Lorista ND pills 100mg+25mg, 60pcs

Composition

1 film-coated tablet contains:

Core:

Active ingredients:

Hydrochlorothiazide 25.00 mg

Losartan Potassium 100,00 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

Mechanism of action

Combination of hydrochlorothiazide + losartan

Components of Lorista® ND hydrochlorothiazide and losartan have an additive antihypertensive effect, reducing the level of blood pressure (BP) to a greater extent than each of the components separately. It is believed that this effect is due to the complementary action of both components. Due to the diuretic effect, hydrochlorothiazide increases the activity of plasma renin (ARP), stimulates the secretion of aldosterone, increases the concentration of angiotensin II and reduces the content of potassium in the blood serum. 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 reduces the severity of diuretic-induced hyperuricemia.

Hydrochlorothiazide

Thiazides usually do not affect normal blood pressure levels.

Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the reabsorption of electrolytes in the distal tubules of the kidneys. Hydrochlorothiazide increases the excretion of sodium and chlorine ions approximately equally. Natriuresis may be accompanied by a small loss of potassium ions and bicarbonates.

Losartan

Angiotensin II is a powerful vasoconstrictor, the main active hormone of the renin-angiotensin-aldosterone system (RAAS), and also a crucial pathophysiological link in the development of arterial hypertension. Angiotensin II binds to AT1receptors found in many tissues (vascular smooth muscle, adrenal glands, kidneys, and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. In addition, angiotensin II stimulates the proliferation of smooth muscle cells. _AT2receptors are the second type of receptors that angiotensin II binds to, but its role in regulating cardiovascular function is unknown.

Losartan is a selective angiotensin II AT1receptor antagonist that is highly effective when taken orally. Losartan and its pharmacologically active carboxylated metabolite (E-3174), both in vitroand in vivo, block all physiological effects of angiotensin II, regardless of its source or pathway of synthesis. Unlike some peptide antagonists of angiotensin II, losartan does not have agonist properties.

Losartan selectively binds to AT_-1receptors, does not bind or block the receptors of other hormones and ion channels that play an important role in regulating the function of the cardiovascular system. In addition, losartan does not inhibit the angiotensin-converting enzyme (ACE, kininase II) responsible for the destruction of bradykinin. Therefore, effects that are not directly related to AT1_{receptor blockade}, such as increased bradykinin-mediated effects or the development of edema (losartan 1.7%, placebo 1.9%), are not related to the effect of losartan.

Pharmacodynamics

Lorista®Preparation ND is a combination drug of losartan and hydrochlorothiazide. In patients with arterial hypertension and left ventricular hypertrophy, losartan, including in combination with hydrochlorothiazide, reduces the risk of cardiovascular morbidity and mortality, which was proved by evaluating the combined incidence of stroke and myocardial infarction, as well as the cardiovascular mortality rate in this category of 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 in the urine and a decrease in the content of potassium in the blood (hypokalemia). Hydrochlorothiazide also increases the excretion of magnesium ions and reduces the excretion of calcium ions in the urine. Thiazide diuretics reduce uric acid excretion by the kidneys and increase its concentration in the esophagus. 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 suppresses the increase in systolic and diastolic blood pressure during angiotensin II infusion.

During losartan use, elimination of the negative feedback consisting in angiotensin II inhibition of renin secretion leads to an increase in ARP. An increase in ARP leads to an increase in the concentration of angiotensin II in blood plasma. During long-term (6-week) treatment of patients with arterial hypertension with losartan at a dose of 100 mg / day, a 2-3-fold increase in the concentration of angiotensin II in blood plasma was observed at the time of reaching the maximum concentration (cmax) of losartan. In some patients, an even greater increase in the concentration of angiotensin II was observed, especially with a short duration of treatment (2 weeks). Despite this, during treatment, the antihypertensive effect and a decrease in the concentration of aldosterone in blood plasma were manifested after 2 and 6 weeks of therapy, which indicates an effective blockade of angiotensin II receptors. After losartan withdrawal, ARP and angiotensin II concentrations decreased within 3 days to the values observed before starting losartan.

