Angiakand - instructions for use, dose, side effects, contraindications

Excipients: pregelatinised maize starch - 20.3 mg Sodium croscarmellose (primelloza) - 3.5 mg, lactose monohydrate (milk sugar) - 64.5 mg Magnesium stearate - 0.7 mg, povidone K30 - 3 mg.

Dosage of 16 mg

1 tablet contains:

active substance: candesartan cilexetil 16 mg;

Excipients: pregelatinised maize starch - 23.8 mg Sodium croscarmellose (primelloza) - 5 mg, lactose monohydrate (milk sugar) - 90 mg Magnesium stearate - 1 mg, povidone K30 - 4.2 mg.

The dosage of 32 mg

1 tablet contains:

active substance: candesartan cilexetil 32 mg;

auxiliary substancesa: corn pregelatinized corn starch - 27.5 mg, croscarmellose sodium (impellose) - 7 mg, lactose monohydrate (sugar milk) - 126 mg, magnesium stearate -1.5 mg, povidone-K30 - 6 mg.

Description:

Tablets are white or almost white, round, biconvex.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.06 Candesartan

Pharmacodynamics:

Candesartan is a selective antagonist of angiotensin II receptor type 1 (AT1 receptors), forms a strong bond with them, followed by a slow dissociation. Has vasodilating, hypotensive and diuretic action. Does not exhibit agonist properties (not inhibit 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 block the ionic channels involved in the regulation of cardiovascular function). As a result of blocking of AT1-receptors of angiotensin II, a compensatory dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in plasma aldosterone concentration occurs.

Arterial hypertension

The antihypertensive effect is due to a decrease in the total peripheral vascular resistance (OPSS), with no effect on the heart rate (heart rate).No cases of severe arterial hypotension after taking the first dose of the drug, as well as the syndrome of "withdrawal" after discontinuation of therapy. The onset of antihypertensive action after taking the first dose usually develops within 2 hours. Against the background of ongoing therapy with the drug in a fixed dose, the maximum reduction in blood pressure (BP) is usually achieved within 4 weeks and persists throughout the treatment.

Candesartan increases renal blood flow and does not change or increases the rate of glomerular filtration, whereas vascular resistance in the kidney and filtration fraction are reduced.

Does not affect the concentration of glucose and the lipid profile in patients with arterial hypertension and type 2 diabetes. Provides a dose-dependent smooth decrease in blood pressure.

Age and sex do not affect the effectiveness of the drug.

Chronic heart failure

In patients with chronic heart failure and a lower left ventricular ejection fraction of less than 40%, candesartan administration contributed to a reduction in OPSS and capillary pressure in the lungs, increased renin activity and angiotensin II concentration in blood plasma, as well as a decrease in aldosterone concentration.

Pharmacokinetics:

Candesartan is a prodrug for oral administration. Rapidly (via ether hydrolysis) is converted into a pharmacologically active candesartan. 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 is about 14% and does not depend on the time of ingestion. The maximum concentration (Cmah) in the blood serum is achieved after 3-4 hours. The concentration in the blood plasma increases linearly with increasing dose in the therapeutic interval (up to 32 mg). The volume of distribution is 0.13 l / kg. Connection with blood plasma proteins - 99,8%.

It is slightly metabolized in the liver (20-30%) with the participation of cytochrome P450 isoenzyme CYP2C9 to form an inactive derivative. The final half-life (T1 / 2) is 9 hours. It does not accumulate.The total clearance is 0.37 ml / min / kg, with a kidney clearance of about 0.19 ml / min / kg. It is excreted by the kidneys and with bile mainly in unchanged form, to an insignificant degree in the form of a metabolite: by kidneys (by glomerular filtration and active tubular secretion) - 26% in the form of candesartan and 7% - in the form of an inactive metabolite, with bile - 56% and 10%, respectively. After a single intake within 72 hours, more than 90% of the dose is withdrawn.

In elderly patients (over 65 years) Cmax and the area under the concentration-time curve (AUC) increase by 50% and 80%, respectively, compared with young patients. However, the antihypertensive effect and incidence of side effects with the drug do not depend on the age of the patients.

In patients with mild to moderate renal impairment, Cmax and AUC increase by 50% and 70%, respectively, whereas T1 / 2 of the drug does not change in comparison with patients with normal renal function.

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

In patients with mild to moderate liver function disorders, an increase AUC on 23%.

Indications:

Arterial hypertension.

Chronic heart failure and impaired systolic function of the left ventricle (reduction of the left ventricular ejection fraction of less than 40%) as adjunctive therapy to angiotensin-converting enzyme (ACE) inhibitors or intolerant ACE inhibitors.

Contraindications:

Hypersensitivity to candesartan or other components of the drug; deficiency of lactase, lactose intolerance, glucose-galactose malabsorption; pregnancy; lactation period; primary hyperaldosteronism (resistance to therapy); severe liver dysfunction and / or cholestasis; age to 18 years.

Carefully:

Severe renal insufficiency (creatinine clearance less than 30 ml / min), bilateral stenosis of the renal arteries, stenosis of the renal artery of a single kidney, after a kidney transplant in history, hemodynamically significant stenosis of the aortic and mitral valve, cerebrovascular disease, ischemic heart disease, hypertrophic obstructive cardiomyopathy, decreased circulating blood volume (BCC), hyperkalemia.

Pregnancy and lactation:

In animal studies, kidney damage in the embryonic and neonatal periods was identified with candesartan.It is assumed that the mechanism of damage is due to the pharmacological action of the drug on the renin-angiotensin-aldosterone system (RAAS).

In the human embryo, the kidney blood supply system, which depends on the development of RAAS, begins to form in the second trimester of pregnancy. Thus, the risk to the fetus increases with candesartan in the second and third trimesters of pregnancy. Drugs that have a direct effect on RAAS can cause fetal developmental disorders or have a negative effect on the newborn, up to a lethal outcome, when the drug is used in the second and third trimesters of pregnancy.

Anhiakand should not be used during pregnancy. If pregnancy is detected during drug treatment, therapy should be discontinued as soon as possible. It is not known whether candesartan in breast milk. Due to the possible undesirable effect on infants, Angiocand should not be used during lactation.

Dosing and Administration:

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

Arterial hypertension

The recommended initial and maintenance dose is 8 mg 1 time per day. Patients who require a further reduction in blood pressure, it is recommended to increase the dose to 16 mg once a day. The maximum daily dose of the drug is 32 mg once a day.

The maximum antihypertensive effect occurs 4 weeks after the start of treatment.

In the event that therapy with the drug Angiakand does not lead to a decrease in blood pressure to the optimal target level, it is recommended to add a thiazide diuretic to therapy.

In elderly patients correction of the initial dose is not required.

In patients with mild to moderate renal impairment (QC more than 30 ml / min) Do not change the initial dose of the drug.

Patients with severe renal dysfunction (SC less than 30 ml / min) and patients with mild to moderate liver dysfunction: the recommended initial dose is 4 mg 1 time per day (possibly using candesartan in another release form).

Chronic heart failure

The recommended initial dose is 4 mg 1 time per day (possibly using candesartan in another release form).

Increasing the dose to 32 mg once a day or up to the maximum tolerated dose is done by doubling it with an interval of at least 2 weeks.

Older patients and patients with impaired renal and / or liver function Do not change the initial dose of the drug.

Angiocand can be used in conjunction with other drugs used in the therapy of chronic heart failure, for example, ACE inhibitors, beta-blockers, diuretics and cardiac glycosides.

Side effects:

Arterial hypertension

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

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

From the musculoskeletal system, connective tissue: backache.

Other: respiratory infections.

Laboratory indicators: decreased hemoglobin, hypercreatininaemia, increased urea concentration in the blood, hyperkalemia, hyponatremia, increased activity of alanine aminotransferase (ALT).

Chronic heart failure

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

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

From the side of the urinary system: impaired renal function.

Laboratory changes: hypercreatininaemia, increased urea concentration in the blood, hyperkalemia.

During the post-marketing application of candesartan, the following side effects were reported (frequency - less than 1/10 000):

On the part of the organs of hematopoiesis: leukopenia, neutropenia and agranulocytosis.

Laboratory indicators: hyperkalemia, hyponatremia.

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

From the digestive system: nausea.

From the liver and biliary tract: increased activity of "liver" transaminases, a violation of liver function or hepatitis.

Allergic reactions: angioedema, skin rash, itching, urticaria.

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

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

From the respiratory system: cough.

Overdose:

Symptoms: marked decrease in blood pressure, dizziness, tachycardia.

Treatment: symptomatic, put the patient on the back, raise the lower limbs above the head level, if necessary - increase the volume of circulating blood (BCC) by infusing 0.9% sodium chloride solution, using sympathomimetics. Hemodialysis is ineffective.

Interaction:

In the combined use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine, and enalapril, no clinically relevant interactions have been identified.

With simultaneous use of lithium preparations with ACE inhibitors, a reversible increase in serum lithium concentration and the development of toxic reactions were reported. Adverse reactions can occur with angiotensin II receptor antagonists, and therefore, it is recommended to monitor the level 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 cyclooxygenase-2 (COX-2) inhibitors and nonselective NSAIDs, for example, acetylsalicylic acid, more than 3 g / day, the hypotensive effect of candesartan may decrease. As in the case of inhibitors ACE, simultaneous use of antagonists of angiotensin II receptors and NSAIDs increases the risk of reducing kidney function, up to the development of renal failure, leading 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 kidney function at the beginning of therapy and in the future.

Drugs that affect RAAS can increase the concentration of urea and creatinine in the blood in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney.

Diuretics and other antihypertensives increase the risk of developing arterial hypotension.

Potassium-sparing diuretics, potassium supplements, salt substitutes that contain potassium, and other drugs that can increase serum potassium levels (eg, heparin) increase the risk of hyperkalemia.

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

Special instructions:

Before and during treatment, it is necessary to monitor blood pressure, kidney function (creatinine in the blood plasma), potassium, lithium in the blood serum (with combined use of medicines).

Arterial hypotension

In patients with chronic heart failure on the background of therapy with the drug Angiakand may develop arterial hypotension. As with the use of other drugs that affect RAAS, the cause of the development of arterial hypotension in patients with hypertension may be a decrease in BCC, as observed in patients receiving large doses of diuretics. Therefore, at the beginning of therapy, care should be taken and, if necessary, correct hypovolemia.

Stenosis of the renal artery

In patients with bilateral renal artery stenosis or stenosis of the single kidney artery, drugs that affect RAAS, 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 in patients who have recently undergone a kidney transplant are not available.

Impaired renal function

Against the background of therapy with the drug Angiakand, as with the use of other drugs that oppress RAAS, in some patients, renal dysfunction may occur. When using the drug Angiakand in patients with arterial hypertension and severe renal failure, it is recommended to periodically monitor the content of potassium and creatinine in the blood serum. Clinical experience with candesartan in patients with severe renal dysfunction or end-stage renal disease (QC less than 15 mL / min) is limited.

Patients with chronic heart failure need periodic monitoring of kidney function, especially in patients aged 75 years and older, as well as in patients with impaired renal function. With an increase in the dose of the drug, Anhiakand is also recommended to monitor the content of potassium and creatinine in the blood plasma. Co-administration with ACE inhibitors in chronic heart failure

With the use of the drug Angiakand in combination with ACE inhibitors, the risk of side effects may increase, especially renal dysfunction and hyperkalemia. In these cases, careful monitoring and monitoring of laboratory indicators is necessary.

General anesthesia and surgery

Patients receiving angiotensin II receptor antagonists can develop arterial hypotension as a result of blockade of RAAS 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 (hypertrophic obstructive cardiomyopathy)

Care should be taken when using the preparation Anghiakand, as well as other vasodilators, in patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant stenosis of the aortic and / or mitral valve.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the activity of RA AS.In this regard, the drug Angiakand is not recommended for use in such patients.

Hyperkalemia

Clinical experience with other drugs that affect RAAS shows that simultaneous use of candesartan with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase the potassium content in the blood (eg heparin) can lead to the development of Hyperkalemia in patients with arterial hypertension.

Are common

Patients in whom vascular tone and renal function predominantly depend on the activity of RAAS (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis) are particularly sensitive to drugs acting on RAAS. The use of such drugs is accompanied in these patients by acute arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. The possibility of developing these effects can not be ruled out when angiotensin II receptor antagonists are used. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular disease of ischemic origin,when using any antihypertensive drugs, can lead to the development of myocardial infarction or stroke.

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

During the treatment period, dizziness and weakness may occur, so care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets 8 mg, 16 mg and 32 mg.

Packaging:

By 7, 10, 20, 28 or 30 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2, 3, 4, 8 contour cell packs of 7 tablets or 1, 2, 3, 4, 5, 6 contour cell packs of 10 tablets, or 1, 2, 3 box packs of 20 tablets, or 1, 2 contour packs of 28 tablets, or 1, 2 contour packs of 30 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001890

Date of registration:25.10.2012 / 13.03.2015

Expiration Date:25.10.2017

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp04.09.2017

Illustrated instructions

Instructions

Angiakand (Angiakand)