Universal reference book for medicines
Name of the preparation: ORDISS H ® (ORDISS H)

Active substance: candesartan, hydrochlorothiazide

Type: Antihypertensive drug

Manufacturer: Teva Pharmaceutical Industries (Israel)
Composition, form of production and packaging
The tablets are
biconvex, capsular, light pink in color, with a risk on both sides;
on one side engraving "C" and "16" on different sides of the risks.
1 tab.

candesartan cilexetil 16 mg

hydrochlorothiazide 12.5 mg

Auxiliary substances: pregelatinized starch - 15 mg, povidone K30 - 16 mg, carmellose calcium - 6.6 mg, poloxamer 188 - 1 mg, microcrystalline cellulose - 72 mg, lactose monohydrate - 177.6 mg, ferric oxide red oxide (E172) 0.1 mg, magnesium stearate - 3.2 mg.

5 pieces.
- blisters (6) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
The tablets are biconvex, capsular, white or almost white in color, with a risk on both sides;
on one side engraving "C" and "32" on different sides of the risks.
1 tab.

candesartan cilexetil 32 mg

hydrochlorothiazide 12.5 mg

Auxiliary substances: pregelatinized starch - 30 mg, povidone K30 - 32 mg, carmellose calcium - 13.2 mg, poloxamer 188 - 2 mg, microcrystalline cellulose - 148 mg, lactose monohydrate - 363.9 mg, magnesium stearate - 6.4 mg.

5 pieces.
- blisters (6) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
The tablets are biconvex, capsular, light pink in color, with a risk on both sides;
on one side engraving "H" and "25" on different sides of the risks; on the other side of the engraving "C" and "32" on the different sides of the risks.
1 tab.

candesartan cilexetil 32 mg

hydrochlorothiazide 25 mg

Auxiliary substances: pregelatinized starch - 30 mg, povidone K30 - 32 mg, carmellose calcium - 13.2 mg, poloxamer 188 - 2 mg, microcrystalline cellulose - 144 mg, lactose monohydrate - 355.2 mg, ferric oxide red oxide (E172) 0.2 mg, magnesium stearate - 6.4 mg.

5 pieces.
- blisters (6) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2017.

PHARMACHOLOGIC EFFECT

Antihypertensive combination drug.
Angiotensin II is the main hormone of RAAS, which plays an important role in the pathogenesis of arterial hypertension, heart failure and other cardiovascular diseases. The main physiological effects of angiotensin II are vasoconstriction, stimulation of aldosterone production, regulation of the water-electrolyte state and stimulation of cell growth. The effects are mediated by the interaction of angiotensin II with angiotensin receptor type 1 (AT 1 receptors).
Candesartan is a selective antagonist of AT 1 -receptor angiotensin II, does not inhibit ACE that converts angiotensin I into angiotensin II, which destroys bradykinin, does not lead to accumulation of bradykinin or substance P. Blocking of AT 1 -receptors of angiotensin II results in a dose-dependent increase in renin content, angiotensin I, angiotensin II, and a decrease in aldosterone in the blood plasma.

When comparing candesartan with ACE inhibitors, the development of cough was less common in patients receiving candesartan.

Candesartan does not bind to the receptors of other hormones and does not block the ion channels involved in the regulation of cardiovascular functions.

Hydrochlorothiazide is a thiazide-like diuretic, inhibits the active reabsorption of sodium, mainly in the distal sections of the renal tubules and enhances the release of sodium, chlorine and water ions.
The excretion of potassium and magnesium by the kidneys intensifies depending on the dose, while calcium begins to be reabsorbed in larger quantities than before.
Hydrochlorothiazide reduces the volume of blood plasma and extracellular fluid, reduces the intensity of blood transport by the heart, reduces blood pressure.
During long-term treatment, the hypotensive effect develops due to the expansion of arterioles. With prolonged use of hydrochlorothiazide, the risk of cardiovascular disease and mortality decreases.
Candesartan and hydrochlorothiazide have a combined hypotensive effect.
In patients with arterial hypertension, the use of candesartan / hydrochlorothiazide causes an effective and prolonged BP reduction without an increase in heart rate. Orthostatic arterial hypotension with the first intake of the drug is not observed, after the end of treatment, hypertension is not increased.
After a single administration of candesartan / hydrochlorothiazide, the main antihypertensive effect develops within 2 hours. The use of the drug 1 time / day effectively and gently reduces blood pressure within 24 hours with a slight difference between the maximum and average effect of action.
With prolonged treatment, a stable decrease in blood pressure occurs within 4 weeks after starting the drug and can be maintained with a long course of treatment.
In clinical trials, the incidence of side effects, especially cough, was less frequent with candesartan / hydrochlorothiazide than with the combination of ACE inhibitors with hydrochlorothiazide.

