Pharmacological properties

Pharmacodynamics. a diokor — antihypertensive medicament which part are the antagonist of receptors of ii angiotensin and thiazide diuretic.

renin-angiotensin-aldosteronovoy of a system is Active hormone angiotensin II which is formed of angiotensin I with the participation of APF. Angiotensin II contacts the specific receptors located on cellular membranes in different fabrics. It possesses a wide range of the physiological effects including both the direct, and mediated participation in regulation of the ABP. As powerful vasoconstrictive substance angiotensin II causes direct angiotonic action. Besides, it stimulates secretion of Aldosteronum and promotes a sodium delay.

Valsartan — the active and specific antagonist of receptors of angiotensin II intended for intake. It affects selectively the receptors of the AT _{1 subtype} which are responsible for effects of angiotensin II. In alsartan does not show any partial agonistic activity concerning receptors of the AT _{1 subtype. The affinity of a valsartan to receptors of the AT 1 subtype p is about 20,000 times higher, than to receptors of the AT 2 subtype .}

Valsartan does not inhibit APF (kininaza of II) which turns angiotensin I into angiotensin II and destroys bradykinin. Do not note any side effects caused by bradykinin. In clinical trials during which valsartan compared to APF inhibitor the frequency of cases of dry cough was much lower at the patients applying valsartan than at the patients applying APF inhibitor. Valsartan does not enter interaction and does not block the receptors of other hormones or ion channels playing an important role in regulation of function of a cardiovascular system.

with hypertensia medicament causes decrease in the ABP In patients, without influencing at the same time ChSS.

At most of patients after reception of a single dose of medicament the beginning of antihypertensive activity is noted within 2 h, and the maximum decrease in the ABP is reached in 4–6 h. The antihypertensive effect remains more than 24 h after reception of a single dose of Diokor. On condition of regular use of medicament the maximum therapeutic effect is usually reached within 2–4 weeks and maintained at the reached level during long therapy. At combination with a hydrochlorothiazide more effective decrease in the ABP is reached.

Point of application of effect of thiazide diuretics is the bast layer of distal twisting renal tubules where the receptors having high sensitivity to effect of diuretics are located and there is an oppression of transport of ions of sodium and chlorine. The mechanism of action of tiazid is connected with oppression of the pump Na ⁺ Cl ^– that occurs due to the competition for places of Cl ^{transport –} . As a result of it excretion of ions of sodium and chlorine increases approximately equally. Owing to diuretic action note reduction of volume of the circulating blood plasma therefore raise activity of renin, secretion of Aldosteronum, removal with urine of potassium and as a result — decrease in potassium concentration in blood plasma. The interrelation between renin and Aldosteronum is mediated by angiotensin II therefore use of the antagonist of receptors of angiotensin II reduces the potassium loss connected with use of thiazide diuretic.

Pharmacokinetics. After intake the absorption of a valsartan and hydrochlorothiazide happens quickly, however extent of absorption varies over a wide range. The average size of absolute bioavailability Diokor is 23%.

Valsartan. In the range of the studied doses the kinetics of a valsartan has linear character. At repeated use of medicament of changes of kinetic indicators did not note. At administration of medicament of 1 times a day the cumulation is insignificant.

Valsartan substantially (for 94–97%) contacts proteins of blood plasma, generally albumine. Equilibrium volume of distribution low (≈17 l). Removal of a valsartan with a stake makes 70% (from the dose accepted inside). With urine ≈30%, generally in not changed look are removed.

At use of a valsartan with AUC food decreases by 48% though, beginning approximately with 8 h after administration of drug, its concentration in blood plasma both at reception on an empty stomach, and at meal time is identical. Reduction of AUC is not followed by considerable decrease in therapeutic effect.

Hydrochlorothiazide. After intake the absorption of a hydrochlorothiazide happens very quickly (t _max — about 2 h). The medicament pharmacokinetics in phases of distribution and removal is described in general by the biexponentsialny descending curve; T _½ a final phase — 6–15 h

average size AUC increases In the therapeutic range of doses in direct ratio to increase in a dose. At repeated uses the pharmacokinetics of a hydrochlorothiazide does not change; at use of 1 times a day the cumulation is insignificant.

At intake the bioavailability of a hydrochlorothiazide is 60–80%. It is removed with urine: 95% of a dose in not changed look and ≈4% — in the form of a hydrolyzate 2-amino-4-chloro-m-benzenedisulfonamida.

At a concomitant use of a hydrochlorothiazide with food were noted both by increase, and decrease in its system bioavailability in comparison with the corresponding indicator at reception on an empty stomach. Range of these changes and clinically we do not mean small.

Valsartan / hydrochlorothiazide. At a concomitant use with valsartany the system bioavailability of a hydrochlorothiazide decreases by ≈30%. Simultaneous use of a hydrochlorothiazide has no significant effect on kinetics of a valsartan. The specified interaction does not affect efficiency of the combined use of a valsartan and a hydrochlorothiazide. In controlled clinical trials the accurate antihypertensive effect of this combination which exceeded that of each of components separately and also effect of placebo is revealed.

Indication

Ag at patients at whom monotherapy is inefficient.

Use

Recommended medicament dose — 1 tablet of 80 mg / 12.5 mg (a diokor 80) 1 time a day. at insufficient decrease hell in 3–4 weeks of treatment 1 tablet of 160 mg / 12, 5 mg (a diokor 160) 1 time a day is recommended to consider the possibility of continuation of treatment in a dosage. the maximum daily dose makes 320 mg / 25 mg. the maximum antihypertensive effect is reached for 2–4 weeks of use. the medicament can be taken irrespective of meal, washing down with a small amount of water.

In a renal failure. For patients with insignificant and moderate renal failures (clearance of creatinine of 30 ml/min.) of dose adjustment it is not required.

In an abnormal liver function. For patients with an insignificant and moderate liver failure of not biliary origin and without cholestasia the dose of a valsartan should not exceed 80 mg, it is necessary to appoint medicament with care.

Patients of advanced age. For patients of advanced age of dose adjustment it is not required.

Duration of use of medicament is defined by the doctor individually.

Contraindication

Hypersensitivity to any of components of medicament and to other medicines which are sulfonamide derivatives.

Heavy abnormal liver functions, biliary cirrhosis and cholestasia.

Heavy renal failures (clearance of creatinine of 30 ml/min.), anury.

Refractory hypopotassemia, hyponatremia, hypercalcemia, symptomatic hyperuricemia. The pregnant women and women planning pregnancy (see Use during pregnancy and feeding by a breast).

Simultaneous use of antagonists of receptors of angiotensin, including valsartan, or inhibitors of angiotensin-converting enzyme with aliskireny patients with diabetes or a renal failure (speed of glomerular filtration of 60 ml/min. / 1.73 m ² ).

Side effects

Side reactions have in general slight and passing character and are given below.

from a cardiovascular system: tachycardia, arterial hypotension, vasculitis.

from the system of blood: neutropenia, thrombocytopenia.

from nervous system: headache, dizziness, hypesthesia, paresthesia, syncope, insomnia, drowsiness.

from an organ of hearing: a noise/ring in ears, vertigo, average otitis.

from an organ of sight: disorder of vision.

from a respiratory system: a nasopharyngitis, cough, congestion of a nose, bronchitis, an acute bronchitis, a stethalgia, an asthma, pharyngolaryngeal pain, sinusitis, it is very rare — the fluid lungs with granulotsitarny infiltration and deposition of IgG in alveolar membranes connected with use of a hydrochlorothiazide. Not cardiogenic fluid lungs can be mediated immunological by idiosyncratic reaction to a hydrochlorothiazide that is noted seldom.

from digestive system: diarrhea, abdominal pain, dyspepsia, dryness in a mouth, a gastroenteritis, nausea, isolated cases of increase in indicators of function of a liver.

metabolism Disturbance: hyperpotassemia, dehydration.

from an urinogenital system: a pollakiuria, it is very rare — a renal failure, OPN, infections of urinary tract, decrease in a libido.

from skin and hypodermic cellulose: the increased sweating, rash, an itching.

from the immune system: reactions of a hypersensitivity/allergy, including a serum disease.

from a musculoskeletal system: dorsodynia, arthralgia, myotonia, muscle strain, neck pain, extremity pain, sprain, myalgia, arthritis.

