Irbesartan 300 mg, 28 film-coated tablets (Ozone) buy in Moscow, price from 540.00 rub. 89 pharmacies in Moscow

Irbesartan 300 mg, 28 film-coated tablets (Ozone)

Registration Certificate Holder

ATOLL (Russia)

Dosage form

Medicine - Irbesartan

Description

Film-coated tablets

white or almost white, round, biconvex; On a cross section, two layers are visible: a white or almost white core and a film shell.

1 tab.

irbesartan 300 mg

Excipients

: lactose monohydrate (milk sugar) - 186.4 mg, microcrystalline cellulose - 96 mg, croscarmellose sodium - 28.8 mg, povidone K25 - 19.2 mg, magnesium stearate - 6.4 mg, colloidal silicon dioxide - 3.2 mg.

Excipients (shell):

hypromellose - 8.8 mg, macrogol-4000 - 2.4 mg, titanium dioxide - 4.8 mg.

3 pcs. — contour cellular packaging (1) — cardboard packs. 3 pcs. — contour cellular packaging (2) — cardboard packs. 3 pcs. — contour cellular packaging (3) — cardboard packs. 3 pcs. — contour cellular packaging (4) — cardboard packs. 3 pcs. — contour cellular packaging (5) — cardboard packs. 3 pcs. — contour cellular packaging (6) — cardboard packs. 3 pcs. — contour cellular packaging (7) — cardboard packs. 3 pcs. — contour cellular packaging (8) — cardboard packs. 3 pcs. — contour cellular packaging (10) — cardboard packs. 4 things. — contour cellular packaging (1) — cardboard packs. 4 things. — contour cellular packaging (2) — cardboard packs. 4 things. — contour cellular packaging (3) — cardboard packs. 4 things. — contour cellular packaging (4) — cardboard packs. 4 things. — contour cellular packaging (5) — cardboard packs. 4 things. — contour cellular packaging (6) — cardboard packs. 4 things. — contour cellular packaging (7) — cardboard packs. 4 things. — contour cellular packaging (8) — cardboard packs. 4 things. — contour cellular packaging (10) — cardboard packs. 7 pcs. — contour cellular packaging (1) — cardboard packs. 7 pcs. — contour cellular packaging (2) — cardboard packs. 7 pcs. — contour cellular packaging (3) — cardboard packs. 7 pcs. — contour cellular packaging (4) — cardboard packs. 7 pcs. — contour cellular packaging (5) — cardboard packs. 7 pcs. — contour cellular packaging (6) — cardboard packs. 7 pcs. — contour cellular packaging (7) — cardboard packs. 7 pcs. — contour cellular packaging (8) — cardboard packs. 7 pcs. — contour cellular packaging (10) — cardboard packs. 10 pieces. — contour cellular packaging (1) — cardboard packs. 10 pieces. — contour cellular packaging (2) — cardboard packs. 10 pieces. — contour cellular packaging (3) — cardboard packs. 10 pieces. — contour cellular packaging (4) — cardboard packs. 10 pieces. — contour cellular packaging (5) — cardboard packs. 10 pieces. — contour cellular packaging (6) — cardboard packs. 10 pieces. — contour cellular packaging (7) — cardboard packs. 10 pieces. — contour cellular packaging (8) — cardboard packs. 10 pieces. — contour cellular packaging (10) — cardboard packs. 14 pcs. — contour cellular packaging (1) — cardboard packs. 14 pcs. — contour cellular packaging (2) — cardboard packs. 14 pcs. — contour cellular packaging (3) — cardboard packs. 14 pcs. — contour cellular packaging (4) — cardboard packs. 14 pcs. — contour cellular packaging (5) — cardboard packs. 14 pcs. — contour cellular packaging (6) — cardboard packs. 14 pcs. — contour cellular packaging (7) — cardboard packs. 14 pcs. — contour cellular packaging (8) — cardboard packs. 14 pcs. — contour cellular packaging (10) — cardboard packs. 15 pcs. — contour cellular packaging (1) — cardboard packs. 15 pcs. — contour cellular packaging (2) — cardboard packs. 15 pcs. — contour cellular packaging (3) — cardboard packs. 15 pcs. — contour cellular packaging (4) — cardboard packs. 15 pcs. — contour cellular packaging (5) — cardboard packs. 15 pcs. — contour cellular packaging (6) — cardboard packs. 15 pcs. — contour cellular packaging (7) — cardboard packs. 15 pcs. — contour cellular packaging (8) — cardboard packs. 15 pcs. — contour cellular packaging (10) — cardboard packs. 20 pcs. — contour cellular packaging (1) — cardboard packs. 20 pcs. — contour cellular packaging (2) — cardboard packs. 20 pcs. — contour cellular packaging (3) — cardboard packs. 20 pcs. — contour cellular packaging (4) — cardboard packs. 20 pcs. — contour cellular packaging (5) — cardboard packs. 20 pcs. — contour cellular packaging (6) — cardboard packs. 20 pcs. — contour cellular packaging (7) — cardboard packs. 20 pcs. — contour cellular packaging (8) — cardboard packs. 20 pcs. — contour cellular packaging (10) — cardboard packs. 25 pcs. — contour cellular packaging (1) — cardboard packs. 25 pcs. — contour cellular packaging (2) — cardboard packs. 25 pcs. — contour cellular packaging (3) — cardboard packs. 25 pcs. — contour cellular packaging (4) — cardboard packs. 25 pcs. — contour cellular packaging (5) — cardboard packs. 25 pcs. — contour cellular packaging (6) — cardboard packs. 25 pcs. — contour cellular packaging (7) — cardboard packs. 25 pcs. — contour cellular packaging (8) — cardboard packs. 25 pcs. — contour cellular packaging (10) — cardboard packs. 30 pcs. — contour cellular packaging (1) — cardboard packs. 30 pcs. — contour cellular packaging (2) — cardboard packs. 30 pcs. — contour cellular packaging (3) — cardboard packs. 30 pcs. — contour cellular packaging (4) — cardboard packs. 30 pcs. — contour cellular packaging (5) — cardboard packs. 30 pcs. — contour cellular packaging (6) — cardboard packs. 30 pcs. — contour cellular packaging (7) — cardboard packs. 30 pcs. — contour cellular packaging (8) — cardboard packs. 30 pcs. — contour cellular packaging (10) — cardboard packs. 10 pieces. - 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Indications