Since losartan is a specific angiotensin_{II AT1}receptor antagonist, it does not inhibit ACE (kininase II), an enzyme that inactivates bradykinin. A study comparing the effects of losartan at 20 mg and 100 mg doses with those of an ACE inhibitor for the effects on angiotensin I, angiotensin II, and bradykinin showed that losartan blocked the effects of angiotensin I and angiotensin II without affecting the effects of bradykinin. This is due to the specific mechanism of action of losartan. The ACE inhibitor blocked the response to angiotensin I and increased the severity of bradykinin-related effects, without affecting the severity of the response to angiotensin II, which demonstrates the pharmacodynamic difference between losartan and ACE inhibitors.

The plasma concentrations of losartan and its active metabolite, as well as the antihypertensive effect of losartan, increase with increasing dose. Since losartan and its active metabolite are ARA II, they both contribute to the antihypertensive effect.

In a single 100 mg losartan study that included healthy male volunteers, oral use of losartan on a high-and low-salt diet did not affect glomerular filtration rate (GFR), effective renal plasma flow, or filtration fraction. Losartan had a natriuretic effect, which was more pronounced with a low-salt diet and, apparently, was not associated with suppression of early sodium reabsorption in the proximal renal tubules. Losartan also caused a transient increase in uric acid excretion by the kidneys.

In patients with arterial hypertension, proteinuria (at least 2 g/24 hours), without diabetes mellitus and taking losartan for 8 weeks at a dose of 50 mg with a gradual increase to 100 mg, a significant decrease in proteinuria (by 42%), fractional excretion of albumin and immunoglobulins (IgG) was observed. In these patients, losartan stabilized GFR and reduced the filtration fraction.

In postmenopausal women with arterial hypertension who took losartan at a dose of 50 mg / day for 4 weeks, there was no effect of therapy on renal and systemic prostaglandin levels.

Losartan does not affect autonomic reflexes and does not have a long-term effect on the concentration of norepinephrine in blood plasma.

In patients with arterial hypertension, losartan at doses up to 150 mg / day did not cause clinically significant changes in fasting serum triglyceride concentrations, total cholesterol, and high-density lipoprotein cholesterol. At the same doses, losartan had no effect on fasting plasma glucose levels.

In general, losartan caused a decrease in the concentration of uric acid in the blood serum (usually less than 0.4 mg / dl), which persisted with long-term treatment. In controlled clinical trials involving patients with arterial hypertension, there were no cases of drug withdrawal due to an increase in serum creatinine or potassium levels.

In a 12-week parallel study, which included patients with left ventricular failure (II-IV functional class NYHA classification), most of which took diuretics and/or cardiac glycosides, we compared the effects of losartan at doses of 2.5 mg/day,10 mg/day,25 mg/day and 50 mg/day with placebo. At doses of 25 mg / day and 50 mg / day, the drug showed positive hemodynamic and neurohormonal effects, which persisted throughout the study. Hemodynamic effects included an increase in cardiac index and a decrease in pulmonary capillary jamming pressure, as well as a decrease in total peripheral vascular resistance, mean systemic blood pressure, and heart rate. The frequency of arterial hypotension in these patients depended on the dose of the drug. Neurohormonal effects included decreased plasma concentrations of aldosterone and norepinephrine.

Pharmacokinetics

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 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

When taken orally, losartan is well absorbed and undergoes metabolism during the “primary passage” through the liver with the formation of an active carboxylated metabolite and inactive metabolites. The systemic bioavailability of losartan in tablet form is approximately 33%. The average_cmax of losartan and its active metabolite is reached after 1 hour and after 3-4 hours, respectively. There was no clinically significant effect on the plasma losartan concentration profile when losartan was used during a normal meal.

Distribution

Losartan and its active metabolite bind to plasma proteins (mainly albumin) by at least 99%. The volume of distribution of losartan is 34 liters. Studies in rats have shown that losartan practically does not penetrate the blood-brain barrier.