There is currently no data on the use of candesartan / hydrochlorothiazide in patients with renal failure, nephropathy, decreased left ventricular function, acute heart failure, and myocardial infarction.

The efficacy of candesartan / hydrochlorothiazide does not depend on sex and age.

PHARMACOKINETICS

Suction and distribution

Candesartan.
When sucked from the gastrointestinal tract of candesartan, cilexitil through ether hydrolysis rapidly turns into an active substance - candesartan, binds firmly to AT 1 -receptors and dissociates slowly, does not have the properties of an agonist. The absolute bioavailability of candesartan after oral administration is about 40%. The relative bioavailability of the tablet form compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. Eating does not have a significant effect on AUC, i.e. food does not significantly affect the bioavailability of the drug.
C max in blood plasma is achieved 3-4 hours after taking the tablet form of the drug.
When the dose is increased within the recommended limits, the concentration of candesartan rises linearly. The binding of candesartan to plasma proteins is more than 99%. Plasma V d candesartan is 0.1 l / kg.
Hydrochlorothiazide.
Hydrochlorothiazide is rapidly absorbed from the digestive tract. Bioavailability is approximately 70%. Concomitant ingestion increases absorption by approximately 15%. Bioavailability can be reduced in patients with heart failure and severe swelling.
Binding to plasma proteins is approximately 60%.
Visible V d is approximately 0.8 l / kg.
Metabolism and excretion

Candesartan.
Candesartan is mainly excreted from the body with urine and bile in unchanged form and only marginally metabolized in the liver. T 1/2 is approximately 9 hours. Cumulation of candesartan in the body is not observed.
The total clearance of candesartan is about 0.37 ml / min / kg, with a kidney clearance of about 0.19 ml / min / kg.
Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion.
When administered radically-labeled candesartan, about 26% of the administered amount is excreted in the urine in the form of candesartan and 7% in the form of an inactive metabolite, whereas in feces 56% of the administered amount in the form of candesartan and 10% in the form of an inactive metabolite is detected.

Hydrochlorothiazide.
Hydrochlorothiazide is not metabolized and is released almost completely as an active form of the drug by glomerular filtration and active tubular secretion in the proximal part of the nephron. T 1/2 is about 8 hours and does not change when taken together with candesartan. Approximately 70% of the dose taken orally is excreted by the kidneys within 48 hours. When using the combination of drugs, no additional accumulation of hydrochlorothiazide is found in comparison with monotherapy.
Pharmacokinetics in special clinical cases

Candesartan.
The pharmacokinetic parameters of candesartan do not depend on the sex of the patient.
In patients older than 65 years, C max and AUC of candesartan increase by 50% and 80%, respectively, compared with younger patients.
However, the hypotensive effect and incidence of side effects with candesartan / hydrochlorothiazide do not depend on the age of the patients.
In patients with mild to moderate renal dysfunction, C max and AUC of candesartan increased by 50% and 70%, respectively, whereas T 1/2 did not change in comparison with patients with normal renal function.

Candesartan increased by 50% and 110%, respectively, in patients with severe renal dysfunction and / or on hemodialysis, and T 1/2 increased 2-fold.

In patients with mild and moderate impairment of liver function, AUC of candesartan was increased by 23%.

Hydrochlorothiazide.
T 1/2 is more prolonged in patients with renal insufficiency.
INDICATIONS

- treatment of arterial hypertension in patients who are shown combined therapy.

DOSING MODE

Is taken orally, regardless of food intake.
The recommended dose is 1 tablet 1 time / day.
It is recommended to titrate the dose of candesartan before transferring the patient to Ordiss H ® therapy.
If necessary, patients are transferred from monotherapy with candesartan to therapy with Ordiss H ® . The main antihypertensive effect is achieved, as a rule, in the first 4 weeks after the start of treatment.
In patients with impaired renal function, it is preferable to use "loop" diuretics in comparison with thiazide.
Prior to the initiation of therapy with Ordiss H ® in patients with mild or moderate renal impairment (GFR> 30 ml / min / 1.73 m 2 ), including patients on hemodialysis, titration of candesartan dose is recommended.starting with 4 mg. Ordis H® is contraindicated in patients with severe renal insufficiency (GFR <30 mL / min / 1.73 m 2 ).
For patients at risk of arterial hypotension (eg, with reduced BCC), titration of the dose of candesartan, starting with 4 mg in the form of monotherapy, is recommended.

In patients with impaired liver function of an average degree prior to initiating therapy with Ordiss H ® , titration of the dose of candesartan, starting at 2 mg, is recommended.
Patients with impaired liver function of a severe degree of use of the drug Ordiss H ® is contraindicated.
In elderly patients, dose adjustment is not required.

SIDE EFFECT

Determination of the incidence of side effects as recommended by WHO: very often - not less than 10%;
often - not less than 1%, but less than 10%; infrequently - not less than 0.1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely (including isolated cases) - less than 0.01%.
Candesartan

From the hemopoietic system: very rarely - leukopenia, neutropenia, agranulocytosis.

From the side of metabolism: very rarely - hyperkalemia, hyponatremia.

From the nervous system: often - dizziness;
very rarely - a headache.
From the side of the digestive system: very rarely - nausea.

From the liver and bile ducts: very rarely - increased activity of liver transaminases, a violation of liver function, hepatitis.

From the respiratory system: very rarely - cough.

From the skin and subcutaneous tissues: very rarely - skin rash, skin itching, hives, angioedema.

From the musculoskeletal system: very rarely - back pain, arthralgia, myalgia.

From the side of the kidneys and urinary tract: very rarely - kidney failure.

Hydrochlorothiazide

On the part of the blood system: rarely - leukopenia, neutropenia, agranulocytosis, thrombocytopenia, aplastic anemia, suppression of bone marrow function, hemolytic anemia, hemoglobin decrease.

From the side of the immune system: rarely - an anaphylactic reaction.

From the side of metabolism and nutrition: often - hyperglycemia, hyperuricemia, hyponatremia, hypokalemia.

From the nervous system: often - dizziness, vergigo;
rarely - sleep disorders, anxiety, depression, paresthesia.
From the side of the organ of vision: rarely - reduced vision, sharp myopia, acute closed angle glaucoma.

From the cardiovascular system: infrequently - postural hypotension;
rarely - arrhythmia, vasculitis.
From the respiratory system: rarely - respiratory distress syndrome, pneumonitis, pulmonary edema.

From the digestive system: infrequently - anorexia, loss of appetite, constipation, diarrhea, irritation of the gastric mucosa;
rarely - pancreatitis.
From the liver and bile ducts: rarely - intrahepatic cholestatic jaundice.

From the skin and subcutaneous tissues: infrequently - rash, urticaria, photosensitization reaction;
rarely - toxic epidermal necrolysis, erythematous reactions, recurrence of cutaneous erythematosis.
From the musculoskeletal system: rarely - muscle spasm.

From the urinary system: often - glucosuria;
rarely - renal dysfunction, interstitial nephritis.
Other: often - weakness, increased concentration of cholesterol, triglycerides in the blood plasma;
rarely - a fever, an increase in the concentration of creatinine, urea in the blood plasma.
CONTRAINDICATIONS

- hypersensitivity to candesartan, hydrochlorothiazide and other components of the drug;

- hypersensitivity to other sulfonamide derivatives;

- primary hyperaldosteronism;

- gout;

- severe renal dysfunction (GFR <30 ml / min / 1.73 m 2 );

severe liver dysfunction;

- cholestasis;

- refractory hypokalemia;

- hypercalcemia;

- condition after kidney transplantation;

- Pregnancy;

- the period of breastfeeding;

- children and adolescence under 18;

- simultaneous use with aliskiren or aliskirenoderzhaschimi drugs in patients with diabetes mellitus and / or renal dysfunction (GFR <60 ml / min / 1.73 m 2 );

lactose intolerance;

- deficiency of lactase;

- Glucose-galactose malabsorption syndrome.

With caution: simultaneous use with other antihypertensive drugs, potassium-sparing diuretics, amphotericin, carbenoxolone, penicillin G sodium preparations, salicylic acid derivatives, cardiac glycosides, antiarrhythmics, lithium preparations, NSAIDs, colestipol, colestyramine, tubocurarine, beta adrenoblockers, anticholinergic drugs, amantadine, cytotoxic drugs, GCS, ACTH, barbiturates, general anesthetics, epinephrine, iodine-containing drugs, alcohol
m; impaired renal function (CK> 30 ml / min), liver failure; severe chronic insufficiency; bilateral stenosis of the renal arteries; stenosis of the artery of a single kidney; hemodynamically significant stenosis of the aortic and / or mitral valve; IHD; hypertrophic obstructive cardiomyopathy; decrease in BCC; diabetes; cerebrovascular diseases; acute myopia;angle-closure glaucoma; systemic lupus erythematosus; with the use of alcohol.
PREGNANCY AND LACTATION

The drug Ordiss H® is contraindicated for use during pregnancy and during breastfeeding.

Patients taking the drug should be warned about this before planning pregnancy so that they can switch to alternative therapy with a proven safety profile for use in pregnancy.
In the case of pregnancy diagnosis, the drug should be discontinued immediately. Means that affect RAAS can cause fetal developmental disorders and / or have a negative impact on the newborn, even fatal if the drug is used during pregnancy. It is known that therapy with angiotensin II receptor antagonists can cause fetal development disorders (renal dysfunction, oligohydramnion, delayed ossification of the skull bones) and development of complications in the newborn (renal dysfunction, arterial hypotension, hyperkalemia).
The experience with hydrochlorothiazide during pregnancy is limited.
Hydrochlorothiazide penetrates the placental barrier. Given the mechanism of action of hydrochlorothiazide, its use in pregnancy can cause violations of the fetoplacental circulation and undesirable effects in the fetus and newborn in the form of jaundice, violations of water-electrolyte balance and thrombocytopenia.
It is not known whether candesartan is excreted in human breast milk.
Candesartan is excreted with the milk of lactating rats. Hydrochlorothiazide is excreted in breast milk.
APPLICATION FOR FUNCTIONS OF THE LIVER

Ordis H is contraindicated in patients with severe renal insufficiency (CC less than 30 ml / min).
It is used with caution in the failure of the function of the kidneys of medium degree.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS

Ordis H is contraindicated in patients with severe hepatic insufficiency.
It is used with caution in the failure of the function of the kidneys of medium degree.
APPLICATION FOR CHILDREN

Contraindicated.

APPLICATION IN ELDERLY PATIENTS

In elderly patients, dose adjustment is not required.

SPECIAL INSTRUCTIONS

Simultaneous use of ACE inhibitors, ARA II or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure).Double blockade of RAAS with the use of ACE inhibitors, ARA II or aliskiren is not recommended.

If a double blockade of RAAS is considered absolutely necessary, then treatment should be carried out only under the supervision of a doctor and with regular monitoring of kidney function, electrolyte content and blood pressure.
ACE inhibitors and ARA II should not be used simultaneously in patients with diabetic nephropathy.
In patients with renal failure, the use of "loop" diuretics is preferable to thiazide.
For patients with renal insufficiency, in the treatment with Ordiss H®, it is recommended to constantly monitor the potassium, creatinine and uric acid content.
Data on the use of Ordiss H ® in patients who have recently undergone kidney transplantation are not available.

Drugs that affect RAAS (eg, ACE inhibitors) can lead to increased urea levels in the blood and serum creatinine levels in patients with bilateral renal artery stenosis or stenosis of the single kidney artery.
A similar effect should be expected from angiotensin II receptor antagonists.
Patients deficient BCC and / or sodium may develop symptomatic hypotension, it is not recommended to apply the preparation Ordiss H ® until symptoms data.
In patients receiving angiotensin II receptor antagonists, during anesthesia and surgery may develop hypotension as a result of the blockade of the RAAS. Very rarely there are cases of severe hypotension requiring on / in the liquid and / or vasoconstrictor.
Patients with impaired liver function or progressive liver disease should be used with caution thiazide diuretics, since minor variations in the volume of fluid and electrolyte composition may precipitate hepatic coma. Data on the use of the drug Ordiss H ®in patients with hepatic insufficiency are absent.
When assigning Ordiss H drug ® patients with obstructive or hypertrophic cardiomyopathy hemodynamically significant stenosis of aortic or mitral valve caution.
Patients with primary hyperaldosteronism generally resistant to therapy with antihypertensive drugs affecting RAAS so apply Ordiss H in these patients ® not recommended.
As in all cases, receive drugs with diuretic effect, it is necessary to control the performance of electrolytes in the blood plasma.
Preparations based thiazides having diuretic action, can reduce the excretion of calcium ions in the urine and can cause abrupt changes and insignificant increase in the concentration of calcium ions in the blood plasma.
Thiazides, including and hydrochlorothiazide, can cause disturbances water-salt balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypochloraemic alkalosis).
Revealed hypercalcaemia may be a sign of latent hyperthyroidism.
The use of thiazide diuretics should be discontinued pending the outcome of parathyroid study analyzes.
Hydrochlorothiazide dose-dependently increases the release of potassium, which may cause hypokalemia. Such action of hydrochlorothiazide appears less if used together with candesartan. The risk of hypokalemia is increased in patients with cirrhosis, increased diuresis receiving liquid having a reduced content of salts extending parallel treatment of ACTH or corticosteroids.
Based on experience with drugs affecting RAAS parallel use of the drug Ordiss H ® and diuretic drugs increasing potassium excretion, can be compensated for the use of food supplements containing potassium or other agents capable of increasing the content of potassium in the blood plasma.
Use of the drug Ordiss H ®can cause hypokalemia, especially in patients with cardiac or renal failure patients (documented similar cases are not registered).
Thiazide diuretics increases the excretion of magnesium, which may cause hypomagnesemia.
The use of thiazide diuretics can change blood glucose concentration up to manifestation flowing latent diabetes. Dose adjustment may require hypoglycemic agents in t. H. Insulin.
With the use of thiazide diuretics associated increase in the content of cholesterol and triglycerides in the blood plasma. However, when applying the drug Ordiss H ®observed minimum quantity or the absence of such effects.
Thiazide diuretics increase the concentration of uric acid in blood plasma and can contribute to gout in predisposed patients.
Patients with vascular tone and renal function is predominantly dependent on the activity of the RAAS (e.g., patients with severe chronic heart failure, kidney diseases, including renal artery stenosis), are especially sensitive to drugs acting on the RAAS. The appointment of these drugs is accompanied by these patients sharp arterial hypotension, azotemia, oliguria, and rarely - acute renal failure. The ability of these effects is not excluded, and the application of angiotensin II receptor antagonists. The sharp decrease in blood pressure in patients with ischemic cardiopathy, cerebrovascular disease, ischemic antitipertenzivnyh using any means, can lead to myocardial infarction or stroke.
Manifestation of hypersensitivity reactions to hydrochlorothiazide are most likely in patients with bronchial asthma, allergic reactions in history, that does not preclude the appearance of allergic symptoms in other patients.
If you are using thiazide diuretics were cases of aggravation or appearance of symptoms of congestive seborrhea.
When using thiazide diuretics were cases worsening of systemic lupus erythematosus.
Hydrochlorothiazide may cause idiosyncratic reaction leading to acute myopia and secondary angle-closure glaucoma. Symptoms include: sudden decrease in vision or pain in the eyes, which appear, usually within a few hours or weeks of therapy hydrochlorothiazide. If untreated, acute angle-closure glaucoma can lead to permanent vision loss. Treatment - as soon as possible to stop taking hydrochlorothiazide. If the intraocular pressure remains uncontrolled, you may need urgent medical treatment or surgery. Risk factors for developing acute angle-closure glaucoma is an allergic reaction to sulfonamides or benzilpenitsilliny history.
The preparation contains lactose, so it should not be taken in patients with rare genetic diseases manifested in the absence of tolerance to lactose, lactose deficiency or malabsorption of glucose and galactose.
Use in Pediatrics

Safety and efficacy of the drug Ordiss H ® in children and adolescents under the age of 18 years have not been established.
Impact on the ability to drive vehicles and manage mechanisms

In the event of adverse effects from drug therapy with CNS Ordiss H ® must be taken when performing actions that require high concentration and psychomotor speed reactions.
OVERDOSE

Symptoms: Analysis of the pharmacological properties of the product suggests that the main manifestation of overdose can be clinically significant decrease in blood pressure, dizziness. Some cases of drug overdose have been described (up to 672 mg of candesartan) ended convalescence patients without severe consequences. The main manifestation of an overdose of hydrochlorothiazide is reduced BCC and disruption of water and electrolyte balance. Also observed symptoms such as dizziness, decreased blood pressure. dry mouth, tachycardia, ventricular arrhythmia, loss of consciousness and muscle cramps.
Treatment:the development of clinically significant reduction in blood pressure is necessary to carry out symptomatic treatment and monitor the patient's condition. Place the patient on his back and lift his legs. If necessary to increase BCC, for example, by on / in a 0.9% sodium chloride solution. sympathomimetic agents may be appointed if necessary. Withdrawal of candesartan and hydrochlorothiazide by hemodialysis is unlikely.
DRUG INTERACTION

The pharmacokinetic studies was studied simultaneous application candesartan / hydrochlorothiazide, hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol / levonorgestrel), glibenclamide, nifedipine and enalapril. Clinically significant drug interactions have been identified.
Candesartan is metabolized in the liver to a small extent with the assistance of isoenzyme CYP2C9. Studies on the interaction of the drug showed no effect on CYP2C9 and CYP3A4, effects on other isozymes of the cytochrome P450 system has not been studied.
With simultaneous use of antagonists of angiotensin II receptors and NSAIDs, including COX-2 inhibitors and non-selective NSAIDs, such as acetylsalicylic acid is more than 3 g / day, may reduce the hypotensive effect of candesartan.
The simultaneous use of candesartan / hydrochlorothiazide with other antihypertensive agents enhances the antihypertensive effect.
Dual blockade of the RAAS using angiotensin II receptor antagonists (ARA II), ACE inhibitors or aliskiren (Renin inhibitor) may be accompanied by an increased risk of arterial hypotension, syncope, hyperkalemia, and renal dysfunction (including acute renal failure) as compared with monotherapy. Requires regular monitoring of blood pressure, renal function and blood electrolytes in patients taking both candesartan / hydrochlorothiazide and other drugs that affect the RAAS.
Candesartan / hydrochlorothiazide should not be used simultaneously with aliskiren or aliskirensoderzhaschimi drugs in patients with diabetes mellitus and / or impaired renal function (GFR <60 mL / min / 1.73 m 2 ).
With simultaneous use of ACE inhibitors of dipeptidyl peptidase type 4 inhibitors (e.g. vildagliptin) may increase the risk of angioedema.
Action hydrochlorothiazide, leading to loss of potassium, can be enhanced by other means, resulting in a loss of potassium and hypokalemia (e.g., diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivatives).
Experience with other drugs acting on the RAAS reveals that concomitant treatment by potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other means which increase the content of potassium in the serum (e.g., heparin) can lead to the development of hyperkalemia.
Hypokalemia and hypomagnesemia caused by receiving diuretics, predispose to cardiac glycosides cardiotoxic effect and antiarrhythmic drugs. When receiving candesartan / hydrochlorothiazide parallel with these drugs requires monitoring the potassium content in the blood plasma.
With simultaneous use of drugs lithium with ACE inhibitors occurs reversible increase in the concentration of lithium in blood serum and the development of toxic reactions. Similar reactions can occur when using angiotensin II receptor antagonists, and therefore it is recommended to control blood serum lithium content.
The diuretic, natriuretic and hypotensive effects hydrochlorothiazide reduced while the use of NSAIDs.
Hydrochlorothiazide absorption decreases with applied colestipol, cholestyramine .
The action of nondepolarizing neuromuscular blocking drugs (such as tubocurarine) can be enhanced hydrochlorothiazide.
Thiazide diuretics may cause increased calcium in the blood plasma due to the decrease in its excretion. If necessary, use of calcium supplements and vitamin D must be monitored in plasma calcium levels and adjust the dose as necessary.
Thiazide diuretics enhance the hyperglycemic effect of beta-blockers and diazoxide.
Anticholinergics (e.g., atropine, biperidin) may increase the bioavailability of thiazide diuretics due to decreased GI motility. Thiazide diuretics may increase the risk of adverse effects of amantadine.
Thiazide diuretics can slow excretion of cytotoxic drugs (such as cyclophosphamide, methotrexate) from the body and to enhance their mielopodavlyayuschee action.
The risk of hypokalemia may increase while receiving corticosteroids or ACTH.
Against the background of the drug Ordiss H ® may increase the incidence of orthostatic hypotension when alcohol consumption, use or general anesthetics barbiturate.
In the treatment of thiazide diuretics may reduce glucose tolerance, and therefore may require a dose selection hypoglycemic drugs (t. H. Insulin).
Hydrochlorothiazide can reduce the influence of vasoconstrictive amines (e.g., epinephrine).
Hydrochlorothiazide may increase the risk of developing acute renal failure, especially in combination with high doses of iodinated filler.
Hydrochlorothiazide significant interaction with food was found.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

CAN-RU-00026-DOK
TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of reach of children at a temperature of no higher than 25 ° C.
Shelf life - 2 years.
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