Lozap - instructions for use, doses, side effects, contraindications

core: microcrystalline cellulose - 160,00 mg, mannitol - 100,00 mg, crospovidone-20,00 mg, silicon dioxide colloidal anhydrous - 4,00 mg, talc - 8,00 mg, magnesium stearate - 8,00 mg;

film sheath: sepiphilm 752 (white) (hypromellose, microcrystalline cellulose, macrogol 2000 stearate, titanium dioxide) - 13.80 mg, macrogol 6000 - 0.20 mg.

Description:White or almost white, oblong, biconvex tablets, covered with a film sheath, with a risk on both sides.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.01 Losartan

C.09.C.A Angiotensin II antagonists

Pharmacodynamics:

Angiotensin II is a potent vasoconstrictor, the main active hormone of the renin-angiotensin-aldosterone system (RAAS), and the main pathophysiological link in the development of hypertension. Angiotensin II selectively binds to AT₁ receptors located in many tissues (in the smooth muscle tissues of blood vessels, in the adrenal gland, kidneys and heart) and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells. Losartan - a highly effective angiotensin II receptor antagonist (type AT₁). Losartan and its pharmacologically active carboxylated metabolite (E-3174) both in vitro and in vivo block all the physiological effects of angiotensin II, regardless of the source or route of synthesis Losartan selectively communicates with AT₁ receptors and does not bind or 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 the angiotensin-converting enzyme (ACE, kininase II), which contributes to the degradation of bradykinin. Consequently, effects that are not directly related to the blockade AT₁ -receptors, in particular, the enhancement of effects associated with the effects of bradykinin or the development of edema, are not relevant to the action of losartan.

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

During the administration of losartan, the elimination of negative feedback, consisting in the suppression of renin secretion by angiotensin II, leads to an increase in plasma renin activity (ARP). The increase in ARP is accompanied by an increase in the concentration of angiotensin II in the blood plasma. With prolonged (6-week) treatment of patients with arterial hypertension 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 time of achieving Cmax losartan, some patients showed an even greater increase in concentration, especially with a short duration of treatment (2 weeks).However, antihypertensive activity and a decrease in plasma aldosterone concentration were manifested at 2 and 6 weeks of therapy, which indicates an effective blockade of angiotensin II receptors. After cancellation of losartan, ARP and angiotensin II concentration were reduced to baseline values, which were observed before the drug was started, after 3 days. 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 20 mg and 100 mg of losartan with the effects of an ACE inhibitor on the response to angiotensin I, angiotensin II, and bradykinin showed that losartan blocks the effects of angiotensin I and angiotensin II, without affecting the effects of bradykinin, which is due to the specific mechanism of action of losartan. In contrast, an ACE inhibitor blocked the response to angiotensin I and increased the response to 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 angiotensin II receptor antagonists (ARAP), both of which contribute to the antihypertensive effect.

Pharmacokinetics:

Suction

Ingestion losartan is well absorbed and metabolized by "primary passage" through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. Systemic bioavailability of losartan in tablet form is approximately 33%. The average maximum concentrations of losartan and its active metabolite 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 more than 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, administered intravenously or by mouth, is converted to its active metabolite. After ingestion and intravenous administration of losartan, labeled ¹⁴C, the radioactivity of circulating blood plasma is primarily associated with the presence in it of losartan and its active metabolite. A low conversion of losartan to its active metabolite was observed in approximately 1% of the patients studied. In addition to the active metabolite, biologically inactive metabolites are formed, including the two main metabolites that result from the 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% of the dose is excreted by the kidneys as an active metabolite. Losartan and its active metabolite have a linear pharmacokinetics when ingested at doses up to 200 mg. After oral administration, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite half-life of approximately 2 and 6-9 hours, respectively.With a single dose of 100 mg losartan, nor its active metabolite significantly accumulate in the body. The excretion of losartan and its metabolites occurs through the intestine and kidneys.

After ingestion of losartan, labeled ¹⁴C, in men about 35% of radioactivity is found in urine and 58% in feces. After intravenous administration of losartan, labeled ¹⁴C, in men approximately 43% of radioactivity is found in urine and 50% in feces.