Metabolism

Approximately 14% of the dose of losartan is converted to its active metabolite by intravenous or oral use. After oral or intravenous use of radiolabeled losartan (14C losartan), the radioactivity of circulating blood plasma is primarily due to the presence of losartan and its active metabolite. Low conversion efficiency of losartan to its active metabolite was observed in approximately 1% of the patients who participated in the study.

In addition to the active metabolite, biologically inactive metabolites are formed, including two main metabolites formed as a result of hydroxylation of the butyl side chain, and one minor – N-2-tetrazole-glucuronide.

Deduction

The plasma clearance of losartan and its active metabolite is approximately 600 ml / min and 50 ml / min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 ml / min and 26 ml / min, respectively. When losartan is taken orally, about 4% of the dose is excreted unchanged by the kidneys and about 6% of the dose is excreted by the kidneys as an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when taking losartan orally at doses up to 200 mg.

After oral use, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final_half-life of approximately 2 hours and 6-9 hours, respectively. When the dosage regimen of the drug is 100 mg once a day, there is no significant accumulation in the blood plasma of either losartan or its active metabolite.

The elimination of losartan and its metabolites is carried out by the kidneys and through the intestines with bile. After ingestion of 14C losartan in men, about 35% of radioactivity is detected in the urine and 58% in the feces. After intravenous use of 14C losartan in men, approximately 43% of radioactivity is detected in the urine and 50% in the feces.

Pharmacokinetics in special patient groups

Gender

It was noted that the concentration of losartan in blood plasma in women with arterial hypertension is 2 times higher than the corresponding value in men with arterial hypertension. This pharmacokinetic difference is not clinically relevant. The concentration of the active metabolite in men and women did not differ.

Liver function disorders

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 healthy male volunteers.

Impaired renal function

Plasma concentrations of losartan in patients with creatinine clearance (CC) above 10 ml / min did not differ from those in patients with unchanged 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 did not change in patients with impaired renal function or in patients undergoing hemodialysis. Losartan and its active metabolite are not eliminated by hemodialysis.

Losartan + hydrochlorothiazide combination

Pharmacokinetics in special patient groups

Elderly patients

The plasma concentrations of losartan and its active metabolite and the rate of absorption of hydrochlorothiazide in elderly patients with arterial hypertension do not significantly differ from those in young patients with arterial hypertension.

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

Application of Lorista® ND is contraindicated during pregnancy.

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.

Medications that directly affect the RAAS can cause serious damage and death to the developing fetus, so when diagnosing pregnancy, Lorista®is recommended. The tax ID must be canceled immediately.

Although there is no experience of using Lorista® ND 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 to the fetus increases if Lorista®is used. ND is used in the second or 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 deformities. 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 trimester 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. If an oligohydramnion is detected, it is necessary to stop taking Lorista® ND, unless it is vital for the mother. Depending on the week 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 Lorista®should be carefully monitored. ND during pregnancy, in order to control arterial hypotension, oliguria and hyperkalemia.

Breast-feeding period

Application of Lorista® ND is contraindicated during breastfeeding.

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.

It is not known whether losartan is excreted in breast milk. 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 discontinue breastfeeding or to discontinue Lorista® ND, taking into account the need for its reception for the mother.

Contraindications

• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, as the composition of the drug Lorista® ND includes lactose.
• Hypersensitivity to losartan, hydrochlorothiazide and other excipients.
• Hypersensitivity to other sulfonamide derivatives.
• Anuria.
• Severe renal impairment (creatinine clearance less than 30 ml / min).
• Severe liver function disorders.
• Pregnancy and breast-feeding period.
• Age up to 18 years (efficacy and safety of use have not been established).
• Concomitant use with aliskiren and drugs containing aliskiren in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 of body surface area).
• Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

Side effects

No adverse reactions specific to this combination were observed in clinical trials with hydrochlorothiazide + losartan. Adverse reactions were limited to those already reported with losartan and/or hydrochlorothiazide alone. The overall frequency of adverse reactions reported with this combination was comparable to that reported with placebo. The frequency of discontinuation was also comparable to that of placebo-treated patients.

