Irbebartan - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate - 25.00 mg, povidone - 3.75 mg, microcrystalline cellulose - 13.88 mg, croscarmellose sodium - 3.38 mg, silicon dioxide colloid - 2.25 mg, sodium stearyl fumarate - 3.25 mg

shell: ready-made mixture "Sepiphilm 003" - 2.22 mg, hypromellose -1.11 mg, macrogol stearate - 0.22 mg, microcrystalline cellulose - 0.89 mg, ready mixture "Sepipers AP7001 white" - 0.44 mg: hypromellose - 0.02 mg, propylene glycol - 0.13 mg, titanium dioxide - 0.13 mg, purified water * - 0.16 mg.

Tablets, film-coated, 150 mg:

One tablet contains:

active substance: irbesartan - 150,00 mg

Excipients: lactose monohydrate - 50.00 mg, povidone - 7.50 mg, microcrystalline cellulose - 27.75 mg, croscarmellose sodium - 6.75 mg, silicon dioxide colloid - 4.50 mg, sodium stearyl fumarate - 6, 50 mg

shell: ready-made mixture "Sepyphilm 003" - 4.43 mg, hypromellose - 2.22 mg, macrogol stearate - 0.44 mg, microcrystalline cellulose - 1.77 mg, ready mixture "Sepipers AP7001 white" - 0.89 mg: hypromellose - 0.04 mg, propylene glycol 0.27 mg, titanium dioxide 0.27 mg, purified water * 0.31 mg.

Film-coated tablets, 300 mg:

One tablet contains:

active substance: irbesartan - 300,00 mg;

Excipients: lactose monohydrate - 100.00 mg, povidone - 150,0 mg, cellulose microcrystalline - 55,50 mg, croscarmellose sodium - 13.50 mg, silicon dioxide colloid - 9.00 mg, sodium stearyl fumarate - 13.00 mg,

Sheath: ready-made mixture "Sepyphilm 003" - 8.86 mg, hypromellose - 4.43 mg, macrogol stearate - 0.89 mg, microcrystalline cellulose - 3.54 mg, ready mixture "Sepipers AP7001 white" - 1.77 mg: hypromellose - 0.09 mg, propylene glycol - 0.53 mg, titanium dioxide - 0.53 mg, purified water * - 0.62 mg.

* - a component of the finished mixture "Sepipers AP7001 white".

Description:The tablets covered with a film cover, white or almost white color, round, biconcave. On the cross section, the core of the tablet is white or almost white in color.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.04 Irbesartan

Pharmacodynamics:

Irbesartan is a selective antagonist of angiotensin II (such as AT₁). Irbesartan does not require metabolic activation to acquire pharmacological activity. Angiotensin II is an important component of the renin-angiotensin-aldosterone system (RAAS) and is involved in the pathogenesis of arterial hypertension, as well as sodium homeostasis.

Irbesartan blocks all physiologically significant effects of angiotensin II, regardless of the source or route of its synthesis, including its pronounced vasoconstrictor and aldosterone-secreting effects, which are realized through AT receptors₁ located on the surface of the smooth muscle cells of the vessels and in the adrenal cortex. He does not have agonistic activity to AT₁ receptors and has a much greater (more than 8500 times) affinity for AT₁receptors than with AT₂receptors (receptors, not associated with regulation of the cardiovascular system). Irbesartan does not inhibit RAAS enzymes (such as renin, angiotensin converting enzyme [ACE]) and does not affect the receptors of other hormones or ion channels,involved in the regulation of blood pressure (BP) and homeostasis of sodium. Blocking Irbesartan AT₁receptors interrupts the feedback loop in the renin-angiotensin system, which leads to an increase in plasma concentrations of renin and angiotensin II. After taking irbesartan in recommended doses, the plasma concentration of aldosterone decreases, without significantly affecting the potassium content in the blood serum (the mean value of its increase is <0.1 mEq / L). Irbesartan has no significant effect on serum concentrations of triglycerides, cholesterol and glucose. Irbesartan does not affect the concentration of uric acid in the blood serum or the rate of excretion of uric acid by the kidneys.

The antihypertensive effect of irbesartan manifests itself after taking its first dose and becomes significant within 1-2 weeks of admission, its maximum effect is reached by 4-6 weeks of treatment. In long-term clinical studies, the antihypertensive effect of irbesartan has been maintained for more than one year.

With a single intake within a day of irbesartan in doses up to 900 mg antihypertensive effect is dose-dependent. Irbesartan at a single dose during the day at doses of 150-300 mg reduces blood pressure, measured in the "lying" or "sitting" position at the end of the inter-dose interval (24 hours after taking the dose of irbesartan, ie, before taking the next dose of irbesartan) an average of 8-13 / 5-8 mm Hg. Art. (systolic / diastolic blood pressure) compared with placebo. The maximum decrease in blood pressure is achieved in 3-6 hours after a single oral intake and is maintained, at least for 24 hours.

The antihypertensive effect of irbesartan before taking the next dose is 60-70% of the maximum values of the decrease in diastolic and systolic blood pressure. The optimal decrease in blood pressure during 24 hours is achieved with the intake of irbesartan once a day. Taking the drug at a dose of 150 mg once a day leads to an antihypertensive effect comparable to a two-time intake of the same dose divided into two doses.

Irbesartan approximately in the same degree reduces BP in the "standing" and "lying". Orthostatic effects are rare, however, as with the administration of ACE inhibitors, in patients with hyponatraemia and / or hypovolemia, excessive BP reduction with clinical manifestations is possible.

The antihypertensive effect of irbesartan and thiazide diuretics is additive. In patients with insufficient blood pressure reduction with monotherapy with irbesartan, the addition of low doses of hydrochlorothiazide (12.5 mg) once a day leads to an additional BP reduction of 7-10 / 3-6 mm Hg. Art. (systolic / diastolic blood pressure) compared with the addition of a placebo.

The effectiveness of irbesartan does not depend on age or sex. As with the use of other drugs that affect RASS, the antihypertensive effect of irbesartan in patients of the Negroid race is markedly less pronounced, however, when irbesartan is used simultaneously with low doses of hydrochlorothiazide (eg 12.5 mg per day), the antihypertensive response in patients of the Negroid race approaches on the effectiveness of this in patients of the Caucasian race.

After discontinuing irbesartan, blood pressure returns to the initial level gradually. The syndrome "cancellation" is not observed.

In a multicenter, randomized, controlled active substance (amlodipine) and placebo, a double-blind clinical trial IDNT, with the participation of 1715 patients with arterial hypertension and type 2 diabetes mellitus (proteinuria ≥ 900 mg / day and serum creatinine concentration in the 1.0-3.0 mg / dl range), 20% (p = 0.024) decrease (compared with placebo) and 23% (p = 0.006) decrease compared with amlodipine) of the relative risk of the first occurrence of any of the following conditions: a doubling of serum creatinine concentration, development of end-stage renal failure, or death from any of the causes (with comparable BP reduction with irbesartan and amlodipine).

In a multicenter, randomized, placebo-controlled, double-blind clinical study on the effects of irbesartan on microalbuminuria in patients with arterial hypertension and type 2 diabetes mellitus (IRMA 2), involving 590 patients with arterial hypertension and type 2 diabetes mellitus having microalbuminuria (20-200 μg / min, 30-300 mg / day) and normal kidney function (serum creatinine concentration <1.5 mg / dl in men and <1.1 mg / dl in women), the effect of long-term treatment (within 2 years) of irbesartan on the progression of clinically significant proteinuria was evaluated. When taking the drug at a dose of 300 mg per day, a 70% reduction in the relative risk of developing clinically significant proteinuria was demonstrated (compared with placebo,p = 0.0004), and at a dose of 150 mg, a 39% reduction in the relative risk of developing clinically significant proteinuria (compared with placebo, p = 0.085). The delay in the progression of clinically significant proteinuria was noted after only three months and continued throughout the 2-year period of the clinical study. The decrease in the 24-hour creatinine clearance between the treatment groups did not differ significantly. The regression of microalbuminuria to normal albuminuria (<20 mcg / min, <30 mg / day) was more frequently observed in the irbesartan group at a dose of 300 mg (34%) compared with the placebo group (21%).

