DR. DOPING

Instructions

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Instructions / Instruction for use: Cozaar

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Dosage form: film coated tablets

Active substance: Losartanum

ATX

C09CA01 Losartan

Pharmacological group

Angiotensin II receptor antagonists (AT1 subtype)

Nosological classification (ICD-10)

I10 Essential (primary) hypertension: hypertension; Arterial hypertension; Arterial hypertension crisis course; Essential Hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Essential hypertension; Primary hypertension; Arterial hypertension, complications of diabetes; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; arterial Hypertension; malignant Hypertension; Hypertonic disease; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; Isolated systolic hypertension

I15 Secondary hypertension: Arterial hypertension, complications of diabetes; hypertension; The sudden increase in blood pressure; Hypertensive disorders of blood circulation; hypertensive condition; hypertensive crises; hypertension; arterial Hypertension; malignant Hypertension; hypertensive crises; accelerated hypertension; malignant hypertension; The aggravation of hypertensive disease; Transient hypertension; hypertension; Arterial hypertension; Arterial hypertension crisis course; renovascular hypertension; Hypertension symptomatic; Renal hypertension; Renovascular hypertension; renovascular hypertension; Symptomatic hypertension

I50 Heart failure: Exacerbation of chronic heart failure; Shortness of breath with acute heart failure; Acute heart failure; Acute heart failure; Heart failure on the background of intoxication; Heart failure on the background of infections; Acute Heart Failure; Chronic myocardial insufficiency; Cardiac dyspnea

I50.0 Congestive heart failure: anasarca heart; Decompensated congestive heart failure; Congestive heart failure; Congestive heart failure with high afterload; Congestive chronic heart failure; Cardiomyopathy with severe chronic heart failure; Compensated chronic heart failure; Swelling with circulatory failure; Edema of cardiac origin; Swelling of the heart; Edematous syndrome in diseases of the heart; Edematous syndrome in congestive heart failure; Edematous syndrome in heart failure; Edematous syndrome in heart failure or liver cirrhosis; right ventricular failure; Congestive Heart Failure; Heart failure stagnant; Heart failure with low cardiac output; Heart failure is a chronic; Cardiac edema; Chronic decompensated heart failure; Chronic Congestive Heart Failure; Chronic heart failure; Change of liver function in heart failure

N08.3 Glomerular lesions in diabetes mellitus (E10-14 + with common fourth sign .2): Nephropathy diabetic; Diabetic Nephropathy; Diabetic nephropathy in the background of type 1 diabetes mellitus; Diabetic nephropathy in patients with type I diabetes; Proteinuria in patients with type 2 diabetes mellitus

Composition

Tablets covered with a film coating.

core

active substance: Losartan potassium 50 mg

Auxiliary substances: MCC - 52.5 mg; Lactose monohydrate - 25.5 mg; Pregelatinized starch - 20.95 mg; Magnesium stearate - 1.05 mg

Membrane film: giprolose (with 0.3% silicon dioxide) - 1.8 mg; Hypromellose - 1,8 mg; Titanium dioxide - 0.9 mg; Carnauba wax - 0.05 mg

Tablets covered with a film coating.

core

active substance: Losartan Potassium 100 mg

Auxiliary substances: MCC - 105 mg; Lactose monohydrate - 51 mg; Pregelatinized starch - 41.9 mg; Magnesium stearate 2.1 mg

Membrane film: giprolose (with 0.3% silicon dioxide) - 3.6 mg; Hypromellose - 3.6 mg; Titanium dioxide - 1.8 mg; Carnauba wax - 0.05 mg

Description of dosage form

Tablets, 50 mg: oval, film-coated, white, with a risk on one side, on the other side is engraved - "952".

Tablets, 100 mg: white, film-coated, drop-shaped, on one side engraved "960", on the other - smooth.

Pharmachologic effect

Mode of action - hypotensive.

