Candesartan-SZ pills 32mg, 30pcs

Composition

1 tablet contains: Active ingredient: candesartan in was tsileksetil – 32.0 mg;excipients: lactose monohydrate (milk sugar) – length: 78.0 mg, microcrystalline cellulose – and 74.0 mg, pregelatinized starch (starch 1500) – 40,0 mg, croscarmellose sodium (Primerose) – 8.0 mg, povidone (polyvinylpyrrolidone middle) – 14.0 mg, silicon dioxide colloid (Aerosil) – 1,5 mg, sodium fumarate – 2.5 mg.

Pharmacological properties

Pharmacotherapeutic group: Antagonist receptor of angiotensin CAD ATKH: C09CA06 Pharmacodynamics :

Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system that 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 type 1 angiotensin receptors (AT1 receptors).

Candesartan is a selective angiotensin II type 1 receptor antagonist. Candesartan does not inhibit the angiotensin-converting enzyme (ACE) that converts angiotensin I to angiotensin II and destroys bradykinin; it 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 receiving candesartan cilexetil. Candesartan does not bind to the receptors of other hormones and does not block ion channels involved in regulating the functions of the cardiovascular system. As a result of blocking AT-1 angiotensin II receptors, there is a dose-dependent increase in the activity of renin angiotensin I angiotensin II and a decrease in the concentration of aldosterone in blood plasma.

Arterial hypertension

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

The onset of antihypertensive effects after taking the first dose of candesartan cilexetil usually develops within 2 hours. With continued treatment with the drug in a fixed dose, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists throughout treatment. Candesartan cilexetil administered once a day provides an effective and smooth reduction in blood pressure for 24 hours with slight fluctuations in blood pressure in the intervals between taking the next dose of the drug. The use of candesartan cilexetil together with hydrochlorothiazide leads to an increased antihypertensive effect.

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

The effectiveness of the drug does not depend on the age and gender of patients. Candesartan cilexetil increases renal blood flow and does not alter or increase glomerular filtration rate, while renal vascular resistance and filtration fraction are reduced. Taking candesartan cilexetil at a dose of 8-16 mg for 12 weeks does not negatively affect glucose concentration and lipid profile in patients with arterial hypertension and type 2 diabetes mellitus.

Chronic heart failure

In patients with chronic heart failure and reduced left ventricular systolic function (LVEF < 40%), candesartan use contributed to a decrease in total peripheral vascular resistance and capillary pressure in the lungs, an increase in renin activity and angiotensin II concentration in blood plasma, as well as a decrease in aldosterone levels.

Pharmacokinetics:

Suction and distribution

Candesartan cilexetil is an oral prodrug. It is rapidly converted to the Active ingredient – candesartan through essential hydrolysis, when absorbed from the digestive tract, binds strongly to AT 1 receptors and slowly dissociates and does not have agonist properties. The absolute bioavailability of candesartan after oral use of candesartan cilexetil solution is about 40%. The relative bioavailability of the tablet preparation compared to the oral solution is approximately 34%. Thus, the estimated absolute bioavailability of the tablet form of the drug is 14%. The maximum concentration in the blood serum (Cmax) is reached 3-4 hours after taking the tablet form of the drug. When the dose of the drug is increased within the recommended limits, the concentration of candesartan increases linearly. The pharmacokinetic parameters of candesartan do not depend on the patient’s gender. Food intake does not significantly affect the area under the concentration – time curve (AUC), i. e. simultaneous food intake does not significantly affect the bioavailability of the drug. Candesartan actively binds to plasma proteins (> 99%). The volume of distribution of candesartan is 01 l/kg.

Metabolism and elimination from the body

Candesartan is mainly excreted unchanged from the body by the kidneys and bile and is only slightly metabolized in the liver. The elimination half-life of candesartan is approximately 9 hours. Accumulation in the body is not observed.

The total clearance of candesartan is about 037 ml/min/kg, while the renal clearance is about 019 ml/min/kg. Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion. When radiolabeled candesartan cilexetil is taken orally, approximately 26% of the administered amount is excreted by the kidneys as candesartan and 7% as an inactive metabolite, while 56% of the administered amount is detected in the feces as candesartan and 10% as an inactive metabolite.

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

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

In patients undergoing hemodialysis, the same pharmacokinetic parameters of candesartan were found as in patients with severe renal impairment.

In patients with mild to moderate hepatic impairment, the AUC of candesartan increased by 23%.

Indications

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

Chronic heart failure (NYHA functional class III-IV) in adult patients with impaired left ventricular systolic function (reduced LVEF < 40%). The drug Candesartan-SZ is used as an adjunct therapy to angiotensin-converting enzyme (ACE) inhibitors or for intolerance to ACE inhibitors.

Use during 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 prior to pregnancy planning so that they can discuss alternative treatment options with their healthcare provider. In case of pregnancy, therapy with Candesartan-SZ should be stopped immediately and alternative treatment should be prescribed if necessary.

