Universal reference book for medicines
Name of the preparation: KANDEKOR ® H 8 (CANDECOR N 8)

Active substance: candesartan, hydrochlorothiazide

Type: Antihypertensive drug

Manufacturer: КРКА-РУС (Russia) produced by KRKA (Slovenia)
Composition, form of production and packaging
Tablets
1 tab.

candesartan cilexetil 8 mg

hydrochlorothiazide 12.5 mg

14 pcs.
- blisters (2) - packs of cardboard.
14 pcs.
- blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2014.

PHARMACHOLOGIC EFFECT

Candesartan

Angiotensin II - the main hormone of the renin-angiotensin-aldosterone system (RAAS), taking part in the pathogenesis of arterial hypertension (AH) and other diseases of the cardiovascular system.

Candesartan is a selective angiotensin II receptor antagonist, subtype 1 (AT 1 -receptor).
Does not exhibit the properties of an agonist. Does not affect the angiotensin-converting enzyme (ACE) and does not lead to the accumulation of bradykinin or substance P. When comparing candesartan with ACE inhibitors (ACE inhibitors), the development of cough was less common in patients receiving candesartan. It does not bind to receptors of other hormones, does not affect the state of ion channels involved in the regulation of cardiovascular activity. As a result of blocking of AT- 1 receptors of angiotensin II, a compensatory dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in aldosterone concentration in the blood plasma occurs.
Hydrochlorothiazide

Hydrochlorothiazide inhibits active sodium absorption primarily in the distal renal tubules and enhances the excretion of sodium, chlorine and water.
Dose-dependent increases the excretion of potassium and magnesium by the kidneys: calcium is reabsorbed to a greater extent. Reduces the volume of blood plasma and extracellular fluid, reduces cardiac output and blood pressure (BP). With long-term therapy, the reduction in total peripheral vascular resistance (OPSS) develops due to the expansion of arterioles. Long-term therapy with hydrochlorothiazide reduces the risk of developing cardiovascular disease and mortality. Candesartan and hydrochlorothiazide have an additive antihypertensive effect.
Arterial hypertension

In patients with AH candesartan causes a prolonged clinically significant decrease in blood pressure without a reflex increase in the heart rate (heart rate).
There is no information on the development of severe arterial hypotension after taking the first dose and the development of the "withdrawal" syndrome with discontinuation of the drug. After a single dose of candesartan, the hypotensive effect usually develops after 2 hours. With continued therapy, a stable decrease in blood pressure is achieved within 4 weeks. The achieved level of blood pressure is maintained with prolonged therapy. With the use of Candecor ® H 8, once a day, an effective and uniform decrease in blood pressure is ensured within 24 hours. The frequency of side effects, especially cough, when combined with hydrochlorothiazide / candesartan combination is lower than with the combination of hydrochlorothiazide / ACE inhibitors.
The efficacy of a combination of hydrochlorothiazide / candesartan does not depend on the sex and age of the patient.

PHARMACOKINETICS

Simultaneous use of a combination of hydrochlorothiazide / candesartan does not have a clinically significant effect on the pharmacokinetics of hydrochlorothiazide and candesartan.

Suction and distribution

Candesartan

Candesartan cilexetil is a prodrug.
After oral administration, candesartan cilexetil is rapidly converted to the active substance candesartan by ether hydrolysis. The absolute bioavailability of candesartan is approximately 40% after the administration of candesartan inward as a solution. The relative bioavailability of candesartan in the tablet dosage form as compared to the oral solution is approximately 34%. The average C max in blood plasma is achieved 3-4 hours after candesartan intake. The concentration of candesartan in the blood plasma increases linearly with increasing doses within the therapeutic range. The pharmacokinetics of candesartan does not depend on the sex of the patient. Eating does not significantly affect the area under the AUC curve.
Actively binds to blood plasma proteins (more than 99%).
The volume distribution of candesartan is 0.1 l / kg.
Hydrochlorothiazide

