Release form, composition and packing
Pill light pink color, round, biconvex, with a notch and engraved with the letter "A" above the line and the letters "CG" - below the line on one side of the tablet and "008" - on the other side, on a break - homogeneous, light- pink.
1 tab. tsileksetil candesartan 8 mg.
Other ingredients: calcium carboxymethylcellulose, hydroxypropyl cellulose, iron dioxide, red-brown (E172), lactose monohydrate, magnesium stearate, corn starch, polyethylene glycol 8000, purified water.
Pill pink, round, biconvex, with a notch and engraved with the letter "A" above the line and the letters "CH" - below the line on one side of the tablet and "016" - on the other side, on a break - homogeneous pink.
1 tab. tsileksetil candesartan 16 mg.
Other ingredients: calcium carboxymethylcellulose, hydroxypropyl cellulose, iron dioxide, red-brown (E172), lactose monohydrate, magnesium stearate, corn starch, polyethylene glycol 8000, purified water.
Pill pink, round, biconvex, with a notch and engraved in letters "CL" on one side and "032" - on the other.
1 tab. tsileksetil candesartan 32 mg.
Other ingredients: calcium carboxymethylcellulose (karmellozy calcium salt), giproloza, stain iron oxide red (E 172), lactose monohydrate, magnesium stearate, maize starch, macrogol.
Clinico-pharmacological group: angiotensin receptor antagonist II.
Pharmacological action
Antihypertensive drug, receptor antagonist of angiotensin II, selectively acting on receptors AT1. Angiotensin II - the main hormone of the renin-angiotensin-aldosterone system, which plays an important role in the pathogenesis of hypertension, heart failure and other cardiovascular diseases.
The main physiological effects of angiotensin II are vasoconstriction and stimulation of aldosterone production, regulation of water and electrolyte homeostasis and stimulation of cell growth. All these effects are mediated by interaction of angiotensin II, angiotensin receptor type 1 (AT1 receptor). Candesartan does not inhibit ACE, which carries out the conversion of angiotensin I to angiotensin II and bradykinin breaks, no effect on ACE and does not lead to accumulation of bradykinin or substance P. A comparison of candesartan with ACE inhibitors develop a cough rarely occurred in patients receiving candesartan tsileksetil. Candesartan does not bind to receptors of other hormones and do not block ion channels involved in regulating the cardiovascular system.
As a result, blocking the AT1 angiotensin II receptor is dose-dependent increase in renin, angiotensin I, angiotensin II and lower concentrations of aldosterone in plasma. Arterial hypertension in hypertension candesartan causes a dose-dependent long-term blood pressure reduction. Antihypertensive effect of the drug due to lower PR, no change in heart rate. No cases of severe hypotension after the first dose of the drug, as well as the effect of withdrawal syndrome ("rebound") after cessation of therapy.
Start of antihypertensive action after the first dose of candesartan tsileksetila usually develops within 2 hours amid continuing therapy with a fixed dose of maximum blood pressure reduction is usually achieved within 4 weeks and continues throughout treatment.
Candesartan tsileksetil appointed 1 time per day, provides effective and smooth blood pressure reduction over 24 hours, with minor fluctuations in blood pressure in the intervals between doses of regular doses of the drug.
The use of candesartan with hydrochlorothiazide tsileksetila leads to increased hypotensive effect. Joint application tsileksetila candesartan and hydrochlorothiazide (or amlodipine) was well tolerated. Effectiveness of the drug does not depend on age and sex of patients. Tsileksetil candesartan increases renal blood flow and does not change or increased glomerular filtration rate, whereas renal vascular resistance and filtration fraction are reduced.
Receiving candesartan tsileksetila dose 8-16 mg for 12 weeks did not adversely affect blood glucose and lipid profile in patients with hypertension and type 2 diabetes mellitus.
Clinical effect of candesartan tsileksetila on morbidity and mortality when receiving a dose of 8-16 mg (mean dose 12 mg) 1 time per day was investigated in a randomized clinical trial involving 4,937 elderly patients (aged from 70 to 89 years, 21% of patients in aged 80 and older) with hypertension mild to moderate severity, receiving treatment candesartan tsileksetilom within an average of 3.7 years (study SSORE - study of cognitive function and prognosis in elderly patients).
Patients received candesartan or placebo, as appropriate, in combination with other antihypertensive drugs. In the group of patients treated with candesartan, decreased blood pressure from 166/90 to 145/80 mm Hg in the control group from 167/90 to 149/82 mm Hg
Statistically significant differences of frequency of cardiovascular events (mortality due to cardiovascular disease, myocardial infarction and stroke, which have not resulted in death) between the two groups of patients were noted. In the group of patients treated with candesartan, was observed 26.7 cases of cardiovascular events per 1000 patient-years compared with 30.0 cases per 1000 patient-years in the control group (hazard ratio = 0.89, 95% confidence interval 0.75-1.06, p = 0.19).
Heart failure
According to the study CHARM (Kadensartan in heart failure - Assessment of Reduction in mortality and morbidity), use of candesartan tsileksetila decreased the frequency of deaths and the need for hospitalization for congestive heart failure and improve left ventricular systolic function.
Patients with chronic heart failure in addition to the primary therapy received candesartan tsileksetil dose of 4-8 mg / day with dose escalation to 32 mg / day or until the maximum tolerated dose therapy (average dose of candesartan was 24 mg). The median duration of follow-up was 37.7 months. After 6 months of therapy 63% of patients who continued to receive candesartan tsileksetil (89%) received a therapeutic dose of 32 mg.
In another study, CHARM-Alternative study (n = 2.028) involved patients with reduced left ventricular ejection fraction (LVEF) ≤ 40%) who did not receive an ACE inhibitor because of intolerance (mainly due to cough - 72%); performance frequency deaths from cardiovascular disease and the first hospitalization for congestive heart failure were significantly lower in patients treated with candesartan compared with placebo (hazard ratio = 0.77, 95% CI 0.67-0.89, p <0.001).
Relative risk reduction was 23%. Statistically in this study to prevent one case of death ot cardiovascular events or hospitalizations for congestive heart failure was needed to treat 14 patients throughout the study period. Combined criterion, which included the frequency of deaths, regardless of their causes and the initial stage of hospitalization for congestive heart failure, was also significantly lower in patients treated with candesartan (hazard ratio = 0.80, 95% confidence interval 0.70-0.92, p = 0.001).
It was also noted positive effects of candesartan on each of the components of this combined criterion - the frequency of deaths and incidence (a measure of the frequency of hospitalizations for heart failure).
The use of candesartan tsileksetila led to an improvement of functional class of chronic heart failure classification NYHA (p = 0.008). In a study of CHARM-PLUS (n = 2.548) in patients with reduced LVEF ≤ 40% receiving ACE inhibitors, a combined criterion, which included the mortality rate from cardiovascular disease and the first hospitalization for congestive heart failure was significantly lower in patients treated with candesartan, compared with the placebo group (hazard ratio = 0.85, 95% confidence interval 0.75-0.96, p = 0.011), which corresponded to a relative risk reduction of 15%.
In this study, to prevent one case of death from cardiovascular complications or hospitalization for congestive heart failure was needed to treat 23 patients throughout the study period. The value of the combined criterion of efficiency, including the assessment of the frequency of deaths, regardless of their causes or frequency of the first hospitalization for congestive heart failure was significantly lower in patients treated with candesartan (hazard ratio = 0.87, 95% confidence interval 0.78-0.98, p = 0.021), which also indicated the positive effect of the application of candesartan.
The use of candesartan tsileksetila led to an improvement of functional class of chronic heart failure classification NYHA (p = 0.020). The study SHARM - prevention (n = 3.023) in patients with preserved systolic function (LVEF> 40%) showed no statistically significant differences in the values of the combined endpoint of which included frequency of deaths and the frequency of the first hospitalization for congestive heart failure in the candesartan and placebo groups (hazard ratio = 0.89, 95% confidence interval 0.77-1.03, p = 0.118).
Slight numerical decline of this criterion was due to reduced rates of hospitalization for chronic heart failure. In the present study did not show the influence of candesartan on the incidence of deaths.
For the separate analysis of results of 3 studies CHARM program was not obtained significant differences in the frequency of deaths in the candesartan and placebo groups. However, the frequency of deaths was estimated in the combined population studies CHARM-Alternative and CHARM-plus, and in all 3 studies (hazard ratio = 0.91, 95% confidence interval 0.83-1.00, p = 0.055).
Reduction in the rate of deaths and hospitalizations for chronic heart failure during therapy with candesartan did not depend on age, gender and concomitant therapy. Candesartan was also effective in patients taking beta-blockers in combination with ACE inhibitors, and the efficacy of candesartan did not depend on whether one considers the patient the optimal dose of ACE inhibitor or not. In patients with chronic heart failure and reduced left ventricular systolic function (LVEF ≤ 40%), receiving candesartan helped reduce the PR and the capillary pressure in the lungs, increasing the activity of renin and angiotensin II concentrations in plasma, as well as lower levels of aldosterone.
Pharmacokinetics
Absorption and distribution
Candesartan tsileksetil is a prodrug for oral administration.
Pill light pink color, round, biconvex, with a notch and engraved with the letter "A" above the line and the letters "CG" - below the line on one side of the tablet and "008" - on the other side, on a break - homogeneous, light- pink.
1 tab. tsileksetil candesartan 8 mg.
Other ingredients: calcium carboxymethylcellulose, hydroxypropyl cellulose, iron dioxide, red-brown (E172), lactose monohydrate, magnesium stearate, corn starch, polyethylene glycol 8000, purified water.
Pill pink, round, biconvex, with a notch and engraved with the letter "A" above the line and the letters "CH" - below the line on one side of the tablet and "016" - on the other side, on a break - homogeneous pink.
1 tab. tsileksetil candesartan 16 mg.
Other ingredients: calcium carboxymethylcellulose, hydroxypropyl cellulose, iron dioxide, red-brown (E172), lactose monohydrate, magnesium stearate, corn starch, polyethylene glycol 8000, purified water.
Pill pink, round, biconvex, with a notch and engraved in letters "CL" on one side and "032" - on the other.
1 tab. tsileksetil candesartan 32 mg.
Other ingredients: calcium carboxymethylcellulose (karmellozy calcium salt), giproloza, stain iron oxide red (E 172), lactose monohydrate, magnesium stearate, maize starch, macrogol.
Clinico-pharmacological group: angiotensin receptor antagonist II.
Pharmacological action
Antihypertensive drug, receptor antagonist of angiotensin II, selectively acting on receptors AT1. Angiotensin II - the main hormone of the renin-angiotensin-aldosterone system, which plays an important role in the pathogenesis of hypertension, heart failure and other cardiovascular diseases.
The main physiological effects of angiotensin II are vasoconstriction and stimulation of aldosterone production, regulation of water and electrolyte homeostasis and stimulation of cell growth. All these effects are mediated by interaction of angiotensin II, angiotensin receptor type 1 (AT1 receptor). Candesartan does not inhibit ACE, which carries out the conversion of angiotensin I to angiotensin II and bradykinin breaks, no effect on ACE and does not lead to accumulation of bradykinin or substance P. A comparison of candesartan with ACE inhibitors develop a cough rarely occurred in patients receiving candesartan tsileksetil. Candesartan does not bind to receptors of other hormones and do not block ion channels involved in regulating the cardiovascular system.
As a result, blocking the AT1 angiotensin II receptor is dose-dependent increase in renin, angiotensin I, angiotensin II and lower concentrations of aldosterone in plasma. Arterial hypertension in hypertension candesartan causes a dose-dependent long-term blood pressure reduction. Antihypertensive effect of the drug due to lower PR, no change in heart rate. No cases of severe hypotension after the first dose of the drug, as well as the effect of withdrawal syndrome ("rebound") after cessation of therapy.
Start of antihypertensive action after the first dose of candesartan tsileksetila usually develops within 2 hours amid continuing therapy with a fixed dose of maximum blood pressure reduction is usually achieved within 4 weeks and continues throughout treatment.
Candesartan tsileksetil appointed 1 time per day, provides effective and smooth blood pressure reduction over 24 hours, with minor fluctuations in blood pressure in the intervals between doses of regular doses of the drug.
The use of candesartan with hydrochlorothiazide tsileksetila leads to increased hypotensive effect. Joint application tsileksetila candesartan and hydrochlorothiazide (or amlodipine) was well tolerated. Effectiveness of the drug does not depend on age and sex of patients. Tsileksetil candesartan increases renal blood flow and does not change or increased glomerular filtration rate, whereas renal vascular resistance and filtration fraction are reduced.
Receiving candesartan tsileksetila dose 8-16 mg for 12 weeks did not adversely affect blood glucose and lipid profile in patients with hypertension and type 2 diabetes mellitus.
Clinical effect of candesartan tsileksetila on morbidity and mortality when receiving a dose of 8-16 mg (mean dose 12 mg) 1 time per day was investigated in a randomized clinical trial involving 4,937 elderly patients (aged from 70 to 89 years, 21% of patients in aged 80 and older) with hypertension mild to moderate severity, receiving treatment candesartan tsileksetilom within an average of 3.7 years (study SSORE - study of cognitive function and prognosis in elderly patients).