General disturbances: fatigue, nervousness, asthenia, fervescence, viral infections, hypostasis, peripheral hypostasis, Quincke's disease.

Laboratory indicators: hypopotassemia, hyponatremia, increase in level of bilirubin, creatinine and urea nitrogen, decrease in level of hemoglobin and indicator of a hematocrit.

Other side reactions characteristic of a hydrochlorothiazide can be potential also for Diokor even if they were not noted at use of the combined medicament (valsartan / a hydrochlorothiazide).

Hydrochlorothiazide is widely applied for many years, and applied in the dose exceeding being Diokor's part more often. When performing monotherapy by thiazide diuretics, including a hydrochlorothiazide, emergence of some side reactions is possible.

Change of electrolytes and metabolism. It was reported about development of a hypopotassemia at treatment by thiazide diuretics. At use of thiazide diuretics the hypercalcemia, a hyponatremia and a gipokhloremichesky alkalosis which can induce hepatic encephalopathy or a hepatic coma can develop. Tiazida cause increase in excretion with magnesium urine which can lead to a hypomagnesiemia. Thiazide diuretics are capable to cause increase in concentration of XC, TG and uric acid in blood plasma which can provoke gout attacks at patients with an asimptomny course of the disease. Decrease in a glyukozotolerantnost is possible that can cause a demonstration of latent diabetes.

Other possible side reactions

from a cardiovascular system: arrhythmia, heart failure, postural hypotension which severity increases at alcohol intake, use of anesthetics or sedatives; nasal bleedings.

from the system of blood: thrombocytopenia, sometimes with a purpura, it is very rare — a leukopenia, an agranulocytosis, oppression of function of marrow, hemolytic anemia, aplastic anemia.

from mentality: sleep disorder, depression, confusion of consciousness, disorientation, change of mood.

from an organ of sight: xanthopsia, acute closed-angle glaucoma.

from a respiratory system: respiratory insufficiency, respiratory distress, pneumonitis.

from digestive system: loss of appetite, moderate nausea and vomiting, disturbances from a GIT, a constipation, feeling of thirst, inflammation of sialadens, it is very rare — pancreatitis.

from a gepatobiliarny system: cholestasia or jaundice, cholecystitis.

from skin and hypodermic cellulose: urticaria and other types of rash, eczema, purpura, photosensitization; very seldom — the necrotizing vasculitis and a toxic epidermal necrolysis, skin reactions reminding a system lupus erythematosus, aggravation of skin manifestations of a system lupus erythematosus, a multiformny erythema.

from an urinary system: interstitial nephrite.

from a reproductive system: impotence.

General disturbances: anaphylactic reactions, shock.

Special instructions

Change of balance of electrolytes. it is necessary to be careful at simultaneous use of a diokor with kaliysberegayushchy diuretics, potassium additives, kaliysoderzhashchy substitutes of edible salt and also with medicines which can cause increase in level of potassium in blood (for example heparin).

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during treatment by thiazide diuretics it was reported about hypopotassemia cases.

recommends to carry out

regular monitoring of level of potassium in blood serum.

As well as at any patients receiving treatment by diuretics through appropriate periods should be determined by

periodically serumal levels of electrolytes.

Patients with deficit in an organism of sodium and/or OCK. Patients with the significant deficit in an organism of sodium and/or OCK, for example at accepting diuretics in high doses, occasionally in an initiation of treatment medicament can have an arterial hypotension with clinical manifestations. Therefore before an initiation of treatment the medicament Diokor recommends to carry out correction of contents in an organism of sodium and/or OCK.

in case of development of hypotension of the patient should be turned to horizontal position and if necessary to carry out in to infusion of physiological solution. After stabilization the ABP the Diokor medicament treatment can be continued.

Patients with heavy heart failure or other cases of activation system renin-angiotensin-aldosteronovoy. At patients whose renal functions depend on activity system renin-angiotensin-aldosteronovoy (for example at patients with acute coronary insufficiency), treatment by APF inhibitors can cause an oliguria and/or a progressive azotemia, in some cases — to lead to development of OPN. Drug use by the patient with heavy chronic heart failure is not proved as it cannot be excluded that because of suppression system renin-angiotensin-aldosteronovoy use of a valsartan can also be connected with a renal failure.

Primary hyper aldosteronism. It is not necessary to use medicament at patients with primary hyper aldosteronism as their renin-angiotenzinovaya the system is not activated.

Aortal and mitral stenosis, subaortic hypertrophic stenosis. As well as with other vazodilatator, patients should be especially careful at medicament use with an aortal and mitral stenosis or a subaortic hypertrophic stenosis.

Renal artery stenosis. At patients with a unilateral or bilateral renal artery stenosis, or a stenosis of an artery of the only kidney valsartan can lead to increase in level of creatinine in plasma or urea in blood therefore this category of patients should not apply it.

Renal failure. When prescribing medicament with a slight or moderate renal failure (clearance of creatinine of ≥30 ml/min.) of dose adjustment it is not required to patients, however periodic control of content of potassium in blood plasma, creatinine and uric acid is recommended. Thiazide diuretics can provoke an azotemia at patients with a chronic renal failure. They are inefficient as monotherapy in a heavy renal failure (clearance of creatinine of 30 ml/min.), however they can be applied with appropriate care in a combination with loopback diuretics even at patients with clearance of creatinine of 30 ml/min.

Simultaneous use of antagonists of receptors of angiotensin, including valsartan, or inhibitors of angiotensin-converting enzyme with aliskireny at patients with a renal failure (speed of glomerular filtration of 60 ml/min. / 1.73) it is contraindicated to m ² . Transplantation of a kidney. There are no data on safety of use of a valsartan for patients from the kidney which is recently carried out by transplantation.

System lupus erythematosus. There are messages that thiazide diuretics can cause aggravation of a system lupus erythematosus.

Other metabolic disturbances. Thiazide diuretics can cause change of tolerance to glucose and also increase in concentration of XC, TG and uric acid in blood. Sick diabetes dose adjustment of insulin or oral hypoglycemic means can be necessary.

Tiazida's

can reduce excretion of calcium with urine and lead to intermittent and small increase in level of calcium in blood serum in the absence of the known disturbances of metabolism of calcium. The considerable hypercalcemia can testify to the latent hyperparathyreosis. Use of tiazid should be stopped before test of function of epithelial bodies.

Abnormal liver function. With insignificant and moderate abnormal liver functions without cholestasia of dose adjustment it is not required from patients. However medicament should be taken with caution. Liver diseases significantly do not change pharmacokinetic parameters of a hydrochlorothiazide.

Fotochuvstvitelnost. There were messages about photosensitization cases at intake of thiazide diuretics. If during treatment there is a reaction of photosensitivity, it is necessary to stop medicament treatment. If there is a need for repeated administration of diuretic, it is recommended to protect vulnerable areas from the sun or artificial ultra-violet radiation.

General. It is necessary to be especially careful at medicament use to patients at whom the hypersensitivity to other antagonists of receptors of angiotensin II was noted. Allergic reactions to a hydrochlorothiazide, most likely, arise at patients with an allergy and OH.

