Lozap tablets p / o 50mg, No. 90

- Arterial hypertension.
- Chronic heart failure (as part of combination therapy, with intolerance or ineffectiveness of therapy with ACE inhibitors).
- To reduce 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 (the ratio of urine albumin and creatinine is more than 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).

The drug LOZAPЃ is taken orally, regardless of food intake, the frequency of administration is 1 time per day.
With arterial hypertension, the average daily dose is 50 mg. In some cases, to achieve a greater therapeutic effect, the dose is increased to 100 mg in two divided doses or once a day.
The initial dose for patients with chronic heart failure is 12.5 mg once a day. Typically, the dose is increased at weekly intervals (i.e. 12.5 mg / day, 25 mg / day, and 50 mg / day) to an average maintenance dose of 50 mg once daily, depending on the patient's tolerance to the drug.
When prescribing the drug to patients receiving diuretics in high doses,the initial dose of LOZAPЃ should be reduced to 25 mg (1/2 tablet of 50 mg) once a day.
No dose adjustment is required in elderly patients.
Reducing the risk of developing cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy: the initial dose of the drug is 50 mg once a day. In the future, low doses of hydrochlorothiazide can be added and / or the dose of LOZAPЃ can be increased to 100 mg per day in one or two doses.
Patients with concomitant type 2 diabetes mellitus with proteinuria: LOZAPЃ is prescribed at an initial dose of 50 mg once a day with a further increase in the dose to 100 mg / day (taking into account the degree of blood pressure reduction) in one or two doses.
Sickwith a history of liver disease , dehydration , during the hemodialysis procedure , as well as patients over 75 years old , a lower initial dose of the drug is recommended - 25 mg (1/2 tablet of 50 mg) 1 time per day.

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

Losartan

- Hypersensitivity to the components of the drug;

- Pregnancy and lactation period;

- Age up to 18 years (efficacy and safety have not been established).

With caution: arterial hypotension, reduced circulating blood volume, disturbances in water and electrolyte balance, bilateral renal artery stenosis or stenosis of an artery of a single kidney, renal / hepatic failure.

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics
Losartan is a specific angiotensin II receptor antagonist (AT1 subtype). Does not inhibit kininase II, an enzyme that catalyzes the conversion of angiotensin I to angiotensin II. Reduces total peripheral vascular resistance (OPSS), blood concentration of adrenaline and aldosterone, blood pressure (BP), pressure in the pulmonary circulation; reduces afterload, has a diuretic effect. Prevents the development of myocardial hypertrophy, increases exercise tolerance in patients with chronic heart failure. Losartan does not inhibit angiotensin-converting enzyme (ACE) kininase II and, accordingly, does not prevent the destruction of bradykinin, therefore side effects indirectly associated with bradykinin (for example, angioedema) are rare.
After a single oral administration, the hypotensive effect (systolic and diastolic blood pressure decreases) reaches a maximum after 6 hours, then gradually decreases within 24 hours.
The maximum hypotensive effect develops 3-6 weeks after starting the drug.
In patients with arterial hypertension without concomitant diabetes mellitus with proteinuria (more than 2 g / day), the use of the drug significantly reduces proteinuria, excretion of albumin and immunoglobulins G.
Stabilizes the level of urea in the blood plasma. Does not affect autonomic reflexes, and does not have a long-term effect on the concentration of norepinephrine in blood plasma. Losartan at a dose of up to 150 mg per day does not affect the level of triglycerides, total cholesterol and high-density lipoprotein cholesterol (HDL) in serum in patients with arterial hypertension. At the same dose, losartan does not affect fasting blood glucose levels.

Pharmacokinetics
Absorption
When taken orally, losartan is well absorbed, and at the same time undergoes metabolism during the 'first pass' through the liver by carboxylation with the participation of the cytochrome CYP2C9 isoenzyme with the formation of an active metabolite. The systemic bioavailability of losartan is about 33%. The maximum concentration of losartan and its active metabolite is reached in serum approximately 1 hour and 3-4 hours after oral administration, respectively. Food intake does not affect the bioavailability of losartan.
Distribution
More than 99% of losartan and its active metabolite binds to plasma proteins, mainly albumin. The volume of distribution of losartan is 34 liters. Losartan practically does not penetrate the blood-brain barrier.
Metabolism
Approximately 14% of losartan administered intravenously or orally to a patient is converted to an active metabolite.
Withdrawal
Plasma clearance of losartan is 600 ml / min, and the active metabolite is 50 ml / min. The renal clearance of losartan and its active metabolite is 74 ml / min and 26 ml / min, respectively. When taken orally, approximately 4% of the dose taken is excreted by the kidneys unchanged and about 6% is excreted by the kidneys in the form of an active metabolite. Losartan and its active metabolite are characterized by linear pharmacokinetics when taken orally in doses up to 200 mg.
After oral administration, the plasma concentrations of losartan and its active metabolite decrease polyexponentially with a terminal half-life of losartan of about 2 hours, and of the active metabolite - about 6-9 hours. When taking the drug at a dose of 100 mg per day, neither losartan nor the active metabolite significantly accumulates in the blood plasma. Losartan and its metabolites are excreted from the body through the intestines and kidneys. In healthy volunteers, after ingestion of the C14 isotope-labeled losartan, about 35% of the radioactive label is found in the urine and 58% in the feces.

Pharmacokinetics in special groups of patients
In patients with alcoholic liver cirrhosis of mild to moderate severity, the concentration of losartan was 5 times, and the concentration of the active metabolite was 1.7 times higher than in healthy male volunteers.
With creatinine clearance (CC) above 10 ml / min. the concentration of losartan in blood plasma does not differ from that with normal renal function. In patients requiring hemodialysis, the area under the concentration-time curve (AUC) is approximately 2 times higher than in patients with normal renal function. Neither losartan nor its active metabolite is removed from the body by hemodialysis.
Plasma concentrations of losartan and its active metabolite in elderly men with arterial hypertension do not differ significantly from the values ??of these parameters in young men with arterial hypertension.
The values ??of plasma concentrations of losartan in women with arterial hypertension are 2 times higher than the corresponding values ??in men with arterial hypertension. The concentrations of the active metabolite in men and women do not differ. This pharmacokinetic difference is of no clinical relevance.

Indications for use:

- 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 hypercreatinemia and proteinuria (the ratio of urine albumin and creatinine is more than 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;

- Pregnancy and lactation period;

- Age up to 18 years (efficacy and safety have not been established).

With caution: arterial hypotension, reduced circulating blood volume, disturbances in water and electrolyte balance, bilateral renal artery stenosis or stenosis of an artery of a single kidney, renal / hepatic failure.

Pregnancy and lactation
There are no data on the use of losartan during pregnancy. However, it is known that drugs acting directly on the renin-angiotensin-aldosterone system, when used in the II and III trimesters of pregnancy, can cause developmental defects or even death of the developing fetus. Therefore, in the event of pregnancy, the use of LOZAPЃ should be discontinued immediately. When administered during lactation, a decision should be made to stop breastfeeding or to discontinue treatment with LOZAPЃ.

Method of administration and dosage

The drug LOZAPЃ is taken orally, regardless of food intake, the frequency of administration is 1 time per day.
With arterial hypertension, the average daily dose is 50 mg. In some cases, to achieve a greater therapeutic effect, the dose is increased to 100 mg in two divided doses or once a day.
The initial dose for patients with chronic heart failure is 12.5 mg once a day. Typically, the dose is increased at weekly intervals (i.e. 12.5 mg / day, 25 mg / day, and 50 mg / day) to an average maintenance dose of 50 mg once daily, depending on the patient's tolerance to the drug.
When prescribing the drug to patients receiving diuretics in high doses,the initial dose of LOZAPЃ should be reduced to 25 mg (1/2 tablet of 50 mg) once a day.
No dose adjustment is required in elderly patients.
Reducing the risk of developing cardiovascular diseases (including stroke) and mortality in patients with arterial hypertension and left ventricular hypertrophy: the initial dose of the drug is 50 mg once a day. In the future, low doses of hydrochlorothiazide can be added and / or the dose of LOZAPЃ can be increased to 100 mg per day in one or two doses.
Patients with concomitant type 2 diabetes mellitus with proteinuria: LOZAPЃ is prescribed at an initial dose of 50 mg once a day with a further increase in the dose to 100 mg / day (taking into account the degree of blood pressure reduction) in one or two doses.
Sickwith a history of liver disease , dehydration , during the hemodialysis procedure , as well as patients over 75 years old , a lower initial dose of the drug is recommended - 25 mg (1/2 tablet of 50 mg) 1 time per day.

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

Side effects
Most often, side effects during treatment with the drug are not observed. With the development of side effects, their nature is transient, therefore, drug withdrawal is usually not required. The following phenomena may rarely disturb: drowsiness, anxiety, memory disorder, depression, paresthesia, tremor, hypesthesia, migraine, hearing impairment, bronchitis, dyspnea, rhinitis, abdominal pain, nausea, diarrhea, dry mouth, gastritis, vomiting, toothache , flatulence, back pain, limbs, chest pain; convulsions, myalgia, arthritis, arthralgia, shoulder pain, tachycardia or bradycardia, angina pectoris, arrhythmia, anemia.

Interaction with other medicinal products:
May be prescribed with other antihypertensive drugs. Mutually enhances the effect of beta-blockers and sympatholytics. The combined use of losartan with diuretics has an additive effect.
There were no pharmacokinetic interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampicin and fluconazole have been reported to reduce plasma levels of the active metabolite. The clinical significance of these interactions is still unknown. As with the use of other drugs that inhibit angiotensin II or its action, the combined use of losartan with potassium-sparing diuretics (for example, spironolactone, triamterene, amiloride), potassium preparations and potassium-containing salts increases the risk of hyperkalemia.
Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2), can reduce the effect of diuretics and other antihypertensive drugs.
With the combined use of angiotensin II and lithium receptor antagonists, an increase in the concentration of lithium in the blood plasma is possible. Given this, it is necessary to weigh the benefits and risks of the combined use of losartan with lithium salts. If it is necessary to use drugs together, it is necessary to regularly monitor the concentration of lithium in the blood plasma.

Special instructions:
It is necessary to correct dehydration before prescribing LOZAPЃ or start treatment with a lower dose of the drug.
Drugs that affect the renin-angiotensin system can increase the concentration of urea in the blood and serum creatinine in patients with bilateral renal stenosis or stenosis of a solitary kidney artery.
In patients with cirrhosis of the liver, the concentration of losartan in the blood plasma increases significantly, and therefore, if there is a history of liver disease, it should be prescribed in lower doses.
During the period of treatment, the concentration of potassium in the blood should be regularly monitored, especially in elderly patients with impaired renal function.
Impact on the ability to concentrate: losartan does not affect the ability to drive or operate machinery.

Storage conditions:

List B.
Store at a temperature not exceeding 30 ? C.
Keep out of the reach of children!

Expiration date:
2 years.
The drug should not be used after the expiration date indicated on the package.

Pharmacy Dispensing Terms:
Prescription