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Active ingredients
Candesartan
Release form
Pills
Composition
Candesartan cilexetil 8 mg; Auxiliary substances: pregelatinized corn starch - 20.3 mg, croscarmellose sodium (primellose) - 3.5 mg, lactose monohydrate (milk sugar) - 64.5 mg, magnesium stearate - 0.7 mg, povidone K30 - 3 mg
Pharmacological effect
A selective antagonist of angiotensin II receptor type 1 (AT1 receptors), forms a strong bond with them, followed by slow dissociation. It has a vasodilating, hypotensive and diuretic effect. Does not show agonist properties (does not inhibit 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 ion channels involved in the regulation of the functions of the cardiovascular system). Blocking the AT1 receptor angiotensin II results in a compensatory dose-dependent increase in the activity of renin, the concentration of angiotensin I, angiotensin II and a decrease in the concentration of aldosterone in the blood plasma; There were no cases of severe arterial hypotension after taking the first dose of the drug, as well as withdrawal syndrome after stopping therapy. The onset of antihypertensive effect after taking the first dose usually develops within 2 hours. Against the background of continued therapy with a fixed dose, the maximum decrease in blood pressure is usually reached during 4 weeks and lasts for the duration of treatment.; Candesartan increases renal blood flow and does not alter or increases GFR, whereas vascular resistance in the kidneys and filtering Naya fraction is reduced;. No effect on the concentration of glucose and the lipid profile in patients with hypertension and Type 2 diabetes. Provides a dose-dependent smooth decrease in blood pressure.; The efficacy of the drug does not depend on the age and sex of patients.; Chronic heart failure; In patients with chronic heart failure and a decrease in the left ventricular ejection fraction of less than 40%, candesartan administration reduced the lung capillary pressure, increased activity renin and angiotensin II plasma concentrations, as well as a decrease in aldosterone concentrations.
Pharmacokinetics
Absorption and distribution; Candesartan is a prodrug for oral administration. Quickly (through ether hydrolysis) is converted to pharmacologically active candesartan. The absolute bioavailability of candesartan after ingestion of a solution of candesartan cilexetil is about 40%. The relative bioavailability of the tablet preparation compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the drug in the form of pills is about 14% and does not depend on meal times. Cmax in serum is reached after 3-4 hours. Concentration in plasma increases linearly with increasing dose in the therapeutic range (up to 32 mg). Vd - 0.13 l / kg. Binding to plasma proteins - 99.8%. Does not cumulate.; Metabolism and excretion; Slightly metabolized in the liver (20-30%) with the participation of CYP2C9 isoenzyme with the formation of an inactive derivative.; Final T1 / 2 - 9 hours. Total clearance - 0.37 ml / min / kg, while renal clearance - about 0.19 ml / min / kg. Excreted by the kidneys and with bile mainly unchanged, to a small extent as a metabolite: by the kidneys (by glomerular filtration and active tubular secretion) - 26% as candesartan and 7% as an inactive metabolite, with bile - 56% and 10%, respectively. After a single oral administration over 72 hours, more than 90% of the dose is eliminated. Pharmacokinetics in special groups of patients; In elderly patients (over 65), Cmax and AUC are increased by 50% and 80%, respectively, compared with younger patients. However, the antihypertensive effect and the incidence of side effects when using the drug does not depend on the age of the patients. In patients with impaired mild and moderate renal function, Cmax and AUC are increased by 50% and 70%, respectively, while T1 / 2 of the drug does not change by compared with patients with normal renal function. In patients with severe impaired renal function, Cmax and AUC are increased by 50% and 110%, respectively, and the T1 / 2 preparation is increased 2-fold. In patients with mild and moderately impaired liver function, an increase in AUC was observed by 23%.
Indications
- arterial hypertension; - chronic heart failure and violation of the systolic function of the left ventricle (reduction of the left ventricular ejection fraction less than 40%) (as an additional therapy to ACE inhibitors or in case of intolerance to ACE inhibitors).
Contraindications
- primary hyperaldosteronism (resistance to therapy); - severe violations of the liver and / or cholestasis; - Lactase deficiency, lactose intolerance, glucose / galactose malabsorption syndrome; - pregnancy; - lactation period; - age up to 18 years; - hypersensitivity to candesartan or other components of the drug.; The drug should be prescribed with caution in case of severe renal failure (CC less than 30 ml / min); bilateral renal artery stenosis, renal artery stenosis of a single kidney; after transplantation of a kidney in the anamnesis; with hemodynamically significant stenosis of the aortic and mitral valve; cerebrovascular diseases; CHD; hypertrophic obstructive cardiomyopathy; lower bcc; hyperkalemia.
Use during pregnancy and lactation
In experimental animal studies, kidney damage was detected in the embryonic and neonatal periods using candesartan. It is assumed that the damage mechanism is due to the pharmacological effect of the drug on the RAAS. Thus, the risk to the fetus increases with the use of candesartan in the II and III trimesters of pregnancy. Drugs that have a direct effect on the RAAS, when applied in the II and III trimesters of pregnancy, can cause fetal developmental disorders or have a negative effect on the newborn, even death.; Angiakand should not be used during pregnancy. If pregnancy occurred during the period of treatment with Angiakand, therapy should be stopped as soon as possible. It is not known whether candesartan is excreted in breast milk. Due to the possible undesirable effect on infants, Angiakand should not be used during lactation.
Dosage and administration
The drug is taken orally, regardless of the meal, 1 time per day; Arterial hypertension; The recommended initial and maintenance dose is 8 mg 1 time per day. Patients who need a further reduction in blood pressure, it is recommended to increase the dose to 16 mg 1 time / day. The maximum daily dose is 32 mg 1 time / day. The maximum antihypertensive effect occurs 4 weeks after the start of treatment.; If therapy with Angiakand does not lead to a decrease in blood pressure to the optimal target level,It is recommended to add thiazide diuretic to therapy.; Elderly patients do not need to adjust the initial dose.; Patients with mild or moderate renal dysfunction (CC more than 30 ml / min) do not need to change the initial dose of the drug.; Patients with severe dysfunction kidney (CC less than 30 ml / min) and patients with mild or moderately impaired liver function, the recommended initial dose is 4 mg 1 time / day (cansartan may be used in another form of release) .; Chronic heart failure; Recomme The recommended starting dose is 4 mg 1 time / day (you can use the drug candesartan in another form of release) .; Increasing the dose to 32 mg 1 time / day or to the maximum tolerated dose is carried out by doubling it at least 2 weeks apart.; Elderly patients age and patients with impaired renal function and / or liver do not need to change the initial dose of the drug.; Angiakand can be used in conjunction with other drugs used in the treatment of chronic heart failure, such as ACE inhibitors, beta-adrenoblock tori, diuretics and cardiac glycosides.
Side effects
Arterial hypertension; The most common side effects (≥1 / 100, <1/10); On the CNS side: dizziness, weakness, headache; On the musculoskeletal system: back pain. On the laboratory side : decrease in hemoglobin, hypercreatininemia, increased urea concentration in the blood, hyperkalemia, hyponatremia, increased ALT activity; Other: respiratory infections; Chronic heart failure; The following side effects are most common (≥1 / 100, <1/10) .; Cardiovascular systems: excessive decrease in blood pressure.; From the urinary system: impaired kidney function; From laboratory tests: hypercreatininemia, increased urea concentration in the blood, hyperkalemia.; During post-marketing use of candesartan, the following side effects were reported (frequency - less than 1/10 000); On the part of the blood-forming organs: leukopenia, neutropenia and agranulocytosis; On the part of the CNS: dizziness, weakness, headache; On the part of the respiratory system: cough.; On the part of the digestive system: nausea,increased activity of hepatic transaminases, abnormal liver function or hepatitis.; From the urinary system: impaired renal function, including acute renal failure in susceptible patients.; From the musculoskeletal system: back pain, arthralgia, myalgia; swelling, skin rash, pruritus, urticaria.; From the laboratory indicators: hyperkalemia, hyponatremia.
Overdose
Symptoms: excessive decrease in blood pressure, dizziness, tachycardia.; Treatment: conducting symptomatic therapy; The patient should be placed in a horizontal position with a low head, if necessary, an increase in the BCC by infusion of a 0.9% sodium chloride solution, and the use of sympathomimetics. Hemodialysis is ineffective.
Interaction with other drugs
With the simultaneous use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine and enalapril, clinically significant interactions were not detected. toxic reactions. Adverse reactions can also occur with the use of angiotensin II receptor antagonists, and therefore, it is recommended to control the concentration of lithium in the blood serum with the combined use of these drugs. 2) and non-selective NSAIDs, for example, acetylsalicylic acid at a dose of> 3 g / day, the hypotensive effect of candesartan may be reduced. As in the case of ACE inhibitors, the simultaneous use of angiotensin II receptor antagonists and NSAIDs increases the risk of reducing renal function, up to 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 kidney function at the beginning of therapy and in the future.; Medications affecting the RAAS,can increase the concentration of urea and creatinine in the blood of patients with bilateral renal artery stenosis or single kidney artery stenosis.; Diuretics and other antihypertensive drugs increase the risk of arterial hypotension; Potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other drugs, which may increase the serum potassium content (eg, heparin), increase the risk of developing hyperkalemia.; Candesartan is metabolized to the liver to a small extent (isofer UNT CYP2C9). Studies on the interaction did not reveal the effect of candesartan on the isoenzymes CYP2C9 and CYP3A4. The effect on other isoenzymes of the cytochrome P450 system has not been studied.
special instructions
Before and during treatment, control of blood pressure, kidney function (plasma creatinine), potassium, lithium in serum (with combined use of drugs) is necessary .; Hypotension; In patients with chronic heart failure, on the background of therapy with Angiakand drug may develop arterial hypotension. As with the use of other drugs that affect the RAAS, the cause of arterial hypotension in patients with arterial hypertension may be a decrease in BCC, as observed in patients receiving diuretics in high doses. Therefore, at the beginning of therapy, caution should be taken and, if necessary, correction of hypovolemia.; Renal artery stenosis; In patients with bilateral renal artery stenosis or arterial stenosis of the only kidney, drugs that affect the RAAS, in particular, ACE inhibitors, can cause an increase in urea concentration and serum creatinine. Such effects can be expected with the appointment of angiotensin II receptor antagonists.; Kidney transplantation; There are no data on the use of candesartan in patients who have recently undergone a kidney transplant.; Kidney dysfunction; Against the background of therapy with Angiakand, as well as using other drugs suppressing the RAAS, some patients may have impaired renal function. When using the drug Angiakand in patients with arterial hypertension and severe renal insufficiency, it is recommended to periodically monitor the content of potassium and creatinine in the blood serum.Clinical experience with candesartan in patients with severely impaired renal function or end-stage renal failure (CC less than 15 ml / min) is limited. In patients with chronic heart failure, it is necessary to periodically monitor renal function, especially in patients 75 years of age and older, and also in patients with impaired renal function. At higher doses of the drug Angiakand it is also recommended to control the content of potassium and creatinine in the blood plasma. Combined use with ACE inhibitors in chronic heart failure. When using 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 control of laboratory parameters is necessary. General anesthesia and surgery Patients receiving angiotensin II receptor antagonists during general anesthesia and during surgical procedures may develop arterial hypotension as a result of blockade of RAAS. Very seldom may occur cases of severe arterial hypotension requiring on / in the liquid and / or vasopressor;. Stenosis of the aortic and mitral valve (hypertrophic obstructive cardiomyopathy); In applying Angiakand preparation, as well as other vasodilators, in patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant caution should be exercised with the type of aortic and / or mitral valve.; Primary hyper aldosteronism; Patients with primary hyper aldosteronism are usually a resistance treatment of antihypertensive drugs that affect the activity of the RAAS. In this regard, the drug Angiakand is not recommended for use in these patients.; Hyperkalemia; Clinical experience with other drugs that affect the RAAS, shows that the simultaneous use of candesartan with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that may increase blood potassium levels (for example, heparin), may lead to the development of hyperkalemia in patients with arterial hypertension.; General; Patients in whom vascular tone and kidney function mainly depend on the activity of the RAAS (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis), are particularly sensitive to drugs acting on the RAAS.The use of such agents is accompanied in these patients with severe arterial hypotension, azotemia, oliguria and, less commonly, acute renal failure. The possibility of the development of these effects can not be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary artery disease or cerebrovascular disease of ischemic origin, when using any antihypertensive drugs, can lead to myocardial infarction or stroke; use caution when driving and doing other potentially hazardous activities that require increased concentration and speed psychomotor reactions.