Candesartan-SZ, 32 mg tablets 30 pcs

Pharmacotherapeutic group: Angiotensin II receptor antagonist

ATC code: C09CA06

Pharmacodynamics:

Indications

Arterial hypertension in adults. Candesartan-SZ may be used in monotherapy or in combination with other hypotensive agents.

Chronic heart failure class III-IV according to NYHA classification) in adults with impaired left ventricular systolic function (decreased RVF ≤40%).

Candesartan-Z is used as adjunctive therapy to angiotensin-converting enzyme (ACE) inhibitors or when ACE inhibitors are intolerant.

Active ingredient

Candesartan

Composition

1 tablet contains:

active ingredient:

Candesartan cylexetil – 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 (polyvinylpyrrolidone medium molecular) – 14.0 mg, colloidal silica (aerosil) – 1.5 mg, sodium stearyl fumarate – 2.5 mg.

How to take, the dosage

Candesartan-SZ should be taken once daily regardless of meals.

Arterial Hypertension in Adult Patients

The recommended starting and maintenance dose of Candesartan-SZ is 8 mg once daily. The dose may be increased to 16 mg once daily. Patients who have not adequately decreased their BP after four weeks of 16 mg daily should increase to 32 mg once daily.

If Candesartan-SZ does not lower BP to optimal levels, modify therapy.

The therapy should be adjusted according to blood pressure levels. Maximum antihypertensive effect is achieved within 4 weeks of treatment initiation.

Patients in the elderly

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

Patients with impaired renal function

The starting daily dose in patients with mild to moderate renal impairment (creatinine clearance ≥30 mL/min/173 m2 body surface area) including those on hemodialysis is 4 mg (1/2 tablet of 8 mg).

The clinical experience with the drug in patients with severe renal impairment (creatinine clearance < 30 ml/min/173 m2 body surface area) or terminal renal failure (creatinine clearance less than 15 ml/min) is limited.

Patients with hepatic impairment

The initial daily dose in patients with mild to moderate hepatic impairment is 4 mg once daily (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”).

Companion therapy

The use of Candesartan-SZ with thiazide-type diuretics (e.g. hydrochlorothiazide) may increase the antihypertensive effect of Candesartan-SZ.

Hypovolemia

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

Chronic heart failure

The recommended starting dose of Candesartan-SZ is 4 mg once daily (1/2 of 8 mg tablet). Increase the dose to 32 mg once daily or to the maximum tolerated dose by doubling it at intervals of at least 2 weeks (see Special Precautions).

Patients in special groups

Patients who are elderly and those with impaired renal hepatic function or hypovolemia do not require a change in the starting dose of the drug.

Compatible Therapy

Candesartan SP can be coadministered with other chronic heart failure therapy products such as ACE inhibitors beta-adrenoblockers diuretics and cardiac glycosides.

Interaction

No clinically relevant pharmacokinetic interaction has been observed between Candesartan-Z and hydrochlorothiazide warfarin digoxin and oral contraceptives (ethinylestradiol/levonorgestrel) glibenclamide nifedipine and enalapril.

Candesartan is slightly metabolized in the liver (by CYP2C9 isoenzyme). The conducted studies on interaction showed no effect of the preparation on CYP2C9 and CYP3A4 isoenzymes; effect on other isoenzymes of cytochrome Р450 system was not studied.

The co-administration of Candesartan-SZ with other antihypertensive agents potentiates the antihypertensive effect.

The experience with other drugs acting on the renin-angiotensin-aldosterone system indicates that concomitant therapy with potassium-saving diuretics, potassium substitutes, and other agents which may increase serum potassium (e.g., heparin) may result in hyperkalemia.

When lithium preparations are coadministered with ACE inhibitors, reversible increase in serum lithium concentration and development of toxic reactions have been reported. Similar reactions can occur when using angiotensin II receptor antagonists, and therefore it is recommended to monitor serum lithium concentrations when combining use of these drugs.

When angiotensin II receptor antagonists and nonsteroidal anti-inflammatory drugs (NSAIDs) including selective cyclooxygenase-2 inhibitors of acetylsalicylic acid are used together, decreased antihypertensive effect may be noted.

As with ACE inhibitors, co-administration of angiotensin II receptor antagonists and NSAIDs may increase the risk of renal dysfunction, including acute renal failure and increased serum potassium concentration especially in patients with reduced renal function. Caution should be exercised when coadministering these drugs especially in elderly patients and patients with reduced circulating blood volume. Patients should compensate fluid loss and carefully monitor renal function after initiation of combined therapy and periodically during such therapy.

The bioavailability of candesartan is not dependent on food intake.

The 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).

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Special Instructions

Renal dysfunction

Kandesartan-SZ, as with other agents that inhibit the renin-angiotensin-aldosterone system, may affect renal function in some patients.

When using Candesartan-SZ in patients with arterial hypertension and significant renal impairment, periodic monitoring of serum potassium and creatinine is recommended. Clinical experience with this drug in patients with severe renal impairment or terminal 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. Potassium and creatinine concentrations should also be monitored when increasing the dose of Candesartan-SZ.

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

Combined use with ACE inhibitors in chronic heart failure

The use of candesartan in combination with ACE inhibitors may increase the risk of adverse effects especially renal dysfunction and hyperkalemia (see section “Adverse effects”). In these cases, close monitoring and control of laboratory parameters are necessary.

Renal artery stenosis

In patients with bilateral renal artery stenosis or artery stenosis of the sole renal artery, drugs affecting the renin-angiotensin-aldosterone system in particular ACE inhibitors may cause increased serum urea and creatinine concentrations. Similar effects can be expected when prescribing angiotensin II receptor antagonists.

Kidney transplantation

There are limited data on the use of Candesartan-SZ in kidney transplant patients.

Arterial hypotension

Candesartan-SZ therapy may cause arterial hypotension in patients with chronic heart failure. As with other agents affecting the renin-angiotensin-aldosterone system, a decrease in circulating blood volume in patients with arterial hypertension as observed in patients treated with high doses of diuretics may be the cause of the development of arterial hypotension. Therefore, caution should be exercised at the beginning of therapy and correction of hypovolemia should be performed if necessary.

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

Double blockade of the renin-angiotensin-aldosterone system by combining candesartan cilexetil and aliskiren is not recommended due to increased risk of hyperkalemia and altered 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 to severe renal impairment (glomerular filtration rate < 60 ml/min/m ) (see

General anesthesia and surgery

Patients receiving angiotensin II antagonists during general anesthesia and surgical procedures may develop arterial hypotension as a result of renin-angiotensin system blockade. Very rarely there may be cases of severe arterial hypotension requiring intravenous administration of fluids and/or vasopressors.

Aortic and mitral valve stenosis or obstructive hypertrophic cardiomyopathy

Patients with obstructive hypertrophic cardiomyopathy or hemodynamically significant aortic or mitral valve stenosis should exercise caution when prescribing Candesartan-SZ as well as other vasodilators.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to therapy with hypotensive drugs affecting the renin-angiotensin-aldosterone system. Therefore, Candesartan-SZ is not recommended for these patients.

Hyperkalemia

. Clinical experience with other potassium-angiotensin-aldosterone drugs has shown that concomitant administration of Candesartan-SZ with potassium-saving diuretics, potassium supplements or other drugs which may increase potassium in the blood (e.g. heparin), may lead to hyperkalemia in patients with arterial hypertension.

Hyperkalemia may occur in patients with chronic heart failure during therapy with Candesartan-SZ. Regular monitoring of potassium concentrations in the blood is recommended in patients with chronic heart failure, especially when combined with ACE inhibitors and potassium-saving diuretics such as spironolactone.

General

. Patients in whom vascular tone and renal function are predominantly dependent on renin-angiotensin-aldosterone activity (e.g., patients with severe chronic heart failure or renal disease, including renal artery stenosis) are particularly sensitive to drugs acting on the renin-angiotensin-aldosterone system. Prescription of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria, and rarely – acute renal failure. The possibility of these effects cannot be excluded even when using angiotensin II receptor antagonists. Sharp decrease of BP in patients with coronary heart disease or cerebrovascular diseases of atherosclerotic genesis while using any hypotensive agents may lead to myocardial infarction or stroke.

Influence on the ability to operate motor vehicles and machinery:

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

When driving motor vehicles and engaging in potentially hazardous activities requiring increased concentration and quick psychomotor reactions, it should be noted that dizziness and increased fatigue may occur with the use of the drug.

Synopsis

Tablets are white or almost white, round, flat-cylindrical with a bevel and a rib.

Contraindications

Hypersensitivity to candesartan cilexetil or other ingredients of the drug.

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

Severe liver dysfunction and/or cholestasis.

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

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

Side effects

Hypertension

The side effects in clinical trials were moderate and transient and were comparable in frequency to the placebo group. The overall incidence of Candesartan-SZ side effects was independent of the dose, gender and age of the patient. The incidence of discontinuation of therapy due to side effects was similar between candesartan cilexetil (31%) and placebo (32%).

The following side effects have been reported frequently (>1/100) with candesartan cilexetil in the analysis of study data. The side effects described were at least 1% more frequent than in the placebo group.

Central nervous system: dizziness weakness headache;

Musculoskeletal connective tissue system: back pain;

Infections: Respiratory infections;

Laboratory parameters: in general, no clinically significant changes in standard laboratory parameters were observed with Candesartan-SZ. As with other inhibitors of the renin-angiotensin-aldosterone system, a slight decrease in hemoglobin may be observed. An increase in creatinine urea or calcium concentration and a decrease in sodium concentration have been observed. Increases in alanine aminotransferase (ALT) activity were slightly more frequent with Candesartan-CZ compared to placebo (13% vs. 05%). Regular monitoring of laboratory values is usually not required with Candesartan-SZ. However, periodic monitoring of serum potassium and creatinine concentrations is recommended in patients with impaired renal function.

Chronic Heart Failure

The side effects noted with Candesartan-SZ in patients with chronic heart failure were consistent with the pharmacological properties of the drug and varied with the patient’s condition.

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

Cardiovascular system: marked decrease in BP; Metabolic disorders and diseases caused by metabolic disorders: hyperkalemia;

Urinary system: impaired renal function; Laboratory changes: increased concentration of urea creatinine and potassium.

The monitoring of serum concentrations of creatinine and potassium is recommended.

The following side effects have been reported very rarely (< 1/10000) during post-marketing use of the drug:

Blood and lymphatic system disorders: leukopenia neutropenia and agranulocytosis;

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

Nervous system: dizziness headache;

Respiratory system chest and mediastinum: cough;

Gastrointestinal tract: nausea;

Liver and biliary tract disorders: Increased activity of “liver” enzymes impaired liver function or hepatitis;

Skin side: angioedema rash urticaria pruritus.

Connective system musculoskeletal system: back pain arthralgia myalgia;

Urinary system: renal dysfunction including renal failure in predisposed patients.

In patients receiving angiotensin II receptor antagonists rare reports of rhabdomyolysis have been reported.

Overdose

Symptoms

An analysis of the pharmacological properties of the drug suggests that the main manifestation of overdose may be a clinically pronounced decrease in BP dizziness and tachycardia and may also manifest bradycardia. There have been overdoses of the drug (up to 672 mg of candesartan cilexetil) in individual cases with recovery without serious sequelae.

Treatment

If clinically significant arterial hypotension develops, symptomatic treatment must be administered and the patient’s condition monitored. The patient should be placed elevated at the foot end of the bed. If necessary, increase circulating plasma volume, e.g., by intravenous injection of 09% sodium chloride solution. Sympathomimetic drugs may be administered if necessary. Excretion of candesartan by hemodialysis is unlikely.

Pregnancy use

Pregnancy

The use of Candesartan-SZ is contraindicated during pregnancy (see section “Contraindications”). Patients taking Candesartan-SZ should be advised of this prior to planning pregnancy so that they can discuss alternative therapies with their physician. If pregnancy occurs, therapy with Candesartan-SZ should be discontinued immediately and alternative treatment should be prescribed if necessary.

The drugs with a direct effect on the renin-angiotensin-aldosterone system may impair fetal development or have adverse effects on the newborn up to and including death if used during pregnancy.

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

Breastfeeding

It is not known at this time whether candesartan passes into breast milk. Because of possible adverse effects on infants, Candesartan-SZ should not be used during breastfeeding.

Similarities

Atakand, Angiacand, Hyposart, Hyposart, Ordiss