Hydrochlorothiazide is rapidly absorbed from the digestive tract.
Bioavailability is approximately 70%. Simultaneous food intake increases suction by about 15%. In patients with chronic heart failure and pronounced edema, bioavailability can be reduced.
The binding of hydrochlorothiazide to plasma proteins is approximately 60%.
The volume of distribution is 0.8 l / kg.
Biotransformation and excretion

Candesartan

Candesartan is excreted mainly unchanged in kidneys, with bile through the intestine and only to a small extent is metabolized in the liver (isoenzyme CYP2C9).
The results of the studies indicate that there is no clinically significant drug interaction with preparations affecting the isoenzymes CYP2C9 and CYP3A4. According to in vitro studies, drug interactions with drugs whose metabolism depends on cytochrome P450 isoenzymes: CYP1A2 are not expected. CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4. T 1/2 of candesartan is approximately 9 hours. When taking repeated doses, it does not accumulate in the body. T 1/2 of candesartan does not change (about 9 hours) after simultaneous use with hydrochlorothiazide.
The total plasma clearance of candesartan is 0.37 ml / min / kg, with renal clearance of about 0.19 ml / ml / kg.
The excretion of candesartan occurs by glomerular filtration and active tubular secretion. After ingestion of radio-labeled candesartan (14C-labeled candesartan), approximately 26% is excreted by the kidneys in the form of candesartan and 7% - in the form of an inactive metabolite, and 56% is excreted with bile through the intestine in the form of candesartan and 10% in the form of an inactive metabolite.
Hydrochlorothiazide

Hydrochlorothiazide is not metabolized and is excreted almost completely unchanged by glomerular filtration and active tubular secretion.
T 1/2 hydrochlorothiazide is approximately 8 hours. Approximately 70% of the ingested hydrochlorothiazide is excreted by the kidney in 48 hours. T 1/2 hydrochlorothiazide does not change when applied simultaneously with candesartan. Additional cumulation of hydrochlorothiazide after repeated use in combination with candesartan in comparison with monotherapy does not occur.
Pharmacokinetics in selected patient groups

Candesartan

Elderly patients

In patients older than 65 years, C max and AUC of candesartan are about 50% and 80% higher, respectively, compared with younger patients.
Nevertheless, the hypotensive effect and frequency of side effects are the same in both age groups.
Impaired renal function

In patients with mild or moderate impairment of renal function, Cmax and AUC candesartan upon repeated application increases by 50% and 70%, respectively: thus, T 1/2 does not change.
Corresponding changes in patients with severe renal dysfunction are 50% and 110%. T1 / 2 candesartan in patients with severe renal dysfunction is approximately doubled. Pharmacokinetics in patients on hemodialysis is similar to that in patients with severe renal dysfunction.
Impaired liver function

In patients with mild or moderate hepatic impairment, the mean AUC of candesartan increases by approximately 20% in one study and 80% in another study.
No experience in patients with severe hepatic insufficiency.
Hydrochlorothiazide

T 1/2 hydrochlorothiazide is increased in patients with impaired renal function.

INDICATIONS

- Arterial hypertension (patients who are shown combined therapy).

DOSING MODE

Inside, once a day, regardless of food intake.
The bioavailability of candesartan is not dependent on food intake. Eating does not have a clinically significant effect on the bioavailability of hydrochlorothiazide.
The recommended dose is 1 tablet once a day.

It is recommended to titrate the dose of candesartan and hydrochlorothiazide before transferring the patient to therapy with Kandecor® H 8. If necessary, the issue of transferring the patient from monotherapy with Candecor® to Kandekor® H 8 can be considered. When transferring a patient with monotherapy with gdrochlorothiazide, titration of candesartan dose is recommended.

In most cases, the hypotensive effect is achieved within 4 weeks from the start of treatment.

Elderly patients: dose adjustment is not required.

