Коапровель®

General characteristics. Structure:

Tablets, film coated, 12,5 mg + 150 mg
Contains in one tablet:
active ingredients: a hydrochlorothiazide - 12,5 mg; ирбесартан - 150 mg; excipients: lactoses monohydrate - 38,5 mg, cellulose microcrystallic - 27,0 mg, croscarmellose sodium - 12,0 mg, a gipromelloza - 5,0 mg, magnesium stearate - 2,5 mg, silicon dioxide - 2,5 mg;
film cover: Опадрай® the II pink 32F24503 * - 10,0 mg, wax of karnaubskiya - less than 0,05 mg.

Tablets, film coated, 12,5 mg + 300 mg
Contains in one tablet:
active ingredients: a hydrochlorothiazide - 12,5 mg; ирбесартан - 300 mg.  excipients:  lactoses monohydrate - 89,5 mg, cellulose microcrystallic - 54,0 mg, croscarmellose sodium - 24,0 mg, a gipromelloza - 10,0 mg, magnesium stearate - 5,0 mg, silicon dioxide - 5,0 mg,
film cover: Опадрай® the II pink 32F24503 * - 20,0 mg, wax of karnaubskiya - less than 0,1 mg.

*® I pink 32F24503 contains lactoses monohydrate - 36,00%, a gipromelloza of-28,00%, a macrogoal-3000 - 10,00%, titanium dioxide (Е 171) - 25,45%, dye ferrous oxide red (Е 172) - 0,24%, dye ferrous oxide yellow (Е 172) - 0,31%.

Description
Tablets, film coated, 12,5 mg + 150 mg
Oval biconvex tablets, film coated salmoncolored color, with an engraving in the form of heart on one party and number 2875 on another. Tablets, film coated, 12,5 mg + 300 mg
Oval biconvex tablets, film coated salmoncolored
colors, with an engraving in the form of heart on one party and number 2876 on another.

Pharmacological properties:

Pharmacodynamics. KOAPROVEL is a combination of the antagonist of receptors angiotenzina-P - an irbesartan and thiazide diuretic - a hydrochlorothiazide. The combination of these ingredients has the additive hypotensive effect, reducing arterial pressure in higher degree, than each of them separately.

Irbesartan is an active dosage form of the selection antagonist of ATI of receptors (the AT subtype |) angiotensin - the Item. The selection antagonism of an irbesartan concerning AT receptors | leads to increase in levels of maintenance of a renin and angiotenzina-P and to decrease in level of maintenance of Aldosteronum in blood serum. Potassium level in blood serum slightly changes against the background of treatment irbesartany at monotherapy in the recommended doses (see the sections "Special Preventions and Precautionary Measures at Use" and "Interactions with Other Medicines and Other Forms of Interaction"). Irbesartan does not suppress APF (kininazu-P) which promotes education angiotenzina-P, and also bradikinin turns into inactive metabolites. Irbesartan does not need metabolic activation for manifestation of the action.

The hydrochlorothiazide is thiazide diuretic. 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 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. Presumably, by means of blockade of the renin-angiotensin-Aldosteronum system combined use of an irbesartan leads to prevention of loss of potassium in the blood serum caused by this diuretic. In case of a hydrochlorothiazide the beginning of a diuresis falls on the first 2 hours after its intake, reaches peak approximately in 4 hours, action remains about 6-12 hours.

The lowering of arterial pressure is shown after reception of the first dose of KOAPROVELYa, the maximum effect is observed in 6-8 weeks of treatment. The effect remains during prolonged treatment (one year). The increase in arterial pressure though which was not studied in case of KOAPROVELYa was not revealed at cancellation of an irbesartan or hydrochlorothiazide applied separately.

Distinctions in reaction to KOAPROVEL depending on age or a floor are not observed.

Pharmacokinetics. After intake of KOAPROVELYa absolute bioavailability of an irbesartan - 60-80%, and a hydrochlorothiazide - 50-80%. After intake the maximum concentration in blood serum are reached in 1,5-2 hours for an irbesartan and in 1-2,5 hours for a hydrochlorothiazide.

Linkng of an irbesartan with proteins of a blood plasma makes about 96%. The volume of distribution of an irbesartan makes 53-93 liters. 68% of a hydrochlorothiazide contact proteins of a blood plasma, the volume of its distribution makes 0,83-1,14 l/kg.

Linear dependence on a dose in the range of doses from 10 to 600 mg is characteristic of pharmacokinetic indicators of an irbesartan. Weaker, than proportional, increase at absorption was observed at oral administration of doses higher than 600 mg. The general and renal clearance makes 157-176 and 3,0-3,5 ml/min., respectively. An elimination half-life of an irbesartan - 11-15 hours. Concentration in blood serum reach steady value within 3 days after the beginning of therapy. At repeated receptions according to the scheme limited accumulation of an irbesartan in a blood plasma is observed once a day (<20%). A little higher concentration of an irbesartan in blood serum were found in women with the increased arterial pressure, than in men. However, there was no distinction in elimination half-lives and accumulation of an irbesartan. Therefore, female patients have no need for correction of a dosage of an irbesartan. AUC values and Stakh were higher at elderly (> than 65 years), than at young people (18-40 years). However, the elimination half-life was not considerably changed. Therefore correction of a dosage is not required from elderly people. The average elimination half-life of a hydrochlorothiazide fluctuates ranging from 5 till 15 o'clock.

After oral administration S-irbesartana 80-85% of the circulating radioactive carriers in a blood plasma represent not changed ирбесартан. Irbesartan is metabolized in a liver by conjugation with glucuronic acid and oxidations. The main circulating metabolite is the glucuronide of an irbesartan (about 6%). The researches in vitro demonstrate to what ирбесартан, is oxidized mainly by means of isoenzyme of p450 CYP2C9 cytochrome. Irbesartan and his metabolites are removed with bile and urine. After intake or intravenous administration of a 14C-irbesartan of 20% of radioactivity it is found in urine and traces - in Calais. Less, than 2% of not changed irbesartan are allocated with urine. The hydrochlorothiazide is not metabolized, but quickly removed through kidneys. At least 61% of the dose accepted inside are removed in not changed look within 24 hours. The hydrochlorothiazide gets through a placental barrier and is allocated in breast milk, but does not pass through a blood-brain barrier.

Renal failure: at patients, with a renal failure or the being on a hemodialysis, pharmacokinetic parameters of an irbesartan change slightly. Irbesartan does not leave by a hemodialysis. It was reported that at patients with clearance of creatinine <20 ml/min. increase in an elimination half-life was observed till 21 o'clock.

Liver failure: at patients with easy and average extent of disturbances of functions of a liver pharmacokinetic parameters of an irbesartan change slightly. At patients with a severe form of a liver failure researches were not conducted.

Indications to use:

Arterial hypertension of moderate or heavy severity.

Route of administration and doses:

Коапровель® accept regardless of meal time once a day. Коапровель® it has to be applied at patients whose ABP is insufficiently controlled irbesartany or a hydrochlorothiazide in monotherapy. The mg drug Коапровель® 12,5 + 150 mg (the tablet containing a hydrochlorothiazide / ирберсантан 12,5 mg + 150 mg, respectively) can be appointed to patients at whom the ABP is insufficiently controlled by a hydrochlorothiazide (12,5 mg/days) or irbesartany (150 mg/days) in monotherapy.
The mg drug Коапровель® 12,5 + 300 mg (the tablet containing a hydrochlorothiazide / ирберсантан 12,5 mg + 300 mg, respectively) can be appointed to patients at whom the ABP is insufficiently controlled irbesartany (300 mg) or the mg drug Коапровель® 12,5 + 150 mg.
In need of use for patients at whom the ABP is insufficiently controlled by the mg drug Коапровель® 12,5 + 300 mg doses of drugs in a combination can be increased to 300 mg of an irbesartan and 25 mg of a hydrochlorothiazide a day: 2 tablets of the drug Коапровель® 12,5 of mg + 150 mg or one tablet of the drug Коапровель® 25 of mg + 300 mg.
Maximum daily dose: 2 tablets of the drug Коапровель® 12,5 of mg + 150 mg or 1 tablet of the drug Коапровель® 25 of mg + 300 mg. Patients with a hypovolemia and/or a hyponatremia
At patients with a hypovolemia and a hyponatremia, for example receiving active diuretic therapy, it is necessary to correct completely before administration of drug of Koaprovel® these disturbances.
Patients with a renal failure
With a renal failure with KK more or the equal 30 ml/min. of dose adjustment of the drug Koaprovel® are not required from patients (see sections of "Contraindication", "With Care", "Special Instructions"). Patients with a liver failure
At a liver failure easy or moderate severity (5-6 and 7-9 points on a scale of Chayld-Pyyu) the drug Koaprovel® dose decline is not required, but it is necessary to be careful (see the section "With Care"). Patients of advanced age
Change of the mode of a drug dosing is not required from patients of advanced age
Коапровель®.
Children
Safety and efficiency of the drug Koaprovel® at children are not established.

Features of use:

Arterial hypotension - decrease in the volume of the circulating blood (VCB)
Occasionally Koaprovel® can cause arterial hypotension in patients with the raised ABP without the accompanying accessory factors of risk of development of arterial hypotension. Development of the arterial hypotension proceeding with symptomatology can be expected at patients with reduced OTsK or a hyponatremia owing to intensive diuretic care, a diet with restriction of table salt, diarrhea or vomiting. Such states have to be corrected prior to therapy by the drug Koaprovel® (see sections of "Contraindication" and "Route of Administration and Doses").
Unilateral or bilateral stenosis of renal arteries, renovascular hypertensia
At these states there is an increased risk factor of development of heavy arterial hypotension and renal failure in patients with a stenosis of one or two renal arteries at use of APF inhibitors or antagonists of receptors of angiotensin P. Though in case of the drug Koaprovel® so far such side effects were not observed completely it is impossible to exclude a possibility of their development.
Renal failure and transplantation of a kidney
When Koaprovel® is applied at patients with an impaired renal function, periodic control of content of potassium, creatinine and uric acid in blood serum is recommended. There is no experience concerning use of the drug Koaprovel® for patients after transplantation of a kidney. Коапровель® it should not be applied at patients with a severe form of a renal failure (KK less than 30 ml/min.). At patients with an impaired renal function thiazide diuretics can provoke strengthening of an azotemia.
Stenosis of the mouth of an aorta and stenosis of the mitral valve, hypertrophic subaortic stenosis
Extra care at appointment is necessary for such patients of vazodilatator, including Koaprovel®. Primary hyper aldosteronism
11rimeneniye the drug Koaprovel® it is inexpedient as such patients usually do not react   to the hypotensive drugs influencing a renin-angiotenzii-aldosteronovuyu system. Metabolic and endocrine effects
Therapy by thiazide diuretics, can reduce tolerance to glucose. At patients with a diabetes mellitus increase in doses of insulin or hypoglycemic means for intake can be required. Therapy by thiazide diuretics can cause manifestation of a latentnoprotekayushchy diabetes mellitus. Therapy by a hydrochlorothiazide in the dose of 12,5 mg which is contained in the drug Koaprovel® practically does not influence concentration of cholesterol and triglycerides. At therapy by thiazide diuretics at some patients the hyperuricemia or an aggravation of a course of gout can be observed.
Disturbances of water and electrolytic balance
Tiazida, including a hydrochlorothiazide, can cause disturbance of water and electrolytic balance (a hypopotassemia, a hyponatremia and a gipokhloremichesky alkalosis). Though at use of thiazide diuretics development of a hypopotassemia, parallel therapy irbesartany is possible can reduce the hypopotassemia caused by diuretic. The risk of a hypopotassemia increases at patients who at the same time receive glucocorticosteroids or adrenocorticotropic hormone. On the contrary, thanks to the irbesartan which is a part of the drug Koaprovel® the hyperpotassemia, especially in the presence of a renal failure and/or heart failure or a diabetes mellitus can take place. Regular control of content of potassium in blood serum at patients of risk group is recommended. Kaliysberegayushchy diuretics, potassium additives or kaliysoderzhashchy solezamenitel have to be appointed with care together with the drug Koaprovel® (see the section "Interactions with other medicines»). There is no confirmation that ирбесартан can reduce or prevent the hyponatremia caused by diuretics. Deficit of chlorides usually happens insignificant and does not demand treatment. Tiazida can reduce removal of calcium through kidneys and cause insignificant increases in content of calcium in blood serum on condition of lack of disturbances in calcium exchange. Noted hypercalcemia can be a sign of a latentnoprotekayushchy hyperparathyreosis. Reception of tiazid has to be stopped before carrying out a research of function of epithelial bodies. It was shown that tiazida increase removal of ions of magnesium kidneys that can lead to a hypomagnesiemia. Anti-doping test
The hydrochlorothiazide can yield a positive take when carrying out a drug test.
Development of allergic reactions to a hydrochlorothiazide is more probable at patients with the burdened allergological anamnesis or patients with bronchial asthma. At use of thiazide diuretics the aggravation of a current of a system lupus erythematosus was noted.
Possible influence on ability to manage vehicles or occupations other potentially dangerous types of activity
Influence of the drug Koaprovel® on ability of control of vehicles and mechanisms was not studied, but on the basis of its pharmakodinamichesky properties, it is improbable that Koaprovel® will influence this ability. During control of vehicles or mechanisms it is necessary to take into account that in rare instances at its reception dizziness and increased fatigue can be observed, it is necessary to be careful.

Side effects:

Frequency of the side reactions given below was defined according to the following: very often (> 1/10), it is frequent (> 1/100, <1/10); sometimes (> 1/1000, <1/100); seldom: (> 1/10000, <1/1000); very seldom (<1/10000), including separate messages.

Combination ирбесартан / hydrochlorothiazide

In placebo - the controlled researches at patients with arterial hypertension, the general frequency of by-effects in groups ирбесартана / a hydrochlorothiazide and placebo did not differ. The termination of therapy because of any clinical or laboratory by-effect was less frequent at the patients accepting combinations of an irbesartan and a hydrochlorothiazide than at the accepting placebos. Frequency of by-effects did not depend on a sex, age, race or a dose. In placebo - controlled researches in which various doses (/6,25 mg to 300 mg / 25 mg ирбесартана / a hydrochlorothiazide) received 898 petsiyent with arterial hypertension from 37,5 mg, the following by-effects were noted:

Disturbances of a nervous system: Often: dizziness Sometimes: orthostatic dizziness

Cordial:

Sometimes: arterial hypotension, hypostases, syncope, tachycardia

Vascular:

Sometimes: inflows

Gastrointestinal: Widespread: nausea/vomiting Sometimes: diarrhea

Skeletal and muscular system, connecting fabrics and bones: Sometimes: hypostasis of upper and lower extremities

Kidneys and urethral system: Often: the broken mocheotdeleniye

Reproductive system and mammary glands:

Sometimes: changes of sexual desire, sexual dysfunction

General condition and condition of an injection site: Often: exhaustion

Laboratory researches: at the patients receiving treatment irbesartanom/a hydrochlorothiazide noted changes of laboratory parameters which seldom reached a threshold of the clinical importance Often: increase in an urea nitrogen, creatinine and creatine kinase of plasma
Sometimes: decrease in levels of potassium and sodium in serum

Besides, from the moment of emergence of a combination of an irbesartan and a hydrochlorothiazide in the market, the following side reactions were also noted:

Disturbances of immune system:

Seldom: as well as at all antagonists of receptors angiotenzina-P, exceptional cases of allergic reactions, such as rash, a small tortoiseshell, a Quincke's disease were celebrated.

Disturbances of metabolism and food: Very seldom: hyperpotassemia

Disturbances of a nervous system: Very seldom: headache

Hearing disorder and vestibular mechanism: Very seldom: a ring in ears

Respiratory: Sometimes: cough

 

Gastrointestinal disturbances:

Very seldom: change of flavoring feelings, dyspepsia

Gepato-bshiarny disturbances:

Very seldom: anomalies of function of a liver, hepatitis

Disturbances of skepetno-muscular system, connecting fabrics and bones: Very seldom: mialgiya, arthralgia

Disturbances of kidneys and urinary system:

Very seldom: disturbance of renal function, including separate cases of a renal failure at patients of the increased risk

Additional information on separate components: In addition to above-mentioned side reactions, other side effects which were earlier reported in case of each of components can be possible side effects in case of KOAPROVELYa,

Irbesartan:

It is general disturbances:

Sometimes: thorax pains

Hydrochlorothiazide,

The by-effects (irrespective of communication with drug) noted at use of a hydrochlorothiazide in monotherapy include the following:

Blood and lymphatic system:

Aplastic anemia, marrow depression, hemolitic anemia, leukopenia,

neutropenia/agranulocytosis. tromopeniya.

Mental disturbances: Depression, sleep disorders

Disturbances of a nervous system: Dizziness, paresthesias, concern,

Vision disorders:

Passing vagueness of sight, xanthopsia

Cordial disturbances: Arrhythmias

Vascular disorders: Postural hypotension

Respiratory disturbances

Respiratory distress a syndrome (including a pneumonitis and hypostasis of a lung)

Gepatobiliarny disturbances:

Jaundice (intra hepatic cholestatic jaundice)

Skin and hypodermic fabrics

Anaphylactic reactions, toxic necrosis of epidermis, skin reactions like a lupus erythematosus, a nekrotizirovanny angiitis (a vasculitis, a skin vasculitis), photosensitivity reactions, rash, an aggravation of skin manifestations of a lupus erythematosus, a small tortoiseshell.

Disturbances of skeletal and muscular system, connecting fabrics and bones: Muscular spasms, weakness

Disturbances of kidneys and urinary system: Intersticial nephrite, dysfunction of kidneys

General disturbances: The increased temperature

Laboratory researches:

Disturbances of electrolytic balance (including a hypopotassemia and a hyponatremia, see section 4.4), a glucosuria, a hyperglycemia, a hyperuricemia, increase in level of cholesterol and triglycerides.

Interaction with other medicines:

The anti-hypertensive effect of the drug Koaprovel® can be strengthened by simultaneous use of other hypotensive drugs, especially ganglioblokator and blockers of beta adrenoceptors, diazoxide. Irbesartan and a hydrochlorothiazide (at doses to 300 mg irbesartana/25 hydrochlorothiazide mg) were safely applied in combination with other hypotensive drugs, including blockers of "slow" calcium channels and beta adrenoblockers. Preliminary therapy by diuretics in high doses can lead to a hypovolemia and the increased risk of development of arterial hypotension (see the section "Special Instructions"), With lithium
Diuretics reduce renal clearance of lithium and increase risk of development of toxic effects of lithium. Besides, at a combination of drugs of lithium to inhibitors of an angiotensin-converting enzyme (APF) increase in plasma concentration of lithium was also observed. At an irbesartan similar effects were observed so far extremely seldom. In case of administration of drug of Koaprovel® the risk of toxic effect of lithium can be increased. Simultaneous use of the drug Koaprovel® with drugs of lithium is not recommended. If this combination after all is necessary, then it is necessary to control serumal concentration of lithium.
With the medicines influencing the content of potassium in blood
Removal of potassium at reception of a hydrochlorothiazide decreases thanks to kaliysberegayushchy effect of an irbesartan. However this effect of a hydrochlorothiazide can be strengthened by other medicines causing loss of potassium and a hypopotassemia (for example, diuretics, laxatives, Amphotericinum, karbenoksolony, sodium salt of penicillin G, derivatives of salicylic acid). On the contrary, based on experience of use of other medicines which reduce activity system renin-angiotensin-aldosteronovoy, the accompanying use of the kaliysberegayushchy diuretics, potassium additives, kaliysoderzhashchy solezamenitel or other medicines capable to increase the content of potassium in blood serum (for example, sodium salt of heparin) can lead to increase in potassium concentration in blood serum. Patients of risk group are recommended to carry out adequate control of content of potassium in blood serum.
With cardiac glycosides, antiarrhytmic means
At combined use with the drug Koaprovel®, in case of the emergence of a hypopotassemia and a hypomagnesiemia caused by the thiazide diuretic which is its part danger of development of arrhythmias including posing hazard to life increases. At use of such combinations carrying out regular control of content of potassium in blood serum is required (see the section "Special Instructions").
With non-steroidal anti-inflammatory drugs (NPVP)
At simultaneous use of antagonists of receptors of angiotensin II and non-steroidal anti-inflammatory drugs (for example, the selection inhibitors of cyclooxygenase 2 (TsOG-2), acetylsalicylic acid (more than 3 g/days) and non-selective NPVP) easing of anti-hypertensive effect of the drug Koaprovel®, due to decrease in efficiency of a hydrochlorothiazide is possible.
As well as in a case with APF inhibitors, combined use of antagonists of receptors of angiotensin II and NPVP can increase risk of disturbance of renal function, including a possibility of development of an acute renal failure and lead to increase in potassium ions in blood serum, especially, at patients with already impaired renal function. At purpose of this combination it is necessary to observe precautionary measures, especially at elderly patients. During a combination therapy patients should not be dehydrated by antagonists of receptors of angiotensin II and NPVP, and at them it is necessary to control indicators of function of kidneys.
Additional information on interaction with other medicines for a nrbssartap
The pharmacokinetics of an irbesartan at its combination to a hydrochlorothiazide and nifedipine does not change. Irbesartan, is generally metabolized by means of an isoenzyme
CYP2C9 and, to a lesser extent, - by a glyukuronirovaniye. Considerable pharmacokinetic and pharmakodinamichesky interactions at combined use of an irbesartan with the warfarin, drug which is exposed to metabolism by means of CYP2C9 isoenzyme were not observed. Effects of inductors of an isoenzyme of CYP2C9, such as rifampicin, on pharmacokinetics of an irbesartan were not estimated. The pharmacokinetics of digoxin and a simvastatin did not change at combined use with irbesartany. Additional information on interaction with other medicines for a hydrochlorothiazide
With ethanol, barbiturates or drugs
Strengthening of the orthostatic hypotension caused by thiazide diuretics by them can be observed.
With hypoglycemic means (for intake and insulin)
Increase in a dose of hypoglycemic means as the hydrochlorothiazide can increase concentration of glucose in blood can be required (see the section "Special Instructions").
With kolestiraminovy pitch or kolestipoly
Absorption of a hydrochlorothiazide in the presence of the anion-exchange pitches decreases. It is necessary to divide on time reception of these drugs not less than for 4 hours. With glucocorticosteroids, adrenocorticotropic hormone
Perhaps, more expressed disturbance of water and electrolytic balance, in particular, increases danger of emergence of a hypopotassemia. With catecholamines (for example, with Norepinephrinum)
The effect of these means can be weakened under the influence of thiazide diuretics. With not depolarizing muscle relaxants (tubocurarine)
The effect of the websites which are not depolarizing миорелак can be strengthened a hydrochlorothiazide of ohms. With antigouty means
At a concomitant use of the drug Koaprovel® and antigouty means increase in doses of antigouty drugs because of a possibility of increase serumal concentration of uric acid can be required at reception of a hydrochlorothiazide. At the same time increase in doses of a probenetsid or Sulfinpyrazonum can be required. Increase in risk of development of allergic reactions to Allopyrinolum. With calcium salts
Thiazide diuretics can increase the content of calcium in blood serum. If the calcic additives or drugs influencing the content of calcium (for example have to be appointed, at therapy by vitamin D), then control of content of calcium in blood serum and carrying out the corresponding correction of a dosage of drugs of calcium is necessary.
With beta adrenoblockers and diazoxide
Thiazide diuretics increase risk of development of their hyper glycemic effects. With anticholinergics (for example, atropine, beperideny) Increase in bioavailability of diuretics of a thiazide row due to delay of motility of digestive tract. With amantadiny
Tiazida can increase risk of emergence of its side effects. With cyclophosphamide, a methotrexate
Tiazida can reduce allocation by kidneys of these cytotoxic means and strengthen their myelosuppressive effects.

Contraindications:

 Hypersensitivity to active agents, to any of excipients (see the section "Structure") or to other derivatives of sulfonamides (the hydrochlorothiazide is to sulphonamide derivatives). A heavy renal failure (KK less than 30 ml/min.), an anury (in connection with existence in composition of drug of a hydrochlorothiazide).
Refractory hypopotassemia, hypomagnesiemia, hypercalcemia (in connection with existence in composition of drug of a hydrochlorothiazide).
Heavy liver failure (a functional class C or more than 9 points on a scale of Chayld-Pyyu), biliary cirrhosis, a cholestasia (in connection with existence in composition of drug of a hydrochlorothiazide as the minimum disturbances of water and water and electrolytic balance at such patients can provoke a hepatic coma).
Pregnancy (see the section "Pregnancy and Period of a Lactation").
The lactation period (see the section "Pregnancy and Period of a Lactation"). Age up to 18 years (efficiency and safety are not established). Hereditary intolerance of a galactose, insufficiency of lactase  or disturbance of absorption of glucose and galactose.
 With care
At a stenosis of the aortal or mitral valve or a hypertrophic subaortic stenosis (GOKMP).
At a hypovolemia, a hyponatremia, the diuretics arising, for example, at treatment, a hemodialysis, observance of a diet with restriction of consumption of table salt, diarrhea, vomiting (danger of an excessive lowering of arterial pressure, especially at reception of the first dose, see the section "Route of Administration and Doses").
At a bilateral or unilateral stenosis of renal arteries, chronic heart failure of the III—IV stage on NYHA classification (as well as at use of other means influencing renin-angiotensin-aldosteronovuyu system it is impossible to exclude existence of risk of development of arterial hypotension, an oliguria and/or azotemia and the progressing acute renal failure and/or death though at use of the drug Koaprovel® of similar effects it was not observed yet).
At coronary heart disease and/or atherosclerotic defeat of vessels of a brain (risk of strengthening of ischemia of a myocardium or brain up to development of a myocardial infarction or a stroke at excessive decrease in the ABP). At a renal failure of easy and moderate severity (KK from 60 to 30 ml/min.) (risk of increase in an azotemia, increase in concentration of uric acid in blood in connection with existence in composition of drug of a hydrochlorothiazide and development of a hyperpotassemia in connection with existence in composition of drug of an irbesartan). After transplantation of a kidney (lack of experience of a clinical use). At a liver failure of a functional class A and B (5-6 points and 7-9 points on criteria for evaluation of a scale of Chayld-Pyyu) (lack of clinical experience, danger of development of a hepatic coma at the slightest disturbances of water and electrolytic balance).
At a diabetes mellitus (in connection with existence in composition of drug of a hydrochlorothiazide decrease in tolerance to glucose, increase in need for insulin and hypoglycemic means for intake is possible).
At the increased concentration of cholesterol and triglycerides in blood (in connection with existence in composition of drug of a hydrochlorothiazide as thiazide diuretics, especially in high doses, can increase concentration of cholesterol and triglycerides in blood; however at a dose of a hydrochlorothiazide of 12,5 mg these effects were minimum or were absent).
At gout (in connection with existence in composition of drug of a hydrochlorothiazide increase in concentration of urates in blood is possible).
At a hyperpotassemia, a concomitant use of kaliysberegayushchy drugs and or the salt substitutes (risk of a hyperpotassemia) containing potassium.
At a system lupus erythematosus (a current aggravation) (in connection with existence in composition of drug of a hydrochlorothiazide the exacerbation of this disease is possible). At a concomitant use of other hypotensive drugs (a possibility of potentiation of their anti-hypertensive action).
At a latentnoprotekayushchy hyperparathyreosis (in connection with existence in structure
hydrochlorothiazide drug, as thiazide diuretics, especially in high
doses, increase risk of development or strengthening of a hypercalcemia).
At a sympathectomy (risk of strengthening of anti-hypertensive effect
hydrochlorothiazide).
Pregnancy and period of a lactation
Pregnancy
Administration of drug of Koaprovel® at pregnancy is contraindicated.
The inhibitors of an angiotensin-converting enzyme coming to a cavity of the uterus at their reception by pregnant women in the second and third trimester of pregnancy caused damage and death of the developing fruit. Therefore, as well as no other drug which influences directly renin-angiotensin-aldosteronovuyu system ирбесартан can be applied at pregnancy.
Thiazide diuretics get through a placental barrier and are found in umbilical blood. Usually use of diuretics for pregnant women is not recommended and subjects mother and a fruit to unnecessary risk, including development of fetalis or neonatal jaundice, thrombocytopenia and perhaps other adverse reactions which are observed at adults. Especially reception of a hydrochlorothiazide in the first trimester of pregnancy is not recommended.
If the patient plans pregnancy or if during treatment the drug Koaprovel® established pregnancy, then administration of drug of Koaprovel® has to be stopped (in case of pregnancy approach, as soon as possible). In need of continuation of hypotensive therapy, the patient should appoint alternative hypotensive therapy the drugs having the established safety profile at pregnancy. Lactation period
It is unknown whether gets ирбесартан or its metabolites into breast milk, the hydrochlorothiazide gets into breast milk.
Коапровель® it is contraindicated to use during the entire period of feeding by a breast because of potential risk for the newborn. In case of the imperative need of administration of drug of Koaprovel® by mother, breastfeeding has to be stopped.

Overdose:

As the most probable manifestations of overdose of an irbesartan it is possible to expect the expressed decrease in the ABP and tachycardia; also bradycardia can take place. The overdose of a hydrochlorothiazide is followed by decrease in content in blood of electrolytes (a hypopotassemia, a hyponatremia, a hypochloraemia, a hypomagnesiemia) and dehydration as a result of an excess diuresis. The most general signs and symptoms of overdose - nausea and drowsiness. The hypopotassemia can lead to spasms and/or strengthening of arrhythmias in case of the accompanying use of digoxin and a sotalol.
There is no special information on drug Koaprovel® overdose treatment. In case of overdose careful control of a condition of the patient is required, therapy has to be symptomatic and supporting. Treatment depends on time which passed from the moment of medicine reception and on weight of symptoms.
The recommended measures include provoking of vomiting and/or a gastric lavage. At overdose there can be useful a use of absorbent carbon. Regular control of content of electrolytes and creatinine in blood serum has to be carried out. In case of the expressed decrease in the ABP of the patient it is necessary to lay on a back in situation with the raised lower extremities and as soon as possible to begin completion of volume of the circulating blood and elimination of disturbances of water and electrolytic balance of blood.
Irbesartan   is also not brought by means of a hemodialysis. Extent of removal of a hydrochlorothiazide by means of a hemodialysis is not established.

Storage conditions:

To store at a temperature not above 30 °C. To store in the place, unavailable to children. Period of validity 3 years.
Not to accept drug after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 12,5 mg + 150 mg and 12,5 mg + 300 mg. On 14 tablets in the blister PVC/PVDH/aluminium.
On 1, 2, 4 or 7 blisters together with the application instruction in a cardboard pack.