Arterial hypertension.

Nephropathy in patients with arterial hypertension and type 2 diabetes mellitus (as part of combination antihypertensive therapy).

Contraindications for use

Pregnancy, childhood, hypersensitivity to irbesartan.

pharmachologic effect

Antihypertensive agent, angiotensin II receptor antagonist. Blocks AT1 receptors, which leads to a decrease in the biological effects of angiotensin II, incl. vasoconstrictor effect, stimulating effect on the release of aldosterone and activation of the sympathetic nervous system. As a result, blood pressure decreases.

Reduces peripheral vascular resistance, reduces afterload. Reduces blood pressure (with a minimal change in heart rate) and pressure in the pulmonary circulation, and the decrease in blood pressure is dose-dependent.

Does not affect the concentration of triglycerides, cholesterol, glucose, uric acid in the blood plasma or the excretion of uric acid in the urine.

Drug interactions

When used simultaneously with potassium-sparing diuretics and potassium supplements, an increase in the potassium content in the blood plasma is possible.

When used simultaneously with hydrochlorothiazide, the additive nature of the hypotensive effect is manifested.

When used simultaneously with lithium carbonate, it is possible to increase the concentration of lithium in the blood plasma.

When used concomitantly, fluconazole may inhibit the metabolism of irbesartan.

Dosage regimen

The initial dose is 150 mg, if necessary, the dose is increased to 300 mg. In some cases (hypochloride diet, treatment with certain diuretics, vomiting or diarrhea preceding treatment, hemodialysis), a lower initial dose is used.

Irbesartan is taken orally 1 time/day, preferably at the same time of day.

Side effect

From the side of the central nervous system:

headache, dizziness.
From the digestive system:
nausea, vomiting.

Other:

malaise, weakness.

special instructions

Use with caution in patients with impaired renal function, after severe vomiting or diarrhea, as well as during simultaneous therapy with potassium-sparing diuretics or potassium preparations.

In experimental studies

The mutagenic, clastogenic and carcinogenic effects of irbesartan have not been established in laboratory animals.
Effect on the ability to drive vehicles and operate machines
There are no indications about the effect of irbesartan on the ability to drive vehicles and operate machines.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - Contraindicated. Restrictions when breastfeeding - Contraindicated.

Contraindicated for use during pregnancy.

If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.

Use for renal impairment

Restrictions for impaired renal function - With caution.

Use with caution in patients with impaired renal function.

Use in children

Restrictions for children - Contraindicated.

Contraindicated in children.

Irbesartan Canon, 150 mg, tablets, 28 pcs.

Age over 75 years.

For aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy (HOCM).

In case of hypovolemia, hyponatremia, which occurs, for example, during intensive diuretic therapy, hemodialysis, following a diet with limited salt intake, diarrhea, vomiting (risk of excessive reduction in blood pressure).

In patients with renal function dependent on the activity of the RAAS, such as patients with arterial hypertension, bilateral or unilateral renal artery stenosis, or patients with chronic heart failure of functional class III-IV (according to the NYHA classification).

With coronary heart disease and/or clinically significant cerebral atherosclerosis (with an excessive decrease in blood pressure, there is a risk of increased ischemic disorders, including the development of acute myocardial infarction and stroke).

In case of renal failure (requires monitoring of potassium levels and creatinine concentrations in the blood), recent kidney transplantation (lack of experience in clinical use).

With simultaneous use of non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 (COX-2) inhibitors (increased risk of developing renal dysfunction, including the possibility of acute renal failure and an increase in serum potassium, especially in elderly patients, patients with hypovolemia [including patients taking diuretics] or with impaired renal function.

When used in combination with ACE inhibitors or aliskiren, since, compared with monotherapy with dual blockade of the RAAS, there is an increased risk of developing an excessive decrease in blood pressure, hyperkalemia and renal dysfunction.

Excessive decrease in blood pressure - patients with hypovolemia.

