Kandesartan-SZ - instructions for use, doses, side effects, contraindications

active substance: candesartan cilexetil - 8.0 mg; Excipients: lactose monohydrate (sugar milk) 39.1 mg, microcrystalline cellulose 41.0 mg, pregelatinized starch (starch 1500) 20.0 mg, croscarmellose sodium (impellose) 4.0 mg, povidone (polyvinylpyrrolidone, medium molecular weight) 6 , 0 mg, silicon dioxide colloid (aerosil) - 0.7 mg, sodium stearyl fumarate - 1.2 mg.

Dosage of 16 mg

active substance: candesartan cilexetil - 16.0 mg; atExcipientslactose monohydrate (sugar milk) - 64.8 mg, microcrystalline cellulose - 68.0 mg, pregelatinized starch (starch 1500) - 32.0 mg, croscarmellose sodium (impellose) - 6.0 mg, povidone (polyvinylpyrrolidone medium molecular weight) - 10.0 mg,silicon dioxide colloid (aerosil) - 1.2 mg, sodium stearyl fumarate - 2.0 mg.

The dosage of 32 mg

active substance: candesartan cilexetil - 32.0 mg; Excipientslactose monohydrate (sugar milk) - 78.0 mg, microcrystalline cellulose - 74.0 mg, pregelatinized starch (starch 1500) - 40.0 mg, croscarmellose sodium (impellose) - 8.0 mg, povidone (polyvinylpyrrolidone medium molecular weight) 14.0 mg, silicon colloidal dioxide (aerosil) - 1.5 mg, sodium stearyl fumarate - 2.5 mg.

Description:Tablets of white or almost white color, round, flat-cylindrical with a facet and a risk.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.06 Candesartan

Pharmacodynamics:

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 water-electrolyte homeostasis 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 antagonist of angiotensin II receptor type 1 (AT₁receptors). Candesartan does not inhibit the angiotensin-converting enzyme (ACE), which converts angiotensin I into angiotensin II and breaks down bradykinin; does not affect the ACE and does not lead to the accumulation of bradykinin or P. In comparing candesartan with ACE inhibitors, the development of cough was less common in patients receiving candesartan cilexetil. Candesartan does not bind to the receptors of other hormones and does not block the ion channels involved in the regulation of the functions of the cardiovascular system. As a result of blocking AT₁ receptors of angiotensin II, a dose-dependent increase in the activity of renin, angiotensin I, angiotensin II, and a decrease in aldosterone in the blood plasma.

Arterial hypertension

With arterial hypertension candesartan causes a dose-dependent long-term reduction in blood pressure (BP). The antihypertensive effect of the drug is due to a decrease in overall peripheral vascular resistance, without changing the heart rate (heart rate).There were no cases of severe arterial hypotension after taking the first dose of the drug, as well as withdrawal syndrome ("ricochet" syndrome) after discontinuation of therapy.

The onset of antihypertensive action after taking the first dose of candesartan cilexetil usually develops within 2 hours. Against the background of ongoing therapy with the drug in a fixed dose, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists throughout the treatment. Candesartan cilexetil, prescribed once a day, provides an effective and smooth decrease in blood pressure within 24 hours with minor fluctuations in blood pressure in the intervals between doses of the next dose of the drug. The use of candesartan cilexetil together with hydrochlorothiazide leads to an increase in antihypertensive action.

The combined use of candesartan cilexetil and hydrochlorothiazide (or amlodipine) is well tolerated.

The effectiveness of the drug does not depend on the age and sex of patients. Candesartan cileksetil increases renal blood flow and does not change or increases the rate of glomerular filtration, whereas renal vascular resistance and filtration fraction decrease.The use of candesartan cilexetil at a dose of 8-16 mg for 12 weeks does not adversely affect glucose concentration and lipid profile in patients with hypertension and type 2 diabetes.

Chronic heart failure

In patients with chronic heart failure and reduced left ventricular systolic function (LVEF ≤ 40%), candesartan administration contributed to a reduction in overall peripheral vascular resistance and capillary pressure in the lungs, increased renin activity and angiotensin II concentration in blood plasma, and a decrease in aldosterone levels.

Pharmacokinetics:

Suction and distribution

Candesartan cilexetil is a prodrug for oral administration. Quickly turns into an active substance - candesartan through ether hydrolysis when absorbed from the digestive tract, firmly binds to the AT₁receptors and dissociates slowly, does not have the properties of an agonist. Absolute bioavailability of candesartan after ingestion of a solution of candesartan cilexetil is about 40%. The relative bioavailability of the tablet preparation as compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. The maximum concentration in serum (Cmah) 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 rises linearly. The pharmacokinetic parameters of candesartan do not depend on the sex of the patient. Eating does not have a significant effect on the area under the concentration-time curve (AUC), i.e., simultaneous intake of food does not significantly affect the bioavailability of the drug. Candesartan actively binds to blood plasma proteins (> 99%). The volume distribution of candesartan is 0.1 l / kg.

Metabolism and excretion from the body

Candesartan, basically, is excreted from the body by the kidneys and bile in unchanged form and only marginally metabolized in the liver. The half-life of candesartan is approximately 9 hours. Cumulation in the body is not observed.

The total clearance of candesartan is about 0.37 ml / min / kg, with a kidney clearance of about 0.19 ml / min / kg. Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion.When ingestion of radio-labeled candesartan cilexetil, about 26% of the administered amount is excreted by the kidneys in the form of candesartan and 7% in the form of an inactive metabolite, whereas in the stool 56% of the administered amount as candesartan and 10% in the form of an inactive metabolite is detected.

In elderly patients (over 65 years) Cmah and AUC candesartan increased by 50% and 80%, respectively, compared with young patients. However, the antihypertensive effect and incidence of side effects with Candesartan-SZ do not depend on the age of the patients.

In patients with mild to moderate renal impairment, Cmah and AUC candesartan increased by 50% and 70%, respectively, whereas the half-life of the drug did not change compared to patients with normal renal function. In patients with severe renal dysfunction Cmah and AUC candesartan increased by 50% and 110%, respectively, and the half-life of the drug increased 2-fold.

Patients on hemodialysis were found to have the same pharmacokinetic parameters of candesartan as in patients with severe renal dysfunction.

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

Indications:

Arterial hypertension in adults. The drug Kandesartan-SZ can be used in monotherapy or in combination with other antihypertensive drugs.

Chronic heart failure III-IV functional class by classification NYHA) in adult patients with a violation of left ventricular systolic function (reduction of LVEF ≤ 40%). Candesartan drug-SOC is used as adjunctive therapy to inhibitors of angiotensin converting enzyme (ACE) or intolerance to ACE inhibitors (cm. "Pharmacodynamics" section).

Contraindications:

Hypersensitivity to candesartan cilexetil or other components that make up the drug.

Pregnancy and the period of breastfeeding (see section "Application during pregnancy and during breast-feeding").

Severe liver dysfunction and / or cholestasis.

Age to 18 years (effectiveness and safety not established). Intolerance to galactose, lactase deficiency and glucose-galactose malabsorption syndrome.

The simultaneous use of aliskiren and aliskirensoderzhaschimi drugs in patients with diabetes or renal function (glomerular filtration rate <60 ml / min / m²) (cm.section "Interaction with other medicinal products").

Carefully:

In patients with severe renal impairment (creatinine clearance less than 30 ml / min), bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, with hemodynamically significant stenosis of the aortic and mitral valve after a kidney transplant in history in patients with cerebrovascular disease and ischemic heart disease (CHD), with hyperkalemia in patients with reduced circulating blood volume, with primary hyperaldosteronism (Not enough data for clinical research) with rods pertrophic cardiomyopathy.

Pregnancy and lactation:

Pregnancy

The use of Candesartan-SZ during pregnancy is contraindicated (see the section "Contraindications"). Patients taking Candesartan-SZ should be warned about this before planning a pregnancy so that they can discuss alternative therapies with their own doctor. In case of pregnancy, therapy with Candesartan-SZ should be stopped immediately and, if necessary, an alternative treatment is prescribed.

Drugs that have a direct effect on the renin-angiotensin-aldosterone system can cause fetal developmental disorders or have a negative effect on the newborn, up to a lethal outcome, when the drug is used during pregnancy.

It is known that therapy with angiotensin II receptor antagonists can cause fetal development disorders (renal dysfunction, oligohydramnion, delayed ossification of the bones of the skull) and development of complications in the newborn (kidney failure, arterial hypotension, hyperkalemia).

Breastfeeding period

At the present time, it is not known whether candesartan in breast milk. Due to possible undesirable effects on infants, Candesartan-SZ should not be used during breastfeeding.