Drugs that have a direct effect on the renin-angiotensin-aldosterone system can cause fetal development disorders or have a negative effect on the newborn up to a fatal outcome when using the drug during pregnancy.

It is known that therapy with angiotensin II receptor antagonists can cause fetal developmental disorders (impaired renal function, oligohydramnios, slowing of ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

Breast-feeding period

Currently, it is not known whether candesartan passes into breast milk. Due to possible undesirable effects on infants, Candesartan-SZ should not be used during breastfeeding.

Contraindications

Hypersensitivity to candesartan cilexetil or other components of the drug.

Pregnancy and lactation (see the section “Use during pregnancy and lactation”).

Severe hepatic impairment and / or cholestasis.

Age up to 18 years (efficacy and safety have not been established). Galactose intolerance lactase deficiency and glucose-galactose malabsorption syndrome.

Concomitant use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (glomerular filtration rate

With caution:

In patients with severe renal insufficiency (creatinine clearance less than 30 ml/min), bilateral renal artery stenosis or stenosis of the artery of a single kidney with a history of hemodynamically significant aortic and mitral valve stenosis after kidney transplantation, in patients with cerebrovascular diseases and coronary heart disease (CHD), with hyperkalemia in patients with reduced circulating blood volume with primary hyperaldosteronism (insufficient data on clinical trials). studies) with hypertrophic cardiomyopathy.

Side effects

Arterial hypertension

Side effects in clinical trials were moderate and transient and were comparable in frequency to the placebo group. The overall incidence of side effects associated with Candesartan-SZ did not depend on the dose, gender, or age of the patient. The frequency of discontinuation of therapy due to side effects was similar with candesartan cilexetil (31%) and placebo (32%).

In the course of analyzing the data of the conducted studies, the following side effects were reported frequently (>1/100) occurring against the background of taking 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;

Musculoskeletal connective tissue disorders: back pain;

Infections: respiratory infections.

Laboratory parameters: in general, no clinically significant changes in standard laboratory parameters were observed with the use of Candesartan-SZ. As with other inhibitors of the renin-angiotensin-aldosterone system, there may be a slight decrease in hemoglobin. There was an increase in urea or calcium creatinine and a decrease in sodium concentration. Increased alanine aminotransferase (ALT) activity was observed slightly more frequently with Candesartan-SZ compared to placebo (13% instead of 05%). When using the drug Candesartan-SZ, regular monitoring of laboratory parameters is usually not required. 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

The side effects detected during the use of Candesartan-SZ in patients with chronic heart failure corresponded to the pharmacological properties of the drug and depended on the patient’s condition.

Most common side effects (≥1/100:

From the cardiovascular system: marked decrease in blood pressure; Metabolic disorders and diseases caused by metabolic disorders: hyperkalemia;

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

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

The following side effects were reported very rarely during post-marketing use of the drug (:

From the circulatory and lymphatic system: leukopenia neutropenia and agranulocytosis;

Metabolic disorders and diseases caused by metabolic disorders: hyperkalemia hyponatremia;

Nervous system disorders: dizziness, headache;

Respiratory, thoracic and mediastinal disorders: cough;

From the gastrointestinal tract: nausea;

From the liver and biliary tract: increased activity of “liver” enzymes liver dysfunction or hepatitis;

From the side of the skin: angioedema rash urticaria pruritus of the skin.

Musculoskeletal connective tissue disorders: back pain arthralgia myalgia;

From the urinary system: impaired renal function including renal failure in predisposed patients.

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

Interaction

No clinically significant pharmacokinetic interactions were observed when Candesartan-SZ was administered with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol/levonorgestrel), glibenclamide, nifedipine, and enalapril.

Candesartan is only slightly metabolized in the liver (by the CYP2C9 isoenzyme). Interaction studies have not revealed the effect of the drug on the isoenzymes CYP2C9 and CYP3A4 The effect on other isoenzymes of the cytochrome P 450 system has not been studied.

Concomitant use of Candesartan-SZ with other antihypertensive agents potentiates the antihypertensive effect.

Experience with the use of 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 the concentration of potassium in the blood serum (for example, heparin) may lead to the development of hyperkalemia.

Reversible increases in serum lithium concentrations and the development of toxic reactions have been reported when lithium preparations are co-administered with ACE inhibitors. 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 blood serum with the combined use of these drugs.

Concomitant use of angiotensin II receptor antagonists and nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 acetylsalicylic acid inhibitors, may reduce the antihypertensive effect.

As with ACE inhibitors concomitant use of angiotensin II receptor antagonists and NSAIDs may increase the risk of impaired renal function including acute renal failure increased serum potassium concentrations especially in patients with reduced renal function. Caution should be exercised when using these drugs together, especially in elderly patients and in patients with reduced circulating blood volume. Patients should compensate for fluid loss and carefully monitor renal function after starting combination therapy and periodically during such therapy.

The bioavailability of candesartan is independent of food intake.

Concomitant use with aliskiren is contraindicated in patients with diabetes mellitus and in patients with renal insufficiency (glomerular filtration rate less than 60 ml / min).

