Lozap: indications, instructions for use of the medicine

Composition and release form

The drug Lozap is available in the form of small tablets for parenteral administration. They are white, slightly elongated and convex on both sides. They have a soluble thin film shell. Packaged in blisters of 10 pieces. One cardboard package contains 3, 6, 9 blisters and includes instructions for use.

The active substance is potassium losartran.

Auxiliary components: cellulose, povidone, talc, magnesium stearate, macrogol, dyes, mannitol, croscarmellose sodium.

pharmachologic effect

The drug belongs to the group of antihypertensive drugs. It is a specific angiotensin receptor agonist. After taking the medicine, there is a decrease in vascular resistance, a decrease in aldosterone and adrenaline levels in the bloodstream. In addition, the pressure in the pulmonary circulation is normalized, a pronounced diuretic effect occurs and the afterload on the body is reduced.

The drug prevents the development of hypertrophy of the muscular lining of the heart and improves people's susceptibility to physical activity.

While taking the drug, the angiotensin-containing enzyme is not blocked. Therefore, the level of bradykinin does not increase and the effect on the kinin system is prevented.

The pharmacological effect of the drug is the same for all patients, regardless of age and gender.

After one dose of medication, the hypotensive effect is observed after 6 hours and gradually decreases throughout the day. When a course is prescribed, pronounced results of therapy appear in patients after 3-4 weeks.

People suffering from liver cirrhosis should be careful when using antihypertensive drugs. The active ingredient occurs in their blood. Therefore, they need dose adjustment.

After oral administration, the tablets are quickly absorbed. The maximum content of the drug in the body is recorded after an hour. The drug is administered through the kidneys and intestines.

Lozap, 12.5 mg, film-coated tablets, 30 pcs.

Hypersensitivity.

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

Arterial hypotension and water-electrolyte imbalance.

It is necessary to either correct these conditions before prescribing Lozap®, or use initial doses of the drug.

Water and electrolyte disturbances.

Water and electrolyte disturbances are typical for patients with impaired renal function in combination with or without diabetes mellitus and require correction. In a clinical study conducted in type 2 diabetic patients with nephropathy, the incidence of hyperkalemia in the losartan group was higher than in the placebo group. This indicates the need for constant monitoring of potassium levels in the blood plasma and creatinine Cl levels - patients with heart failure and creatinine Cl levels from 30 to 50 ml/min require especially strict monitoring.

Prescribing potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes simultaneously with Lozap® is not recommended.

Liver dysfunction.

Taking into account pharmacokinetic data indicating a significant increase in plasma concentrations of losartan in patients with cirrhosis, patients with a history of impaired liver function (more than 9 points on the Child-Pugh scale) are recommended to prescribe the drug in lower doses. There is no experience with the use of the drug in patients with severe liver failure. Taking this into account, Lozap® is contraindicated in patients with severe liver failure.

Double blockade of the RAAS.

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

The use of Lozap® in combination with aliskiren is contraindicated in patients with diabetes mellitus and/or moderate or severe renal failure (GFR <60 ml/min/1.73 m2) and is not recommended in other patients (see “Contraindications”).

The use of Lozap® in combination with an ACE inhibitor is contraindicated in patients with diabetic nephropathy and is not recommended for other patients (see “Contraindications”).

IHD and cerebrovascular diseases.

As with the use of any antihypertensive drugs, too sharp a decrease in blood pressure in patients with coronary artery disease and cerebrovascular diseases can lead to myocardial infarction or ischemic stroke.

Heart failure.

In patients with heart failure with or without renal impairment, as with other drugs acting on the RAAS, there is a risk of developing severe hypotension and acute renal failure.
experience with the use of losartan in the treatment of patients with heart failure and concomitant severe renal failure in patients with severe CHF (functional class IV according to the NYHA
), as well as in patients with heart failure and life-threatening arrhythmias. With this in mind, caution should be exercised when prescribing losartan to these categories of patients.

Combined use with ACE inhibitors for CHF.

When using Lozap® in combination with ACE inhibitors, the risk of side effects may increase, especially renal dysfunction and hyperkalemia (see “Side Effects”). In these cases, careful observation and monitoring of laboratory parameters is necessary.

Hemodialysis.

During hemodialysis, the sensitivity of blood pressure to the action of AT1 receptor antagonists increases as a result of a decrease in blood volume and activation of the RAAS. It is necessary to adjust the dose of Lozap® under careful monitoring of blood pressure in patients on hemodialysis.

