Lorist - instructions for use, dose, side effects, contraindications

Excipients: cellulose 80 * 218.70 mg, pregelatinized starch 75.00 mg, corn starch 75.00 mg, microcrystalline cellulose 75.00 mg, silicon dioxide colloid 1.80 mg, magnesium stearate 4.50 mg;

Film Sheath: hypromellose 10.83 mg, talc 0.99 mg, propylene glycol 0.84 mg, iron dye red oxide (E172) 0.06 mg, titanium dioxide (E171) 2.28 mg.

* Zellactose 80 - a mixture of lactose monohydrate and cellulose, dried by spraying.

Description:

Oval, biconvex tablets, covered with a film coat of light pink color.

View of the fracture: a rough mass of white color with a film coating of light pink color.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.01 Losartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

Mechanism of action

Angiotensin II is a potent vasoconstrictor, the main active hormone of the renin-angiotensin-aldosterone system (RAAS), and the decisive pathophysiological link in the development of hypertension (AH).

Angiotensin II binds to AT₁receptors in many tissues (in the smooth muscle tissues of the vessels, in the adrenal gland, 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.

AT₂-receptors - the second type of receptors with which angiotensin II binds, but their role in regulating the function of the cardiovascular system is unknown.

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

Losartan selectively binds to AT₁-receptors and does not bind, and does not block receptors of other hormones and ion channels, which play an important role in regulating the function of the cardiovascular system. Besides, losartan does not inhibit angiotensin-converting enzyme (ACE) - kininase II, responsible for the destruction of bradykinin. Consequently, effects that are not directly related to AT blockade₁-receptors, such as increased bradykinin-mediated effects or development of edema (losartan 1.7%, placebo 1.9%), are not related to the action of losartan.

Pharmacodynamics

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

When losartan is administered internally, elimination of negative feedback, consisting in the suppression of renin secretion by angiotensin II, leads to an increase in plasma renin activity (ARP). Increased ARP leads to an increase in the concentration of angiotensin II in blood plasma. At long-term (6-week) treatment of patients with AH losartan at a dose of 100 mg / day there was a 2-3-fold increase in the concentration of angiotensin II in blood plasma at the moment of reaching C_mOh losartan. In some patients, an even greater increase in angiotensin II concentration was observed, especially with a short duration of treatment (2 weeks). Despite this, during the treatment, the antihypertensive effect and the decrease in the plasma aldosterone concentration were manifested after 2 and 6 weeks of therapy, which indicates an effective blockade of the angiotensin II receptors. After cancellation of losartan, ARP and angiotensin II concentrations decreased within 3 days to the values observed before the start of losartan.

Because the losartan is a specific antagonist AT₁receptors of angiotensin II, it does not inhibit ACE (kininase II), an enzyme that inactivates bradykinin.A study comparing the effects of losartan in doses of 20 mg and 100 mg with the effects of an ACE inhibitor on the effect on angiotensin I, angiotensin II, and bradykinin showed that losartan blocks 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 the effects caused by the action of bradykinin, without affecting the severity of the response to angiotensin II, which demonstrates the pharmacodynamic difference between losartan and ACE inhibitors.

The concentration of losartan and its active metabolite in the blood plasma, as well as the antihypertensive effect of losartan increase with increasing dose of the drug. As losartan and its active metabolite are APA II, they both contribute to the antihypertensive effect.

In a study with a single dose of losartan in a dose of 100 mg, in which healthy volunteers (men) were included, taking the drug inward under high and low-fat diet conditions did not affect the glomerular filtration rate (GFR), the effective renal plasma flow and the filtration fraction. Losartan had a natriuretic effect that was more pronounced with a low-sal diet and, apparently, was not associated with the suppression of early sodium reabsorption in the proximal renal tubules. Losartan also caused a transient increase in the excretion of uric acid by the kidneys.

In patients with AH, 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, there was a significant decrease in proteinuria (by 42%), fractional excretion of albumin and immunoglobulins (IgG). In these patients losartan stabilized GFR and reduced the filtration fraction.

In postmenopausal women with AH, who took losartan in a dose of 50 mg for 4 weeks, there was no effect of therapy on the renal and systemic levels of prostaglandins.

Losartan does not affect vegetative reflexes and does not have a lasting effect on the concentration of noradrenaline in the blood plasma.

In patients with AH losartan in doses up to 150 mg / day did not cause clinically significant changes in serum concentrations of fasting triglycerides, total cholesterol and high-density lipoprotein cholesterol. In the same doses losartan did not affect the concentration of glucose in the blood on an empty stomach.

A clinical study evaluating the effect of high and low doses of ARA II (losartan) on the outcome of treatment of patients with chronic heart failure (CHF) included patients with CHF (II-IV functional class by classification NYHA) and intolerance to ACE inhibitors. Patients were observed for more than 4 years to compare the effects of losartan at a dose of 50 mg / day and at a dose of 150 mg / day on reducing mortality from all causes or hospitalization for heart failure.

This study showed that losartan at a dose of 150 mg / day significantly reduced the risk of mortality from all causes or the risk of hospitalization for heart failure compared with a dose of 50 mg / day.

Generally, 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 hypertension, cases of withdrawal of losartan due to an increase in serum creatinine or serum potassium levels have not been reported.

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

Pharmacokinetics:

Suction

Ingestion losartan is well absorbed and metabolized by "primary passage" through the liver to form an active carboxylated metabolite and inactive metabolites.Systemic bioavailability of losartan in dosage form - film-coated tablets is approximately 33%. Average C_mOh losartan and its active metabolite in blood plasma are reached after 1 hour and after 3-4 hours, respectively. When losartan was taken during the usual meal, there was no clinically significant effect on the profile of losartan concentration in the blood plasma.

Distribution

Lozartan 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 for intravenous administration or ingestion is converted into its active metabolite. After ingestion or intravenous administration of radiolabeled radiolabel (¹⁴With losartan) the radioactivity of circulating blood plasma is primarily due to the presence in it of losartan and its active metabolite. In addition to the active metabolite, biologically inactive metabolites are formed, including the two main metabolites formed as a result of hydroxylation of the butyl side chain, and one secondary - N-2-tetrazole-glucuronide.

Excretion

The 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 taking losartan, about 4% of the dose is excreted by the kidneys unchanged and about 6% dose is excreted by the kidneys as an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when administered to losartan in doses up to 200 mg.

After ingestion, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite half-life of approximately 2 and 6-9 hours, respectively. When the dosing 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 excretion of losartan and its metabolites is carried out by the kidneys and through the intestine with bile. After oral administration ¹⁴With losartan in men, about 35% of radioactivity is found in urine and 58% in feces. After intravenous administration ¹⁴With losartan in men, approximately 43% of radioactivity is found in urine and 50% in feces.

Pharmacokinetics in selected patient groups

Elderly patients

The concentrations of losartan and its active metabolite in blood plasma in elderly patients with male hypertension do not significantly differ from those in young male patients with AH.

Gender features

Concentrations of losartan in the blood plasma in women with AH were 2 times higher than the corresponding values in men with AH. The concentrations of active metabolite in blood plasma in men and women did not differ. This apparent pharmacokinetic difference, however, has no clinical significance.

Impaired liver function

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

Impaired renal function

Concentrations of losartan in blood plasma 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 greater than the value AUC losartan in patients with normal renal function. The concentrations of the active metabolite in the blood plasma did not change in patients with impaired renal function or patients on hemodialysis. Losartan and its active metabolite is not output by the hemodialysis procedure.

Indications:

Chronic heart failure with ineffective treatment with ACE inhibitors or intolerance to ACE inhibitors. It is not recommended to transfer patients with heart failure and stable hemodynamic parameters when taking ACE inhibitors for losartan therapy.

Contraindications:

- Hypersensitivity to any of the components of this drug;

- bVariability and the period of breastfeeding;

- atozrast to 18 years (efficacy and safety of use not established);

- aboutsimultaneous use with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (glomerular filtration rate [GFR] is less than 60 ml / min / 1.73 m²) (see the section "Interaction with other drugs");

- Mr.hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

- severe liver dysfunction (no experience of use).

Carefully:

Two-sided stenosis of the renal arteries or stenosis of the single kidney artery, hyperkalemia, condition after kidney transplantation (no experience), aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy (GOCMP), heart failure with concomitant severe renal dysfunction, severe chronic heart failure (functional IV classification class NYHA), heart failure with life-threatening arrhythmias, ischemic heart disease (IHD), cerebrovascular disease, primary hyperaldosteronism, angioedema in history.

Patients with reduced circulating blood volume (BCC) (eg, receiving treatment with large doses of diuretics) may develop symptomatic arterial hypotension.