Pharmacodynamics

Mechanism of action

Angiotensin II is a potent vasoconstrictor, the main active hormone of RAAS, as well as the crucial pathophysiological link in the development of hypertension. Angiotensin II selectively binds to AT1 receptors found in many tissues (in smooth muscle tissues of blood vessels, adrenal glands, kidneys and the heart), and performs several important biological functions, including vasoconstriction and aldosterone release. Angiotensin II also stimulates proliferation of smooth muscle cells. Lozartan is a highly effective ingestion of an 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. Unlike some peptide angiotensin II antagonists, losartan does not have the effects of an agonist.

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 CCC function. In addition, losartan does not inhibit ACE (kininase II), which contributes to the degradation of bradykinin. Therefore, effects that are not directly related to the blockade of AT1 receptors, particularly the enhancement of effects associated with bradykinin, or the development of edema (losartan - 1.7%, placebo - 1.9%), are not related to the action of losartan.

Losartan suppresses the increase in SAD and DAD, observed with the introduction of angiotensin II. At the time Cmax of losartan in the blood plasma after taking losartan at a dose of 100 mg, the above effect is suppressed by approximately 85%; And 24 hours after a single and multiple appointments - 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 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 Cmax losartan; In some patients there was an even greater increase in concentration, especially with a short duration of treatment (2 weeks). In the course of treatment, antihypertensive activity and a decrease in plasma aldosterone concentration were manifested after 2 and 6 weeks of therapy, which indicates an effective blockade of angiotensin II receptors. After cancellation of losartan, ARP and angiotensin II concentration decreased for 3 days to the baseline values observed before the drug was started.

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 effects of 20 and 100 mg of losartan with ACE inhibitor effects on the reaction 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 a specific mechanism Action of losartan. In contrast, the 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. Since losartan and its active metabolite are angiotensin II receptor antagonists (ARA II), both contribute to the antihypertensive effect.

In a study with a single dose of 100 mg of losartan, in which healthy volunteers (men) were included, ingestion in a high- and low-fat diet did not affect the glomerular filtration rate (GFR), the effective renal plasma flow and the filtration fraction. Losartan has a natriyuretic effect, which was more pronounced with a low-fat diet and, apparently, was not associated with the suppression of early sodium reabsorption in the proximal renal tubules. Losartan also caused a transient increase in the excretion of uric acid by the kidneys. In patients with arterial hypertension, proteinuria (≥2 g / 24 h), not suffering from diabetes mellitus and taking losartan for 8 weeks at a dose of 50 mg with a gradual increase to 100 mg, there was a significant decrease in proteinuria by 42%, fractional albumin excretion and Immunoglobulins (IgG). In these patients, losartan stabilized GFR and reduced the filtration fraction.

In postmenopausal women with arterial hypertension who took losartan at a dose of 50 mg / day for 4 weeks, the effect of therapy on renal and systemic GH levels was not revealed.

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

In patients with arterial hypertension, losartan at doses up to 150 mg / day does not cause clinically significant changes in the concentration of fasting triglycerides, total cholesterol and HDL cholesterol. In the same doses, losartan does not affect the concentration of glucose in the blood on an empty stomach.

A clinical study of HEAAL to evaluate the effect of high and low doses of ARA II (losartan) on the outcome of treatment of patients with chronic heart failure (CHF) included patients (n = 3834) with CHF (II-IV functional class according to the NYHA classification) that were Tolerant to therapy with ACE inhibitors. Patients were observed for 4 years (median follow-up was 4.7 years) to compare the effect of losartan 50 mg / day with a dose of 150 mg / day to reduce all causes of death or hospitalization for heart failure. This study showed that losartan at a dose of 150 mg / day significantly reduced the risk of death from all causes or hospitalization for heart failure compared with a dose of 50 mg / day (risk ratio (OR) 0.899; p = 0.027).

In general, losartan caused a decrease in the concentration of uric acid in the blood serum (usually <0.4 mg / dl), which persisted with long-term treatment. In controlled clinical trials involving hypertensive patients, no withdrawal of the drug due to an increase in serum creatinine or serum potassium was recorded.

In a 12-week parallel study, which included patients with left ventricular failure (NYHA class II-IV functional class), and most of whom took diuretics and / or cardiac glycosides (digitalis), the effects of losartan were measured at doses of 2.5, 10 , 25 and 50 mg / day with placebo. At doses of 25 and 50 mg / day, the drug exhibited positive hemodynamic and neurohormonal effects, which persisted throughout the study. Hemodynamic effects included an increase in the cardiac index and a decrease in the wedge pressure in the pulmonary capillaries, as well as a decrease in the OPSS, the mean systemic BP, and heart rate. The incidence of arterial hypotension in these patients depended on the dose of the drug. Neurohormonal effects included a decrease in the concentration of aldosterone and norepinephrine in the blood.

Pharmacokinetics

Suction. When administered orally, losartan is well absorbed and metabolized during primary passage through the liver, resulting in the formation of an active carboxylated metabolite and inactive metabolites. Systemic bioavailability of losartan in tableted form is approximately 33%. The average Cmax of losartan and its active metabolite is reached after 1 and 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%. Vd of losartan is 34 liters. Studies in rats have shown that losartan practically does not penetrate the BBB.

Metabolism. Approximately 14% of the dose of losartan administered intravenously or inward is converted to its active metabolite. After oral or intravenous administration of radio-labeled losartan (14C-losartan), the radioactivity of the circulating blood plasma is primarily due to the presence of losartan and its active metabolite in it.

Low conversion efficiency of losartan in its active metabolite was observed in approximately 1% of patients included in the data analysis.

In addition to the active metabolite, biologically inactive metabolites are formed, incl. Two major metabolites formed as a result of hydroxylation of the butyl side chain, and one secondary metabolite is N-2-tetrazole-glucuronide.

Excretion. The 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 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 administered to losartan in doses up to 200 mg. After oral administration, plasma concentrations of losartan and its active metabolite decrease polyexponentially with a finite T1 / 2 of about 2 and 6-9 hours, respectively. When the dosing regimen of the drug is 100 mg once a day, there is no significant accumulation in the blood plasma of either losartan or its active metabolite. The excretion of losartan and its metabolites occurs through the intestine with bile and kidneys. After ingestion of 14C-losartan in men, about 35% of radioactivity is found in urine and 58% in feces. After iv injection of 14C-losartan 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. Values of losartan concentration in blood plasma in women with arterial hypertension were 2 times higher than the corresponding values in men with arterial hypertension. The concentrations of active metabolite in men and women did not differ. This apparent pharmacokinetic difference, however, has no clinical significance.

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

Patients with impaired renal function. Concentrations of losartan in blood plasma in patients with Cl creatinine above 10 ml / min did not differ from those in patients with unchanged renal function. The aUC of losartan in patients on hemodialysis was approximately 2 times greater than that of losartan AUC in patients with normal renal function. The concentrations of active metabolite in plasma did not change in patients with impaired renal function or patients on hemodialysis. Lozartan and its active metabolite are not excreted by the procedure of hemodialysis.

Indications of the drug Cozaar

arterial hypertension;

Reduction in the risk of associated cardiovascular morbidity and mortality in patients with hypertension and left ventricular hypertrophy, manifested by a cumulative reduction in the incidence of cardiovascular mortality, stroke and myocardial infarction;

Protection of kidney function in patients with type 2 diabetes mellitus with proteinuria - slowing the progression of renal failure, manifested by a decrease in the frequency of hypercreatininaemia; Frequency of development of the terminal stage of chronic renal failure (CRF), requiring hemodialysis or kidney transplantation and mortality rates;

Chronic heart failure with ineffective treatment with ACE inhibitors or intolerance to ACE inhibitors.

Contraindications

Hypersensitivity to any of the components of this drug;

Simultaneous application with aliskiren in patients with diabetes mellitus (see "Interaction");

Severe liver dysfunction (no experience of use);

Hereditary lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

Pregnancy and the period of breastfeeding;

Age to 18 years (efficacy and safety of use not established).

With caution: bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney; Hyperkalemia; State after kidney transplantation (no experience of application); Aortic or mitral stenosis; Obstructive hypertrophic cardiomyopathy; Heart failure with concomitant severe renal insufficiency; Severe heart failure (IV functional class according to the NYHA classification); Heart failure with life-threatening arrhythmias; cardiac ischemia; Cerebrovascular diseases; Primary hyperaldosteronism; Angioedema in history. Patients with reduced BCC (eg receiving treatment with large doses of diuretics) may experience symptomatic arterial hypotension.

Application of pregnancy and breastfeeding

The use of drugs directly affecting RAAS in the second and third trimesters of pregnancy can cause serious damage and even death of the developing fetus, therefore, when diagnosing pregnancy, the Cozaar drug should be immediately canceled and, if necessary, an alternative antihypertensive therapy is prescribed.

Therapy with COSAAR should not be started during pregnancy. If patients planning a pregnancy continue the therapy with losartan is considered necessary, losartan should be replaced with alternative antihypertensive drugs that have an established safety profile when applied during pregnancy.

Although there is no experience of using Cozaar in pregnant women, preclinical studies in animals have shown that the use of Cozaar leads to the development of serious embryonic and neonatal injuries and death of the fetus or offspring. It is believed that the mechanism of these phenomena is due to the impact on the RAAS.

Renal perfusion in the fetus, depending on the development of RAAS, appears in the II trimester, so the risk to the fetus increases if the drug Cozaar is used in the II or III trimesters of pregnancy. The use of ARA II in the II or III trimesters of pregnancy has a toxic effect on the fetus (decreased kidney function, development of oligohydramnion, slowing ossification of the skull) and newborn (renal failure, arterial hypotension, hyperkalemia). If the drug Cozaar was used in the second trimester of pregnancy and later, an ultrasound of the skull and kidney function is recommended.

Newborns, whose mothers took the drug Cozaar during pregnancy, should be carefully screened for the detection of arterial hypotension.

It is not known whether losartan is excreted in breast milk. Since many drugs are excreted in breast milk and there is a risk of developing potential adverse effects in a breastfed infant, a decision should be made to stop breastfeeding or to discontinue the drug, taking into account the need for taking the drug for the mother.

Side effects

In general, the preparation Cozaar is well tolerated by patients with hypertension, undesirable phenomena are of an easy and transient nature and do not require withdrawal of the drug. The total frequency of side effects of the drug Cozaar is comparable with this indicator when taking placebo. In controlled clinical trials of the drug in hypertensive patients, the only undesirable treatment-related response observed more often than with placebo was dizziness recorded in the Cozaar group with a frequency of ≥ 1%. In addition, ≤1% of patients had orthostatic reactions, depending on the dose of the drug. Rarely (≥0.01% and <0.1% of cases) reported skin rash, but the incidence was less than with placebo.

In these studies, ≥1% of patients with hypertension had the following adverse events when taking Cozaar (n = 2085) or placebo (n = 535), regardless of their association with treatment.

General: pain in the stomach - 1,7% (placebo - 1,7%); Weakness and increased fatigue - 3.8% (placebo - 3.9%); Chest pain - 1,1% (placebo - 2,6%); Peripheral edema - 1,7% (placebo - 1,9%).

From the CVS: a palpitation - 1% (placebo - 0.4%); Tachycardia - 1% (placebo - 1.7%).

From the digestive tract: diarrhea - 1.9% (placebo - 1.9%); Dyspepsia 1.1% (placebo 1.5%); Nausea - 1.8% (placebo - 2.8%).

From the musculoskeletal system: back pain - 1.6% (placebo - 1.1%); Muscle spasms - 1% (placebo - 1.1%).

From the side of the central nervous system: dizziness - 4.1% (placebo - 2.4%); Headache - 14.1% (placebo - 17.2%); Insomnia - 1,1% (placebo - 0,7%).

On the part of the respiratory system: cough - 3.1% (placebo - 2.6%); Edema of the nasal mucosa - 1.3% (placebo - 1.1%); Pharyngitis 1.5% (placebo 2.6%); Sinusitis - 1% (placebo - 1.3%); Infections of the upper respiratory tract - 6.5% (placebo - 5.6%).

Controlled clinical studies have shown that the Cozaar preparation is generally well tolerated by patients with hypertension and left ventricular hypertrophy. The most frequent adverse reactions associated with taking the drug were systemic and non-systemic dizziness, asthenia / weakness.

Controlled clinical studies have shown that the Cozaar preparation is generally well tolerated by patients with type 2 diabetes mellitus and proteinuria. The most frequent adverse reactions associated with taking the drug were dizziness, asthenia / weakness, marked decrease in blood pressure and hyperkalemia.

Controlled clinical studies have shown that the drug, Cozaar is generally well tolerated by patients with CHF. The adverse events observed during clinical trials were characteristic of this group of patients. The most frequent adverse reactions associated with taking the drug were dizziness and marked decrease in blood pressure.

In the HEAAL clinical trial (see Pharmacodynamics), the following clinically relevant adverse reactions associated with drug administration were observed more frequently in the group of patients taking the 150-mg Cozaar drug compared to the group of patients taking Cozaar at a dose of 50 mg : Hyperkalaemia, acute renal dysfunction, acute renal failure, marked decrease in blood pressure and an increase in the concentration of creatinine, urea and potassium in the blood. These unwanted reactions did not lead to much more frequent cancellation of therapy in patients taking the drug Cozaar in a dose of 150 mg.

The following undesirable reactions were noted in clinical practice during the post-marketing period.

Hypersensitivity reactions: anaphylactic reactions, angioedema with involvement of the larynx and pharynx, causing airway obstruction and / or edema of the face, lips, throat and / or tongue were rarely observed in patients taking losartan. Some of these patients had a history of angina stroke with other medications, including ACE inhibitors. Rarely reported on the occurrence of vasculitis, including purple Shenlaine-Genoch.

From the side of the digestive tract: hepatitis (rarely), a violation of the liver, vomiting.

General disorders and disorders at the injection site: a feeling of general discomfort.

On the part of the blood system: anemia, thrombocytopenia (rarely).

From the musculoskeletal system: myalgia, arthralgia.

From the side of the central nervous system: migraine, dysgeusia.

From the genitals and the breast: erectile dysfunction / impotence.

From the respiratory system: cough.

From the skin: urticaria, skin itching, redness of the skin, photosensitivity.

Laboratory indicators

In controlled clinical trials in patients with hypertension, clinically significant changes in standard laboratory parameters were rarely associated with the use of Cozaar. In 1.5% of patients, hyperkalemia was noted (serum potassium> 5.5 meq / L).

In a study in patients with type 2 diabetes mellitus with proteinuria, hyperkalemia developed in 9.9% of patients receiving Cozaar and 3.4% of patients receiving placebo (see "Specific guidance", Violation of the electrolyte balance). Elevated levels of ALT were noted in rare cases and usually returned to normal after the abolition of therapy.

Interaction

In clinical studies on the pharmacokinetic interactions of drugs, clinically significant interactions of losartan with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital and erythromycin have not been identified.

Rifampicin, as an inducer of the metabolism of drugs, reduces the concentration of the active metabolite of losartan in the blood. The clinical significance of this interaction is not established.

In clinical studies, the use of two inhibitors of the isoenzyme P450 3A4: ketoconazole and erythromycin has been studied. Ketoconazole did not affect the metabolism of losartan to the active metabolite after intravenous administration of losartan. Erythromycin did not have a clinically significant effect when taking losartan inside.

Fluconazole, an inhibitor of the isoenzyme P450 2C9, decreases the concentration of the active metabolite of losartan, however the pharmacodynamic significance of the simultaneous use of losartan and inhibitors of the isoenzyme P450 2C9 has not been studied. It is shown that in patients who do not metabolize losartan in the active metabolite, there is a very rare and specific defect in the isoenzyme P450 2C9. These data make it possible to assume that the metabolism of losartan to the active metabolite is carried out by the P450 2C9 isoenzyme, and not by the P450 3A4 isoenzyme.

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

As with the use of other drugs that affect the excretion of sodium, losartan may reduce the excretion of lithium. Therefore, with simultaneous use of lithium and ARA II preparations, careful monitoring of lithium concentration in serum should be carefully monitored.

NSAIDs, in t.ch. Selective inhibitors of COX-2, can reduce the effect of diuretics and other antihypertensive agents. Therefore, the antihypertensive effect of ARA II or ACE inhibitors can be weakened by simultaneous application of c NSAIDs, incl. With selective inhibitors of COX-2.

In some patients with impaired renal function (for example, in elderly patients or patients with dehydration, including those taking diuretics) receiving NSAID therapy, incl. Selective COX-2 inhibitors, the simultaneous use of ARA II or ACE inhibitors may cause further impairment of kidney function, including the development of acute renal failure. These effects are usually reversible. Therefore, the simultaneous use of these drugs should be conducted with caution in patients with impaired renal function.

Double blockade of RAAS with APA II, ACE inhibitors or aliskiren (renin inhibitor) is associated with an increased risk of arterial hypotension, hyperkalemia and renal dysfunction (including the development of acute kidney failure) compared with monotherapy. Regular monitoring of blood pressure, kidney function and electrolyte content in the blood are required for patients taking both Cosaar and other drugs that affect RAAS. Cosaar preparation should not be used simultaneously with aliskiren in patients with diabetes mellitus. It is necessary to avoid the simultaneous use of Cosaar and aliskiren in patients with renal insufficiency (glomerular filtration rate less than 60 ml / min).

Dosing and Administration

Inside, regardless of food intake.

The drug Cozaar can be taken in combination with other antihypertensive drugs. To provide the necessary dosing regimen, it is possible to take Cozaar in a dose of 50 mg.

Arterial hypertension. The standard initial and maintenance dose for the majority of patients is 50 mg of Cozaar preparation 1 time per day.

The maximum antihypertensive effect is achieved in 3-6 weeks from 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 Cozaar preparation once a day. In patients with reduced BCC (for example, when taking large doses of diuretics) the initial dose of losartan should be reduced to 25 mg once a day (see "Special instructions").

There is no need to select an initial dosage in elderly patients and patients with renal insufficiency, including patients on dialysis.

Patients with a history of liver disease are recommended to prescribe lower doses of the drug (see "Special instructions").

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

Kidney protection in patients with type 2 diabetes mellitus and proteinuria. The standard initial dose of Cozaar is 50 mg once a day. In the future, it is recommended to increase the dose of Cozaar to the maximum daily dose of 100 mg once a day, taking into account the degree of BP reduction.

The drug Cozaar can be prescribed in combination with other antihypertensive agents (diuretics, CCB, α- and β-adrenoblockers, antihypertensives for central ingestion), insulin and other hypoglycemic agents (sulfonylurea derivatives, glitazones and glucosidase inhibitors).

Chronic heart failure. The initial dose of Cozaar for patients with CHF is 12.5 mg once a day. Typically, the dose titrated with a weekly interval (ie 12.5, 25, 50, 100 mg / day, up to a maximum dose of 150 mg once a day), depending on individual tolerability.

Overdose

Symptoms: Overdose information is limited. The most likely manifestation of an overdose is a marked decrease in blood pressure and tachycardia; Bradycardia can occur due to parasympathetic (vagal) stimulation.

Treatment: symptomatic therapy. Lozartan and its active metabolite are not removed from the bloodstream by hemodialysis.

Special instructions

Hypersensitivity reactions. Angioedema (see "Side effects").

Arterial hypotension and disturbance of water-electrolyte balance or decrease in BCC. In patients with reduced BCC (eg, receiving treatment with large doses of diuretics) symptomatic arterial hypotension may occur. Correction of such conditions should be done prior to the appointment of Cosaar or to start treatment with a lower dose of Cosaar (see "Method of administration and dose").

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

During treatment with COSAAR, patients should not take potassium preparations or potassium-containing substitutes for table salt without first consulting with the doctor.

Aortic or mitral stenosis, obstructive hypertrophic cardiomyopathy. Like all drugs that have a vasodilating effect, ARA II should be administered with caution to patients with aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.

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

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

There is a lack of experience in using Cozaar in patients with heart failure and concomitant severe renal failure, in patients with severe heart failure (NYHA functional class IV), as well as in patients with heart failure and symptomatic life-threatening arrhythmias. Therefore, the drug Cozaar should be administered with caution to patients of these groups.

Primary hyperaldosteronism. In patients with primary hyperaldosteronism, as a rule, there is no positive response to therapy with antihypertensive drugs that act by inhibiting RAAS, so the use of Cozaar is not recommended in this group of patients.

Violation of the function of the liver. Data from pharmacokinetic studies indicate that the concentration of losartan in the blood plasma in patients with cirrhosis increases significantly, so patients with a history of liver disease should be prescribed a drug at a lower dose. There is no experience with the use of Cozaar in patients with severe impairment of liver function, so the drug should not be used in this group of patients (see Pharmacodynamics, Pharmacokinetics, Contraindications, Administration and Dosage).

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

Some drugs that affect RAAS can increase the concentration of urea in the blood and serum creatinine in patients with bilateral stenosis of the renal arteries or stenosis of the renal artery of a single kidney. It was reported about the occurrence of similar effects with the drug Cozaar. Similar violations of kidney function can be reversible after the abolition of therapy.

Special patient groups

Race. Analysis of the data of the entire population of patients included in the LIFE study of the effect of losartan on reducing the frequency of development of the main evaluation criterion in patients with AH (n = 9193) showed that the ability of losartan compared to atenolol reduces the risk of stroke and myocardial infarction, and Also reduce the rate of cardiovascular mortality in patients with AH and left ventricular hypertrophy (by 13%, p = 0.021) does not apply to patients of the Negroid race, although both regimens effectively lowered the level of blood pressure in these pa- ientov. Moreover, patients of the Negroid race who received atenolol had a lower risk of developing a basic composite evaluation criterion (ie, a lower combined rate of cardiovascular mortality, stroke, and myocardial infarction) compared to patients of the same race who took losartan (p = 0.03).

Based on observations, it can be concluded that ACE inhibitors and angiotensin antagonists are less effective in lowering blood pressure in patients of the Negroid race than in patients of other races. This effect is probably due to the high prevalence of patients with a reduced concentration of renin in the blood plasma in a population of patients of negroid race with AH.

Children and teenagers. The effectiveness and safety of the use of the drug Cozaar in children and adolescents under 18 years are not established.

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

Influence on the ability to drive vehicles and work with machinery. No studies have been conducted to assess the effect on the ability to drive vehicles and work with mechanisms, but some of the undesirable effects observed with the use of Cozaar may affect the ability to drive vehicles and work with mechanisms (see "Side effects").

Release form

Tablets, film-coated, 50 mg. On the 14 table. In PVC / aluminum blister. For 1 or 2 blisters are placed in a cardboard box.

Tablets, film-coated, 100 mg. By 7 or 14 table. In PVC / aluminum blister. 1 or 2 blisters are placed in a cardboard box.

Conditions of supply of pharmacies

On prescription.

Storage conditions of the drug Cozaar

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

The shelf life of the drug Cozaar

3 years.

Do not use beyond the expiration date printed on the package.