Pharmacokinetics in specific patient groups

Elderly patients

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

Floor

Concentrations of losartan in blood plasma were 2 times higher in women with arterial hypertension compared with men with arterial hypertension. The concentrations of active metabolite in men and women did not differ. This apparent pharmacokinetic difference is not clinically significant.

Dysfunction of the liver

When losartan was taken orally by patients with mild and moderate alcoholic cirrhosis, the concentrations of losartan and its active metabolite in the blood plasma were, respectively,in 5 and 1,7 times more than in young healthy male volunteers.

Renal impairment

Concentrations of losartan in blood plasma in patients with creatinine clearance above 10 ml / min did not differ from those in patients with unchanged renal function. When comparing the area under the concentration-time curve (AUC) of losartan in patients with normal renal function and patients on hemodialysis, the value of AUC of losartan was approximately 2 times greater in patients on hemodialysis. Plasma concentrations of the active metabolite do not change in patients with impaired renal function or patients on hemodialysis. Losartan and its active metabolite can not be removed by hemodialysis.

Indications:

- Arterial hypertension;

- Chronic heart failure (as part of combination therapy, with intolerance or inefficiency of therapy with ACE inhibitors);

- reduction in the risk of developing cardiovascular diseases (including stroke) and mortality in patients with hypertension and left ventricular hypertrophy;

- diabetic nephropathy in hypercreatininaemia and proteinuria(urine albumin and creatinine ratio more than 300 mg / g) in patients with type 2 diabetes and concomitant arterial hypertension (reduction in the progression of diabetic nephropathy to the terminal stage of chronic renal failure).

Contraindications:

- Hypersensitivity to the components of the drug;

- simultaneous use with preparations containing aliskiren, in patients with diabetes mellitus and patients with renal insufficiency (glomerular filtration rate [GFR] less than 60 ml / min / 1.73 m² body surface area) (see the sections "Interaction with other drugs" and "Special instructions");

- concomitant use with angiotensin-converting enzyme (ACE inhibitors) in patients with diabetic nephropathy (see "Interactions with other drugs" and "Special instructions");

- severe liver dysfunction (no experience with application) (more than 9 points on the Child-Pugh scale);

- pregnancy and the period of breastfeeding;

- age under 18 years (efficiency and safety not established).

Carefully:Arterial hypotension,heart failure with concomitant severe renal insufficiency, severe chronic cardiac insufficiency IV functional class according to the NYHA classification, heart failure with life-threatening arrhythmias, coronary heart disease, cerebrovascular disease, hyperkalemia, age over 75 years, use in representatives of the Negroid race, reduced circulating blood volume, disturbance of water-electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, renal / nocturnal insufficiency, condition after kidney transplantation (no experience of application), aortic and mitral stenosis, angioedema in history, primary hyperaldosteronism, hypertrophic obstructive cardiomyopathy.

Pregnancy and lactation:

Application of the drug LOZAP^® in the first trimester of pregnancy is not recommended. Application of the drug LOZAP^®in the second and third trimesters of pregnancy is contraindicated.

Epidemiological data on the risk of teratogenic effects of ACE inhibitors in the first trimester of pregnancy are not convincing enough, however, the risk for the fetus can not be completely ruled out.Despite the fact that controlled epidemiological studies using angiotensin II receptor antagonists have not been conducted, this class of drugs may have similar risks. With the exception of cases when continued treatment with ARAP is considered necessary, patients planning pregnancy should be transferred to other types of antihypertensive therapy, the safety of which is confirmed by the results of clinical studies. When confirming the fact of pregnancy, the drug LOZAP^® should be discontinued immediately and, if necessary, another treatment should be prescribed.

It is known that the use of ARAII in the second and third trimesters of pregnancy has a toxic effect on the fetal organism (decreased kidney function, development of oligohydramnion, slowing ossification of the skull bones) and newborn (renal failure, arterial hypotension, hyperkalemia). If, for some reason, a woman took LOPAP^® in the second trimester or later in pregnancy, it is recommended that an ultrasound examination of the fetus is carried out to monitor kidney function and the condition of the bones of the skull.

Children whose mothers took the drug LOZAP^® during pregnancy, should be under the careful supervision of the pediatrician because of the risk of developing arterial hypotension.

