Losartan Teva tablets p / o 50mg, No. 30

? 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 or hypercreatininemia and proteinuria (urine albumin to creatinine ratio more than 300 mg / day) 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 Losartan-Teva is taken orally, regardless of food intake.
The tablets are swallowed without chewing with water. Frequency rate of admission - 1 time per day.
Arterial hypertension
In arterial hypertension, the average daily dose is 50 mg 1 time / day. To achieve a greater therapeutic effect, the dose is increased to 100 mg once a day.
Chronic heart failure The
starting 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 1 time per day, depending on the patient's tolerance to the drug.
No dose adjustment of the drug 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 1 time / day. In the future, hydrochlorothiazide can be added in low doses or the dose of Losartan-Teva can be increased to 100 mg in one or two doses, taking into account the decrease in blood pressure (BP).
Patients with concomitant type 2 diabetes mellitus with proteinuria: the drug Losartan-Teva is prescribed in 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.
In patients with reduced BCC(for example, when taking diuretics in high doses), the recommended initial dose of Losartan-Teva is 25 mg 1 time / day.
Patients with hepatic impairment (less than 9 points on the Child-Pugh scale), during the hemodialysis procedure, as well as patients over 75 years old, are recommended a lower initial dose of the drug - 25 mg 1 time per day.
The safety and efficacy of the drug in children under 18 years of age has not been established. There is not enough experience in the use of the drug in patients with severe hepatic impairment, therefore the drug is not recommended in this category of patients (see section 'Contraindications').

active substance:
losartan potassium 25 mg / 50 mg / 100 mg;
excipients:
lactose monohydrate 4.50 mg / 9.00 mg / 18.00 mg;
microcrystalline cellulose 39.50 mg / 79.00 mg / 158.00 mg;
pregelatinized starch 30.25 mg / 60.50 mg / 121.00 mg;
magnesium stearate 0.75 mg / 1.50 mg / 3.00 mg;
Opadrv II85F18422 white sheath:
polyvinyl alcohol (partially hydrolyzed) 1,200 mg / 2,400 mg / 4,800 mg;
titanium dioxide (E 171) 0.750 mg / 1,500 mg / 3,000 mg;
macrogol 0.606 mg / 1.212 mg / 2.424 mg;
talc 0.444 mg / 0.888 mg / 1.776 mg.

Hypersensitivity to the components of the drug; severe liver failure (more than 9 points on the Child-Pugh scale); age under 18; hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome; pregnancy and lactation.

With care
Arterial hypotension, reduced volume of circulating blood (BCC), disturbances in water and electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, renal failure, liver failure (less than 9 points on the Child-Pugh scale).

Trade name : Losartan-Teva

International Non-Proprietary Name (INN) : Losartan

Dosage form : film-coated tablets

Composition (for 1 tablet):
active substance:
potassium losartan 25 mg / 50 mg / 100 mg;
excipients:
lactose monohydrate 4.50 mg / 9.00 mg / 18.00 mg;
microcrystalline cellulose 39.50 mg / 79.00 mg / 158.00 mg;
pregelatinized starch 30.25 mg / 60.50 mg / 121.00 mg;
magnesium stearate 0.75 mg / 1.50 mg / 3.00 mg;
Opadrv II85F18422 white sheath:
polyvinyl alcohol (partially hydrolyzed) 1,200 mg / 2,400 mg / 4,800 mg;
titanium dioxide (E 171) 0.750 mg / 1,500 mg / 3,000 mg;
macrogol 0.606 mg / 1.212 mg / 2.424 mg;
talc 0.444 mg / 0.888 mg / 1.776 mg.

Description
Tablets 25 mg:
white oval biconvex film-coated tablets with a scored on both sides. One of the sides is engraved with '2' and '5'.
Tablets 50 mg:
white oval biconvex film-coated tablets. On one side there is a dividing line, on the other - engraving '50'.
Tablets 100 mg:
white oval biconvex film-coated tablets. On one side there is a dividing line, on the other - engraving '100'.

Pharmacotherapeutic group : angiotensin II receptor antagonist

Pharmacological properties
Pharmacodynamics
Losartan is a specific antagonist of angiotensin II receptors (AT1 subtype) for oral administration. Angiotensin II binds selectively to AT1 receptors found in many tissues (vascular smooth muscle, adrenal, kidney, and heart) and has several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates the proliferation of smooth muscle cells.
Losartan and its pharmacologically active 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, which play an important role in the regulation of the function of the cardiovascular system. In addition, losartan does not inhibit the 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.
When losartan is used, the absence of negative feedback on renin secretion leads to an increase in plasma renin activity. An increase in renin activity leads to an increase in the concentration of angiotensin II in the blood plasma. However, antihypertensive activity and a decrease in the concentration of aldosterone in blood plasma persist, which indicates an effective blockade of angiotensin P receptors. Losartan and its active metabolite have a greater affinity for angiotensin I receptors than for angiotensin I receptors.The active metabolite is 10-40 times more active than losartan.
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 reliably reduces proteinuria, the excretion of albumin and immunoglobulin G. It stabilizes the urea content 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 150 mg per day does not affect the concentration of triglycerides, total cholesterol and high density lipoprotein cholesterol (HDL) in the blood serum of patients with arterial hypertension. At the same dose, losartan does not affect the fasting blood glucose concentration.
Pharmacokinetics
Absorption
When taken orally, losartan is well absorbed from the gastrointestinal tract (GIT) and is metabolized during the 'first pass' through the liver by carboxylation with the participation of the isoenzyme CYP2C9 with the formation of an active metabolite.
The systemic bioavailability of losartan is approximately 33% g. 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 bind 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 to a patient intravenously or orally is converted to an active metabolite.
Withdrawal
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 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, 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 its 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 losartan labeled with C14 isotope, about 35% of the radioactive label is found in urine and 59% in feces.
Pharmacokinetics in special groups of patients
In patients with alcoholic cirrhosis of mild and moderate severity, the concentration of losartan was 5 times, and 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.

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 or hypercreatininemia and proteinuria (urine albumin to creatinine ratio more than 300 mg / day) 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 drug components; severe liver failure (more than 9 points on the Child-Pugh scale); age under 18; hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome; pregnancy and lactation.

With care
Arterial hypotension, reduced volume of circulating blood (BCC), disturbances in water and electrolyte balance, bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, renal failure, liver failure (less than 9 points on the Child-Pugh scale).

Application during pregnancy and during breastfeeding
The use of the drug Losartan-Teva during pregnancy is contraindicated. It is known that drugs acting directly on the renin-angiotensin-aldosterone system (RAAS), when used in the II and III trimesters of pregnancy, can cause developmental defects or even death of the developing fetus. Therefore, when diagnosing pregnancy, the drug Lozartan-Teva should be stopped immediately.
It is not known whether losartan is excreted in breast milk. It is not recommended to take the drug Losartan-Teva during lactation. If taking the drug Losartan-Teva is necessary during lactation, then breastfeeding should be discontinued.

Dosage and administration The drug Losartan-Teva is taken orally, regardless of food intake.
The tablets are swallowed without chewing with water. Frequency rate of admission - 1 time per day.
Arterial hypertension
In arterial hypertension, the average daily dose is 50 mg 1 time / day. To achieve a greater therapeutic effect, the dose is increased to 100 mg once a day.
Chronic heart failure The
starting 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 1 time per day, depending on the patient's tolerance to the drug.
No dose adjustment of the drug 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 1 time / day. In the future, hydrochlorothiazide can be added in low doses or the dose of Losartan-Teva can be increased to 100 mg in one or two doses, taking into account the decrease in blood pressure (BP).
Patients with concomitant type 2 diabetes mellitus with proteinuria: the drug Losartan-Teva is prescribed in 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.
In patients with reduced BCC(for example, when taking diuretics in high doses), the recommended initial dose of Losartan-Teva is 25 mg 1 time / day.
Patients with hepatic impairment (less than 9 points on the Child-Pugh scale), during the hemodialysis procedure, as well as patients over 75 years old, are recommended a lower initial dose of the drug - 25 mg 1 time per day.
The safety and efficacy of the drug in children under 18 years of age has not been established. There is not enough experience in the use of the drug in patients with severe hepatic impairment, therefore the drug is not recommended in this category of patients (see section 'Contraindications').