Quincke's disease. About developing of a Quincke's edema (including a laryngeal edema and a glottis that leads to obstruction of airways, and/or a face edema, lips, a throat and/or language) it was reported at the patients receiving valsartan. Some of them had in the anamnesis a Quincke's edema at use of other drugs, including other antagonists of receptors of angiotensin II. At edematization of Quincke the medicament treatment should be stopped immediately. Contraindicated repeated use of drug.

Acute closed-angle glaucoma. Use of a hydrochlorothiazide, sulfonamide was connected with emergence of idiosyncratic reaction which can lead to acute tranzitorny short-sightedness and acute closed-angle glaucoma. Sharp decrease in visual acuity or eye pain is noted. This symptomatology usually proceeds within several hours a week at medicament use. Not treated glaucoma can lead to irreversible loss of sight. It is necessary to stop medicament use immediately. Risk factor of developing acute closed-angle glaucoma is allergic reaction to use of sulfonamide or penicillin. The hydrochlorothiazide can reduce the level of the iodine connected with proteins in blood plasma.

Hydrochlorothiazide is capable to increase concentration of free bilirubin in blood serum.

Use during pregnancy and feeding by a breast. Pregnancy. Valsartan. Use of antagonists of receptors of angiotensin II is contraindicated to the pregnant women and women planning pregnancy. The women planning pregnancy should appoint alternative antihypertensive therapy with the established safety profile concerning use during pregnancy. If pregnancy is revealed during treatment by Diokor, medicament should be cancelled immediately and if necessary to replace with other medicine allowed for use for pregnant women.

Considering the mechanism of action of antagonists of receptors of angiotensin II, it is impossible to exclude risk for a fruit at use of the medicament Diokor in the I trimester. It is known that use of antagonists of receptors of angiotensin II during II and III trimester can induce a fetotoksichnost (depression of function of kidneys, an oligoamnios, a delay of ossification of bones of a skull) and neonatal toxicity (renal failure, hypotension, a hyperpotassemia).

If antagonists of receptors of angiotensin II applied

, since the II trimester of pregnancy, carrying out ultrasonic examination of function of kidneys and a skull is recommended. Babies whose mothers antagonists of receptors of angiotensin II accepted need careful observation concerning hypotension.

Hydrochlorothiazide. The hydrochlorothiazide gets through a placental barrier. On the basis of pharmacological mechanisms of action of a hydrochlorothiazide its use in II and III trimester of pregnancy can lead to disturbance of fetoplacental blood circulation and cause in a fruit and the newborn such effects as jaundice, disturbance of electrolytic balance and thrombocytopenia.

feeding Period breast. It is unknown whether gets valsartan into breast milk. The hydrochlorothiazide gets into breast milk in insignificant quantity. Tiazida in high doses cause a diuresis which can lead to decrease in producing breast milk. During feeding by a breast it is necessary to give preference to alternative methods of treatment with more studied safety profile concerning use during feeding by a breast.

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If needs extremely use of drug, feeding by a breast should be stopped.

Children. Safety and efficiency of use of Diokor for children are not established therefore medicament should not be used in pediatric practice.

Ability to influence speed of response at control of vehicles or work with other mechanisms. At the beginning of therapy by medicament (1–2 days) it is necessary to refrain from control of vehicles or work with other mechanisms. Further it is necessary to consider that speed of response can be reduced in the presence of such symptoms as dizziness, a headache, fatigue or nausea.

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Interaction

Interaction, connected with a combination valsartan / a hydrochlorothiazide

does not recommend simultaneous use

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Lities. At simultaneous use of medicaments of lithium with APF inhibitors or thiazide diuretics, including a hydrochlorothiazide, reversible increase in concentration of lithium in blood plasma and toxicity was noted. Experience of simultaneous use of Dikor and medicaments of lithium is absent therefore such combination is not recommended. If medicament use nevertheless is necessary, then control of concentration of lithium in blood plasma at their simultaneous use is recommended.

Simultaneous use demanding extra care

Other antihypertensive drugs. Strengthening of antihypertensive effect at the combined use of Diokor with other antihypertensive medicaments is possible (for example APF inhibitors, blockers of β-adrenoceptors, blockers of calcium channels).

Pressor amines (for example noradrenaline, adrenaline). Decrease in the answer to pressor amines, however not so that it was necessary to exclude use can be noted.

NPVP, including selection TsOG-2 inhibitors, acetylsalicylic acid of 3 g/days and non-selective NPVP. Decrease in antihypertensive effect both the antagonist of angiotensin II, and a thiazide component at simultaneous use with NPVP is possible (for example derivatives of salicylic acid, indometacin). Simultaneous use of the specified medicines can lead to depression of function of kidneys and increase in level of potassium in blood plasma. Therefore control of function of kidneys is recommended during treatment and also control of adequate hydration of the patient.

Interaction, connected with valsartany

does not recommend simultaneous use

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Double blockade of RAAS by medicaments of groups of the antagonists of receptors of angiotensin (ARA), APF inhibitors or aliskireny. It is necessary to be careful at simultaneous use of medicines of group of ARA, including a valsartan, with other means blocking RAAS, such as medicines of group of APF inhibitors or aliskiren.

Simultaneous use of antagonists of receptors of angiotensin, including valsartan, or APF inhibitors with aliskireny to patients with diabetes or to patients with a renal failure (the speed of glomerular filtration (SGF) of 60 ml/min. / 1.73 to m ² ) it is contraindicated to

.

Kaliysberegayushchy diuretics, potassium additives, the salt substitutes containing potassium, or other medicines which can increase potassium level in blood plasma. It is necessary to be careful and to often control potassium content in blood plasma in need of use of means which influence potassium level in combination with valsartany.

Conveyors. By results of the researches in vitro valsartan is substrate for the hepatic conveyor of capture OATP1B1/OATP1B3 and the hepatic conveyor of removal of MRP2. The clinical value of these data is unknown. Simultaneous use of inhibitors of the conveyor of capture (for example rifampicin, cyclosporine) or the removal conveyor (for example a ritonavira) can increase system exposure of a valsartan. It is necessary to take appropriate measures at the beginning and at the end of the accompanying use of these medicines.

Interaction are absent. Clinically significant interactions when performing monotherapy valsartany are noted at use of such medicines: Cimetidinum, warfarin, furosemide, digoxin, atenolol, indometacin, hydrochlorothiazide, amlodipin, glibenclamide.

Digoxin and indometacin can interact with a hydrochlorothiazide in a combination valsartan / a hydrochlorothiazide.

Interaction, connected with a hydrochlorothiazide

Simultaneous use demanding extra care. Risk of development of a hypopotassemia increases at simultaneous use of saluretics, depletive, corticosteroids, AKTG, Amphotericinum, a karbenoksolon, penicillin G and derivatives of salicylic acid. These medicines can strengthen action of a hydrochlorothiazide on potassium level in blood therefore it is necessary to control potassium content in blood.

Medicines which can cause ventricular tachycardia on type a pirouette: antiarrhytmic means of Ia of a class (quinidine, Disopyramidum); antiarrhytmic means of the III class (for example Amiodaronum, sotalol, dofetilid, ibutilid); some antipsychotic means (for example thioridazine, Chlorpromazinum, levomepromazinum, trifluoperazin, tsiamemazin, Sulpiridum, sultoprid, amisulprid, tiaprid, Pimozidum, haloperidol, Droperidolum); others (for example bepridit, tsizaprid, difemanit, erythromycin for in/in introductions, galofantrin, ketanserin, mizolastin, pentamidine, sparfloksatsin, terfenadin, Vincaminum for in/in introductions).

Because of risk of emergence of a hypopotassemia a hydrochlorothiazide should be applied with care with the specified medicines

Cardiac glycosides. Thiazide diuretics can cause such side effects as a hypopotassemia or a hypomagnesiemia which, in turn, increase risk of developing arrhythmia in glikozidny intoxication.