Pregnancy and lactation:

Drugs that affect directly the RAAS can cause serious damage and death of the developing fetus, so when confirming the fact of pregnancy, the drug Laurista® should be immediately canceled and, if necessary, an alternative hypotensive therapy is prescribed.

Therapy with Lorista® should not be started during pregnancy. If patients planning a pregnancy continue hypotensive therapy with losartan is considered necessary, it should be replaced losartan on alternative antihypertensive drugs that have an established safety profile for use during pregnancy.

Although there is no experience with the use of Lorista® in pregnant women, preclinical studies in animals have shown that taking Lorista® leads to the development of serious embryonic and neonatal lesions and fetal or progenital death. It is believed that the mechanism of these phenomena is due to the impact on the RAAS.

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

The use of drugs that affect RAAS in the second and third trimesters of pregnancy reduces the function of the kidneys of the fetus and increases the incidence and mortality of the fetus and newborns. The development of oligohydramnion can be associated with fetal lung hypoplasia and skeletal deformities.Possible adverse events in newborns include hypoplasia of the skull bones, anuria, arterial hypotension, renal failure and death.

The above undesirable outcomes are usually due to the use of drugs that affect RAAS in the second and third trimesters of pregnancy. Most epidemiological studies on the development of fetal anomalies after the use of antihypertensive drugs in the first trimester of pregnancy have not revealed differences between drugs that affect RAAS and other antihypertensive drugs. When prescribing antihypertensive therapy for pregnant women, it is important to optimize the possible outcomes for the mother and fetus.

If it is not possible to select alternative therapy instead of therapy with drugs that affect RAAS, it is necessary to inform the patient about the possible risk of therapy for the fetus. It is necessary to conduct periodic ultrasound examinations to assess the intra-amniotic space. When identifying oligohydramnion, it is necessary to stop taking Lorista®,If only it is not vital for the mother. Depending on the week of pregnancy, appropriate fetal tests are necessary. Patients and physicians should be aware that the oligohydramnios may not be detected until irreversible damage to the fetus occurs. Careful observation of newborns, whose mothers took Lorista® during pregnancy, to control arterial hypotension, oliguria, and hyperkalemia.

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

Dosing and Administration:

The drug Lorista® is taken orally regardless of the time of ingestion.

The initial dose of losartan for patients with CHF is 12.5 mg once a day (with the administration of losartan in low dosages, it is possible to use Lorista® in tablets of 12.5 mg).Typically, the dose is selected at a weekly interval (ie 12.5 mg / day, 25 mg / day, 50 mg / day, 100 mg / day to a maximum dose of 150 mg once a day), depending on individual tolerability.

Side effects:

Classification of incidence of adverse events (AEs) recommended by the World Health Organization (WHO):

Often	≥ 1/10
often	from ≥ 1/100 to <1/10
infrequently	from ≥ 1/1000 to <1/100
rarely	from ≥ 1/10000 to <1/1000
rarely	< 1/10000
frequency unknown	can not be estimated from the available data.

Generally losartan well tolerated by patients with AH.

NEAs are of an easy and transient nature and do not require discontinuation of therapy.

The total frequency of AE when taking losartan is comparable with this indicator when taking placebo. In controlled clinical trials, the frequency of discontinuation of therapy due to clinically significant AE was 2.3% in the group of patients taking losartan, and 3,7% - in the group of patients taking placebo.

Controlled clinical studies have shown that losartan, in general, is well tolerated by patients with CHF. AEs observed in clinical trials were characteristic of this group of patients.

Violations from the blood and lymphatic system:

often: anemia.

Disturbances from the nervous system:

often: dizziness;

infrequently: headache, drowsiness, sleep disturbances;

rarely: paresthesia.

Heart Disease:

rarely: fainting, atrial fibrillation, impaired cerebral circulation.

Vascular disorders:

often: (orthostatic) hypotension (including dose-mediated orthostatic effects) (especially in patients with reduced BCC, for example, in patients with severe CHF or patients receiving high doses of diuretics).

Disturbances from the respiratory system, chest and mediastinal organs:

infrequently: shortness of breath, cough.

Disorders from the gastrointestinal tract:

infrequently: diarrhea, nausea, vomiting, abdominal pain.

Disturbances from the skin and subcutaneous tissues:

infrequently: urticaria, itchy skin, skin rash.

Disorders from the kidneys and urinary tract:

often: renal dysfunction, kidney failure.

General disorders:

infrequently: weakness, fatigue, swelling.

