Ko-Irbesan

General characteristics. Structure:

Active ingredients: 150 mg or 300 mg of an irbesartan, 12,5 mg of Hydrochlorthiazidum.

Excipients: tsellaktoza 80 (lactoses monohydrate of 75% + cellulose powder of 25%), cellulose microcrystallic PH 102, sodium of a kroskarmelloz, aerosil 200, magnesium stearate.

Structure of a cover of Opadry Pink OY - 349448: gipromelloza 2910 (E464), macrogoal/PEG 400, titanium dioxide (E171), gland (III) oxide red (E172).

Pharmacological properties:

Pharmacodynamics. КО-ИРБЕСАН® is a combination irbesartana-the selection antagonist of receptors of angiotensin ІІ (AT1 type) and Hydrochlorthiazidum - diuretic of a class of tiazid. At combined use of an irbesartan and Hydrochlorthiazidum the anti-hypertensive effect increases. Irbesartan 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 of an irbesartan 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 APF (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. TO - ИРБЕСАН® the ABP at the minimum change of the heart rate (HR) reduces. 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. Purpose of 1 tablet 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 TO - ИРБЕСАН®в to a dosage of 150 mg/12,5 mg of 1 times a day is accorded by the effect similar to that which is reached at division of this daily dose into 2 receptions. At regular use during 1–2 weeks the effect gains stability and in 4–6 weeks reaches a maximum. The hypotensive effect remains at prolonged treatment. After the termination of treatment of the ABP gradually is returned to initial level.

Hydrochlorthiazidum exerts impact on mechanisms of a reabsorption of electrolytes in renal tubules, directly strengthening allocation of ions of sodium and chlorine in approximately identical quantities. Indirectly, as a result of diuretic activity of Hydrochlorthiazidum, the blood plasma volume therefore activity of a renin increases in plasma decreases, secretion of Aldosteronum increases, loss of potassium increases in urine and the content of potassium in blood serum decreases. The hydrochlorothiazide is thiazide diuretic of tiazid and is used at treatment of hypertensia and hypostases. Thiazide diuretics influence renal mechanisms of a reabsorption of electrolytes, increasing excretion of sodium and chlorides in approximately equivalent quantities, brake a sodium reabsorption. The mechanism of action is connected with influence on distal tubules of nephron where the reabsorption of ions of sodium, chlorine and water decreases. Excretion of potassium ions, magnesium and bicarbonate increase, calcium ions are late in an organism. The hydrochlorothiazide reduces plasma volume, increasing activity of a renin in plasma and secretion of Aldosteronum, with the subsequent increase in content of potassium in urine and decrease in its content in blood serum. By means of blockade combined use of an irbesartan leads system renin-angiotensin-aldosteronovoy to prevention of loss of potassium in the blood serum caused by this diuretic.

In too time diuretics of group of tiazid render hypotensive effect by means of decrease in peripheric resistance.

At combined use Hydrochlorthiazidum not only strengthens, but also angiotensin II extends anti-hypertensive action of blockers of receptors. Besides, combined use of blockers of receptors and thiazide diuretic drugs leads angiotensin II to noticeable decrease in the ABP at patients both with high, and with low activity of a renin, and "answer" to this combination therapy makes about 80% and above.

Pharmacodynamics. КО-ИРБЕСАН® is a combination irbesartana-the selection antagonist of receptors of angiotensin ІІ (AT1 type) and Hydrochlorthiazidum - diuretic of a class of tiazid. At combined use of an irbesartan and Hydrochlorthiazidum the anti-hypertensive effect increases. Irbesartan 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 of an irbesartan 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 APF (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. TO - ИРБЕСАН® the ABP at the minimum change of the heart rate (HR) reduces. 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. Purpose of 1 tablet 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 TO - ИРБЕСАН®в to a dosage of 150 mg/12,5 mg of 1 times a day is accorded by the effect similar to that which is reached at division of this daily dose into 2 receptions. At regular use during 1–2 weeks the effect gains stability and in 4–6 weeks reaches a maximum. The hypotensive effect remains at prolonged treatment. After the termination of treatment of the ABP gradually is returned to initial level.

Hydrochlorthiazidum exerts impact on mechanisms of a reabsorption of electrolytes in renal tubules, directly strengthening allocation of ions of sodium and chlorine in approximately identical quantities. Indirectly, as a result of diuretic activity of Hydrochlorthiazidum, the blood plasma volume therefore activity of a renin increases in plasma decreases, secretion of Aldosteronum increases, loss of potassium increases in urine and the content of potassium in blood serum decreases. The hydrochlorothiazide is thiazide diuretic of tiazid and is used at treatment of hypertensia and hypostases. Thiazide diuretics influence renal mechanisms of a reabsorption of electrolytes, increasing excretion of sodium and chlorides in approximately equivalent quantities, brake a sodium reabsorption. The mechanism of action is connected with influence on distal tubules of nephron where the reabsorption of ions of sodium, chlorine and water decreases. Excretion of potassium ions, magnesium and bicarbonate increase, calcium ions are late in an organism. The hydrochlorothiazide reduces plasma volume, increasing activity of a renin in plasma and secretion of Aldosteronum, with the subsequent increase in content of potassium in urine and decrease in its content in blood serum. By means of blockade combined use of an irbesartan leads system renin-angiotensin-aldosteronovoy to prevention of loss of potassium in the blood serum caused by this diuretic.

In too time diuretics of group of tiazid render hypotensive effect by means of decrease in peripheric resistance.

At combined use Hydrochlorthiazidum not only strengthens, but also angiotensin II extends anti-hypertensive action of blockers of receptors. Besides, combined use of blockers of receptors and thiazide diuretic drugs leads angiotensin II to noticeable decrease in the ABP at patients both with high, and with low activity of a renin, and "answer" to this combination therapy makes about 80% and above.

Indications to use:

- essetsialny arterial hypertension;

- arterial hypertension symptomatic, including at patients with diseases of kidneys and a diabetes mellitus ІІ type (as a part of anti-hypertensive therapy).

Route of administration and doses:

Patients from whom it is not possible to achieve adequate control of arterial pressure at monotherapy irbesartany or Hydrochlorthiazidum, can be transferred to administration of drug КО-ИРБЕСАН®

To patients with the arterial pressure (AP) more than 160/100 mm of mercury at a combination to a diabetes mellitus or/and a chronic renal failure the combination therapy can be appointed on start of treatment from purpose of 1 tablet CO-IRBESAN® in a dosage of 150 mg/12,5 mg of 1 times a day which afterwards, if necessary, to raise to 300 mg / 12,5мг 1 times in days.

Initial and maintenance dose - 1 tablet CO-IRBESAN®v to a dosage of 150 mg / 12,5 mg a day regardless of meal. The effective dose of Hydrochlorthiazidum usually makes 12,5 mg/days.

КО-ИРБЕСАН® in a dosage of 150 mg / 12,5 the mg of 1 times a day usually provides optimum 24 - hour control of the ABP. At insufficient efficiency of a dose of 150 mg / 12,5 mg of the drug КО-ИРБЕСАН® 1 of times a day appoint 300 mg / 12,5мг drug.

Use of drug in doses of more than 300 mg irbesartana/25 is not recommended to mg of a hydrochlorothiazide of 1 times/days.

Features of use:

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 hyponatremia have to be eliminated prior to drug CO-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 a renin - angiotensin - aldosteronovy system, concern to group of the increased risk concerning development of heavy arterial hypotension or a renal failure. Though such cases for drug TO - ИРБЕСАН® 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 CO-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 - OPN.

There are no clinical data on drug TO use - ИРБЕСАН® at the patients who transferred transplantation     of kidneys.

At establishment of pregnancy КО-ИРБЕСАН® it is necessary to cancel as soon as possible. For detection of malformations it is recommended to carry out ultrasonography of a fruit. It is unknown whether it is excreted ирбесартан in breast milk.

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:

- dizziness, orthostatic dizziness, general weakness;

- orthostatic hypotension;

- nausea, vomiting, dispeptic phenomena, heartburn;

- cough, rhinitis, pharyngitis;

- musculoskeletal pains (mialgiya, glossodynias, thorax pains);

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

Seldom:

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

- tachycardia, blood "inflows";

- rash, urticaria, Quincke's disease;

- disturbance of flavoring feelings;

- abnormal liver function, hepatitis;

- abdominal cavity pains;

- infections of urinary tract, a renal failure (in isolated cases - a renal failure at patients of group of the increased risk);

- decrease in level of hemoglobin.

Interaction with other medicines:

At simultaneous use КО-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.

- 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, digoxin, Cimetidinum;

- 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), did not reveal noticeable pharmacokinetic or pharmakodinamichesky  interactions;

- КО-ИРБЕСАН® it is possible to combine safely with blockers β ‑ adrenoceptors, antagonists of calcium of long action and thiazide diuretics. КО-ИРБЕСАН® in a dosage of 150 mg / 12,5мг does not influence digoxin pharmacokinetics. Operation of the inductors CYP 2C9, such as rifampicin, is unknown.

Contraindications:

- hypersensitivity to drug components;

- primary hyper aldosteronism;

- a hypovolemia (including against the background of high doses of diuretics);

- anury;

- pregnancy and period of a lactation;

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

Overdose:

Symptoms: arterial hypotension and tachycardia, is possible bradycardia.

Treatment: it is necessary to wash out a stomach, to appoint absorbent carbon, 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 a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 14 (for a dosage of 150 mg / 12,5 mg) or 7 (for a dosage of 300 mg / 12,5 mg) tablets place in a blister strip packaging from a film of white PVH/PE/PVDH and printing aluminum foil.

On 1 or 2 (for a dosage of 150 mg / 12,5 mg) or 2 or 4 (for a dosage of 300 mg / 12,5 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 firm – producer.