Lorista, 60 pcs., 50 mg, film-coated tablets

Lorista, 60 pcs., 50 mg, film-coated tablets

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

The results of the studies demonstrated the following data:

— in the “Take Off” study, Lorista® (losartan from KRKA) significantly reduced uric acid levels by 32.6% in patients with arterial hypertension (AH) and concomitant hyperuricemia and/or gout. 100% of patients participating in the study achieved the target blood pressure level. Therapy with Lorista has a pronounced positive effect on the elasticity of the vascular wall in patients with hypertension1;

— in the open-label multicenter clinical trial LAURA2 (Lorista® and uric acid), the relationship between treatment with Lorista and its fixed combination with hydrochlorothiazide (Lorista® H and Lorista® HD) and hyperuricemia was studied. Based on the results of the study in patients with hypertension and hyperuricemia, Lorista®, Lorista® H and Lorista® ND, due to their apparent ability to lower uric acid levels, can be used as the preferred therapy;

— the EFFECT3 study proved the effectiveness and safety of losartan (Lorista®) in patients with mild and moderate hypertension. In addition, it is important to emphasize the safety of using Lorista (adverse effects in less than 1% of patients), which makes the drug an indispensable assistant in the fight against hypertension;

— as a result of the international study Gemera4, the effectiveness and safety of the use of Lorista® and a fixed combination with hydrochlorothiazide (Lorista® N) in patients with stage 1–2 hypertension was confirmed. 100% of patients achieved CAP.

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

Literature

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

2. Svishchenko E.P., Bezrodnaya L.V., Gorbas I.M. Clinical and uricosuric efficacy of losartan in patients with arterial hypertension. Results of the open multicenter clinical trial LAURA. Arterial hypertension.- 2012.- 5 (25).- P.25–32.

3. Drapkina O.M., Kozlova E.V. The place of angiotensin receptor antagonists in the treatment of cardiovascular diseases. Study EFFECT: use of Lorista in patients with mild and moderate arterial hypertension in real clinical practice. Problems of women's health.- 2009.- 4(4).- P.17–26.

4. Chazova I.E., Martynyuk T.V. Federal State Budgetary Institution Russian Cardiology Research and Production Complex of the Ministry of Health of the Russian Federation, Moscow. First results of the international clinical trial GEMERA: two therapeutic regimens for the effective treatment of patients with stage 1–2 arterial hypertension.

Lorista tablets ppo 50 mg No. 90

Compound

Active ingredient: losartan potassium 50 mg.
Excipients: cellactose 801, pregelatinized starch, corn starch, microcrystalline cellulose, colloidal silicon dioxide, magnesium stearate.

Film coating: hypromellose, talc, propylene glycol, quinoline yellow dye (E104) (for tablets 12.5 mg and 25 mg), titanium dioxide (E171).

1 Cellactose 80: lactose monohydrate, cellulose.

Pharmacokinetics

Suction

When taken orally, losartan is well absorbed and undergoes first-pass metabolism through the liver to form an active carboxylated metabolite and inactive metabolites. The systemic bioavailability of losartan in the dosage form of film-coated tablets is approximately 33%. The average Cmax of losartan and its active metabolite in blood plasma is reached after 1 hour and after 3-4 hours, respectively. When taking losartan during a normal meal, there was no clinically significant effect on the plasma concentration profile of losartan.

Distribution

Losartan and its active metabolite are bound 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 a dose of losartan, when administered intravenously or taken orally, is converted into its active metabolite. After oral or intravenous administration of radioactive carbon-labeled 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 patients participating in the study. In addition to the active metabolite, biologically inactive metabolites are formed, including two major metabolites formed as a result of hydroxylation of the butyl side chain, and one minor one, N-2-tetrazole glucuronide.

Removal

Plasma clearance of losartan and its active metabolite is about 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 in the form of an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when losartan is administered orally in doses up to 200 mg.

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

Losartan and its metabolites are excreted by the kidneys and through the intestines with bile. After oral administration of 14C losartan in men, about 35% of radioactivity is found in urine and 58% in feces. After intravenous administration of 14C losartan in men, approximately 43% of the radioactivity is found in the urine and 50% in the feces.

Pharmacokinetics in selected patient groups

Elderly patients

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

Floor

Plasma concentrations of losartan in women with hypertension were 2 times higher than the corresponding values ​​in men with hypertension. Concentrations of the active metabolite in blood plasma did not differ between men and women. This apparent pharmacokinetic difference is, however, not clinically significant.

Patients with liver dysfunction

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

Patients with 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 value of the area under the curve “conInteraction with other drugs”).

With caution:
Bilateral renal artery stenosis or stenosis of the artery of a single kidney, hyperkalemia, condition after kidney transplantation (no experience with use), aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (HOCM), heart failure with concomitant severe renal impairment, severe heart failure ( IV functional class according to the NYHA classification), heart failure with life-threatening arrhythmias, coronary heart disease (CHD), cerebrovascular diseases, primary hyperaldosteronism, history of angioedema.

In patients with reduced circulating blood volume (CBV) (for example, patients receiving treatment with large doses of diuretics) symptomatic arterial hypotension may develop.

Directions for use and doses

The drug Lorista® is taken orally, regardless of the time of meal. Lorista® can be taken in combination with other antihypertensive drugs.

Arterial hypertension

The standard initial and maintenance dose for most patients is 50 mg of Lorista® once daily. The maximum antihypertensive effect is achieved 3-6 weeks from the start of therapy. In some patients, to achieve greater effect, the dose may be increased to a maximum dose of 100 mg of Lorista® once a day.

In patients with reduced blood volume (for example, when taking large doses of diuretics), the initial dose of Lorista should be reduced to 25 mg 1 time per day (see section "Special Instructions").

There is no need to select the initial dose of Lorista® for elderly patients and patients with impaired renal function, including patients on dialysis.

For patients with a history of liver disease, it is recommended to use lower doses of Lorista® (see section "Special Instructions").

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

The standard starting dose of Lorista® is 50 mg once a day. In the future, it is recommended to add hydrochlorothiazide to therapy in low doses or increase the dose of Lorista® to a maximum dose of 100 mg 1 time per day, taking into account the degree of blood pressure reduction.

Kidney protection in patients with type 2 diabetes and proteinuria

The standard starting dose of Lorista® is 50 mg once a day. In the future, the dose of Lorista® can be increased to a maximum dose of 100 mg 1 time per day, taking into account the degree of blood pressure reduction.

Lorista® can be used in combination with other antihypertensive agents (for example, diuretics, slow calcium channel blockers (SCBCs), alpha and beta blockers, centrally acting antihypertensive agents), insulin and other hypoglycemic agents (for example, sulfonylureas, glitazones and glucosidase inhibitors).

Chronic heart failure

The initial dose of Lorneta® for patients with CHF is 12.5 mg once a day. Typically, the dose is titrated at weekly intervals (i.e., 12.5 mg/day, 25 mg/day, 50 mg/day, 100 mg/day to a maximum dose [for this indication only] of 150 mg once daily) depending on individual tolerance.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging. Keep out of the reach of children.

Best before date

5 years. Do not use the drug after the expiration date.

special instructions

Hypersensitivity reactions

Patients with a history of angioedema (swelling of the face, lips, pharynx/larynx and/or tongue) should be under strict medical supervision when using Lorista® (see section “Side Effects”).

Embryotoxicity

The use of drugs that affect the RAAS during the second and third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and mortality. The development of oligohydramnios may be associated with fetal pulmonary hypoplasia and skeletal deformities. Possible AEs in newborns include calvarial hypoplasia, anuria, hypotension, renal failure and death. If pregnancy is diagnosed, Lorista® should be discontinued immediately (see section “Use during pregnancy and breastfeeding”).

Arterial hypotension and water-electrolyte imbalance or decreased blood volume

In patients with reduced blood volume (for example, those receiving treatment with large doses of diuretics), symptomatic arterial hypotension may develop. Correction of such conditions must be carried out before using the drug Lorista® or treatment must begin with a lower dose of the drug Lorista® (see section “Method of administration and dosage”).

Fluid and electrolyte imbalance is common in patients with impaired renal function with or without diabetes mellitus, so careful monitoring of these patients is necessary. In clinical trials in patients with type 2 diabetes mellitus with proteinuria, the incidence of hyperkalemia was greater in the losartan group than in the placebo group. Several patients discontinued therapy due to hyperkalemia (see section “Side effects”, subsection “Laboratory and instrumental data”).

During treatment with Lorista®, it is not recommended to take potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes.

Aortic or mitral stenosis, HOCM

Like all drugs that have a vasodilating effect, ARA II should be used with caution in patients with aortic or mitral stenosis or HOCM.

IHD and cerebrovascular diseases

Like all drugs that have a vasodilating effect, ARA II should be used with caution in patients with coronary artery disease 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 the use of other drugs that act on the RAAS, patients with CHF and with or without impaired renal function are at risk of developing severe hypotension or acute renal impairment.

Since there is insufficient experience with the use of Lorista® in patients with heart failure and concomitant severe renal impairment, in patients with severe heart failure (NYHA functional class IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias, the drug Lorista® should be used with caution in patients in these groups.

Primary hyperaldosteronism

Since patients with primary hyperaldosteronism, as a rule, do not have a positive response to therapy with antihypertensive drugs that act by inhibiting the RAAS, the use of Lorista is not recommended in this group of patients.

Liver dysfunction

Data from pharmacokinetic studies indicate that the concentration of losartan in the blood plasma in patients with cirrhosis of the liver is significantly increased, therefore patients with a history of impaired liver function should use the drug Lorista® at a lower dose. There is no experience with the use of losartan in patients with severe liver dysfunction, so Lorista® should not be used in this group of patients (see sections “Pharmacological properties” [subsection “Pharmacokinetics”], “Contraindications”, “Dosage and Administration”).

Renal dysfunction

Due to inhibition of the RAAS, changes in renal function, including the development of renal failure, have been observed in some susceptible patients. These changes in renal function may return to normal after treatment is stopped.

Some drugs that affect the RAAS may increase serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or renal artery stenosis of a solitary 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 solitary kidney.

Special patient groups

Ethnic characteristics

Analysis of data from the entire population of patients included in a clinical trial to study 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 showed that the ability of losartan, compared with atenolol, to reduce the risk of stroke and myocardial infarction, and also reducing the rate of cardiovascular mortality in patients with hypertension and left ventricular hypertrophy (by 13.0%) does not apply to patients of the Negroid race, 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 blacks. However, in this study, black patients receiving atenolol had a lower risk of the study's primary composite endpoint (i.e., lower combined incidence of cardiovascular death, stroke, and myocardial infarction) compared with race-matched patients receiving losartan.

Children and teenagers

The effectiveness and safety of losartan in children and adolescents under 18 years of age have not been established.

If oliguria or arterial hypotension develops in newborns whose mothers took losartan during pregnancy, 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 renal function.

Elderly patients

Clinical studies have not revealed any particularities regarding the safety and effectiveness of losartan in elderly patients (over 65 years of age).

Description

Angiotensin II receptor antagonist.

Dosage form

Pills

Use in children

The effectiveness and safety of losartan in children and adolescents under 18 years of age have not been established.

If oliguria or arterial hypotension develops in newborns whose mothers took losartan during pregnancy, 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 renal function.

Pharmacodynamics

Mechanism of action

Angiotensin II is a powerful vasoconstrictor, the main active hormone of the renin-angiotensin-aldosterone system (RAAS), and a decisive pathophysiological link in the development of arterial hypertension (AH). Angiotensin II binds to AT1 receptors in many tissues (vascular smooth muscle, adrenal glands, kidneys and heart) and has several important biological functions, including vasoconstriction and aldosterone release. In addition, angiotensin II stimulates the proliferation of smooth muscle cells. AT2 receptors are the second type of receptor to which angiotensin II binds, but their role in regulating cardiovascular function is unknown.