How to take, course of use and dosage

The drug Candesartan-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 daily. 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 are recommended to increase the dose to 32 mg once a day.

If 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 according to 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 or moderate renal impairment (creatinine clearance ≥30 ml/min/173 m2 of body surface area), including patients on hemodialysis, is 4 mg (1/2 tablet of 8 mg).

Clinical experience of using the drug in patients with severe renal impairment (creatinine clearance

Patients with impaired liver function

The initial daily dose in patients with mild to moderate hepatic impairment is 4 mg once a day (1/2 tablet of 8 mg). Clinical experience with the drug in patients with severe hepatic impairment and / or cholestasis is limited (see section “Contraindications”).

Concomitant therapy

The use of Candesartan-SZ in combination with thiazide-type diuretics (for example, hydrochlorothiazide) may increase the antihypertensive effect of Candesartan-SZ.

Hypovolemia

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

Chronic heart failure

The recommended starting dose of Candesartan-SZ is 4 mg once a day (1/2 tablet of 8 mg). Increasing the dose to 32 mg once a day or to the maximum tolerated dose is carried out by doubling it at intervals of at least 2 weeks (see the section “Special instructions”).

Special patient groups

Elderly patients and patients with impaired renal hepatic function or hypovolemia do not need to change the initial dose of the drug.

Concomitant therapy

Candesartan-SZ can be co-administered with other agents used in the treatment of chronic heart failure such as ACE inhibitors beta-blockers diuretics and cardiac glycosides

Overdose

Symptoms

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

Treatment

With the development of clinically pronounced arterial hypotension, it is necessary to conduct symptomatic treatment and monitor the patient’s condition. Lay the patient down and lift the foot end of the bed. If necessary, the volume of circulating plasma should be increased, for example, by intravenous use of 09% sodium chloride solution. If necessary, sympathomimetic drugs may be prescribed. Elimination of candesartan by hemodialysis is unlikely.

Description

Tablets are white or almost white in color, round, flat-cylindrical with a chamfer and risk.

Special instructions

Impaired renal function

Some patients may experience impaired renal function during Candesartan-SZ therapy, as with other drugs that inhibit the renin-angiotensin-aldosterone system.

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

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

Patients with creatinine concentrations > 265 mmol/l (>3 mg/dl) were excluded from clinical trials of the drug in chronic heart failure.

Concomitant use with ACE inhibitors in chronic heart failure

When using candesartan in combination with ACE inhibitors, the risk of side effects may increase, especially impaired renal function and hyperkalemia (see the section “Side effects”). In these cases, careful monitoring and monitoring of laboratory parameters is necessary.

Renal artery stenosis

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

Kidney transplant

Data on the use of Candesartan-SZ in patients undergoing kidney transplantation are limited.

Arterial hypotension

Hypotension may occur in patients with chronic heart failure treated with Candesartan-SZ. As with other drugs that affect the renin-angiotensin-aldosterone system, the cause of hypotension in patients with arterial hypertension may be a decrease in the volume of circulating blood, as is observed in patients receiving high doses of diuretics. Therefore, at the beginning of therapy, care should be taken and, if necessary, correction of hypovolemia should be carried out.

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

Double blockade of the renin-angiotensin-aldosterone system by combining candesartan cilexetil and aliskiren is not recommended due to the increased risk of hypotension, hyperkalemia and changes in renal function.

The use of candesartan cilexetil in combination with aliskiren is contraindicated in patients with diabetes mellitus (type 1 or 2) or with moderate or severe renal insufficiency (glomerular filtration rate

General anesthesia and surgery

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

Aortic and mitral valve stenosis or obstructive hypertrophic cardiomyopathy

Caution should be exercised when prescribing Candesartan-SZ as well as other vasodilators to patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant aortic or mitral valve stenosis.

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 for such patients.

Hyperkalemia

Clinical experience with other drugs that affect the renin-angiotensin-aldosterone system shows that concomitant use 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) it can lead to the development of hyperkalemia in patients with arterial hypertension.

Hyperkalaemia may occur in patients with chronic heart failure treated with Candesartan-SZ. When prescribing Candesartan-SZ to patients with chronic heart failure, it is recommended to regularly monitor the concentration of potassium in the blood, especially when co-administered with ACE inhibitors and potassium-sparing diuretics such as spironolactone.

General information

Patients whose 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 diseases including renal artery stenosis) are particularly sensitive to drugs acting on the renin-angiotensin – aldosterone system. The use of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria, and less often-acute renal failure. The possibility of developing these effects cannot be excluded even when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular diseases of atherosclerotic origin with the use of any antihypertensive agents can lead to the development of myocardial infarction or stroke.

Influence on the ability to drive vehicles and mechanisms:

The effect on the ability to drive vehicles or work with machinery has not been studied, but the pharmacodynamic properties of the drug indicate that there is no such effect.

When driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions, it should be borne in mind that dizziness and increased fatigue may occur when using the drug.

Storage conditions

In a dry place protected from light at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 3 years.

Active ingredient

Candesartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets