Expiration date: 08/2026
Dosage form: tablets
Composition:
Dosage 8 mg
1 tablet contains:
active substance: candesartan in has tsileksetil 8 mg,
excipients: corn starch pregelatinization to 20.3 mg, croscarmellose sodium (Primerose) - 3.5 mg, lactose monohydrate (milk sugar) and 64.5 mg, magnesium stearate - 0.7 mg, povidone-K30 - 3 mg.
A dosage of 16 mg
1 tablet contains:
active substance: candesartan in has tsileksetil 16 mg,
excipients: corn starch pregelatinization – 23,8 mg, croscarmellose sodium (Primerose) 5 mg, lactose monohydrate (milk sugar) - 90 mg, magnesium stearate - 1 mg, povidone-K30 – 4,2 mg.
Dosage 32 mg
1 tablet contains:
active substance: candesartan in has tsileksetil 32 mg,
excipients: corn starch pregelatinization – 27,5 mg, croscarmellose sodium (Primerose) - 7 mg, lactose monohydrate (milk sugar) is 126 mg magnesium stearate 1.5 mg, povidone-K30 – 6 mg.
Description:
Tablets white or almost white, round, lenticular.
Pharmacotherapeutic group: angiotensin II receptor antagonist.
Pharmacological properties:
Pharmacodynamics
Candesartan is a selective antagonist of the angiotensin II receptor type 1 (AT1 receptors), forming with them a strong relationship with subsequent slow dissociation. Has vasodilating, hypotensive and diuretic action. Does not exhibit the properties of an agonist (does not inhibit angiotensin converting enzyme (ACE) and does not lead to accumulation of bradykinin or substance P, is not associated with other hormone receptors, does not block ion channels involved in the regulation of the functions of the cardiovascular system). In the blocking AT1-receptors of angiotensin II dose-dependent compensatory increase in renin activity, concentration of angiotensin I, angiotensin II and reduced concentration of aldosterone in blood plasma.
Hypertension
The antihypertensive effect is due to a decrease in total peripheral vascular resistance (OPSS), with no effect on heart rate (HR). There were no cases of arterial expressed hypotension after the first dose of the drug, and the syndrome "cancel" after the cessation of therapy. A start of antihypertensive action after the first dose usually develops within 2 hours. Against the background of ongoing drug therapy in a fixed dose maximum reduction in blood pressure (BP) is usually achieved within 4 weeks and maintained throughout the treatment.
Candesartan increases renal blood flow and does not change or increases glomerular filtration rate, whereas vascular resistance in the kidney and the filtration fraction are reduced.
Does not affect glucose concentration and lipid profile in patients with arterial hypertension and diabetes mellitus 2 type. Provides dose-dependent gradual decline in blood pressure.
Age and gender do not affect the efficacy of the drug.
Chronic heart failure
In patients with chronic heart failure and reduced ejection fraction of left ventricle less than 40% of the candesartan in admission contributed to the reduction of systemic vascular resistance and capillary pressure in the lungs, increased renin activity and concentration of angiotensin II in blood plasma and decrease the concentration of aldosterone.
Pharmacokinetics
Candesartan is a prodrug for oral administration. Quickly (via the ether hydrolysis) is converted into the pharmacologically active candesartan. The absolute bioavailability of candesartan in after ingestion of a solution of candesartan in has tsileksetil is about 40 %. The relative bioavailability of tablets of the drug compared to an oral solution is approximately 34 %. Thus, the estimated absolute bioavailability of a tablet form is about 14% and does not depend on time of meals. The maximum concentration (Cmax) in plasma is reached after 3-4 h. Concentration in blood plasma increases linearly with increasing doses in the therapeutic range (up to 32 mg). The volume of distribution of 0.13 l/kg. the Relationship with blood plasma proteins is 99.8 %.
Slight metabolised in the liver (20-30%), with the participation of isoenzyme of cytochrome P450 CYP2C9 with the formation of active derivative. The final elimination half-life (T1/2) - 9 p.m. Not koumouliruet. Total clearance – 0,37 ml/min/kg, with renal clearance of about 0.19 ml/min/kg. Excreted by the kidneys and bile mostly in unchanged form, to a small extent in the form of metabolites: kidneys (glomerular filtration and active tubular secretion) – 26 % in the candesartan in kind and 7% in the form of inactive metabolite in the bile is 56% and 10 %, respectively. After a single ingestion for 72 h displayed more than 90 % of the dose.
In elderly patients (over 65 years) Cmax and area under the curve "concentration-time" (AUC) increased by 50% and 80 %, respectively, compared to the young 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 mild to moderate degrees of renal impairment Cmax and AUC are increased by 50% and 70 %, respectively, whereas T1/2 of the drug is not changed compared to patients with normal renal function.
In patients with severe renal impairment Cmax and AUC are increased by 50% and 110 %, respectively, and T1/2 of the drug increased by 2 times.
In patients with mild to moderate degree of liver dysfunction was observed increase in AUC of 23 %.
Indications for use:
Hypertension.
Chronic heart failure and systolic dysfunction of the left ventricle (reduced ejection fraction of left ventricle less than 40 %) as adjunctive therapy to angiotensin converting enzyme inhibitors (ACE) or in case of intolerance to ACE inhibitors.
Contraindications:
- hypersensitivity to candesartan or other components of the drug,
- lactase deficiency, lactose intolerance, glucose-galactose malabsorption,
- pregnancy,
- lactation,
- primary hyperaldosteronism (resistance to treatment),
- severe liver and/or cholestasis,
- the age 18 years.
With caution:
Severe renal insufficiency (creatinine clearance (CC) less than 30 ml/min) bilateral renal artery stenosis, renal artery stenosis to a solitary kidney, after kidney transplantation, a history of hemodynamically signicant stenosis of the aortic or mitral valve disease, cerebrovascular disease, ischemic heart disease, hypertrophic obstructive cardiomyopathy, reduction of volume of circulating blood (BCC), hyperkalemia.
Use in pregnancy and lactation:
In studies on animals revealed kidney damage in the embryonic and neonatal periods with the use of candesartan in. It is assumed that the mechanism of damage due to the pharmacological effects of the drug on the renin-angiotensin-aldosterone system (RAAS).
The human embryo is the circulatory system of the kidney, which depends on the development of the RAAS begins to form in the second trimester of pregnancy. Thus, the risk to the fetus increases with the use of candesartan in the second and third trimesters of pregnancy. Drugs have a direct effect on the RAAS can cause abnormalities of fetal development or to have a negative effect on the newborn, including death, in applying the drug in the second and third trimesters of pregnancy.
Angieland should not be used during pregnancy. If pregnancy is detected during treatment with the drug, therapy should be terminated as quickly as possible.
Not known whether candesartan is allocated in breast milk. In connection with possible adverse effects on infants, Angieland should not be used during breast-feeding.
Method of application and dose:
Inside, regardless of the meal, 1 time a day.
Hypertension
The recommended starting and maintenance dose is 8 mg 1 times per day. Patients requiring 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 within 4 weeks after the start of treatment.
If the therapy with Angieland does not reduce blood pressure to the optimal target level, it is recommended to add to the therapy thiazide diuretic.
In patients older initial dose adjustment is not required.
In patients with easy or moderate impaired renal function (QC over 30 ml/min) no alteration to the initial dose of the drug.
Patients with severe impairment of renal function (KK less 30 ml/min) and patients with hepatic impairment mild and moderate: recommended initial dose – 4 mg 1 time a day (perhaps the use of the drug candesartan in other form of release).
Chronic heart failure
The recommended initial dose is 4 mg 1 time a day (perhaps the use of the drug candesartan in other form of release).
Increase the dose to 32 mg once a day 1 or until maximum tolerated dose is held by doubling at intervals of not less than 2 weeks.
Elderly patients and patients with impaired renal function and/or liver does not require modification of the initial dose.
Angiokard can be used in conjunction with other drugs used in the treatment of chronic heart failure, e.g. ACE inhibitors, beta-adrenoblokatorami, dioretikami and cardiac glycosides.
Side effects:
Hypertension
The most common side effects (>,1/100, <,1 10="" :="" br="">,part of the Central nervous system: dizziness, weakness, headache,
From the side of musculoskeletal system and connective tissue: back pain,
Other: respiratory infections,
The laboratory parameters: reduced hemoglobin, gipercreatininemia, increasing the concentration of urea in the blood, hyperkalemia, hyponatremia, increased activity of alanine aminotransferase (ALT).
Chronic heart failure
The most common side effects (>,1/100, <,1 10="" :="" br="">,From the side of cardiovascular system: expressed lower AD,
From the side of urinary system: violation of kidney function,
Laboratory changes: gipercreatininemia, increasing the concentration of urea in the blood, hyperkalemia.
During post-marketing use of candesartan in was reported the following side effects (frequency less than 1/10 000):
Organs of hematopoiesis: leukopenia, neutropenia and agranulocytosis,
Laboratory parameters: hyperkalemia, hyponatremia,
From the Central nervous system: dizziness, weakness, headache,
From the digestive system: nausea,
The liver and biliary tract: increased activity of "liver" transaminases, abnormal liver function or hepatitis,
Allergic reactions: angioedema, skin rash, itching, hives,
From the side of musculoskeletal system and connective tissue: back pain, arthralgia, myalgia,
From the side of urinary system: impaired renal function, including acute renal failure in predisposed patients.
The respiratory system: cough.
Overdose:
Symptoms: expressed lower AD, dizziness, tachycardia.
Treatment: symptomatic, to lay the patient on his back, to raise the lower extremities above the level of the head, if necessary - increase the volume of circulating blood (BCC) by infusion of 0.9% solution of sodium chloride, the use of sympathomimetics. Hemodialysis is ineffective.
Interaction with other medicinal products:
With the concomitant use of candesartan in hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril clinically significant interactions have not been identified.
With simultaneous use of drugs lithium and ACE inhibitors have reported a reversible increase in the concentration of lithium in the blood serum and the development of toxic reactions. Adverse reactions can occur when the use of receptor antagonists of angiotensin II, therefore, it is recommended to monitor the level of lithium in serum by the combined use of these drugs.
While the use of antagonists of angiotensin II receptor and non-steroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2) and non-selective NSAIDs, e.g., aspirin, more than 3 g/day, may decrease the hypotensive effect of candesartan in. As with ACE inhibitors, concomitant use of antagonists of angiotensin II receptor and NSAIDs increases the risk of loss of kidney function, until 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 liquid. It is necessary to monitor renal function at the beginning of therapy in the future.
Drugs that affect the RAAS can increase the concentration of urea and creatinine in patients with bilateral renal artery stenosis or stenosis of the artery only kidneys.
Diuretics and other antihypertensives increased risk of hypotension.
Kalisberegate dioretiki, drugs potassium, salt substitutes containing potassium and other drugs that can increase potassium levels in the blood serum (e.g., heparin), increase the risk of hyperkalemia.
Candesartan metabolized in the liver to a small extent (CYP2C9 isoenzyme). The study on the interaction showed no effect of candesartan in the isozymes CYP2C9 and CYP3A4. Effect on other isoenzymes of cytochrome P450 have not been studied.
Special instructions:
Before and during treatment requires monitoring AD, kidney function (creatinine in blood plasma), content of potassium, of lithium in the blood serum (the combined use of medicines).
Hypotension
In patients with chronic heart failure during therapy with the drug Angieland may develop hypotension. As the use of other drugs affecting the RAAS, the cause of arterial hypotension in patients with arterial hypertension can be a decrease in BCC, as has been observed in patients receiving large doses of diuretics. Therefore, at the beginning of therapy should be used with caution and, if necessary, correction of hypovolemia.
Renal artery stenosis
In patients with bilateral renal artery stenosis or stenosis of artery only kidneys drugs affecting the RAAS, in particular ACE inhibitors, may cause increased concentrations of urea and creatinine in the serum. Similar effects can be expected in the appointment of antagonists of angiotensin II receptors.
Kidney transplant
Data on the use of candesartan in patients who recently had a kidney transplant, no.
Violation of kidney function
On the background of drug therapy Angieland, as the use of other means, oppressive RAAS, some patients may experience dysfunction of the kidneys.
In applying the drug Angieland in patients with hypertension and renal insufficiency is recommended to periodically monitor potassium and creatinine in serum. Clinical experience with the use of candesartan in patients with severe impairment of renal function or end-stage renal failure (KK less 15 ml/min) is limited.
In patients with chronic heart failure it is necessary to periodically monitor renal function, especially in patients aged 75 years and older, and in patients with impaired renal function. When the dose of the drug Angieland is also recommended to monitor potassium and creatinine in blood plasma.
Combined use with ACE inhibitors in chronic heart failure
In applying the drug Angieland in combination with ACE inhibitors may increase the risk of side effects, especially renal dysfunction and hyperkalemia. In these cases, careful monitoring and control of laboratory parameters.
General anesthesia and surgery
Patients receiving antagonists of angiotensin II receptors during General anesthesia and during surgery may develop hypotension due to the blockade of RAAS. Very rarely observed cases of severe arterial hypotension, requiring intravenous fluids and/or vasopressors.
Stenosis of the aortic and mitral valve (hypertrophic obstructive cardiomyopathy)
In applying the drug Angieland, as with other vasodilators patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant aortic stenosis and/or mitral valve should be used with caution.
Primary hyperaldosteronism
Patients with primary hyperaldosteronism is usually resistant to treatment, antihypertensive drugs affecting the activity of the RAAS. In this regard, the drug Angieland is not recommended in these patients.
Hyperkalemia
Clinical experience with the use of other drugs affecting the RAAS, shows that concurrent use of candesartan in potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium, or other drugs that may increase potassium levels (e.g. heparin) may lead to the development of hyperkalemia in patients with hypertension.
Common
Patients in whom vascular tone and renal function depend predominantly on the activity of the RAAS (e.g., patients with severe congestive heart failure or kidney disease, including renal artery stenosis), are particularly sensitive to drugs acting on the RAAS. The use of such tools in these patients is accompanied by an abrupt arterial hypotension, azotemia, oliguria and rarely acute renal failure. The possibility of the development of the listed effects may not be excluded and the application of antagonists of angiotensin II receptors. A sharp decrease in blood pressure in patients with ischemic heart disease or cerebrovascular disease of ischemic origin, with the use of any antihypertensive drugs, could lead to the development of myocardial infarction or stroke.
Effects on ability to drive transportation vehicles, mechanisms.
During treatment may occur dizziness, weakness, so you need to be careful when driving and occupation of other potentially hazardous activities, require high concentration and psychomotor speed reactions.
Form of issue:
Tablets 8 mg, 16 mg and 32 mg.
For 7, 10, 20, 28 or 30 tablets in a contour cell package made of polyvinylchloride film and aluminum foil printed patent.
1, 2, 3, 4, 8 contour cell packs of 7 tablets or 1, 2, 3, 4, 5, 6 contour sells packaging of 10 tablets or 1, 2, 3 contour sells packaging of 20 tablets, or 1, 2 contour cell packs of 28 tablets, or 1, 2 contour cell packs of 30 tablets along with instructions for use is placed in cardboard pack.
Storage conditions:
In a dry, protected from light place at temperature not above 25 C. Keep out of reach of children.
Expiration date:
2 years. Do not use after expiration date.
