Description
Release form
Pills
Packing
28 pcs.
Pharmacological action
Pharmacodynamics
Candesartan is a selective antagonist of type 1 angiotensin receptors (AT1 receptors), forms a strong bond with them, followed by slow dissociation. It has a vasodilating, hypotensive and diuretic effect. It does not exhibit the properties of an agonist (it does not inhibit the angiotensin converting enzyme (ACE) and does not lead to the accumulation of bradykinin or substance P, it does not bind to receptors of other hormones, it does not block the ion channels involved in the regulation of the functions of the cardiovascular system). As a result of the blocking of AT1 receptors of angiotensin II, 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 blood plasma occurs.
Arterial 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 severe arterial hypotension after taking the first dose of the drug, as well as the “withdrawal” syndrome after discontinuation of therapy. The onset of antihypertensive action after taking the first dose usually develops within 2 hours. Against the background of continued therapy with the drug in a fixed dose, the maximum decrease in blood pressure (BP) is usually achieved within 4 weeks and remains throughout the treatment.
Candesartan increases renal blood flow and does not alter or increase glomerular filtration rate, while vascular resistance in the kidneys and filtration fraction decrease.
Does not affect glucose concentration and lipid profile in patients with arterial hypertension and type 2 diabetes. Provides a dose-dependent smooth decrease in blood pressure.
Age and gender do not affect the effectiveness of the drug.
Chronic heart failure
In patients with chronic heart failure and a decrease in the ejection fraction of the left ventricle of less than 40%, candesartan was used to reduce OPSS and capillary pressure in the lungs, increase renin activity and angiotensin II concentration in blood plasma, and also reduce the concentration of aldosterone.
Pharmacokinetics
Candesartan is an oral prodrug. Quickly (through ether hydrolysis) turns into pharmacologically active candesartan. The absolute bioavailability of candesartan after oral administration of candesartan cilexetil is about 40%. The relative bioavailability of the tablet formulation compared to the oral solution is approximately 34%. Thus, The estimated absolute bioavailability of the tablet form is about 14% and does not depend on the time of eating. The maximum concentration (Cmax) in blood serum is reached after 3-4 hours. The concentration in the blood plasma increases linearly with increasing dose in the therapeutic interval (up to 32 mg). Distribution volume – 0,13 l / kg. Communication with blood plasma proteins – 99.8%.
Slightly metabolized in the liver (20-30%) with the participation of the cytochrome P450 isoenzyme CYP2C9 with the formation of an inactive derivative. The final half-life (T1 / 2) is 9 hours. It does not cumulate. The total clearance is 0.37 ml / min / kg, while the renal clearance is about 0.19 ml / min / kg. It is excreted by the kidneys and with bile mainly in an unchanged form, to a small extent – in the form of a metabolite: 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 oral administration for 72 hours, more than 90% of the dose is excreted.
In elderly patients (over 65), Cmax and the area under the concentration-time curve (AUC) increase by 50% and 80%, respectively, compared with younger patients. However, the antihypertensive effect and the incidence of side effects when using 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, while T1 / 2 of the drug does not change compared with patients with normal renal function.
In patients with severely impaired renal function, Cmax and AUC increase by 50% and 110%, respectively, and T1 / 2 of the drug increases by 2 times.
In patients with mild to moderate hepatic impairment, an increase in AUC of 23% was observed.
Indications
– Arterial hypertension.
– Chronic heart failure and impaired systolic function of the left ventricle (decrease in the ejection fraction of the left ventricle of less than 40%) as an adjunct therapy to angiotensin converting enzyme (ACE) inhibitors or intolerance to ACE inhibitors.
Contraindications
hypersensitivity to candesartan or other components Angiakand
lactase deficiency, lactose intolerance, glucose-galactose malabsorption
primary hyperaldosteronism / srpk srdl .
Precautions: severe renal failure (Cl creatinine less than 30 ml / min) bilateral renal artery stenosis of a single kidney renal artery stenosis after a kidney transplant has a history of hemodynamically significant aortic and mitral valve stenosis cerebrovascular disease coronary heart disease hypertrophic obstructive cardioma.
Use in pregnancy and lactation
In animal studies, kidney damage was detected in the embryonic and neonatal periods with the use of candesartan. Supposed that the damage mechanism is due to the pharmacological effect of the drug on RAAS.
In a human embryo, the blood supply system of the kidney, which depends on the development of RAAS, begins to form in the second trimester of pregnancy. 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 RAAS can cause fetal development disorders or have a negative effect on the newborn, even fatal, when used in the II and III trimesters of pregnancy.
Angiakand should not be used during pregnancy. If pregnancy is detected during the period of treatment with the drug, 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.
Special instructions
Before and during treatment, blood pressure monitoring is necessary, kidney function (creatinine in plasma), potassium, lithium in blood serum (with the combined use of drugs).
Arterial hypotension. Arterial hypotension may develop in patients with chronic heart failure during treatment with Angiakand. As with other drugs that affect RAAS, the cause of the development of arterial hypotension in patients with arterial hypertension may be a decrease in BCC, as is observed in patients receiving high doses of diuretics. Therefore, caution should be exercised at the beginning of therapy and, if necessary, the correction of hypovolemia.
Renal artery stenosis. In patients with bilateral renal artery stenosis or stenosis of a single kidney artery, drugs that affect RAAS, in particular ACE inhibitors, may cause an increase in serum urea and creatinine concentrations. Similar effects can be expected with the administration of angiotensin II receptor antagonists.
kidney transplant. There are no data on the use of candesartan in patients who have recently undergone a kidney transplant.
Impaired renal function. During therapy with Angiakand, as with other drugs that inhibit RAAS, some patients may have impaired renal function.
When using Angiakand in patients with arterial hypertension and severe renal failure, it is recommended that serum potassium and creatinine be periodically monitored. Clinical experience with candesartan in patients with severe renal impairment or end-stage renal failure (Cl creatinine
In patients with chronic heart failure, it is necessary to periodically monitor renal 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 Angiakand, it is also recommended to control the content of potassium and creatinine in blood plasma
Joint use with ACE inhibitors in chronic heart failure.When using Angiakand in combination with ACE inhibitors, the risk of side effects, especially impaired renal function and hyperkalemia, may increase.In these cases, careful monitoring and control of laboratory parameters is necessary.
General anesthesia and surgery. In patients receiving angiotensin II receptor antagonists, arterial hypotension as a result of RAAS blockade may develop during general anesthesia and during surgical interventions. Very rarely, cases of severe arterial hypotension may be noted, requiring iv administration of fluid and / or vasopressor agents.
Aortic and mitral valve stenosis (hypertrophic obstructive cardiomyopathy). When using Angiakand, like other vasodilators, caution should be exercised 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 antihypertensive drugs. affecting the activity of RAAS. 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 the simultaneous use of candesartan with potassium-sparing diuretics, potassium preparations, or salt substitutes containing potassium, or other drugs that can increase blood potassium (for example, heparin), can lead to the development of hyperkalemia in patients with arterial hypertension.
General. Patients whose vascular tone and renal function mainly depend on RAAS activity (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis), are especially sensitive to drugs that act on RAAS. The use of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria, and less commonly, acute renal failure. The possibility of developing these effects cannot be excluded with the use of angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular diseases of ischemic origin with the use of any antihypertensive drugs can lead to the development of myocardial infarction or stroke.
Influence on ability to steer vehicles, mechanisms. During the treatment period, dizziness, weakness may occur, therefore caution must be exercised when driving vehicles and engaging in other potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.
Composition of
1 tablet contains:
active substance:
candesartan cilexetil 8 mg
excipients:
pregelatinized corn starch,
croscarmellose sodium (primrose), srtl
Dosage and administration
Inside, regardless of the meal, 1 time per day.
Arterial hypertension. The recommended starting and maintenance dose is 8 mg once daily. Patients who require a further decrease in blood pressure are recommended to increase the dose to 16 mg once a day. The maximum daily dose of the drug is 32 mg 1 time per day.
The maximum antihypertensive effect occurs 4 weeks after the start of treatment.
If therapy with Angiakand does not reduce blood pressure to the optimal target level, it is recommended to add a thiazide diuretic to therapy.
In elderly patients, initial dose adjustment is not required.
In patients with mild or moderate impaired renal function (Cl creatinine> 30 ml / min), an initial dose change is not required.
Patients with severe renal impairment (Cl creatinine Chronic heart failure. Recommended starting dose is 4 mg once a day (candesartan may be used in a different dosage form).
Increase dosage to 32 mg once a day or to the maximum tolerated dose performed by doubling it with an interval of at least 2 weeks
Elderly patients and patients with impaired renal and / or liver function do not need to change the initial dose of the drug
Side effects
Arterial hypertension, the most common side effects (? 1/100,
From the central nervous system: dizziness, weakness, headache.
From the musculoskeletal system, connective tissue: backache.
Other: respiratory infections.
Laboratory indicators: hemoglobin decrease, hypercreatininemia, increased blood urea concentration, hyperkalemia, hyponatremia, increased ALT activity.
Chronic heart failure, the most common side effects (? 1/100,
From the CCC: marked decrease in blood pressure.
From the urinary system: impaired renal function.
Laboratory changes: hypercreatininemia, increased concentration of urea in the blood, hyperkalemia.
During the post-marketing use of candesartan, the following side effects were reported (frequency – less than 1/10000)
From the hemopoietic organs: leukopenia, neutropenia and agranulocytosis.
Laboratory parameters: hyperka . Iemiya, hyponatremia
CNS: dizziness, weakness, headache.
From the digestive system: nausea.
From the liver and biliary tract: increased activity of hepatic transaminases, impaired liver function or hepatitis.
Allergic reactions: angioedema, skin rash, itching, urticaria.
From the musculoskeletal system, connective tissue: back pain, arthralgia, myalgia.
From the urinary system: impaired renal function, including acute renal failure in susceptible patients.
From the respiratory system: cough.
Drug Interactions
With the combined use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine and enalapril, no clinically significant interactions were detected.
With the simultaneous use of lithium preparations with ACE inhibitors, a reversible increase in serum lithium concentration and the development of toxic reactions have been reported. Adverse reactions can also occur with the use of angiotensin II receptor antagonists, in connection with which it is recommended to control the level of lithium in blood serum with the combined use of these drugs.
With the simultaneous use of angiotensin II receptor antagonists and NSAIDs, including selective COX-2 inhibitors and non-selective NSAIDs (for example, acetylsalicylic acid at a dose of more than 3 g / day), the hypotensive effect of candesartan can be reduced. As in the case of ACE inhibitors, the simultaneous use of angiotensin II receptor antagonists and NSAIDs increases the risk of decreased 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 renal function at the beginning of therapy and in the future.
Drugs that affect RAAS can increase blood urea and creatinine concentrations in patients with bilateral renal artery stenosis or single kidney artery stenosis.
Diuretics and other antihypertensive drugs increase the risk of hypotension.
Potassium-sparing diuretics, potassium preparations, potassium-containing salt substitutes, and other drugs that can increase serum potassium (such as heparin) increase the risk of hyperkalemia.
Candesartan is slightly metabolized in the liver (CYP2C9 isoenzyme). The interaction studies did not reveal the effect of candesartan on the CYP2C9 and CYP3A4 isoenzymes. The effect on other isoenzymes of the cytochrome P450 system has not been studied.
Overdose
Symptoms: severe BP, dizziness, tachycardia.
Treatment: symptomatic. Put the patient on his back, raise his lower extremities above head level, increase BCC if necessary by infusion of 0.9% sodium chloride solution, appoint sympathomimetics. Hemodialysis is ineffective.
Storage Conditions
In a dry, dark place at a temperature not exceeding 25 ° C.
Shelf life
2 years.
Deystvuyushtee substance
Candesartan
Prescription conditions
pharmacy prescription
dosage form
tablets
Prescribing
Prescribing
For adults as prescribed by a doctor
Kanonfarma, Russia
