Irbesartan pills 300mg, 28pcs

Composition

Active ingredient:

irbesartan – 300,00 mg.

Excipients (core):

lactose monohydrate (milk sugar) – 186.40 mg,

microcrystalline cellulose-96.00 mg,

croscarmellose sodium-28.80 mg,

povidone-K 25-19.20 mg,

magnesium stearate-6.40 mg,

colloidal silicon dioxide-3.20 mg.

Excipients (shell): hypromellose-8.80 mg, macrogol-4000-2.40 mg, titanium dioxide-4.80 mg

Pharmacological action

Pharmacotherapy group

Angiotensin II receptor antagonist

ATX code

C09CA04

Pharmacodynamics :

Irbesartan is a selective angiotensin II (type AT1) receptor antagonist. Reduces the concentration of aldosterone in blood plasma (does not inhibit kinase II that destroys bradykinin); eliminates the vasoconstrictive effect of angiotensin II; reduces total peripheral vascular resistance reduces afterload systemic blood pressure (BP) and pressure in the “small” circulatory circle. It does not affect the concentration of triglycerides of 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 reduction in blood pressure is 60-70% compared to the maximum reduction in diastolic and systolic blood pressure in response to the drug. When taking 1 time/day at a dose of 150-300 mg, the degree of reduction in blood pressure (systolic/diastolic) at the end of the inter-dose interval (i. e. 24 hours after taking the drug) in the patient’s lying or sitting position is on average 8-13/5-8 mm Hg (respectively) more than placebo. Taking the drug at a dose of 150 mg 1 time / day causes the same antihypertensive response (a decrease in blood pressure before taking the next dose of the drug and an 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 discontinuation of treatment, blood pressure gradually returns to the initial value of the “withdrawal” syndrome was not observed.

The effectiveness of the drug does not depend on age and gender.

Patients of the black race are less responsive to irbesartan monotherapy (as well as to all other drugs that affect the renin-angiotensin-aldosterone system (RAAS)).

Pharmacokinetics:

Suction

After oral use, irbesartan is well absorbed from the gastrointestinal tract (GIT). The maximum concentration (Cmax) of irbesartan in blood plasma is reached 15-2 hours after oral use. Absolute bioavailability is 60-80%. Simultaneous food intake does not significantly affect the bioavailability of the drug. Irbesartan has linear and dose-proportional pharmacokinetics in the dose range from 10 to 600 mg; at doses above 600 mg (2 times the recommended maximum dose), the kinetics of irbesartan becomes nonlinear (decrease in absorption).

Distribution

Binding to plasma proteins is approximately 96%. Binding to the cellular components of the blood is insignificant. The volume of distribution is 53-93 liters. With a daily intake of 1 time/day, the equilibrium concentration is reached after 3 days. With repeated doses of 1 time/day, there is a limited accumulation of irbesartan in the blood plasma (less than 20%). After oral or intravenous use of 14C-irbesargan,80-85% of radioactivity in the circulating blood is accounted for by unchanged irbesartan.

Metabolism

Irbesartan is biotransformed in the liver by oxidation and conjugation with glucuronic acid.

Irbesartan is mainly oxidized by the CYP2C9 isoenzyme the participation of the CYP3A4 isoenzyme in the metabolism of irbesartan is insignificant. The main metabolite found in the systemic circulation is irbesartan glucuronide (about 6%). Irbesartan is not metabolized by most of the isoenzymes that are normally involved in drug metabolism (isoenzymes CYP1A1 CYP1A2 CYP2A6 CYP2B6 CYP2D6 or CYP2E1) and does not cause their inhibition or induction. Irbesartan does not induce or inhibit the CYP3A4 isoenzyme.

Deduction

Total clearance and renal clearance are 157-176 ml / min and 3-3.5 ml / min, respectively. The final half-life (T 1/2) is 11-15 hours. Irbesartan and its metabolites are excreted by the kidneys through the intestines with bile. After ingestion of 14C-irbesartan, about 20% of the radioactivity is detected in the urine, the rest in the feces.

Less than 2% of the administered dose is excreted by the kidneys as unchanged irbesartan.

Special patient groups

Effect of gender on the pharmacokinetics of irbesartan

Slightly higher plasma concentrations of irbesartan are observed in women (compared to men). However, there were no differences in the T 1/2 value and irbesartan accumulation. No dose adjustment of irbesartan is required in women.

There were no gender-related differences in the effects of irbesartan.

Pharmacokinetics of irbesartan in elderly patients

The values of AUC (area under the concentration-time curve) and Ctax of irbesartan were slightly higher in elderly patients (older than 65 years) However, the values of the final T 1/2 did not significantly differ from those of younger patients. No dose adjustment of irbesartan is required in elderly patients.

Pharmacokinetics in patients with impaired renal function

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

Pharmacokinetics in patients with impaired liver function

In patients with mild (Child-Pugh score 5-6) or moderate (Child-Pugh score 7-9) cirrhosis, the pharmacokinetic parameters of irbesartan do not change significantly. Pharmacokinetic studies in patients with severe (more than 9 points on the Child-Pugh scale) hepatic insufficiency have not been conducted.

Effect of race on the pharmacokinetics of irbesartan

In non-hypertensive black volunteers, irbesartan AUC and T 1/2 were approximately 20-25% higher than in Caucasian subjects; their CMAX of Irbesartan was almost the same as that of Caucasian subjects.

Indications

-Arterial hypertension (in monotherapy and in combination with other antihypertensive agents, for example, thiazide diuretics, beta-blockers, long-acting slow calcium channel blockers);

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

Use during pregnancy and lactation

There is no experience with the use of Irbesartan during pregnancy. Taking into account the fact that when taking ACE inhibitors in pregnant women in the second and third trimester of pregnancy, damage and death of the developing fetus were observed, irbesartan, like any other drug that directly affects the RAAS, should not be used during pregnancy. If pregnancy is established during treatment with Irbesartan, it should be discontinued as soon as possible.

It is not known whether irbesartan and its metabolites are excreted in breast milk. Irbesartan is contraindicated during breastfeeding. Therefore, after evaluating the ratio of the expected benefit of taking the drug for the mother and the potential risk for the child, you should stop breastfeeding or taking Irbesartan.

Contraindications

– Hypersensitivity to irbesartan to any of the auxiliary components of the drug;

– pregnancy;

– the period of breastfeeding;

– children’s and teenage age up to 18 years (efficacy and safety not established);

– intolerance to galactose, lactase deficiency syndrome glucose-galactose malabsorption;

– simultaneous use with aliskiren and iliskilendirmesi drugs in patients with diabetes or moderate-to-severe renal insufficiency (glomerular filtration rate (GFR) less than 60 ml/min/173 m 2 of the body surface area).

– concomitant use with angiotensin-converting enzyme (ACE) inhibitors in patients with diabetic nephropathy.

– severe hepatic insufficiency (more than 9 points on the Child-Pugh scale) (no clinical experience of use).

With caution:

The drug should be used with caution in patients with aortic or mitral valve stenosis hypertrophic obstructive cardiomyopathy hypovolemia hyponatremia diarrhea vomiting a diet with limited salt intake diuretic therapy; bilateral renal artery stenosis unilateral stenosis of the artery of a single kidney chronic heart failure of NYHA functional class III-IV coronary heart disease (CHD) and/or atherosclerotic lesions of the brain vessels renal hyperkalemia age over 75 years; when used concomitantly with nonsteroidal anti-inflammatory drugs including cyclooxygenase II inhibitors; when used in combination with ACE inhibitors or aliskiren, since compared with monotherapy with double RAAS blockade, there is an increased risk of excessive blood pressure reduction, hyperkalemia and impaired renal function; primary hyperaldosteronism.

Side effects

The following adverse events are presented according to the following frequency gradations (according to the World Health Organization classification): very common (≥1/10) common (≥1/100 – <1/10) uncommon (≥1/1 000 – <1/100) rare (≥1/10 000 – <1/1 000) very rare (

Adverse events observed in placebo controlled trials in arterial hypertension

From the central nervous system: often – dizziness headache; infrequently-orthostatic dizziness.

From the cardiovascular system: infrequently – edema tachycardia.

Respiratory system disorders: infrequently-cough.

From the digestive system: often – nausea, vomiting; infrequently-diarrhea, dyspepsia, heartburn.

From the side of the reproductive system: infrequently-sexual dysfunction.

From the body as a whole: often – increased fatigue; infrequently – chest pain.

Laboratory parameters: no clinically significant changes in laboratory parameters were observed in patients with arterial hypertension during the study.

Arterial hypertension and type 2 diabetes mellitus with impaired renal function

Adverse events were similar to those in patients with hypertension, with the exception of orthostatic symptoms (dizziness (102%) (with placebo 6%) orthostatic vertigo (54%) (with placebo 27%) and orthostatic hypotension (54%) (with placebo 32%).

Hyperkalemia

In the IDNT clinical trial, the percentage of patients with hyperkalemia (greater than 6 mEq / L) was 186% in the irbesartan group versus 60% in the placebo group. In the IRMA2 study, the percentage of patients with hyperkalemia (greater than 6 mEq / L) was 1% in the irbesartan group and no hyperkalemia was observed in the placebo group.

In the IDNT clinical trial, the rate of discontinuation due to hyperkalemia with irbesartan and placebo was 21% and 036%, respectively. In the IRMA2 clinical trial, the frequency of discontinuation of treatment due to hyperkalemia with irbesartan and placebo was 05% and 00%, respectively.

Adverse events observed with post marketing use of irbesartan

From the immune system: very rarely – allergic reactions (urticaria angioedema).

From the side of metabolism and nutrition: frequency unknown-hyperkalemia.

Nervous system disorders: frequency unknown-vertigo.

From the liver: the frequency is unknown-increased activity of “liver” enzymes and bilirubin concentration in the blood hepatitis jaundice.

From the side of the hearing organ: frequency unknown-tinnitus.

Musculoskeletal disorders: frequency unknown – myalgia.

From the side of the kidneys and urinary system: frequency unknown-impaired renal function, including the development of renal failure in patients at risk (see section “Special instructions”).

General violations: the frequency is unknown-asthenia.

Interaction

With medicinal products containing aliskiren

Concomitant use of irbesartan with medicinal products containing aliskiren is contraindicated in patients with diabetes mellitus or moderate to severe renal insufficiency (GFR less than 60 ml / min/173 m2 of body surface area) and is not recommended in other patients (see sections “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 sections “Contraindications” “With caution” “Special instructions”).

Diuretics and other antihypertensive agents

Concomitant use of irbesartan with other antihypertensive agents may increase the antihypertensive effect. Irbesartan has been used in combination with other antihypertensive drugs such as long-acting beta-blockers and thiazide diuretics.

Previous treatment with high-dose diuretics may lead to dehydration and an increased risk of hypotension at the beginning of treatment with Irbesartan.

Potassium preparations and potassium-sparing diuretics heparin

Based on the experience gained with the use of other drugs that affect the RAAS with the simultaneous use of potassium preparations water electrolyte solutions containing potassium potassium-sparing diuretics or other drugs that can increase the content of potassium in the blood, including heparin, it is possible to increase the content of potassium in the blood serum.

Lithium

Reversible increases in serum lithium concentrations or toxicity were observed when lithium was co-administered with ACE inhibitors. To date, such effects have been extremely rare with the use of irbesartan.

If it is necessary to use this combination, then during treatment, the concentration of lithium in the blood serum should be carefully monitored.

Nonsteroidal anti-inflammatory drugs (NSAIDs including cyclooxygenase-2 (COX-2) inhibitors)

Concomitant use of angiotensin II receptor antagonists (ARA II) and NSAIDs (including selective COX-2 inhibitors of acetylsalicylic acid (more than 3 g/day) and non-selective NSAIDs) may weaken the antihypertensive effect of irbesartan.

As with the concomitant use of ACE inhibitors and NSAIDs, the combined use of ARA II and NSAIDs may increase the risk of impaired renal function, including the possibility of acute renal failure and increased serum potassium levels, especially in patients with already impaired renal function. This combination should be used with caution, especially in elderly patients and in patients with hypovolemia. It is necessary to restore the volume of circulating blood and during the entire period of combination therapy, as well as periodically after its end, monitor kidney function.

Other types of interaction

Based on in vitro studies, no interaction of irbesartan with drugs metabolized by the isoenzymes CYP1A1 CYP1A2 CYP1A6 CYP2B6 CYP2E1 or CYP3A4 is expected.

Irbesartan is mainly metabolized with the participation of the CYP2C9 isoenzyme and undergoes less glucuronidation. No significant pharmacokinetic or pharmacodynamic interaction was observed when irbesartan was co-administered with warfarin with drugs metabolized by the CYP2C9 isoenzyme. The effect of inducers of CYP2C9 activity (including rifampicin) on the pharmacokinetics of irbesartan has not been studied.