Impaired renal function

Patients with impaired renal function prefer to use loop diuretics in comparison with thiazide.
Patients with mild to moderate renal impairment (QC greater than 30 mL / min) are advised to select a dose of candesartan by titration (by monotherapy with Candecore ® ), starting at a dose of 4 mg. The drug Kandekor ® H 8 is contraindicated in patients with severe renal dysfunction (KK less than 30 ml / min).
Impaired liver function

Patients with mild or moderate impairment of liver function are advised to select a dose of candesartan by titration (through monotherapy with Candecore ® ), starting at a dose of 4 mg.

The drug Kandekor ® H 8 is contraindicated in patients with severe impairment of liver function and / or cholestasis.

Patients with reduced BCC

Patients with reduced BCC (risk of developing hypotension) are recommended to select a dose of candesartan by titration (through monotherapy with Candecore ® ), starting at a dose of 4 mg.

Children and teenagers under 18 years of age

The safety and effectiveness of the use of Candecor ® H 8 in children and adolescents under 18 years are not established.

SIDE EFFECT

The side effects observed in the clinical trials of the combination hydrochlorothiazide / candesartan were mild and transient and were comparable (2.3-3.3%) in frequency with the placebo group (2.7%).

The side effects of the hydrochlorothiazide / candesartan combination are limited to side effects previously recorded separately for candesartan and / or hydrochlorothiazide.

Classification of the frequency of development of side effects of the World Health Organization (WHO):

very often? 1/10

often from? 1/100 to <1/10

infrequently from? 1/1000 to <1/100

rarely from? 1/10000 to <1/1000

very rarely from <1/10000

the frequency of the unknown can not be estimated from the available data.

In each group, undesirable effects are presented in order of decreasing severity.

Candesartan

From the nervous system:

often: dizziness / vertigo, headache;

From the genitourinary system:

very rarely: a violation of kidney function, including renal failure in predisposed patients;

From the hematopoiesis:

Very rarely: leukopenia, neutropenia and agranulocytosis;

From the digestive system :

very rarely: nausea, increased activity of "liver" transaminases, a violation of liver function or hepatitis;

From the musculoskeletal system:

very rarely: back pain, arthralgia, myalgia;

From the respiratory system:

often: respiratory infections;

very rarely: cough;

From the skin:

very rarely: angioedema, skin rash, skin itching, urticaria;

Laboratory indicators:

very rarely: gyerkalemia, hyponatremia.

Hydrochlorothiazide

In monotherapy with hydrochlorothiazide, usually at a dose of 25 mg or more, the following side effects were noted:

From the nervous system:

often: mild dizziness, vertigo;

rarely: sleep disorders, depression, anxiety, paresthesia;

From the cardiovascular system:

infrequently: orthostatic hypotension;

rarely: arrhythmia, necrotizing angiitis (vasculitis, cutaneous vasculitis);

From the respiratory system:

rarely: respiratory distress syndrome (including pneumonitis, pulmonary edema);

From the digestive system:

infrequently: anorexia, loss of appetite, stomach irritation, diarrhea, constipation;

rarely: pancreatitis, intrahepatic cholestatic jaundice;

From the hematopoiesis:

rarely: leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, oppression of bone marrow hematopoiesis, hemolytic anemia;

From the sense organs:

rarely: transient impairment of visual perception;

frequency unknown: acute myopia, acute angle-closure glaucoma;

From the skin:

infrequently: skin rash, hives, photosensitization reactions;

rarely: toxic epidermal necrolysis, skin lupus-like reactions, exacerbation of cutaneous manifestations of systemic lupus erythematosus;

From the urinary system:

often: glucosuria;

rarely: renal dysfunction and interstitial nephritis;

From the musculoskeletal system:

rarely: muscle spasms;

Allergic reactions:

rarely: anaphylactic reactions;

Laboratory indicators:

often: hyperglycemia, hyperuricemia, disturbance of water-electrolyte balance (including hyponatremia and hypokalemia), increased concentration of cholesterol and triglycerides;

rarely: an increase in the concentration of residual nitrogen and creatinine in the blood plasma;

Other:

often: weakness;

rarely: a fever.