Overall, treatment with the combination of hydrochlorothiazide + losartan was well tolerated. In most cases, the adverse reactions were mild, transient, and did not require discontinuation of therapy.

In controlled clinical trials in the treatment of arterial hypertension, dizziness was the only drug-related adverse reaction that was more than 1% higher than that of placebo.

Losartan in combination with hydrochlorothiazide has been shown in controlled clinical trials to be generally well tolerated in patients with arterial hypertension and left ventricular hypertrophy. The most common adverse reactions were systemic and non-systemic dizziness, weakness/fatigue.

The following additional adverse reactions have been reported during post-marketing use of this combination, clinical trials conducted, and/or post-marketing use of individual active substances of the combination.

Disorders of the blood and lymphatic system: thrombocytopenia, anemia, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis.

Immune system disorders: anaphylactic reactions, angioedema including swelling of the larynx and of the vocal folds with the development of airway obstruction and/or swelling of the face, lips, pharynx and/or tongue in patients treated with losartan was observed rarely (≥ 0.01% and < 0,1% of cases), some of these patients there were indications the development of angioedema in history when the use of other drugs, including ACE inhibitors.

Metabolic and nutritional disorders: anorexia, hyperglycemia, hyperuricemia, disorders of blood electrolyte balance, including hyponatremia and hypokalemia.

Mental disorders: insomnia, anxiety.

Nervous system disorders: dysgeusia, headache, migraine, paresthesia.

Visual disturbances: xanthopsy, a transient visual impairment.

Cardiac disorders: palpitation, tachycardia.

Vascular disorders: dose-dependent orthostatic effects, necrotizing angiitis (vasculitis), cutaneous vasculitis.

Respiratory, thoracic and mediastinal disorders: cough, nasal congestion, pharyngitis, sinus disorders (sinusitis), upper respiratory tract infections, adult respiratory distress syndrome (including pneumonitis and pulmonary edema).

Disorders of the digestive system: dyspepsia, abdominal pain, esophageal reflux, gastrointestinal colic, diarrhea, constipation, nausea, vomiting, pancreatitis, sialadenitis.

Liver and biliary tract disorders: hepatitis, jaundice (intrahepatic cholestatic jaundice).

Skin and subcutaneous tissue disorders: skin rash, pruritus, purpura (including Schonlein-Henoch purpura), toxic epidermal necrolysis, urticaria, erythroderma, photosensitivity, lupus-like syndrome.

Musculoskeletal and connective tissue disorders: back pain, muscle cramps, muscle spasms, myalgia, arthralgia.

Kidney and urinary tract disorders: glucosuria, impaired renal function, interstitial nephritis, renal failure.

Genital and breast disorders: erectile dysfunction/impotence.

General disorders and disorders at the injection site: chest pain, swelling, malaise, fever, weakness.

Laboratory and instrumental data: impaired liver function (rarely increased alanine aminotransferase activity in blood plasma).

Laboratory parameters

In controlled clinical trials, clinically significant changes in standard laboratory parameters were rarely observed while taking the combination of hydrochlorothiazide + losartan. Hyperkalemia (serum potassium > 5.5 mEq / L) was observed in 0.7% of patients, but in these studies there was no need to cancel the combination of hydrochlorothiazide + losartan due to the occurrence of hyperkalemia. Increased alanine aminotransferase activity in blood plasma was rarely observed and usually returned to normal after discontinuation of therapy.

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 (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.

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.

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 be accompanied by regular monitoring of blood plasma potassium levels, ECG readings, and, if necessary, adjustment of 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 calcium content in the blood 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, or phenobarbital have been identified in clinical studies of pharmacokinetic drug interactions. Rifampicin, being an inducer of drug metabolism, reduces the concentration of the active metabolite of losartan in blood plasma. Two inhibitors of the CYP3A4 isoenzyme, ketoconazole and erythromycin, were used in clinical trials. . Ketoconazole did not affect the metabolism of losartan to the active metabolite after intravenous use of losartan. Erythromycin did not have a clinically significant effect when taking losartan orally. Fluconazole, an inhibitor of the CYP2C9 isoenzyme, reduces the concentration of the active metabolite of losartan in blood plasma, but the pharmacodynamic significance of concomitant use of losartan and inhibitors of the CYP2C9 isoenzyme has not been studied. Patients who do not metabolize losartan to the active metabolite have been shown to have a very rare and specific defect in the CYP2C9 isoenzyme. These data suggest that losartan is metabolized to the active metabolite by the CYP2C9 isoenzyme, and not by the CYP3A4 isoenzyme.