Dosing and Administration:The drug Kandesartan-SZ should be taken once a day, regardless of food intake.

Arterial hypertension in adult patients

The recommended initial and maintenance dose of Candesartan-SZ is 8 mg once a day. The dose can be increased to 16 mg once a day.Patients who failed to sufficiently reduce blood pressure after 4 weeks of taking Candesartan-SZ at a dose of 16 mg per day, it is recommended to increase the dose to 32 mg once a day.

If the therapy with Candesartan-SZ does not lead to a decrease in blood pressure to the optimal level, it is recommended to change the treatment regimen.

Therapy should be adjusted in accordance with the level of blood pressure. The maximum antihypertensive effect is achieved within 4 weeks from the start of treatment.

Elderly patients

In elderly patients, there is no need to adjust the initial dose of the drug.

Patients with impaired renal function

The initial daily dose in patients with mild to moderate renal impairment (creatinine clearance ≥ 30 mL / min / 1.73 m² body surface area), including patients on hemodialysis, is 4 mg (1/2 tablets of 8 mg each).

Clinical experience of the drug in patients with severe renal impairment (creatinine clearance <30 ml / min / 1.73 m² body surface area) or terminal renal failure (creatinine clearance less than 15 mL / min) is limited.

Patients with impaired hepatic function

The initial daily dose in patients with mild and moderate impairment of liver function is 4 mg once a day (1/2 tablets of 8 mg). Clinical experience of the drug in patients with severe a violation of the function of the liver and / or cholestasis is limited (see the section "Contraindications").

Concomitant therapy

The use of Candesartan-SZ together with thiazide type diuretics (for example, hydrochlorothiazide) can enhance the antihypertensive effect of Candesartan-SZ.

Hypovolemia

The recommended initial dose of Candesartan-SZ is 4 mg once a day (1/2 tablets of 8 mg).

Chronic heart failure

The recommended initial dose of Candesartan-SZ is 4 mg once a day (1/2 tablets of 8 mg). An increase in the dose to 32 mg once a day or up to the maximum tolerated dose is carried out by doubling it at intervals of not less than 2 weeks (see section "Special instructions").

Special patient groups

Older patients and patients with impaired renal, hepatic or hypovolemic function do not need to change the initial dose of the drug.

Concomitant therapy

Candesartan-SZ can be administered together with other agents used in the therapy of chronic heart failure, for example, with ACE inhibitors, beta-blockers, diuretics and cardiac glycosides (see sections "Special instructions", "Pharmacodynamics").

Side effects:

Arterial hypertension

Side effects in clinical trials were mild and transient and were comparable in frequency with the placebo group. The overall incidence of side effects associated with Candesartan-SZ was independent of the dose, sex and age of the patient. The incidence of discontinuation due to side effects was similar when using candesartan cilexetil (3.1%) and placebo (3.2%).

During the analysis of the data of the conducted studies, the following side effects were reported, often (> 1/100) occurring against the background of the reception of candesartan cilexetil. The described side effects were observed with a frequency of at least 1 % more than in the placebo group.

From the central nervous system: dizziness, weakness, headache;

From the musculoskeletal system, connective tissue: backache;

Infections: Respiratory infections;

Laboratory indicators: In general, with the use of Candesartan-SZ, there were no clinically significant changes in standard laboratory indicators. As with other inhibitors of the renin-angiotensin-aldosterone system, a slight decrease in hemoglobin can be observed. There was an increase in the concentration of creatinine, urea or calcium and a decrease in the concentration of sodium. The increase in activity of alanine aminotransferase (ALT) was observed somewhat more frequently with the use of Candesartan-SZ compared with placebo (1.3% instead of 0.5%). When using Candesartan-SZ, it is usually not necessary to regularly monitor laboratory parameters. However, in patients with impaired renal function, it is recommended to periodically monitor the concentration of potassium and creatinine in the blood serum.

Chronic heart failure

Side effects, identified with the use of the drug Candesartan-SZ in patients with chronic heart failure, corresponded to the pharmacological properties of the drug and depended on the patient's condition.

The most common side effects (≥1 / 100, <1/10):

From the side of the cardiovascular system: marked decrease in blood pressure; Disturbance of metabolism and diseases caused by violation metabolism: hyperkalemia;

From the side of the urinary system: impaired renal function; Laboratory changes: increasing the concentration of creatinine, urea and potassium.

It is recommended to monitor the concentration of creatinine and potassium in the blood serum.

About the following side effects during the postmarketing use of the drug reported very rarely (<1/10000):

From the side of the blood and lymphatic system: leukopenia, neutropenia and agranulocytosis;

Disturbance of metabolism and diseases caused by violation metabolism: hyperkalemia, hyponatremia;

From the nervous systems: dizziness, headache;

On the part of the respiratory system, the organs of the thorax and the mediastinum: cough;

From the gastrointestinal tract: nausea;

From the liver and biliary tract: increased activity of "hepatic" enzymes, a violation of liver function or hepatitis;

From the skin: angioedema, rash, hives, itching.

From the musculoskeletal system, connective tissue: back pain, arthralgia, myalgia;

From the side of the urinary systems: impaired kidney function, including renal failure in predisposed patients.

Rare reports of rhabdomyolysis have been reported in patients receiving angiotensin II receptor antagonists.

Overdose:

Symptoms

Analysis of pharmacological properties of the drug suggests that the main manifestation of an overdose may be a clinically pronounced decrease in blood pressure, dizziness and tachycardia, and bradycardia may also appear. Individual cases of drug overdose (up to 672 mg of candesartan cilexetil), which resulted in the recovery of patients without severe consequences, were described.

Treatment

When developing clinically pronounced arterial hypotension, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Lay the patient, lift the foot of the bed. If necessary, increase the volume of circulating plasma, for example, by intravenous administration of 0.9% solution of sodium chloride.If necessary, sympathomimetic preparations may be prescribed. The withdrawal of candesartan by hemodialysis is unlikely.

Interaction:When using Candesartan-SZ with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine, and enalapril, there was no clinically significant pharmacokinetic interaction.

Candesartan is metabolized in the liver to an insignificant degree (isoenzyme CYP2C9). The conducted studies on the interaction did not reveal the effect of the drug on isozymes CYP2C9 and CYP3A4, the effect on other isoenzymes of the cytochrome P450 system has not been studied.

Joint use of Candesartan-SZ with other antihypertensive drugs potentiates antihypertensive effect.

The experience of using other drugs acting on the renin-angiotensin-aldosterone system shows that concomitant therapy with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other agents that can increase serum potassium concentration (eg, heparin) may lead to the development of hyperkalemia.

When combined prescription of lithium preparations with ACE inhibitors, a reversible increase in the concentration of lithium in serum and the development of toxic reactions were reported. Similar reactions may occur with the use of angiotensin II receptor antagonists, and therefore, it is recommended to monitor the concentration of lithium in the serum when combined with these drugs.

With the combined use of angiotensin II receptor antagonists and non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2, acetylsalicylic acid, a decrease in antihypertensive action may be noted.

As with the use of ACE inhibitors, the combined use of angiotensin II receptor antagonists and NSAIDs may increase the risk of renal impairment, including acute renal failure, an increase in serum potassium concentration, especially in patients with reduced renal function. Caution should be exercised in the joint use of these drugs, especially in elderly patients and in patients with reduced circulating blood volume.Patients need to compensate for fluid loss and closely monitor kidney function after initiating combination therapy and periodically against such therapy.

The bioavailability of candesartan is not dependent on food intake.

Contraindicated simultaneous use with aliskiren in patients with diabetes mellitus and in patients with renal failure (glomerular filtration rate less than 60 ml / min).

Special instructions:

Impaired renal function

Against the background of therapy with Candesartan-SZ, as with the use of other drugs that depress the renin-angiotensin-aldosterone system, some patients may have impaired renal function.

When using Candesartan-SZ in patients with arterial hypertension and severe renal failure, it is recommended to periodically monitor the concentration of potassium and creatinine in the blood serum. The clinical experience of using the drug in patients with severe renal dysfunction or terminal stage of renal failure is limited (creatinine clearance less than 15 ml / min).

Patients with chronic heart failure need to periodically monitor kidney function,especially in patients aged 75 years and older, as well as in patients with impaired renal function. When the dose of Candesartan-SZ is increased, it is also recommended to monitor the concentration of potassium and creatinine.

Clinical studies of the drug in chronic heart failure did not include patients with a creatinine concentration> 265 μmol / L (> 3 mg / dL).