Breast-feeding

It is not known whether losartan in breast milk. Since no information on the use of losartan during breastfeeding was obtained, from the appointment of the drug LOZAP^®lactating women should refrain, preferring alternative treatments with a more studied safety profile, especially when feeding a newborn or premature baby. If it is necessary to use during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Inside, regardless of food intake.

The drug LOZAP ® can be taken in combination with other antihypertensive drugs.

Arterial hypertension

The standard initial and maintenance dose for most patients is 50 mg of LOZAP® once a day (1/2 tablet of 100 mg, the tablet is at risk).

The maximum antihypertensive effect is achieved 3-6 weeks after the initiation of therapy.In some patients, to achieve a greater effect, the dose may be increased to a maximum daily dose of 100 mg of LOZAP® once a day.

In patients with a reduced volume of circulating blood (for example, when taking large doses of diuretics), the initial dose of the drug LOZAP® should be reduced to 25 mg once a day (Ug tablets of 50 mg, the tablet is at risk).

In patients with renal insufficiency, including patients on dialysis, dose adjustment is not required.

Patients with liver disease (more than 9 on the Child-Pugh scale) are recommended to prescribe lower doses of the drug in an anamnesis.

In patients older than 75 years, treatment with LOZAP® is recommended starting at a dose of 25 mg per day (1/2 tablet of 50 mg, the tablet is at risk), however, dose adjustment is usually not required.

Chronic heart failure

The initial dose of LOZAP® for patients with chronic heart failure is 12.5 mg once a day (LOZAP® should be used in a suitable form of release). Typically, the dose is titrated at a weekly interval (i.e., 12.5 mg / day, 25 mg / day, 50 mg / day, 100 mg / day .It is exceptional for this indication to increase the maximum daily dose to 150 mg 1 time per day) depending on individual tolerability.

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

The standard initial dose of the drug LOZAP® is 50 mg once a day (1/2 tablet of 100 mg, the tablet is at risk). It is recommended to add hydrochlorothiazide in low doses or increase the dose of LOZAP® to a maximum daily dose of 100 mg once a day, taking into account the degree of BP reduction.

Nephroprotection in Patients with Type 2 Diabetes and Proteinuria

The standard initial dose of the drug LOZAP® is 50 mg once a day (1/2 tablet of 100 mg, the tablet is at risk). In the future, it is recommended to increase the dose of the drug LOZAP® to a maximum daily dose of 100 mg once a day, taking into account the degree of decrease in blood pressure. The drug LOZAP® can be administered in combination with other antihypertensive agents (diuretics, blockers of the slow calcium channels with alpha and beta-blockers, central antihypertensive agents), insulin and other hypoglycemic agents (sulfonylurea derivatives, glitazones and alpha-glucosidase inhibitors) .

Children under 18 years old

Safety and efficacy of the drug in children under 18 years of age have not been established.

Side effects:

The side effects of losartan are usually transient and do not require withdrawal of the drug.

When losartan was used to treat essential hypertension in controlled trials, only the incidence of dizziness differed from placebo by more than 1% (4.1% vs. 2.4%) among all adverse events.

The dose-dependent orthostatic effect, characteristic of antihypertensive agents, was less than 1% in patients with losartan.

The frequency of adverse reactions was determined according to the following gradation (classification of the World Health Organization):

- very frequent - more than 1/10,

- Frequent - from more than 1/100 to less than 1/10,

- infrequent - from more than 1/1000 to less than 1/100,

- rare - from more than 1/10000 to less than 1/1000,

- very rare, including individual messages - from less than 1/10000,

- an unknown frequency (if it is impossible to estimate from the available data).

Table 1. Prevalence of adverse reactions from placebo-controlled clinical trials and post-registration follow-up

By-side

reaction

Prevalence of adverse reactions according to indications for use

Other

Arterial

hypertension

Patients with

arterial

hypertension and

hypertrophy

left

ventricle

Chronic

cardiac

failure

Arterial hypertension and type 2 diabetes mellitus with impaired renal function

Poster

the

observation

Disorders from the blood and lymphatic system

anemia

frequent

frequency

unknown

thrombocytopenia

frequency

unknown

Immune system disorders

allergic reactions, anaphylactic reactions, Quincke's edema¹ and vasculitis²

rare

Disorders of the psyche

depression

frequency

unknown

Disturbances from the nervous system

dizziness

frequent

drowsiness

infrequent

headache

infrequent

sleep disturbance

infrequent

paresthesia

rare

migraine

frequency

unknown

violation of

taste

frequency

unknown

Hearing disorders and labyrinthine disorders

vertigo

infrequent

frequent

noise in ears

frequency

unknown

Heart Disease

sensation

palpitation

infrequent

angina pectoris

infrequent

fainting

rare

ciliary

arrhythmia

rare

sharp

violation of

cerebral

circulatory

AND I

rare

Vascular disorders

(orthostatic)

marked decrease in blood pressure (including dose-dependent orthostatic effects)³

infrequent

frequent

Disturbances from the respiratory system, groovecell and mediastinum

dyspnea

infrequent

cough

infrequent

frequency

unknown

Disorders from the gastrointestinal tract

stomach ache

infrequent

intestinal

obstruction

infrequent

diarrhea

infrequent

frequency

unknown

nausea

infrequent

vomiting

infrequent

Disturbances from the liver and bile ducts

pancreatitis

frequency

unknown

hepatitis

sparse

violations

function

liver

frequency

unknown

Disturbances from the skin and subcutaneous tissues

hives

infrequent

frequency

unknown

itchy skin

infrequent

frequency

unknown

rash

infrequent

frequency

unknown

photosensitized

mission

frequency

unknown

Disturbances from musculoskeletal and connective tissue

myalgia

frequency

unknown

arthralgia

frequency

unknown

rhabdomyolysis

frequency

unknown

muscle spasm

infrequent

Disorders from the kidneys and urinary tract

violation of

function

kidneys

frequent

renal

failure

frequent

Violations of the genitals and mammary glands

erectile

dysfunction

/impotence

frequency

unknown

General disorders and disorders at the site of administration

asthenia

infrequent

frequent

infrequent

frequent

weakness

infrequent

frequent

infrequent

frequent

edema

infrequent

malaise

frequency

unknown

Impact on the results of laboratory and instrumental studies

hyperkalemia

frequent

infrequent⁴

frequent⁵

rise

activity

alanine amine

transferases

(ALT)⁶

rare

increased concentrations of urea, creatinine and potassium in blood plasma

frequent

hypo-

sodiumemia

frequency

unknown

hypoglycemia

frequent

¹Including swelling of the larynx, vocal cords, face, lips, pharynx and / or tongue (which leads to impaired airway patency); in some of these patients, Quincke's edema was noted earlier in connection with the appointment of other drugs, including ACE inhibitors.

²Including hemorrhagic vasculitis (Shenlaine-Henoch disease).

³ Especially in patients with hypovolemia, for example, in patients with severe heart failure or patients receiving diuretics in high doses.

⁴It is often noted in patients who received losartan in a dose of 150 mg instead of 50 mg.

⁵In a clinical study involving patients with type 2 diabetes mellitus and nephropathy, hyperkalemia> 5.5 mmol / L developed in 9.9% of patients who received losartan in tablets, and in 3.4% of patients receiving a placebo.

⁶Usually passes after the withdrawal of treatment.

The following additional adverse reactions were more frequent in patients who received losartan, than in patients receiving placebo (exact rates are unknown): back pain, urinary tract infections and flu-like symptoms.

Disorders from the kidneys and urinary tract:

As a consequence of inhibition of RAAS in patients at risk, impaired renal function including acute renal failure was noted. These changes on the part of the kidney function can be reversible in the case of timely withdrawal of treatment.

Overdose:

Symptoms

Data on the overdose of losartan in humans are few. Analysis of the pharmacological properties of the drug suggests that the main manifestation of an overdose may be dizziness, tachycardia (bradycardia may develop due to parasympathetic (vagal) stimulation) and a clinically pronounced decrease in blood pressure, which can lead to loss of consciousness and collapse.

Treatment

When developing clinically pronounced arterial hypotension, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Lay the patient on his back, give the body a position with a low head and elevated leg position. If necessary, increase the volume of circulating blood, for example, by intravenous administration of 0.9% sodium chloride solution. If necessary, sympathomimetic preparations may be prescribed. Elimination of losartan and its active metabolite by hemodialysis is ineffective.

Interaction:

There is evidence that the simultaneous use of ACE inhibitors, ARAII or aliskirep increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) when compared with the use of a single drug that affects RAAS.

Application of the drug LOZAP^® together with aliskirenom in patients with diabetes mellitus is contraindicated. It should be excluded the use of the drug LOZAP^® with aliskiren-containing drugs in patients with renal insufficiency (GFR less than 60 ml / min / 1.73 m² body surface area) and is not recommended for other patients (see section "Contraindications").

Application of the drug LOZAP^® in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended to other patients (see section "Contraindications").

Can be prescribed with other antihypertensive drugs. enhances the effect of beta-adrenergic blockers and sympatholytics. The combined use of losartan with diuretics has an additive effect.

Simultaneous use with other drugs. capable of causing the development of arterial hypotension as an undesirable reaction (eg, tricyclic antidepressants, antipsychotics, baclofen and amifostine), may increase the risk of developing arterial hypotension.

There were no pharmacokinetic interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole, erythromycin.

Losartan is predominantly metabolized by the CYP2C9 isoenzyme of the cytochrome P450 system to form an active metabolite of the carboxylic acid. In a clinical study, it was shown that fluconazole (inhibitor of the isoenzyme CYP2C9) reduces the formation of the active metabolite by approximately 50%. It was established that the simultaneous use of losartan with rifampicin (an inducer of metabolic enzymes) leads to a decrease in the concentration of the active metabolite by 40% in blood plasma. The clinical significance of this effect remains unclear. With the simultaneous use of the drug with fluvastatin (a weak inhibitor of the isoenzyme CYP2C9), there was no change in the concentration of the metabolite. The experience of using other drugs acting on RAAS shows that concomitant therapy with potassium-sparing diuretics (srinonolactone and its derivative eplersnop, triamterep, amiloride), potassium preparations, salt substitutes containing potassium, and other agents that can increase the level of potassium in the blood plasma (eg, heparin), can lead to the development of hyperkalemia. The anti-hypertensive effect of the drug may be weakened when combined with non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxigysia-2 (COX-2). As with the inhibitors of the aigiotensin-converting enzyme,co-administration of losartan and NSAIDs may lead to an increased risk of dysfunction, including possible acute renal failure and hyperkalemia, especially in patients with an existing renal dysfunction. This combination should be taken with caution, especially elderly patients. Patients receiving joint treatment with losargan and NSAIDs should receive an adequate amount of fluid and be under the supervision of a physician with simultaneous monitoring of renal function indicators.

Reported a reversible increase in lithium concentrations in plasma and its toxic effect during the concomitant use of lithium preparations with ACE inhibitors. In very rare cases, similar reports were recorded in the joint use of lithium preparations with ARAII. If it is proved necessary to use this combination, during the treatment it is recommended that patients regularly monitor the lithium content in the blood plasma.

Special instructions:

Hypersensitivity

Patients with Quinck's edema in the anamnesis (swelling of the face, lips, throat and / or tongue) should be under strict supervision.

Arterial hypotension and disturbances of water-electrolyte balance

Hypotension with clinical manifestations, especially after the first dose and after dose escalation may occur in patients with hypovolemia and / or hyponatremia resulting diuretics in high doses, diet restriction salt, diarrhea or vomiting. It is necessary either to correct these conditions before prescribing LOZAP^®, or use or prescribe smaller doses of the drug.

Water-electrolyte disturbances

Water-electrolyte disturbances are characteristic for patients with renal dysfunction in combination with or without diabetes mellitus and require correction. In a clinical study involving patients with type 2 diabetes with nephropathy, hyperkalemia frequency in the group treated losartan, was higher than in the placebo group. This indicates a need for regular monitoring the potassium content in the blood plasma and indicators creatinine clearance (CC) - require especially strict observation patients with heart failure and QC 30 to 50 ml / min. Purpose of potassium-sparing diuretics, potassium and potassium-containing drugs with drug solezameniteley simultaneously Losap^® Not recommended.

Impaired liver function

Given the pharmacokinetics data indicating a significant increase in plasma losargan in patients with cirrhosis of the liver, patients with impaired liver function (more than 9 on the Child-Pugh scale) are recommended to prescribe the drug in lower doses. The experience of using the drug in patients with severe hepatic insufficiency is absent. With this in mind, the drug LOZAP^® contraindicated in patients with severe hepatic insufficiency.

Double blockade of the renin-angiotensin-aldosterone system

There is evidence that simultaneous use of ACE inhibitors. ARAII or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure).

Application of the drug LOZAP^® together with alneciren is contraindicated in patients with diabetes mellitus or renal dysfunction (GFR less than 60 ml / min / 1.73 m² body surface area) and is not recommended for other patients (see section "Contraindications").

Application of the drug LOZAP^® in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended to otherspatients (see the section "Contraindications").

Ischemic heart disease (CHD) and cerebrovascular disease

As with any antihypertensive drug, a too sharp decrease in blood pressure in patients with ischemic heart disease and cerebrovascular disease can lead to myocardial infarction or ischemic stroke.

Heart failure

In patients with heart failure with or without kidney function, as with other drugs acting on RAAS, there is a risk of severe arterial hypotension and acute renal failure.

Practically there is no experience with losartan in the treatment of patients with heart failure and concomitant severe renal insufficiency, in patients with severe chronic heart failure (IV functional class according to the NYHA classification), as well as in patients with heart failure and life-threatening arrhythmias. With this in mind, with the appointment of the drug LOZAP^® These categories of patients should be careful.

Co-administration with ACE inhibitors in chronic heart failure (CHF)

When using the drug LOZAP^® in combination with ACE inhibitors, the risk of side effects may increase, especially renal dysfunction and hyperkalemia (see "Side effect" section). In these cases, careful monitoring and monitoring of laboratory indicators is necessary.

Hemodialysis

When conducting hemodialysis, the sensitivity of blood pressure to the action of antagonists increases AT₁ -receptors as a result of reduction of BCC and activation of RAAS. It is necessary to adjust the dose of the drug LOZAP^® to under careful monitoring of blood pressure in patients on hemodialysis. Kidney transplantation Data on the use of the drug LOZAP^® patients who have recently undergone kidney transplantation are not present.

General anesthesia

Patients receiving angiotensin II antagonists may develop arterial hypotension as a result of blockade of the renin-angiotensin-aldosterone system during general anesthesia and during surgical interventions. Very rarely, cases of severe arterial hypotension, requiring replenishment of bcc and / or vasopressor preparations, can be noted.

Stenosis of aortic and mitral titanium, hypertrophic obstructive cardiomyopathy

When using the drug LOZAP^®, as well as other vasodilators, caution should be exercised in patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect RAAS. In connection with this, the drug LOZAP^® it is not recommended to appoint such patients.

Patients older than 75 years

As a rule, patients older than 75 years of treatment with the drug LOZAP^® it is recommended to start with a dose of 25 mg per day.

Other special instructions and precautions

As the clinical experience of the use of ACE inhibitors, losartan and other antagonists AT₁receptors, these drugs less effectively reduce blood pressure in patients of the Negroid race than in representatives of other races, possibly due to low renin activity in patients of this race.

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

Effect of LOZAP preparation^® on the ability to drive vehicles or work with machinery has not been studied.

Care should be taken when driving vehicles and practicing potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions. when using the drug, dizziness, drowsiness and fainting can occur.

Form release / dosage:Film coated tablets 100 mg.

Packaging:For 10 or 15 tablets in a blister of PVC / PVDC / A1 or A1 / A1. For 2, 4 or 6 blisters (15 tablets) or 3, 6 or 9 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:Store at a temperature not exceeding 30 ° C.

Shelf life:

2 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-004055/10

Date of registration:07.05.2010 / 16.08.2017

Expiration Date:Unlimited

The owner of the registration certificate:SANOFI RUSSIA, CJSCSANOFI RUSSIA, CJSC

Manufacturer: & nbsp

Saneca Pharmaceuticals a.s. The Slovak Republic

Representation: & nbspSanofi Russia, JSCSanofi Russia, JSCRussia

Information update date: & nbsp12.04.2018

Illustrated instructions

Instructions

Lozap (Lozap)