Candesartan-SZ, 32 mg tablets 30 pcs

Pharmacotherapeutic group: Angiotensin II receptor antagonist

ATC code: C09CA06

Pharmacodynamics:

Indications

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

Chronic heart failure III-IV functional class according to the NYHA classification) in adult patients with impaired left ventricular systolic function (decrease in LVEF ≤40%). The drug Candesartan-SZ is used as an additional therapy to angiotensin-converting enzyme (ACE) inhibitors or in cases of intolerance to ACE inhibitors.

Pharmacological effect

Pharmacotherapeutic group: Angiotensin II receptor antagonist

ATX code: C09CA06

Pharmacodynamics:

Special instructions

Renal dysfunction

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

When using the drug 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. 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 periodically monitored, especially in patients aged 75 years and older and 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.

Clinical studies of the drug in chronic heart failure did not include patients with creatinine concentrations > 265 µmol/l (> 3 mg/dl).

Combined use with ACE inhibitors in chronic heart failure

When using candesartan in combination with ACE inhibitors, the risk of side effects, especially renal dysfunction and hyperkalemia, may increase (see section “Side effects”). In these cases, careful observation 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 affecting the renin-angiotensin-aldosterone system, in particular ACE inhibitors, can cause an increase in the concentration of urea and creatinine in the blood serum. Similar effects can be expected when prescribing angiotensin II receptor antagonists.

Kidney transplant

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

Arterial hypotension

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

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

Dual blockade of the renin-angiotensin-aldosterone system by combining candesartan cilexetil and aliskiren is not recommended due to the increased risk of arterial 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 impairment (glomerular filtration rate <60 ml/min/m) (see section "Contraindications")

General anesthesia and surgery

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

Aortic and mitral valve stenosis or obstructive hypertrophic cardiomyopathy

When prescribing Candesartan-SZ, like other vasodilators, to patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve, caution should be exercised.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to treatment 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 the use of other drugs that affect the renin-angiotensin-aldosterone system shows that the simultaneous administration of Candesartan-SZ with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium or other drugs that can increase the level of potassium in the blood (for example, heparin) can lead to the development of hyperkalemia in patients with arterial hypertension.

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

General

Patients whose vascular tone and renal function primarily depend 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 acting on the renin-angiotensin-aldosterone system. The prescription of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, less often, acute renal failure. The possibility of developing the listed effects cannot be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular diseases of atherosclerotic origin when using any antihypertensive drugs can lead to the development of myocardial infarction or stroke.

Impact on the ability to drive vehicles. Wed and fur.:

The effect on the ability to drive vehicles or operate 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 hazardous activities that require increased concentration and speed of psychomotor reactions, it should be taken into account that when using the drug, dizziness and increased fatigue may occur.

Active ingredient

Candesartan

Composition

1 tablet contains:

active substance:

candesartan cilexetil – 32.0 mg;

excipients: lactose monohydrate (milk sugar) – 78.0 mg, microcrystalline cellulose – 74.0 mg, pregelatinized starch (starch 1500) – 40.0 mg, croscarmellose sodium (primellose) – 8.0 mg, povidone (medium molecular weight polyvinylpyrrolidone) – 14.0 mg, silicon dioxide colloidal (aerosil) – 1.5 mg, sodium stearyl fumarate – 2.5 mg.

Pregnancy

Pregnancy

The use of Candesartan-SZ during pregnancy is contraindicated (see section “Contraindications”). Patients taking Candesartan-SZ should be warned about this before planning pregnancy so that they can discuss alternative treatment options with their doctor. If pregnancy occurs, therapy with Candesartan-SZ should be stopped immediately and, if necessary, alternative treatment should be prescribed.

Drugs that have a direct effect on the renin-angiotensin-aldosterone system can cause developmental disorders in the fetus or have a negative effect on the newborn, including death when used during pregnancy.

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

Breastfeeding period

It is currently 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 included in the drug.

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

Severe liver dysfunction 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 <60 ml/min/m2).

With caution:

In patients with severe renal failure (creatinine clearance less than 30 ml/min) with bilateral renal artery stenosis or stenosis of the artery of a single kidney with hemodynamically significant stenosis of the aortic and mitral valve after a history of 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 from clinical studies) with hypertrophic cardiomyopathy.

Side Effects

Arterial hypertension

Side effects during clinical trials were moderate and transient and were comparable in frequency to the placebo group. The overall incidence of side effects while taking Candesartan-SZ did not depend on the dose of the drug, gender and age of the patient. Discontinuation rates due to side effects were similar between candesartan cilexetil (31%) and placebo (32%).

During the analysis of data from studies, the following side effects were reported frequently (>1/100) while taking candesartan cilexetil. The described side effects were observed with a frequency of at least 1% greater than in the placebo group.

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

From the musculoskeletal system of connective tissue: back pain;

Infections: respiratory infections;

Laboratory parameters: in general, when using the drug Candesartan-SZ, there were no clinically significant changes in standard laboratory parameters. As with other inhibitors of the renin-angiotensin-aldosterone system, a slight decrease in hemoglobin may be observed. An increase in the concentration of urea creatinine or calcium and a decrease in the concentration of sodium were observed. An increase in alanine aminotransferase (ALT) activity was observed slightly more often when using the drug 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

Side effects identified during 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 cardiovascular system: pronounced decrease in blood pressure; Metabolic disorders and diseases caused by metabolic disorders: hyperkalemia;

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

It is recommended to monitor serum creatinine and potassium concentrations.

The following side effects have been reported very rarely (< 1/10,000) 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;

From the nervous system: dizziness, headache;

From the respiratory system of the chest and mediastinum: cough;

From the gastrointestinal tract: nausea;

From the liver and biliary tract: increased activity of liver enzymes; impaired liver function or hepatitis;

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

From the musculoskeletal system of connective tissue: 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 receiving angiotensin II receptor antagonists.

Interaction

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

Candesartan is metabolized in the liver to a small extent (by the CYP2C9 isoenzyme). Interaction studies have not revealed any effect of the drug on the isoenzymes CYP2C9 and CYP3A4; the effect on other isoenzymes of the cytochrome P450 system has not been studied.

The combined use of Candesartan-SZ with other antihypertensive drugs 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 drugs that can increase the concentration of potassium in the blood serum (for example, heparin) can lead to the development of hyperkalemia.

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

When combined with angiotensin II receptor antagonists and nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors of acetylsalicylic acid, a decrease in the antihypertensive effect may be observed.

As with the use of ACE inhibitors, the combined use of angiotensin II receptor antagonists and NSAIDs may increase the risk of renal dysfunction including acute renal failure and 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 be compensated for fluid loss and closely monitor renal function after initiating 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 failure (glomerular filtration rate less than 60 ml/min).

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, dizziness and tachycardia, and bradycardia may also appear. Isolated cases of drug overdose (up to 672 mg of candesartan cilexetil) were described, resulting in the recovery of patients without serious consequences.

Treatment

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

Storage conditions

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

Shelf life

3 years.

Manufacturer

North Star NAO, Russia