Concomitant use of losartan, as well as other drugs that block angiotensin II or its effects, with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride, eplerenone), potassium-containing supplements or potassium salts may lead to an increase in serum potassium.

As with other medications that affect the elimination of sodium, losartan may reduce the elimination of lithium. Therefore, when lithium and ARA II preparations are used simultaneously, it is necessary to carefully monitor the concentration of lithium in the blood serum.

Nonsteroidal anti-inflammatory drugs (NSAIDs)Some drugs, including selective cyclooxygenase-2 (COX-2) inhibitors, may reduce the effect of diuretics and other antihypertensive agents. As a result, the antihypertensive effect of ARA II or ACE inhibitors may be weakened when used concomitantly with NSAIDs, including selective COX-2 inhibitors.

In some patients with impaired renal function (for example, in elderly patients or patients with dehydration, including those taking diuretics), receiving NSAID therapy, including selective COX-2 inhibitors, the simultaneous use of ARA II or ACE inhibitors may cause further deterioration of renal function, including the development of acute renal failure. These effects are usually reversible, so the concomitant use of these drugs should be carried out with caution in patients with impaired renal function.

Dual blockade of the RAAS with ARA II, ACE inhibitors, or aliskiren (a renin inhibitor) is associated with an increased risk of hypotension, syncope, hyperkalemia, and impaired renal function (including acute renal failure) compared to monotherapy. Regular monitoring of blood pressure, renal function, and plasma electrolyte levels is necessary in patients taking Lorista concomitantly. ND and other drugs that affect the RAAS. 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 m2 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.

How to take, course of use and dosage

Lorista®Preparation ND is taken orally, regardless of the time of food intake, once a day. Lorista®Preparation ND can be taken simultaneously with other antihypertensive agents.

Arterial hypertension

The initial and maintenance dose is 1 tablet of Lorista ® ND once a day. Lorista®Preparation ND is prescribed in the absence of an adequate therapeutic effect against the background of a combination of hydrochlorothiazide at a dose of 12.5 mg and losartan at a dose of 50 mg once a day for 2-4 weeks. The maximum daily dose is 1 tablet of Lorista ® ND once a day.

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

Lorista®Preparation ND is used in a dose of 1 tablet 1 time a day. Lorista®Preparation ND is prescribed to patients who fail to achieve the target blood pressure values against the background of taking a combination of hydrochlorothiazide at a dose of 12.5 mg and losartan at a dose of 50 mg once a day.

Special patient groups

Patients with impaired renal function or patients undergoing hemodialysis

Lorista®Preparation ND should not be used for initial therapy in patients with moderate renal impairment (creatinine clearance 30-50 ml / min). Lorista®Preparation ND is not recommended for patients undergoing hemodialysis. Lorista®Preparation ND should not be used in patients with severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Patients with reduced BCC

Lorista®Preparation ND should not be used for initial therapy in patients with reduced BCC.

Patients with impaired liver function

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

Elderly patients

Lorista®Preparation ND should not be used for initial therapy in elderly patients.

Overdose

There are no data on specific treatment of overdose with a combination of hydrochlorothiazide + losartan. Treatment is symptomatic and supportive. Taking Lorista® ND 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 reduce blood pressure by standard methods.

Hydrochlorothiazide

Symptoms

The most common manifestation of hydrochlorothiazide overdose is increased diuresis, accompanied by acute fluid loss (dehydration) and electrolyte disturbances (hypokalemia, hyponatremia, gnpochloremia). Overdose with hydrochlorothiazide can manifest the following symptoms::

• from the side of cardiovascular system: tachycardia, decreased blood pressure, shock;
• from the nervous system: weakness, confusion, dizziness, and cramps of the calf muscles, paresthesia, impaired consciousness, fatigue;
• gastrointestinal: 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 the nitrogen content of urea 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 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, in case of development of symptomatic arterial hypotension, maintenance therapy is indicated.

Losartan and its active metabolite are not eliminated by hemodialysis.

Description

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

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

Lorista®Preparation ND should not be used for initial therapy in patients with moderate renal impairment (creatinine clearance 30-50 ml / min). Lorista®Preparation ND is not recommended for patients undergoing hemodialysis. Lorista®Preparation ND should not be used in patients with severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Patients with reduced BCC

Lorista®Preparation ND should not be used for initial therapy in patients with reduced BCC.

Patients with impaired liver function

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

Elderly patients

Lorista®Preparation ND should not be used for initial therapy in elderly patients.

Application of Lorista® ND in patients with acute myocardial infarction is not recommended due to insufficient clinical experience. Also the drug Lorista® ND should not be used to relieve a hypertensive crisis.

The drugLorista® ND

Hypersensitivity reactions

In patients with a history of angioedema (swelling of the face, lips, pharynx/larynx and/or tongue), the use of the drug should be monitored (see the section “Side effects”).

Impaired kidney and liver function

Lorista®Preparation ND is contraindicated for use in patients with severe hepatic impairment and severe renal impairment (creatinine clearance less than 30 ml / min) (see section “Contraindications”).

Embryotoxicity

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 deformities. Possible adverse events in newborns include cranial hypoplasia, anuria, hypotension, renal failure, and death. When diagnosing pregnancy, the drug Lorista® ND should be immediately discontinued (see the section “Use during pregnancy and lactation”).

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 content of potassium in blood plasma and the development of hypokalemia (potassium concentration 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. 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 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

Double blockade of the RAAS

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 m2 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.

Arterial hypotension and BCC reduction

Patients with reduced BCC or plasma sodium levels due to intensive diuretic therapy, a salt-restricted diet, diarrhea, or vomiting may develop symptomatic hypotension, especially after taking the first dose of Lorista HD. Correction of such conditions should be carried out before prescribing Lorista ® ND.

Violation 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 Lorista® ND it is not recommended to take potassium-sparing diuretics, potassium preparations, or potassium-containing salt substitutes.

Aortic or mitral stenosis, HOCMP

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

CHD and cerebrovascular diseases

Like all drugs with vasodilating effects, ARA II should be used 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.

Chronic heart failure (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 or acute renal failure.

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® ND is not recommended in this group of patients.

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® ND should be administered 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 Lorista® ND should not be used in this group of patients (see section “Contraindications”).

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 the concentration of urea and creatinine in blood plasma 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.

Special patient groups

Race

Analysis of data from the entire population 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 arterial hypertension and left ventricular hypertrophy (n = 9193) showed that the ability of losartan compared with atenolol to reduce the risk of stroke and myocardial infarction, as well as to reduce the cardiovascular mortality rate in patients with arterial hypertension and left ventricular hypertrophy (by 13.0%, p = 0.021) It applies to patients of the black race, although both treatment regimens effectively reduced the level of blood pressure in these patients. In this study, losartan compared with atenolol reduced cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy of all races except negroid (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).

Children and teenagers

The efficacy and safety of using the combination of hydrochlorothiazide + losartan in children and adolescents under 18 years of age have not been established.

If in newborns whose mothers have taken Lorista® ND during pregnancy, the development of oliguria or arterial hypotension is observed, it is necessary to conduct symptomatic therapy aimed at maintaining blood pressure and renal perfusion. Blood transfusions or dialysis may be required to prevent hypotension and / or maintain kidney function.

Elderly patients

Clinical studies have not revealed any specific features regarding the safety and efficacy of Lorista® ND in elderly patients (older than 65 years).

Special information on excipients

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

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, care should be taken.

Form of production

Film-coated tablets,25 mg + 100 mg.

During production at JSC “KRKA, D. D., Novo Mesto”, 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 30 ° 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

Prevention of heart attacks and strokes, Hypertension