Lorista N pills 100mg+12.5mg, 90pcs

Composition

1 film-coated tablet contains:

Core:

Active ingredients:

Hydrochlorothiazide 12.50 mg

Losartan Potassium 100,00 mg

Auxiliary substances:

Pregelatinized starch, microcrystalline cellulose, lactose monohydrate, magnesium stearate

Film shell:

Hypromellose, macrogol-4000, titanium dioxide (E 171), talc

Pharmacological action

antihypertensive combined agent (diuretic + angiotensin II receptor antagonist)

Clinical Pharmacology

Pharmacodynamics

Lorista ® H 100 is a combination drug that includes losartan and hydrochlorothiazide, which have an additive antihypertensive effect, reducing blood pressure (BP) to a greater extent than each of the components separately.

Due to the diuretic effect, hydrochlorothiazide increases the activity of plasma renin, stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the content of potassium in blood plasma. Losartan blocks all the physiological effects of angiotensin II and, due to the suppression of the effects of aldosterone, can help reduce the potassium loss associated with taking a diuretic.

Losartan has a moderate and transient uricosuric effect.

Hydrochlorothiazide causes a slight increase in the concentration of uric acid in the blood plasma, the combination of losartan and hydrochlorothiazide helps to reduce the severity of hyperuricemia caused by a diuretic.

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 blood (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 a selective angiotensin II (ARA II) receptor antagonist (type AT₁) for oral use. Under the conditions of invivo and invitro, losartan and its pharmacologically active metabolite E-3174 block all physiologically significant effects of angiotensin II on AT1receptors, regardless of the pathway of its synthesis: it leads to an increase in plasma renin activity, reduces the concentration of aldosterone in blood plasma. Losartan indirectly causes activation_{of AT2}receptors by increasing the concentration of angiotensin II in blood plasma.

It does not inhibit the activity of kininase II, an enzyme involved in bradykinin metabolism. Reduces total peripheral vascular resistance (OPSS), pressure in the “small” circulatory circle, reduces afterload on the myocardium, 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. Losartan evenly controls blood pressure throughout the day, while the antihypertensive effect corresponds to the natural circadian rhythm. The reduction in blood pressure at the end of the dosing interval was approximately 70-80% of the effect of losartan observed 5-6 hours after use. There is no “withdrawal” syndrome. Losartan has no clinically significant effect on heart rate (HR).

Losartan is equally effective in men and women, as well as in patients under 65 years of age and elderly patients with arterial hypertension (AH).

Pharmacokinetics

Hydrochlorothiazide + losartan

The pharmacokinetics of losartan and hydrochlorothiazide when used simultaneously do not differ from those when used in monotherapy.

Special patient groups

Elderly patients

Concentrations of losartan and its active metabolite in blood plasma and the rate of absorption of hydrochlorothiazide in elderly patients with hypertension do not significantly differ from these indicators in young patients with hypertension.

Hydrochlorothiazide

Suction and distribution

Hydrochlorothiazide is not fully absorbed, but it is rapidly 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 oral 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 by 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).

Special patient groups

Impaired renal function

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

Losartan

Suction

Losartan is well absorbed from the gastrointestinal tract when taken orally. It undergoes significant metabolism during the “primary” passage through the liver, forming a pharmacologically active carboxylated metabolite (E-3174) and inactive metabolites. Bioavailability is approximately 33%. The average_cmaxof losartan and its active metabolite is reached in 1 hour and 3-4 hours, respectively.

Distribution

Losartan and its active metabolite bind to plasma proteins (mainly albumins) by more than 99%. The volume of distribution of losartan is 34 liters.

Very poorly penetrates the blood-brain barrier.

Metabolism

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

Deduction

The 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-lives of losartan and the active metabolite are 2 hours and 6-9 hours, respectively. It is mainly excreted with bile through the intestines (58%), kidneys-35%. It doesn’t accumulate.

When taken orally at doses up to 200 mg, losartan and its active metabolite have linear pharmacokinetics.

Special patient groups

Gender

The concentration of losartan in blood plasma was 2 times higher in women with hypertension compared to men with hypertension. This pharmacokinetic difference is not clinically relevant. The concentration of the active metabolite in men and women does not differ.

Impaired liver and kidney function

When taking losartan orally in patients with mild and moderate alcoholic cirrhosis of the liver, the concentrations of losartan and its active metabolite in blood plasma were 5 and 1.7 times higher, respectively, than in young male volunteers.