Side effects
Side effects of losartan are usually transient and do not require discontinuation of the drug.
When losartan was used for the treatment of hypertension in controlled trials, among the side effects, only the incidence of dizziness differed from placebo by more than 1% (4.1% versus 2.4%).
Dose-dependent hypotensive effect, characteristic of antihypertensive drugs, with losartan was observed in less than 1% of patients.

Side effects occurring with a frequency of less than 1%
From the cardiovascular system: orthostatic hypotension (dose-dependent), epistaxis, bradycardia, arrhythmias, angina pectoris, vasculitis, myocardial infarction.
From the digestive system: anorexia, dryness of the oral mucosa, toothache, vomiting, flatulence, gastritis, constipation, hepatitis, liver dysfunction.
On the part of the skin: dry skin, erythema, ecchymosis, photosensitivity, increased sweating, alopecia.
Allergic reactions: urticaria, skin rash, itching, angioedema (including swelling of the larynx and tongue, causing airway obstruction and / or swelling of the face, lips, pharynx).
From the hematopoietic system:anemia (a slight decrease in hemoglobin and hematocrit, on average by 0.11 g% and 0.09 volume%, respectively, rarely having clinical significance), thrombocytopenia, eosinophilia, Schonlein-Henoch purpura.
From the musculoskeletal system: arthralgia, arthritis, pain in the shoulder, knee, fibromyalgia.
From the nervous system and sensory organs: anxiety, sleep disorders, drowsiness, memory impairment, peripheral neuropathy, paresthesia, hypoesthesia, tremor, ataxia, depression, fainting, ringing in the ears, taste disturbance, visual impairment, conjunctivitis, migraine.
From the genitourinary and reproductive system: urge to urinate, urinary tract infections, impaired renal function, decreased libido, impotence.
Others:gout.
Laboratory indicators: often - hyperuricemia (plasma potassium content is more than 5.5 mmol / l); infrequently - an increase in the concentration of urea and residual nitrogen and creatinine in the blood serum; very rarely - a moderate increase in the activity of 'hepatic' transaminases: aspartate aminotransferase (ACT) and alanine aminotransferase (ALT), hyperbilirubinemia.

Overdose
Symptoms: marked decrease in blood pressure and tachycardia; bradycardia can result from parasympathetic stimulation.
Treatment: forced diuresis, symptomatic therapy; hemodialysis is not effective.

Interaction with other medicinal products
Can be used concurrently with other antihypertensive drugs. Mutually enhances the effect of beta-blockers and sympatholytics. The combined use of losartan with diuretics causes 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 concentrations 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, salts containing potassium 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 jointly use drugs, it is necessary to regularly monitor the concentration of lithium in the blood plasma.

Special instructions
Before using the drug Losartan-Teva, it is necessary to correct the BCC or start treatment with the use of the drug at a lower dose.
Drugs that affect the RAAS can increase the concentration of urea in the blood and the concentration of serum creatinine in patients with bilateral renal artery stenosis or stenosis of a solitary kidney artery.
During the period of treatment, the potassium content in the blood should be regularly monitored, especially in elderly patients with impaired renal function.

Influence on the ability to drive vehicles and work with equipment .
There were no special clinical studies to assess the effect of the drug on the ability to drive vehicles and work with equipment. It should be borne in mind the possibility of drowsiness and dizziness, therefore, care must be taken when performing work that requires increased attention, especially at the beginning of treatment, when increasing the dose of the drug and when driving.

Release form
Film-coated tablets, 25 mg, 50 mg, 100 mg.
Tablets 25 mg:
10 tablets in a blister of polyvinyl chloride and aluminum foil. 3 or 5 blisters together with instructions for use in a cardboard box.
Tablets 50 mg:
14 tablets in a blister of PVC and aluminum foil.
1 blister with instructions for use in a cardboard box.
10 tablets in a blister of polyvinyl chloride and aluminum foil. 3 blisters together with instructions for use in a cardboard box.
Tablets 100 mg:
10 tablets in a blister of PVC and aluminum foil.
3 blisters with instructions for use in a cardboard box.

Storage
conditions Store at a temperature not exceeding 25 ? C. Keep out of the reach of children.

Shelf life
3 years
Do not use later than the date indicated on the package.

Pharmacy
Dispensing Conditions Prescription.