Losartan is a selective antagonist of angiotensin II AT1 receptors, highly effective when taken orally. Losartan and its pharmacologically active carboxylated metabolite (E-3174), in both in vitro and in vivo conditions, block all physiological effects of angiotensin II, regardless of its source or route of synthesis. Unlike some peptide angiotensin II antagonists, losartan does not have agonist properties.

Losartan selectively binds to AT1 receptors and does not bind to or block 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 angiotensin-converting enzyme (ACE) kininase II, which is responsible for the destruction of bradykinin. Therefore, effects 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 action of losartan.

Pharmacodynamics

Losartan suppresses the increase in systolic and diastolic blood pressure (BP) during angiotensin II infusion. At the moment of reaching the maximum concentration of losartan (Cmax) in the blood plasma after taking losartan at a dose of 100 mg, the above effect of angiotensin II is suppressed by approximately 85%, and 24 hours after single and multiple doses - by 26-39%.

When taking losartan, elimination of the negative feedback, which consists in the suppression of renin secretion by angiotensin II, leads to an increase in plasma renin activity (PRA). An increase in ARP leads to an increase in the concentration of angiotensin II in the blood plasma.

Since losartan is a specific antagonist of angiotensin II AT1 receptors, it does not inhibit ACE (kininase II), an enzyme that inactivates bradykinin.

A study comparing the effects of losartan at doses of 20 mg and 100 mg with the effects of an ACE inhibitor 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 responses to angiotensin I and increased the effects due to bradykinin without affecting the response to angiotensin II, demonstrating a pharmacodynamic difference between losartan and ACE inhibitors.

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

Losartan therapy in postmenopausal women with hypertension does not affect the renal and systemic levels of prostaglandins.

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

In patients with hypertension, losartan in doses up to 150 mg/day does not cause clinically significant changes in serum concentrations of fasting triglycerides, total cholesterol and high-density lipoprotein cholesterol. At the same doses, losartan has no effect on fasting blood glucose concentrations.

In patients with chronic heart failure (CHF) functional class II-IV according to the NYHA classification and intolerance to ACE inhibitors, losartan at a dose of 150 mg/day significantly reduces the risk of all-cause mortality or the risk of hospitalization for heart failure compared with a dose of 50 mg/day .

In patients with left ventricular failure (NYHA functional class II-IV), most of whom are taking diuretics and/or cardiac glycosides, losartan in doses of 25 and 50 mg/day exhibits positive hemodynamic and neurohormonal effects.

Hemodynamic effects include an increase in cardiac index and a decrease in pulmonary capillary wedge pressure, as well as a decrease in total peripheral vascular resistance (TPVR), mean systemic blood pressure and heart rate (HR). The incidence of arterial hypotension in such patients depends on the dose of losartan.

Neurohormonal effects include decreased serum aldosterone and norepinephrine concentrations.

Side effects

The use of losartan was studied in the following clinical studies:

• in a controlled clinical trial involving more than 3,000 adult patients aged 18 years and older with essential hypertension;
• in a controlled clinical trial involving 177 children aged 6 to 16 years with arterial hypertension;
• in a controlled clinical trial involving more than 9,000 patients aged 55 to 80 years with arterial hypertension and left ventricular hypertrophy;
• in a controlled clinical trial involving more than 7,700 adult patients with chronic heart failure;
• in a controlled clinical trial involving more than 1,500 patients aged 31 years and older with type 2 diabetes mellitus with proteinuria.

In these clinical studies, the most common adverse event was dizziness.

Classification of the frequency of side effects recommended by the World Health Organization (WHO):

• very common ≥ 1/10
• often from ≥ 1/100 to < 1/10
• uncommon ≥ 1/1000 to < 1/100
• rarely from ≥ 1/10000 to < 1/1000
• very rare < 1/10000
• frequency unknown cannot be estimated from available data.

Table 1. Incidence of adverse reactions identified in placebo-controlled clinical trials and post-registration use

*Including laryngeal edema, narrowing of the glottis, swelling of the face, lips, pharynx and/or tongue (resulting in airway obstruction), angioedema has been previously reported in some of these patients in association with other medications, including ACE inhibitors .

**Including hemorrhagic vasculitis (Henoch-Schönlein disease).

║Especially in patients with reduced blood volume, for example, in patients with severe heart failure or receiving treatment with diuretics in high doses.

†Often in patients treated with losartan 150 mg instead of 50 mg.

‡In a clinical study of patients with type 2 diabetes mellitus with nephropathy, 9.9% of patients treated with losartan tablets developed hyperkalemia >5.5 mmol/L, as did 3.4% of patients treated placebo.

§Usually resolved upon discontinuation of drug use.

The following additional adverse reactions occurred more frequently in patients receiving losartan than in patients receiving placebo (frequency unknown): back pain, urinary tract infections, and flu-like symptoms.

Renal and urinary tract disorders:

Impaired renal function, including renal failure, has been reported in patients at risk due to RAAS suppression. These changes in renal function may be reversible if treatment is discontinued (see section "Special Instructions").

Use during pregnancy and breastfeeding

Medicines that act directly on the RAAS can cause serious damage and death to the developing fetus, therefore, when pregnancy is diagnosed, Lorista® should be immediately discontinued and, if necessary, alternative antihypertensive therapy should be prescribed.

Therapy with Lorista® should not be started during pregnancy. If continued antihypertensive therapy with losartan is considered necessary in patients planning pregnancy, losartan should be replaced with alternative antihypertensive agents that have an established safety profile for use in pregnancy.

Although there is no experience with the use of losartan in pregnant women, preclinical studies in animals have shown that administration of 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 effect on the RAAS.

Renal perfusion in the fetus, dependent on the development of the RAAS, appears in the second trimester, so the risk to the fetus increases if Lorista® is used in the second or third trimester of pregnancy.

The use of drugs that affect the RAAS during the second and third trimester of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and mortality. The development of oligohydramnios may be associated with fetal pulmonary hypoplasia and skeletal deformities. Potential adverse events (AEs) in neonates include calvarial hypoplasia, anuria, hypotension, renal failure and death.

The above undesirable outcomes are usually caused by the use of drugs that affect the RAAS in the second and third trimester of pregnancy. Most epidemiological studies examining the development of fetal abnormalities following the use of antihypertensive drugs in the first trimester of pregnancy have found no differences between drugs acting on the RAAS and other antihypertensive drugs. When using antihypertensive therapy in pregnant women, it is important to optimize possible outcomes for the mother and fetus.

If it is impossible to select an alternative therapy instead of therapy with drugs that affect the RAAS, it is necessary to inform the patient about the possible risk of therapy to the fetus. Periodic ultrasound examinations are necessary to assess the intra-amniotic space. If oligohydramnios is detected, it is necessary to stop taking the drug Lorista, unless it is vital for the mother. Depending on the stage of pregnancy, appropriate tests on the fetus are necessary. Patients and physicians should be aware that oligohydramnios may not be detected until irreversible fetal damage occurs. Careful monitoring of newborns whose mothers took Lorista during pregnancy is necessary to monitor arterial hypotension, oliguria and hyperkalemia.

It is not known whether losartan is excreted in breast milk. Since many drugs are excreted in breast milk and there is a risk of possible adverse effects in a breastfed baby, a decision should be made to stop breastfeeding or discontinue the drug, taking into account the need for the mother.

Interaction

Other antihypertensive drugs may enhance the antihypertensive effect of losartan.

Concomitant use with other drugs that can cause hypotension (such as tricyclic antidepressants, antipsychotics, baclofen and amifostine) may increase the risk of developing arterial hypotension.

In clinical studies examining pharmacokinetic drug interactions, no clinically significant interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital were identified.

Rifampin, being an inducer of drug metabolism, reduces the concentration of the active metabolite of losartan in the blood plasma.

Clinical studies have examined the use of two inhibitors of the CYP3A4 isoenzyme: ketoconazole and erythromycin. Ketoconazole did not affect the metabolism of losartan to its active metabolite after intravenous administration of losartan. Erythromycin did not have a clinically significant effect when losartan was taken orally.

Fluconazole, an inhibitor of the CYP2C9 isoenzyme, reduces the concentration of the active metabolite of losartan in the blood plasma, but the pharmacodynamic significance of the simultaneous use of losartan and inhibitors of the CYP2C9 isoenzyme has not been studied. It has been shown that patients who do not metabolize losartan into the active metabolite have a very rare and specific defect in the CYP2C9 isoenzyme. These data suggest that the metabolism of losartan to the active metabolite is carried out 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, eplerenone, triamterene, amiloride), potassium supplements or potassium salts may lead to an increase in serum potassium.

As with the use of other drugs that affect the excretion of sodium ions, losartan can reduce the excretion of lithium, therefore, when using lithium preparations and ARA II simultaneously, it is necessary to carefully monitor the lithium content in the blood serum.

Nonsteroidal anti-inflammatory drugs (NSAIDs), 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 simultaneously with NSAIDs, including selective COX-2 inhibitors.

In some patients with impaired renal function (for example, elderly or dehydrated patients, including those taking diuretics) receiving NSAID therapy, including selective COX-2 inhibitors, concomitant use of ARB II or ACE inhibitors may cause further deterioration renal function, including the development of acute renal failure. These effects are usually reversible.

The simultaneous use of these drugs should be done with caution in patients with impaired renal function. Dual blockade of the RAAS using ARB II, ACE inhibitors or aliskiren (renin inhibitor) is associated with an increased risk of arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy. Regular monitoring of blood pressure, renal function and electrolyte levels in the blood plasma is necessary in patients taking Lorista® and other drugs that affect the RAAS at the same time.

The simultaneous use of ARA II with drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or moderate to severe renal failure (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Overdose

Information about overdose is limited.

Symptoms: the most likely manifestation of an overdose is a pronounced decrease in blood pressure and tachycardia; bradycardia can occur due to parasympathetic (vagal) stimulation. In case of development of symptomatic arterial hypotension, maintenance therapy is indicated.

Treatment: symptomatic therapy. Losartan and its active metabolite are not eliminated by hemodialysis.

Impact on the ability to drive vehicles and operate machinery

No studies have been conducted to evaluate the effect of losartan on the ability to drive vehicles and operate machines, but caution should be exercised when using antihypertensive therapy and driving or operating machines, since dizziness and drowsiness may develop, especially at the beginning of therapy or when the dose of the drug is increased Lorista®.

Lorista N tablets 50 mg + 12.5 mg 30 pcs. in Moscow

The use of Lorista® N in patients with acute myocardial infarction is not recommended due to insufficient experience in clinical use. It should also not be used to relieve a hypertensive crisis.

Hydrochlorothiazide

Renal dysfunction

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 CK is necessary. If renal dysfunction progresses and/or oliguria (anuria) occurs, hydrochlorothiazide should be discontinued.

Liver dysfunction

When using thiazide diuretics in patients with impaired liver function, hepatic encephalopathy may develop. In patients with severe liver failure or hepatic encephalopathy, the use of thiazides is contraindicated. In patients with mild to moderate hepatic impairment and/or progressive liver disease, hydrochlorothiazide should be used with caution, since even slight changes in fluid and electrolyte balance and serum ammonium accumulation 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 blood volume (hypovolemia) and disturbances in water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis). Clinical symptoms of water-electrolyte balance disorders are dryness of the oral mucosa, thirst, weakness, lethargy, fatigue, drowsiness, anxiety, muscle pain or cramps, muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, arrhythmia and gastrointestinal disorders (such such as nausea and vomiting). In patients receiving hydrochlorothiazide therapy (especially with long-term course treatment), clinical symptoms of water-electrolyte imbalance should be identified and the content of electrolytes in the 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. A concomitant decrease in 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 while 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 (potassium content in the blood plasma less than 3.4 mmol/l). Hypokalemia increases the risk of developing heart rhythm disturbances (including severe arrhythmias) and enhances 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 be fatal.

Hypokalemia poses the greatest danger to the following groups of patients: elderly people, patients simultaneously receiving 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, coronary artery disease, CHF . In addition, patients with an increased QT interval are at increased risk. It does not matter whether this increase is caused by congenital causes or the effect of drugs.

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

Calcium

Thiazide diuretics may reduce the excretion of calcium ions by the kidneys, leading to a slight and temporary increase in plasma calcium levels. In some patients, with long-term 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). Severe hypercalcemia may be a manifestation of previously undiagnosed hyperparathyroidism.

Because of their effect on calcium metabolism, thiazides may interfere with laboratory parameters of parathyroid function. Thiazide diuretics (including hydrochlorothiazide) should be discontinued before testing parathyroid function.

Magnesium

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

Glucose

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

Uric acid

In patients with gout, the frequency of attacks may increase or the course of gout may worsen. Careful monitoring of patients with gout and impaired uric acid metabolism (hyperuricemia) is necessary.

Lipids

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

Acute myopia/secondary angle-closure glaucoma

Hydrochlorothiazide can cause an idiosyncratic reaction, leading to the development of acute myopia and an acute attack of secondary angle-closure glaucoma. Symptoms include: sudden loss of visual acuity or eye pain, usually occurring within hours to weeks of starting hydrochlorothiazide therapy. If left untreated, acute angle-closure glaucoma can lead to irreversible vision loss. If symptoms appear, you should stop taking hydrochlorothiazide as soon as possible. If intraocular pressure remains uncontrolled, emergency medical treatment or surgery may be required. Risk factors for the development of acute angle-closure glaucoma include a history of an allergic reaction to sulfonamides or penicillin. Immune system disorders

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

In patients receiving thiazide diuretics, hypersensitivity reactions may occur even in the absence of a history of allergic reactions or bronchial asthma.

Photosensitivity

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

Non-melanoma skin cancer (NMSC)

Two pharmacoepidemiological studies using data from the Danish National Cancer Registry demonstrated an association between hydrochlorothiazide use and an increased risk of NMSC—basal cell carcinoma and squamous cell carcinoma. The risk of developing NMSC increased with increasing total (cumulative) dose of hydrochlorothiazide. A possible mechanism for the development of NMSC is the photosensitizing effect of hydrochlorothiazide. Patients taking hydrochlorothiazide as monotherapy or in combination with other drugs should be aware of the risk of developing NMSC. It is recommended that such patients undergo regular skin examination to identify any new suspicious lesions as well as changes in existing skin lesions.

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

To minimize the risk of developing NMSC, patients should be advised to follow preventive measures, such as limiting exposure to sunlight and UV rays, and using appropriate protective equipment.

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

Athletes

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

Other

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 causing signs of thyroid dysfunction.

Losartan

Angioedema

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

Arterial hypotension and hypovolemia (dehydration)

In patients with hypovolemia (dehydration) and/or reduced sodium content in the blood plasma, against the background of diuretic therapy, limited salt intake, diarrhea or vomiting, symptomatic arterial hypotension may develop, especially after taking the first dose of Lorista® N. Before using the drug, you should restore the blood volume and/or sodium content in the blood plasma.

Water-electrolyte imbalance

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

Concomitant use of ARA II with aliskiren and drugs containing aliskiren is contraindicated in patients with diabetes mellitus and/or with moderate or severe renal impairment (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients . Concomitant use of ARB II with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

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

Liver dysfunction

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

Renal dysfunction

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

Renal artery stenosis

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

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

Kidney transplant

There is no experience with the use of Lorista® N in patients who have recently undergone kidney transplantation.

Primary hyperaldosteronism

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

IHD and cerebrovascular diseases

As with the treatment of any antihypertensive drugs, a pronounced decrease in blood pressure in patients with coronary artery disease or cerebrovascular diseases can lead to the development of myocardial infarction or stroke.

Heart failure

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

Stenosis of the aortic and/or mitral valves, HOCM

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

Ethnic characteristics

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

Special information on excipients

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

Impact on driving vehicles and machinery

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