Atacand Plus is a combination drug for the treatment of hypertension. Terms and conditions of storage

Dosage form

Tablets

Compound

One tablet contains

active substances: candesartan cilexetil 16 mg, hydrochlorothiazide 12.5 mg,

excipients: calcium carboxymethyl cellulose, hydroxypropyl cellulose, iron oxide yellow CI 77492 (E172), iron oxide red CI 77491 (E172), lactose monohydrate, magnesium stearate, corn starch, polyethylene glycol 8000.

Description

Peach-coloured, oval, biconvex tablets, scored on both sides and debossed with "" on one side.

Pharmacotherapeutic group

Angiotensin II antagonists in combination with diuretics.

ATX code C09DA06

Pharmacological properties

Pharmacokinetics

Co-administration of candesartan cilexetil and hydrochlorothiazide has no clinically significant effect on the pharmacokinetics of either of these medicinal products.

Suction and distribution

Candesartan cilexetil

Candesartan cilexetil is an oral prodrug. It quickly turns into the active substance - candesartan through ether hydrolysis during absorption from the digestive tract, binds strongly to AT1 receptors and slowly dissociates, has no agonist properties. The absolute bioavailability of candesartan after oral administration of a solution of candesartan cilexetil is approximately 40%. The relative bioavailability of the tablet formulation compared to the oral solution is approximately 34%. The maximum concentration in blood serum (Cmax) is reached 3-4 hours after taking the tablet form of the drug. With an increase in the dose of the drug within the recommended limits, the concentration of candesartan increases linearly. The pharmacokinetic parameters of candesartan do not depend on the gender of the patient. Food intake does not significantly affect the area under the concentration-time curve (AUC), i.e. food does not significantly affect the bioavailability of the drug. Candesartan actively binds to plasma proteins (more than 99%). The plasma volume of distribution of candesartan is 0.1 L/kg.

Hydrochlorothiazide

Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract, bioavailability is approximately 70%. Concomitant food intake increases absorption by about 15%. Bioavailability may be reduced in patients with heart failure and severe edema. Communication with blood plasma proteins is approximately 60%. The apparent volume of distribution is approximately 0.8 l/kg.

Metabolism and excretion

Candesartan cilexetil

Candesartan is mainly excreted in the urine and bile unchanged and is only slightly metabolized in the liver.

Available interaction studies have shown no effect on CYP2C9 and CYP3A4. Based on in vitro data, no interactions are expected in the body with drugs whose metabolism is dependent on cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, or CYP3A4. The elimination half-life of candesartan is approximately 9 hours. Cumulation of the drug in the body is not observed. The elimination half-life of candesartan remains unchanged (approximately 9 hours) after administration of candesartan cilexetil with hydrochlorothiazide. There is no additional accumulation of candesartan after multiple doses of the combination drug compared to monotherapy.

The total clearance of candesartan is about 0.37 ml/min/kg, while the renal clearance is about 0.19 ml/min/kg. Renal excretion of candesartan is by glomerular filtration and active tubular secretion. When radiolabeled candesartan cilexetil is ingested, about 26% of the administered amount is excreted in the urine as candesartan and 7% as an inactive metabolite, while 56% of the administered amount is found in the feces as candesartan and 10% as an inactive metabolite.

Hydrochlorothiazide

Hydrochlorothiazide is not metabolized and is excreted almost completely in the form of the active form of the drug by glomerular filtration and active tubular secretion in the proximal nephron. The half-life is approximately 8 hours. Approximately 70% of an oral dose is excreted in the urine within 48 hours. The elimination half-life does not change when taken together with candesartan. When using a combination of drugs, no additional accumulation of hydrochlorothiazide was detected in comparison with monotherapy.

Pharmacokinetics of candesartan in special groups

In elderly patients (over 65 years of age), Cmax and AUC of candesartan are increased by 50% and 80%, respectively, compared with young patients. However, the hypotensive effect and the incidence of side effects when using Atacanda® Plus do not depend on the age of the patients.

In patients with mild and moderate renal impairment, Cmax and AUC of candesartan increased by 50% and 70%, respectively, while the half-life of the drug does not change compared with patients with normal renal function. In patients with severe renal impairment, Cmax and AUC of candesartan increased by 50% and 110%, respectively, and the half-life of the drug increased by 2 times. In patients on hemodialysis, the same pharmacokinetic parameters of candesartan were found as in patients with severe renal impairment.

In patients with mild to moderate hepatic impairment, an increase in the AUC of candesartan by 20% - 80% was observed according to clinical studies.

Hydrochlorothiazide

The elimination half-life is longer in patients with renal insufficiency.

Pharmacodynamics

Atacand® Plus is a combination of a non-peptide selective blocker of AT1 angiotensin II receptors - cadesartan, which is contained in the dosage form as a prodrug (cadesartan cilexetil) and a thiazide diuretic - hydrochlorothiazide.

Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system, 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 fluid and electrolyte status, and stimulation of cell growth. All these effects are mediated by the interaction of angiotensin II with angiotensin type 1 receptors (AT1 receptors).

Candesartan is a selective type 1 angiotensin II receptor antagonist (AT1 receptor), does not inhibit angiotensin-converting enzyme (ACE), which converts angiotensin I to angiotensin II and destroys bradykinin; does not affect ACE and does not lead to the accumulation of bradykinin or substance P. When comparing candesartan with ACE inhibitors, the development of cough was less common in patients treated with candesartan cilexetil. Candesartan does not bind to other hormone receptors and does not block ion channels involved in the regulation of the functions of the cardiovascular system. As a result of blocking the AT1 receptors of angiotensin II, a dose-dependent increase in the level of renin, angiotensin I, angiotensin II and a decrease in the concentration of aldosterone in the blood plasma occurs.

Hydrochlorothiazide inhibits active sodium reabsorption, mainly in the distal renal tubules and enhances the release of sodium, chloride and water ions. Excretion of potassium and magnesium by the kidneys increases in a dose-dependent manner, while calcium begins to be reabsorbed in greater quantities than before. Hydrochlorothiazide reduces the volume of blood plasma and extracellular fluid and reduces the intensity of blood transport by the heart and blood pressure. During long-term treatment, the hypotensive effect develops due to the expansion of arterioles.

Long-term use of hydrochlorothiazide has been shown to reduce the risk of cardiovascular disease and mortality.

Candesartan and hydrochlorothiazide have a combined antihypertensive effect.

In patients suffering from arterial hypertension, Atacand® Plus causes an effective and long-lasting decrease in blood pressure without an increase in heart rate (HR). Orthostatic hypotension at the first dose of the drug is not observed, and arterial hypertension does not increase after the end of treatment. After a single dose of Atacanda® Plus, the main hypotensive effect develops within 2 hours. With prolonged treatment, a stable decrease in blood pressure occurs within 4 weeks after the start of the drug and can be maintained with a long course of treatment. Atacand® Plus, when taken once a day, effectively and gently lowers blood pressure within 24 hours with little difference between the maximum and average effect of action. In clinical studies, the incidence of side effects, especially cough, was less common with Atacanda Plus than with a combination of ACE inhibitors with hypothiazide.

The effectiveness of the combination of candesartan and hydrochlorothiazide does not depend on the sex and age of the patient. Currently, there are no data on the use of candesartan / hydrochlorothiazide in patients with renal insufficiency / nephropathy, reduced left ventricular function / acute heart failure and patients who have had myocardial infarction.

Indications for use

Treatment of arterial hypertension in patients for whom combination therapy is indicated

Dosage and administration

Atacand® Plus should be taken once a day, regardless of the meal.

The main hypotensive effect is achieved, as a rule, in the first 4 weeks after the start of treatment.

Elderly patients

In elderly patients, dose adjustment is not required.

Patients with renal insufficiency

In patients with impaired renal function, loop diuretics are preferred over thiazide diuretics. Prior to initiation of therapy with Atacand® Plus, in patients with mild or moderate renal impairment (creatinine clearance ≥ 30 ml / min / 1.73 m2), including patients on hemodialysis, it is recommended to titrate the dose of candesartan (via Atacand monotherapy), starting with 4 mg.

Atacand® Plus is contraindicated in patients with severe renal insufficiency (creatinine clearance< 30 мл/мин/1,73 м2 BSA).

Patients with reduced circulating blood volume

For patients at risk of arterial hypotension, for example, for patients with reduced circulating blood volume, it is recommended to titrate the dose of candesartan (through Atacand monotherapy) starting from 4 mg.

Patients with liver failure

An increase in the dose of candesartan cilexetil is recommended in patients with mild or moderate hepatic impairment for treatment with Atacand® Plus (the recommended starting dose of candesartan cilexetil is 4 mg in such patients). The use of Atacand® Plus is contraindicated in patients with severe hepatic insufficiency and / or cholestasis.

Side effects

Often (> 1/100,< 1/10)

Headache, dizziness

Respiratory tract infections

Very rarely (< 1/10 000)

Nausea

Leukopenia, neutropenia and agranulocytosis

Hyperkalemia, hyponatremia

Increased activity of "liver" enzymes, abnormal liver function or hepatitis

Angioedema, rash, urticaria, pruritus

Back pain, arthralgia, myalgia

Impaired renal function, including renal failure in predisposed patients

During therapy with hydrochlorothiazide, usually at a dose of 25 mg or more, the following side effects have been noted: infrequently (> 1/1000 and<1/100), редко (<1/1000) и неизвестно (нет достаточных данных для оценки частоты):

Uncommon (> 1/1000,< 1/100)

photosensitivity reactions

Rare (> 1/10,000,< 1/1 000)

Leukopenia, neutropenia/agranulocytosis, thrombocytopenia, aplastic anemia

Anaphylactic reactions

Necrotizing vasculitis

Respiratory distress syndrome (including pneumonia and pulmonary edema)

pancreatitis

Jaundice (intrahepatic cholestatic)

Toxic epidermal necrolysis,

Renal dysfunction and interstitial nephritis

unknown

Acute myopia, acute angle-closure glaucoma

Contraindications

Hypersensitivity to the active or auxiliary components that make up the drug, sulfonamide derivatives

Pregnancy and lactation

Severe liver failure and/or cholestasis

Severe renal failure (creatinine clearance less than 30 ml/min/1.73 m2)

Refractory hypokalemia and hypercalcemia

Gout

Children under 18 years of age (efficacy and safety not established)

With caution: severe chronic heart failure, bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, hemodynamically significant stenosis of the aortic and mitral valve, in patients with cerebrovascular diseases and coronary heart disease, hypertrophic obstructive cardiomyopathy, in patients with reduced circulating blood volume, liver cirrhosis , in patients suffering from lactose intolerance, malabsorption of lactose and galactose, hyponatremia, primary hyperaldosteronism, surgery, in patients after kidney transplantation, renal failure, diabetes mellitus.

Drug Interactions

In pharmacokinetic studies, the combined use of Atacanda® Plus with warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine was studied. No clinically significant pharmacokinetic interactions have been identified.

Candesartan is metabolized in the liver to a small extent (CYP2C9). Conducted interaction studies did not reveal the effect of the drug on CYP2C9 and CYP3A4. The combined use of Atacanda® Plus with other antihypertensive agents potentiates the hypotensive effect.

It should be expected that the effect of hydrochlorothiazide, leading to loss of potassium, may be enhanced by other agents leading to loss of potassium and hypokalemia (eg, diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivatives, steroids, ACTH).

Experience with other drugs that act on the renin-angiotensin-aldosterone system shows that concomitant therapy with potassium-sparing diuretics, potassium preparations, salt substitutes and other drugs that can increase serum potassium levels (eg, heparin) can lead to the development of hyperkalemia .

Diuretic-induced hypokalemia and hypomagnesemia predispose to the possible cardiotoxic effects of digitalis glycosides and antiarrhythmic agents. When taking Atacand® Plus in parallel with such drugs, it is necessary to control the level of potassium in the blood.

With the combined administration of lithium preparations with ACE inhibitors or hydrochlorothiazide, a reversible increase in the concentration of lithium in the blood serum and the development of toxic reactions have been reported. Similar reactions can also occur with the use of angiotensin II receptor antagonists, and therefore it is recommended to control the level of lithium in the blood serum with the combined use of these drugs.

The bioavailability of candesartan is independent of food intake.

The diuretic, natriuretic and hypotensive effects of hydrochlorothiazide are weakened by non-steroidal anti-inflammatory drugs.

The absorption of hydrochlorothiazide is weakened by the use of colestipol or cholestyramine.

The action of non-depolarizing muscle relaxants (for example, tubocurarine) can be enhanced by hydrochlorothiazide.

Thiazide diuretics can cause an increase in the level of calcium in the blood due to a decrease in its excretion. If calcium supplements or vitamin D are required, plasma calcium levels should be monitored and the dose adjusted if necessary.

Thiazides enhance the hyperglycemic action of beta-blockers and diazoxide.

Anticholinergics (eg, atropine, biperidine) may increase the bioavailability of thiazide diuretics due to decreased gastrointestinal motility.

Thiazides may increase the risk of adverse effects of amantadine.

Thiazides can slow down the excretion of cytotoxic drugs (such as cyclophosphamide, methotrexate) from the body and increase their myelosuppressive effect.

The risk of hypokalemia may increase with concomitant use of steroid drugs or adrenocorticotropic hormone.

Against the background of taking the drug, the incidence of orthostatic hypotension may increase when taking alcohol, barbiturates or anesthetics.

Treatment with thiazides may reduce glucose tolerance. It may be necessary to adjust the dose of antidiabetic drugs, including insulin.

Hydrochlorothiazide may reduce the effect of vasoconstrictor amines (eg, epinephrine (adrenaline)).

Hydrochlorothiazide may increase the risk of developing acute renal failure, especially in combination with large doses of iodinated contrast agent.

With concomitant use with cyclosporine, the risk of hyperuricemia and gout may increase.

Concomitant use of baclofen, tricyclic antidepressants or antipsychotics may lead to increased antihypertensive effect and may cause hypotension.

special instructions

Impaired kidney function

In this situation, the use of loop diuretics is preferable to thiazide ones. For patients with renal insufficiency, when using Atacand® Plus, it is recommended to constantly monitor the level of potassium, creatinine and uric acid.

kidney transplant

Data on the use of Atacanda® Plus in patients who have recently undergone a kidney transplant are not available.

Renal artery stenosis

Other drugs that affect the renin-angiotensin-aldosterone system, such as ACE inhibitors, can lead to an increase in blood urea and serum creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. A similar effect should be expected from angiotensin II receptor antagonists.

Decrease in circulating blood volume

Patients with intravascular volume and/or sodium deficiency may develop symptomatic hypotension, as described for other drugs that affect the renin-angiotensin-aldosterone system. Therefore, it is not recommended to use Atacand® Plus until these symptoms disappear.

Anesthesia and surgery

In patients receiving angiotensin II antagonists, arterial hypotension may develop during anesthesia and during surgical interventions as a result of blockade of the renin-angiotensin system. Very rarely, cases of severe arterial hypotension may occur, requiring intravenous fluids and / or vasopressors.

Liver failure

In patients with impaired liver function or progressive liver disease, thiazides should be used with caution, since slight fluctuations in fluid volume and electrolyte composition can cause hepatic coma. Data on the use of Atacand® Plus in patients with hepatic insufficiency are not available.

Aortic and mitral valve stenosis (hypertrophic obstructive cardiomyopathy)

Caution should be exercised when prescribing Atacanda® Plus, as with other vasodilators, in patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant aortic or mitral valve stenosis.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to antihypertensive therapy that affects the renin-angiotensin-aldosterone system. In this regard, it is not recommended to prescribe Atacand® Plus to such patients.

Violation of the water-salt balance

As in all cases of taking drugs that have a diuretic effect, plasma electrolytes should be monitored.

Thiazide-based diuretic drugs can reduce the excretion of calcium ions in the urine and can cause a periodic and slight increase in the concentration of calcium ions in the blood plasma.

Thiazides, including hydrochlorothiazide, can cause disturbances in the water-salt balance (hypercalcemia, hypokalemia, hyponatremia, hypomagnesemia and hypochloremic alkalosis).

Identified hypercalcemia may be a sign of latent hyperparathyroidism. Thiazide agents should be discontinued until the results of the parathyroid test are available.

Hydrochlorothiazide dose-dependently increases potassium excretion, which can cause hypokalemia. This effect of hydrochlorothiazide is less pronounced when used in combination with candesartan cilexetil. The risk of hypokalemia is increased in patients with cirrhosis of the liver, in patients with increased diuresis and in patients taking fluids with a low salt content, and in patients undergoing concomitant treatment with corticosteroids or taking adrenocorticotropic hormone.

Based on the experience with the use of drugs that affect the renin-angiotensin-aldosterone system, the parallel use of Atacand® Plus and diuretics that increase potassium excretion can be compensated by the use of food supplements containing potassium or other drugs that can increase the content of potassium in the blood plasma.

The use of Atacand® Plus with angiotensin-converting enzyme inhibitors or angiotensin II receptor inhibitors may cause hypokalemia, especially if the patient suffers from heart failure or renal failure, although such cases have not been documented.

Thiazides have been shown to increase magnesium excretion, which can cause hypomagnesemia.

Influence on metabolism and endocrine system

Treatment with thiazides can disrupt blood glucose levels. It may be necessary to adjust the dose of hypoglycemic agents, including insulin. During therapy with thiazide, latent diabetes mellitus may occur. Increases in cholesterol and triglyceride levels have also been associated with thiazide treatment. However, when using Atacanda® Plus, containing a dose of 12.5 mg, a minimal number of such effects were observed. Thiazide diuretics increase the concentration of uric acid in the blood plasma and may contribute to the onset of gout in predisposed patients.

Patients in whom vascular tone and renal function are predominantly dependent on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis) are especially sensitive to drugs that act on the renin-angiotensin-aldosterone system. system. The appointment of such drugs in these patients is accompanied by acute arterial hypotension, azotemia, oliguria, and less often - acute renal failure. The possibility of the development of these effects cannot be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with ischemic heart disease or cerebrovascular diseases of ischemic origin, when using any antihypertensive drugs, can lead to the development of myocardial infarction or stroke.

The manifestation of hypersensitivity reactions to hydrochlorothiazide is possible in patients who have not previously had allergies or bronchial asthma, but it is more likely for patients who have had similar symptoms.

When using thiazide diuretics, there have been cases of exacerbation or the appearance of symptoms of systemic lupus erythematosis.

The drug contains lactose, so it should not be taken by patients suffering from rare hereditary diseases, manifested in galactose intolerance, congenital lactase deficiency or glucose-galactose malabsorption.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

The effect on the ability to drive a car or work with machinery has not been studied, but the pharmacodynamic properties of the drug indicate that there is no such effect. Patients should be careful when driving or operating machinery, as dizziness and increased fatigue may occur during treatment.

Overdose

Symptoms: Isolated cases of drug overdose (up to 672 mg of candesartan cilexetil) have been described, resulting in the recovery of patients without serious consequences.

The main manifestation of an overdose of hydrochlorothiazide is an acute loss of fluid and electrolytes. Symptoms such as dizziness, decreased blood pressure, dry mouth, tachycardia, ventricular arrhythmia, sedation, loss of consciousness and muscle cramps were also observed.

Treatment: With the development of a clinically pronounced decrease in blood pressure, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Lay the patient on their back and raise their legs. If necessary, the volume of circulating blood should be increased, for example, by intravenous administration of isotonic sodium chloride solution. If necessary, sympathomimetic agents may be prescribed. Removal of candesartan and hydrochlorothiazide by hemodialysis is unlikely.

Country of origin

Product group

Antihypertensive drug

Release forms

• 14 - blisters (2) - packs of cardboard tablets 28 pcs.

Description of the dosage form

• Pink, oval, biconvex tablets, scored on both sides and debossed "A/CS" on one side. Pink, oval, biconvex tablets, scored on both sides and debossed "A/CS" on one side.

pharmachologic effect

Pharmacokinetics

Special conditions

Compound

• candesartan cilexetil 16 mg hydrochlorothiazide 12.5 mg Excipients: calcium carmellose, hyprolose, lactose monohydrate, magnesium stearate, corn starch, macrogol, iron dye yellow oxide, iron dye red oxide.

Atacand Plus indications for use

• - treatment of arterial hypertension in patients who are indicated for combination therapy

Atacand Plus contraindications

• - abnormal liver function and / or cholestasis; - impaired renal function (KK

Atacand Plus dosage

• 16 mg + 12.5 mg

Atacand plus side effects

• Side effects identified during clinical trials were moderate and transient and were comparable in frequency to the placebo group. The discontinuation rate due to adverse events was similar between candesartan/hydrochlorothiazide (3.3%) and placebo (2.7%). In a pooled analysis of the results of clinical studies, the following side effects were noted caused by the appointment of a combination of candesartan and hydrochlorothiazide. The described side effects were observed with a frequency of at least 1% more than in the placebo group. From the side of the central nervous system: dizziness, weakness. Candesartan cilexetil The following side effects have been reported very rarely during post-marketing use of the drug (

drug interaction

Overdose

Storage conditions

• store at room temperature 15-25 degrees
• keep away from children

Sartans or angiotensin II antagonists are a promising group of antihypertensive drugs, gaining more and more popularity every year. A representative of this group is the drug Atacand, a drug designed specifically to effectively lower blood pressure in essential hypertension.

Blood pressure lowering drug

Atacand is a drug in the form of tablets based on candesartan. Atacand contains:

• 8 or 16 mg candesartan;
• corn starch;
• lactose;
• magnesium stearate;
• shell components.

The inclusion of additional components must be taken into account for people with starch and lactose intolerance. Tablets are packed in blisters, 14 pieces each. The package contains 2 blisters of Atacanda 16 mg or 8 mg tablets, and detailed instructions for use.

There are two types of medicine - tablets Atakand and Atakand Plus. Their differences lie in the composition and dosage of the active substance.

Atacand Plus is a combined drug, which additionally contains a diuretic of the thiazide group. The drug contains 16 mg of candesartan and 12.5 mg of hydrochlorothiazide. Auxiliary and formative substances in the composition are the same as in Atakand tablets.

Atakand Plus tablets contain two active substances

The drug belongs to prescription drugs. To purchase a medicine at a pharmacy, you must provide the pharmacist with a prescription from your doctor.

Atacanda 8 mg tablets are light pink in color with a notch on one side. Atacanda 16 mg tablets are bright pink in color. The combined drug Atacand Plus is peach-colored.

pharmachologic effect

The mechanism of development of arterial hypertension is closely related to the activity of the renin-angiotensin-aldosterone system. An increase in blood pressure occurs due to the release of aldosterone, which has a vasoconstrictive effect, thereby increasing vascular tone. The production of aldosterone is carried out by complex transformations of other hormones, and primarily angiotensin II. The release of this substance entails vasoconstriction of blood vessels, an increase in the amount of aldosterone, and an increase in blood pressure.

Preparations of the sartans group directly affect the cause of the increase in blood pressure - the release of angiotensin II.

When taking Atacand, the activity of receptors is blocked, in response to the activity of which an angiotensin-converting enzyme is released. Under the action of this enzyme, the hormone angiotensin I is converted to angiotensin II. Thus, with the help of candesartan, the process is interrupted, which results in an increase in vascular tone and narrowing of the lumen of the walls of the vessels. At the same time, Atakand does not affect the release of other hormones involved in ensuring the normal functioning of the cardiovascular system and the whole organism.

Features of the therapeutic action of the drug Atacand:

• gradual decrease in blood pressure;
• blocking the mechanisms of increasing blood pressure;
• reducing the load on the heart and blood vessels;
• preventing the development of complications of hypertension;
• prevention of hypertensive crises and heart attacks in patients with hypertension.

Atakand Plus additionally contains a diuretic in the composition, providing a more pronounced antihypertensive effect by stimulating the removal of excess fluid from the body. This medicine is prescribed for severe forms of arterial hypertension. The drug reduces the load on the myocardium, normalizes blood pressure, reduces swelling and prevents their further occurrence.

Indications for use

Atacand is a drug designed specifically for hypertensive patients.

The main indication for the use of the drug is the treatment of essential arterial hypertension. At the same time, Atakand is used for mild and moderate hypertension, and Atakand Plus is prescribed for severe forms of the disease.

As an auxiliary drug, Atacand can be prescribed as part of a complex therapy for heart failure. The drug is also used in the treatment of violations of the systolic function of the left ventricle.

In heart failure, Atacand reduces mortality, reduces the frequency of hospitalizations and increases the life expectancy of patients, reducing the risk of sudden cardiac death.

The drug has a dose-dependent effect. A stable antihypertensive effect is observed 3-4 weeks after the start of regular medication. The drug acts cumulatively, so the effect persists for several weeks after the drug is discontinued. In this case, the first dose of the drug begins to act 2 hours after administration.

Scheme of administration and dosing regimen

The initial dose is 8 mg of the drug per day. Therapy begins with the appointment of the drug Atacand. Atacand Plus is used in severe forms of the disease, or when switching from another combination drug for hypertension.

The tablet should be taken once a day, preferably in the morning. A stable antihypertensive effect is noted after 4 weeks of regular medication at a dosage of 8 mg.

Instructions for the use of Atacand tablets warns that the recommended initial dosage should not be increased earlier than 28 days after the start of therapy. In this case, the patient must undergo a comprehensive examination to evaluate the effectiveness of this method of treatment. In the case when the therapeutic effect is lower than expected, after 4 weeks, the dosage of the drug can be doubled.

Reception of Atacand at a dosage of 16 mg is carried out for a few more weeks. All this time, you should keep a diary of fluctuations in blood pressure. Then the doctor again evaluates the results of treatment and decides on further adjustment of the dose of the drug.

The maximum allowable amount of the drug is 32 mg per day. In this case, the reception is carried out once a day, regardless of food.

With low efficacy of treatment with 16 mg of the drug, it is preferable not to increase the amount of candesartan, but to add a diuretic to the treatment regimen. Clinical studies show that taking 16 mg of candesartan and 12.5 mg of hydrochlorothiazide is much more effective than monotherapy with high doses of an angiotensin II antagonist. In this case, the drug Atacand Plus is prescribed.

You can switch to taking a combined medication both after Atacand monotherapy and after treatment with thiazide diuretics alone, which is often practiced in hypertension of 1 and 2 degrees.

Atacand Plus should be taken one tablet once a day, regardless of the meal. It is not advisable to increase the dosage or number of doses with the ineffectiveness of therapy with this drug. If after 4 weeks the expected therapeutic effect does not appear, the treatment regimen should be reviewed, or the drug group of the prescribed drugs should be replaced.

Use during pregnancy and lactation

During pregnancy, the use of Atacand is contraindicated.

The exact effect of the drug Atakand on the course of pregnancy and fetal development has not been established, therefore the drug is contraindicated in pregnant women. In cases where the patient becomes aware of pregnancy during the course of therapy with sartan, it is necessary either to stop taking the medication or continue treatment, taking appropriate measures to minimize the negative impact on the fetus.

The drug passes into breast milk, therefore, during lactation, treatment with Atacand is not prescribed. In the case when it is not possible to postpone therapy, breastfeeding should be stopped.

Use in pathologies of the liver and kidneys

The description of the drug Atacand, given in the official instructions for use, allows the appointment of this drug in patients with moderate renal impairment. The experience of taking the drug in severe renal failure is limited, so it is recommended to consult a doctor.

Patients with kidney pathologies should undergo regular examinations to assess the functioning of the organ. If renal function deteriorates, therapy with angiotensin II receptor blockers should be discontinued.

The drug Atacand Plus is contraindicated for use in severe renal impairment, while Atacand therapy without hydrochlorothiazide in the composition is possible, but requires a reduction in the recommended dosage.

With mild and moderately severe violations of the liver, you can take the drug. The initial dose in this case is 4 mg candesartan per day. If after a month of therapy with small doses of the drug, the liver function has not deteriorated, it is allowed to increase the amount of medication taken to 8, and then to 16 mg per day.

In severe forms of liver dysfunction, the drug is prohibited.

Features of use in the elderly

The drug can be administered to the elderly, while the correction of the recommended dosage is not required. The only limitation is a violation of kidney function in people over 70 years of age. In this case, therapy should be carried out with a reduced dose of medication. Treatment begins with 4 mg of the drug, gradually increasing the amount to 16 mg per day.

During therapy, kidney, liver and myocardial function should be regularly monitored. If you feel worse, therapy should be discontinued.

Atacand Plus can also be taken by elderly patients, however, at the beginning of the therapeutic course, kidney function should be carefully monitored and blood pressure fluctuations recorded in a special diary.

Contraindications

Contraindications to the use of the drug Atacand are individual intolerance to the drug, severe liver dysfunction and cholestasis. The drug is not used in pediatric practice.

Atacand Plus is contraindicated in the following cases:

• intolerance to thiazide diuretics;
• intolerance to candesartan;
• pregnancy and lactation;
• age up to 18 years;
• severe renal and hepatic insufficiency;
• hypokalemia;
• hypercalcemia;
• gout.

The drug Atacand Plus requires caution, therefore, it can be used only after agreeing the treatment regimen with the attending physician.

Side effects

With symptoms of dizziness, the drug should be discontinued immediately.

Since we are talking about two active substances, it is advisable to separately consider the possible side effects of candesartan and hydrochlorothiazide.

Side effects of candesartan that may occur while taking Atacand:

• respiratory infections;
• coughing;
• migraine;
• dizziness;
• confusion;
• allergic reactions.

There is evidence of the occurrence of Quincke's edema during drug therapy. This type of allergic reaction is observed in isolated cases.

Since hydrochlorothiazide is present in the composition of the Atakand drug, the likelihood of developing the following side effects should be taken into account:

• hyperglycemia;
• hyponatremia and hypokalemia;
• dizziness;
• vertigo;
• orthostatic hypotension;
• loss of appetite;
• stomach ache;
• diarrhea;
• glycosuria;
• metabolic disease;
• increased levels of uric acid and cholesterol.

When taking Atacand Plus, orthostatic hypotension is often observed at the very beginning of drug therapy. Monotherapy with candesartan without a diuretic rarely causes this disorder.

Overdose symptoms

An overdose of Atacand causes dizziness, confusion, fainting, and a severe drop in blood pressure. If such symptoms occur, the patient should take a supine position, fixing the legs above the level of the body. Symptomatic therapy is necessary to eliminate symptoms; hemodialysis is ineffective in case of an overdose of candesartan.

In case of an overdose of the combined drug Atacand Plus, the following symptoms occur:

• tachycardia;
• arrhythmia;
• angina;
• hypokalemia;
• muscle cramps;
• lowering blood pressure;
• fainting.

Place the patient comfortably and call for emergency medical attention. Atacand Plus is not excreted by hemodialysis. In case of an overdose, symptomatic therapy is necessary, the normalization of the water and electrolyte balance by infusion of special preparations. If an overdose is suspected, self-medication is unacceptable.

special instructions

Atacand Plus should not be taken by people who are lactose intolerant

Medicines from the sartans group can cause a decrease in pressure to critical values ​​during elective operations. It is necessary to warn the doctor about therapy with this medicine some time before the operation. If there is a risk of developing a dangerous condition, the drug should be stopped a few days before the operation.

Atacand Plus should not be taken by patients with gout and diabetes mellitus. This drug negatively affects the metabolism. While taking Atacand Plus, there was an increase in the level of uric acid, excretion of glucose in the urine, hyperglycemia. All this worsens the course of the disease and can be life-threatening for the patient.

Candesartan may mask the symptoms of hyperglycemia, so patients with diabetes should regularly monitor their glucose levels.

Lactose is present in Atakand and Atakand Plus medicines. Drugs are not prescribed for patients with lactose intolerance.

Against the background of taking Atacand and Atacand Plus tablets, drowsiness, loss of strength, confusion may appear, and therefore, driving should be abandoned for the duration of therapy.

Drug Interactions

1. When taking candesartan with potassium preparations, potassium-sparing diuretics or salt substitutes, there is a risk of developing hyperkalemia.
2. When taken simultaneously with lithium preparations, an increase in the toxic effects of the latter is noted, therefore this combination is contraindicated.
3. The simultaneous use of non-steroidal anti-inflammatory drugs with candesartan leads to a decrease in the antihypertensive effect of the drug on pressure. It also increases the deterioration of kidney function and the development of acute renal failure. Simultaneous administration of drugs of these two groups is not recommended.
4. When taking Atacand Plus, there is a risk of developing hypokalemia, which can lead to disruption of the action of glycosides used in the treatment of heart failure and arrhythmia.
5. Non-steroidal anti-inflammatory drugs inhibit the diuretic effect of Atacand Plus.
6. With the simultaneous use of barbiturates, antipsychotics or alcoholic beverages with the drug Atacand Plus, there is an increase in the symptoms of orthostatic hypotension.
7. Patients with type 2 diabetes should regularly monitor their glucose levels, as there is evidence of a decrease in the effectiveness of hypoglycemic drugs while taking Atacand tablets.
8. It is forbidden to take Atacand and Atacand Plus to patients with diabetes mellitus who are taking medicines with aliskiren in their composition.

Cost and analogues

Candesartan has a similar composition and dosage

When prescribing Atacand, the price matters, because this medication is often indicated for long-term use. The drug is produced in the UK, which is the reason for its high cost. Most often, therapy is carried out with a drug at a dosage of 16 mg, the cost of a package of which is approximately 2,500 rubles. This number of tablets is designed for 28 days of admission.

Atakand Plus costs a little more - about 2600-2750 rubles, depending on the place of purchase.

Full analogues of the drug:

• Candesartan;
• Kasark;
• Kandecor;
• Cantab;
• Advant.

All drugs have the same composition and dosage. An affordable analogue of the drug is Ordiss tablets, the cost of packaging of which is approximately 500 rubles.

There is no difference in therapeutic effect, however, cheap substitutes for the original drug may cause more side effects.

Atakand Plus analogues are combined drugs Ordiss N, Kandecor N, Khizart N. The cost of combined drugs starts from 650 rubles.

If you need to choose analogues of the drug Atacand, you should consult with your doctor. In case of intolerance to drugs of the sartans group, the patient may be offered drugs from the group of ACE inhibitors for the treatment of hypertension.

"Atakand" is a classic drug that has the ability to reduce pressure during severe hypertensive attacks. It is produced mainly in a box of 28 tablets in various dosages (from 8 to 32 milligrams). The medicine has a characteristic red tint, which makes it possible to identify it in the mass of first-aid kit medicines.

Description

The drug itself, Candesartan, is produced under various trade names: Irbesartan, Atakand - analogues with similar effects, properties and activity. Storage conditions - dark dry place away from children. Expiration date - 36 months. According to doctors, despite the high cost, this drug showed excellent results, so many cardiologists recommend Atakand. Instructions for use, price, analogues - all this will be discussed in our material.

Compound

One tablet accounts for (depending on the labeling):

• Cilexetil candesartan - from 8 to 32 mg (for example, "Atakand 16 No. 28").
• Auxiliary components: talc, red dye (in the form of iron oxide), starch and many others that do not have therapeutic effects.

The number after the number in the name indicates the number of tablets in one package, the number after the name of the drug itself is the dosage in milligrams. This is especially often indicated on Nortivan tablets, analogues may not always provide this information on the package.

Application

It is used orally once a day as a prophylactic, on an empty stomach. The initial dose is half the lowest dosage (4 mg), in the presence of liver and / or kidney damage, the initial amount of the drug is halved. Gradually, the dosage of "Atakanda" is increased to 8 milligrams, the largest allowable portion of the drug is 16 mg. The effect lasts from 24 to 36 hours and does not depend on natural indicators: weight, height, age and gender.

Indications for use

The main indication for use is any kind of arterial hypertension (popularly - hypertension). Also, additional conditions for the appointment are:

• Large age (from forty years and older).
• Sedentary lifestyle.
• Predisposition to hypertensive crises, determined by the medical records of relatives in past generations.

Contraindications

Candesartan has a small number of contraindications, due to which it cannot be prescribed to all patients:

• Various forms of liver failure, in particular - cholestasis.
• Hypersensitivity to candesartan, which manifests itself in many forms, from urticaria and slight itching to allergic reactions and anaphylactic shock.
• Pregnancy and feeding of a child - the drug can penetrate the placental barrier and is able to reduce the pressure in the fetus, disrupting its viability and development.

It has far fewer side effects than Irbesartan. Instructions for use states that it has a much higher chance of provoking side effects: nausea, dizziness. Also, this drug should not be prescribed to children under eighteen years of age.

Side effects

The drug has few side effects compared to drugs of the same class of the first generation:

• From the side of the central nervous system: severe sudden dizziness.
• In the respiratory apparatus: flu-like symptoms in the initial stage, cough, pharyngitis, rhinitis. Increases the chance of acute respiratory infections.
• From the gastrointestinal tract: pain in the abdomen and pelvis may provoke gastric ulcer and duodenal ulcer.
• From the circulatory system - an increase in the appearance of various edema, "cottonness" of the limbs.
• Often there may be unusual pain in the lumbar region (lumbalgia), not accompanied by serious problems in the body.

In case of an overdose, the following symptoms are observed: severe dizziness, disorientation, the appearance of primary symptoms of a sharp drop in pressure (hypotension), such as vomiting, tinnitus, drowsiness, loss of consciousness is possible. Treatment without complications was observed even when the dose was exceeded up to 672 mg (an attempt to settle accounts with life by taking 21 tablets of Candesartan at a time).

In case of an overdose, control over the main vital signs (pressure, pulse, brain and respiratory activity), rest and lying position is prescribed. Sometimes droppers with saline are placed. Hemodialysis does not have the desired effect: the drug is not precipitated and is not excreted by blood-purifying reagents, therefore it remains in the body and retains toxicity for the entire period of action until it is completely decomposed in the liver, this is especially true for Irbesartan tablets, instructions for use describe in detail the method of rehabilitation after an overdose.

Interaction with other medicines

Of the significant effects of candesartan with other drugs, the following can be distinguished:

• When taken with potassium-sparing medications, potassium retention in the body increases.
• The situation is similar with lithium-containing drugs.
• The use of painkillers (specifically, non-steroidal anti-inflammatory drugs) reduces the main effect of the drug on lowering blood pressure. The risk of impaired renal function increases, in persons with renal insufficiency, the content of potassium in the blood increases.

Analogues and prices

This drug has many generics that match in properties, but Atakand is considered the best. An analogue of the drug is presented: "Irbesartan", "Nortivan", "Presartan". The active substance is the same everywhere. It can also be replaced with AIRA-Sanovel tablets. Each of them has its own advantages and disadvantages.

First of all, these medicines have a different cost, which is very different from the Atakand drug. The Presartan analogue is the cheapest of this group, its price ranges from 150 to 175 rubles for a package of 30 tablets. Other generics: "Irbesartan" - 410-580 rubles, "Nortivan" - 120-290. Pure "Kandesartan" costs 175 rubles, while "Atakand" itself costs from 1300 to 1500 rubles.

Tablets - 1 tab.:

• active substance: candesartan cilexetil - 16 mg; hydrochlorothiazide - 12.5 mg.
• excipients: calcium carmellose (carmellose calcium salt) - 5.6 mg; giprolose - 4 mg; lactose monohydrate - 68 mg; magnesium stearate - 1.3 mg; corn starch - 20 mg; macrogol - 2.6 mg; iron dye yellow oxide Cl 77492 - 0.21 mg; iron dye red oxide Cl77491 - 0.05 mg

Description of the dosage form

Pink oval biconvex tablet, scored on both sides and debossed "A/CS" on one side.

Tablets. 14 tab. in a PVC/aluminum blister; 2 blisters in a cardboard box.

pharmachologic effect

Hypotensive, diuretic, blocking AT 1 receptors.

Pharmacokinetics

Suction and distribution

Candesartan cilexetil. Candesartan cilexetil is an oral prodrug. It quickly turns into the active substance - candesartan - by ether hydrolysis upon absorption from the digestive tract, binds strongly to AT 1 receptors and slowly dissociates, does not have agonist properties. The absolute bioavailability of candesartan after oral administration of a solution of candesartan cilexetil is approximately 40%. The relative bioavailability of the tablet formulation compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. C max in blood serum is achieved 3-4 hours after taking the tablet form of the drug. With an increase in the dose of the drug within the recommended limits, the concentration of candesartan increases linearly. The pharmacokinetic parameters of candesartan do not depend on the gender of the patient. Food intake does not significantly affect AUC, i.e. food does not significantly affect the bioavailability of the drug. Candesartan actively binds to plasma proteins (more than 99%). The plasma volume of distribution of candesartan is 0.1 L/kg.

Hydrochlorothiazide. Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract, bioavailability is approximately 70%. Concomitant food intake increases absorption by about 15%. Bioavailability may be reduced in patients with heart failure and severe edema. Communication with blood plasma proteins is approximately 60%. The apparent V d is about 0.8 l/kg.

Metabolism and excretion

Candesartan. Candesartan is mainly excreted in the urine and bile unchanged and is only slightly metabolized in the liver. T 1/2 of candesartan is approximately 9 hours. The accumulation of the drug in the body is not observed.

The total clearance of candesartan is about 0.37 ml/min/kg, while the renal clearance is about 0.19 ml/min/kg. Renal excretion of candesartan is by glomerular filtration and active tubular secretion. When radiolabeled candesartan cilexetil is ingested, about 26% of the administered amount is excreted in the urine as candesartan and 7% as an inactive metabolite, while 56% of the administered amount is found in the feces as candesartan and 10% as an inactive metabolite. .

Hydrochlorothiazide. Hydrochlorothiazide is not metabolized and is excreted almost completely in the form of the active form of the drug by glomerular filtration and active tubular secretion in the proximal nephron. T 1/2 is approximately 8 hours. Approximately 70% of the dose taken orally is excreted in the urine within 48 hours. T 1/2 does not change when taken together with candesartan. When using a combination of drugs, no additional accumulation of hydrochlorothiazide was detected in comparison with monotherapy.

Pharmacokinetics in special groups of patients

Candesartan. In elderly patients (over 65 years of age), Cmax and AUC of candesartan are increased by 50% and 80%, respectively, compared with young patients. However, the hypotensive effect and the incidence of side effects when using Atacanda Plus do not depend on the age of the patients.

In patients with mild and moderate renal impairment, Cmax and AUC of candesartan increased by 50 and 70%, respectively, while T 1/2 of the drug does not change compared with patients with normal renal function. In patients with severe renal impairment, Cmax and AUC of candesartan increased by 50 and 110%, respectively, and T 1/2 of the drug increased by 2 times. In patients on hemodialysis, the same pharmacokinetic parameters of candesartan were found as in patients with severe renal impairment.

In patients with mild to moderate hepatic impairment, an increase in the AUC of candesartan by 23% was noted.

Hydrochlorothiazide. T 1/2 is longer in patients with renal insufficiency.

Pharmacodynamics

Angiotensin II is the main hormone of the 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 fluid and electrolyte status, and stimulation of cell growth. All these effects are mediated by the interaction of angiotensin II with angiotensin type 1 receptors (AT 1 receptors).

Candesartan is a selective type 1 angiotensin II receptor antagonist that does not inhibit ACE, which converts angiotensin I to angiotensin II and destroys bradykinin; does not affect ACE and does not lead to the accumulation of bradykinin or substance P. When comparing candesartan with ACE inhibitors, the development of cough was less common in patients treated with candesartan cilexetil. Candesartan does not bind to other hormone receptors and does not block ion channels involved in the regulation of CCC functions. As a result of blocking the AT 1 receptors of angiotensin II, a dose-dependent increase in the level of renin, angiotensin I, angiotensin II and a decrease in the concentration of aldosterone in the blood plasma occur.

The clinical effect of candesartan cilexetil on morbidity and mortality at a dose of 8–16 mg (mean dose 12 mg) once daily was investigated in a randomized clinical trial in 4937 elderly patients (age 70 to 89 years, 21% of patients in aged 80 years and older) with mild to moderate hypertension treated with candesartan cilexetil for an average of 3.7 years (the SCOPE study - a study of cognitive function and prognosis in elderly patients). Patients received candesartan or placebo, if necessary in combination with other antihypertensive agents. In the group of patients treated with candesartan, there was a decrease in blood pressure from 166/90 to 145/80 mm Hg. Art. and in the control group - from 167/90 to 149/82 mm Hg. Art. There were no statistically significant differences in the incidence of cardiovascular complications (mortality due to cardiovascular diseases, the incidence of myocardial infarction and non-fatal stroke) between the two groups of patients.

Hydrochlorothiazide inhibits active sodium reabsorption, mainly in the distal renal tubules, and enhances the release of sodium, chloride and water ions. The excretion of potassium and magnesium by the kidneys increases in a dose-dependent manner, while calcium begins to be reabsorbed in larger quantities than before. Hydrochlorothiazide reduces the volume of blood plasma and extracellular fluid and the intensity of blood transport by the heart and blood pressure. During long-term treatment, the hypotensive effect develops due to the expansion of arterioles.

It has been shown that long-term use of hydrochlorothiazide reduces the risk of cardiovascular disease and mortality.

Candesartan and hydrochlorothiazide have an additive hypotensive effect.

In patients suffering from arterial hypertension, Atakand Plus causes an effective and prolonged decrease in blood pressure without an increase in heart rate. Orthostatic hypotension at the first dose of the drug is not observed, and arterial hypertension does not increase after the end of treatment. After a single dose of Atacand Plus, the main hypotensive effect develops within 2 hours. With prolonged treatment, a stable decrease in blood pressure occurs within 4 weeks after the start of the drug and can be maintained with a long course of treatment. Atacand Plus, when taken once a day, effectively and gently lowers blood pressure for 24 hours with little difference between the maximum and average effect of action. In clinical studies, the incidence of side effects, especially cough, was less common with Atacand Plus than with a combination of ACE inhibitors with Hypothiazide.

The effectiveness of the combination of candesartan and hydrochlorothiazide does not depend on the sex and age of the patient. Currently, there are no data on the use of candesartan / hydrochlorothiazide in patients with renal insufficiency / nephropathy, reduced left ventricular function / acute heart failure and patients who have had myocardial infarction.

Indications for use Atacand plus

Treatment of arterial hypertension in patients for whom combination therapy is indicated.

Contraindications to the use of Atacand plus

• hypersensitivity to the active or auxiliary components that make up the drug, sulfonamide derivatives;
• abnormal liver function and / or cholestasis;
• renal dysfunction (Cl creatinine<30 мл/мин/1,73 м 2);
• anuria;
• refractory hypokalemia and hypercalcemia;
• gout;
• pregnancy;
• lactation period;
• age up to 18 years (efficacy and safety have not been established).

With caution: severe chronic heart failure; bilateral stenosis of the renal arteries; stenosis of the artery of a single kidney; hemodynamically significant stenosis of the aortic and mitral valve; in patients with cerebrovascular diseases and ischemic heart disease; hypertrophic obstructive cardiomyopathy; in patients with reduced BCC; cirrhosis of the liver; in patients suffering from lactose intolerance, with impaired absorption of lactose and galactose; hyponatremia; primary hyperaldosteronism; surgical intervention; in patients after kidney transplantation; kidney failure; diabetes.

Atacand plus Use in pregnancy and children

Experience with the use of Atacand Plus in pregnant women is limited.

These data are not enough to judge the possible danger to the fetus in the first trimester of pregnancy. In the human embryo, the circulatory system of the kidney, which depends on the development of the RAAS, begins to form in the second trimester of pregnancy. Thus, the risk to the fetus increases with the appointment of Atacanda Plus in the last 6 months of pregnancy. Drugs that have a direct effect on the RAAS can cause fetal developmental disorders or have a negative effect on the newborn (arterial hypotension, impaired renal function, oliguria and / or anuria, oligohydramnios, hypoplasia of the skull bones, intrauterine growth retardation), up to death when used drug in the last 6 months of pregnancy. Cases of pulmonary hypoplasia, facial anomalies, and limb contractures have also been described.

Animal studies have shown fetal and neonatal kidney damage with candesartan. It is assumed that the mechanism of damage is due to the pharmacological effect of the drug on the RAAS.

Hydrochlorothiazide is able to reduce the volume of blood plasma, as well as reduce uteroplacental blood flow, and can also cause thrombocytopenia in the newborn.

Based on the information received, Atacand Plus should not be used during pregnancy. If pregnancy occurs during the period of treatment with Atacand Plus, therapy should be discontinued.

It is currently unknown whether candesartan passes into breast milk. However, candesartan is excreted from the milk of lactating rats. Hydrochlorothiazide passes into mother's milk.

Due to the possible undesirable effect on infants, Atakand Plus should not be used during breastfeeding.

Atacand plus side effects

Side effects identified during clinical trials were moderate and transient and were comparable in frequency to the placebo group. The discontinuation rate due to adverse events was similar between candesartan/hydrochlorothiazide (3.3%) and placebo (2.7%).

In a pooled analysis of the results of clinical studies, the following side effects were noted caused by the appointment of candesartan / hydrochlorothiazide.

Increases in plasma uric acid and ALT and blood glucose levels were noted as side effects occurring with candesartan cilexetil (approximate complaint rates of 1.1, 0.9 and 1%, respectively) slightly more frequently than with placebo (0 .4, 0, and 0.2%, respectively). In some patients taking candesartan / hydrochlorothiazide, there was a slight decrease in hemoglobin concentration and an increase in plasma AST.

An increase in the content of creatinine, urea, hyperkalemia and hyponatremia was also observed.

drug interaction

In pharmacokinetic studies, the combined use of Atacanda ® Plus with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine and enalapril was studied. No clinically significant drug interactions have been identified.

Candesartan is metabolized in the liver to a small extent (CYP2C9). Conducted interaction studies did not reveal the effect of the drug on CYP2C9 and CYP3A4, the effect on other isoenzymes of the cytochrome P450 system has not been studied.

The combined use of Atacanda ® Plus with other antihypertensive agents potentiates the hypotensive effect.

It should be expected that the effect of hydrochlorothiazide, leading to loss of potassium, can be enhanced by other means leading to loss of potassium and hypokalemia (for example, diuretics, laxatives, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid derivatives).

Experience with other drugs that act on the RAAS shows that concomitant therapy with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other drugs that can increase the level of potassium in the blood serum (for example, heparin) can lead to the development of hyperkalemia.

Diuretic-induced hypokalemia and hypomagnesemia predispose to the possible cardiotoxic effects of digitalis glycosides and antiarrhythmic agents. When taking Atacand ® Plus in parallel with such drugs, it is necessary to control the level of potassium in the blood.

With the combined appointment of lithium preparations with ACE inhibitors, a reversible increase in the concentration of lithium in the blood serum and the development of toxic reactions have been reported. Similar reactions can also occur with the use of angiotensin II receptor antagonists, and therefore it is recommended to control the level of lithium in the blood serum with the combined use of these drugs.

The bioavailability of candesartan is independent of food intake.

The diuretic, natriuretic and hypotensive effects of hydrochlorothiazide are weakened by NSAIDs.

The absorption of hydrochlorothiazide is weakened by the use of colestipol or cholestyramine.

The action of non-depolarizing muscle relaxants (eg tubocurarine) can be enhanced by hydrochlorothiazide.

Thiazide diuretics can cause an increase in the level of calcium in the blood due to a decrease in its excretion. If it is necessary to take calcium-containing dietary supplements or vitamin D, the level of calcium in the blood plasma should be monitored and the dose adjusted if necessary.

Thiazides enhance the hyperglycemic action of beta-blockers and diazoxide.

Anticholinergics (eg, atropine, biperidine) may increase the bioavailability of thiazide diuretics due to decreased GI motility.

Thiazides may increase the risk of adverse effects of amantadine.

Thiazides can slow down the excretion of cytotoxic drugs (such as cyclophosphamide, methotrexate) from the body and increase their myelosuppressive effect.

The risk of hypokalemia may increase with concomitant use of steroid drugs or adrenocorticotropic hormone.

Against the background of taking the drug, the incidence of orthostatic hypotension may increase when taking alcohol, barbiturates or general anesthetics.

Treatment with thiazides may reduce glucose tolerance. It may be necessary to adjust the dose of antidiabetic drugs, incl. insulin.

Hydrochlorothiazide may reduce the effect of vasoconstrictive amines such as epinephrine (adrenaline).

Hydrochlorothiazide may increase the risk of developing acute renal failure, especially in combination with large doses of iodinated filler.

Significant interaction of hydrochlorothiazide with food was not found.

Dosage of Atacand plus

Inside, 1 time per day, regardless of the meal.

The main hypotensive effect is achieved, as a rule, in the first 4 weeks after the start of treatment.

Elderly patients. In elderly patients, dose adjustment is not required.

Patients with impaired renal function. In patients with impaired renal function, loop diuretics are preferred over thiazide diuretics. Prior to initiation of therapy with Atacand Plus in patients with mild or moderate renal impairment (Cl creatinine ≥30 ml / min / 1.73 m 2), including patients on hemodialysis, it is recommended to titrate the dose of candesartan (through Atacand monotherapy), starting with 4 mg.

The drug Atacand Plus is contraindicated in patients with severe renal insufficiency (Cl creatinine<30 мл/мин/1,73 м 2).

Patients with reduced BCC. For patients at risk of arterial hypotension, for example, for patients with reduced BCC, it is recommended to titrate the dose of candesartan (through Atacand monotherapy) starting from 4 mg.

Use in children and adolescents. The safety and efficacy of Atacanda Plus in children and adolescents (under 18 years of age) have not been established.

Overdose

Symptoms: analysis of the pharmacological properties of the drug suggests that the main manifestation of an overdose may be a clinically pronounced decrease in blood pressure and dizziness. Individual cases of overdose of the drug (up to 672 mg of candesartan) have been described, which ended in the recovery of patients without serious consequences.

The main manifestation of an overdose of hydrochlorothiazide is an acute loss of fluid and electrolytes. Symptoms such as dizziness, decreased blood pressure, dry mouth, tachycardia, ventricular arrhythmia, loss of consciousness and muscle cramps were also observed.

Treatment: with the development of a clinically pronounced decrease in blood pressure, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Lay the patient on their back and raise their legs. If necessary, the BCC should be increased, for example, by intravenous administration of an isotonic sodium chloride solution. If necessary, sympathomimetic agents may be prescribed. Removal of candesartan and hydrochlorothiazide by hemodialysis is unlikely.