Pharmacokinetics:

Absorption

After oral administration irbesartan quickly and completely absorbed, its absolute bioavailability is approximately 60-80%. Simultaneous food intake does not significantly affect the bioavailability of irbesartan. After oral administration, the maximum plasma concentration (C_m_Oh) irbesartan is achieved after 1.5-2 h.

Distribution.

The connection with plasma proteins is approximately 96%. Binding to the cellular components of blood is negligible. The volume of distribution is 53-93 liters.

Metabolism.

After ingestion or intravenous administration ¹⁴C-irbesartan 80-85% of the radioactivity circulating in the blood plasma is due to the unchanged irbesartan. Irbesartan metabolized by the liver by oxidation and conjugation with glucuronic acid. The main metabolite in the systemic circulation is irbesartan glucuronide (approximately 6%). Oxidation of irbesartan is carried out, mainly, with the help of cytochrome P450 isoenzyme CYP2C9, isoenzymatic participation CYP3A4 in the metabolism of irbesartan is insignificant. Irbesartan is not metabolized by most isoenzymes, which usually participate in the metabolism of drugs (isozymes CYP1A1, CYP1A2, CYP2A6, CYP2B6, CYP2D6 or CYP2E1), and does not cause their inhibition or induction. Irbesartan Does not induce or inhibit isoenzyme CYP3A4.

Excretion.

Irbesartan and its metabolites are excreted from the body, both through the intestines (with bile) and the kidneys. After ingestion or intravenous administration ¹⁴C-irbesartan, about 20% of the radioactivity is found in the urine, and the rest is in the feces. Less than 2% of the administered dose is excreted by the kidneys in the form of unchanged irbesartan.

The final half-life (T_1/2) irbesartan is 11-15 hours.The total clearance of intravenously administered irbesartan is 157-176 ml / min, and its renal clearance is 3-3.5 ml / min. With a daily once-daily irbesartan intake, the equilibrium plasma concentration (Css) is achieved after 3 days, while its limited accumulation in the blood plasma (less than + 20%) is observed.

Special patient groups

Influence of sex on the pharmacokinetics of irbesartan

In women (compared with men), slightly higher plasma concentrations of irbesartan were observed. However, gender-related differences in T_1/2and the accumulation of irbesartan was not detected. Correction of irbesartan dose in women is not required. There were no gender-related differences in the effects of irbesartan.

The pharmacokinetics of irbesartan in elderly patients

Values AUC (area under the pharmacological curve "concentration-time") and C_m_Oh irbesartan in elderly patients (65-80 years old) with clinically normal renal and hepatic function were approximately 20-50% higher than in younger patients (18-40 years old). Finite T₁_/2 are comparable. There were no age-related differences in the effects of irbesartan.

The pharmacokinetics of irbesartan in liver function disorder

In patients with mild (functional class A or 5-6 points on the Child-Pugh scale) and moderately expressed (functional class B or 7-9 on the Child-Pugh scale) with hepatic insufficiency due to cirrhosis, the pharmacokinetic parameters of irbesartan do not change significantly.

The pharmacokinetics of irbesartan in renal dysfunction

In patients with impaired renal function or patients undergoing hemodialysis, the pharmacokinetics of irbesartan do not change significantly. Irbesartan is not excreted from the body by hemodialysis.

Influence of race on the pharmacokinetics of irbesartan

In representatives of the Negroid race without hypertension AUC and T |_/2irbesartan were approximately 20-25% higher than in the representatives of the Caucasoid race; FROM_m_Oh irbesartan in them was almost identical with that of representatives of the Caucasoid race.

The pharmacokinetic parameters of irbesartan are linear and proportional in the dose range from 10 to 600 mg; at doses in excess of 600 mg (a dose twice the recommended maximum dose of the drug), the kinetics of irbesartan becomes nonlinear (decrease in absorption).

Indications:

- Arterial hypertension (in monotherapy and in combination with other antihypertensive drugs, for example, thiazide diuretics, beta-adrenoblockers, blockers of "slow" calcium channels of long-acting BCCC).

- Nephropathy in arterial hypertension and type 2 diabetes mellitus (as part of combined antihypertensive therapy).

Contraindications:

Hypersensitivity to irbesartan or any of the excipients of the drug;

Simultaneous use with medicinal products containing aliskiren, in patients with diabetes mellitus or with moderately severe and severe renal failure (glomerular filtration rate [GFR] <60 ml / min / 1.73 m²body surface);

Simultaneous use with ACE inhibitors in patients with diabetic nephropathy;

Pregnancy;

The period of breastfeeding;

Age to 18 years (effectiveness and safety not established).

Hereditary intolerance to galactose, insufficiency of lactase or glucose-galactose malabsorption;

In severe hepatic insufficiency (functional class C or more than 9 points on the Child-Pugh scale) (lack of clinical experience).

Carefully:

Age over 75 years.

With stenosis of the aortic or mitral valve or hypertrophic obstructive cardiomyopathy (GOKMP).

With hypovolemia, hyponatremia, arising, for example, with intensive diuretic therapy, hemodialysis, adherence to a diet with restricted intake of table salt, diarrhea, vomiting (the risk of excessive blood pressure lowering).

In patients with renal function that depends on RAAS activity, such as patients with hypertension with bilateral or unilateral stenosis of the renal arteries or patients with chronic heart failure III-IV functional class (according to classification NYHA) (see "Special instructions").

In ischemic heart disease and / or clinically significant atherosclerosis of the cerebral vessels (with excessive decrease in blood pressure there is a risk of increasing ischemic disorders, up to the development of acute myocardial infarction and stroke).

In case of renal insufficiency (control of potassium content and creatinine concentration in the blood is required), recent kidney transplantation (lack of clinical experience).

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

When used in combination with ACE inhibitors or aliskiren, as compared to monotherapy with double blockade of RAAS, there is an increased risk of excessive blood pressure lowering, hyperkalemia and renal dysfunction (see section "Special instructions").

Pregnancy and lactation:

Pregnancy

Experience with the use of irbesartan in pregnancy is absent. Taking into account the fact that during the reception of ACE inhibitors by pregnant women in the second and third trimesters of pregnancy, the developing fetus was damaged and died, irbesartan, like any other drug that acts directly on RAAS, can not be used during pregnancy (I, II, III trimesters).

In the diagnosis of pregnancy during treatment with irbesartan should be as soon as possible to stop taking it.

Breastfeeding period

It is not known whether the blood is excreted irbesartan or its metabolites into breast milk. Irbesartan is contraindicated during breastfeeding. Therefore, after evaluating the ratio of the perceived benefit from taking the drug to the mother and the potential risk to the baby, stop breastfeeding or taking irbesartan.

Dosing and Administration:

The drug should be taken orally, regardless of the time of ingestion. The tablet is swallowed whole, washed down with water.

Usually the initial dose of irbesartan is 150 mg once a day. Patients who, in order to achieve target BP values, require an additional reduction, the dose can be increased to 300 mg once daily.

In case of insufficient blood pressure reduction during monotherapy treatment irbesartan may be added diuretics (e.g. hydrochlorothiazide 12.5 mg per day) or other antihypertensives (e.g. beta-blockers BCCI or long-acting).

In patients with nephropathy in hypertension and type 2 diabetes mellitus, the preferred maintenance dose is 300 mg once daily.

Patients with reduced circulating blood volume (COC) (including diarrhea, vomiting) with hyponatremia, on the background of diuretic treatment or a diet with restricted intake of table salt, or who are on hemodialysis, or patients older than 75 years, the recommended dose of irbesartan is 75 mg /day.

Use in selected patient groups

Children and teens

At the moment, the safety and effectiveness of the drug in patients of childhood and adolescence is not established.

Elderly patients

Usually, elderly patients do not need a dose reduction. Patients who took irbesartan in clinical studies, overall, there was no difference in efficacy and safety between patients 65 years of age and older and younger patients. It is recommended that treatment of patients over the age of 75 begin with a dose of 75 mg.

Patients with hepatic insufficiency

Usually in patients with impaired liver function (mild and moderate severity)no dose reduction is required. The experience of using the drug in patients with severe hepatic insufficiency is absent.

The initial dose of the drug in patients on hemodialysis should be 75 mg / day.

Patients with renal insufficiency

Usually, patients with renal insufficiency (regardless of its severity) do not need a dose reduction.

Patients with hypovolaemia

In patients with severe hypovolemia and / or hyponatremia, such as patients receiving intensive diuretic therapy or who are on hemodialysis, hypovolemia and hyponatremia should be corrected before starting irbesartan.

Side effects:

The following undesirable phenomena are presented in accordance with the following gradations of their incidence (according to the classification of the World Health Organization (WHO)): very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000, including individual messages); unknown frequency (according to available data, it is not possible to determine the frequency of occurrence of an undesirable phenomenon).

The safety of irbesartan has been studied in clinical studies in approximately 5,000 patients, including 1,300 patients with hypertension,who took the drug for more than 6 months, and 400 patients who took the drug for one year or more. Adverse events in patients taking irbesartan, were usually mild and transitory, and their frequency was not related to the magnitude of the dose taken. The incidence of adverse events was independent of sex, age, and race.

In placebo-controlled studies in which 1,655 patients took irbesartan (on average for 1-3 months), discontinuation of treatment due to the development of any clinical or laboratory adverse events was required in 3.3% of patients taking irbesartan, and in 4.5% of patients taking placebo (the differences were statistically significant).

Undesirable phenomenon, observed in placebo-controlled clinical trials with the use of irbesartan in hypertension, probably or possibly related to its reception, or without the established relationship with taking the drug

The incidence of the following adverse events with irbesartan was statistically not significantly different from that observed with placebo.

Disturbances from the nervous system

Often: dizziness, headache;

Infrequent: orthostatic dizziness.

Heart Disease

Infrequent: swelling, tachycardia

Disturbances from the respiratory system, chest organs and the mediastinum

Infrequently: cough

Disorders from the gastrointestinal tract

Often: nausea / vomiting

Infrequent: diarrhea, indigestion / heartburn

Violations of the genitals and mammary gland

Infrequently: sexual dysfunction

Common violations

Often: increased fatigue

Infrequent: chest pain

Laboratory and instrumental data

During controlled clinical trials in patients with hypertension, there were no clinically significant changes in laboratory parameters. No special monitoring of laboratory parameters for patients with hypertension is required, irbesartan.

Adverse events observed in controlled clinical trials, when irbesartan is used in patients with nephropathy in hypertension and type 2 diabetes mellitus (clinical trials IDNT and IRMA 2)

Adverse events were similar to those in patients with hypertension, with the exception of orthostatic symptoms (dizziness (10.2%) (with placebo 6%), orthostatic dizziness (5.4%) (when taking placebo 2.7%) and orthostatic hypotension (5.4%) (when taking placebo 3.2%).

The percentage of discontinuation due to orthostatic symptoms when taking irbesartan compared with placebo was 0.3 for dizziness, 0.5% for vertigo, 0.2 for orthostatic dizziness and 0.0% for orthostatic hypotension, and 0.0% for orthostatic hypotension. , 0%, respectively.

Violations from laboratory indicators

Hyperkalemia

In a clinical study IDNT the percentage of patients with hyperkalemia (> 6 mEq / L) was 18.6% in the irbesartan group, compared with 6% in the placebo group. In a clinical study IRMA 2 percent of patients with hyperkalemia (> 6 mEq / L) was 1.0 % in the irbesartan group, and in the placebo group, hyperkalaemia was not observed.

In a clinical study IDNT the frequency of cessation of treatment due to the development of hyperkalemia with the use of irbesartan and placebo was 2.1% and 0.36%, respectively. In a clinical study IRMA the frequency of cessation of treatment due to the development of hyperkalemia with the use of irbesartan and placebo was 0.5% and 0%, respectively.

Undesirable effects observed during post-marketing application of irbesartan

Immune system disorders

Rarely: like all of angiotensin II receptor antagonists, noted very rare cases of allergic reactions such as urticaria, angioedema.

The following undesirable phenomena were identified when irbesartan was used since the moment of entering the irbesartan market.

Violations of the blood and lymphatic system

Unknown frequency: thrombocytopenia

Disorders from the metabolism and nutrition

Unknown frequency: hyperkalaemia

Disturbances from the nervous system

Unknown frequency: Vertigo

Disturbances from the liver and bile ducts

Unknown frequency: increased activity of "hepatic" enzymes and concentration of bilirubin in the blood, hepatitis, jaundice

Hearing disorders

Unknown frequency: ringing in the ears

Disturbances from musculoskeletal and connective tissue

Unknown frequency: myalgia

Disorders from the kidneys and urinary tract

Unknown frequency: renal dysfunction, including cases of renal failure in patients at risk (see section "Special instructions").

Common violations

Unknown frequency: asthenia.

Overdose:

The experience of using the drug in adults at doses up to 900 mg / day for 8 weeks showed no toxicity.

There is no specific information regarding the treatment of an overdose of irbesartan. It is necessary to establish constant monitoring of the patient's condition and, if necessary, to carry out symptomatic and supportive therapy. In case of overdose, it is recommended to induce vomiting and / or gastric lavage. Irbesartan is not excreted from the body by hemodialysis.

Symptoms of an overdose are a marked decrease in blood pressure, tachycardia, rarely bradycardia.

Interaction:

Based on the research data in vitro, it is not expected that irbesartan will interact with drugs metabolized with isoenzymes CYP1 Al, CYP1A2, CYP2A6, CYP2B6, CYP2E1 or CYP3A4. Irbesartan, in general, is metabolized by isoenzyme CYP2C9 and, to a lesser extent, undergoes glucuronation. No significant pharmacokinetic and pharmacodynamic interactions were observed with the combined use of irbesartan with warfarin, a drug metabolized by isoenzyme CYP2C9. Effects of inductance inducers CYP2C9 , such as rifampicin, the pharmacokinetics of irbesartan have not been studied.

Irbesartan does not change the pharmacokinetics of digoxin and simvastatin.

With the combined use of irbesartan with hydrochlorothiazide or nifedipine, the pharmacokinetics of irbesartan do not change.

With medications containing aliskiren

Simultaneous use of irbesartan with drugs containing aliskiren, is contraindicated in patients with diabetes mellitus or moderate and severe renal insufficiency (GFR <60 mL / min / 1.73 m² body surface) and is not recommended in other patients (see "Contraindications", "With caution", "Special instructions").

With ACE inhibitors

The use of irbesartan in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients (see the sections "Contraindications", "With caution", "Special instructions").

With potassium preparations and potassium-sparing diuretics, heparin

Based on the experience obtained with the use of other drugs that affect RAAS, with the simultaneous use of drugs potassium; substitutes for salt containing potassium; potassium-sparing diuretics, or others capable of increasing potassium levels in blood with drugs (heparin), can sometimes significantly increase serum potassium concentration, which requires careful monitoring of blood plasma potassium in patients during treatment.

With NSAIDs, including selective inhibitors of COX-2

With simultaneous use of angiotensin II receptor antagonists and NSAIDs (including selective inhibitors of COX-2, acetylsalicylic acid (more than 3 g / day) and nonselective NSAIDs), the antihypertensive effect of irbesartan may be weakened. It should be used with caution, this combination, especially in elderly patients and patients with hypovolemia. In elderly patients, patients with hypovolemia or with impaired renal function, the use of NSAIDs, including COX-2 inhibitors, concomitantly with angiotensin II receptor antagonists, including irbesartan, can lead to impaired renal function, including the possible development of acute renal failure. These effects are usually reversible. Patients before the start of combination therapy need to restore BCC, as well as monitor the function of the kidney before the start of therapy and periodically during the combination therapy.

With lithium preparations

An increase in serum lithium concentrations and an increase in its toxicity was reported with the simultaneous use of lithium salts and irbesartan. If there is a need for this combination, it is recommended that the concentration of lithium in the serum be monitored regularly during treatment.

With diuretics and other antihypertensive agents

With the simultaneous use of irbesartan and other hypotensive means may increase the antihypertensive effect. Irbesartan without any problems were applied simultaneously with other antihypertensive agents, such as beta-blockers, long-acting BCCC and thiazide diuretics.

Prior treatment with diuretics in high doses can lead to hypovolemia and an increased risk of excessive reductionAD at the beginning of irbesartan treatment.

Special instructions:

Excessive BP reduction - patients with hypovolemia.

The use of irbesartan to date has rarely been accompanied by an excessive decrease in blood pressure in patients with hypertension without concomitant diseases. As with ACE inhibitors, excessive reduction in blood pressure is accompanied by clinical symptoms may develop in patients with hyponatremia / hypovolemia (e.g., as a result of intensive diuretic therapy, diarrhea or vomiting, dieting with restriction of salt intake), as well as in patients who are on hemodialysis. Before starting the use of irbesartan, it is necessary to correct hypovolemia and / or hyponatraemia.

Patients with renal function, depending on the activity of RAAS

As a consequence of inhibition of RAAS, it is possible to expect impairment of renal function in predisposed patients. In patients with renal function, depending on the activity of the RAAS (patients with hypertension and renal artery stenosis of one or both kidneys, patients with chronic heart failure III and IV functional class by [classification NYHA]), treatment with drugs that affect RAAS is associated with oliguria and / or progressive azotemia and rarely with acute renal failure and / or death. It can not be ruled out that such an effect can occur when angiotensin receptor antagonists are used II, including irbesartan.

Renal failure and kidney transplantation

When irbesartan is used in patients with renal insufficiency, periodic monitoring of the potassium content and serum creatinine concentration is recommended. There are no clinical data on 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 favorable effect of irbesartan on slowing the progression of renal and cardiovascular disorders had varying degrees of severity in different groups of patients, less pronounced in women and patients not belonging to the Europoid race.

In a clinical study IDNT in patients with arterial hypertension and type 2 diabetes mellitus with proteinuria (> 900 mg / day) in a subgroup of patients witha high risk of stenosis of the renal arteries in any patient who took irbesartan, there was no acute early increase in serum creatinine concentration associated with stenosis of the renal arteries.

Double blockade RAAS when combined with irbesartan with ACE inhibitors or aliskirenom

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

The simultaneous use of irbesartan with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency with GFR <60 ml / min / 1.73 m²surface of the body (see the sections "Contraindications", "Interaction with other medicines") and is not recommended for other patients.

Simultaneous use of irbesartan in combination with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see "Contraindications", "Interaction with other drugs") and is not recommended in other patients.

Hyperkalemia

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

Stenosis of the aortic or mitral valve, hypertrophic obstructive cardiomyopathy

As with the use of other vasodilators, when taking irbesartan in patients with aortic or mitral stenosis or with hypertrophic obstructive cardiomyopathy, be careful.

Primary hyperaldosteronism

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

Patients with ischemic heart disease and / or clinically significant atherosclerosis of cerebral vessels

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

Effect on the ability to drive transp. cf. and fur:

The influence of irbesartan on the ability to drive vehicles or engage in other potentially hazardous activities requiring increased attention and high speed of psychomotor reactions has not been studied. However, based on its pharmacodynamic properties, irbesartan should not affect the ability to drive vehicles and engage in other potentially hazardous activities (work at altitude, the work of an air traffic controller, work with mechanisms, etc.). But in the case of dizziness and weakness, attention may decrease and psychomotor reactions may slow down. In patients who have such undesirable reactions, the decision on the possibility of engaging in any potentially dangerous activities should be taken by the physician individually.

Form release / dosage:

Film-coated tablets, 75 mg, 150 mg or 300 mg.

Packaging:

For 14 tablets in a contour mesh box made of PVC / PVDC film and aluminum foil. 2 contour mesh packs together with instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use the product after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001677

Date of registration:28.04.2012 / 20.06.2017

Expiration Date:Unlimited

The owner of the registration certificate:Kern Pharma S.L.Kern Pharma S.L. Spain

Manufacturer: & nbsp

KERN PHARMA, S.L. Spain

Representation: & nbspINDUKERN-RUS LLCINDUKERN-RUS LLCRussia

Information update date: & nbsp30.11.2017

Illustrated instructions

Instructions

Irbesartan (Irbesartan)