Сasark HD 32mg / 25mg 30 tablets — Made in India — Free Delivery

Pharmacological properties

Pharmacodynamics. Candesartan cilexetil is a prodrug that is rapidly converted to the active substance candesartan by ester hydrolysis during absorption from the digestive tract. candesartan is a selective antagonist of the at1-angiotensin II receptors with strong binding and slow dissociation with them. it does not show agonist activity. Candesartan is not inhibited by APF, which converts angiotensin I to angiotensin II and degrades bradykinin. there is no effect on APF and potentiation of bradykinin or substance p. when comparing candesartan with APF inhibitors, the development of cough was less common in patients receiving candesartan.

Candesartan does not bind to other hormone receptors and does not block ion channels known to play a role in cardiovascular regulation. Antagonism of AT1 receptors leads to a dose-dependent increase in the level of renin in the blood plasma, angiotensin I and angiotensin II, as well as to a decrease in the level of aldosterone in the blood plasma.

The effect of candesartan cilexetil at a dose of 16 mg 1 time per day on morbidity and mortality from cardiovascular diseases was studied in a randomized clinical study in elderly patients with mild to moderate hypertension. Patients took candesartan or placebo with other antihypertensive preparations as needed. Blood pressure dropped from 166/90 to 145/80 mm Hg. Art. in the candesartan group, and from 167/90 to 149/82 mm Hg. Art. in the control group. There was no statistically significant difference in the number of significant cardiovascular events.

Hydrochlorothiazide blocks sodium reabsorption, mainly in the distal renal tubules, and promotes the excretion of sodium, chloride and water. Renal excretion of potassium and magnesium increases depending on the dose of the preparation, while calcium is reabsorbed to a greater extent. Hydrochlorothiazide reduces plasma and extracellular fluid volume and decreases cardiac output and blood pressure. With long-term therapy, reduced peripheral resistance contributes to a decrease in blood pressure.

Candesartan and hydrochlorothiazide exhibit additive antihypertensive effects. In patients with hypertension, Сasark HD leads to a dose-dependent and long-term decrease in blood pressure. Antihypertensive activity is predetermined by a decrease in systemic peripheral resistance without a reflex increase in heart rate. There is no information regarding severe or excessive arterial hypotension after taking the first dose or withdrawal syndrome.

After taking a single dose of Сasark  HD, the onset of the antihypertensive effect usually occurs within 2 hours. With continuous treatment, the maximum decrease in blood pressure with any dose is usually achieved within 4 weeks and is maintained with prolonged treatment.

Сasark HD, when taken 1 time per day, provides an effective and uniform decrease in blood pressure over 24 hours, with a small difference between the maximum and minimum effect during the dosing interval. Сasark HD is equally effective in patients regardless of age and gender.

There are currently no data on the use of candesartan cilexetil / hydrochlorothiazide in patients with kidney disease / nephropathy, decreased left ventricular function / congestive heart failure, and post-myocardial infarction.

Pharmacokinetics. Absorption and distribution

Candesartan cilexetil. Candesartan cilexetil is excreted mainly unchanged in the urine and bile, and only in small amounts is metabolized by the liver (CYP 2C9). Existing interaction studies indicate no effect on CYP 2C9 and CYP 3A4. Based on in vitro data, in vivo interaction with preparations whose metabolism depends on the isoenzymes CYP 1A2, CYP 2A6, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1 or CYP 3A4 of cytochrome P450 is not expected.

T½ of candesartan is about 9 hours. Cumulation of the preparation after repeated multiple doses does not occur. T1 / 2 of candesartan after administration of candesartan cilexetil in combination with hydrochlorothiazide does not change. An increase in the AUC (15-18%) and Cmax (23-24%) indices of candesartan is noted when used in combination with hydrochlorothiazide, but this has no clinical significance. In addition, before switching to the use of Сasark N, separate titration of the constituent components of the preparation is recommended. There was no additional cumulation of candesartan after repeated doses of this combination compared with monotherapy.

The total plasma clearance of candesartan is about 0.37 ml / min / kg, and the renal clearance is about 0.19 ml / min / kg. Candesartan is excreted by the kidneys by glomerular filtration and active tubular secretion. After oral administration of 14C-labeled candesartan cilexetil, about 26% of the dose is excreted in the urine as candesartan and 7% as an inactive metabolite, while 56% of the dose is detected in feces as candesartan and 10% as an inactive metabolite.

Hydrochlorothiazide. Hydrochlorothiazide is rapidly absorbed in the digestive tract with an absolute bioavailability of 70%. Food intake improves the absorption of hydrochlorothiazide by about 15%. Bioavailability may decrease in patients with heart failure and severe edema. The binding of hydrochlorothiazide to blood plasma proteins is about 60%. The apparent volume of distribution is about 0.8 l / kg of body weight.

Metabolism and excretion from the body

Candesartan cilexetil. Candesartan is mainly excreted in the urine and bile unchanged and to a small extent by hepatic metabolism. T1 / 2 of candesartan is about 9 hours. After taking multiple doses, no cumulation of the preparation in the body was detected. The total plasma clearance of candesartan is about 0.37 ml / min / kg, and the renal clearance is about 0.19 ml / min / kg. Renal excretion of candesartan is mediated by both glomerular filtration and active tubular secretion. After taking an oral dose of 14C-labeled candesartan cilexetil, about 26% of the dose is excreted in the urine as candesartan and 7% as inactive metabolite, although about 56% of the dose is determined in feces as candesartan and 10% as inactive metabolite.

Hydrochlorothiazide. Hydrochlorothiazide is not metabolized and is excreted mainly unchanged by glomerular filtration and active tubular secretion. The final T1 / 2 is 8 hours. About 70% of the dose taken orally is excreted in the urine within 48 hours. T1 / 2 of hydrochlorothiazide remains unchanged when combined with candesartan cilexetil. There was no additional cumulation of hydrochlorothiazide after repeated administration of the combination compared with monotherapy.

Pharmacokinetics in special categories of patients

Candesartan cilexetil. In elderly patients (over 65 years of age), the Cmax and AUC of candesartan are increased by approximately 50 and 80%, respectively, compared with young patients. However, the blood pressure response and the incidence of side effects are the same after taking the prescribed dose of candesartan in young and elderly patients.

In patients with mild to moderate renal impairment, compared with patients with normal renal function, the Cmax and AUC of candesartan increase after repeated dosing by approximately 50 and 70%, respectively, while the T½ of the preparation remains unchanged. Corresponding changes in patients with severe renal insufficiency are about 50 and 110%, and the T½ of the preparation is doubled. The AUC of candesartan in hemodialysis patients is similar to that in patients with severe renal impairment.

In patients with mild to moderate hepatic impairment, an increase in the AUC of candesartan was observed by 23% in one study and by 80% in another study. There is no experience of using the preparation in patients with severe liver dysfunction.

Hydrochlorothiazide. The terminal T1 / 2 of hydrochlorothiazide is increased in patients with renal insufficiency.

Indications

Essential hypertension in cases where candesartan monotherapy with cilexetil or hydrochlorothiazide is insufficient.

Application

Dosage. the recommended initial and usual maintenance dose of Сasark HD is 16 mg / 12.5 mg (½ tablet of Сasark HD or 1 tablet of Сasark H) 1 time per day. if sufficient control of blood pressure is not achieved after 4 weeks of treatment, the dose of 16 mg / 12.5 mg 1 time per day can be increased to 32 mg / 25 mg (1 tablet of Сasark HD) 1 time per day. if sufficient control of blood pressure is not achieved after 4 weeks of treatment at a dose of 12.5 mg once a day, then the dose can be increased to 25 mg once a day. therapy must be corrected in accordance with the reaction of hell. the maximum antihypertensive effect is achieved within 4 weeks from the start of treatment. before transferring the patient to casark hd, the dose of candesartan cilexetil should be titrated taking into account blood pressure. in case of clinical feasibility, a direct transition from monopreparations to the combined preparation casark hd can be considered. if sufficient control of blood pressure is not achieved with the use of Сasark HD at a dose of 32/25 mg 1 time per day, the feasibility of alternative therapies should be considered.

Application. Сasark HD should be taken once a day with or without food.

Elderly patients. Correction of the initial dose in elderly patients is not required.

Use in patients with reduced BCC. For patients at risk of arterial hypotension, for example with a possible decrease in BCC, an initial dose of 4 mg candesartan cilexetil should be considered. Such patients are not recommended to prescribe a combined preparation at a dose of 16 / 12.5 or 32/25 mg. They are prescribed the monopreparation of candesartan cilexetil (Сasark ) at a dose of 4 or 8 mg, depending on the severity and tolerance, with the addition of an appropriate dose of hydrochlorothiazide, if necessary.

Application for renal failure. In this category of patients, it is advisable to use loop diuretics rather than thiazide diuretics. Сasark HD should not be used to treat patients with severe renal impairment (creatinine clearance 30 ml / min / 1.73 m2 body surface area). Dose titration of candesartan cilexetil is recommended for patients with renal insufficiency whose creatinine clearance is ≥30 ml / min / 1.73 m2 of body surface area prior to treatment with Kasarcom HD (for patients with mild to moderate renal insufficiency, the recommended starting dose of candesartan cilexetil is is 4 mg).

Application for liver failure. Dose titration of candesartan cilexetil is recommended for patients with mild to moderate hepatic impairment before starting treatment with Сasark  HD (the recommended starting dose of candesartan cilexetil for these patients is 2 mg). The dose can be adjusted based on blood pressure. Сasark HD should not be used to treat patients with severe hepatic impairment and / or cholestasis.

Contraindications

Hypersensitivity to active ingredients or any of the excipients of the preparation. severe renal impairment (creatinine clearance 30 ml / min / 1.73 m2 body surface area), severe hepatic impairment and / or bile stasis (cholestasis), persistent hypokalemia or hypercalcemia, gout, pregnancy and lactation, children under 18 years of age ... patients with diabetes mellitus or impaired renal function (scf 60 ml / min / 1.73 m2) are contraindicated in the simultaneous use of Сasark HD with preparations containing aliskiren (see interactions).

Side effects

According to data from controlled clinical trials, when using a combination of candesartan cilexetil / hydrochlorothiazide, adverse reactions were mild and temporary. study discontinuation due to side effects was similar with the combination of candesartan cilexetil / hydrochlorothiazide (2.3–3.3%) and placebo (2.7–4.3%).

According to clinical studies, with the use of the combined preparation candesartan cilexetil / hydrochlorothiazide, adverse reactions were the same as with candesartan cilexetil and / or hydrochlorothiazide.

The frequency of adverse reactions is as follows: very often (≥ 1/10), often (≥ 1/100 to 1/10), infrequently (≥1 / 1000 to 1/100), rarely (≥1 / 10,000 to 1/1000) , very rare (1/10 000) and unknown (cannot be estimated from the available data).

Candesartan cilexetil / hydrochlorothiazide

From the nervous system: often - dizziness / vertigo, headache.

Candesartan cilexetil

• Infections and invasions: often - respiratory tract infections;
• on the part of the blood and lymphatic system: very rarely - leukopenia, neutropenia and agranulocytosis;
• from the side of the vessels: very rarely - arterial hypotension;
• on the part of the respiratory system, organs of the chest cavity and mediastinum: very rarely - cough;
• from the nervous system: often - dizziness, headache;
• from the gastrointestinal tract: very rarely - nausea;
• on the part of the skin and subcutaneous tissue: very rarely - angioedema, rash, urticaria, itching;
• from the musculoskeletal system: very rarely - back pain, arthralgia, myalgia;
• from the urinary system: very rarely - impaired renal function, including renal failure in predisposed patients;
• on the part of the hepatobiliary system: very rarely - an increase in the level of liver enzymes, impaired liver function or hepatitis;
• metabolic changes and nutritional disorders: very rarely - hyperkalemia, hyponatremia.

Hydrochlorothiazide

• On the part of the blood and lymphatic system: rarely - leukopenia, neutropenia / agranulocytosis, thrombocytopenia, aplastic anemia, bone marrow suppression, hemolytic anemia;
• from the immune system: rarely - anaphylactic reactions;
• metabolic and nutritional disorders: often - hyperglycemia, hyperuricemia, electrolyte imbalance (including hyponatremia and hypokalemia);
• mental disorders: rarely - sleep disturbances, depression, anxiety;
• from the nervous system: often - dizziness, vertigo; rarely - paresthesia;
• on the part of the organ of vision: rarely - temporary blurred vision, acute myopia, acute angle-closure glaucoma;
• on the part of the cardiovascular system: infrequently - postural hypotension; rarely - cardiac arrhythmia; necrotizing angiitis (vasculitis, cutaneous vasculitis);
• from the respiratory system, chest and mediastinal organs: rarely - respiratory disorders (including pneumonitis and pulmonary edema);
• from the digestive system: infrequently - anorexia, loss of appetite, irritation of the gastric mucosa, diarrhea, constipation; rarely - pancreatitis;
• hepatobiliary disorders: rarely - jaundice (intrahepatic cholestatic jaundice);
• on the part of the skin and subcutaneous tissue: infrequently - rash, urticaria, photosensitivity reactions; rarely - toxic epidermal necrolysis, skin reactions like systemic lupus erythematosus, reactivation of the cutaneous form of systemic lupus erythematosus;
• from the musculoskeletal system: rarely - muscle spasm;
• from the urinary system: often - glucosuria; rarely - renal dysfunction and interstitial nephritis;
• general disorders and changes at the injection site: often - weakness; rarely - fever;
• changes in laboratory parameters and data from instrumental studies: often - increased levels of cholesterol and triglycerides; infrequently - increased levels of blood urea nitrogen and plasma creatinine; data were obtained on cases of increased levels of uric acid, glucose and ALT in the blood plasma, a slight decrease in hemoglobin levels and an increase in AST, an increase in the level of creatinine, urea or potassium, and a decrease in sodium levels.

special instructions

Double blockade of the renin-angiotensin-aldosterone system (raac). there is evidence that the simultaneous use of APF inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of arterial hypotension, hyperkalemia and decreased renal function (including OPN). as a result, a double blockade of raac occurs, therefore the combined use of APF inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see interactions).

If double blockade is absolutely necessary, it should be done only under the supervision of a specialist and subject to frequent close monitoring of renal function, electrolyte levels and blood pressure. Patients with diabetic nephropathy should not use ACE inhibitors and angiotensin II receptor blockers at the same time.

Pregnancy. There were no special studies of Сasark  HD during pregnancy and lactation. The effect is associated with the effect of individual components of the preparation.

Do not start treatment with angiotensin II receptor antagonists during pregnancy. Except when long-term treatment with angiotensin II receptor antagonists is considered necessary, patients planning a pregnancy should switch to alternative antihypertensive preparations that are safe to use during pregnancy. When pregnancy is established, the preparation should be discontinued immediately and, if necessary, alternative treatment should be started (see CONTRAINDICATIONS and Use during pregnancy and lactation).

The use of angiotensin II receptor antagonists is contraindicated during pregnancy. When pregnancy is established, the preparation should be discontinued immediately. If necessary, alternative therapy should be prescribed (see Use during pregnancy and lactation).

Other antihypertensive medicines. The effect of lowering blood pressure when using Сasark HD can be enhanced by the combined use of other antihypertensive preparations.

Renal failure In these patients, it is desirable to use loop diuretics rather than thiazides. When using Сasark  HD in patients with renal insufficiency, periodic monitoring of the level of potassium, creatinine and uric acid in the blood plasma is recommended.

Kidney transplant. There is no experience with the use of Сasark HD in patients who have recently undergone kidney transplantation.

Renal artery stenosis. Medicines that affect the RAAS, such as ACE, can increase blood urea and plasma creatinine levels in patients with bilateral or monolateral renal artery stenosis. A similar effect can be expected with the use of angiotensin II receptor antagonists.

Decrease in BCC. In patients with a decrease in BCC and / or hyponatremia, symptomatic hypotension may occur, as with the use of other preparations that affect the RAAS. Therefore, it is not recommended to use Сasark HD until the BCC has been corrected.

Anesthesia and surgery. In patients receiving treatment with angiotensin II receptor antagonists, arterial hypotension may develop during anesthesia and surgery due to RAAS blockade. In some cases, arterial hypotension can be so severe that IV fluids and / or vasopressors may be required.

Liver failure. Thiazides should be used with caution in patients with hepatic impairment or with progressive liver disease, since minor changes in water and electrolyte balance can provoke hepatic coma. There is no clinical experience of using Сasark HD in patients with hepatic insufficiency.

Stenosis of the aorta or mitral valve, obstructive hypertrophic cardiomyopathy. As with the use of other vasodilators, special care must be taken when treating patients with hemodynamically significant stenosis of the aorta or mitral valve or obstructive hypertrophic cardiomyopathy.

Primary hyperaldosteronism. Patients with primary hyperaldosteronism usually do not respond to antihypertensive preparations that act by inhibiting the RAAS. Therefore, it is not recommended to use the preparation in such patients.

Electrolyte imbalance. As with any patients receiving diuretic therapy, the level of electrolytes in the blood plasma should be determined after appropriate periods. Thiazides, including hydrochlorothiazide, can cause water or electrolyte imbalance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia, and hypochloremic alkalosis). Thiazide diuretics can reduce the excretion of calcium in the urine and cause a transient and insignificant increase in the concentration of calcium in the blood plasma. Severe hypercalcemia may be a sign of latent hyperparathyroidism. Before monitoring the function of the parathyroid gland, the use of thiazides should be discontinued. Hydrochlorothiazide dose-dependently increases the excretion of potassium in the urine, which can lead to hypokalemia. This effect of hydrochlorothiazide is less pronounced when used in combination with candesartan cilexetil. The risk of hypokalemia may be increased in patients with cirrhosis of the liver, increased diuresis, inadequate oral electrolyte intake, and in patients receiving concomitant corticosteroid or ACTH therapy. Based on experience with other preparations that affect the renin-angiotensin-aldosterone system, the simultaneous use of Сasark HD and potassium-sparing diuretics, potassium supplements or salt substitutes, or other preparations that can increase the level of potassium in the blood plasma (for example, heparin) can lead to an increase in the level of potassium in the blood plasma. Treatment with ACE inhibitors or angiotensin II receptor antagonists can cause hyperkalemia, especially in the presence of heart and / or renal failure. Thiazides increase the excretion of magnesium in the urine, which can lead to hypomagnesemia.

Impact on metabolism and the endocrine system. Treatment with thiazide diuretics may interfere with glucose tolerance. Dose adjustment of antidiabetic preparations, including insulin, may be necessary. During therapy with thiazides, latent diabetes mellitus may appear. An increase in cholesterol and triglyceride levels was associated with thiazide diuretic therapy. However, with a dose of 12.5 mg hydrochlorothiazide, side effects are minimal or not. Thiazide diuretics increase the concentration of uric acid in the blood plasma and can provoke gout in patients prone to it.

Light sensitivity. During therapy with thiazide diuretics, cases of photosensitivity reactions have been noted. If photosensitivity reactions occur, it is recommended to discontinue treatment. If there is a need to re-prescribe diuretics, it is recommended to protect vulnerable areas from exposure to the sun or artificial ultraviolet sources.

General information. In patients in whom vascular tone and renal function depend predominantly on the activity of the RAAS (for example, patients with severe congestive heart failure or with kidney disease, including renal artery stenosis), treatment with other preparations that affect this system has been associated with acute arterial hypotension. azotemia, oliguria, or, in rare cases, with acute renal failure. The possibility of such effects cannot be excluded when using angiotensin II receptor antagonists. As with any antihypertensive preparation , an excessive decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular disease can lead to myocardial infarction or stroke.

Hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without allergies, or a history of asthma, but are more likely in patients with such diseases. Possible exacerbation or activation of systemic lupus erythematosus with the use of thiazide diuretics.