Kidney transplantation.

There are no data on the use of Lozap® in patients who have recently undergone a kidney transplant.

General anesthesia.

Patients receiving ARA II during general anesthesia and surgical procedures may develop arterial hypotension as a result of blockade of the RAAS. Very rarely, cases of severe arterial hypotension may occur, requiring IV fluids and/or vasopressors.

Aortic and mitral valve stenosis, 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 treatment with antihypertensive drugs that affect the RAAS. In this regard, Lozap® is not recommended for use in such patients.

Elderly patients.

As a rule, patients over 75 years of age are recommended to start treatment with Lozap® with a dose of 25 mg/day.

Other special instructions and precautions.

As clinical experience with the use of ACE inhibitors, losartan and other AT1 receptor antagonists shows, these drugs are less effective in reducing 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.

Impact on the ability to drive vehicles and machinery.

Not studied. When driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, it should be taken into account that when using the drug, dizziness, drowsiness and fainting may occur.

Lozap indication

The use of Lozap is relevant for the following conditions:

High blood pressure.
Chronic course of heart failure.
Prevention of the development of severe vascular and cardiac diseases among patients with hypertension and left ventricular enlargement.
Nephropathy and high blood pressure in people with diabetes.
Contraindications
Absolute contraindications for use are:
Increase in potassium levels in the blood.
Low pressure.
Individual intolerance to the medicinal components included in the composition.
The time of bearing a child.
Breastfeeding.
Symptoms of dehydration.
Children under 18 years of age.

Side effects

As a rule, during the course of therapy, patients experience virtually no side effects. If they appear, they go away on their own and quickly, so there is no need to discontinue the drug. The following side effects are possible when taking Lozap:

Dizziness, increased fatigue, headache, problems falling asleep. Migraines, anxiety, tremor, and depression are less common.
Infection of the respiratory system. Signs of rhinitis, bronchitis and respiratory distress may appear.
Dyspeptic symptoms, rarely gastritis, dry mouth, flatulence.
Disturbance of the musculoskeletal system. Possible pain in the back and muscles, cramps.
Signs of cardiac dysfunction are expressed in tachycardia, bradycardia, arrhythmia.
Rarely, kidney problems, sexual dysfunction and infections of the urinary system appear.
Allergic reactions, dry dermis, excessive sweating.

Lozap, 100 mg, film-coated tablets, 30 pcs.

Hypersensitivity.

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

Arterial hypotension and water-electrolyte imbalance.

It is necessary to either correct these conditions before prescribing Lozap®, or use initial doses of the drug.

Water and electrolyte disturbances.

Prescribing potassium-sparing diuretics, potassium supplements and potassium-containing salt substitutes simultaneously with Lozap® is not recommended.

Liver dysfunction.

Double blockade of the RAAS.

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

The use of Lozap® in combination with an ACE inhibitor is contraindicated in patients with diabetic nephropathy and is not recommended for other patients (see “Contraindications”).

IHD and cerebrovascular diseases.

Heart failure.

Combined use with ACE inhibitors for CHF.

Hemodialysis.

Kidney transplantation.

There are no data on the use of Lozap® in patients who have recently undergone a kidney transplant.

General anesthesia.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy.

Primary hyperaldosteronism.

Patients with primary hyperaldosteronism are usually resistant to treatment with antihypertensive drugs that affect the RAAS. In this regard, Lozap® is not recommended for use in such patients.

Elderly patients.

As a rule, patients over 75 years of age are recommended to start treatment with Lozap® with a dose of 25 mg/day.

Other special instructions and precautions.

Impact on the ability to drive vehicles and machinery.

Instructions for use of Lozap

The medicine is intended for oral administration, regardless of the time of meal. It is recommended to take the tablets once a day.

For severe hypertension, patients are prescribed 50 mg. According to clinical indications, the dosage can be doubled.

According to the attached instructions, in case of cardiac insufficiency, patients are prescribed 12.5 mg once a day. Every week the dose of the drug is increased by 2 times until it reaches 50 mg per day.

In cases where patients are simultaneously taking diuretic drugs, the therapeutic dose of Lozap should be reduced to 25 mg.

Elderly people and those with kidney problems do not need to change the therapeutic dosage.

Lozap 100 mg 30 pcs. film-coated tablets

pharmachologic effect

Angiotensin II receptor antagonist.

Composition and release form Lozap 100 mg 30 pcs. film-coated tablets

Tableti - 1 tablet:

active substance: losartan potassium - 100 mg;
excipients: microcrystalline cellulose - 160.00 mg, mannitol - 100.00 mg, crospovidone -20.00 mg, colloidal anhydrous silicon dioxide - 4.00 mg, talc - 8.00 mg, magnesium stearate - 8.00 mg;
film shell: sepifilm 752 (white) (hypromellose, microcrystalline cellulose, macrogol 2000 stearate, titanium dioxide) - 13.80 mg, macrogol 6000 - 0.20 mg.

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

Description of the dosage form

White or almost white, oblong, biconvex film-coated tablets, scored on both sides.

Directions for use and doses

Inside, regardless of food intake. Lozap can be taken in combination with other antihypertensive drugs.

Arterial hypertension. The standard initial and maintenance dose for most patients is 50 mg Lozap once daily. The maximum antihypertensive effect is achieved 3–6 weeks after the start of therapy. In some patients, to achieve a greater effect, the dose can be increased to a maximum daily dose of 100 mg of Lozap once a day.

In patients with reduced blood volume (for example, when taking large doses of diuretics), the initial dose of Lozap should be reduced to 25 mg once a day (1/2 tablet of 50 mg, the tablet has a score).

There is no need to adjust the initial dosage in patients with renal failure, including patients on dialysis.

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

As a rule, for patients over 75 years of age, treatment with Lozap is recommended to begin with a dose of 25 mg/day (1/2 tablet of 50 mg, the tablet has a score), however, it is usually not necessary to adjust the dose when prescribing the drug to elderly patients.

CHF. The initial dose of Lozap for patients with CHF is 12.5 mg once a day. As a rule, the dose is titrated at 7-week intervals (i.e. 12.5; 25; 50; 100 mg / day, and only for this indication it is possible to increase to a maximum daily dose of 150 mg 1 time per day), depending depending on individual tolerance.

Reducing the risk of associated cardiovascular morbidity and mortality in patients with arterial hypertension and left ventricular hypertrophy. The standard starting dose of Lozap is 50 mg once a day. In the future, it is recommended to add hydrochlorothiazide in low doses or increase the dose of Lozap to the maximum daily dose of 100 mg once a day, taking into account the degree of blood pressure reduction.

Kidney protection in patients with type 2 diabetes mellitus and proteinuria. The standard starting dose of Lozap is 50 mg once a day. In the future, it is recommended to increase the dose of Lozap to the maximum daily dose of 100 mg once a day, taking into account the degree of blood pressure reduction. The drug Lozap can be prescribed in combination with other antihypertensive drugs (diuretics, CCBs α- and β-blockers, centrally acting antihypertensive drugs), insulin and other hypoglycemic drugs (sulfonylurea derivatives, glitazones and α-glucosidase inhibitors).

Application in pediatrics. The safety and effectiveness of the drug in children under 18 years of age have not been established.

Pharmacodynamics

Angiotensin II is a powerful vasoconstrictor, the main active hormone of the RAAS, and also the main pathophysiological link in the development of arterial hypertension. Angiotensin II selectively binds to AT receptors found in many tissues (vascular smooth muscle, adrenal glands, 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 is 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 physiological effects of angiotensin II, regardless of the source or route of synthesis. Losartan selectively binds to AT1 receptors and does not bind or block receptors of other hormones and ion channels that play an important role in the regulation of cardiovascular function. In addition, losartan does not inhibit ACE (kininase II), which promotes the degradation of bradykinin. Therefore, effects not directly related to AT1 receptor blockade, in particular increased effects associated with bradykinin or the development of edema, are not related to the action of losartan.

Losartan suppresses the increase in SBP and DBP observed with the administration of angiotensin II. When the Cmax of losartan in the blood plasma is reached after taking losartan at a dose of 100 mg, the above effect is suppressed by approximately 85%, and 24 hours after single and multiple doses - by 26–39%.

During the period of 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 is accompanied by an increase in the concentration of angiotensin II in the blood plasma. With long-term (6-week) treatment of patients with arterial hypertension with losartan at a dose of 100 mg/day, a 2-3-fold increase in the concentration of angiotensin II in the blood plasma was observed.

When the Cmax of losartan was reached, some patients experienced an even greater increase in concentration, especially with a short duration of treatment (2 weeks). However, antihypertensive activity and a decrease in plasma aldosterone concentrations appeared after 2 and 6 weeks of therapy, indicating effective blockade of angiotensin II receptors. After discontinuation of losartan, ARP and angiotensin II concentrations decreased to the initial values observed before starting the drug after 3 days.

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 20 and 100 mg losartan with the effects of an ACE inhibitor on the response to angiotensin I, angiotensin II and bradykinin showed that losartan blocked the effects of angiotensin I and angiotensin II without affecting the effects of bradykinin, due to a specific mechanism actions of losartan. In contrast, the ACE inhibitor blocked the response to angiotensin I and increased the response 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. Because losartan and its active metabolite are APAII, they both contribute to the antihypertensive effect.

Pharmacokinetics

Suction. When taken orally, losartan is well absorbed and undergoes first pass metabolism through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. The systemic bioavailability of losartan in tablet form is approximately 33%. The average Cmax of losartan and its active metabolite is reached after 1 hour and after 3–4 hours, respectively. 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 more than 99% bound to plasma proteins (mainly albumin). Vd of losartan is 34 l. Studies in rats have shown that losartan practically does not penetrate the BBB.

Metabolism. Approximately 14% of a dose of losartan administered intravenously or orally is converted into its active metabolite. After oral and intravenous administration of 14C-labeled losartan, the radioactivity of circulating blood plasma is primarily associated with the presence of losartan and its active metabolite. Low conversion of losartan to its active metabolite was observed in approximately 1% of patients studied.

In addition to the active metabolite, biologically inactive metabolites are formed, incl. 2 major, resulting from hydroxylation of the butyl side chain, and 1 minor - N-2-tetrazole glucuronide.

Excretion. Plasma clearance of losartan and its active metabolite is about 600 and 50 ml/min, respectively. The renal clearance of losartan and its active metabolite is approximately 74 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 as an active metabolite. Losartan and its active metabolite have linear pharmacokinetics when taken orally in doses up to 200 mg. After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a final T1/2 of approximately 2 and 6–9 hours, respectively. With a single dose of 100 mg, neither losartan nor its active metabolite accumulates significantly in the body. Excretion of losartan and its metabolites occurs in the bile and kidneys.

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

Pharmacokinetics in special groups of patients

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

Floor. Plasma concentrations of losartan were 2 times higher in women with hypertension compared with men with hypertension. Concentrations of the active metabolite did not differ between men and women. This apparent pharmacokinetic difference is not clinically significant.

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.

Renal dysfunction. Plasma concentrations of losartan in patients with creatinine Cl above 10 ml/min did not differ from those in patients with unchanged renal function. When comparing the AUC of losartan in patients with normal renal function and those on hemodialysis, the 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 on hemodialysis. Losartan and its active metabolite cannot be removed by hemodialysis.

Indications for use Lozap 100 mg 30 pcs. film-coated tablets

arterial hypertension;
chronic heart failure (as part of combination therapy, with intolerance or ineffectiveness of therapy with ACE inhibitors);
reducing the risk of developing cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy;
diabetic nephropathy with hypercreatininemia and proteinuria (urine albumin to creatinine ratio >300 mg/g) in patients with type 2 diabetes mellitus and concomitant arterial hypertension (reducing the progression of diabetic nephropathy to end-stage chronic renal failure).

Contraindications

hypersensitivity to the components of the drug;
simultaneous use with aliskiren in patients with diabetes mellitus and patients with renal failure (Cl creatinine less than 60 ml/min);
severe liver dysfunction (more than 9 points on the Child-Pugh scale - no experience with use);
pregnancy;
lactation period;
age under 18 years (efficacy and safety have not been established).

With caution: arterial hypotension; heart failure with concomitant severe renal failure; severe chronic heart failure functional class IV according to the NYHA classification; heart failure with life-threatening arrhythmias; cardiac ischemia; cerebrovascular diseases; hyperkalemia, age over 75 years; use in representatives of the Negroid race; decreased blood volume, water-electrolyte imbalance, bilateral renal artery stenosis or stenosis of the artery of a single kidney; renal/liver failure; condition after kidney transplantation (no experience of use); aortic and mitral stenosis; history of angioedema; primary hyperaldosteronism; hypertrophic obstructive cardiomyopathy.

Application of Lozap 100 mg 30 pcs. film-coated tablets during pregnancy and breastfeeding

The use of Lozap in the first trimester of pregnancy is not recommended; in the II and III trimesters - contraindicated.

Epidemiological data on the risk of teratogenic effects of ACE inhibitors in the first trimester of pregnancy are not convincing enough, but the risk to the fetus cannot be completely excluded. Although controlled epidemiological studies have not been conducted with angiotensin II receptor antagonists, this class of drugs may have similar risks. Except in cases where continued treatment with ARAII is considered necessary, patients planning pregnancy should be transferred to other types of antihypertensive therapy, the safety of which has been confirmed by the results of clinical studies. If pregnancy is confirmed, treatment with Lozap should be stopped immediately and, if necessary, other 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 fetus (decreased renal function, development of oligohydramnios, slower ossification of the skull bones) and the newborn (renal failure, arterial hypotension, hyperkalemia). If for some reason a woman took the drug Lozap in the second trimester or later stages of pregnancy, it is recommended to conduct an ultrasound of the fetus to monitor kidney function and the condition of the skull bones.

Children whose mothers took Lozap during pregnancy should be closely monitored by a pediatrician due to the risk of developing arterial hypotension.

It is not known whether losartan is excreted in breast milk. Since no information has been received on the use of losartan during breastfeeding, nursing women should refrain from prescribing Lozap, giving preference to alternative treatments with a more studied safety profile, especially when feeding a newborn or premature baby. If use is necessary during lactation, breastfeeding should be discontinued.

special instructions

Hypersensitivity

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

Arterial hypotension and water-electrolyte imbalance

Symptomatic hypotension, especially after the first dose or after dose increases, may occur in patients with hypovolemia and/or hyponatremia as a result of high-dose diuretics, a salt-restricted diet, diarrhea or vomiting. It is necessary to either correct these conditions before prescribing the drug LOZAP®, or use or prescribe lower doses of the drug.

Fluid and electrolyte disturbances

Water and electrolyte disturbances are typical for patients with impaired renal function in combination with or without diabetes mellitus and require correction. In a clinical study conducted in patients with type 2 diabetes mellitus with nephropathy, the incidence of hyperkalemia in the losartan group was higher than in the placebo group. This indicates the need for regular monitoring of potassium levels in the blood plasma and creatinine clearance (CC) indicators - patients with heart failure and creatinine clearance from 30 to 50 ml/min require especially strict monitoring. Prescribing potassium-sparing diuretics, potassium preparations and potassium-containing salt substitutes simultaneously with LOZAP® is not recommended.

Liver dysfunction

Taking into account pharmacokinetic data indicating a significant increase in plasma concentrations of losargan in patients with cirrhosis, patients with a history of impaired liver function (more than 9 points on the Child-Pugh scale) are recommended to prescribe the drug in lower doses. There is no experience with the use of the drug in patients with severe liver failure. Taking this into account, LOZAP® is contraindicated in patients with severe liver failure.

Dual blockade of the renin-angiotensin-aldosterone system

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

The use of LOZAP® together with alnekiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended for other patients.

The use of LOZAP® in combination with an ACE inhibitor is contraindicated in patients with diabetic nephropathy and is not recommended for other patients.

Coronary heart disease (CHD) and cerebrovascular diseases

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

Heart failure

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

There is virtually no experience with the use of losartan in the treatment of patients with heart failure and concomitant severe renal failure, in patients with severe chronic heart failure (NYHA functional class IV), as well as in patients with heart failure and life-threatening arrhythmias. Taking this into account, caution should be exercised when prescribing the drug LOZAP® to these categories of patients.

Combined use 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. In these cases, careful observation and monitoring of laboratory parameters is necessary.

Hemodialysis

During hemodialysis, the sensitivity of blood pressure to the action of AT1 receptor antagonists increases as a result of a decrease in blood volume and activation of the RAAS. It is necessary to adjust the dose of LOZAP® under close monitoring of blood pressure in patients on hemodialysis. Kidney transplantation There are no data on the use of LOZAP® in patients who have recently undergone kidney transplantation.

General anesthesia

In patients receiving angiotensin II antagonists, arterial hypotension may develop during general anesthesia and surgical procedures as a result of blockade of the renin-angiotensin-aldosterone system. Very rarely, cases of severe arterial hypotension may occur, requiring replenishment of blood volume and/or vasopressor drugs.

Aortic and mitral titanium stenosis, 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 treatment with antihypertensive drugs that affect the RAAS. In this regard, the drug LOZAP® is not recommended for such patients.

Patients over 75 years of age

As a rule, patients over 75 years of age are recommended to start treatment with LOZAP® with a dose of 25 mg per day.

Other special instructions and precautions

As clinical experience with the use of ACE inhibitors, losartan and other AT1 receptor antagonists shows, these drugs are less effective in reducing blood pressure in patients of the Black race than in representatives of other races, possibly due to low renin activity in patients of this race.

Impact on the ability to drive vehicles and operate machinery

The effect of LOZAP® on the ability to drive vehicles or operate machinery has not been studied.

When driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, you should be careful, because When using the drug, dizziness, drowsiness and fainting may occur.

Overdose

Symptoms: There is limited data on losartan overdose in humans. 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: with the development of clinically significant arterial hypotension, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Place the patient on his back with his legs elevated. If necessary, the volume of blood volume should be increased, for example, by intravenous administration of 0.9% sodium chloride solution. If necessary, sympathomimetic drugs can be prescribed. Removal of losartan and its active metabolite by hemodialysis is ineffective.

Side effects Lozap 100 mg 30 pcs. film-coated tablets

Side effects of losartan are usually transient and do not require discontinuation of the drug. When using losartan for the treatment of essential hypertension in controlled studies, among all side effects, only the incidence of dizziness differed from placebo by more than 1% (4.1 vs. 2.4%).

A dose-dependent orthostatic effect, characteristic of antihypertensive drugs, was observed in less than 1% of patients when using losartan.

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

From the kidneys and urinary tract: as a result of inhibition of the RAAS, renal dysfunction, including acute renal failure, has been observed in patients at risk. These changes in renal function may be reversible if treatment is discontinued in a timely manner.

Drug interactions

The use of Lozap with aliskiren in patients with diabetes mellitus is contraindicated. The use of Lozap with aliskiren should be excluded in patients with renal failure (Cl creatinine

May be prescribed with other antihypertensive drugs. Mutually enhances the effect of β-blockers and sympatholytics. The combined use of losartan with diuretics has an additive effect.

Combination use with other drugs that can cause the development of arterial hypotension as an undesirable reaction (for example, 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, or erythromycin.

Losartan is predominantly metabolized by the CYP2C9 isoenzyme of the cytochrome P450 system to form the active metabolite carboxylic acid. In a clinical study, fluconazole (an inhibitor of the CYP2C9 isoenzyme) was shown to reduce the formation of the active metabolite by approximately 50%. It has been established that the combined use of losartan with rifampicin (an inducer of metabolic enzymes) leads to an increase in the concentration of the active metabolite by 40% in the blood plasma. The clinical significance of this effect remains unclear.

When the drug was combined with fluvastatin (a weak inhibitor of the CYP2C9 isoenzyme), no change in the concentration of the metabolite was observed.

Experience with the use of other drugs acting on the RAAS shows that concomitant therapy with potassium-sparing diuretics (spironolactone and its derivative eplerenone; triamterene, amiloride), potassium preparations, salt substitutes containing potassium, and other drugs that can increase the content of potassium in the blood plasma ( for example heparin), can lead to the development of hyperkalemia. The antihypertensive effect of the drug may be weakened when used together with NSAIDs, incl. selective COX-2 inhibitors.

As with ACE inhibitors, coadministration of losartan and NSAIDs may result in an increased risk of renal impairment, including possible acute renal failure and hyperkalemia, especially in patients with pre-existing renal impairment. This combination should be used with caution, especially in elderly patients. Patients receiving concomitant treatment with losartan and NSAIDs should receive adequate fluids and be under medical supervision while monitoring renal function tests.

The prescription of combination therapy with an ACE inhibitor and angiotensin-converting enzyme inhibitors should be limited to exceptional cases based on individual indications and carried out against the background of strict monitoring of renal function. Clinical trial results have shown that in patients with documented atherosclerosis, heart failure, or diabetes mellitus with end-organ damage, dual blockade of the RAAS is associated with an increased risk of hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) compared with using RAAS inhibitors individually.

Interactions with drugs

Combining the drug with Fluconazole and Rifampicin leads to a decrease in the active substance.

Lozap increases the pharmacological activity of other antihypertensive drugs.

It is not recommended to take the medicine in parallel with non-steroidal anti-inflammatory drugs.

When interacting with potassium and potassium-sparing diuretics, it is important to monitor the level of the element in the blood to prevent the occurrence of hyperkalemia.

Patients with obvious symptoms of dehydration while taking diuretics may experience a rapid decrease in blood pressure when taking an antihypertensive drug.