Cough

Lorista n 50mg 12 5mg yellow tablets. Lorista n - instructions for use

Lorista® H

Active ingredient

Hydrochlorothiazide + Losartan*(Hydrochlorothiazidum + Losartanum*)

ATX

C09DA01 Losartan in combination with diuretics

Pharmacological group

Antihypertensive combination drug (angiotensin II receptor antagonist + diuretic) [Angiotensin II receptor antagonists (AT1 subtype) in combinations]

Nosological classification (ICD-10)

I10 Essential (primary) hypertension I15 Secondary hypertension I50.1 Left ventricular failure

Compound

Film-coated tablets 1 tablet active ingredients: hydrochlorothiazide 12.5 mg 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

Pharmacological action

Pharmacological action - hypotensive.

Indications

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

Contraindications

hypersensitivity to losartan, hydrochlorothiazide and other sulfonamide derivatives, as well as to 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 diseases of the biliary tract; 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 ;lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, because Lorista® N contains lactose; pregnancy; breastfeeding. With caution: severe hyponatremia and/or conditions accompanied by a decrease in blood volume (including a diet with limited salt, diarrhea, vomiting, therapy with high doses of diuretics); disturbances in the water-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 of functional class III–IV according to the NYHA classification and other conditions accompanied by activation of the RAAS; bilateral renal artery stenosis or stenosis of the artery of a single kidney; condition after kidney transplantation; primary hyperaldosteronism; coronary heart disease and cerebrovascular diseases, because 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 (HOCM); aggravated allergic history (the patient has a history of angioedema when using drugs, including ACE inhibitors and AR II) and bronchial asthma; systemic lupus erythematosus; acute myopia and secondary acute angle-closure glaucoma; symptomatic hyperuricemia/gout.

Use during pregnancy and breastfeeding

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 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, you should stop taking Lorista® N and, if necessary, transfer the patient to alternative antihypertensive therapy. Lorista® N, like other drugs that have a direct effect on the RAAS, may cause adverse effects in the fetus (impaired renal function, slow ossification of fetal skull bones, oligohydramnios) and neonatal toxic effects (renal failure, hypotension, hyperkalemia). If, nevertheless, the drug Lorista® N was used in the II–III trimesters of pregnancy, then it is necessary to conduct an ultrasound of the kidneys and skull bones of the fetus. Hydrochlorothiazide penetrates 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 are possible. Hydrochlorothiazide should not be used for the treatment of gestosis in the second half of pregnancy (edema, hypertension or preeclampsia ( nephropathy)) due to the risk of a decrease in blood volume 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 pregnant women, except in rare cases when alternative agents cannot be used. Newborns whose mothers took Lorista® N during pregnancy should be monitored because the development of arterial hypotension in a newborn is possible. 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 breast milk in small quantities. Thiazide diuretics in high doses cause intense diuresis, thereby suppressing lactation.

Description of the dosage form

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

Pharmacodynamics

Hydrochlorothiazide/losartan Lorista® N is a combination 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 its diuretic effect, hydrochlorothiazide increases plasma renin activity, aldosterone secretion, reduces serum potassium levels and increases the concentration of angiotensin II in blood plasma. Losartan blocks the physiological effects of angiotensin II and, by inhibiting aldosterone secretion, can neutralize the loss of potassium ions caused by the diuretic. Losartan has a uricosuric effect. Hydrochlorothiazide causes a moderate increase in uric acid concentrations; When losartan is used simultaneously with hydrochlorothiazide, hyperuricemia caused by the diuretic is reduced. 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 patients (under 65 years) and elderly (65 years and older) age. Losartan Losartan is an angiotensin II receptor antagonist for oral administration of a non-protein nature. Angiotensin II is a powerful vasoconstrictor and the main hormone of the RAAS. Angiotensin II binds to AT1 receptors, which are found in many tissues (eg, vascular smooth muscle, adrenal glands, kidneys, and myocardium) and mediate 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 hormonal receptors or ion channels important in the regulation of the cardiovascular system. Losartan does not suppress 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 activation of AT2 receptors by increasing the concentration of angiotensin II in the blood plasma. Suppression of the regulation of renin secretion by angiotensin II by a negative feedback mechanism during treatment with losartan causes an increase in renin activity blood plasma, 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 initial values within 3 days. Losartan and its main active metabolite have a significantly higher affinity for AT1 receptors compared to AT2 receptors. The active metabolite is 10–40 times more active than losartan. The incidence of cough is comparable when using losartan or hydrochlorothiazide and is significantly lower than when using an ACE inhibitor. In patients with arterial hypertension, proteinuria and without diabetes, treatment with losartan significantly reduces proteinuria and excretion albumin and IgG. Losartan supports glomerular filtration and reduces the filtration fraction. Losartan reduces serum uric acid concentrations (usually less than 0.4 mg/dL) throughout therapy. Losartan has no effect on autonomic reflexes and does not affect the concentration of norepinephrine in the blood plasma. In patients with left ventricular failure, losartan in 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, round-trip resistance, and mean Blood pressure and heart rate and a decrease in plasma concentrations of aldosterone and norepinephrine. The risk of developing 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 DBP. The hypotensive effect continues for 24 hours while maintaining the natural circadian rhythm of blood pressure. The degree of reduction in blood pressure 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 and older) and younger patients (under 65 years old). Discontinuation of losartan in patients with arterial hypertension does not lead to a sharp increase in blood pressure (there is no drug withdrawal syndrome). Losartan does not have a clinically significant effect on heart rate. Hydrochlorothiazide Thiazide diuretic, the mechanism of hypotensive action of which has not been fully established. Thiazides alter the reabsorption of electrolytes in the distal nephron and increase the excretion of sodium and chloride ions to approximately equal extent. The diuretic effect of hydrochlorothiazide leads to a decrease in blood volume, an increase in plasma renin activity and aldosterone secretion, which leads to an increase in the excretion of potassium ions and bicarbonates by the kidneys and a decrease in serum potassium levels. The connection between renin and aldosterone is mediated by angiotensin II, therefore the simultaneous use of ARA II suppresses the loss of potassium ions during treatment with thiazide diuretics. After oral administration, the diuretic effect occurs within 2 hours, reaches a maximum after about 4 hours and persists for 6–12 hours; the hypotensive effect persists for 24 hours.

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide when taken simultaneously does not differ from that when they are used separately. Absorption. Losartan: After oral administration, losartan is well absorbed and undergoes first-pass metabolism through the liver to form an active carboxyl metabolite (EXP-3174) and inactive metabolites. Systemic bioavailability is approximately 33%. Cmax in blood plasma of losartan and its active metabolite is achieved 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 achieved 1–5 hours after oral administration. Distribution. Losartan: More than 99% of losartan and EXP-3174 are bound to plasma proteins, predominantly albumin. Vd of losartan is 34 l. It penetrates the BBB very poorly. Hydrochlorothiazide: binding to plasma proteins is 64%; penetrates the placenta, but not through the BBB and is excreted in breast milk. Biotransformation. Losartan: Approximately 14% of a dose of losartan administered intravenously or taken orally is metabolized to form an active metabolite. After oral and/or intravenous administration of 14C-losartan potassium, the circulating radioactivity of the blood plasma 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. Elimination. Losartan: 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 an 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. Excreted mainly by the intestines with bile - 58%, by the kidneys - 35%. Hydrochlorothiazide: quickly excreted through the kidneys. T1/2 is 5.6–14.8 hours. About 61% of the dose taken orally is excreted unchanged. Selected patient groupsHydrochlorothiazide/losartan. Plasma concentrations of losartan and its active metabolite and hydrochlorothiazide in elderly patients with arterial hypertension did not differ significantly from those in young patients. Losartan. In patients with mild and moderate alcoholic cirrhosis of the liver after oral administration 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.

Interaction

Concomitant 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. Concomitant use of losartan, as well as other drugs acting on the RAAS, with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements or salt substitutes containing potassium may lead to an increase in serum potassium levels. Simultaneous use is not recommended. A decrease in the excretion of lithium ions is possible. Therefore, with simultaneous use of ARA II with lithium salts, serum lithium concentrations should be carefully monitored. With simultaneous use of angiotensin II antagonists with NSAIDs (for example, selective COX-2 inhibitors, and non-selective NSAIDs, acetylsalicylic acid in doses that have an anti-inflammatory effect), 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 levels (especially in patients with a history of renal dysfunction). Concomitant use with NSAIDs should be done with caution, especially in elderly patients. In this case, it is necessary to adequately replenish the volume of blood volume and periodically monitor renal function from the moment of initiation of therapy and subsequently. In some patients with impaired renal function using NSAIDs, incl. selective COX-2 inhibitors, simultaneous use of ARA II may cause further reversible deterioration of 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 careful monitoring of renal function. In patients with atherosclerosis, heart failure or diabetes mellitus with target organ damage, double blockade of the RAAS (with simultaneous use of ARA II and ACE inhibitors) is accompanied by increased the incidence of arterial hypotension, fainting, hyperkalemia and renal dysfunction (including acute renal failure) in comparison with the use of a drug from one of the listed groups. When used simultaneously with other drugs that cause arterial hypotension, incl. tricyclic antidepressants, antipsychotics (neuroleptics), baclofen, amifostine increases the risk of developing arterial hypotension. Hydrochlorothiazide Ethanol, barbiturates, general anesthetics or antidepressants: may potentiate the risk of orthostatic hypotension. Oral hypoglycemic agents and insulin: dosage adjustment of hypoglycemic agents may be required because hydrochlorothiazide affects glucose tolerance. Metformin should be used with caution due to the risk of lactic acidosis due to renal impairment caused by hydrochlorothiazide. Other antihypertensive drugs: additive effect. Cholestyramine and colestipol: absorption of hydrochlorothiazide is reduced. Cholestyramine 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 electrolyte levels, especially hypokalemia. Pressor amines (for example, epinephrine and norepinephrine): a slight decrease in the severity of the response to the introduction of pressor drugs is possible amines, but does not exclude the possibility of their use. Non-depolarizing muscle relaxants (for example, tubocurarine): the effect of muscle relaxants may be enhanced. Lithium: the renal clearance of lithium may be reduced 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 serum uric acid concentrations. 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: the myelosuppressive effect increases by slowing elimination 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 be enhanced. Methyldopa: isolated cases of hemolytic anemia with simultaneous use have been described. Concomitant use of cyclosporine increases the risk of developing hyperuricemia and exacerbation of gout. Cardiac glycosides: hypokalemia and hypomagnesemia caused by the use of thiazide diuretics increase the risk of developing arrhythmias during treatment with cardiac glycosides. Drugs that may cause side effects when serum potassium levels change:

Side effects

WHO classification of the frequency of side effects: very common? 1/10; often from?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.Нежелательные реакции при применении комбинации гидрохлоротиазид/лозартан наблюдались ранее при применении лозартана и/или гидрохлоротиазида.Постмаркетинговое применение комбинации гидрохлоротиазид/лозартанДополнительные нежелательные реакцииСо стороны пищеварительной системы: редко- гепатит.Лабораторные данные: редко- гиперкалиемия, повышение активности АЛТ.Нежелательные реакции, которые встречались при применении в монотерапии лозартана или гидрохлоротиазида могут быть при применении комбинации гидрохлоротиазид/лозартан:ЛозартанСо стороны органов кроветворения: нечасто- анемия, пурпура Шенлейна-Геноха, экхимозы, гемолиз; частота неизвестна- тромбоцитопения.Со стороны ССС: нечасто- выраженное снижение АД, ортостатическая гипотензия, боль в груди, стенокардия, AV блокада II степени, нарушение мозгового кровообращения, инфаркт миокарда (при чрезмерном снижении АД), ощущение сердцебиения, аритмия (фибрилляция предсердий, синусовая брадикардия, тахикардия, желудочковая тахикардия, фибрилляция желудочков), васкулит.Со стороны органов чувств: нечасто- вертиго, шум в ушах, нечеткость зрительного восприятия, чувство жжения/чувство покалывания в глазах, конъюнктивит, снижение остроты зрения.Со стороны пищеварительной системы: часто- боль в животе, тошнота, диарея, диспепсия; нечасто- запор, боль в зубах, сухость слизистой оболочки полости рта, вздутие живота, гастрит, рвота, непроходимость кишечника; частота неизвестна- панкреатит, нарушение функции печени.Аллергические реакции: редко- гиперчувствительность, анафилактические реакции, ангионевротический отек, включая отек гортани и глотки, вызывающий обструкцию дыхательных путей, и/или отек лица, губ, глотки и/или языка; у некоторых пациентов ангионевротический отек отмечался также в анамнезе при лечении другими препаратами, включая ингибиторы АПФ.Со стороны опорно-двигательного аппарата: часто- судороги в мышцах, боль в спине, боль в ногах, миалгия; нечасто- боль в руках, опухание суставов, боль в коленях, скелетно-мышечные боли, боль в плечах, скованность, артралгия, артрит, коксалгия, фибромиалгия, мышечная слабость; частота неизвестна- рабдомиолиз.Со стороны нервной системы: часто- головная боль, головокружение, бессонница; нечасто- нервозность, парестезия, периферическая нейропатия, тремор, мигрень, обморок, тревожность, тревожное расстройство (чрезмерное, неконтролируемое и часто иррациональное беспокойство о повседневных событиях), паническое расстройство (повторяющиеся панические атаки), спутанность сознания, депрессия, кошмарные сновидения, нарушения сна, сонливость, нарушение памяти.Со стороны мочеполовой системы: часто- нарушение функции почек, почечная недостаточность; нечасто- никтурия, учащенное мочеиспускание, инфекции мочевых путей.Со стороны репродуктивной системы: нечасто- снижение либидо, эректильная дисфункция/импотенция.Со стороны дыхательной системы: часто- кашель, инфекции верхних дыхательных путей, заложенность носа, синусит, нарушение проходимости верхних дыхательных путей; нечасто- чувство дискомфорта в глотке, фарингит, ларингит, одышка, бронхит, носовое кровотечение, ринит, застойные явления в дыхательных путях.Со стороны кожных покровов: нечасто- алопеция, дерматит, сухость кожных покровов, эритема, ощущение приливов крови к коже лица, фоточувствительность, кожный зуд, кожная сыпь, крапивница, повышенное потоотделение.Прочие: часто- астения, повышенная утомляемость, анорексия; нечасто- отек лица, отеки, лихорадка; частота неизвестна- гриппоподобные симптомы, недомогание.Лабораторные показатели: часто- гиперкалиемия, незначительное снижение Hb и гематокрита, гипогликемия; нечасто- незначительное увеличение сывороточных концентраций мочевины и креатинина; очень редко- повышение активности печеночных ферментов и концентрации билирубина в плазме крови; частота неизвестна- гипонатриемия.ГидрохлоротиазидСо стороны органов кроветворения: нечасто- агранулоцитоз, апластическая анемия, гемолитическая анемия, лейкопения, пурпура, тромбоцитопения.Аллергические реакции: редко- анафилактическая реакция.Со стороны обмена веществ: нечасто- анорексия, гипергликемия, гиперурикемия, гипокалиемия, гипонатриемия.Со стороны нервной системы: часто- головная боль; нечасто- бессонница.Со стороны органов чувств: нечасто- преходящее нарушение зрительного восприятия, ксантопсия; частота неизвестна- острая миопия и острая закрытоугольная глаукома..Со стороны ССС: нечасто- некротизирующий ангиит (васкулит, кожный васкулит).Со стороны дыхательной системы: нечасто- респираторный дистресс-синдром, включая пневмонит и отек легких.Со стороны пищеварительной системы: нечасто- сиалоаденит, спазм, раздражение желудка, тошнота, рвота, диарея, запор, желтуха (внутрипеченочный холестаз), панкреатит.Со стороны кожных покровов: нечасто- фоточувствительность, крапивница, токсический эпидермальный некролиз.Со стороны опорно-двигательного аппарата: нечасто- судороги в мышцах.Со стороны мочеполовой системы: нечасто- глюкозурия, интерстициальный нефрит, нарушение функции почек, почечная недостаточность.Прочие: нечасто- лихорадка, головокружение.

In one tablet of the drug Lorista N contains:

50 mg losartan potassium ;
12.5 mg;

Tablets of the drug Lorista ND contain:

100 mg losartan potassium ;
25 mg nidrochlorothisiad ;
magnesium stearate, MCC, lactose monohydrate, pregelatinized starch.

The shell consists of hypromellose , quinoline dye (yellow), talc, macrogol 4000 and titanium dioxide (E171).

Release form

Pills Lorista N biconvex, oval, yellow (in some cases with a greenish tint) color, marked on one side; Lorista ND– oval tablets, biconvex in shape, yellow to greenish in color, without marks.

Pharmacological action

Renders hypotensive effect .

Pharmacodynamics and pharmacokinetics

Both drugs (Lorista N and Lorista ND) are a combination drug that has an antihypertensive effect.

Leads to an increase in renin activity and also reduces the plasma concentration of aldosterone. Reduces peripheral vascular resistance, the level of pressure in the pulmonary circulation, has a diuretic effect, and reduces afterload.

Losartan prevents the occurrence myocardial hypertrophy , increases exercise tolerance in those patients who suffer from heart failure. Taking losartan helps lower blood pressure. Doesn't call withdrawal syndrome , does not affect heart rate.

Effective in people of any gender, as well as in older people (over 65 years old).

Hydrochlorothiazide provides antihypertensive effect due to the dilation of arterioles. The effect after administration is achieved after 1-2 hours, the maximum is observed after 4 hours, lasts up to 12 hours. The hypotensive effect is achieved after administration after 3-4 days, but to achieve the optimal effect it takes up to 4 weeks.

When used separately, pharmacokinetics hydrochlorothiazide And losartan differs from that when used simultaneously.

Losartan is absorbed from the gastrointestinal tract. Serum concentration does not depend on the drug taken simultaneously with food. Bioavailability is at 33%. The maximum concentration is observed after 60 minutes. About 35% of the drug is excreted through the kidneys, 58% with bile.

Digestibility hydrochlorothiade is about 60-80% after oral administration. The maximum concentration is achieved from 1 hour to 5 hours. It is quickly eliminated through the kidneys as it is not metabolized.

Indications for use

Medicine Lorista N And Lorista ND have the same indications for use:

reducing the risk of cardiovascular diseases ;
reduction in mortality rate in patients with left ventricular hypertrophy and arterial hypertension ;
arterial hypertension (combination therapy).

Contraindications

Both drugs should not be used in the following cases:

deficit lactase ;
hyperkalemia ;
refractory hypokalemia ;
impaired renal or liver function;
galactosemia ;
arterial hypotension ;
pregnancy;
glucose or galactose malabsorption syndrome;
lactation;
sensitivity to any component, to sulfonamide derivatives;
up to 18 years old.

Should be used with caution when:

bilateral renal artery stenosis ;
disturbance of the water-electrolyte balance of the blood ( hypomagnesemia , hypochloremic alkalosis , hyponatremia , hypokalemia );
renal artery stenosis ;
systemic blood diseases;
hyperuricemia ;
allergy history;
hypercalcemia ;
simultaneously with NSAIDs.

Side effects

The following side effects may result from taking this medicine:

(non-systemic and systemic), , headache, fatigue;
palpitations, dose-dependent orthostatic hypotension, in severe cases - vasculitis ;
cough, swelling of the nasal mucosa, respiratory tract infections (upper sections);
nausea, abdominal pain, vomiting, ; in rare cases - hepatitis, increased activity of liver enzymes, bilirubin, impaired liver function;
back pain, arthralgia, myalgia ;
Henoch-Schönlein purpura , anemia ;
weakness, chest pain, asthenia , peripheral edema;
itching, anaphylactic reactions, angioedema.

Taking this drug may also affect laboratory parameters : hyperkalemia, increased levels of creatinine, urea, increased concentration of hematocrit and hemoglobin.

Instructions for use of Lorista N (Method and dosage)

The medicine is intended for oral administration. Possible combination with other drugs that have an antihypertensive effect. Taking the drug does not depend on food intake.

At arterial hypertension The minimum dose prescribed is 1 tablet. After a three-week course, the maximum hypotensive effect is achieved. To achieve a stronger effect, it is enough to take 2 tablets once a day, which is the maximum dose.

For patients with reduced blood volume You must take 25 mg of losartan per day. If a decrease in blood volume occurred while taking significant doses of diuretics, then before starting therapy with Lorista N, it is necessary to stop taking diuretics.

The initial dose does not require adjustment in patients undergoing on dialysis, suffering renal failure (moderate) and elderly patients (over 65 years old).

A daily dose of losartan of 50 mg is prescribed to reduce the risk of cardiovascular disease and mortality in those patients diagnosed with left ventricular hypertrophy or arterial hypertension. If it was not possible to reduce blood pressure when taking 50 mg, then it is necessary to combine losartan with hydrochlorothiazide (12.5 mg). If necessary, the dose of losartan can be increased to 100 mg without changing the dose of hydrochlorothiazide. The maximum daily dose of the drug should not exceed 2 tablets once.

Instructions for use of Lorista ND : this drug is prescribed in the absence of a therapeutic effect from taking Lorista N. The drug Lorista ND is taken in the same daily doses as Lorista N.

Overdose

Overdose losartan has the following symptoms: significant decrease in blood pressure, bradycardia , tachycardia . If symptoms of overdose are detected, treatment is recommended: symptomatic treatment, forced diuresis. Hemodialysis is ineffective in this case.

In case of overdose hydrocholorothiazide The following symptoms may appear: hypochloremia , hypokalemia , hyponatremia . In this case, symptomatic treatment is prescribed.

Interaction

Clinically significant interaction of losartan with, phenobarbital , hydrochlorothiazide , ketoconazole warfarin , And cimetidine not identified.

The level of the active metabolite decreases when taking losartan with and. However, this interaction has not been studied clinically.

Hyperkalemia may result from combination with potassium-sparing diuretics ( triamterene , amiloride ), potassium salts or additives containing potassium.

The effectiveness of losartan may be reduced by taking NSAIDs And selective COX-2 inhibitors .

Admission may lead to a decrease in the hypotensive effect lazortana .

Ethanol , narcotic drugs And barbiturates when combined with hydrochlorothiazide, they can cause orthostatic hypotension.

Simultaneous Adoption hypoglycemic agents (incl. insulin ) may require dose adjustment.

An additive effect may occur when combining treatment with other antihypertensive drugs .

The following drugs can interfere with the absorption of hydrochlorothiazide: colestipol or cholestyramine .

Hydrochorothiazide may enhance the effectiveness of muscle relaxants ( tudokurarine ).

The natriuretic, hypotensive and diuretic effects of hydrochlorothiazide may be reduced due to the use of NSAIDs (including COX-2 inhibitors).

Laboratory results studying the functions of the parathyroid glands may be distorted due to the effect of hydrochlorothiazide on calcium metabolism.

Terms of sale

Sold in pharmacies only with a prescription.

Storage conditions

The drug should be stored in a dark, non-humid place. Maximum temperature – 30 °C.

Best before date

Special instructions

Combination with other antihypertensive drugs is possible.

The initial dose for elderly patients is not specifically adjusted.

Taking hydrochlorothiazide may lead to increased arterial hypotension and disrupt water-electrolyte balance . It is also possible to have impaired glucose tolerance and a decrease in the level of calcium excretion in the urine, which in turn can lead to a slight increase in calcium levels in the blood.

Taking the drug for II or III trimester during pregnancy can cause fetal death. The drug should be discontinued if pregnancy occurs. A newborn or fetus may experience jaundice , from the mother - thrombocytopenia .

Taking the drug in most patients does not affect the ability to perform tasks requiring concentration. However, some patients may experience a significant decrease in blood pressure and dizziness at the beginning of treatment. Before starting such work, it is necessary to assess the condition after taking the medicine.

Analogues

Level 4 ATX code matches:

Analogues of Lorista N include: angizar plus ,co-sentor , lockard , nostasartan n , tozaar-g .

All of the above analogues also apply to Lorista ND.

KRKA KRKA d.d. KRKA d.d., Novo mesto/KRKA-RUS, LLC KRKA, d.d., Novo mesto KRKA, d.d., Novo mesto, JSC KRKA-RUS, LLC

Country of origin

Russia Slovenia Slovenia/Russia

Product group

Cardiovascular drugs

Antihypertensive combined drug (angiotensin II receptor blocker + diuretic)

Release forms

10 - blisters (3) - cardboard packs. 30 tabs in pack 7 - blisters (14) - cardboard packs. 7 - blisters (14) - cardboard packs. 7 - blisters (2) - cardboard packs. 7 - blisters (4) - cardboard packs. 7 - blisters (8) - cardboard packs. 7 - blisters (12) - cardboard packs. 7 - blisters (14) - cardboard packs. Film-coated tablets 100 mg + 25 mg - 30 tablets per pack. Film-coated tablets 100 mg + 25 mg - 60 tablets per pack. pack of 30 tablets, pack of 60 tablets, pack of 90 tablets

Description of the dosage form

Film-coated tablets Film-coated tablets are yellow to yellow with a greenish tint, oval, slightly biconvex, scored on one side. Film-coated tablets from yellow to yellow with a greenish tint, oval, slightly biconvex.

Pharmacological action

Lorista N - combination drug; has a hypotensive effect. Losartan is a selective angiotensin II receptor antagonist (type AT1) for oral administration, of a 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 the activity of plasma renin, reduces the concentration of aldosterone in the blood plasma, etc. Losartan indirectly causes 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 (TPVR), pressure in the “lesser” circulation; reduces afterload and 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 drug dose was approximately 70-80% of the effect at the peak of the drug effect, 5-6 hours after administration. There is no “withdrawal” syndrome; losartan also does not have a clinically significant effect on heart rate (HR). Losartan is effective in men and women, as well as in older (> 65 years) and younger patients (

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide when administered simultaneously does not differ from that when administered separately. Losartan. Losartan is well absorbed from the gastrointestinal tract. It undergoes significant metabolism during the “first pass” through the liver, forming an active metabolite (EXP-3174) 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. TStax-1 hour after oral administration, and its active metabolite (EXP-3174) - 3-4 hours. More than 99% of losartan and EXP-3174 bind to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. It penetrates the blood-brain barrier very poorly. Losartan is metabolized to form an active (EXP-3174) metabolite (14%) and inactive ones, including two major metabolites formed by hydroxylation of the butyl group of the chain and a less significant metabolite, N-2-tetrazole glucuronide. Plasma clearance of losartan and its active metabolite is approximately 10 ml/sec. (600 ml/min.) and 0.83 ml/sec. (50 ml/min.) respectively. The renal clearance of losartan and its active metabolite is approximately 1.23 ml/sec. (74 ml/min.) and 0.43 ml/sec. (26 ml/min.). The half-life of losartan and the active metabolite is 2 hours and 6-9 hours, respectively. Excreted mainly with bile - 58%, kidneys - 35%. Hydrochlorothiazide After oral administration, the absorption of hydrochlorothiazide is 60-80%. The maximum concentration of hydrochlorothiazide in the blood is achieved 1-5 hours after oral administration. The binding of hydrochlorothiazide to plasma proteins is 64%. Hydrochlorothiazide is not metabolized and is rapidly excreted through the kidneys. The half-life is 5-15 hours.

Special conditions

There is no need for special selection of the initial dose for elderly patients. Possible co-administration with other antihypertensive drugs. May increase plasma urea and creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. Hydrochlorothiazide can increase hypotension and water-electrolyte imbalance (decrease in 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 cholesterol and TG concentrations, provoke the occurrence of hyperuricemia and/or gout. Taking medications that directly affect the RAAS in the II-III trimesters of pregnancy can lead to fetal death. If pregnancy occurs, discontinuation is indicated (thiazides penetrate the BBB). For relatively healthy pregnant women, the use of diuretics is usually not recommended due to the risk of fetal and neonatal jaundice and maternal thrombocytopenia. Diuretic therapy does not prevent the development of pregnancy toxicosis. Can be prescribed together with other antihypertensive drugs. There is no need for special selection of the initial dose in elderly patients. The drug may increase plasma urea and creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary kidney. Hydrochlorothiazide may increase arterial hypotension and water-electrolyte imbalance (decreased blood volume, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce urinary calcium excretion and cause a transient, slight increase in the concentration of calcium in the blood plasma, increase cholesterol concentrations and TG, provoke the occurrence of hyperuricemia and/or gout. Lorista® ND contains lactose, so the drug is not prescribed to patients with lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome. Effect on the ability to drive vehicles and operate machinery Almost all patients during therapy with Lorista® ND can perform actions that require increased attention (for example, driving a car or driving dangerous technical equipment). In some individuals, at the beginning of therapy, the drug may cause hypotension and dizziness and thus indirectly affect their psychophysical state. For safety reasons, patients should first assess their response to treatment before engaging in activities requiring increased alertness.

Compound

1 tab. losartan potassium 100 mg hydrochlorothiazide 25 mg Excipients: pregelatinized starch - 69.84 mg, microcrystalline cellulose - 175.4 mg, lactose monohydrate - 126.26 mg, magnesium stearate - 3.5 mg. Film shell composition: hypromellose - 10 mg, macrogol 4000 - 1 mg, quinoline yellow dye (E104) - 0.11 mg, titanium dioxide (E171) - 2.89 mg, talc - 1 mg. losartan potassium 100 mg hydrochlorothiazide 12.5 mg Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate. Shell composition: hypromellose, macrogol 4000, quinoline yellow dye (E104), titanium dioxide (E171), talc. losartan potassium 100 mg hydrochlorothiazide 25 mg Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate. Shell composition: hypromellose, macrogol 4000, quinoline yellow dye (E104), titanium dioxide (E171), talc. losartan potassium 50 mg hydrochlorothiazide 12.5 mg Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate Shell composition: hypromellose, macrogol 4000, quinoline yellow dye (E104), titanium dioxide (E171), talc. losartan potassium 50 mg hydrochlorothiazide 12.5 mg Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate. Shell composition: hypromellose, macrogol 4000, quinoline yellow dye (E104), titanium dioxide (E171), talc.

Lorista N indications for use

* Arterial hypertension (patients for whom combination therapy is indicated). * Reducing the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy.

Lorista N contraindications

Hypersensitivity to losartan, to drugs that are sulfonamide derivatives and other components of the drug, anuria, severe renal dysfunction (creatinine clearance (CC) less than 30 ml/min.), hyperkalemia, dehydration (including while 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: disturbances in the water-electrolyte balance of the blood (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), bilateral renal artery stenosis or stenosis of the artery of a single kidney, diabetes mellitus, hypercalcemia, hyperuricemia and/or gout, aggravated allergic history (in some patients, angioedema developed previously when taking other drugs, including AP inhibitors

Lorista N dosage

100 mg+25 mg 12.5 mg + 100 mg 12.5 mg + 50 mg 25 mg + 100 mg 25 mg+100 mg 50 mg+12.5 mg

Lorista N side effects

Blood and lymphatic system disorders: uncommon: anemia, Henoch-Schönlein purpura. From the immune system: rarely: anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing obstruction of the airways and/or swelling of the face, lips, pharynx). From the central nervous system and peripheral nervous system: often: headache, systemic and non-systemic dizziness, insomnia, fatigue; uncommon: migraine. From the cardiovascular system: often: orthostatic hypotension (dose-dependent), palpitations, tachycardia; rarely: vasculitis. From the respiratory system: often: cough, upper respiratory tract infections, 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. From the skin and subcutaneous fat: uncommon: urticaria, itching. From the musculoskeletal system and connective tissue: often: myalgia, back pain; uncommon: arthralgia. Other: often: asthenia, weakness, peripheral edema, chest pain. Laboratory indicators: often: hyperkalemia, increased hemoglobin concentration and hematocrit (not clinically significant); uncommon: moderate increase in serum urea and creatinine levels; very rarely: increased activity of liver enzymes and bilirubin.

Drug interactions

Losartan In clinical studies, no clinically significant pharmacokinetic interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin were revealed. Rifampicin and fluconazole reduce the level of the active metabolite of losartan (this interaction has not been clinically studied). Concomitant use of losartan with potassium-sparing diuretics (spironolactone, triamterene, amiloride), potassium supplements or potassium salts may lead to hyperkalemia. NSAIDs, incl. selective COX-2 inhibitors may reduce the effectiveness of diuretics and other antihypertensive drugs, including losartan. In patients with impaired renal function who have been treated with NSAIDs (including COX-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 When used concomitantly with thiazide diuretics, ethanol, barbiturates and narcotic drugs may potentiate the risk of orthostatic hypotension. When used simultaneously with hypoglycemic agents (for oral administration and insulin), dose adjustment of the hypoglycemic agents may be required. When taken in combination with other antihypertensive drugs, an additive effect is observed. Cholestyramine and colestipol interfere with the absorption of hydrochlorothiazide. When used simultaneously with GCS and ACTH, a pronounced decrease in electrolyte levels is observed, in particular hypokalemia. Hydrochlorothiazide reduces the response to pressor amines (eg, epinephrine, norepinephrine). Hydrochlorothiazide enhances the effect of non-depolarizing muscle relaxants (for example, tubocurarine). Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity (simultaneous use is not recommended). NSAIDs (including COX-2 inhibitors) may reduce the diuretic, natriuretic and hypotensive effects of diuretics. Due to the effect on calcium metabolism, taking thiazide diuretics may distort the results of studies of parathyroid function.

Overdose

Losartan Symptoms: marked decrease in blood pressure, tachycardia, bradycardia caused by parasympathetic (vagal) stimulation. Treatment: forced diuresis, symptomatic therapy, hemodialysis is ineffective. Hydrochlorothiazide Symptoms: The most common symptoms are the result of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When taking cardiac glycosides simultaneously, hypokalemia may aggravate the course of arrhythmias. Treatment: symptomatic therapy

Storage conditions

keep away from children

Information provided

Film-coated tablets from yellow to yellow with a greenish tint, oval, slightly biconvex, with a notch on one side.

Excipients: pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate.

Shell composition: hypromellose, macrogol 4000, quinoline yellow dye (E104), titanium dioxide (E171), talc.

7 pcs. - blisters (2) - cardboard packs.
7 pcs. - blisters (4) - cardboard packs.
7 pcs. - blisters (8) - cardboard packs.
7 pcs. - blisters (12) - cardboard packs.
7 pcs. - blisters (14) - cardboard packs.
10 pcs. - blisters (3) - cardboard packs.
10 pcs. - blisters (6) - cardboard packs.
10 pcs. - blisters (9) - cardboard packs.
14 pcs. - blisters (1) - cardboard packs.
14 pcs. - blisters (2) - cardboard packs.
14 pcs. - blisters (4) - cardboard packs.
14 pcs. - blisters (6) - cardboard packs.
14 pcs. - blisters (7) - cardboard packs.

Clinical and pharmacological group

Antihypertensive drug

Pharmacological action

Combined antihypertensive drug.

Losartan- selective antagonist of angiotensin II type AT 1 receptors of 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 AT 1 receptors, regardless of the route of its synthesis: it leads to an increase in plasma renin activity and reduces the concentration of aldosterone in the blood plasma.

Losartan indirectly causes activation of AT 2 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 peripheral vascular resistance, pressure in the pulmonary circulation; reduces afterload and 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 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 drug dose was approximately 70-80% of the effect at the peak of the drug effect, 5-6 hours after administration. No withdrawal syndrome is observed; losartan also 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- 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 and uric acid. Has antihypertensive properties; the hypotensive effect develops due to the expansion of arterioles. Has 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 within 3-4 days, but 3-4 weeks may be required to achieve optimal therapeutic effect.

Pharmacokinetics

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

Losartan

Suction

Well absorbed from the gastrointestinal tract. Taking the drug with food does not have a clinically significant effect on its serum concentrations. Bioavailability is about 33%. The Cmax of losartan in blood plasma is achieved 1 hour after oral administration, and the Cmax of EXP-3174 is achieved after 3-4 hours.

Distribution

More than 99% of losartan and EXP-3174 are bound to plasma proteins, predominantly albumin. V d of losartan is 34 l. It penetrates the BBB very poorly.

Metabolism

It undergoes significant metabolism during the “first pass” through the liver, forming the active metabolite EXP-3174 (14%) and a number of inactive metabolites.

Removal

Plasma clearance of losartan and EXP-3174 is approximately 10 ml/s (600 ml/min) and 0.83 ml/s (50 ml/min), respectively. The renal clearance of losartan and EXP-3174 is approximately 1.23 ml/s (74 ml/min) and 0.43 ml/s (26 ml/min), respectively. T1/2 of losartan and EXP-3174 is 2 hours and 6-9 hours, respectively. About 58% of the drug is excreted in the bile, 35% in the kidneys.

Hydrochlorothiazide

Suction and distribution

After oral administration, absorption of hydrochlorothiazide is 60-80%. Cmax in the blood is reached 1-5 hours after oral administration. The binding of hydrochlorothiazide to plasma proteins is 64%.

Metabolism and excretion

Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. T 1/2 is 5-15 hours.

Indications for use of the drug

- arterial hypertension (patients for whom combination therapy is indicated);

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

Dosage regimen

The drug is taken orally, regardless of food intake. Lorista N can be combined with other antihypertensive drugs.

At arterial hypertension initial and maintenance dose - 1 tablet. 1 time/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. 1 time/day The maximum daily dose is 2 tablets.

With reduced blood volume (for example, while taking diuretics in high doses), the recommended initial dose of losartan in patients with hypovolemia is 25 mg 1 time / 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 failure (creatinine clearance 30-50 ml/min), including patients on dialysis, no adjustment of the initial dose of the drug is required.

For 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 1 time / day. Patients who have failed to achieve the target blood pressure level while taking losartan 50 mg / day require selection of therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg), and, if necessary, the dose of losartan should be increased to 100 mg in combination with hydrochlorothiazide at a dose of 12.5 mg/day, then increase the dose of Lorista N to 2 tablets. 1 time/day

Side effect

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

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

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

From the digestive system: often - diarrhea, dyspepsia, nausea, vomiting, abdominal pain; rarely - hepatitis, liver dysfunction; very rarely - increased activity of liver enzymes and bilirubin.

From the musculoskeletal system: often - myalgia, back pain; sometimes - arthralgia.

From the hematopoietic system: infrequently - anemia, Henoch-Schönlein purpura.

From the laboratory parameters: often - hyperkalemia, increased hemoglobin concentration and hematocrit (clinically insignificant); sometimes - a moderate increase in the level of urea and creatinine in the blood serum.

Allergic reactions: sometimes - urticaria, itchy skin; rarely - anaphylactic reactions, angioedema (including swelling of the larynx and tongue, causing obstruction of the airways and/or swelling of the face, lips, pharynx).

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

Contraindications to the use of the drug

- anuria;

- severe renal dysfunction (KR)

- hyperkalemia;

— dehydration (including while taking diuretics in high doses);

- severe liver dysfunction;

- refractory hypokalemia;

- arterial hypotension;

- lactase deficiency;

- galactosemia or glucose/galactose malabsorption syndrome;

- pregnancy;

- lactation period;

- age under 18 years (efficacy and safety have not been established);

- hypersensitivity to losartan and other components of the drug;

- hypersensitivity to sulfonamide derivatives.

WITH caution should be used for disorders of the water-electrolyte balance of the blood (hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), bilateral renal artery stenosis or stenosis of the artery of a single kidney, diabetes mellitus, hypercalcemia, hyperuricemia and/or gout, with a burdened allergic history (in some patients angioedema) edema developed earlier when taking other medications, including ACE inhibitors) and bronchial asthma, systemic blood diseases (including SLE), simultaneously with NSAIDs (including COX-2 inhibitors).

Use of the drug 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 2nd and 3rd trimesters, because Taking medications that directly act on the renin-angiotensin system during the second and third trimesters of pregnancy can lead to fetal death.

The use of diuretics during pregnancy is not recommended due to the risk of jaundice in the fetus and newborn and thrombocytopenia in the mother. Diuretic therapy does not prevent the development of pregnancy toxicosis.

If pregnancy is established, therapy with Lorista N should be discontinued immediately.

If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Use for liver dysfunction

Use for renal impairment

Special instructions

Can be prescribed together with other antihypertensive drugs.

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

Hydrochlorothiazide may increase arterial hypotension and water-electrolyte imbalance (decreased blood volume, hyponatremia, hypochloremic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce urinary calcium excretion and cause a transient, slight increase in the concentration of calcium in the blood plasma, increase cholesterol concentrations and TG, provoke the occurrence of hyperuricemia and/or gout.

Lorista ® N contains lactose, so the drug is not prescribed to patients with lactase deficiency, galactosemia or glucose/galactose malabsorption syndrome.

Impact on the ability to drive vehicles and operate machinery

Almost all patients during therapy with Lorista ® N can perform activities that require increased attention (for example, driving a car or driving dangerous technical equipment). In some individuals, at the beginning of therapy, the drug may cause hypotension and dizziness and thus indirectly affect their psychophysical state. For safety reasons, patients should first assess their response to treatment before engaging in activities requiring increased alertness.

Overdose

Losartan

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

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

Hydrochlorothiazide

Symptoms: The most common symptoms are the result of electrolyte deficiency (hypokalemia, hypochloremia, hyponatremia) and dehydration due to excessive diuresis. When taking cardiac glycosides simultaneously, hypokalemia may aggravate the course of arrhythmias.

Treatment: carrying out symptomatic therapy.

Drug interactions

Losartan

Clinical studies did not reveal clinically significant pharmacokinetic interactions of losartan 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 supplements or potassium salts may lead to hyperkalemia.

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

In patients with impaired renal function who have been treated with NSAIDs (including COX-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

When used concomitantly with thiazide diuretics, ethanol, barbiturates and narcotic drugs may potentiate the risk of developing orthostatic hypotension.

When used simultaneously with hypoglycemic agents (for oral administration and insulin), dose adjustment of the hypoglycemic agents may be required.

When taken in combination with other antihypertensive drugs, there is an additive effect.

Cholestyramine and colestipol interfere with the absorption of hydrochlorothiazide.

When used simultaneously with GCS and ACTH, a pronounced decrease in electrolyte levels is observed, in particular hypokalemia.

Hydrochlorothiazide reduces the response to pressor amines (eg, epinephrine, norepinephrine).

Hydrochlorothiazide enhances the effect of non-depolarizing muscle relaxants (for example, tubocurarine).

Diuretics reduce the renal clearance of lithium and increase the risk of lithium toxicity (simultaneous use is not recommended).

NSAIDs (including COX-2 inhibitors) may reduce the diuretic, natriuretic and hypotensive effects of diuretics.

Due to the effect on calcium metabolism, taking thiazide diuretics may distort the results of studies of parathyroid function.

Conditions for dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

List B. The drug should be stored out of the reach of children at a temperature not exceeding 30°C. Shelf life - 3 years.

Antihypertensive drug

INN

hydrochlorothiazide(hydrochlorothiazide)

losartan(losartan)

Excipients: pregelatinized starch - 34.92 mg, microcrystalline cellulose - 87.7 mg, lactose monohydrate - 63.13 mg, magnesium stearate - 1.75 mg.

Film shell composition: 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.

Film-coated tablets, 12.5 mg + 50 mg. 7, 10 or 14 tablets each. in a blister (blister pack) made of combined material PVC/PVDC-aluminum foil.

2, 4, 8, 12 or 14 bl. (blister packs) 7 tablets each), or 3, 6 or 9 bl. (blister packs) of 10 tablets), or 1, 2, 4, 6 or 7 bl. (blister packs) 14 tablets each) are placed in a cardboard pack.

Film-coated tablets from yellow to yellow with a greenish tint, oval, slightly biconvex, with a notch on one side; Cross-sectional view of the tablet - the core of the tablet is white.

Pharmacological action- hypotensive.

Concomitant use with aliskiren in patients with diabetes mellitus or impaired renal function (creatinine clearance 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.

Concomitant use of losartan, as well as other drugs acting on the RAAS, with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium supplements or salt substitutes containing potassium may lead to an increase in serum potassium levels. Simultaneous use is not recommended.

Possible reduction in the excretion of lithium ions. Therefore, when using ARA II concomitantly 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 levels (especially in patients with a history of renal dysfunction). Concomitant use with NSAIDs should be done with caution, especially in elderly patients. In this case, it is necessary to adequately replenish the volume of blood volume and periodically monitor renal function from the moment of initiation of therapy and subsequently.

In some patients with impaired renal function using NSAIDs, incl. selective COX-2 inhibitors, simultaneous use of ARA II may cause further reversible deterioration of 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 careful monitoring of renal function.

In patients with atherosclerosis, heart failure or diabetes mellitus with target organ damage, double blockade of the RAAS (with simultaneous use of ARB II and ACE inhibitors) is accompanied by an increased incidence of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) in comparison with the use of a drug from one of the listed groups.

When used simultaneously with other drugs that cause arterial hypotension, incl. tricyclic antidepressants, antipsychotics (neuroleptics), baclofen, amifostine increases the risk of developing arterial hypotension.

Hydrochlorothiazide

Alcohol, barbiturates, anesthetics or antidepressants: may potentiate the risk of orthostatic hypotension.

Oral hypoglycemic agents and insulin: dosage adjustment of hypoglycemic agents may be required because hydrochlorothiazide affects glucose tolerance.

Metformin should be used with caution due to the risk of lactic acidosis due to renal impairment caused by hydrochlorothiazide.

Other antihypertensive drugs: additive effect.

Cholestyramine and colestipol: absorption of hydrochlorothiazide is reduced. Cholestyramine 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 (for example, 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 (for example, tubocurarine): the effect of muscle relaxants may be enhanced.

Lithium: there may be a decrease in the renal clearance of lithium and, accordingly, the risk of developing lithium intoxication. Therefore, simultaneous use is not recommended.

Medicines used to treat gout (probenecid, sulfinpyrazone and allopurinol): dose adjustment of uricosuric drugs may be required because hydrochlorothiazide may cause an increase in serum uric acid concentrations. 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: the myelosuppressive effect increases by slowing elimination 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 be enhanced.

Methyldopa: Isolated cases of hemolytic anemia have been reported during concomitant use.

Concomitant use of cyclosporine increases the risk of developing hyperuricemia and exacerbation of gout.

Cardiac glycosides: Hypokalemia and hypomagnesemia caused by the use of thiazide diuretics increase the risk of arrhythmias when treated with cardiac glycosides.

Drugs that may cause side effects due to changes in serum potassium levels:

It is recommended to periodically monitor potassium levels in the blood serum and ECG when used simultaneously with cardiac glycosides and drugs that prolong the interval QT(risk of developing ventricular tachycardia of the “pirouette” type);

IA class of antiarrhythmic drugs (for example, quinidine, disopyramide);

Class III antiarrhythmic drugs (for example, 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: simultaneous use of thiazide diuretics with vitamin D or calcium salts increases the calcium level in the blood serum, because calcium excretion decreases. If it is necessary to use calcium or vitamin D supplements, the calcium level in the blood serum should be monitored and, possibly, the dose of these drugs should be adjusted;

Carbamazepine: risk of developing symptomatic hyponatremia. It is necessary to monitor clinical and biological parameters.

Hydrochlorothiazide may increase the risk of acute renal failure, especially when used concomitantly with high doses of iodinated contrast agents. Before using them, it is necessary to restore the bcc.

Amphotericin B (for IV administration), stimulant laxatives or ammonium glycyrrhizinate (found in licorice): Hydrochlorothiazide may increase fluid and electrolyte disturbances, especially hypokalemia.

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 undergoes first-pass metabolism through the liver to form an active carboxyl metabolite (EXP-3174) and inactive metabolites. Systemic bioavailability is approximately 33%. Cmax in blood plasma of losartan and its active metabolite is achieved 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 achieved 1–5 hours after oral administration.

Distribution. Losartan: More than 99% of losartan and EXP-3174 are bound to plasma proteins, predominantly albumin. V d of losartan is 34 l. It penetrates the BBB very poorly. Hydrochlorothiazide: binding to plasma proteins is 64%; penetrates the placenta, but not the BBB, and is excreted in breast milk.

Biotransformation. Losartan: Approximately 14% of a dose of losartan administered intravenously or taken orally is metabolized to form an active metabolite. After oral and/or intravenous administration of 14 C-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.

Excretion. Losartan: 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 an 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 eliminated through the kidneys. T1/2 is 5.6–14.8 hours. About 61% of the dose taken orally is excreted unchanged.

Selected patient groups

Hydrochlorothiazide/losartan. Plasma concentrations of losartan and its active metabolite and hydrochlorothiazide in elderly patients with arterial hypertension did not differ significantly from those in young patients.

Losartan. In patients with mild to moderate alcoholic cirrhosis after oral administration 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.

Hydrochlorothiazide/losartan

Lorista ® N is a combination 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 its diuretic effect, hydrochlorothiazide increases plasma renin activity, aldosterone secretion, reduces serum potassium levels and increases the level of angiotensin II in blood plasma. Losartan blocks the physiological effects of angiotensin II and, by inhibiting aldosterone secretion, can neutralize the loss of potassium ions caused by the diuretic.

Losartan has a uricosuric effect. Hydrochlorothiazide causes a moderate increase in uric acid concentrations; When losartan is used simultaneously with hydrochlorothiazide, hyperuricemia caused by the diuretic is reduced.

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 older (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 powerful vasoconstrictor and the main hormone of the RAAS. Angiotensin II binds to AT 1 receptors, which are found in many tissues (eg, vascular smooth muscle, adrenal glands, kidneys and myocardium) and mediate 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 AT 1 receptors. In vivo And in vitro losartan and its biologically active carboxyl metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on AT 1 receptors, regardless of the route of its synthesis. Losartan does not have agonism and does not block other hormonal receptors or ion channels important in the regulation of cardiovascular system. Losartan does not suppress 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 incidence of bradykinin-mediated adverse effects.

Losartan indirectly causes activation of AT 2 receptors by increasing the level of angiotensin II in the blood plasma.

Suppression of the regulation of renin secretion by angiotensin II through a negative feedback mechanism during treatment with 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 concentrations decrease to baseline values within 3 days.

Losartan and its main active metabolite have a significantly higher affinity for AT 1 receptors compared to AT 2 receptors. The active metabolite is 10–40 times more active than losartan.

The incidence of cough is comparable with the use of losartan or hydrochlorothiazide and significantly lower than with the use of an ACE inhibitor.

In patients with hypertension and proteinuria who do not have diabetes mellitus, treatment with losartan significantly reduces proteinuria, albumin and IgG excretion. Losartan supports glomerular filtration and reduces the filtration fraction. Losartan reduces serum uric acid concentrations (usually less than 0.4 mg/dL) throughout therapy. Losartan has no effect on autonomic reflexes and does not affect the concentration of norepinephrine in the blood plasma.