Laboratory and instrumental data:

often: an increase in the concentration of creatinine, urea and potassium in the blood plasma;

infrequently: hyperkalemia (more often in patients taking losartan in a dose of 150 mg per day than in patients taking losartan in a dose of 50 mg per day);

rarely: increased activity of alanine aminotransferase (ALT) in blood plasma (usually returned to normal after withdrawal of therapy).

The following AEs were observed in clinical practice during the post-marketing period

Violations of the blood and lymphatic system:

frequency unknown: anemia, thrombocytopenia.

Immune system disorders:

rarely: hypersensitivity reactions, anaphylactic reactions, angioedema (including angioneurotic edema of the larynx, pharynx, face, lips and / or tongue (causing airway obstruction), some of these patients had a history of angina stroke with other medications , including ACE inhibitors), vasculitis (including Shenlen-Henoch purpura).

Disorders of the psyche:

frequency is unknown: depression.

Disturbances from the nervous system:

frequency unknown: migraine, dysgeusia.

Hearing disorders and labyrinthine disorders:

frequency unknown: tinnitus.

Disturbances from the respiratory system, chest and mediastinal organs:

frequency unknown: cough.

Disorders from the digestive system:

frequency unknown: diarrhea, pancreatitis.

Disturbances from the liver and bile ducts:

rarely: hepatitis;

frequency unknown: impaired liver function.

Disturbances from the skin and subcutaneous tissues:

frequency unknown: urticaria, skin itch, skin rash, photosensitivity.

Disturbances from musculoskeletal and connective tissue:

frequency unknown: myalgia, arthralgia, rhabdomyolysis.

Violations of the genitals and mammary gland:

frequency unknown: erectile dysfunction / impotence.

General disorders:

frequency unknown: general malaise.

Laboratory and instrumental data:

frequency unknown: hyponatremia.

Overdose:

Information on overdose is limited. The most likely manifestation of an overdose is a marked decrease in blood pressure and tachycardia, a bradycardia can result from parasympathetic (vagal) stimulation. In the case of symptomatic arterial hypotension, maintenance therapy is indicated.

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

Interaction:

In clinical studies on the pharmacokinetic interactions drugs showed no clinically significant interactions losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital.

Rifampicin, as an inducer of the metabolism of drugs, reduces the concentration of the active metabolite of losartan in the blood plasma.

In clinical studies, the use of two inhibitors of isoenzyme CYP3A4: ketoconazole and erythromycin. Ketoconazole did not affect the metabolism of losartan to the active metabolite after intravenous administration of losartan. Erythromycin did not have a clinically significant effect when taking losartan inside.

Fluconazole, inhibitor of isoenzyme CYP2C9, 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 isoenzyme CYP2C9 has not been studied. It was shown that in patients not metabolizing losartan in the active metabolite, there is a very rare and specific defect of the isoenzyme CYP2C9.These data suggest that the metabolism of losartan to the active metabolite is carried out by isoenzyme CYP2C9, rather than an isoenzyme CYP3A4.

The simultaneous use of losartan, as well as other drugs blocking angiotensin II or its effects, with potassium-sparing diuretics (eg spironolactone, eplerenone, triamterene, amiloride), potassium supplements or potassium salts can lead to an increase in potassium in the serum.

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

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

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

Double blockade of RAAS with APA II, ACE inhibitors or aliskiren (renin inhibitor) is associated with an increased risk of developing arterial hypotension, syncope, hyperkalemia and renal dysfunction (including acute renal failure) compared with monotherapy.

Regular monitoring of blood pressure, kidney function and electrolyte content in blood plasma in patients taking both Lorist® and other drugs that affect RAAS is necessary. The Lorista® drug should not be used concomitantly with aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / min / 1.73 m²).

Special instructions:

Hypersensitivity reactions

Patients with an angioneurotic edema in the anamnesis (edema of the face, lips, pharynx / larynx and / or tongue) need control of the use of Lorista® (see section "Side effect").

Embryotoxicity

The use of drugs that affect RAAS in the second and third trimester of pregnancy reduces kidney function in the fetus and increases the incidence and mortality of the fetus and newborns. The development of oligohydramnion can be associated with fetal lung hypoplasia and skeletal deformities. Possible adverse events in newborns include hypoplasia of the skull bones, anuria, arterial hypotension, renal failure and death. When confirming the fact of pregnancy, the drug Lorista® should be immediately canceled (see the section "Application during pregnancy and during breast-feeding").

Arterial hypotension and disturbance of water-electrolyte balance or decrease in BCC

In patients with reduced BCC (eg, receiving treatment with large doses of diuretics) symptomatic arterial hypotension may develop.Correction of such conditions should be performed prior to the appointment of Lorista® or begin treatment with a lower dose of Lorista® (see the section "Dosing and Administration").

Violation of the water-electrolyte balance is characteristic of patients with impaired renal function with diabetes mellitus or without diabetes mellitus, therefore careful monitoring of these patients is necessary. In clinical studies involving patients with type 2 diabetes mellitus with proteinuria, the incidence of hyperkalemia was greater in the group taking losartan, than in the group taking placebo. Several patients discontinued therapy due to hyperkalemia (see "Side effect", subsection "Laboratory indicators").

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

Aortic or mitral stenosis, hypertrophic obstructive cardiomyopathy

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

IHD and cerebrovascular disease

Like all drugs that have a vasodilating effect, ARA II should be used with caution in patients with coronary artery disease or cerebrovascular disease, as excessive reduction in blood pressure in this group of patients can lead to myocardial infarction or stroke.

CHF

As with the use of other drugs that have an effect on RAAS, patients with CHF and with or without renal dysfunction have a risk of developing severe hypotension or acute renal dysfunction.

Since there is a lack of experience in using Lorest's drug^® in patients with heart failure and concomitant severe renal dysfunction, in patients with severe heart failure (class IV functional class NYHA), as well as in patients with heart failure and symptomatic life-threatening arrhythmias, Lorista® should be used with caution in patients in these groups.

Primary hyperaldosteronism

Since in patients with primary hyperaldosteronism, as a rule, there is no positive response to therapy with antihypertensive drugs,which act by inhibiting RAAS, the use of Lorista® 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 liver dysfunction should use Lorista® at a lower dose. There is no experience with losartan in patients with severe hepatic impairment, so Lorista® should not be used in this group of patients (see the sections "Pharmacological properties" [Pharmacokinetics subsection], "Contraindications", "Dosage and administration").

Impaired renal function

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

Some drugs that affect RAAS can increase serum urea and creatinine concentrations in patients with bilateral renal artery stenosis or stenosisrenal artery of the only kidney. Similar violations of kidney function can be reversible after the abolition of therapy.

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

Special patient groups

Ethnic Features

Analysis of the data of the entire population of patients included in the study on the effect of losartan on reducing the incidence of the main composite test in patients with hypertrophy and left ventricular hypertrophy showed that the ability of losartan compared to atenolol to reduce the risk of stroke and myocardial infarction, and to reduce the rate of cardiovascular mortality in patients with AH and left ventricular hypertrophy (by 13.0%, p = 0.021) does not apply to patients of the Negroid race, although both modes of therapy eff su- reduced blood pressure in these patients. In this study losartan in comparison with atenolol reduced the incidence of cardiovascular morbidity and mortality in patients with AH and left ventricular hypertrophy of all races except Negroid. However, in this study, patients of the Negroid race who received atenolol, had a lower risk of developing the main composite test evaluation criterion (ie, a lower combined rate of cardiovascular mortality, stroke, and myocardial infarction) compared to patients of the same race who took losartan.

Children and teens

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

If newborns whose mothers were taking losartan in pregnancy, there is a development of oliguria or arterial hypotension, it is necessary to carry out symptomatic therapy aimed at maintaining blood pressure and renal perfusion. You may need a blood transfusion or dialysis to prevent the development of arterial hypotension and / or maintain kidney function.

Elderly patients

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

Effect on the ability to drive transp. cf. and fur:

There have been no studies to assess the impact on the ability to drive vehicles and work with mechanisms,However, care must be taken when applying antihypertensive therapy and driving or working with mechanisms, since dizziness and drowsiness may develop, especially at the onset of therapy or with an increase in the dose of losartan.

Form release / dosage:

Tablets, film-coated, 150 mg.

Packaging:

For 7 or 10 tablets in a contour acheikova packing of the combined material PVC / PVDC and aluminum foil.

2 contour cell packs (7 tablets each) or 3, 6, 9 contour cell packs (10 tablets each), along with instructions for use, are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003683

Date of registration:16.06.2016

Expiration Date:16.06.2021

Date of cancellation:2018-02-27

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp19.03.2018

Illustrated instructions

Instructions

Lorista® (Lorista®)