Co-administration with ACE inhibitors in chronic heart failure

When applying candesartan in combination with ACE inhibitors, the risk of side effects may increase, especially kidney and hyperkalemia (see "Side effect" section). In these cases, careful monitoring and monitoring of laboratory indicators is necessary.

Stenosis of the renal artery

In patients with bilateral renal artery stenosis or stenosis of the single kidney artery, drugs that affect the renin-angiotensin-aldosterone system, in particular ACE inhibitors, can cause an increase in the concentration of urea and creatinine in the serum. Similar effects can be expected with the appointment of angiotensin II receptor antagonists.

Kidney transplantation

Data on the use of Candesartan-SZ in patients who have undergone kidney transplantation is limited.

Arterial hypotension

In patients with chronic heart failure, with the drug Candesartan-SZ, arterial hypotension may develop. As with other drugs that affect the renin-angiotensin-aldosterone system, the cause of the development of arterial hypotension in patients with hypertension can be a decrease in the volume of circulating blood, as observed in patients receiving high doses of diuretics. Therefore, at the beginning of therapy, care should be taken and, if necessary, correct hypovolemia.

Double blockade of the renin-angiotensin-aldosterone system when using preparations containing aliskiren

The double blockade of the renin-angiotensin-aldosterone system is not recommended by combining candesartan cilexetil and aliskiren, in view of the increased risk of arterial hypotension, hyperkalemia, and renal function changes.

The use of candesartan cilexetil in combination with aliskiren is contraindicated in patients with diabetes mellitus (type 1 or type 2) or with moderate or severerenal failure (glomerular filtration rate <60 ml / min / m) (see the section "Contraindications"),

General anesthesia and surgery

Patients receiving angiotensin II antagonists may develop arterial hypotension as a result of blockade of the renin-angiotensin system during general anesthesia and during surgical interventions. Very rarely, cases of severe arterial hypotension requiring intravenous fluid and / or vasopressors can be noted.

Stenosis of the aortic and mitral valve or obstructive hypertrophic cardiomyopathy

Caudesartan-SZ, like other vasodilators, should be used with caution in patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the renin-angiotensin-aldosterone system. In this regard, the drug Candesartan-SZ is not recommended to appoint such patients.

Hyperkalemia

Clinical experience with other drugs that affect the renin-angiotensin-aldosterone system shows that simultaneous administration of Candesartan-SZ with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase the potassium content in the blood (for example , heparin), can lead to the development of hyperkalemia in patients with arterial hypertension.

In patients with chronic heart failure against the background of therapy with Candesartan-SZ, hyperkalemia can develop. When prescribing Candesartan-SZ for patients with chronic heart failure, regular monitoring of the potassium concentration in the blood is recommended, especially when co-administered with ACE inhibitors and potassium-sparing diuretics, such as spironolactone.

Are common

Patients with vascular tone and kidney function are primarily 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 particularly sensitive to drugs acting on the renin-angiotensin-aldosterone system.The appointment of such agents is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. The possibility of developing these effects can not be ruled out when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular diseases of atherosclerotic genesis, with the use of any antihypertensive drugs, can lead to the development of myocardial infarction or stroke.

Effect on the ability to drive transp. cf. and fur:

Influence on the ability to drive vehicles or work with machinery has not been studied, but the pharmacodynamic properties of the drug indicate that such an effect is absent.

When driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, it should be taken into account that when using the drug, dizziness and fatigue can occur.

Form release / dosage:

Tablets of 8 mg, 16 mg and 32 mg.

Packaging:

For 10, 14 or 30 tablets per contour cell package.

For 20 tablets in a can of polymer or in a bottle of polymer.

Each bank or vial, 3, 6 contour cell packs of 10 tablets, 2, 4 contour packs of 14 tablets or 1, 2 contour packs of 30 tablets together with the instruction for use are placed in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Terms of leave from pharmacies:On prescription

Registration number:LP-002525

Date of registration:08.07.2014

Expiration Date:08.07.2019

The owner of the registration certificate:NORTH STAR, CJSC NORTH STAR, CJSC Russia

Manufacturer: & nbsp

NORTH STAR, CJSC Russia

Representation: & nbspNORTH STAR CJSC NORTH STAR CJSC Russia

Information update date: & nbsp21.11.2017

Illustrated instructions

Instructions

Candesartan-SZ (Candesartan-SZ)