Salt of calcium and vitamin D. At simultaneous use with vitamin D or salts of calcium the potentiation of increase in level of calcium in blood plasma is possible.

Antidiabetic means (oral drugs, insulin). Thiazide diuretics can cause change of tolerance to glucose. Dose adjustment of insulin or oral glucose-lowering medicaments at patients with diabetes can be required. Simultaneous use of metformin and a hydrochlorothiazide at functional insufficiency of kidneys can lead to development of a metabolic acidosis.

Blockers of β-adrenoceptors and diazoxide. Simultaneous use of thiazide diuretics, including a hydrochlorothiazide, with blockers of β-adrenoceptors can increase risk of development of a hyperglycemia. Thiazide diuretics, including a hydrochlorothiazide, can increase hyper glycemic effect of diazoxide.

Medicines applied to treatment of gout (probenetsid, Sulfinpyrazonum and Allopyrinolum). Dose adjustment of the uricosuric means stimulating removal of uric acid as the hydrochlorothiazide can increase the level of uric acid in blood plasma can be required. Increase in a dose of a probenetsid or Sulfinpyrazonum can be required.

Simultaneous use of thiazide diuretics can increase the frequency of development of reactions of hypersensitivity to Allopyrinolum.

Anticholinergics (for example atropine, Biperidinum). Increase in bioavailability of thiazide diuretic is noted at simultaneous use of blockers of holinoretseptor (for example atropine, Biperidinum) that, perhaps, it is connected with decrease in physical activity of a digestive tract and a delay of gastric emptying.

Amantadin. Tiazida, including a hydrochlorothiazide, can increase risk of development of side effects of an amantadin.

Holestiramin and cholesterol. Absorption of a hydrochlorothiazide is broken in the presence of the anion-exchange pitches. Colestyraminum slows down absorption of thiazide diuretics.

Cytotoxic medicaments (for example cyclophosphamide, methotrexate). Decrease in removal by kidneys of cytotoxic medicaments (for example cyclophosphamide, a methotrexate) can lead to potentiation of their myelosuppressive action.

not depolarizing muscle relaxants (for example tubocurarine). Tiazida exponentiate action of kurarepodobny muscle relaxants.

Cyclosporine. Simultaneous use of cyclosporine can increase risk of development of a hyperuricemia and emergence of the symptoms reminding exacerbation of gout.

Alcohol, anesthetics and sedatives. Can increase severity of orthostatic hypotension.

Methyldopum. It was reported about cases of development of hemolytic anemia at simultaneous use of thiazide diuretic and Methyldopums.

Karbamazepin. Risk of development of a hyponatremia can increase. Nebkhody clinical control of a condition of the patient and laboratory control of blood.

Contrast agents containing iodine. In dehydration caused by diuretics the risk of emergence of OPN can increase, especially at administration of contrast agent in high doses. Before administration of iodine it is necessary to restore water balance.

Overdose

Is not present data on cases of overdose of a diokor.

Main manifestation of overdose.

At overdose of a hydrochlorothiazide the following signs and symptoms can arise: the nausea, drowsiness, a hypovolemia, electrolytic disturbances associated with arrhythmia and muscular spasms. Characteristic signs of overdose are also tachycardia, weakness, confusion of consciousness, dizziness, paresthesia, exhaustion, vomiting, thirst, a polyuria, an oliguria, an anury, an alkalosis, the increased urea nitrogen level in blood (generally renal failure).

If the medicament was taken by

recently, it is necessary to cause vomiting or to carry out gastric lavage. A priority is blood circulation stabilization. If there is arterial hypotension, the patient should give a dorsal decubitus and as soon as possible to fill the content of salts and liquid in an organism. Valsartan it is impossible to bring out of an organism by a hemodialysis in view of considerable linking with proteins of blood plasma though for removal from a hydrochlorothiazide organism the hemodialysis is effective.

Storage conditions

Out of children's reach in original packing at a temperature not above 25 °C.

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