The preparation contains lactose as an excipient, so it should not be taken by patients with rare hereditary diseases of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

The preparation contains tartrazine, so it can cause allergic reactions.

Use during pregnancy and lactation. Pregnancy. Angiotensin II receptor antagonists. Сasark HD is contraindicated for use by pregnant women or women planning to become pregnant. If pregnancy is confirmed during treatment, its use must be stopped immediately and replaced with another preparation approved for use by pregnant women.

Hydrochlorothiazide. The experience of using hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. The results of animal experiments are insufficient.

Hydrochlorothiazide crosses the placental barrier. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use in the II and III trimester of pregnancy can disrupt placental circulation and cause fetal and neonatal complications such as jaundice, electrolyte imbalance and thrombocytopenia.

Hydrochlorothiazide should not be used for gestational edema, gestational hypertension in pregnant women or preeclampsia due to the risk of a decrease in blood plasma volume and the development of placental hypoperfusion and the absence of any positive effects on the course of the disease.

Hydrochlorothiazide should not be used in essential hypertension in pregnant women, except in rare cases when there is no other alternative treatment for such patients.

Lactation. Angiotensin II receptor antagonists. You should switch to alternative means, the use of which is safe during breastfeeding, especially for newborns and premature babies.

Hydrochlorothiazide. Hydrochlorothiazide passes into breast milk in small amounts. Thiazides in high doses that cause increased urine output can reduce the amount of breast milk.

Children. The safety and efficacy of Сasark HD in children have not been established, therefore it is not prescribed to patients of this age category.

The ability to influence the reaction rate when driving or working with other mechanisms. The effect of the preparation on the ability to drive vehicles or work with other mechanisms has not been studied, however, given the pharmacodynamic properties of candesartan, it is unlikely that it has such an ability. When driving or working with other mechanisms, one should take into account the possibility of arterial hypotension during treatment with Сasark HD, which may be accompanied by dizziness and increased fatigue.

Interactions

Clinically significant preparation interactions of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives such as ethinyl estradiol / levonorgestrel, glibenclamide and nifedipine have not been identified.

Other antihypertensive preparations can enhance the antihypertensive effect of Сasark HD with these preparations. It can be expected that the decrease in potassium levels, which is characteristic of hydrochlorothiazide, is enhanced by other preparations that are associated with potassium loss and hypokalemia (for example, other potassium-sparing diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivatives). Experience with other preparations that affect the RAAS suggests that the simultaneous use of Сasark HD with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other preparations that can increase potassium levels (for example, heparin) may lead to an increase in potassium in the blood plasma.

Diuretic-induced hypokalemia and hypomagnesemia contribute to the potential cardiotoxic effects of digitalis glycosides and antiarrhythmics. With the simultaneous use of the preparation Сasark HD with these preparations, it is recommended to periodically monitor the level of potassium in the blood plasma.

Plasma potassium monitoring is recommended if Casark HD is administered concomitantly with these preparations, as well as with the following preparations that can cause torsades de pointes (paroxysmal ventricular tachycardia of the pirouette type):

class Ia antiarrhythmics (eg quinidine, hydroquinidine, disopyramide);

class III antiarrhythmics (eg amiodarone, sotalol, dofetilide, ibutilide);

some antipsychotic preparations (for example, thioridazine, chlorpromazine, levomepromazine, trifluorperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperiodol);

other preparations (for example, bepridil, cisapride, diphemanil, erythromycin for i.v. use, halofantrine, ketanserin, mizolastine, pentamidine, sparfloxacin, terfenadine, vincamine for i.v. use).

A reversible increase in the concentration of lithium in the blood plasma and its toxicity during the simultaneous use of lithium with ACE inhibitors or hydrochlorothiazide is possible. A similar effect can occur with antagonists of angiotensin II receptors, therefore, with simultaneous use, careful monitoring of the level of lithium in the blood plasma is recommended.

With the simultaneous use of ARA II with NSAIDs, for example, selective COX-2 inhibitors, acetylsalicylic acid (3 g / day) and non-selective NSAIDs), the hypotensive effect may be weakened.

As with the use of ACE inhibitors, the simultaneous use of angiotensin II receptor antagonists with NSAIDs may increase the risk of developing renal failure, including acute renal failure, as well as an increase in plasma potassium levels, especially in patients with a history of impaired renal function. This combination should be used with caution, especially in elderly patients. Patients should receive a sufficient amount of fluid, and should also consider the need to monitor renal function after the start of concomitant therapy and periodic monitoring thereafter.

NSAIDs reduce the severity of the diuretic, natriuretic and antihypertensive effect of hydrochlorothiazide.

Colestipol or cholestyramine reduces the absorption of hydrochlorothiazide.

Hydrochlorothiazide may potentiate the effect of non-polarizing skeletal muscle relaxants (eg tubocurarine).

Thiazide diuretics can increase the level of calcium in the blood plasma due to its reduced excretion. When prescribing calcium supplements or vitamin D, it is necessary to monitor the level of calcium in the blood plasma and adjust the dose accordingly.

Thiazides can enhance the hyperglycemic effect of β-adrenergic receptor blockers and diazoxide.

Anticholinergic preparations (such as atropine, biperiden) can increase the bioavailability of thiazide-type diuretics, reducing gastrointestinal motility and gastric emptying rate.

Thiazides may increase the risk of side effects caused by amantadine.

Thiazides can reduce the excretion of cytotoxic preparations (such as cyclophosphamide, methotrexate) by the kidneys and potentiate their myelosuppressive effects.

The decrease in potassium levels characteristic of hydrochlorothiazide can be expected to be enhanced by other preparations associated with potassium loss and hypokalemia (eg, steroids, ACTH).

Concomitant use of alcohol, barbiturates, or anesthetics can cause postural hypotension.

Treatment with thiazide diuretics may impair glucose tolerance. There may be a need to adjust the dose of antidiabetic agents, including insulin.

Metformin should be used with caution, given the risk of lactic acidosis due to possible functional renal failure associated with hydrochlorothiazide.

Hydrochlorothiazide may cause a decrease in the response of the arteries to pressor amines (such as epinephrine), but this is not sufficient to eliminate the pressor effect.

Hydrochlorothiazide, when used simultaneously with an iodine-containing radiopaque contrast agent in high doses, may increase the risk of acute renal failure.

When used in combination with cyclosporine, the risk of hyperuricemia and complications such as gout may increase.

Simultaneous use with baclofen, amifostine, tricyclic antidepressants or antipsychotics can lead to an increase in the hypotensive effect and cause arterial hypotension.

According to clinical studies, double blockade of the RAAS resulting from the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher incidence of side effects such as arterial hypotension, hyperkalemia and decreased renal function (including ARF), according to compared with the use of a single preparation that affects the RAAS (see CONTRAINDICATIONS, SPECIAL INSTRUCTIONS).

Food intake does not affect the bioavailability of candesartan.

There is no clinically significant interaction between hydrochlorothiazide and food intake.

Overdose

Symptoms the main manifestations of an overdose of candesartan cilexetil include symptomatic hypotension and dizziness.

The main manifestation of an overdose of hydrochlorothiazide is an acute loss of fluid and electrolytes. Symptoms such as dizziness, hypotension, thirst, tachycardia, ventricular arrhythmias, sedation / loss of consciousness, and muscle cramps may also be noted.

Treatment. There is no information regarding the treatment of preparation overdose. However, in the event of an overdose, such measures are offered. Induce vomiting or gastric lavage. If symptomatic arterial hypotension occurs, symptomatic treatment and monitoring of vital functions should be started. The patient should be placed on his back with raised lower limbs. If this is not enough, the volume of blood plasma should be increased by infusion, for example, isotonic saline solution. If necessary, the electrolyte and acid balance of blood plasma should be monitored and adjusted. If the above measures are not enough, symptomatic medications can be used.

Candesartan is not excreted by hemodialysis. The degree of elimination of hydrochlorothiazide by hemodialysis is unknown.

Storage conditions

In its original packaging at a temperature not exceeding 30 ° C.