Irbesartan does not alter the pharmacokinetics of digoxin and simvastatin. When irbesartan is co-administered with hydrochlorothiazide or nifedipine, the pharmacokinetics of irbesartan do not change.

In elderly patients and patients with impaired renal function, concomitant use of ACE and ARA II inhibitors with sulfamethoxazole/trimethoprim was accompanied by severe hyperkalemia, which is believed to be caused by trimethoprim. The drug should be used with caution with drugs containing trimethoprim regularly monitoring the potassium content in the blood.

How to take, course of use and dosage

The drug should be taken orally regardless of the time of food intake. The tablet is swallowed whole with water.

The initial and maintenance dose is 150 mg 1 time / day, regardless of the meal time. The 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 there is insufficient therapeutic effect when using Irbesartan at a dose of 150 mg 1 time/day, the dose can be increased to 300 mg once a day.

If there is insufficient reduction in blood pressure in monotherapy with Irbesartan, diuretics (for example, hydrochlorothiazide 125 mg per day) or other antihypertensive agents (for example, beta-blockers or long-acting BMCC) can be added to treatment.

In patients with hypertension and type 2 diabetes, treatment should begin with a dose of 150 mg once daily and gradually increase to 300 mg, which is the preferred maintenance dose for the treatment of nephropathy.

Use in special patient groups

In general, no differences in efficacy and safety were observed in clinical trials between patients aged 65 years and older and younger patients.

Although it is recommended to start treatment of patients over the age of 75 years with a dose of 75 mg, usually elderly patients do not need to adjust the dosage regimen.

Patients with impaired renal function

No dosage adjustment is required in patients with impaired renal function.

Patients with hypovolemia

In patients with impaired water-electrolyte balance, the volume of circulating blood (BCC) should be restored and/or hyponatremia should be eliminated before starting the drug.

For patients undergoing hemodialysis, the initial dose should be 75 mg / day.

Patients with impaired liver function

No dosage adjustment is required in patients with mild (Child-Pugh score 5-6) or moderate (Child-Pugh score 7-9) hepatic impairment. There is no clinical experience of using the drug in patients with severe (more than 9 points on the Child-Pugh scale) liver function disorders (see the section “Contraindications”).

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

Overdose

Symptoms: a marked decrease in blood pressure is most likely. tachycardia bradycardia.

Treatment: if the drug is accidentally taken in high doses, artificial vomiting and/or gastric lavage activated charcoal are indicated, and symptomatic and maintenance therapy is indicated. Hemodialysis is ineffective.

Special instructions

Excessive lowering of blood pressure – patients with hypovolemia

To date, the use of 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 may develop in patients with hyponatremia/hypovolemia (for example, as a result of intensive diuretic therapy for diarrhea or vomiting, adherence to a diet with limited consumption of table salt), as well as in patients on hemodialysis. Hypovolemia and/or hyponatremia should be corrected before starting Irbesartan.

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 RAAS activity (patients with arterial hypertension and renal artery stenosis of one or both kidneys, patients with NYHA functional class III and IV chronic heart failure), treatment with drugs that affect RAAS has been associated with oliguria and/or progressive azotemia and rarely with acute renal failure and/or death. It is impossible to exclude the possibility of a similar effect with the use of ARA II including irbesartan.

Impaired kidney function and kidney transplantation

When using Irbesartan in patients with impaired renal function, 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 beneficial effect of irbesartan on slowing the progression of renal and cardiovascular disorders was different in different groups of patients, it was less pronounced in women and in patients not belonging to the Caucasian race.

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

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

The use of Irbesartan in combination with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR less than 60 ml/min/173 m2 of 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” and “Interaction with other drugs”) and is not recommended in other patients.

Hyperkalemia

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

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 acting through RAAS inhibition. Therefore, the use of the drug in such cases is impractical.

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

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

Influence on the ability to drive vehicles and mechanisms:

The effect of Irbesartan on the ability to drive vehicles or engage in other potentially dangerous activities that require increased attention and high speed of psychomotor reactions has not been studied. However, based on the pharmacodynamic properties, the drug Irbesartan should not affect the ability to drive vehicles and engage in other potentially dangerous activities (working at altitude, working as an air traffic controller, working with mechanisms, etc. ), but in case of dizziness and weakness, it is possible to reduce psychomotor reactions, so it is better to refrain from such activities.

Storage conditions

At a temperature not exceeding 25 °C.

Keep out of reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Irbesartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets