Irbesan

General characteristics. Structure:

Active ingredient: 75 mg, 150 mg or 300 mg of an irbersartan.

Excipients: tsellaktoza 80 (lactoses monohydrate of 75% + cellulose powder of 25%), cellulose microcrystallic PH 102, starch prezhelatinizirovanny, sodium of a kroskarmelloz, silicon dioxide colloid anhydrous (Aerosil 200), magnesium stearate,

Structure of a cover of Opadry YS-1 7003 White: gipromelloza of E3, gipromelloz of E6, polyethyleneglycol 400, polysorbate 80, titanium dioxide (E 171).

Pharmacological properties:

Pharmacodynamics. ИРБЕСАН® - anti-hypertensive drug, the selection antagonist of receptors of angiotensin ІІ (AT1 type). Blocks all physiologically significant effects of angiotensin II which are implemented through receptors like AT1 irrespective of a source or a way of synthesis of angiotensin II. Specific antagonistic action concerning receptors of angiotensin II (AT1) leads to increase in concentration of a renin and angiotensin II in a blood plasma and to decrease in concentration of Aldosteronum in a blood plasma. When using drug in the recommended dose concentration of potassium ions in blood serum significantly does not change. Does not inhibit AKF (a kininaz of II - the enzyme which is responsible for formation of angiotensin II), causes metabolic degradation of bradikinin with formation of inactive metabolites. Manifestation of effect does not require metabolic activation. ИРБЕСАН® reduces the arterial pressure (AP) at the minimum change of the heart rate (HR).

Decrease in the ABP at reception of 1 times a day has dozozavisimy character, with a tendency to an exit to the plateau at appointment in doses more than 300 mg. At appointment in a dose of 150 - 300 mg of 1 times a day causes decrease in the ABP during 24 h after administration of drug (in a prone position or sitting). The maximum decrease in the ABP level is reached in 3–6 h after administration of drug, the hypotensive effect remains at least during 24 h. In 24 h after reception in the recommended doses decrease in the ABP makes 50-70% in comparison with the maximum level of decrease in the diastolic and systolic ABP.

Administration of drug in a dose of 150 mg of 1 times a day is accorded by effect (at the end of the interdose period and on average for 24 h), similar to that which is reached at division of this daily dose into 2 receptions. Anti-hypertensive action ИРБЕСАНА® becomes noticeable within 1-2 weeks, and the maximum effect is reached on 4-6 week from an initiation of treatment. The hypotensive effect remains at prolonged treatment. After the termination of treatment of the ABP gradually is returned to initial level.

Pharmacokinetics. After intake it is well soaked up, absolute bioavailability makes about 60-80%. The maximum concentration in a blood plasma are reached in 1,5-2 h. The concomitant use of food significantly does not influence bioavailability of an irbesartan. Linkng with proteins of a blood plasma makes about 96% at insignificant linkng with cellular components of blood.

The volume of distribution makes 53-93 l. The elimination half-life of an irbesartan in a terminal phase makes 11-15 h. Equilibrium concentration in a blood plasma is reached within 3 days since the beginning of use of drug at reception of 1 times a day. At repeated receptions of 1 times a day limited accumulation of an irbesartan in a blood plasma is noted (<20%). The general clearance of an organism and renal clearance is made by 157-176 and 3-3,5 ml/min. respectively. 80-85% of activity in the circulating blood plasma are necessary on not changed ирбесартан. Irbesartan is metabolized in a liver by conjugation with formation of a glucuronide and oxidation. The main metabolite circulating in blood is the irbesartana a glucuronide (about 6%).

Irbesartan is oxidized, mainly, with participation of P450 CYP cytochrome 2C9 while the isoenzyme of CYP 3A4 is of little importance. Irbesartan and his metabolites are brought out of an organism both with bile, and with urine. About 20% are removed with urine, and other part - with a stake. Less than 2% of the accepted dose are allocated with urine in the form of not changed irbesartan.

Indications to use:

- essetsialny arterial hypertension;

- arterial hypertension at patients with diseases of kidneys and a diabetes mellitus 2 types (as a part of complex therapy).

Route of administration and doses:

Adults the Initial and maintenance dose makes 150 mg of 1 times a day regardless of meal. The pill is taken inside, washing down with enough liquid (for example, one glass of water). ИРБЕСАН® in a dose of 150 mg of 1 times a day usually provides more optimum 24-hour control of the ABP, than in a dose of 75 mg/days. However to the patients who is on a hemodialysis, and patients 75 years drug are aged more senior appoint 75 mg/days in an initial dose. At insufficient efficiency of a dose of 150 mg of 1 times a day appoint a dose of 300 mg, or it is necessary to appoint other anti-hypertensive means. In particular it was shown that purpose of diuretic, such as a hydrochlorothiazide, strengthened action of an irbesartan.

Patients with a diabetes mellitus have 2 types with arterial hypertension, treatment should be begun with 1 tablet ИРБЕСАН® 150 of mg of 1 times a day which is raised afterwards to 300 mg of 1 times a day – the dose which is a preferable maintenance dose for treatment of a nephropathy.

Maximum daily dose of 300 mg.

At patients with disturbance of water and electrolytic balance prior to reception ИРБЕСАНА® it is necessary to recover the volume of the circulating blood (VCB) and/or to eliminate a hyponatremia.

Special groups of patients. Correction of a dose is not required to patients with an impaired renal function. Dose adjustment for patients with abnormal liver functions of easy or moderate severity is not required. Clinical experience of use of drug by the patient suffering from heavy abnormal liver functions no.

Use for children. ИРБЕСАН® it is not recommended for use to children and teenagers up to 18 years because of insufficient data on safety and efficiency.

Features of use:

At a combination of an irbesartan with diuretic (hydrochlorothiazide) the additive effect is noted.

At patients with dehydration and at patients with a hyponatremia who resulted from intensive treatment by diuretics of diarrhea, vomiting or limited consumption of salt, symptomatic hypotension, especially after reception of the first dose of drug can develop. The hypovolemia and a hyponatremia have to be eliminated prior to drug IRBESAN® use. Patients with a bilateral stenosis of renal arteries or a stenosis of an artery of the only functioning kidney which accept other drugs influencing renin-angiotensin-aldosteronovuyu system treat group of the increased risk concerning development of heavy arterial hypotension or a renal failure. Though such cases for the drug IRBESAN® are not described, the similar effect can be expected when using antagonists of receptors of angiotensin II. As well as in case of purpose of any other hypotensive drug, excessive decrease in the ABP at patients with an ischemic cardiopathy or an ischemic heart disease can lead to a myocardial infarction or a stroke. As well as when using other drugs influencing a renin-angio-tenzin-aldosteronovuyu system during treatment by the drug IRBESAN® the hyperpotassemia, especially in the presence of a renal failure, the proteinuria caused by a diabetic nephropathy and/or heart diseases can be observed. For identification of a hyperpotassemia during treatment drug recommends monitoring of level of potassium and creatinine in blood serum.

As well as when using other vazodilatator, it is necessary to take special precautionary measures for patients with an aortal or mitral stenosis or a subaortic hypertrophic stenosis. At patients, the vascular tone and which function of kidneys depend preferential on activity system renin-angiotensin-aldosteronovoy (for example, at severe forms of congestive heart failure or diseases of kidneys, including a renal artery stenosis), treatment by APF inhibitors or antagonists of receptors of angiotensin ІІ can cause acute arterial hypotension, an azotemia, an oliguria and in rare instances – an acute renal failure.

ИРБЕСАН® does not exert impact on the level of uric acid in blood serum or on its allocation with urine.

With an impaired renal function of dose adjustment it is not required from patients. Lower initial dose (75 mg) can be required for patients, with abnormal liver functions of easy or moderate severity. For patients with heavy abnormal liver functions clinical data are absent.

There are no clinical data on use of an irbesartan for the patients who transferred transplantation of kidneys.

Use ИРБЕСАНА® at primary aldosteronism is not recommended as patients with primary aldosteronism do not react to the anti-hypertensive medicines inhibiting a renin-angiotenzinovuyu system.

Use in pediatrics. Safety and efficiency of drug at children are not established. Use in geriatrics

Though at patients 75 years the recommended dose for initial therapy are aged more senior makes 75 mg, usually it is not required from patients of advanced age of dose adjustment.

Pregnancy and period of a lactation. During pregnancy it is impossible to begin treatment by antagonists of receptors of angiotensin-II (APAII). If continuous therapy of APAII is not considered necessary, then the patients planning pregnancy need to be transferred to alternative anti-hypertensive treatment with the safety profile established at pregnancy. At establishment of pregnancy ИРБЕСАН® it is necessary to stop immediately and if it is pertinent, then to begin alternative therapy. For detection of malformations it is recommended to carry out ultrasonography of a fruit.

In view of lack of information use ИРБЕСАНА® is not recommended by the breast touching use ИРБЕСАНА® during feeding, alternative therapy with more fully the established safety profile is preferable, especially during feeding of newborn and premature children.

Features of influence of medicine on ability to manage vehicles and potentially dangerous mechanisms. It is necessary to pay attention to a possibility of development of side effects (for example, dizzinesses) which can affect ability to manage the vehicle or potentially dangerous mechanisms. Patients need to be warned about danger of performance of the work requiring special attention and speed of psychomotor reactions before disappearance of these side effects.

Side effects:

Often:

- dizziness, orthostatic dizziness, orthostatic hypotension;

- fervescence;

- nausea, vomiting;

- mialgiya, ossalgiya, arthralgia, muscular spasm;

- increase in the KFK level in a blood plasma, a hyperpotassemia.

Sometimes:

- sinusopatiya, sinusitis, pharyngitis, rhinitis, cough;

- dispeptic phenomena, heartburn, diarrhea;

- thorax pain;

- sexual dysfunction;

- leykotsitoklastichesky vasculitis;

- tachycardia, rushes of blood.

Seldom:

- a headache, a ring in ears, fatigue, a condition of alarm/excitability;

- disturbance of flavoring feelings, abnormal liver function, hepatitis;

- abdominal cavity pain;

- infections of urinary tract, renal failure;

- decrease in level of hemoglobin;

- rash, urticaria, Quincke's disease.

Isolated cases:

- a renal failure (patients have groups of the increased risk).

Interaction with other medicines:

At simultaneous use ИРБЕСАН® with:

- thiazide diuretics: the anti-hypertensive effect of an iryobesartan amplifies, the previous treatment by diuretics in high doses can lead to dehydration and increases risk of development of symptomatic hypotension in an initiation of treatment irbesartany;

- with the kaliysberegayushchy diuretics and drugs of potassium, substitutes of table salt and other drugs increasing potassium level in blood serum (for example, heparin): the risk of development of a hyperpotassemia increases;

- other anti-hypertensive drugs: the hypotensive effect amplifies; let's combine with beta adrenoblockers, blockers of calcium channels;

 - lithium drugs: increase in concentration of lithium in a blood plasma and development of its toxic effects therefore such combination is not recommended is possible; if such combination is necessary, it is recommended to carry out careful control of level of lithium in blood serum;

- warfarin, Tolbutamidum (CYP 2C9 substrates), and also nifedipine (CYP 2C9 inhibitor): noticeable pharmacokinetic or pharmakodinamichesky interactions are not revealed. Irbesartan in a dose of 150 mg does not influence digoxin pharmacokinetics. The pharmacokinetics of an irbesartan does not change at simultaneous use with a hydrochlorothiazide. Operation of the inductors CYP 2C9, such as rifampicin, on pharmacokinetics of an irbesartan, is unknown.

At simultaneous use of antagonists of angiotensin II and non-steroidal anti-inflammatory drugs (NPVS), including the selection TsOG-2 inhibitors, acetylsalicylic acid (˃3 g/days) and non-selective NPVS easing of hypotensive effect is possible.

As well as at simultaneous use of APF and NPVS inhibitors, at combined use of antagonists of NPVS angiotensin II the risk of a renal failure, including a possibility of development of an acute renal failure, and increase in serumal level of potassium, especially at patients with already impaired renal function can increase. It is necessary to apply with care this combination, especially at patients of advanced age. Patients need to recover OTsK and during all combination therapy, and periodically after its termination to control function of kidneys.

Contraindications:

- hypersensitivity to drug components;

- primary hyper aldosteronism;

- pregnancy and period of a lactation;

- hereditary intolerance of a galactose, insufficiency of lactase or disturbance of absorption of glucose and galactose;

- children's and teenage age up to 18 years.

With care it is necessary to use drug at a stenosis of the aortal or mitral valve, a hypertrophic subaortic stenosis, dehydration, a hyponatremia, diarrhea, vomiting, observance of a diet with limited consumption of table salt, therapy by diuretics, a bilateral stenosis of renal arteries, a unilateral stenosis of an artery of the only kidney, chronic heart failure of the III-IV functional class on classification of NYHA, IBS and/or atherosclerotic defeat of vessels of a brain, a hyperpotassemia, a renal failure, a hemodialysis, recent transplantation of a kidney (lack of clinical experience of use), a heavy liver failure (lack of clinical experience of use).

Overdose:

Symptoms: arterial hypotension and tachycardia, is possible bradycardia.

Treatment: it is necessary to wash out a stomach, to appoint absorbent carbon, to carry out a symptomatic and maintenance therapy. Irbesartan is not brought from an organism at a hemodialysis.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

On 14 (for dosages of 75 mg and 150 mg) or 7 tablets (for a dosage of 300 mg) in a blister strip packaging from a film of opaque PVH/PE/PVDH and printing aluminum foil.

On 1 or 2 (for dosages of 75 mg and 150 mg) or 2 or 4 (for a dosage of 300 mg) planimetric packaging together with the instruction on a medical use in the state and Russian languages place in a pack cardboard with the hologram of manufacturing firm.