - a transient visual impairment, xanthopsia; frequency unknown - acute myopia and acute angle-closure glaucoma ..
From the CCC: infrequently - necrotizing angiitis (vasculitis, cutaneous vasculitis).
From the respiratory system: infrequently - respiratory distress syndrome, including pneumonitis and pulmonary edema.
From the digestive system: infrequently - sialadenitis, spasm, stomach irritation, nausea, vomiting, diarrhea, constipation, jaundice (intrahepatic cholestasis), pancreatitis.
From the skin: infrequently - photosensitivity, urticaria, toxic epidermal necrolysis.
From the musculoskeletal system: infrequently - muscle cramps.
From the genitourinary system: infrequently - glucosuria, interstitial nephritis, impaired renal function, renal failure.
Other: infrequently - fever, dizziness.

drug interaction

Simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml / min) is contraindicated.
Losartan
Rifampicin and fluconazole reduced the concentration of the active metabolite. The clinical significance of this interaction has not been studied.
The simultaneous use of losartan, as well as other drugs that affect the RAAS, with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations or salt substitutes containing potassium, may lead to an increase in serum potassium. Simultaneous use is not recommended.
Possible decrease in the excretion of lithium ions. Therefore, with the simultaneous use of ARA II with lithium salts, serum lithium concentrations should be carefully monitored.
With the simultaneous use of angiotensin II antagonists with NSAIDs (for example, selective COX-2 inhibitors, and non-selective NSAIDs, high doses (more than 3 g / day) of acetylsalicylic acid), a decrease in the hypotensive effect is possible. The simultaneous use of angiotensin II antagonists or diuretics with NSAIDs is accompanied by an increased risk of developing renal dysfunction, incl. the development of acute renal failure and an increase in serum potassium (especially in patients with a history of renal dysfunction). It should be used with caution simultaneously with NSAIDs, especially in elderly patients. At the same time, it is necessary to adequately replenish the BCC and periodically monitor kidney function from the start of therapy and subsequently.
In some patients with impaired renal function who use NSAIDs, incl. selective COX-2 inhibitors, the simultaneous use of ARA II may cause further reversible deterioration in renal function.
Double blockade of the RAAS: double blockade of the RAAS, i.e. the addition of an ACE inhibitor to ARA II therapy is possible only in selected cases under close monitoring of renal function.
In patients with atherosclerosis, heart failure, or diabetes mellitus with target organ damage, dual blockade of the RAAS (with the simultaneous use of ARA II and ACE inhibitors) is accompanied by an increased incidence of arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) in compared with the use of the drug of one of the listed groups.
With simultaneous use with other drugs that cause arterial hypotension, incl. tricyclic antidepressants, antipsychotics (neuroleptics), baclofen, amifostine increases the risk of arterial hypotension.
Hydrochlorothiazide
Alcohol, barbiturates, anesthetics or antidepressants: may potentiate the risk of orthostatic hypotension.
Hypoglycemic agents for oral administration and insulin: dose adjustment of hypoglycemic agents may be required, because. hydrochlorothiazide affects glucose tolerance.
Metformin should be used with caution due to the risk of developing lactic acidosis against the background of impaired renal function caused by hydrochlorothiazide.
Other antihypertensive drugs: additive effect.
Colestyramine and colestipol: The absorption of hydrochlorothiazide is reduced. Colestyramine and colestipol in a single dose bind hydrochlorothiazide and reduce its absorption in the gastrointestinal tract by 85 and 43%, respectively.
Corticosteroids, ACTH: marked decrease in electrolytes, especially hypokalemia.
Pressor amines (e.g. epinephrine and norepinephrine): a slight decrease in the severity of the response to the administration of pressor amines is possible, but does not exclude the possibility of their use.
Non-depolarizing muscle relaxants (eg, tubocurarine): May increase the effect of muscle relaxants.
Lithium: possible decrease in renal clearance of lithium and, accordingly, the risk of developing lithium intoxication. Therefore, simultaneous use is not recommended.
Drugs used to treat gout (probenecid, sulfinpyrazone and allopurinol): dose adjustment of uricosuric drugs may be required, because. hydrochlorothiazide may cause an increase in the serum concentration of uric acid. Thiazide diuretics may increase the incidence of hypersensitivity reactions to allopurinol.
Anticholinergic drugs (eg atropine, biperiden): increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility. Cytostatic drugs, for example, cyclophosphamide, methotrexate: myelosuppressive effect is increased by slowing down excretion from the body.
Salicylates: when used simultaneously with salicylates (for example, acetylsalicylic acid) in high doses, their toxic effect on the central nervous system may increase.
Methyldopa: isolated cases of hemolytic anemia have been described with simultaneous use.
The simultaneous use of cyclosporine increases the risk of developing hyperuricemia and exacerbation of the course of gout.
Cardiac glycosides: Hypokalemia and hypomagnesaemia caused by the use of thiazide diuretics increase the risk of arrhythmias in the treatment of cardiac glycosides.
Drugs that can cause side effects when serum potassium levels change:
it is recommended to periodically monitor the content of potassium in the blood serum and ECG while using it with cardiac glycosides and drugs that prolong the QT interval (risk of developing ventricular tachycardia of the "pirouette" type);
class IA antiarrhythmics (eg quinidine, disopyramide);
Class III antiarrhythmic drugs (eg amiodarone, sotalol, dofetilide).
Some antipsychotics (eg thioridazine, chlorpromazine, levomepromazine, trifluoperazine, sulpiride, amisulpride, tiapride, haloperidol, droperidol).
Other drugs (for example, cisapride, difemanil methyl sulfate, erythromycin for intravenous administration, halofantrine, ketanserin, mizolastine, sparfloxacin, terfenadine, vincamine for intravenous administration).
Vitamin D and calcium salts: the simultaneous use of thiazide diuretics with vitamin D or calcium salts increases the content of calcium in the blood serum, because. decreased excretion of calcium. If it is necessary to use calcium or vitamin D supplements, the calcium content in the blood serum should be monitored and, possibly, the dose of these drugs should be adjusted;
Carbamazepine: risk of symptomatic hyponatremia. It is necessary to monitor clinical and biological parameters.
Hydrochlorothiazide may increase the risk of developing acute renal failure, especially when high doses of iodine-containing contrast agents are used simultaneously. Before their use, it is necessary to restore the BCC.
Amphotericin B (for intravenous administration), stimulant laxatives, or ammonium glycyrrhizinate (part of licorice): hydrochlorothiazide may increase fluid and electrolyte imbalance, especially hypokalemia.

Dosage

Inside, regardless of the meal, drinking plenty of water, once a day. Lorista® N can be taken simultaneously with other antihypertensive drugs.
Arterial hypertension. The combination of hydrochlorothiazide/losartan is indicated in patients who, when hydrochlorothiazide or losartan are used separately, do not provide adequate blood pressure control.
It is recommended to titrate the dose of losartan and hydrochlorothiazide before transferring the patient to Lorista N therapy.
Initial and maintenance dose - 1 tab. the drug Lorista® N (hydrochlorothiazide 12.5 mg and losartan 50 mg). The maximum hypotensive effect is achieved within 3 weeks of therapy. To achieve a more pronounced effect, it is possible to increase the dose of Lorista® N. The maximum daily dose is 2 tablets. Lorista® N 1 time per day.
Special patient groups
Patients with impaired renal function or on hemodialysis. In patients with moderate renal impairment (Cl creatinine 30-50 ml / min), adjustment of the initial dose of the drug is not required.
Losartan and hydrochlorothiazide are not recommended for patients on hemodialysis.
Patients with low BCC. The recommended starting dose of losartan is 25 mg once daily.
Before starting treatment with Lorista® N, the diuretic should be discontinued, the BCC and / or the content of sodium ions should be restored.
Elderly patients. Dose adjustment is usually not required.
Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy
The standard starting dose of losartan is 50 mg/day. Patients who fail to achieve target blood pressure levels while taking losartan 50 mg / day require selection of therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg). If necessary, increase the dose of losartan to 100 mg / day simultaneously with hydrochlorothiazide at a dose of 12.5 mg / day, then increase to 2 tablets. the drug Lorista® N (only 25 mg of hydrochlorothiazide and 100 mg of losartan per day) once a day. If additional blood pressure reduction is required, other antihypertensive drugs should be added.

Overdose

Lorista® N
There is no information on overdose of the hydrochlorothiazide/losartan combination.
Treatment: symptomatic and supportive therapy. Lorista® H should be discontinued and the patient monitored closely. If necessary: ​​induce vomiting (if the patient has recently taken the drug), replenish the BCC, correct violations of water and electrolyte metabolism and a pronounced decrease in blood pressure.
Losartan (data limited)
Symptoms: pronounced decrease in blood pressure, tachycardia; possible bradycardia due to parasympathetic (vagal) stimulation.
Treatment: symptomatic therapy, hemodialysis is ineffective.
Hydrochlorothiazide
Symptoms: The most common symptoms are: hypokalemia, hypochloremia, hyponatremia and dehydration as a result of excessive diuresis. With the simultaneous administration of cardiac glycosides, hypokalemia can aggravate the course of arrhythmias.
Treatment: symptomatic.

Precautionary measures

Losartan
Angioedema. Patients with a history of angioedema (face, lips, pharynx and/or larynx) should be closely monitored.
Arterial hypotension and hypovolemia (dehydration). Symptomatic arterial hypotension may develop in patients with hypovolemia (dehydration) and / or reduced sodium content in the blood plasma against the background of diuretic therapy, restriction of salt intake, diarrhea or vomiting, especially after taking the first dose of Lorista® N. Before using the drug, restore BCC and / or sodium content in blood plasma.
Violations of water and electrolyte balance. Violations of water and electrolyte balance are often found in patients with impaired renal function, especially against the background of diabetes mellitus. In this regard, it is necessary to carefully monitor the content of potassium in the blood plasma and creatinine clearance, especially in patients with heart failure and Cl creatinine 30-50 ml / min.
Simultaneous use with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other drugs that can increase the content of potassium in the blood plasma (for example, heparin) is not recommended.
Impaired liver function. Plasma concentrations of losartan are significantly increased in patients with cirrhosis of the liver, so Lorista® H should be used with caution in patients with mild or moderate hepatic impairment.
Impaired kidney function. It is possible to develop impaired renal function, including renal failure, due to inhibition of the RAAS (especially in patients whose kidney function depends on the RAAS, for example, with severe heart failure or a history of kidney dysfunction).
Stenosis of the renal artery. In patients with bilateral renal artery stenosis, as well as stenosis of the artery of the only functioning kidney, drugs that affect the RAAS, incl. and ARA II, can reversibly increase plasma urea and creatinine concentrations.
Losartan should be used with caution in patients with bilateral renal artery stenosis or arterial stenosis of a single kidney.
Kidney transplant. There is no experience with the use of Lorista® N in patients who have recently undergone kidney transplantation.
Primary hyperaldosteronism. Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect the RAAS, so the use of Lorista® N is not recommended in such patients.
ischemic heart disease and cerebrovascular disease. As with any antihypertensive drug, excessive blood pressure reduction in patients with coronary artery disease or cerebrovascular disease can lead to myocardial infarction or stroke.
Heart failure. In patients whose renal function depends on the state of the RAAS (for example, with CHF III-IV functional class according to the NYHA classification, accompanied or not accompanied by impaired renal function), therapy with drugs that affect the RAAS may be accompanied by severe arterial hypotension, oliguria and / or progressive azotemia, in rare cases - acute renal failure. It is impossible to exclude the development of these disorders due to the suppression of RAAS activity while taking ARA II.
Stenosis of the aortic and / or mitral valve, GOKMP. Lorista® N, like other vasodilators, should be used with caution in patients with hemodynamically significant aortic and/or mitral valve stenosis or HOCMP.
Ethnic features. Losartan (like other drugs that affect the RAAS) has a less pronounced antihypertensive effect in patients of the black race compared with representatives of other races, possibly due to the higher incidence of hyporeninemia in these patients with arterial hypertension.
Hydrochlorothiazide
Arterial hypotension and disorders of water and electrolyte metabolism. It is necessary to control blood pressure, clinical signs of impaired water and electrolyte metabolism, incl. dehydration, hyponatremia, hypochloremic alkalosis, hypomagnesemia or hypokalemia, which may develop against the background of diarrhea or vomiting.
Serum electrolytes should be monitored periodically.
Metabolic and endocrine effects. Caution is required in all patients treated with hypoglycemic agents for oral administration or insulin, because. hydrochlorothiazide may weaken their effect. During therapy with thiazide diuretics, latent diabetes mellitus may manifest.
Thiazide diuretics, including hydrochlorothiazide, can cause fluid and electrolyte imbalance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia, and hypokalemic alkalosis).
Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause a temporary and slight increase in the content of calcium in the blood plasma.
Severe hypercalcemia may be a sign of latent hyperparathyroidism. Before conducting a study of the function of the parathyroid glands, thiazide diuretics must be discontinued.
Against the background of treatment with thiazide diuretics, an increase in the concentration of cholesterol and triglycerides in the blood serum is possible.
Therapy with thiazide diuretics in some patients may exacerbate hyperuricemia and / or exacerbate the course of gout.
Losartan reduces the concentration of uric acid in the blood plasma, so its use in combination with hydrochlorothiazide eliminates hyperuricemia caused by a thiazide diuretic.
Impaired liver function. Thiazide diuretics should be used with caution in patients with impaired liver function or progressive liver disease, as they can cause intrahepatic cholestasis, and even minimal disturbances in water and electrolyte balance can contribute to the development of hepatic coma.
Lorista® N is contraindicated in patients with severe hepatic impairment, as there is no experience of using the drug in this category of patients.
Acute myopia and secondary acute angle-closure glaucoma. Hydrochlorothiazide is a sulfonamide that can cause an idiosyncratic reaction resulting in transient acute myopia and acute angle-closure glaucoma. Symptoms include: a sudden decrease in visual acuity or pain in the eyes, which usually appear within a few hours or weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to permanent vision loss.
Treatment: stop taking hydrochlorothiazide as soon as possible. If IOP remains uncontrolled, emergency medication or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are: an allergic reaction to a sulfonamide or benzylpenicillin in history.
Are common
In patients taking thiazide diuretics, hypersensitivity reactions may develop with or without a history of an allergic reaction or bronchial asthma, but are more likely if they are present in history.
There are reports of exacerbation of the course of systemic lupus erythematosus with the use of thiazide diuretics.
Special information on excipients
The drug Lorista® N contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.
Influence on the ability to perform potentially hazardous activities that require special attention and quick reactions (for example, driving vehicles, working with moving mechanisms). At the beginning of therapy, Lorista® N may cause a decrease in blood pressure, dizziness or drowsiness, thus indirectly affecting the psycho-emotional state. For safety reasons, before starting activities requiring increased attention, patients should first evaluate their response to the treatment being carried out.

Doctors say that arterial hypertension is an extremely common disease that often develops completely imperceptibly (or almost imperceptibly), but at the same time poses a serious threat to health. And in fact, in the absence of adequate, constant and complete therapy, this disease can lead to a variety of complications, ranging from loss of working capacity and ending with the development of myocardial infarction and renal failure. Treatment of arterial hypertension should be carried out under the supervision of a physician and with the use of a number of different medications. Among them may be the drug we are considering. Let's clarify what the instruction says about Lorista N 50 mg and the use of this drug, we will give real reviews about such a medicine and consider its existing analogues.

What is Lorista N?

So, Lorista H 50mg is a fairly common medication used in the treatment of arterial hypertension. It is based on such an active ingredient as losartan potassium in the amount of fifty milligrams, as well as hydrochlorothiazide in the amount of 12.5 mg. It is these substances that determine how Lorista N acts on the human body.

So, losartan is a representative of angiotensin II receptor blockers. Such a substance blocks the activity of angiotensin II, which is a hormone normally produced by the kidneys. Such an effect leads to relaxation of blood vessels and to a natural decrease in blood pressure.

Hydrochlorothiazide is a diuretic, in other words a diuretic. To date, drugs with this effect are one of the drugs of choice for hypertension. They remove excess water and salts from the human body, which helps to reduce blood pressure. Hydrochlorothiazide helps to eliminate (reduce) swelling and reduce the workload on the heart.

Quite often, in the treatment of hypertension, doctors prescribe angiotensin II receptor blockers and diuretics separately, but Lorista N combines these components, which makes it effective and convenient to use.

Indications for use Lorista N 50mg

To date, this medication is used to treat patients with arterial hypertension (an increase in blood pressure above normal), if complex therapy is necessary. Also, this medicine can be prescribed to those readers of "Popular about Health" who are diagnosed with arterial hypertension and left ventricular hypertrophy. In the latter case, Lorista N, according to the instructions, is designed to reduce the likelihood of cardiovascular morbidity, as well as reduce the risk of mortality.

How to take Lorista N 50mg

The treatment regimen is selected exclusively by the attending physician. Self-medication can be hazardous to health.

Lorista H 50 mg is usually taken once a day. The medicine has a prolonged effect, helping to prevent an increase in pressure for the whole day. The daily dosage is one tablet. Reception is carried out without reference to the time of the meal, the medicine must be washed down with a sufficient amount of liquid.

It is worth noting that in some cases, the use of Lorist N can be combined with the use of other medications that reduce pressure (if such a treatment regimen is prescribed by a doctor).

In the event that the medicine does not give a pronounced (expected) effect, the doctor may recommend increasing the dosage. So, the maximum daily dose is two tablets of Lorist N, but the reception is still carried out at a time - once a day.

It should be borne in mind that with a low volume of circulating blood in patients, Lorist N should be started with 25 mg. In other patients (with moderate impairment of the liver, as well as in the elderly), dose adjustment is not necessary.

Are there any contraindications?

Medication Lorista H 50mg has certain contraindications for consumption. So, it is not prescribed for individual hypersensitivity (allergy) to the components of the drug, with severe renal failure and anuria. This medicine is also not indicated in patients with severe hepatic insufficiency, cholestasis and obstruction of the biliary tract. Lorista H cannot be combined with aliskiren (for diabetes mellitus or impaired renal function). Still, such a medicine is not prescribed in children under eighteen years of age, during breastfeeding and pregnancy. Contraindications include lactase deficiency or lactose intolerance, symptomatic hyperuricemia/gout, hypokalemia and hypercalcemia, and refractory hyponatremia.

Are there analogues for Lorist N?

To date, there are several analogues of Lorist N on sale. Among them:

Blocktran GT;
- Vazotens N;
- Losartan-N Canon;
- Gizaar;
- Lozap plus;
- Losarel Plus.

The doctor will help you choose the most suitable medication or an adequate replacement for the prescribed medication.