The use of irbesartan to date has rarely been accompanied by an excessive decrease in blood pressure in patients with arterial hypertension without concomitant diseases. As with the use of ACE inhibitors, an excessive decrease in blood pressure, accompanied by clinical symptoms, can develop in patients with hyponatremia/hypovolemia (for example, as a result of intensive diuretic therapy, diarrhea or vomiting, following a diet with limited sodium intake), as well as in patients on hemodialysis. Before starting the use of irbesartan, it is necessary to correct hypovolemia and/or hyponatremia.

Patients with renal function dependent on the activity of the RAAS.

As a consequence of RAAS inhibition, deterioration of renal function can be expected in predisposed patients. In patients with renal function dependent on the activity of the RAAS (patients with arterial hypertension and renal artery stenosis of one or both kidneys; patients with chronic heart failure of functional class III and IV [NYHA classification]), treatment with drugs that affect the RAAS, has been associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. The possibility of a similar effect when using angiotensin II receptor antagonists, including irbesartan, cannot be excluded.

Kidney failure and kidney transplantation.

When using irbesartan in patients with renal failure, periodic monitoring of potassium levels and creatinine concentrations in the blood serum is recommended. There are no clinical data regarding the use of irbesartan in patients who have recently undergone a kidney transplant.

Patients with arterial hypertension and type 2 diabetes mellitus with impaired renal function.

The beneficial effect of irbesartan in slowing the progression of renal and cardiovascular disorders had varying degrees of severity in different groups of patients, it was less pronounced in women and non-Caucasian patients.

In the IDNT clinical trial in hypertensive patients with type 2 diabetes mellitus with proteinuria (>900 mg/day) in the subgroup of patients at high risk for renal artery stenosis, no patients receiving irbesartan experienced an acute early increase in serum creatinine concentrations. associated with renal artery stenosis.

Double blockade of the RAAS when combining irbesartan with ACE inhibitors or aliskiren.

Double blockade of the RAAS when using a combination of irbesartan with ACE inhibitors or aliskiren is not recommended, because Compared with monotherapy, there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and renal dysfunction.

Concomitant use of irbesartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure with GFR <60 ml/min/1.73 m2 body surface area and is not recommended in other patients.

Concomitant use of irbesartan in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

Hyperkalemia.

As with the use of other drugs that affect the RAAS, hyperkalemia may develop during treatment with irbesartan, especially in the presence of renal failure and/or heart disease. In such patients, it is recommended to monitor serum potassium levels.

Aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy.

As with other vasodilators, caution should be exercised when taking irbesartan in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.

Primary hyperaldosteronism.

Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act through inhibition of the RAAS. Therefore, the use of irbesartan in such cases is inappropriate.

Patients with coronary heart disease and/or clinically significant cerebral atherosclerosis.

As with the use of other antihypertensive drugs, a significant decrease in blood pressure in patients with coronary heart disease and/or severe cerebral atherosclerosis can lead to the development of myocardial infarction or stroke. Treatment of such patients should be carried out under strict blood pressure control.

Irbesartan tablet p o film 300 mg x28

Irbesartan Irbesartan

Compound

1 tablet 75 mg Active substances: irbesartan - 75.00 mg 1 tablet 150 mg Active substances: irbesartan - 150.00 mg 1 tablet 300 mg Active substances: irbesartan - 300.00 mg.

Pharmacotherapeutic group

Angiotensin II receptor antagonist

ATX code

C09CA04

pharmachologic effect

Irbesartan is a selective antagonist of angiotensin II receptors (AT1 type). Reduces the concentration of aldosterone in the blood plasma (does not suppress kinase II, which destroys bradykinin), eliminates the vasoconstrictor effect of angiotensin II, reduces total peripheral vascular resistance, reduces afterload, systemic blood pressure (BP) and pressure in the “lesser” circulation. Does not affect the concentration of triglycerides, cholesterol, glucose, uric acid in plasma and the excretion of uric acid. The maximum reduction in blood pressure is achieved 3-6 hours after taking the drug orally, and the antihypertensive effect persists for at least 24 hours. 24 hours after taking the recommended doses, the decrease in blood pressure is 60-70% compared to the maximum decrease in diastolic and systolic blood pressure in response to the use of the drug. When taken once a day at a dose of 150-300 mg, the degree of reduction in blood pressure (systolic/diastolic) at the end of the interdose interval (i.e., 24 hours after taking the drug) with the patient lying or sitting is on average 8-13/5- 8 mmHg (respectively) more compared to placebo. Taking the drug at a dose of 150 mg 1 time / day causes the same antihypertensive response (decrease in blood pressure before taking the next dose of the drug and the average decrease in blood pressure over 24 hours) as taking the same dose divided into 2 doses. The antihypertensive effect of irbesartan develops within 1-2 weeks, and the maximum therapeutic effect is achieved 4-6 weeks after the start of treatment. The antihypertensive effect persists during long-term treatment. After cessation of treatment, blood pressure gradually returned to its original value; no withdrawal syndrome was observed. The effectiveness of the drug does not depend on age and gender. Patients of the Negroid race respond less poorly to monotherapy with irbesartan (as well as to all other drugs that affect the renin-angiotensin-aldosterone system (RAAS)).

Indications for use

• Arterial hypertension (in monotherapy and in combination with other antihypertensive drugs, for example, thiazide diuretics, beta-blockers, long-acting slow calcium channel blockers (SCBCs), • nephropathy in arterial hypertension and type 2 diabetes mellitus (as part of a combination antihypertensive therapy).

Contraindications

• Hypersensitivity to irbesartan and to any of the auxiliary components of the drug, • pregnancy, • breastfeeding, • childhood and adolescence under 18 years of age (efficacy and safety have not been established), • galactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome, • simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or with moderate to severe renal failure (glomerular filtration rate (GFR) less than 60 ml/min/1.73 m2 body surface area). • simultaneous use with angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic nephropathy. • severe liver failure (more than 9 points on the Child-Pugh scale) (lack of clinical experience with use).

Method of administration and dosage

The drug should be taken orally regardless of the time of meal. Swallow the tablet whole with water. The initial and maintenance dose is 150 mg 1 time/day, regardless of meal time. Use of the drug at this dose provides more optimal 24-hour blood pressure control than at a dose of 75 mg/day. However, in some cases, especially in patients on hemodialysis or in patients over 75 years of age, the initial dose should be 75 mg. If the therapeutic effect is insufficient when using the drug Irbesartan at a dose of 150 mg 1 time / day, the dose can be increased to 300 mg once a day. In case of insufficient reduction in blood pressure in monotherapy with Irbesartan, diuretics (for example, hydrochlorothiazide 12.5 mg per day) or other antihypertensive drugs (for example, beta-blockers or long-acting BMCCs) may be added to treatment. In patients with arterial hypertension and type 2 diabetes mellitus, treatment should begin with a dose of 150 mg 1 time / day and gradually increase to 300 mg - the dose that is the preferred maintenance dose for the treatment of nephropathy. Use in Special Populations In clinical studies, there were generally no differences in efficacy and safety between patients aged 65 years and older and younger patients. Although it is recommended that patients over the age of 75 years begin treatment with a dose of 75 mg, usually no dosage adjustment is required in elderly patients. Patients with impaired renal function In patients with impaired renal function, no dosage adjustment is required. Patients with hypovolemia In patients with water-electrolyte imbalance, before starting the drug, circulating blood volume (CBV) should be restored and/or hyponatremia should be eliminated. For patients on hemodialysis, the initial dose should be 75 mg/day. Patients with impaired liver function In patients with impaired liver function of mild (5-6 points on the Child-Pugh scale) or moderate (7-9 points on the Child-Pugh scale) severity, no dosage adjustment is required. There is no clinical experience with the use of the drug in patients with severe (more than 9 points on the Child-Pugh scale) liver dysfunction. The safety and effectiveness of the drug in patients under 18 years of age have not been established.

Release form

Film-coated tablets 75, 150 and 300 mg. 3, 4, 7, 10, 14, 15, 20, 25 or 30 tablets in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil. 10, 14, 20, 28, 30, 40, 50, 60 or 100 tablets in polyethylene terephthalate jars for medicines, sealed with screw caps with first opening control or a “push-turn” system made of polypropylene or polyethylene, or polypropylene jars for medicines, sealed with tamper-evident pull-on lids made of polyethylene or polypropylene jars for medicines, sealed with tamper-evident pull-on lids made of high-density polyethylene. One can or 1, 2, 3, 4, 5, 6, 7, 8 or 10 blisters along with instructions for use are placed in a cardboard package (pack).

Terms of release from pharmacies

Dispensed by prescription.

Irbesartan

Excessive decrease in blood pressure - patients with hypovolemia

To date, the use of the drug irbesartan has rarely been accompanied by an excessive decrease in blood pressure in patients with arterial hypertension without concomitant diseases. As with the use of ACE inhibitors, an excessive decrease in blood pressure, accompanied by clinical symptoms, can develop in patients with hyponatremia/hypovolemia (for example, as a result of intensive diuretic therapy, diarrhea or vomiting, following a diet with limited sodium intake), as well as in patients on hemodialysis. Before starting the use of Irbesartan, it is necessary to correct hypovolemia and/or hyponatremia.

Use in patients with renal function dependent on RAAS activity

As a consequence of RAAS inhibition, deterioration of renal function can be expected in predisposed patients. In patients with renal function dependent on the activity of the RAAS (patients with arterial hypertension and renal artery stenosis of one or both kidneys, patients with chronic heart failure of NYHA functional class III and IV), treatment with drugs that affect the RAAS was associated with oliguria and/or progressive azotemia and, rarely, acute renal failure and/or death. The possibility of a similar effect when using ARA II, including irbesartan, cannot be excluded.

Renal dysfunction and kidney transplantation

When using the drug Irbesartan in patients with impaired renal function, periodic monitoring of potassium levels and creatinine concentrations in the blood serum is recommended. There are no clinical data regarding the use of irbesartan in patients who have recently undergone a kidney transplant.