CONTRAINDICATIONS

- hypersensitivity to the active substances or auxiliary components of the drug, as well as derivatives of the sulfonamide;

- Pregnancy and the period of breastfeeding;

- severe renal dysfunction (CK less than 30 ml / min), incl.
anuria;
severe liver dysfunction and / or cholestasis;

- refractory hypokalemia or hypercalcemia;

- gout;

- age under 18 years (efficiency and safety not established);

- lactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.

With caution: severe chronic heart failure, bilateral stenosis of the renal arteries, stenosis of the single kidney artery, hemodynamically significant stenosis of the aortic and / or mitral valve, cerebrovascular disease, coronary heart disease, hypertrophic obstructive cardiomyopathy (GOCMP), reduced circulating blood volume (BCC) cirrhosis of the liver, hyponatremia, primary hyperaldosteronism, surgical intervention, condition after recent kidney transplantation, renal failure
liver failure, diabetes mellitus.
PREGNANCY AND LACTATION

Pregnancy

The use of angiotensin II receptor antagonists in the first trimester of pregnancy is not recommended.
The drug Kandekor ® H 8 should not be used during pregnancy, as well as in women planning pregnancy. When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile. In case of pregnancy, stop taking the drug Candecor ® H 8 and, if necessary, transfer to alternative antihypertensive therapy.
The drug Kandekor ® H 8, as well as other drugs having a direct effect on RAAS, is contraindicated in the II-III trimesters of pregnancy, because it can cause fetotoxic effects (renal dysfunction, osteopenia of the fetal skull, oligihydramnion) and neonatal toxic effects (renal failure , arterial hypotension, hyperkalemia).
If nevertheless used the drug in the II-III trimesters of pregnancy, then it is necessary to carry out ultrasound of the kidneys and bones of the fetal skull.
Hydrochlorothiazide penetrates the placenta.
With the use of thiazide diuretics in the II-III trimester of pregnancy, it is possible to reduce uteroplacental blood flow, the development of thrombocytopenia, jaundice, a violation of water-electrolyte balance in a fetus or newborn.
When planning pregnancy, it is recommended that the patient be transferred to alternative antihypertensive therapy, taking into account the safety profile.
When confirming the pregnancy, Kandekor ® H 8 should be discontinued as soon as possible. Newborns, whose mothers took the drug Candecor ® H 8 during pregnancy, should be monitored, because it is possible to develop an arterial hypotension in a newborn.
Breastfeeding period

There is no data on the isolation of candesartan in breast milk.
However, candesartan is released from the milk of lactating rats.
Hydrochlorothiazide penetrates the breast milk of the mother in small amounts.
Thiazide diuretics in high doses cause intense diuresis, thereby suppressing lactation.The drug Kandekor ® H 8 is not recommended during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER

Patients with impaired renal function prefer to use loop diuretics in comparison with thiazide.
Patients with mild to moderate renal impairment (QC greater than 30 mL / min) are advised to select a dose of candesartan by titration (by monotherapy with Candecore ® ), starting at a dose of 4 mg. The drug Kandekor ® H 8 is contraindicated in patients with severe renal dysfunction (KK less than 30 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Patients with mild or moderate impairment of liver function are advised to select a dose of candesartan by titration (through monotherapy with Candecore ® ), starting at a dose of 4 mg.

The drug Kandekor ® H 8 is contraindicated in patients with severe impairment of liver function and / or cholestasis.

APPLICATION FOR CHILDREN

The drug is contraindicated in children under 18 years of age (efficacy and safety not established).

APPLICATION IN ELDERLY PATIENTS

Older patients do not need a dose adjustment.

SPECIAL INSTRUCTIONS

Impaired renal function

In patients with impaired renal function, it is preferable to use "loop" diuretics.
If Kandekor ® H 8 is used in patients with impaired renal function, it is recommended to periodically monitor the potassium content and the concentration of creatinine and uric acid in the blood plasma.
Kidney Transplantation

Experience with the drug Kandekor ® H 8 patients newly transplanted kidney, is absent.
Renal artery stenosis
In patients with bilateral renal artery stenosis, and stenosis of the artery only functioning kidney drugs that affect the RAAS, including and antagonists of angiotensin II receptors, can increase the concentration of urea and creatinine in plasma.
Reduced bcc (hypovolemia) and / or hyponatremia
patients with hypovolemia and / or hyponatremia in patients receiving the drug Kandekor ® H 8 may develop symptomatic hypotension, as well as the use of other drugs affecting RAAS. Therefore it is not recommended to use Kandekor preparation ®H 8 to address these conditions.
General anesthesia / surgery
prior to surgery (including dental) must notify anesthetist of drug application Kandekor ® H 8.
When carrying out surgical operations under general anesthesia in patients treated with angiotensin II receptor antagonists may develop hypotension due to blockade of the RAAS. Very rarely, hypotension may be severe and require intravenous fluids and / or vasopressor.
Abnormal liver function
Thiazide diuretics should be used with caution in patients with impaired hepatic function or progressive liver disease, since even a minimum disruption of water and electrolyte balance may contribute to the development of hepatic coma. Experience with the drug Kandekor ® H 8 patients with impaired liver function is missing.
Stenosis of the aortic sewing mitral valve GOKMP
drug Kandekor ® H 8, like other vasodilators, must be used with caution in patients with aortic stenosis gemodinamncheski significant and / or mitral valves, or GOKMP.
primary aldosteronism
Patients with primary hyperaldosteronism resistant to antihypertensive drugs affecting RAAS therefore such patients use Kandekor preparation ® H 8 are not recommended.
Violations of water-electrolyte balance
in all patients taking diuretics, it is necessary to periodically monitor the content of electrolytes in the blood plasma.
Thiazide diuretics including hydrochlorothiazide, can cause disruption of water-electrolyte balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and gipokalimichesky alkalosis).
Thiazide diuretics may reduce renal excretion of calcium and cause a temporary and insignificant increase of calcium in the blood plasma.
Marked hypercalcaemia may be a sign of hidden hyperparathyroidism. Prior to the investigation of the function of the parathyroid glands, thiazide diuretics should be abolished.
Hydrochlorothiazide in a dose dependent increases potassium excretion and may cause hypokalemia. This effect is less pronounced hydrochlorothiazide while the use of candesartan. The risk of hypokalemia increased in patients with cirrhosis, hypovolaemic or in patients treated liquid having a reduced content of salts, or simultaneously taking steroids or ACTH. Application Kandekor preparation ®H 8 may provoke hyperkalemia, especially in patients with heart failure and / or renal failure. The simultaneous use of potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other means capable of increase the content of potassium in the blood plasma (e.g., heparin) can lead to the development of hyperkalemia. If necessary to control the content of potassium in serum.
Thiazide diuretics increase the renal excretion of magnesium, which may result in hypomagnesemia.
Metabolic and endocrine effects
Caution is required in all patients treated with hypoglycemic agents for oral or insulin, as hydrochlorothiazide may attenuate their action. During therapy with thiazide diuretics latent diabetes may go into overt.
Against the background of treatment with thiazide diuretics may increase the concentration of cholesterol and triglycerides in the serum. However, with the combination hydrochlorothiazide / candesartan comprising hydrochlorothiazide 12.5 mg, observed minimum quantity or the absence of such effects.
Treatment with thiazide diuretics in some patients may exacerbate hyperuricemia and / or exacerbate gout.
photosensitivity
There are cases of photosensitivity in patients receiving hydrochlorothiazide. In the case of the manifestations of photosensitivity recommended to discontinue therapy. If necessary, continuation of therapy is recommended to protect exposed areas of the body from exposure to the sun and ultraviolet rays.
Are common
Patients with renal function which depends on the RAAS (e.g., chronic heart failure Ill-IVfunktsionalnogo class NYHA classification, kidney disease, including renal artery stenosis), drug therapy, affecting the RAAS may be accompanied by a sharp arterial hypotension oliguria and / or progressive azotemia, in rare cases - acute renal failure. Not exclude the development of these disorders due to suppression of the RAAS in patients receiving angiotensin II receptor antagonists. The sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases, using any antihypertensives, can lead to myocardial infarction or stroke.
Patients taking thiazide diuretics, hypersensitivity reactions can develop both in the presence and absence of a history of allergy or asthma, but more likely in the presence of such a history. There have been reports of exacerbation of systemic lupus erythematosus with the use of thiazide diuretics.
The simultaneous use of other antihypertensive drugs potentiates the hypotensive effect of the drug Kandekor ® H 8.
Special Information on excipients
drug Kandekor ® H 8 contains lactose, and the drug is contraindicated in patients with lactase deficiency, lactose intolerance syndrome glucose-galactose malabsorption.
The effect on the ability to drive vehicles and other complex mechanisms:
Influence of preparation Kandekor ® H 8 to drive vehicles and work with complex technical devices has not been studied, but the pharmacodynamic properties of the drug indicate that this effect is absent. Nevertheless, caution should be exercised when driving and busy with other potentially hazardous activities, due to the possibility of side effects (dizziness, etc.).
OVERDOSE

In view of the pharmacological properties of the drug can be assumed that the main manifestation of overdose can be marked reduction in blood pressure and dizziness. There are cases of drug overdose (672 mg candesartan), patient recovery ended without severe consequences. The main manifestation of an overdose of hydrochlorothiazide is acute loss of fluid and electrolytes. However, against the background of the drug Kandekor ® H 8, the following overdosage symptoms:reduced blood pressure, dizziness, thirst, disturbance of water-electrolyte balance, tachycardia, ventricular arrhythmia, depression / loss of consciousness and muscle cramps.
Treatment:induce vomiting to gastric lavage. Next - symptomatic therapy under the control of vital functions. The patient must be translated into a horizontal position and lift legs to take measures to increase the bcc (isotonic sodium chloride solution i.v.). It is necessary to monitor the status of water and electrolyte and acid-base balance of the blood serum and, if necessary, to carry out their correction. symptomatic agents may be appointed if necessary. Candesartan is output via hemodialysis; hydrochlorothiazide elimination is unlikely.
DRUG INTERACTION

No clinically significant drug interactions candesartan with warfarin, digoxin, oral contraceptives (ethinylestradiol / levonorgestrel), glibenclamide and nifedipine were detected.
Diuretics, laxatives, amphotericin B and salicylic acid derivatives, steroids and ACTH
When applied simultaneously with hydrochlorothiazide furosemide, amphotericin B, salicylic acid derivatives, steroids and ACTH or abuse laxatives may increase the excretion of potassium ions. The simultaneous use of potassium supplements, potassium-sparing diuretics (triamterene, spironolactone, amiloride, eplerenone) or salt substitutes, or other means capable of increase the content of potassium in the blood plasma (e.g., heparin) can lead to an increase in the potassium content in the blood serum. If necessary to control the content of potassium in serum.
Cardiac glycosides and antiarrhythmics
Hypokalemia and hypomagnesemia during therapy with thiazide diuretics may exacerbate cardiac toxicity of cardiac glycosides and antiarrhythmics. It is recommended to periodically monitor serum potassium content while the use of cardiac glycosides and drugs prolong the interval QT (the risk of ventricular tachycardia type "pirouette» ( "torsades de pointes»):
• IA class antiarrhythmics (e.g., quinidine, disopyramide);
• III class antiarrhythmics (e.g., amiodarone, sotalol, dofetilide);
• Some antipsychotic agents (e.g., thioridazine, chlorpromazine, levomepromazine, trifluoperazine, sulpiride, amisulpride, tiapride, haloperidol, d. roperidol);
• Other medicinal agents (e.g., cisapride, difemanila methylsulfate, intravenous erythromycin, halofantrine, ketanserin, mizolastine, sparfloxacin, terfenadine, vincamine intravenous).
Lithium
With simultaneous use of drugs lithium and ACE inhibitors or hydrochlorothiazide cases transient increase the concentration of lithium have been observed in plasma and of toxic effects. A similar effect is possible by simultaneous use of drugs lithium and angiotensin receptor antagonists II.Odnovremennoe use of candesartan and hydrochlorothiazide with lithium therapy is not recommended. If necessary, the simultaneous application should carefully monitor the serum concentration of lithium.
Nonsteroidal anti-inflammatory drugs (NSAIDs)
The simultaneous use of NSAIDs (including selective cyclooxygenase-2 inhibitors, acetylsalicylic acid (more than 3 g / d) and non-selective NSAIDs) can attenuate the antihypertensive effect of angiotensin II receptor antagonists.
As in the case of ACE inhibitors, angiotensin II simultaneous application of receptor antagonists and NSAIDs increases the risk of loss of kidney function, until the development of renal failure, which leads to hyperkalemia, particularly in patients with impaired kidney function available. This combination should be used with caution, especially in elderly patients. All patients should receive adequate amounts of fluids. You need to monitor renal function at the beginning of concurrent therapy and periodically throughout the course of treatment.
NSAIDs can reduce diuretic and hypotensive effects of thiazide diuretics.
Anion-exchange resins (cholestyramine and colestipol)
Absorption of hydrochlorothiazide is significantly reduced in the presence of anion-exchange resins. A single dose of cholestyramine or colestipol hydrochlorothiazide reduces absorption in the gastrointestinal tract by 85% and 43%, respectively.
Non-depolarizing muscle relaxants
thiazide diuretics may increase the effect of tubocurarine chloride.
Vitamin D and calcium salts
The simultaneous use of thiazide diuretics with vitamin D or calcium salts increases in serum calcium levels, as reduced calcium excretion. If necessary, use of calcium or vitamin D preparations, should be controlled in serum calcium levels and may adjust the dose of these drugs.
The simultaneous use of hydrochlorothiazide with beta-blockers and diazoxide potentiates their hyperglycemic action.
Anticholinergics, e.g., atropine, biperiden increase the bioavailability of thiazide diuretics by decreasing gastrointestinal motility. With simultaneous use of amantadine increases the risk of side effects of amantadine due to reduced excretion.
Cytotoxic drugs such as cyclophosphamide, methotrexate - mielopodavlyayuschee increased effect due to deceleration of excretion.
Together with the admission ethanol, barbiturates, narcotic analgesics can be increased incidence of orthostatic hypotension.
Hypoglycemic agents for oral and insulin
simultaneous use of hypoglycemic agents for oral and insulin with thiazide diuretics may require correction of their doses.
Metformin
should be used with caution in conjunction with metformin, as there is a risk of lactic acidosis induced by renal insufficiency during treatment with hydrochlorothiazide.
Sympathomimetics (pressor amines, e.g., epinephrine and norepinephrine)
Thiazide diuretics may reduce the effectiveness agonists (epinephrine, norepinephrine).
Hydrochlorothiazide may increase the risk of developing acute renal failure, especially with concomitant use of high doses of iodinated contrast media .
The simultaneous use of cyclosporin increases the risk of worsening the flow hyperuricemia and gout);
Baclofen, amifostine, neuroleptics or tricyclic antidepressants increase the hypotensive effect of the risk of hypotension.
TERMS OF RELEASE FROM PHARMACY

Shelf life - 2 years.

TERMS AND CONDITIONS OF STORAGE

At a temperature of not higher than 30 ° C, in the original package.
Keep out of the reach of children.
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