Lorista N pills 50mg+12.5mg, 60pcs

Composition

1 film-coated tablet contains:

Core:

Active ingredients:

Hydrochlorothiazide 12.50 mg

Losartan Potassium 50.00 mg

Auxiliary substances:

Pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate

Film shell:

Hypromellose, macrogol-4000, quinoline yellow dye (E 104), titanium dioxide (E 171), talc

Pharmacological action

antihypertensive combined agent (diuretic + angiotensin II receptor antagonist).

Clinical Pharmacology

Pharmacodynamics

Combination of hydrochlorothiazide + losartan

Lorista® N is a combination drug, the components of which have an additive antihypertensive effect and cause a more pronounced decrease in blood pressure (BP) compared to their separate use. Due to its diuretic action, hydrochlorothiazide increases plasma renin activity, aldosterone secretion, reduces serum potassium content, 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 an uricosuric effect. Hydrochlorothiazide causes a moderate increase in the concentration of uric acid, when losartan is used simultaneously with hydrochlorothiazide, hyperuricemia caused by the diuretic decreases.

The antihypertensive effect of the combination of hydrochlorothiazide + losartan persists for 24 hours. Despite a significant reduction in blood pressure, the use of a combination of hydrochlorothiazide + losartan does not have a clinically significant effect on heart rate (HR).

The combination of hydrochlorothiazide + losartan is effective in men and women, as well as in younger (under 65 years) and older (65 years and older) patients.

Hydrochlorothiazide

The mechanism of action of thiazide diuretics (thiazides) is not fully understood. Thiazides block the reabsorption of sodium and chlorine ions at the beginning of the renal tubules. Thus, they increase the excretion of sodium and chlorine and, consequently, the elimination of water from the body.

As a result of the diuretic effect of hydrochlorothiazide, the volume of circulating fluid (BCC) decreases, which increases the activity of renin and the content of aldosterone in blood plasma. This leads to an increase in the excretion of potassium ions by the kidneys and a decrease in the content of potassium in the blood plasma (hypokalemia). Hydrochlorothiazide also increases the excretion of magnesium ions and reduces the excretion of calcium ions by the kidneys. Thiazide diuretics reduce uric acid excretion by the kidneys and increase its concentration in blood plasma. Thiazide diuretics also reduce carbonic anhydrase activity by increasing the elimination of bicarbonate ions. But this effect is usually weak and does not affect the pH of urine.

At maximum therapeutic doses, the diuretic / natriuretic effect of all thiazide diuretics is approximately the same. Natriuresis and diuresis occur within 2 hours and reach their maximum in about 4 hours. The duration of diuretic action of hydrochlorothiazide is from 6 to 12 hours.

Hydrochlorothiazide has an antihypertensive effect. Thiazide diuretics do not affect normal blood pressure.

Losartan

Losartan is an oral angiotensin II receptor antagonist (ARA II) of a non-protein nature.

Angiotensin II is a potent vasoconstrictor and the main hormone of the renin-angiotensin-aldosterone system (RAAS). Angiotensin II binds to AT1receptors, which are found in many tissues (for example, 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 smooth muscle cell proliferation.

Losartan selectively blocks AT_-1receptors. Under the conditionsof invivo and invitro, losartan and its biologically active carboxyl metabolite (EXP-3174) block all physiologically significant effects of angiotensin II on AT1receptors, regardless of the pathway of its synthesis. Losartan has no agonism and does not block other hormone receptors or ion channels that are important in the regulation of the cardiovascular system. Losartan does not inhibit the activity of angiotensin-converting enzyme (ACE) (kininase II), an enzyme involved in bradykinin metabolism. 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 blood plasma.

Suppression of the regulation of renin secretion by angiotensin II by the “negative feedback” mechanism during losartan treatment causes an increase in plasma renin activity, which leads to an increase in the concentration of angiotensin II in blood plasma. However, the antihypertensive effect and inhibition of aldosterone secretion remain, indicating an 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 affinityfor AT1 receptors compared to AT2 receptors. The active metabolite is 10-40 times more active than losartan.

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

In patients with arterial hypertension, proteinuria and without diabetes mellitus, losartan treatment significantly reduces proteinuria, albumin and immunoglobulin G (IgG) excretion. Losartan supports glomerular filtration and reduces the filtration fraction. Losartan reduces the serum uric acid concentration (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 blood plasma.

In patients with left ventricular insufficiency, losartan in doses of 25 mg and 50 mg has positive hemodynamic and neurohumoral effects, characterized by an increase in cardiac index and a decrease in pulmonary capillary jamming pressure, total peripheral vascular resistance (OPSS), average blood pressure, heart rate, and a decrease in plasma concentrations of aldosterone and norepinephrine. The risk of 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 systolic and diastolic blood pressure. The antihypertensive effect lasts for 24 hours while maintaining the natural circadian rhythm of blood pressure. The degree of BP reduction at the end of the dosing interval is 70-80% compared to the antihypertensive 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). Withdrawal of losartan in patients with arterial hypertension does not lead to a sharp increase in blood pressure (there is no “withdrawal” syndrome of the drug). Losartan has no clinically significant effect on heart rate.

Pharmacokinetics

The pharmacokinetics of losartan and hydrochlorothiazide when taken simultaneously do not differ from those when they are used separately.

Hydrochlorothiazide

Suction and distribution

Hydrochlorothiazide is incompletely, but fairly quickly absorbed from the gastrointestinal tract (GIT). After oral use at a dose of 100 mg, the maximum concentration (cmax) of hydrochlorothiazide in blood plasma is reached in 1.5-2.5 hours. At the maximum diuretic activity (approximately 4 hours after use), the concentration of hydrochlorothiazide in blood plasma is 2 mcg / ml. The binding to plasma proteins is 40%.

Hydrochlorothiazide penetrates the placental barrier and is excreted in breast milk, but does not cross the blood-brain barrier.

Metabolism

Hydrochlorothiazide is not metabolized in the human body.

Deduction

The primary route of excretion through the kidneys (filtration and secretion) in unchanged form. Approximately 61% of the oral dose is eliminated within 24 hours. In patients with normal renal function, the half-life (_half-life) is from 5.6 to 14.8 hours (average 6.4 hours).

Pharmacokinetics in special patient groups

Impaired renal function

In patients with moderate renal insufficiency, the_half-life of hydrochlorothiazide is an average of 11.5 hours, and in patients with creatinine clearance (CC) less than 30 ml/min, it is 20.7 hours.

Losartan

Suction

After oral use, losartan is well absorbed and undergoes metabolism during the “primary passage” through the liver with the formation of an active carboxyl metabolite (EXP-3174) and inactive metabolites. The systemic bioavailability is approximately 33%. Mean _{plasma cmax values of}losartan and its active metabolite are reached after 1 hour and 3-4 hours, respectively.

Distribution

More than 99% of losartan and EXP-3174 bind to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters.Very poorly penetrates the blood-brain barrier.

Metabolism

Approximately 14% of the dose of losartan administered intravenously or taken orally is metabolized to form the active metabolite. After oral and/or intravenous use of 14C-losartan potassium, circulating plasma radioactivity was mainly determined by losartan and its active metabolite. In addition to the active metabolite, inactive metabolites are formed, including two main metabolites formed by hydroxylation of the butyl group of the chain, and a minor metabolite-N-2-tetrazole glucuronide.

Taking the drug with food does not have a clinically significant effect on its serum concentrations.

Deduction

The plasma clearance of losartan and its active metabolite is 600 ml / min and 50 ml/min, respectively, and the renal clearance of losartan and its active metabolite is 74 ml / min and 26 ml/min, respectively. After oral use, only about 4% of the dose is excreted unchanged by the kidneys and about 6% as the active metabolite. The pharmacokinetic parameters of losartan and its active metabolite when taken orally (in doses up to 200 mg) are linear.

The_half-life 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 mainly excreted through the intestines with bile (58%), kidneys -35%.

Pharmacokinetics in special patient groups

Liver function disorders

In patients with mild and moderate alcoholic cirrhosis of the liver after oral use of losartan, the concentrations of losartan and the active metabolite in blood plasma were 5 and 1.7 times higher than in young male volunteers, respectively.

Losartan and its active metabolite are not removed by hemodialysis.

Elderly patients

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

Indications

* Arterial hypertension (patients who are indicated for combination therapy).

· Reduction of the risk of cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy, manifested by a combined decrease in the frequency of cardiovascular mortality, stroke and myocardial infarction.

Use during pregnancy and lactation

Pregnancy

Application of Lorista® H is contraindicated during pregnancy. When planning pregnancy, it is recommended to transfer the patient to alternative antihypertensive therapy, taking into account the safety profile. If pregnancy is confirmed, Lorista® H should be discontinued and, if necessary, switched to alternative antihypertensive therapy.

Lorista ® H, like other drugs that have a direct effect on the RAAS, may cause adverse events in the fetus (impaired renal function, slowing ossification of the fetal skull bones, oligohydramnion) and neonatal toxic effects (renal failure, hypotension, hyperkalemia). If the drug Lorista®was still used If in the II-III trimesters of pregnancy, it is necessary to conduct an ultrasound examination of the kidneys and skull bones of the fetus.

There is limited experience with the use of hydrochlorothiazide during pregnancy (especially in the first trimester). Preclinical safety data are insufficient. Hydrochlorothiazide penetrates the placental barrier, is detected in the umbilical cord blood. Taking into account the mechanism of pharmacological action of hydrochlorothiazide, its use in the second and third trimesters of pregnancy can disrupt fetoplacental perfusion and lead to the development of complications in the fetus and newborn such as jaundice, impaired water-electrolyte balance and thrombocytopenia. Cases of thrombocytopenia in newborns whose mothers received thiazide diuretics are described.

The use of hydrochlorothiazide during pregnancy is contraindicated. Hydrochlorothiazide should not be used for the treatment of gestosis in the second half of pregnancy (edema, hypertension, or preeclampsia), as it increases the risk of BCC reduction and placental hypoperfusion, but does not have a beneficial effect on the course of these pregnancy complications. Diuretics do not prevent the development of gestosis.

Breast-feeding period

Lorista®Preparation H is contraindicated during breastfeeding, as there is no experience of using it. 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 penetrates into the mother’s milk, and therefore its use during breastfeeding is contraindicated. If the use of hydrochlorothiazide during lactation is absolutely necessary, then breastfeeding should be discontinued.

Contraindications

* Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, as the composition of the drug Lorista® N includes lactose.

·  Hypersensitivity to losartan, hydrochlorothiazide and other sulfonamide derivatives, as well as to excipients.

·  Age up to 18 years (efficacy and safety of use have not been established).

* Pregnancy, breast-feeding period.

* Hypokalemia or hypercalcemia that is resistant to therapy.

* Refractory hyponatremia.

* Anuria, severe renal failure (creatinine clearance less than 30 ml / min).

·  Severe hepatic insufficiency (more than 9 points on the Child-Pugh scale), cholestasis and obstructive biliary tract diseases.

* Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and / or moderate to severe renal impairment (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 of body surface area).

* Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

Interaction

Hydrochlorothiazide

Not recommended drug combinations

Lithium preparations

Concomitant use of hydrochlorothiazide and lithium preparations decreases the renal clearance of lithium, which can lead to an increase in the concentration of lithium in blood plasma and increase its toxicity. If concomitant use of hydrochlorothiazide is necessary, the dose of lithium preparations should be carefully selected, the concentration of lithium in blood plasma should be regularly monitored, and the dose of the drug should be adjusted accordingly.

Drug combinations that require special attention

Drugs that can cause polymorphic ventricular tachycardia of the “pirouette”type

Special caution should be exercised when using hydrochlorothiazide concomitantly with medications such as::

· Class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide);

· Class III antiarrhythmic drugs (dofetilide, ibutilide, bretilia tosylate, sotalol, dronedarone, amiodarone);

· other (non-antiarrhythmic) drugs, such as:

– neuroleptics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamides (amisulpride, sultopride, sulpride, tiapride), butyrophenones (droperidol, haloperidol), pimozide, sertindol;

– antidepressants: tricyclic antidepressants, selective serotonin reuptake inhibitors (citalopram, escitalopram);

– antibacterial agents: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin), macrolides (intravenous erythromycin, azithromycin, clarithromycin, roxithromycin, spiramycin), co-trimoxazole;

– antifungal agents:the azoles (voriconazole, Itraconazole, ketoconazole, fluconazole);

– anti-malarial drugs (quinine, chloroquine, mefloquine, halofantrine, lumefantrine);

– Antiprotozoal drugs (pentamidine for parenteral use);

– anti-anginal agents (ranolazine, bepridil);

-antineoplastic agents (vandetanib, arsenic trioxide, oxaliplatin, tacrolimus);

– antiemetics (domperidone, ondansetron);

– means of influencing the motility of the gastrointestinal tract (cisapride);

– antihistamines (astemizole, terfenadine, mizolastine);

– other medicines (anagrelide, vasopressin, has diphemanil metilsulfate, ketanserin, probucol, propofol, sevoflurane, terlipressin, terodiline, Cilostazol).

Due to the increased risk of ventricular arrhythmias, especially polymorphic ventricular tachycardia of the “pirouette” type (risk factor – hypokalemia), the potassium content in the blood plasma should be determined and, if necessary, adjusted before starting combination therapy with hydrochlorothiazide with the above drugs.It is necessary to monitor the patient’s clinical condition, blood plasma electrolyte content, and ECG parameters. In patients with hypokalemia, it is necessary to use drugs that do not cause polymorphic ventricular tachycardia of the “pirouette”type.

Medications that can increase the duration of the QT interval

Concomitant use of hydrochlorothiazide with medicinal products capable of prolonging the QT interval should be based on a careful assessment of the ratio of expected benefit and potential risk for each patient (there may be an increased risk of developing polymorphic ventricular tachycardia of the “pirouette” type). When using such combinations, it is necessary to regularly record an ECG (to detect prolongation of the QT interval), as well as monitor the content of potassium in the blood plasma.

Drugs that can cause hypokalemia: amphotericin B (with intravenous use), gluco-and mineralocorticosteroids (with systemic use), tetracosactide (ACTH), glycyrrhizic acid(carbenoxolone, licorice root preparations), laxatives that stimulate intestinal motility. Increased risk of hypokalemia when co-administered with hydrochlorothiazide (additive effect). It is necessary to regularly monitor the content of potassium in the blood plasma, if necessary – its correction. Against the background of hydrochlorothiazide therapy, it is recommended to use laxatives that do not stimulate intestinal motility.

Cardiac Glycosides

Hypokalemia and hypomagnesemia due to the action of thiazide diuretics increase the toxicity of cardiac glycosides. Concomitant use of hydrochlorothiazide and cardiac glycosides should regularly monitor the concentration of potassium in the blood plasma, ECG indicators, and, if necessary, adjust therapy.

Drug combinations that require attention

Other antihypertensive drugs

Potentiation of the antihypertensive effect of hydrochlorothiazide (additive effect). It may be necessary to adjust the dose of simultaneously prescribed antihypertensive drugs.

It is recommended to stop taking hydrochlorothiazide 2-3 days before the start of ACE inhibitor therapy to prevent the development of symptomatic hypotension. If this is not possible, then the initial dose of ACE inhibitors should be reduced.

Ethanol, barbiturates, antipsychotics (neuroleptics), antidepressants, anxiolytics, narcotic analgesics, and general anaesthetics

It is possible to increase the antihypertensive effect of hydrochlorothiazide and potentiate orthostatic hypotension (additive effect).

Non-depolarizing muscle relaxants (e. g. tubocurarine)

It is possible to increase the effect of non-depolarizing muscle relaxants.

Adrenomimetics (pressor amines)

Hydrochlorothiazide may reduce the effect of adrenomimetics such as epinephrine (epinephrine) and norepinephrine (norepinephrine).

Nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors and high doses of acetylsalicylic acid (>>3 g / day)

NSAIDs may reduce the diuretic and antihypertensive effects of hydrochlorothiazide. With simultaneous use, there is a risk of developing acute renal failure due to a decrease in GFR. Hydrochlorothiazide may increase the toxic effects of high-dose salicylates on the central nervous system.

Hypoglycemic agents for oral use and insulin

Thiazide diuretics affect glucose tolerance (hyperglycemia may develop) and reduce the effectiveness of hypoglycemic agents (dose adjustment of hypoglycemic agents may be required).

Caution should be exercised when concomitantly using hydrochlorothiazide and metformin due to the risk of lactic acidosis due to impaired renal function caused by hydrochlorothiazide.

Beta-blockers, diazoxide

Concomitant use of thiazide diuretics (including hydrochlorothiazide) with beta-blockers or diazoxide may increase the risk of hyperglycemia. Medications used to treat gout (probenecid, sulfinpyrazone, allopurinol)

It may be necessary to adjust the dose of uricosuric drugs, since hydrochlorothiazide increases the concentration of uric acid in the blood serum. Thiazide diuretics may increase the frequency of hypersensitivity reactions to allopurinol.

Amantadine

Thiazide diuretics (including hydrochlorothiazide) may reduce the clearance of amantadine, lead to an increase in the concentration of amantadine in blood plasma, and increase the risk of its undesirable effects.

Anticholinergic drugs (cholinoblockers)

Anticholinergic drugs (for example, atropine, biperiden) increase the bioavailability of thiazide diuretics by reducing gastrointestinal motility and gastric emptying rate.

Cytotoxic (antitumor) drugs

Thiazide diuretics reduce the renal excretion of cytotoxic drugs (for example, cyclophosphamide and methotrexate) and potentiate their myelosuppressive effect.

Methyldopa

Cases of hemolytic anemia with simultaneous use of hydrochlorothiazide and methyldopa are described.

Antiepileptic drugs (carbamazepine, oxcarbazepine, topiramate)

Risk of developing symptomatic hyponatremia. With simultaneous use of hydrochlorothiazide and carbamazepine, it is necessary to monitor the patient’s condition and monitor the sodium content in the blood serum. With simultaneous use of hydrochlorothiazide and topiramate, the content of topiramate in the blood serum should also be monitored, if necessary, potassium preparations should be prescribed or the dose of topiramate should be adjusted.

Selective serotonin reuptake inhibitors

When used concomitantly with thiazide diuretics, hyponatremia may be potentiated. It is necessary to monitor the sodium content in the blood plasma.

Cyclosporine

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

Oral anticoagulants

Thiazide diuretics may reduce the effect of oral anticoagulants.

Iodine-containing contrast agents

Dehydration of the body while taking thiazide diuretics increases the risk of acute renal failure, especially when using high doses of iodine-containing contrast agents. Before applying iodine-containing contrast agents, it is necessary to compensate for the loss of fluid.

Calcium supplements

With simultaneous use, it is possible to increase the content of calcium in the blood plasma and develop hypercalcemia due to a decrease in the excretion of calcium ions by the kidneys. If simultaneous use of calcium-containing drugs is necessary, then the content of calcium in the blood plasma should be monitored and the dose of calcium preparations adjusted.

Anionic exchange resins (colestyramine and colestipol)

Anionic exchange resins reduce the absorption of hydrochlorothiazide. Single doses of colestyramine and colestipol reduce the absorption of hydrochlorothiazide in the gastrointestinal tract by 85% and 43%, respectively.

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 that affect the RAAS, with potassium-sparing diuretics (spironolactone, triamterene, amiloride, eplerenone), potassium preparations or salt substitutes containing potassium, may lead to an increase in serum potassium content. Simultaneous use is not recommended.

It is possible to reduce the rate of removal of lithium ions. Therefore, when ARA II is co-administered with lithium salts, serum lithium concentrations should be carefully monitored.

Concomitant use of ARA II with NSAIDs (e. g., selective cyclooxygenase 2 (COX-2) inhibitors)and non-selective NSAIDs, acetylsalicylic acid in doses that have an anti-inflammatory effect) may reduce the antihypertensive effect. Concomitant use of ARA II or diuretics with NSAIDs is associated with an increased risk of developing impaired renal function, including acute renal failure, and an increase in serum potassium (especially in patients with a history of renal dysfunction). Concomitantly used with NSAIDs should be used with caution, especially in elderly patients. At the same time, it is necessary to adequately replenish the BCC and periodically monitor kidney function from the moment of starting therapy and in the future.

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

Double blockade of the RAAS

Concomitant use of ARA II with aliskiren and drugs containing aliskirenis contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m%^%2 of body surface area) and is not recommended in other patients. Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

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 an increased incidence of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared with the use of one of the listed groups as monotherapy.

When used concomitantly with other drugs that cause hypotension, including tricyclic antidepressants, antipsychotics (neuroleptics), baclofen, amifostine, the risk of hypotension increases.

How to take, course of use and dosage

Inside, regardless of the time of eating, with a sufficient amount of water,1 time a day. Lorista®Preparation H can be taken simultaneously with other antihypertensive drugs.

Arterial hypertension

The initial and maintenance dose is 1 tablet of Lorista ® H (hydrochlorothiazide 12.5 mg and losartan 50 mg) once a day. In patients without an adequate therapeutic response to taking 1 tablet of Lorista® N 1 time per day for 2-4 weeks, the dose of the drug can be increased to 2 tablets of Lorista® N 1 time per day. The maximum daily dose is 2 tablets of Lorista® H once a day. Usually, the maximum antihypertensive effect is achieved within 3 weeks after the start of therapy.

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

The standard initial dose of losartan is 50 mg once a day. Patients who failed to reach the target BP values while taking losartan 50 mg/day should be selected for therapy by combining losartan with low doses of hydrochlorothiazide (12.5 mg). If necessary, you can increase the dose of losartan to 100 mg / day in combination with hydrochlorothiazide at a dose of 12.5 mg / day, and then increase it to 2 tablets of Lorista® H (a total of 25 mg of hydrochlorothiazide and 100 mg of losartan)once a day. If an additional reduction in blood pressure is necessary, other antihypertensive drugs should be added.

Special patient groups

Patients with impaired renal function or patients undergoing hemodialysis

In patients with moderate renal impairment (creatinine clearance 30-50 ml/min), no adjustment of the initial dose of the drug is required. Lorista®Preparation H is not recommended for patients undergoing hemodialysis. Lorista®Preparation H should not be used in patients with severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Patients with reduced BCC

Before starting treatment with Lorista®BCC and/or sodium ion levels in the blood plasma should be restored.

Patients with impaired liver function

Lorista®Preparation H is contraindicated in patients with severe hepatic impairment (see section “Contraindications”).

Elderly patients

Dose adjustment of Lorista® H is not required.

Overdose

Combination of hydrochlorothiazide + losartan

There is no information about overdose with the combination of hydrochlorothiazide + losartan.

Treatment:symptomatic and supportive care. Lorista®should be discontinued N and monitor the patient carefully. If necessary: induce vomiting(if the patient has recently taken the drug), fill up the BCC, correct violations of water and electrolyte metabolism and a pronounced decrease in blood pressure.

Hydrochlorothiazide

Symptoms: the most common manifestations of hydrochlorothiazide overdose are increased diuresis, accompanied by acute fluid loss (dehydration) and electrolyte disturbances (hypokalemia, hyponatremia, hypochloremia). Overdose with hydrochlorothiazide can manifest the following symptoms::

· from the cardiovascular system: tachycardia, decreased blood pressure, shock;

· the nervous system: weakness, confusion, dizziness, and cramps of the calf muscles, paresthesia, disturbance of consciousness, fatigue;

· gastrointestinal: nausea, vomiting, thirst;

· the part of the kidney and urinary tract disorders: polyuria, oliguria or anuria (due to hemoconcentration).

* laboratory parameters: hypokalemia, hyponatremia, hypochloremia, alkalosis, increased urea nitrogen content in the blood (especially in patients with renal insufficiency).

Treatment: in case of overdose, symptomatic and supportive therapy is performed. If the drug has been taken recently, induction of vomiting or gastric lavage is indicated for the elimination of hydrochlorothiazide. Absorption of hydrochlorothiazide can be reduced by ingestion of activated carbon. In case of a decrease in blood pressure or shock, BCC should be replenished (by introducing plasma-substituting fluids) and electrolyte deficiency (potassium, sodium). In case of respiratory disorders, oxygen inhalation or artificial ventilation of the lungs is indicated. It is necessary to monitor the water-electrolyte balance (especially the potassium content in the blood serum) and kidney function before their normalization. There is no specific antidote. Hydrochlorothiazide is eliminated by hemodialysis, but the degree of its elimination has not been established.

Losartan (data is limited)

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

Treatment: symptomatic therapy, hemodialysis is ineffective.

Description

Oval, slightly biconvex tablets, film-coated from yellow to yellow with a greenish tinge of color, with a risk on one side.

View on the break: white rough mass with a film shell from yellow to yellow with a greenish tinge of color.

Special instructions

Bilateral renal artery stenosis or single kidney artery stenosis, hyperkalemia, post-kidney transplant conditions (no experience), aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), chronic heart failure (CHF) with concomitant severe renal impairment, severe heart failure (NYHA Functional Class IV), CHF with life-threatening arrhythmias, coronary heart disease (CHD), cerebrovascular diseases, primary hyperaldosteronism, a history of angioedema, hypotension, liver function disorders, renal function disorders, water-electrolyte balance disorders, patients with reduced BCC (for example, treated with high doses of diuretics) due to the possibility of symptomatic arterial hypotension, hypokalemia, hyponatremia, hypercalcemia, concomitant use of medications that can cause polymorphic ventricular failure hyperparathyroidism, hyperuricemia, gout, non-melanoma skin cancer (NSCC) in the anamnesis (see the section “Special instructions”).

Contraindicated in persons under 18 years of age (efficacy and safety of use have not been established).

Patients with impaired renal function or patients undergoing hemodialysis

In patients with moderate renal impairment (creatinine clearance 30-50 ml/min), no adjustment of the initial dose of the drug is required. Lorista®Preparation H is not recommended for patients undergoing hemodialysis. Lorista®Preparation H should not be used in patients with severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Patients with reduced BCC

Before starting treatment with Lorista®, the BCC and/or the content of sodium ions in the blood plasma should be restored.

Patients with impaired liver function

Lorista ® H is contraindicated in patients with severe hepatic impairment (see section “Contraindications”).

Elderly patients

No dose adjustment of Lorista® is required.

Application of Lorista® H is not recommended in patients with acute myocardial infarction due to insufficient clinical experience. Also, it should not be used to stop a hypertensive crisis.

Hydrochlorothiazide

Impaired renal function

In patients with impaired renal function, hydrochlorothiazide may cause azotemia. In case of renal failure, accumulation of hydrochlorothiazide is possible.

In patients with reduced renal function, periodic monitoring of creatinine clearance is necessary. If renal impairment progresses and / or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.

Liver function disorders

When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe hepatic insufficiency or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic insufficiency and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even a small change in the water-electrolyte balance and accumulation of ammonium in the blood serum can cause hepatic coma. If symptoms of encephalopathy occur, diuretics should be discontinued immediately.

Water-electrolyte balance and metabolic disorders

Thiazide diuretics (including hydrochlorothiazide) can cause a decrease in BCC (hypovolemia) and disturbances in the water-electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of water-electrolyte balance disorders include dryness of the oral mucosa, thirst, weakness, lethargy, fatigue, drowsiness, restlessness, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia, and gastrointestinal disorders (such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with prolonged treatment), clinical symptoms of water-electrolyte balance disorders should be identified, and the content of electrolytes in blood plasma should be regularly monitored.

Sodium

All diuretics can cause hyponatremia, sometimes leading to severe complications. Hyponatremia and hypovolemia can lead to dehydration and orthostatic hypotension. Concomitant reduction of chlorine ions can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the content of sodium ions in the blood plasma before starting treatment and regularly monitor this indicator against the background of taking hydrochlorothiazide.

Potassium

When using thiazide and thiazide-like diuretics, there is a risk of a sharp decrease in the potassium content in the blood plasma and the development of hypokalemia (the potassium content in the blood plasma is less than 3.4 mmol/l). Hypokalemia increases the risk of developing cardiac arrhythmias (including severe arrhythmias) and increases the toxic effect of cardiac glycosides. In addition, hypokalemia (as well as bradycardia) is a condition that contributes to the development of polymorphic ventricular tachycardia of the “pirouette” type, which can lead to death.

Hypokalemia is most dangerous for the following groups of patients: elderly people, patients receiving simultaneous therapy with antiarrhythmic and non-antiarrhythmic drugs that can cause polymorphic ventricular tachycardia of the “pirouette” type or increase the duration of the QT interval on the ECG, patients with impaired liver function, CHD, CHF. In addition, patients with an extended QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the action of medications.

In all the cases described above, it is necessary to avoid the risk of hypokalemia and regularly monitor the potassium content in the blood plasma. The first measurement of potassium ions in the blood plasma should be carried out within the first week after the start of treatment. If hypokalemia occurs, appropriate treatment should be prescribed. Hypokalemia can be corrected by using potassium-containing medications or by taking foods rich in potassium (dried fruits, fruits, vegetables).

Calcium

Thiazide diuretics can reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in the content of calcium in the blood plasma. In some patients with prolonged use of thiazide diuretics, pathological changes in the parathyroid glands were observed with hypercalcemia and hyperphosphatemia, but without the typical complications of hyperparathyroidism (nephrolithiasis, decreased bone mineral density, peptic ulcer disease). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.

Because of their effect on calcium metabolism, thiazides can affect laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued prior to parathyroid function testing.

Magnesium

Thiazides have been found to increase the excretion of magnesium by the kidneys, which can lead to hypomagnesemia. The clinical significance of hypomagnesemia remains unclear.

Glucose

Treatment with thiazide diuretics may impair glucose tolerance. When using hydrochlorothiazide in patients with manifest or latent diabetes mellitus, it is necessary to regularly monitor the concentration of glucose in the blood plasma. Dose adjustment of hypoglycemic medications may be required.

Uric acid

In patients with gout, the frequency of seizures may increase or the course of gout may worsen. Patients with gout and impaired uric acid metabolism (hyperuricemia) should be carefully monitored.

Lipids

When using hydrochlorothiazide, the concentration of both cholesterol and triglycerides in the blood plasma may increase.

Acute myopia / secondary angle-closure glaucoma

Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: a sudden decrease in visual acuity or pain in the eyes, which usually manifests itself within a few hours or weeks from the start of hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to permanent vision loss. If symptoms occur, stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, urgent medical treatment or surgery may be required. Risk factors for acute angle-closure glaucoma include a history of allergic reactions to sulfonamides or penicillin. Immune system disorders

There are reports that thiazide diuretics (including hydrochlorothiazide) can cause exacerbation or progression of systemic lupus erythematosus, as well as lupus-like reactions.

Hypersensitivity reactions may occur in patients receiving thiazide diuretics even if there is no indication of a history of allergic reactions or bronchial asthma.

Photosensitivity

There is information about cases of photosensitivity reactions when taking thiazide diuretics. If photosensitivity occurs while taking hydrochlorothiazide, treatment should be discontinued. If continued use of the diuretic is necessary, then the skin should be protected from exposure to sunlight or artificial ultraviolet rays (UV rays).

Non-melanoma skin cancer (NSCLC)

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide intake and an increased risk of NSCLC-basal cell carcinoma and squamous cell carcinoma. The risk of developing NSCLC increased with an increase in the total (accumulated) dose of hydrochlorothiazide. A possible mechanism for the development of NSCLC is the photosensitizing effect of hydrochlorothiazide. Patients taking hydrochlorothiazide alone or in combination with other medications should be aware of the risk of developing NSCLC. Such patients are advised to have their skin examined regularly to identify any new suspicious lesions, as well as changes to existing skin lesions.

All suspicious skin changes should be reported to your doctor immediately. Suspicious skin areas should be examined by a specialist. To clarify the diagnosis, histological examination of skin biopsies may be required.

In order to minimize the risk of developing NSCLC, patients should be advised to take preventive measures, such as limiting exposure to sunlight and UV rays, as well as using appropriate protective equipment.

In patients with a history of NSCLC, it is recommended to reconsider the use of hydrochlorothiazide.

Athletes

Hydrochlorothiazide can give a positive result during doping control in athletes.

Other things

In patients with severe atherosclerosis of the cerebral and coronary arteries, hydrochlorothiazide should be used with extreme caution.

Thiazide diuretics can reduce the amount of iodine bound to plasma proteins without showing signs of thyroid dysfunction.

Losartan

Angioedema

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

Hypotension and hypovolemia (dehydration)

Patients with hypovolaemia (dehydration) and/or reduced plasma sodium levels may develop symptomatic hypotension during diuretic therapy, restriction of salt intake, diarrhea or vomiting, especially after taking the first dose of Lorista® N. BCC and/or plasma sodium levels should be restored before using the drug.

Violations of the water-electrolyte balance

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

Concomitant use of ARA II with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal impairment (GFR less than 60 ml/min / 1.73 m%^%2 of body surface area) and is not recommended in other patients. Concomitant use of ARA II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

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

Impaired liver function

Significantly increases the concentration of losartan in the blood plasma in patients with cirrhosis of the liver, so the drug Lorista® H should be used with caution in patients with mild to moderate hepatic impairment.

Impaired renal function

Impaired renal function, including renal failure, may occur due to RAAS inhibition (especially in patients whose renal function depends on RAAS, for example, with a history of severe heart failure or renal dysfunction).

Renal artery stenosis

In patients with bilateral renal artery stenosis, as well as stenosis of the artery of a single functioning kidney, drugs that affect RAAS, including ARA II, can reversibly increase the concentration of urea and creatinine in blood plasma.

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

Kidney transplantation

Experience with Lorista® H is absent in patients who have recently undergone a kidney transplant.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect the RAAS, so the use of Lorista®in such patients is recommended. H is not recommended.

IHD and cerebrovascular diseases

As with any antihypertensive medication, a marked decrease in blood pressure in patients with CHD or cerebrovascular diseases can lead to the development of myocardial infarction or stroke.

Heart failure

In patients whose renal function depends on the condition of the RAAS (for example, with CHF of NYHA functional class III-IV, accompanied or not accompanied by impaired renal function), therapy with drugs that affect the RAAS may be accompanied by severe hypotension, oliguria and/or progressive azotemia, in rare cases – acute renal failure. It is impossible to exclude the development of these disorders due to the suppression of RAAS activity during the use of ARA II.

Aortic and/or mitral valve stenosis, HOCMP

Lorista ® H, like other vasodilators, should be used with caution in patients with hemodynamically significant aortic and/or mitral valve stenosis or with HOCMP.

Ethnic features

Losartan (as well as other drugs that affect the RAAS) has a less pronounced antihypertensive effect in patients of the black race compared to representatives of other races, possibly due to the higher frequency of hyporeninemia in these patients with arterial hypertension.

Special information on excipients

Lorista®Preparation H contains lactose, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome.

At the beginning of therapy, the drug Lorista® H can cause a decrease in blood pressure, dizziness or drowsiness, and thus indirectly affect the psychoemotional state. For safety reasons, patients should first evaluate their response to treatment before starting activities that require increased attention.

Form of production

Film-coated tablets,12.5 mg + 50 mg.

During production at KRKA JSC, Novo Mesto village, Slovenia:

7,10 or 14 tablets in a blister (contour cell package) made of combined PVC material/PVDH and aluminum foil.

2,4,8,12 or 14 blisters (contour cell packages) of 7 tablets, or 3,6 or 9 blisters (contour cell packages) of 10 tablets, or 1,2,4,6 or 7 blisters (contour cell packages) of 14 tablets together with the instructions for use are placed in a cardboard pack.

During production at KRKA-RUS LLC, Russia:

7,10 or 14 tablets in a contour cell package (blister) made of combined PVC material/PVDH and aluminum foil.

2,4,8,12 or 14 contour cell packs (blisters) of 7 tablets, or 3,6 or 9 contour cell packs (blisters) of 10 tablets, or 1,2,4,6 or 7 contour cell packs (blisters) of 14 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions

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

Keep out of reach of children.

Shelf

life is 5 years.

Do not use the drug after the expiration date.

Active ingredient

Hydrochlorothiazide, Losartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Prevention of heart attacks and strokes