Ирсар®

General characteristics. Structure:

Active agent: ирбесартан 150 mg or 300 mg;
excipients: starch prezhelatinizirovanny 51 mg or 102 mg, croscarmellose sodium (primelloza) of 12 mg or 24 mg, lactoses monohydrate (sugar milk) 44 mg or 88 mg, magnesium stearate of 2 mg or 4 mg, povidon-K30 10 mg or 20 mg, talc of 3 mg or 6 mg, cellulose of microcrystallic 28 mg or 56 mg.

Description:

Tablets of white or almost white color, round, biconvex from risky. The insignificant mramornost is allowed.

Pharmacological properties:

Pharmacodynamics. Irbesartan is the selection antagonist of receptors of angiotensin II (AT1 type). Blocks all physiologically significant effects of angiotensin II mediated by AT1 receptors irrespective of a source or a way of synthesis of angiotensin II. The selection antagonism to receptors of angiotensin II (AT1) leads to increase in plasma concentration of a renin and angiotensin II and decrease in plasma concentration of Aldosteronum. Serumal potassium concentrations usually significantly do not change at reception of an irbesartan in the recommended doses. Irbesartan does not inhibit an angiotensin-converting enzyme (APF) (kininazu-II), the enzyme participating in synthesis of angiotensin II and splitting bradykinin to inactive metabolites. Manifestation of action of an irbesartan does not require its metabolic activation.
Irbesartan reduces the arterial pressure (AP) at the minimum change of the heart rate (HR). At reception in doses to 300 mg once a day decrease in the ABP has dozozavisimy character, however, at further increase in a dose of an irbesartan the gain of anti-hypertensive effect is insignificant.
The maximum decrease in the ABP is reached in 3-6 h after a single dose inside and remains, at least, for 24 hours. In 24 hours of the ABP remains at the level of 60-70% of the maximum decrease in the diastolic and systolic ABP at reception of the recommended doses. After reception of 150-300 mg of 1 times a day in 24 hours (i.e. at the end of an interdose interval) the ABP (systolic/diastolic) in position of the patient "lying" or "sitting" decreases by 8-13/5-8 mm hg, respectively, that significantly it is more, than at placebo reception.
Administration of drug in a dose of 150 mg results in the hypotensive effect comparable to double reception of the same dose divided into two receptions once a day.
Stable anti-hypertensive action develops within 1-2 weeks of therapy, and the maximum therapeutic effect is reached in 4-6 weeks after an initiation of treatment. At drug withdrawal the syndrome of "cancellation" is absent.
Efficiency of the drug Irsar® does not depend on age and a sex. Patients of negroid race react to monotherapy by the drug Irsar® more weakly (as well as to all other medicines influencing the renin-angiotensin-aldosteronovuyu system (RAAS)).
Irbesartan practically does not influence concentration of uric acid in blood serum or on removal of uric acid kidneys.

Pharmacokinetics. After intake ирбесартан it is well soaked up, its absolute bioavailability makes about 60-80%. The concomitant use of food significantly does not influence bioavailability of an irbesartan.
Communication with proteins of a blood plasma makes about 96%. The volume of distribution makes 53-93 l.
Irbesartan is metabolized in a liver by oxidation and conjugation with glucuronic acid with formation of the main metabolite – an irbesartana of a glucuronide (about 6%). Oxidation of an irbesartan is carried out, mainly, by means of P450 cytochrome, participation of an isoenzyme of CYP3A4 in metabolism of an irbesartan is insignificant.
Pharmacokinetic parameters of an irbesartan have linear and proportional character in the range of doses from 10 to 600 mg; at doses over 600 mg (the dose twice exceeding the recommended maximum dose of drug) the kinetics of an irbesartan becomes nonlinear (absorption reduction).
After intake the maximum concentration (Cmax) in a blood plasma is reached in 1,5-2 h.
The general clearance and renal clearance make 157-176 and 3-3,5 ml/min., respectively. The final elimination half-life (T1/2) makes 11-15 h. At a daily single dose in an irbesartan equilibrium plasma concentration is reached in 3 days.
Irbesartan and his metabolites are brought out of an organism as with bile (80%), and kidneys (20%), and less than 2% of the accepted dose of an irbesartan are removed by kidneys in not changed look.
Special groups of patients:
At female patients (in comparison with male patients) with arterial hypertension higher concentration of an irbesartan in a blood plasma were observed. However distinctions in T1/2 and accumulation of an irbesartan it was revealed not. Dose adjustment of drug is not required from female patients.
AUC values (the areas under a pharmacokinetic curve concentration time) and Cmax of an irbesartan at patients of advanced age (65 years are more senior) slightly higher, than at patients of younger age (18-40 years). Final T1/2 at patients of advanced age is changed slightly. Dose adjustment is not required from elderly patients.
Renal failure and hemodialysis: indicators of pharmacokinetics of an irbesartan essentially do not change. The hemodialysis is inefficient.
Abnormal liver function: at patients with cirrhosis easy or moderate severity of a current pharmacokinetic parameters of an irbesartan significantly do not change. Pharmacokinetic researches at patients with a heavy liver failure were not conducted.

Indications to use:

Essential hypertensia.
Nephropathy at arterial hypertension and a diabetes mellitus 2 types (as a part of the combined hypotensive therapy).

Route of administration and doses:

Inside, the tablet is swallowed entirely, washing down with water. To accept 1 time a day, regardless of meal.
Usually recommended initial and maintenance dose makes 150 mg of 1 times a day.
To patients with a reduced the volume of the circulating blood (VCB) (including diarrhea, vomiting), with a hyponatremia, against the background of treatment by diuretics or diets with the restriction of consumption of table salt or which is on a hemodialysis, or to patients are more senior than 75 years the recommended initial dose of the drug Irsar® makes 75 mg / cутки (1/2 tablets on 150 mg). At insufficient expressiveness of therapeutic effect the dose of drug is increased to 300 mg/days. Further increase in a dose with an interval of 1-2 weeks (more than 300 mg/days) does not lead to strengthening of expressiveness of anti-hypertensive effect.
In case of lack of effect at monotherapy the combination with other hypotensive drug, for example with low doses of diuretics is possible (hydrochlorothiazide).
For treatment of a nephropathy to patients with arterial hypertension and a diabetes mellitus 2 types the recommended initial dose of the drug Irsar® makes 150 mg once a day, at insufficiency of therapeutic effect the dose can be increased (with an interval of 2 weeks) to 300 mg once a day – the dose which is a preferable maintenance dose for treatment of a nephropathy.

Renal failure
With an impaired renal function of correction of the mode of dosing it is not required from patients.
The initial dose of drug at the patients who are on a hemodialysis has to make 75 mg/days (1/2 tablets on 150 mg).
Abnormal liver function
Easy and moderate severity of correction of doses of drug is not required to patients with an abnormal liver function. Clinical experience of use for patients with heavy abnormal liver functions is absent.
Patients of advanced age
Treatment of patients aged is recommended 75 years are more senior to begin with a dose 75 mg (1/2 tablets on 150 mg).

Features of use:

Disturbance of water and electrolytic balance. Before use of the drug Irsar® for patients with decrease in OTsK (including owing to diarrhea or vomiting, an intensive care diuretics, diets with restriction of consumption of table salt) it is necessary to recover the volume of the circulating blood, to eliminate a hyponatremia since there is a risk of development of symptomatic arterial hypotension, especially after reception of the first dose.
Renovascular hypertensia. Potentially the risk of development of heavy arterial hypotension and renal failure in patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only functioning kidney increases.
Renal failure and transplantation of a kidney. It is recommended to control the content of potassium and creatinine in blood serum at patients with a renal failure. There are no clinical data on use of the drug Irsar® for patients after transplantation of a kidney.
Patients with arterial hypertension and a diabetes mellitus of type 2 with a renal failure.
The favorable action noted at an irbesartan concerning delay of progressing of renal and cardiovascular disturbances has different degree of manifestation at different groups of patients: it is less expressed at women and at the patients who are not belonging to Caucasian race.
Hyperpotassemia. It is recommended to control the content of potassium at the patients who are at the same time accepting with the drug Irsar® potassium drugs, kaliysberegayushchy diuretics, heparin, especially in the presence of a renal failure and/or diseases from cardiovascular system.
Stenosis of the aortal and mitral valve, GOKMP. As at use of any vazodilatator, it is necessary to use the drug Irsar® with care.
Primary hyper aldosteronism. Use of the drug Irsar® at primary hyper aldosteronism is inexpedient.
Others. At patients, the vascular tone and which function of kidneys preferential depends on activity of RAAS (for example, patients with chronic heart failure of the III-IV functional class on NYHA classification, associated diseases of kidneys, including with a renal artery stenosis), therapy by APF inhibitors or angiotensin II of receptors antagonists is followed by development of arterial hypotension, an azotemia, an oliguria and, in rare instances, an acute renal failure. As well as at reception of other antihypertensives, considerable decrease in the ABP at patients with an ischemic heart disease and/or atherosclerotic defeat of vessels of a brain can lead to development of a myocardial infarction, stroke. At treatment of such patients it is necessary to control the ABP strictly.
Influence on ability to manage vehicles and to perform the works demanding the high speed of psychomotor reactions.
During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

Classification of frequency of development of the side effects given below was defined according to the following (classification of World Health Organization):
very often    > 1/10
often from          > 1/100    to <1/10
infrequently from      > 1/1000  to <1/100
seldom from          > 1/10000 to <1/1000
very seldom from <1/10000, including separate messages.
Arterial hypertension
From the central nervous system (CNS): often – dizziness, increased fatigue, an adynamy.
From cardiovascular system: infrequently – tachycardia; infrequently – "inflows" of blood to face skin.
From respiratory system: infrequently – cough.
From a musculoskeletal system: infrequently – thorax pain.
From the alimentary system: often – nausea and/or vomiting; infrequently – diarrhea, dyspepsia and/or heartburn.
From reproductive system: infrequently – sexual dysfunction.
Laboratory indicators: often – increase in activity of a kreatininfosfokinaza (KFK) (without clinical manifestations from a musculoskeletal system and lack of a hyperpotassemia).
Nephropathy at arterial hypertension and a diabetes mellitus 2 types
From TsNS: often – dizziness at change of position of a body (transition from situation "lying" in a standing position).
From cardiovascular system: often – the expressed decrease in the ABP, including orthostatic hypotension.
From a musculoskeletal system: often – an arthralgia, a mialgiya.
Laboratory indicators: very often - a hyperpotassemia, decrease in hemoglobin (clinically insignificant).
During post-marketing use of an irbesartan the following by-effects which frequency cannot be established were also noted (according to spontaneous messages).
From TsNS: headache.
Allergic reactions: hypersensitivity reactions (skin rash, small tortoiseshell, Quincke's disease), leukocytic vasculitis.
From an acoustic organ: sonitus.
From the alimentary system: dysgeusia, abnormal liver function, hepatitis.
From a musculoskeletal system: an arthralgia, a mialgiya (it is in certain cases associated with increase in activity of KFK), muscular spasms.
From an urinary system: very seldom – a renal failure (including separate cases of development of a renal failure in patients of risk group).
At development of heavy side effects treatment has to be stopped.

Interaction with other medicines:

Other antihypertensives and diuretics can strengthen anti-hypertensive effect of an irbesartan. Irbesartan can be applied in combination with such drugs as beta adrenoblockers, blockers of "slow" calcium channels of the prolonged action and thiazide diuretics.
The previous therapy by diuretics in high doses can lead to dehydration and increase in risk of arterial hypotension at the beginning of therapy by the drug Irsar®.
Simultaneous use of an irbesartan with drugs of potassium and kaliysberegayushchy diuretics, and also heparin can increase the content of potassium in blood serum.
At simultaneous use of an irbesartan with lithium drugs potentially perhaps reversible increase in content of lithium in blood serum and increase in its toxicity. Therefore it is regularly recommended to control concentration of lithium in blood serum.
At simultaneous use with non-steroidal anti-inflammatory drugs (NPVP) (including the selection inhibitors of cyclooxygenase 2, acetylsalicylic acid (more than 3 g/days) and non-selective NPVP) decrease in anti-hypertensive effect is possible. In case of simultaneous use with NPVP increase in risk of renal failures up to development of an acute renal failure and a hyperpotassemia is potentially possible (especially at patients with already impaired renal function). It is necessary to apply with care this combination, especially at patients of advanced age. Patients before a combination therapy need to recover OTsK, and also to control functions of kidneys before therapy and periodically in the course of carrying out a combination therapy.
The hydrochlorothiazide, nifedipine do not influence pharmacokinetic parameters of an irbesartan.
Irbesartan is metabolized preferential by an isoenzyme of CYP2C9 and, to a lesser extent, by a glyukuronirovaniye. Significant pharmacokinetic and pharmakodinamichesky interaction with warfarin (CYP2C9, metaboliziruyemy with participation of an isoenzyme) is noted. Effects of inductors of an isoenzyme of CYP2C9, such as rifampicin, on pharmacokinetics of an irbesartan are not studied. Irbesartan does not influence pharmacokinetic parameters of digoxin.

Contraindications:

- hypersensitivity to an irbesartan or to any component of drug;
- deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption;
- pregnancy;
- lactation period;
- age up to 18 years.

With care: the hyponatremia, a diet with restriction of consumption of table salt, a bilateral stenosis of renal arteries or a stenosis of an artery of the only functioning kidney, decrease in the volume of the circulating blood (VCB) (including diarrhea, vomiting), the previous therapy by diuretics, a renal failure, a hemodialysis, a state after transplantation of a kidney (lack of experience of a clinical use), a heavy liver failure (lack of experience of a clinical use), a hyperpotassemia, a concomitant use with lithium drugs, a stenosis of aortal and mitral valves, a hypertrophic subaortic stenosis (GOKMP), primary hyper aldosteronism, chronic heart failure (the III-IV functional class on NYHA classification), the coronary heart disease (CHD) and/or atherosclerotic defeat of vessels of a brain, patients is more senior than 75 years.

Use at pregnancy and in the period of a lactation:
As well as any drug which influences directly RAAS the drug Irsar® cannot be used at pregnancy.
Use of antagonists of receptors of angiotensin II is not recommended in vremyai a pregnancy trimester. Drug is contraindicated in the II-III trimesters of pregnancy as use in the II-III trimesters of pregnancy can cause fetotoksichesky effects (depression of function of kidneys, an oligoamnios, delay of ossification of bones of a skull of a fruit) and neonatal toxic effects (a renal failure, arterial hypotension, a hyperpotassemia). In case of administration of drug in the II-III trimesters of pregnancy it is necessary to conduct ultrasound examination of kidneys and bones of a skull of a fruit.
Transition to the corresponding alternative hypotensive therapy has to be made prior to pregnancy planning. At pregnancy approach the drug Irsar® needs to be cancelled as soon as possible.
It is unknown whether it is allocated ирбесартан in breast milk.
In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Symptoms: the expressed decrease in the ABP, tachycardia, is rare – bradycardia.
Treatment: gastric lavage, reception of absorbent carbon. Carrying out a symptomatic and maintenance therapy under constant observation of the patient. The hemodialysis is inefficient.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity: 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets of 150 mg and 300 mg.
On 7, 10, 14 or 15 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.
On 1, 2, 4, 8 blister strip packagings on 7 tablets or on 1, 2, 3, 6 blister strip packagings on 10 tablets, or on 1, 2, 4 blister strip packagings on 14 tablets or on 1, 2, 4 blister strip packagings on 15 tablets together with the application instruction place in a pack from a cardboard.