In patients with left ventricular failure, losartan in 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 developing 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 DBP. The hypotensive effect continues 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 older patients (65 years of age and older) and younger patients (under 65 years of age). Discontinuation of losartan in patients with arterial hypertension does not lead to a sharp increase in blood pressure (there is no drug withdrawal syndrome). Losartan does not have a clinically significant effect on heart rate.

Hydrochlorothiazide

A thiazide diuretic, the mechanism of hypotensive action of which has not been fully established. Thiazides alter the reabsorption of electrolytes in the distal nephron and increase the excretion of sodium and chloride ions to approximately equal extent. The diuretic effect of hydrochlorothiazide leads to a decrease in blood volume, an increase in plasma renin activity and aldosterone secretion, which leads to an increase in the excretion of potassium ions and bicarbonates by the kidneys and a decrease in serum potassium levels. The connection between renin and aldosterone is mediated by angiotensin II, therefore the simultaneous use of ARA II suppresses the loss of potassium ions during treatment with thiazide diuretics.

After oral administration, the diuretic effect occurs within 2 hours, reaches a maximum after approximately 4 hours and persists for 6–12 hours; the hypotensive effect persists for 24 hours.

arterial hypertension (patients for whom combination therapy is indicated);

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

hypersensitivity to losartan, sulfonamide derivatives and other excipients;

anuria, severe renal failure (creatinine Cl less than 30 ml/min);

severe liver failure (more than 9 points on the Child-Pugh scale), cholestasis and obstructive diseases of the biliary tract;

simultaneous use with aliskiren in patients with diabetes mellitus or impaired renal function (Cl creatinine less than 60 ml/min);

age under 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, because Lorista ® N contains lactose;

pregnancy;

breastfeeding period.

With caution: severe hyponatremia and/or conditions accompanied by a decrease in blood volume (including a diet with limited salt, diarrhea, vomiting, therapy with high doses of diuretics); disturbances in the water-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 classification NYHA and other conditions accompanied by activation of the RAAS; bilateral renal artery stenosis or stenosis of the artery of a single kidney; condition after kidney transplantation; primary hyperaldosteronism; coronary heart disease and cerebrovascular diseases, because 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 (HOCM); aggravated allergic history (the patient has a history of angioedema when using drugs, including ACE inhibitors and AR II) and bronchial asthma; systemic lupus erythematosus; acute myopia and secondary acute angle-closure glaucoma; symptomatic hyperuricemia/gout.

The use of ARA II in the first trimester of pregnancy is not recommended.

The drug Lorista ® N should not be used during pregnancy, or in women planning 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, you should stop taking Lorista ® N and, if necessary, transfer the patient to alternative antihypertensive therapy.

The drug Lorista ® N, like other drugs that have a direct effect on the RAAS, can cause adverse effects in the fetus (impaired renal function, delayed ossification of fetal skull bones, oligohydramnios) and neonatal toxic effects (renal failure, arterial hypotension, hyperkalemia). If, nevertheless, the drug Lorista ® N was used in the II–III trimesters of pregnancy, then it is necessary to conduct an ultrasound of the kidneys and bones of the fetal skull.

Hydrochlorothiazide crosses the placenta. When using thiazide diuretics in the 2nd–3rd trimester of pregnancy, a decrease in uteroplacental blood flow, the development of thrombocytopenia, jaundice, and water-electrolyte imbalance in the fetus or newborn are possible.

Hydrochlorothiazide should not be used to treat gestosis in the second half of pregnancy (edema, hypertension or preeclampsia (nephropathy)) due to the risk of a decrease in blood volume 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 when alternative agents are not available.

Newborns whose mothers took Lorista ® N during pregnancy should be monitored because the development of arterial hypotension in the newborn is possible.

It is not known whether losartan is excreted in breast milk.

Hydrochlorothiazide passes into mother's breast milk in small quantities. Thiazide diuretics in high doses cause intense diuresis, thereby suppressing lactation.

Inside, regardless of food intake, with a sufficient amount of water, once a day. Lorista ® N can be taken simultaneously with other antihypertensive drugs.

Arterial hypertension. The combination of hydrochlorothiazide/losartan is indicated for patients in whom adequate blood pressure control is not achieved with the separate use of hydrochlorothiazide or losartan.

It is recommended to titrate the dose of losartan and hydrochlorothiazide before transferring the patient to therapy with Lorista ® N. If necessary (if blood pressure control is inadequate), transferring the patient from therapy with Lorista ® (losartan) to therapy with Lorista ® N may be considered.

Initial and maintenance dose - 1 tablet. 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. drug Lorista ® N 1 time per day.

Special patient groups

Patients with impaired renal function or on hemodialysis. In patients with moderate renal impairment (creatinine clearance 30–50 ml/min), no adjustment of the initial dose of the drug is required.

Patients with low blood volume. The recommended starting dose of losartan is 25 mg once daily.

Before starting treatment with Lorista ® N, the diuretic should be discontinued and the blood volume and/or sodium ion content 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 failed 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, and then increase to 2 tablets. drug Lorista ® N (total 25 mg of hydrochlorothiazide and 100 mg of losartan per day) once a day. If additional blood pressure reduction is necessary, other antihypertensive drugs should be added.

WHO classification of the incidence of side effects:

very often?1/10; often from?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 the hydrochlorothiazide/losartan combination were previously observed with the use of losartan and/or hydrochlorothiazide.

Post-marketing use of the hydrochlorothiazide/losartan combination

Additional adverse reactions

rarely - hepatitis.

Laboratory data: rarely - hyperkalemia, increased ALT activity.

Adverse reactions that occurred when using losartan or hydrochlorothiazide in monotherapy may occur when using a combination of hydrochlorothiazide/losartan:

Losartan

infrequently - anemia, Henoch-Schönlein purpura, ecchymosis, hemolysis; frequency unknown - thrombocytopenia.

From the SSS side: infrequently - pronounced decrease in blood pressure, orthostatic hypotension, chest pain, angina pectoris, AV block of the second degree, cerebrovascular accident, myocardial infarction (with an excessive decrease in blood pressure), palpitations, arrhythmia (atrial fibrillation, sinus bradycardia, tachycardia, ventricular tachycardia, fibrillation ventricles), vasculitis.

From the senses: uncommon - vertigo, tinnitus, blurred vision, burning/tingling sensation in the eyes, conjunctivitis, decreased visual acuity.

From the digestive system: often - abdominal pain, nausea, diarrhea, dyspepsia; uncommon - constipation, tooth pain, dry oral mucosa, bloating, gastritis, vomiting, intestinal obstruction; frequency unknown - pancreatitis, liver dysfunction.

Allergic reactions: rarely - hypersensitivity, anaphylactic reactions, angioedema, including swelling of the larynx and pharynx causing airway obstruction, and/or swelling of the face, lips, pharynx and/or tongue; Some patients also had a history of angioedema during treatment with other drugs, including ACE inhibitors.

often - muscle cramps, back pain, leg pain, myalgia; uncommon - arm pain, joint swelling, knee pain, musculoskeletal pain, shoulder pain, stiffness, arthralgia, arthritis, coxalgia, fibromyalgia, muscle weakness; frequency unknown - rhabdomyolysis.

From the nervous system: often - headache, dizziness, insomnia; uncommon - nervousness, paresthesia, peripheral neuropathy, tremor, migraine, syncope, anxiety, anxiety disorder (excessive, uncontrollable and often irrational worry about everyday events), panic disorder (repeated panic attacks), confusion, depression, nightmares, sleep disturbances , drowsiness, memory impairment.

often - impaired renal function, renal failure; uncommon - nocturia, frequent urination, urinary tract infections.

From the reproductive system: uncommon - decreased libido, erectile dysfunction/impotence.

often - cough, upper respiratory tract infections, nasal congestion, sinusitis, obstruction of the upper respiratory tract; uncommon - discomfort in the throat, pharyngitis, laryngitis, shortness of breath, bronchitis, nosebleeds, rhinitis, congestion in the respiratory tract.

From the skin: uncommon - alopecia, dermatitis, dry skin, erythema, feeling of flushing of the face, photosensitivity, itching, skin rash, urticaria, increased sweating.

Others: often - asthenia, increased fatigue, anorexia; infrequently - facial swelling, edema, fever; frequency unknown - flu-like symptoms, malaise.

Laboratory indicators: often - hyperkalemia, slight decrease in Hb and hematocrit, hypoglycemia; infrequently - a slight increase in serum concentrations of urea and creatinine; very rarely - increased activity of liver enzymes and bilirubin concentration in the blood plasma; frequency unknown - hyponatremia.

Hydrochlorothiazide

From the hematopoietic organs: uncommon - agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia.

Allergic reactions: rarely - anaphylactic reaction.

From the side of metabolism: uncommon - anorexia, hyperglycemia, hyperuricemia, hypokalemia, hyponatremia.

From the nervous system: often - headache; infrequently - insomnia.

From the senses: infrequently - transient disturbance of visual perception, xanthopsia; frequency unknown - acute myopia and acute angle-closure glaucoma.

From the SSS side: infrequently - necrotizing angiitis (vasculitis, cutaneous vasculitis).

From the respiratory system: uncommon - respiratory distress syndrome, including pneumonitis and pulmonary edema.

From the digestive system: uncommon - sialadenitis, spasm, stomach irritation, nausea, vomiting, diarrhea, constipation, jaundice (intrahepatic cholestasis), pancreatitis.

From the skin: uncommon - photosensitivity, urticaria, toxic epidermal necrolysis.

From the musculoskeletal system: infrequently - muscle cramps.

From the genitourinary system: uncommon - glycosuria, interstitial nephritis, renal dysfunction, renal failure.

Others: infrequently - fever, dizziness.

Lorista ® N

There is no information about an overdose of the hydrochlorothiazide/losartan combination.

Treatment: symptomatic and supportive therapy. The drug Lorista ® N should be discontinued and the patient should be carefully monitored. If necessary: induce vomiting (if the patient has recently taken the drug), replenish blood volume, correct disorders of water and electrolyte metabolism and a pronounced decrease in blood pressure.

Losartan(data limited)

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

Treatment: symptomatic therapy, hemodialysis is ineffective.

Hydrochlorothiazide

Symptoms: The most common symptoms are: hypokalemia, hypochloremia, hyponatremia and dehydration as a result of excessive diuresis. When taking cardiac glycosides simultaneously, hypokalemia may aggravate the course of arrhythmias.

Treatment: symptomatic.

Losartan

Angioedema. Patients with a history of angioedema (of the face, lips, pharynx and/or larynx) should be closely monitored.

Arterial hypotension and hypovolemia (dehydration). In patients with hypovolemia (dehydration) and/or reduced sodium content in the blood plasma during diuretic therapy, restriction of salt intake, diarrhea or vomiting, symptomatic arterial hypotension may develop, especially after taking the first dose of Lorista ® N. Before using the drug, the drug should be restored BCC and/or sodium content in blood plasma.

Water-electrolyte balance disorders. Fluid and electrolyte imbalances are common in patients with impaired renal function, especially in the setting of diabetes mellitus. In this regard, it is necessary to carefully monitor the potassium content in the blood plasma and creatinine clearance, especially in patients with heart failure and creatinine Cl 30-50 ml/min.

Concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that can increase the level of potassium in the blood plasma (for example, heparin) is not recommended.

Liver dysfunction. The concentration of losartan in the blood plasma increases significantly in patients with liver cirrhosis, so Lorista ® N should be used with caution in patients with mild or moderate liver dysfunction.

Renal dysfunction. Impaired renal function, including renal failure, may occur due to inhibition of the RAAS (especially in patients whose renal function is dependent on the RAAS, such as those with severe heart failure or a history of renal dysfunction).

Renal artery stenosis. In patients with bilateral renal artery stenosis, as well as stenosis of the artery of the only functioning kidney, drugs affecting the RAAS, incl. and ARA II, can reversibly increase the concentrations of urea and creatinine in the blood plasma.

Losartan should be used with caution in patients with bilateral renal artery stenosis or arterial stenosis of a solitary kidney.

Kidney transplantation. 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, therefore, in such patients, the use of Lorista ® N is not recommended.

IHD and cerebrovascular diseases. As with the treatment of any antihypertensive drugs, an excessive decrease in blood pressure in patients with coronary artery disease or cerebrovascular diseases can lead to the development of 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 affecting the RAAS may be accompanied by severe arterial hypotension, oliguria and/or progressive azotemia, and in rare cases, acute renal failure. It is impossible to exclude the development of these disorders due to suppression of RAAS activity while taking ARA II.

Stenosis of the aortic and/or mitral valve, HOCM. Lorista ® N, like other vasodilators, should be used with caution in patients with hemodynamically significant stenosis of the aortic and/or mitral valve, or HOCM.

Ethnic characteristics. Losartan (like other drugs that affect the RAAS) has a less pronounced hypotensive effect in patients of the Negroid race compared to representatives of other races, possibly due to the higher incidence of hyporeninemia in these patients with arterial hypertension.

Hydrochlorothiazide

Arterial hypotension and disturbances of water and electrolyte metabolism. It is necessary to monitor 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 electrolyte levels should be monitored periodically.

Metabolic and endocrine effects. Caution is necessary in all patients receiving treatment with oral hypoglycemic agents or insulin, because hydrochlorothiazide may weaken their effect. During therapy with thiazide diuretics, latent diabetes mellitus can manifest itself.

Thiazide diuretics, including hydrochlorothiazide, can cause fluid and electrolyte imbalance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypokalemic alkalosis).

Thiazide diuretics may reduce renal excretion of calcium and cause a temporary and slight increase in plasma calcium.

Severe hypercalcemia may be a sign of hidden hyperparathyroidism. Before testing the function of the parathyroid glands, thiazide diuretics must be discontinued.

During treatment with thiazide diuretics, it is possible to increase the concentration of cholesterol and triglycerides in the blood serum.

Therapy with thiazide diuretics may worsen hyperuricemia and/or aggravate gout in some patients.

Losartan reduces the concentration of uric acid in the blood plasma, so its use in combination with hydrochlorothiazide neutralizes the hyperuricemia caused by the thiazide diuretic.

Liver dysfunction. 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.

The drug Lorista ® N is contraindicated in patients with severe liver dysfunction, because There is no experience in 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 leading to transient acute myopia and acute angle-closure glaucoma. Symptoms include: sudden decrease in visual acuity or eye pain, usually occurring within hours to 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 medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma are: a history of an allergic reaction to sulfonamide or benzylpenicillin.

General

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 there is a history of such.

There are reports of exacerbation of systemic lupus erythematosus with the use of thiazide diuretics.

Special information on excipients

The drug Lorista ® N contains lactose, therefore the drug is contraindicated in patients with lactase deficiency, lactose intolerance, and glucose-galactose malabsorption syndrome.

Impact 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, the drug Lorista ® N may cause a decrease in blood pressure, dizziness or drowsiness, thus indirectly affecting the psycho-emotional state. For safety reasons, patients should first assess their response to treatment before engaging in activities requiring increased alertness.

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of the reach of children.

More than 20,000 patients took part in studies on the effectiveness and safety of Lorista.

The results of the studies demonstrated the following data:

In the Takeoff study, Lorista ® (losartan from KRKA) significantly reduced uric acid levels by 32.6% in patients with arterial hypertension (AH) and concomitant hyperuricemia and/or gout. 100% of patients participating in the study achieved the target blood pressure level. Therapy with Lorista has a pronounced positive effect on the elasticity of the vascular wall in patients with hypertension 1;

The open-label, multicenter clinical trial LAURA 2 (Lorista ® and uric acid) examined the association between treatment with Lorista and its fixed combination with hydrochlorothiazide (Lorista ® H and Lorista ® HD) and hyperuricemia. Based on the results of the study in patients with hypertension and hyperuricemia, Lorista ® , Lorista ® H and Lorista ® ND, due to their apparent ability to lower uric acid levels, can be used as the preferred therapy;

The EFFECT 3 study proved the effectiveness and safety of losartan (Lorista ®) in patients with mild and moderate hypertension. In addition, it is important to emphasize the safety of using Lorista (adverse effects in less than 1% of patients), which makes the drug an indispensable assistant in the fight against hypertension;

As a result of the international study Gemera 4, the effectiveness and safety of the use of Lorista ® and a fixed combination with hydrochlorothiazide (Lorista ® N) in patients with stage 1–2 hypertension was confirmed. 100% of patients achieved CAP.

The results of clinical studies conducted with the drug KRKA Lorista (losartan) and its fixed combinations with hydrochlorothiazide further indicate that the drug contributes not only to the effective and well-tolerated treatment of hypertension, but also to the reduction of cardiovascular risk.

1. Nedogoda S.V., Ledyaeva A.A., Chumachok E.V., Tsoma V.V., Salasyuk A.S. Possibilities of losartan in angioprotection against hyperuricemia in patients with arterial hypertension. Systemic hypertension. - 2012. - No. 4. - P.50–54.

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