Plasma concentrations of losartan in patients with creatinine clearance above 10 ml / min did not differ from those in patients with preserved renal function. The area under the concentration-time curve (AUC) of losartan in patients on hemodialysis was approximately 2 times larger than the AUC of losartan in patients with normal renal function. Plasma concentrations of the active metabolite do not change in patients with impaired renal function or in patients undergoing hemodialysis. Losartan and its active metabolite cannot be removed by hemodialysis.

Indications

• Arterial hypertension (patients who are indicated for combination therapy).
• Reduced risk of associated cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy, resulting in a combined reduction in the incidence of cardiovascular mortality, stroke, and myocardial infarction.

Use during pregnancy and lactation

Pregnancy

Hydrochlorothiazide + losartan

The use of Lorista® N 100 is contraindicated during pregnancy. Drugs that affect the renin-angiotensin-aldosterone system (RAAS) can cause serious damage and death of the fetus, so when diagnosing pregnancy, the combination of hydrochlorothiazide + losartan should be immediately discontinued.

If an oligohydramnion is detected, the combination of hydrochlorothiazide + losartan should be discontinued, unless it is vital for the mother. Depending on the duration of pregnancy, appropriate fetal tests should be performed. Patients and doctors should be aware that oligohydramnion may not be detected until permanent fetal damage occurs. Newborns whose mothers have taken a combination of hydrochlorothiazide + losartan during pregnancy should be carefully monitored for hypotension, oliguria, and hyperkalemia.

Hydrochlorothiazide

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 and 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 such as jaundice, impaired water-electrolyte balance and thrombocytopenia in the fetus and newborn. 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.

Losartan

Although there is no experience of using losartan in pregnant women, preclinical animal studies have shown that taking losartan leads to the development of serious fetal and neonatal damage and death of the fetus or offspring. It is believed that the mechanism of these phenomena is due to the impact on the RAAS.

Renal perfusion in the fetus, which depends on the development of RAAS, occurs in the second trimester, so the risk for the fetus increases if the combination of hydrochlorothiazide + losartan is used in the second and third trimester of pregnancy.

The use of drugs that affect the RAAS in the second and third trimester of pregnancy reduces fetal kidney function and increases the morbidity and mortality of the fetus and newborns. The development of oligohydramnios may be associated with fetal lung hypoplasia and skeletal deformity. Possible adverse events in newborns include cranial hypoplasia, anuria, hypotension, renal failure, and death.

The above-mentioned adverse outcomes are usually caused by the use of drugs that affect the RAAS in the second and third trimesters of pregnancy. Most epidemiological studies on the development of fetal abnormalities after the use of antihypertensive drugs in the first Trimester of pregnancy did not reveal differences between drugs that affect the RAAS and other antihypertensive drugs. When prescribing antihypertensive therapy to pregnant women, it is important to optimize possible outcomes for the mother and fetus.

If it is not possible to choose an alternative therapy to replace therapy with drugs that affect the RAAS, it is necessary to inform the patient about the possible risk of therapy for the fetus. Periodic ultrasound examinations should be performed to assess the intra-amniotic space.

Breast-feeding period

Hydrochlorothiazide + losartan

The use of Lorista ® N 100 is contraindicated during breastfeeding. Since many medications are excreted in breast milk, and there is a risk of possible adverse effects in a breastfed child, a decision should be made to stop breastfeeding or to discontinue the drug, taking into account the need for its use for the mother.

Hydrochlorothiazide

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.

Losartan

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

Contraindications

Hypersensitivity to any of the components of the drug, hypersensitivity to other sulfonamide derivatives, anuria, severe renal dysfunction (creatinine clearance less than 30 ml/min), therapy-resistant hypokalemia or hypercalcemia, severe liver function disorders, cholestasis and biliary tract obstruction, resistant hyponatremia, symptomatic hyperuricemia/gout, dehydration, severe hypotension, difficult-to-control diabetes mellitus, Addison’s disease concomitant use with aliskiren or 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 angiotensin converting enzyme (ACE)inhibitors in patients with diabetic nephropathy, pregnancy, breast-feeding, age under 18 years (efficacy and safety have not been established), lactase deficiency, hereditary lactose intolerance, glucose-galactose malabsorption syndrome.

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 I antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide, procainamide);

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

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

– antipsychotics: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoperazine, fluphenazine), benzamide (amisulpride, sultopride, sulpiride, tiapride), butyrophenones (droperidol, haloperidol), pimozide, sertindole;

– antidepressants: tricyclic antidepressants, selective inhibitors of serotonin reuptake (SSRIs) (citalopram, ESCITALOPRAM);

– antibacterial agents: fluoroquinolones (levofloxacin, moxifloxacin, sparfloxacin, ciprofloxacin), macrolides (erythromycin intravenous use, azithromycin, clarithromycin, and 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 drug (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.

