Kandekor - instructions for use, doses, side effects, contraindications

Angiotensin II is the main enzyme of the renin-angiotensin-aldosterone system (RAAS), which takes part in the pathogenesis of arterial hypertension (AH),heart failure and other cardiovascular diseases.

Candesartan is a selective antagonist of angiotensin II receptors, subtype 1 (AT1 receptors). Does not exhibit agonist properties (does not affect angiotensin-converting enzyme (ACE) and does not lead to the accumulation of bradykinin or substance P, does not bind to receptors of other hormones, does not affect the state of ion channels involved in the regulation of cardiovascular activity). As a result of blocking AT1-receptor angiotensin II compensatory dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in aldosterone in the blood plasma.

Arterial hypertension

The intake of candesartan inside provides a dose-dependent, smooth decrease in blood pressure by decreasing the total peripheral vascular resistance (OPSS) without a reflex increase in the heart rate (heart rate). There is no data on the development of severe arterial hypotension after taking the first dose or about the development of the "withdrawal" syndrome after discontinuation of therapy.

The onset of antihypertensive action after taking the first dose of the drug usually develops within 2 hours, the duration of the effect is 24 hours.Against the background of continued therapy with candesartan in a fixed dose, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists throughout the treatment.

Adding a thiazide diuretic hydrochlorothiazide to candesartan enhances its antihypertensive effect.

Age and sex of the patient do not affect the effectiveness of the drug. Increases renal blood flow and does not change or increases the rate of glomerular filtration, while renal vascular resistance and filtration fraction are reduced.

Candesartan has a less pronounced antihypertensive effect in patients of the Negroid race (a population with predominantly low renin activity in the blood plasma).

There is no data on the effect of candesartan on the progression of diabetic nephropathy. In patients with arterial hypertension and type 2 diabetes mellitus candesartan does not adversely affect the concentration of glucose in the blood and the lipid profile.

Heart failure

Candesartan therapy reduces the mortality rate and hospitalization rate in patients with chronic heart failure (CHF), regardless of age, sex and concomitant therapy, leading to a decrease in the functional class of CHF according to classification NYHA.

Candesartan is effective in patients taking beta-blockers simultaneously. combination with ACE inhibitors; while its effectiveness does not depend on the dose of the ACE inhibitor. In patients with CHF and reduced systolic function of the left ventricle (left ventricular ejection fraction (LVEF) less than 40%) candesartan reduces OPSS and wedging pressure in the pulmonary capillaries.

Pharmacokinetics:

Suction and distribution

The absolute bioavailability of candesartan is approximately 40% after oral administration. The relative bioavailability is approximately 34%.

The maximum concentration (C_max) in the blood serum is achieved 3-4 hours after ingestion.

The concentration in the blood plasma increases linearly with increasing dose in the therapeutic interval (up to 32 mg).

The association with plasma proteins is high (more than 99%). The volume distribution of candesartan is 0.13 l / kg.

Metabolism and excretion

It is slightly metabolized in the liver (20-30%) with the participation of isoenzyme CYP2C9 to form an inactive derivative.

The half-life (T1 / 2) of candesartan is approximately 9 hours. Do not cumulate. The total clearance is about 0.37 ml / min / kg, with the renal clearance of the drug - 0.19 ml / min / kg. After oral administration ¹⁴C-labeled candesartan cilexetil 26% of the dose was excreted by the kidneys in the form of candesartan and 7% in the form of an inactive metabolite, while 56% of the dose is excreted through the intestines with bile in the form of candesartan and 10% in the form of an inactive metabolite.

After a single dose of 72 hours, more than 90% of the dose is withdrawn.

Special patient groups

In elderly patients (over 65 years) Cmax and the area under the concentration-time curve (AUC) candesartan increase in comparison with patients of young age by approximately 50% and 80%, respectively.

However, the response from BP and the possible side effects with candesartan do not depend on the age of the patients.

In patients with mild to moderate renal impairment Cmax and AUC candesartan increases by approximately 50% and 70%, respectively, while T1 / 2 does not change compared to patients with preserved renal function.

In patients with severe renal dysfunction Cmax and AUC increase by 50% and 110% respectively, and T1 / 2 of the drug is doubled.

In patients with mild or moderate impairment of liver function an increase AUC candesartan by 23%.

Indications:

Arterial hypertension.

Chronic heart failure and impaired systolic function of the left ventricle (LVEF <40%) as adjunctive therapy to ACE inhibitors or with intolerance to ACE inhibitors (see section "Pharmacodynamics").

Contraindications:

Hypersensitivity to candesartan or excipients of the drug.

Pregnancy and lactation.

Galactosemia, lactase deficiency, glucose-galactose malabsorption syndrome.

Age to 18 years (effectiveness and safety not established).

Severe liver dysfunction and / or cholestasis.

Carefully:Severe renal impairment (creatinine clearance less than 30 ml / min), hemodialysis, bilateral stenosis of the renal arteries or stenosis of the single kidney, hemodynamically significant stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy (GOCMP), post-transplant condition kidneys, cerebrovascular disorders of ischemic origin and coronary heart disease (IHD), hyperkalemia, in patients with reduced circulating blood volume (BCC), general anesthesia and surgical interventions (risk of developing arterial hypotension, due to the blockade of RAAS), primary hyperaldosteronism.

Pregnancy and lactation:

Pregnancy

The drug KANDEKOR ® is contraindicated in pregnancy, tk. candesartan has a direct effect on RAAS, can cause fetal developmental disorders or have a negative impact on the newborn, up to a lethal outcome.

When diagnosing pregnancy, KANDEKOR® should be discontinued as soon as possible.

When planning pregnancy, it is necessary to transfer the patient to adequate alternative therapy.

Lactation period

It is not known whether the candesartan in breast milk, but it is known that it penetrates into the breast milk of lactating rats.

During treatment with KANDEKOR®, breastfeeding should be discontinued.

Newborns, whose mothers were taken during pregnancy KANDEKOR®, should be under careful medical supervision because of the likelihood of developing arterial hypotension.

Dosing and Administration:

Inside, 1 time per day, regardless of food intake.

Arterial hypertension

The recommended initial and maintenance dose of KANDEKOR® is 8 mg 1 time / day. If necessary, the dose can be increased to 16 mg 1 time / day.The maximum antihypertensive effect is achieved within 4 weeks of therapy. The maximum daily dose is 32 mg 1 time / day.

If the background of the maximum daily dose does not achieve adequate control of blood pressure, it is recommended to add a thiazide diuretic to therapy.

Patients with reduced BCC: in patients at risk of developing arterial hypotension, it is recommended to start therapy with an initial dose of 4 mg.

Patients with impaired renal function: in patients with mild or moderate renal dysfunction (CC greater than 30 ml / min / 1.73 m² body surface area), there is no need to change the initial dose of KANDEKOR® (8 mg).

Clinical experience of using the drug in patients with severe renal dysfunction (CC less than 30 ml / min / 1.73 m² surface area of the body) is limited; in this case, the possibility of starting therapy with a dose of 4 mg / day should be considered.

Patients with impaired hepatic function: in patients with a mild or moderate liver function disorder, correction of the dose of KANDEKOR® is not required. Clinical experience of the drug in patients with severe impairment of liver function and / or cholestasis is not available (see Contraindications section).

Chronic heart failure

The recommended initial dose of KANDEKOR® is 4 mg 1 time / day. The increase to the maximum daily dose of 32 mg 1 time / day or up to the maximum tolerated dose is carried out by doubling the dose with an interval of at least 2 weeks.

Elderly patients: correction of the dose of KANDEKOR® is not required.

Application in children and adolescents

The safety and efficacy of KANDEKOR® in children and adolescents under 18 years of age have not been established (see "Contraindications").

Concomitant therapy

The drug KANDEKOR® can be used simultaneously with other drugs for the treatment of CHF, including ACE inhibitors, beta-blockers, diuretics, cardiac glycosides or combinations of these drugs (see the sections "Pharmacodynamics" "Special instructions").

Side effects:

Classification of the incidence of adverse events of the World Organization Health (WHO):

very often> 1/10

often from> 1/100 to <1/10

infrequently from> 1/1000 to <1/100

rarely from> 1/10000 to <1/1000

very rarely from <1/10000, including individual messages.

Side effects of candesartan are mild and transient.

The frequency of side effects does not depend on the dose of the drug and the age of the patient.

From the nervous system: often - dizziness, headache, weakness.

From the respiratory system: often - respiratory infections, pharyngitis, rhinitis.

From the side of the cardiovascular system: often a marked decrease in blood pressure.

From the genitourinary system: often - a violation of kidney function, including renal failure in predisposed patients.

On the part of the hematopoiesis and lymphatic system: very rarely - leukopenia, neutropenia, thrombocytopenia and agranulocytosis.

From the digestive system: very rarely - nausea.

From the hepatobiliary system: very rarely - increased activity of "liver" transaminases, a violation of liver function or hepatitis.

From the side of the musculoskeletal system: very rarely - back pain, arthralgia, myalgia.

Laboratory indicators: very rarely - hyperkalemia, hyponatremia, increased creatinine concentration in the blood, hyperuricemia, a slight decrease in hemoglobin.

Allergic reactions: very rarely - angioedema, skin rash, itching, urticaria.

Other: exacerbation of gout, "hot flashes" of blood to the skin of the face.

Overdose:

Symptoms: marked decrease in blood pressure, dizziness, tachycardia.Individual cases of overdose of candesartan (up to 672 mg of candesartan cilexetil), which resulted in the recovery of patients without severe consequences, are described.

Treatment: transfer the patient into a "lying" position on his back with his legs raised up; further measures should be taken to increase bcc (introduction of 0.9% sodium chloride solution intravenously).

Symptomatic therapy under the control of vital body functions. Hemodialysis is ineffective.

Interaction:

The simultaneous use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine and enalapril has been studied.

Candesartan is slightly metabolized in the liver (using isoenzyme CYP2C9). No effect on isozymes CYP2C9 and CYP3A4; The effect on other cytochrome P450 isoenzymes is currently unknown. Antihypertensive agents potentiate the hypotensive effect of candesartan. The experience of using other drugs acting on RAAS shows that the simultaneous use of candesartan and potassium-sparing diuretics,potassium preparations, salt substitutes containing potassium, or other agents that can increase the serum potassium content (eg, heparin), can lead to the development of hyperkalemia.

With simultaneous use of lithium preparations and ACE inhibitors, cases of transient increase in serum lithium concentration and the development of toxic effects were noted. A similar effect is possible with simultaneous use of lithium preparations and angiotensin II receptor antagonists, which requires periodic monitoring of the concentration of lithium in the serum when combined with these drugs.

With simultaneous use of angiotensin II receptor antagonists and non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs, for example, acetylsalicylic acid more than 3 g / day, can decrease the hypotensive effect of candesartan.

As with ACE inhibitors, the simultaneous use of angiotensin II receptor antagonists and NSAIDs increases the risk of reducing kidney function, including the development of renal failure,which leads to hyperkalemia in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. All patients should receive a sufficient amount of fluid; it is necessary to monitor the function of the kidneys at the beginning of therapy and in the future.

Special instructions:

Ethnic Features

The antihypertensive effect of candesartan in patients of the Negroid race is less pronounced compared with patients of other races, and therefore an increase in the dose of KANDEKOR® and a combination with other antihypertensive drugs are more often required.

Impaired renal function

The experience of using the drug in patients with severe renal failure or end-stage renal failure (QC less than 15 ml / min) is limited. Such patients require a strict selection of the dose of KANDEKOR ® under the careful control of blood pressure.

In patients with CHF, especially older than 75 years, and in patients with impaired renal function, it is necessary to periodically monitor kidney function. During the selection of the dose of KANDEKOR ® it is recommended to monitor the concentration of creatinine and potassium in the blood serum.

Combination therapy with an ACE inhibitor in CHF

When using KANDEKOR ® in combination with an ACE inhibitor, the risk of developing side effects may increase: renal dysfunction and hyperkalemia (see "Side effect" section). In these cases, careful monitoring and monitoring of relevant laboratory indicators is necessary.

Hemodialysis

During hemodialysis, blood pressure may be particularly sensitive to blockade AT₁receptors as a result of a decrease in bcc and activation of AS AS. Therefore, patients on hemodialysis need control of blood pressure and individual selection of the dose of KANDEKOR ®.

Stenosis of the renal artery

Drugs that affect RAAS, such as ACE inhibitors, can cause hyperuricemia and hypercreatininaemia in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney. A similar effect may develop with the use of angiotensin II receptor antagonists.

Kidney transplantation

The experience of using KANDEKOR ® in patients who have recently undergone kidney transplantation is absent.

Arterial hypotension

In patients with CHF, receiving the drug KANDEKOR®, hypotension may develop. It is also possible to develop arterial hypotension in patients with reduced BCC, for example, receiving large doses of diuretics. At the beginning of therapy, care must be taken and, if necessary, compensated for BCC.

General anesthesia / surgery

When performing surgical interventions under general anesthesia, patients receiving angiotensin II receptor antagonists may develop arterial hypotension due to RAAS blockade. Very rarely arterial hypotension can be pronounced and require intravenous fluid and / or vasopressors.

Stenosis of aortic and / or mitral valves, GOKMP

The drug KANDEKOR® should be used with caution in patients with hemodynamically significant stenosis of the aortic and / or mitral valves or with GOKMP.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect RAAS; therefore, such patients are not recommended for using KANDEKOR®.

Hyperkalemia

The simultaneous use of KANDEKOR® and potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other agents capable of increasing the serum potassium content (eg, heparin) may lead to hyperkalemia in patients with hypertension.

Hyperkalemia can develop in patients with CHF who are taking KANDEKOR®. Against the background of therapy with KANDEKOR ® in patients with CHF it is recommended to conduct periodic monitoring of potassium content in blood serum, especially with simultaneous use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene, amiloride).

Are common

Patients who have vascular tone and kidney function predominantly depend on RAAS activity (for example, patients with severe decompensated CHF or concomitant renal disease, including unilateral renal artery stenosis), therapy with other drugs that affect through RAAS may be accompanied by the development of arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. This can not be ruled out for angiotensin II receptor antagonists.Excessive reduction in blood pressure in patients with ischemic cardiomyopathy or cerebrovascular disease of ischemic origin can lead to the development of myocardial infarction or stroke.

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

The effect of KANDEKOR® on vehicle management and work with complex mechanisms has not been studied, but the pharmacodynamic properties of the drug indicate that such an effect is absent.

Care must be taken when driving vehicles and engaging in potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets of 4 mg, 8 mg, 16 mg, 32 mg.

Packaging:

For 7, 14 or 15 tablets per blister.

- Blister for 7 tablets: 2, 4, 8, 12 or 14 blisters together with instructions for use in a cardboard pack;

- blister for 14 tablets: 1, 2, 4, 6 or 7 blisters together with instructions for use in a pack of cardboard;

- blister for 15 tablets: 2, 4 or 6 blisters together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-006856/10

Date of registration:20.07.2010

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA, d.d. Slovenia

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp20.07.2010

Illustrated instructions

Instructions

Candecor® (Candecor®)