Patients with arterial hypertension and type 2 diabetes mellitus with impaired renal function

Dual blockade of the RAAS when used with ACE inhibitors or aliskiren

Double blockade of the RAAS with simultaneous use of irbesartan with ACE inhibitors or aliskiren is not recommended, since, compared with monotherapy, there is an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and renal dysfunction.

The use of Irbesartan in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR less than 60 ml/min/1.73 m2 body surface area) (see sections “Contraindications”, “Interaction with other drugs”) and is not recommended in other patients.

The use of Irbesartan in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see sections “Contraindications”, “Interaction with other drugs”) and is not recommended in other patients.

Hyperkalemia

As with the use of other drugs that affect the RAAS, hyperkalemia may develop during therapy with Irbesartan, especially in the presence of renal failure and/or heart disease. In such patients, it is recommended to monitor serum potassium levels.

Aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy

As with the use of other vasodilators, caution should be exercised when taking Irbesartan in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act through inhibition of the RAAS. Therefore, the use of the drug in such cases is inappropriate.

Patients with coronary heart disease and/or clinically significant cerebral atherosclerosis

Cardiovascular disease is a leading cause of death and disability. One of the first places among cardiovascular pathologies belongs to arterial hypertension (AH), which currently causes 5.8% of all deaths. About 50 million, or 20%, of adults in the United States have hypertension, defined as a mean systolic blood pressure (SBP) ≥ 140 mmHg. Art., mean diastolic pressure (DBP) ≥ 90 mm Hg. Art. or the need for continuous use of antihypertensive drugs. The course of the disease is not controlled in 40–70% of patients of various ages [1].

Hypertension is the main cause of target organ damage: the heart, brain and kidneys. Characteristic attributes of hypertension are diseases such as heart and kidney failure, myocardial infarction, stroke and dissecting aortic aneurysm [4]. According to the American Heart Association (AHA), hypertension is one of the main risk factors for stroke, the incidence of which has increased by approximately 10% in the United States over the past 3 years. To prevent this trend from accelerating further, the AHA is pushing for increased oversight of hypertension treatment.

Unfortunately, modern antihypertensive therapy, despite its proven effect on mortality from hypertension, only provides effective blood pressure control in some patients. It is believed that among patients receiving drug treatment, normalization of blood pressure (SBP)

Accurate compliance by patients with medical prescriptions and their adherence to treatment are mandatory conditions for achieving hypertension control [2]. In addition, these factors affect the cost of treatment. The varying side effect profile of modern antihypertensive agents, such as diuretics, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers, may limit patient adherence to treatment and, consequently, the overall effectiveness of therapy. It has been shown that the likelihood of a patient discontinuing treatment is determined by the drug prescribed for initial therapy, likely reflecting varying tolerability of antihypertensive agents. An analysis of more than 3 million prescriptions of antihypertensive drugs demonstrated that only 26% of patients who began treatment with ACE inhibitors continued to take them at the 5th year of treatment, and for calcium channel blockers, diuretics and beta-blockers this figure was even lower (20, 19 and 16% respectively). It follows from this that an extremely important goal of therapy is to achieve the most accurate compliance by patients with medical prescriptions due to a favorable efficiency/tolerability ratio of treatment, which undoubtedly affects the control of the course of the disease as a whole.

In recent years, health authorities in many countries have been concerned about the widespread prevalence of diabetes mellitus (DM), especially type 2, which accounts for 97% of all DM cases. If in 2000 there were 115 million people with type 2 diabetes worldwide, by 2025 their number is projected to reach 300 million [3, 4]. It is known that diabetes can lead to the development of coronary artery disease, lesions of peripheral arteries, gangrene of the lower extremities, stroke, diabetic retinopathy, diabetic nephropathy with the possible development of renal failure, etc. In Russia, approximately 4.2 people suffer from diabetes, according to the Russian Endocrinology Center. % of the population.

It is known that 39% of patients with hypertension have type 2 diabetes, and, on the contrary, 71% of patients with type 2 diabetes have hypertension. It has also been established that 30–75% of diabetes complications are associated with hypertension. Type 2 diabetes is one of the main causes of the development of renal disorders, which, according to US experts, are detected in 43% of newly diagnosed patients. Approximately 10–40% of patients with type 2 diabetes subsequently develop chronic kidney disease, often requiring hemodialysis.

Irbesartan is an angiotensin II (AII) receptor blocker and is characterized by high selectivity and irreversible blockade of AT1 receptors, and its efficacy and tolerability profile helps to increase patient adherence to treatment. The effectiveness of irbesartan increases with increasing dose, while tolerability remains the same across different dosages as for placebo. Irbesartan (Aprovel) was developed at the Sanofi research center. This drug has been extensively studied in clinical studies.

Irbesartan lowers blood pressure by blocking the renin-angiotensin system (RAS) at the level of AII receptors. The RAS is a key regulator of blood pressure and sodium homeostasis. The effects of RAS are realized both at the cellular and organ levels through various physiological and pathophysiological mechanisms.

The function of the RAS is determined by a cascade of substrate-enzyme interactions, starting with the formation of angiotensin in the liver. Renin, secreted by the cells of the juxtaglomerular apparatus of the kidneys, converts angiotensinogen into angiotensin I (AI), an inactive decapeptide. Subsequently, ACE ensures the conversion of AI into the multifunctional peptide AII. Physiological effects of AII include increased blood pressure, vasoconstriction, stimulation of renal sodium reabsorption, release of aldosterone, negative feedback for the release of renin and vasopressin, stimulation of thirst, release of catecholamines from the adrenal glands and nerve endings, and release of prostaglandins. The RAS is also a mediator of metabolic, inotropic activity and myocardial hypertrophy processes. AII plays an important role in the pathophysiology of such clinical conditions as essential hypertension, renal hypertension, congestive heart failure, coronary insufficiency and various kidney diseases associated with albuminuria.

AII binds to receptors of the AT1 and AT2 subtypes. All known effects of AII that contribute to the development of hypertension are mediated through AT1 receptors. AT2 receptors have been found in fetal tissue, immature brain, skin wounds, and atretic ovarian follicles and are thought to be involved in growth and maturation. However, the physiological functions of these receptors remain unclear, in particular their role in the regulation of blood pressure is unknown. Recent studies performed on cell cultures have shown that activation of AT2 receptors under the influence of AII inhibits the growth of endothelial cells and smooth muscle cells of the vascular wall [6, 7].

Due to the fact that the RAS is likely involved in the development of hypertension and its complications, blocking the cascade reactions of this system has been the subject of many pharmacological studies. It turns out that adrenergic blockers can indirectly interrupt the cascade by inhibiting sympathetic stimulation of renin formation and release [15]. ACE inhibitors block the conversion of AI to AII. More complete blockade of the RAS can be achieved with either renin inhibitors or AII receptor blockers. Although renin inhibitors prevent AII synthesis, drugs with this mechanism of action have not yet been developed for clinical use due to their inadequate oral bioavailability.

ACE inhibition differs from AT1 receptor blockade in a number of important ways. Although high doses of ACE inhibitors suppress the conversion of AI to AII, there may be alternative pathways for this transformation. Unlike ACE inhibition, blockade of AT1 receptors completely suppresses the action of AII at the receptor level. Another important difference is determined by the effects of ACE inhibitors outside the RAS. ACE is identical to kinase II, the enzyme that degrades bradykinin, so ACE inhibitors, by blocking kinase II, promote the accumulation of bradykinin.

Blockade of kinase II, accumulation of bradykinin, neurotensin, met-enkephalin and substance P, observed with the use of ACE inhibitors [16], may be of great importance in the development of side effects such as cough and possibly angioedema. These side effects do not occur with complete blockade of AII action.

A study of the hypotensive effect of irbesartan in healthy male volunteers showed that a single dose of 150–300 mg of this drug provides complete blockade of the pressor action of AII 2–4 hours after administration; A 24-hour decrease in DBP after administration of 25–300 mg of irbesartan was observed in 30–70% of volunteers.

In randomized pharmacodynamic crossover studies in healthy volunteers, the blocking effect of equivalent doses of irbesartan, valsartan and losartan on DBP in the presence of exogenous angiotensin II was studied. The effect of irbesartan and valsartan was maximum after 4 hours, losartan - after 10 hours. The effect of irbersartan on DBP within 24 hours was significantly more pronounced than that of valsartan and losartan. With candesartan, irbesartan had approximately the same effect.

Changes in the time required to achieve a sustained reduction in blood pressure in patients with hypertension when taking irbesartan demonstrates the progression of the antihypertensive effect of the drug after the start of daily dosing. The hypotensive effect was observed within a few hours after taking the first dose of irbesartan, stabilized within 1–2 weeks and reached a maximum by 4–6 weeks of treatment. When taking the drug in doses of 150 and 300 mg once a day, the T/P ratio (the ratio of the residual hypotensive effect to the peak) for DBP was above 60%, which corresponds to a smooth 24-hour effect.

At a dose of 150 mg when taken once a day, irbesartan provided an optimal effect on blood pressure for 24 hours in an outpatient setting.

In an 8-week, double-blind study, the efficacy and safety of irbesartan administered orally at doses of 75 mg once daily, 150 mg once daily, and 75 mg twice daily were assessed using 24-hour ambulatory BP monitoring compared with placebo in patients with mild and moderate hypertension (DBP 95–110 mm Hg, with 24-hour monitoring > 85 mm Hg). The decrease in mean daily blood pressure was clinically and statistically significant in all three groups of patients. The same hypotensive effect was observed when irbesartan was prescribed in doses of 75 mg 2 times a day and 150 mg once a day, which indicates that there is no advantage when taking the drug twice a day. All three regimens for irbesartan were well tolerated by patients. At a dose of 150 mg once daily, the drug provided a clinically significant continuous reduction in blood pressure over 24 hours with the highest T/R ratio.

A meta-analysis of the results of 7 placebo-controlled studies of the effectiveness of irbesartan showed the same degree of reduction in SBP and DBP from baseline in men and women. Analysis of the effectiveness of the drug depending on age demonstrated identical values of the peak and residual effects of the drug in older and younger patients, which was confirmed in long-term open studies. The hypotensive effect of irbesartan manifested itself regardless of the race of the patients, although in black patients (low-renin population) it was somewhat less pronounced.

Irbesartan has a hypotensive effect in patients with any degree of hypertension. When analyzing the results of placebo-controlled studies, patients with hypertension were divided into 2 groups: with mild or moderate or severe hypertension, depending on the initial DBP (

It has been shown that irbesartan provides effective control of blood pressure in patients with hypertension and in the presence of renal failure. In an open, uncontrolled study, hypertensive patients with impaired renal function were divided into groups depending on the degree of renal failure: moderate, severe (creatinine clearance 30–60 ml/min and

In a number of randomized studies, the antihypertensive effect of irbesartan in patients with mild and moderate hypertension (DBP 95–110 mm Hg) was compared with the effect of atenolol, enalapril and amlodipine. The studies did not differ in the number of patients (about 100 in each treatment group), the distribution of patients by gender, age, race, or severity of hypertension. Decrease in blood pressure compared to baseline and the proportion of patients with normalization of blood pressure during treatment with irbesartan (DBP

In a 24-week double-blind study, treatment with irbesartan (75 mg/day with dose titration to 150 mg/day) provided a hypotensive effect comparable to that of atenolol (50 mg/day with dose titration to 100 mg/day), but the number of patients those who responded to irbesartan therapy by week 12 of treatment were higher (72 and 63%, respectively). Heart rate did not change in the group of patients receiving irbesartan, but, as expected, decreased in the atenolol group. The study showed that irbesartan, at least not inferior to atenolol in terms of hypotensive effect, was superior to it in terms of tolerability.

Another study compared irbesartan (75 mg/day with possible dose titration to 150–300 mg/day) with the ACE inhibitor enalapril, used in the full therapeutic dose range (10 mg/day with dose titration to 20–40 mg/day). Both drugs significantly reduced blood pressure without significant differences in effectiveness. Proportion of patients in whom it was possible to achieve normalization of blood pressure (DBP)

Another study compared irbesartan with enalapril in patients with severe hypertension (initial DBP 115–130 mmHg). The results of blood pressure measurements at week 12 of treatment showed that the administration of irbesartan (150 mg/day with possible dose titration to 300 mg/day) followed by the addition of hydrochlorothiazide and then atenolol and/or nifedipine to therapy was comparable in effectiveness to enalapril (20–40 mg/day) in combination with the same additional drugs. In both groups, blood pressure decreased by 40/30 mm Hg. Art. at the end of the interdose interval and at 45/36 mm Hg. Art. at the peak of action (3 hours after administration). At week 12, blood pressure normalized in 59% of patients receiving irbesartan and in 57% in the enalapril group. In patients who completed the 12th week of the study, blood pressure normalized more quickly when treated with irbesartan. On the other hand, patients receiving enalapril more often required 3 or more drugs. The incidence of cough as a side effect of therapy was significantly higher in the enalapril group (13 vs. 2%; p

In a randomized placebo-controlled trial, irbesartan at a dose of 300 mg was superior in antihypertensive efficacy to losartan at a dose of 100 mg. After 8 weeks of therapy, irbesartan 300 mg, irbesartan 150 mg and losartan 100 mg reduced DBP by 11.6; 9.7 and 8 mm Hg. Art. from the initial level, respectively. The differences between the hypotensive effects of irbesartan 300 mg and losartan 100 mg were significant starting from 1 week of treatment. The decrease in SBP by the 8th week of therapy when using irbesartan 300 mg was also more pronounced. By this time, 63, 60 and 56% of patients responded to treatment with irbesartan in doses of 300 and 150 mg and losartan in a dose of 100 mg, respectively [10]. Both drugs were well tolerated. The incidence of side effects and drug discontinuation due to side effects was comparable with losartan (57 and 3.6%) and placebo (53 and 3.4%). These phenomena occurred less frequently during treatment with irbesartan: the incidence of side effects when using this drug at a dose of 300 mg and its withdrawal was 44 and 1.4%, respectively.

Irbesartan demonstrated comparable efficacy to amlodipine in a pilot study in patients with type 2 diabetes with diabetic nephropathy and hypertension (SBP ≥ 135 mm Hg, DBP ≥ 85 mm Hg). In this 12-week randomized study, irbesartan was prescribed at a daily dose of 75–300 mg once daily to 24 patients, amlodipine at a daily dose of 2.5–10 mg once daily to 23 patients (initial doses could be doubled at 4 and 8 weeks ). Clinical characteristics of patients in both groups, including duration of diabetes, were identical.

Both treatments resulted in comparable reductions in DBP at the respective time points, although the mean reduction in SBP was slightly greater with amlodipine. Irbesartan reduced urinary protein excretion by 8.5% of baseline values, while amlodipine increased this figure by 19.7%. Despite the similar hypotensive effect of the drugs, creatinine clearance increased when using irbesartan, and decreased when using amlodipine. The difference in changes in creatinine clearance during treatment with irbesartan and amlodipine was statistically significant (p

It has been established that in half of patients with type 2 diabetes, proteinuria is detected 5–10 years after the onset of the disease. In addition, it is known that in developed countries, patients with severe renal failure undergo regular hemodialysis in 2/3 of cases, and every third patient undergoes a kidney transplant. Thus, the cost burden for the government due to kidney failure is enormous. Thus, in the USA, 15 billion dollars are spent annually on the treatment of severe renal failure, including 59 thousand per patient with type 2 diabetes. Mortality from renal failure caused by diabetic nephropathy is 1.5–2 times higher than Among patients without diabetes, only 20% of patients with diabetes and severe renal failure live more than 5 years from the start of hemodialysis [10]. All this makes the problem of preventing the development of new cases of type 2 diabetes and diabetic nephropathy extremely urgent. In recent years, the possibility of using RAS blockers—ACE inhibitors and AII antagonists—for this purpose, including in patients with hypertension, has been actively studied.

In the LIFE study [11], one year after the start of the use of losartan and atenolol in patients with hypertension, there were no differences in the incidence of new cases of type 2 diabetes, but by the end of the study (an average of 4.8 years), the risk of developing diabetes in the losartan group was lower. 25% lower than in the atenolol group (p

In the recently completed larger VALUE study [13], which included 15,245 hypertensive patients treated with valsartan or amlodipine, the risk of developing diabetes during treatment with an AII antagonist was 23% lower than with treatment with a calcium antagonist (p

In the small ALPINE study, patients with hypertension received candesartan in addition to felodipine or hydrochlorothiazide in combination with atenolol for a year. The number of cases of type 2 diabetes in the candesartan group at the end of the study was lower than in the hydrochlorothiazide group. Favorable changes in glucose and insulin levels were found with the use of candesartan.

Considering the renoprotective properties of irbesartan, Pohler et al. conducted a pilot study in which this drug was prescribed to patients with hypertension in combination with type 2 diabetes and diabetic nephropathy for 12 months. Irbesartan has been shown to reduce proteinuria by 9%. A larger, randomized, placebo-controlled trial using a similar protocol was performed as part of the PRIME program [13].

The IRMA-2 study (Irbesartan Microalbuminuria Type 2 Diabetic Study) included 590 patients suffering from hypertension and type 2 diabetes with the initial stage of renal damage (microalbuminuria 20–200 mg/min) and normal blood creatinine levels. About 400 patients received irbesartan 150 or 300 mg/day, 201 received placebo [14].

Irbesartan in both doses reduced SBP and DBP, and when used at a dose of 150 mg/day, additional antihypertensive drugs were prescribed to 45% of patients, and at a dose of 300 mg/day – to 43% of patients. In the placebo group, other antihypertensive agents (diuretics, beta-blockers, or calcium antagonists) were required in 56% of cases. Normalization of the rate of urinary excretion of albumin was observed in 21% of patients in the control group and 34% of patients receiving irbesartan at a dose of 300 mg/day. It should be noted that in one small study, irbesartan similarly reduced proteinuria in hypertensive or normotensive patients.

A continuation of the IRMA-2 study was the larger IDNT study (Irbesartan Diabetic Nephropathy Trial), which included 1714 patients with hypertension and type 2 diabetes who had proteinuria more than 900 mg/day and an increase in creatinine levels. Patients were randomized to receive irbesartan 300 mg/day, amlodipine 10 mg/day, or placebo. The average duration of follow-up for patients was 2.6 years.

The primary endpoints of the IDNT study were doubling of blood creatinine, development of end-stage renal disease requiring dialysis or kidney transplantation, and all deaths. In addition, the combined risk of fatal and nonfatal vascular events, including heart failure requiring hospitalization, stroke, and lower limb amputations, was assessed.

A doubling of creatinine levels when taking irbesartan was observed in 17% of patients, and in the amlodipine and placebo groups - in 25 and 24% of patients, respectively. Thus, the relative risk of achieving this endpoint in the irbesartan group was 33% (p = 0.003) and 37% (p

The risk of developing end-stage renal failure in the group of patients receiving irbesartan was 23% lower than when taking amlodipine and placebo. The average annual rate of change in glomerular filtration rate was the lowest with irbesartan use. A decrease in proteinuria was observed in 33% of patients receiving irbesartan, versus 6 and 10% in the amlodipine and placebo groups, respectively.

The combined incidence of cardiovascular complications in the irbesartan group was slightly lower than in the amlodipine and placebo groups.

Comparison of the data obtained in the IDNT study with the results of the RENAAL study [17], which was similar in design, which used losartan, allows us to compare the effectiveness of two AII receptor inhibitors. In particular, it was shown that, compared with the placebo group, the relative risk of doubling creatinine levels, developing end-stage renal failure or death was reduced with losartan by 16% (p = 0.02), and with irbesartan by 20% (p = 0.02). Separate analysis of outcomes showed that the risk of doubling creatinine levels was reduced by 25% (p = 0.005) when treated with losartan, and by 33% (p = 0.003) when treated with irbesartan. Large studies using irbesartan (Aprovel) to prevent kidney damage in hypertension and hypertension in combination with type 2 diabetes are currently ongoing or have just been completed, data on which are presented in the table. It is hoped that the results of these multicenter studies, the publication of which is expected in the near future, will add to the evidence base for the use of AII receptor antagonists to prevent kidney damage both in patients with isolated hypertension and in patients with a combination of hypertension and type 2 diabetes.