Medicationsthat 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 (when administered intravenously), gluco-and mineralocorticosteroids (when used systemically), tetracosactide (adrenocorticotropic hormone [ACTH]), glycyrrhizic acid (carbenoxolone, licorice root preparations), laxativesthat 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 be accompanied by regular monitoring of blood plasma potassium levels, ECG readings, and, if necessary, adjustment of therapy.

Drug combinationsthat 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.

SSRIs

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

No clinically significant interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, or erythromycin were detected in clinical trials.

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

Concomitant use with potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations or potassium-containing substitutes for table salt, as well as the use of other drugs that increase the content of potassium in blood plasma, increases the risk of hyperkalemia.

NSAIDs, including selective COX-2 inhibitors, may reduce the effect of diuretics and other antihypertensive agents, including losartan. The antihypertensive effect of losartan, as with other antihypertensive agents, may be reduced with Indometacin. Concomitant use of ARA II or diuretics with NSAIDs may be associated with an increased risk of worsening renal function, including acute renal failure, and increased blood potassium levels, especially in patients with baseline renal impairment. Combined treatment should be administered with caution, especially in elderly patients. Patients should be adequately hydrated and renal function monitored after starting combination treatment and periodically during treatment. In some patients with impaired renal function treated with NSAIDs, including selective COX-2 inhibitors, concomitant use of ARA II may worsen impaired renal function. These effects are usually reversible.

Double blockade of the RAAS

Concomitant use of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal insufficiency (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.

According to clinical studies, double blockade of the RAAS by concomitant use of ACE inhibitors, ARA II or aliskiren has been shown to be associated with a higher incidence of adverse events such as hypotension, hyperkalemia and decreased renal function (including acute renal failure) compared to monotherapy with a drug that affects the RAAS.

It is possible to reduce the removal of lithium ions. Therefore, with simultaneous use of ARA IIwith lithium saltsSerum lithium concentrations should be carefully monitored.

Other drugs that cause a decrease in blood pressure, such as tricyclic antidepressants, antipsychotics, baclofen, amifostine: concomitant use of losartan with these drugs may increase the risk of hypotension.

How to take, course of use and dosage

Inside, regardless of the meal time.

Lorista ® H 100 can be used simultaneously with other antihypertensive agents.

Arterial hypertension

Recommended dose: 1 tablet (combination of hydrochlorothiazide 12.5 mg + losartan 100 mg)once a day. As a rule, the maintenance dose is 1 tablet (combination of hydrochlorothiazide 12.5 mg + losartan 50 mg) once a day. The maximum dose is 1 tablet of a combination of hydrochlorothiazide 25 mg + losartan 100 mg once a day. Usually, the antihypertensive effect is achieved within 3-4 weeks after the start of therapy. 1 tablet (combination of hydrochlorothiazide 12.5 mg + losartan 100 mg) once a day is prescribed to patients who need additional blood pressure monitoring when taking 100 mg of losartan.

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

1 tablet (combination of hydrochlorothiazide 12.5 mg + losartan 100 mg) 1 time per day. The drug in this dosage is prescribed to patients who fail to reach the target values of blood pressure levels against the background of taking hydrochlorothiazide 12.5 mg and losartan 50 mg once a day.

Special patient groups

Use in patients with impaired renal function and in patients undergoing hemodialysis

It is not necessary to select the initial dose of the drug in patients with moderate renal impairment (creatinine clearance 30-50 ml / min). The use of a combination of hydrochlorothiazide + losartan is not recommended in patients undergoing hemodialysis. The combination of hydrochlorothiazide + losartan should not be used in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Use in patients with reduced BCC

Lorista ® H 100 should not be used at the initial stage of therapy in patients with reduced BCC.

Use in patients with impaired liver function

Lorista ® H 100 is contraindicated in patients with severe hepatic impairment (see section “Contraindications”).

Use in elderly patients

Lorista ® H 100 should not be used at the initial stage of therapy in elderly patients.

Overdose

Hydrochlorothiazide + losartan

There are no data on specific treatment of overdose with a combination of hydrochlorothiazide + losartan. Treatment is symptomatic and supportive. Lorista ® H 100 should be discontinued and the patient should be monitored. If the drug is taken recently, it is recommended to provoke vomiting, as well as eliminate dehydration, water-electrolyte disorders, hepatic coma and lowering blood pressure by standard methods.

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, impaired consciousness, fatigue;

· the gastro-intestinal tract: nausea, vomiting, thirst;

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

· laboratory findings: hypokalemia, hyponatremia, gipohloremia, alkalosis, increased concentration of residual nitrogen urea in blood plasma (particularly in patients with renal insufficiency).

Treatment

In case of overdose, symptomatic and supportive therapy is performed. If hydrochlorothiazide has been taken recently, induction of vomiting or gastric lavage is indicated for its elimination. 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 with the introduction of plasma-substituting fluids and electrolyte deficiency (potassium, sodium). In case of respiratory failure, oxygen inhalation or artificial ventilation 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

Information about overdose is limited.

Symptoms

The most likely manifestation of overdose is a marked decrease in blood pressure and tachycardia, bradycardia may occur due to parasympathetic (vagal) stimulation.

Treatment

Symptomatic therapy. If symptomatic hypotension develops, maintenance therapy is indicated.

Losartan and its active metabolite are not eliminated by hemodialysis.

Description

Oval, biconvex tablets, covered with a white film coating.

View at the break: a white rough mass with a white film shell.

Special instructions

Bilateral renal artery stenosis or single kidney artery stenosis, hyperkalemia, conditions after kidney transplantation (no experience), aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), CHF with concomitant severe renal impairment, severe CHF (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 tachycardia of the “pirouette” type or increase the risk of heart failure. duration of the QT interval on the ECG, concomitant use of medications that can cause hypokalemia, cardiac glycosides, a history of allergic reactions to penicillin, hyperparathyroidism, hyperuricemia, gout, non-melanoma skin cancer (NSCLC) in the anamnesis (see the section “Special instructions”).

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

Use in patients with impaired renal function and in patients undergoing hemodialysis

It is not necessary to select the initial dose of the drug in patients with moderate renal impairment (creatinine clearance 30-50 ml / min). The use of a combination of hydrochlorothiazide + losartan is not recommended in patients undergoing hemodialysis. The combination of hydrochlorothiazide + losartan should not be used in patients with severe renal insufficiency (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Use in patients with reduced BCC

Lorista ® H 100 should not be used at the initial stage of therapy in patients with reduced BCC.

Use in patients with impaired liver function

Lorista ® H 100 is contraindicated in patients with severe hepatic impairment (see section “Contraindications”).

Use in elderly patients

Lorista ® H 100 should not be used at the initial stage of therapy in elderly patients.

The use of Lorista ® H 100 in patients with acute myocardial infarction is not recommended due to insufficient clinical experience.

Also, the drug Lorista® H 100 should not be used to stop a hypertensive crisis.

Combination of hydrochlorothiazide + losartan

Children and teenagers

There is no experience of using the combination of hydrochlorothiazide + losartan in children and adolescents.

If newborns whose mothers took Lorista® H 100 during pregnancy develop oliguria or hypotension, symptomatic therapy aimed at maintaining blood pressure and renal perfusion is necessary. Blood transfusions or dialysis may be required to prevent hypotension and / or maintain kidney function.

Elderly patients

Clinical studies have not revealed any features regarding the safety and efficacy of the combination of hydrochlorothiazide + losartan in elderly patients (over 65 years of age).

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 the chlorine content in blood plasma can lead to secondary compensatory metabolic alkalosis, but the frequency and severity of this effect are insignificant. It is recommended to determine the sodium content 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 determination of the potassium content 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 with hypercalcemia and hyperphosphatemia were observed, 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 ions 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. 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 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 reaction 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 (UV) rays.

NMRC

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 (swelling of the face, lips, pharynx/larynx and / or tongue) when using losartan should be under strict medical supervision (see the section “Side effects”).

Arterial hypotension and BCC reduction

Patients with reduced BCC and/or plasma sodium levels may develop symptomatic hypotension, especially after taking the first dose of losartan, while taking diuretics, a diet with limited salt intake, diarrhea or vomiting.Correction of such conditions should be carried out before prescribing Lorista ® H 100 (see the sections “Indications for use” and “Contraindications”).

Violations of the water-electrolyte balance

Impaired water-electrolyte balance is characteristic of patients with renal insufficiency with or without diabetes mellitus, so careful monitoring of these patients is necessary. Careful monitoring of plasma potassium or creatinine clearance is necessary, especially in patients with heart failure and creatinine clearance of 30-50 ml/min.

During treatment with the drug, it is not recommended to take potassium-sparing diuretics, potassium preparations or food salt substitutes containing potassium (see the section “Interaction with other drugs”).

Impaired liver function

Data from pharmacokinetic studies indicate that the concentration of losartan in the blood plasma in patients with cirrhosis of the liver is significantly increased, so patients with a history of mild or moderate hepatic impairment Lorista® H 100 should be prescribed with caution. There is no experience of using losartan in patients with severe hepatic impairment (more than 9 points on the Child-Pugh scale), so the drug should not be used in this group of patients (see the sections ” Pharmacological properties. Pharmacokinetics”, “Contraindications” and “Method of use and dosage”).

Double blockade of the RAAS

There is evidence that concomitant use of ACE inhibitors, ARA II, or aliskiren increases the risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure). Concomitant use of losartan with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal insufficiency (GFR less than 60 ml/min / 1.73 m2 of body surface area) and is not recommended in other patients. Concomitant use of losartan with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Impaired renal function

Due to RAAS inhibition, some predisposed patients experienced changes in renal function, including the development of renal failure. These changes in renal function may return to normal after discontinuation of treatment.

Some medications that affect the RAAS may increase serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or stenosis of the renal artery of a single kidney. Similar effects have been reported with losartan. Such renal dysfunction may be reversible after discontinuation of therapy. Losartan should be used with caution in patients with bilateral renal artery stenosis or renal artery stenosis of a single kidney.

Kidney transplantation

There is no experience of using it in patients who have recently undergone a kidney transplant.

Primary hyperaldosteronism

Since patients with primary hyperaldosteronism usually do not show a positive response to therapy with antihypertensive agents that act by inhibiting the RAAS, the use of Lorista® H 100 is not recommended in this group of patients.

IHD and cerebrovascular diseases

Like all drugs with vasodilating effects, ARA II should be administered with caution in patients with CHD or cerebrovascular diseases, since a pronounced decrease in blood pressure in this group of patients can lead to the development of myocardial infarction or stroke.

CHF

As with other medications that affect the RAAS, patients with CHF with or without impaired renal function are at risk of developing severe hypotension and renal failure (often acute).

Aortic stenosis or mitral stenosis, HOCMP

Like all drugs with vasodilating effects, ARA II should be used with caution in patients with aortic or mitral valve stenosis or with HOCMP.

Ethnic features

As with ACE inhibitors, losartan and other ARA II drugs are likely to be less effective in lowering blood pressure in black people than in other races, possibly due to the higher prevalence of hypertension with low renin activity in this population.

Analysis of data from the entire group of patients included in the LIFE study on the effect of losartan on reducing the incidence of the main composite criterion for evaluating the study in patients with hypertension and left ventricular hypertrophy (n = 9193) showed that the ability of losartan to reduce the risk of stroke and myocardial infarction, as well as to reduce the cardiovascular mortality rate in patients with hypertension and left ventricular hypertrophy (by 13.0%, p = 0.021) does not apply to black patients although both treatment regimens effectively reduced blood pressure in these patients. In this study, losartan compared with atenolol reduced cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy of all races except black (n = 8660, p = 0.003). However, in this study, black patients treated with atenolol had a lower risk of developing the main composite criterion for evaluating the study (i. e., a lower combined incidence of cardiovascular mortality, stroke, and myocardial infarction) compared to patients of the same race taking losartan (p = 0.03).

Pregnancy

Do not use ARA II during pregnancy. If there is no need for continuous ARA II therapy, patients planning pregnancy should replace ARA II with alternative antihypertensive drugs with an established safety profile during pregnancy. If pregnancy is diagnosed, the use of Lorista® H 100 should be stopped immediately and, if necessary, alternative therapy should be initiated (see sections “Contraindications”, “Use during pregnancy and lactation”).

Special information about thebenefits ofx substancesx

Lorista ® H 100 contains lactose as an auxiliary substance, so the drug is contraindicated in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (see the section “Contraindications”).

No studies have been conducted to assess the impact on the ability to drive vehicles and work with mechanisms.

When driving vehicles or working with mechanisms, caution should be exercised due to the possibility of developing dizziness or weakness (see the section “Side effects”).

Form of production

Film-coated tablets,12.5 mg + 100 mg.

10,14 or 15 tablets in a blister of combined PVC material/PVDC – aluminum foil.

1,3,5,6 or 9 blisters of 10 tablets, or 1,2,4 or 6 blisters of 14 tablets, or 1,2,4 or 6 blisters of 15 tablets are placed in a cardboard pack together with the instructions for use.

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