Patients received candesartan or placebo, as appropriate, in combination with other antihypertensive drugs. In the group of patients treated with candesartan, decreased blood pressure from 166/90 to 145/80 mm Hg in the control group from 167/90 to 149/82 mm Hg
Statistically significant differences of frequency of cardiovascular events (mortality due to cardiovascular disease, myocardial infarction and stroke, which have not resulted in death) between the two groups of patients were noted. In the group of patients treated with candesartan, was observed 26.7 cases of cardiovascular events per 1000 patient-years compared with 30.0 cases per 1000 patient-years in the control group (hazard ratio = 0.89, 95% confidence interval 0.75-1.06, p = 0.19).
Heart failure
According to the study CHARM (Kadensartan in heart failure - Assessment of Reduction in mortality and morbidity), use of candesartan tsileksetila decreased the frequency of deaths and the need for hospitalization for congestive heart failure and improve left ventricular systolic function.
Patients with chronic heart failure in addition to the primary therapy received candesartan tsileksetil dose of 4-8 mg / day with dose escalation to 32 mg / day or until the maximum tolerated dose therapy (average dose of candesartan was 24 mg). The median duration of follow-up was 37.7 months. After 6 months of therapy 63% of patients who continued to receive candesartan tsileksetil (89%) received a therapeutic dose of 32 mg.
In another study, CHARM-Alternative study (n = 2.028) involved patients with reduced left ventricular ejection fraction (LVEF) ≤ 40%) who did not receive an ACE inhibitor because of intolerance (mainly due to cough - 72%); performance frequency deaths from cardiovascular disease and the first hospitalization for congestive heart failure were significantly lower in patients treated with candesartan compared with placebo (hazard ratio = 0.77, 95% CI 0.67-0.89, p <0.001).
Relative risk reduction was 23%. Statistically in this study to prevent one case of death ot cardiovascular events or hospitalizations for congestive heart failure was needed to treat 14 patients throughout the study period. Combined criterion, which included the frequency of deaths, regardless of their causes and the initial stage of hospitalization for congestive heart failure, was also significantly lower in patients treated with candesartan (hazard ratio = 0.80, 95% confidence interval 0.70-0.92, p = 0.001).
It was also noted positive effects of candesartan on each of the components of this combined criterion - the frequency of deaths and incidence (a measure of the frequency of hospitalizations for heart failure).
The use of candesartan tsileksetila led to an improvement of functional class of chronic heart failure classification NYHA (p = 0.008). In a study of CHARM-PLUS (n = 2.548) in patients with reduced LVEF ≤ 40% receiving ACE inhibitors, a combined criterion, which included the mortality rate from cardiovascular disease and the first hospitalization for congestive heart failure was significantly lower in patients treated with candesartan, compared with the placebo group (hazard ratio = 0.85, 95% confidence interval 0.75-0.96, p = 0.011), which corresponded to a relative risk reduction of 15%.
In this study, to prevent one case of death from cardiovascular complications or hospitalization for congestive heart failure was needed to treat 23 patients throughout the study period. The value of the combined criterion of efficiency, including the assessment of the frequency of deaths, regardless of their causes or frequency of the first hospitalization for congestive heart failure was significantly lower in patients treated with candesartan (hazard ratio = 0.87, 95% confidence interval 0.78-0.98, p = 0.021), which also indicated the positive effect of the application of candesartan.
The use of candesartan tsileksetila led to an improvement of functional class of chronic heart failure classification NYHA (p = 0.020). The study SHARM - prevention (n = 3.023) in patients with preserved systolic function (LVEF> 40%) showed no statistically significant differences in the values of the combined endpoint of which included frequency of deaths and the frequency of the first hospitalization for congestive heart failure in the candesartan and placebo groups (hazard ratio = 0.89, 95% confidence interval 0.77-1.03, p = 0.118).
Slight numerical decline of this criterion was due to reduced rates of hospitalization for chronic heart failure. In the present study did not show the influence of candesartan on the incidence of deaths.
For the separate analysis of results of 3 studies CHARM program was not obtained significant differences in the frequency of deaths in the candesartan and placebo groups. However, the frequency of deaths was estimated in the combined population studies CHARM-Alternative and CHARM-plus, and in all 3 studies (hazard ratio = 0.91, 95% confidence interval 0.83-1.00, p = 0.055).
Reduction in the rate of deaths and hospitalizations for chronic heart failure during therapy with candesartan did not depend on age, gender and concomitant therapy. Candesartan was also effective in patients taking beta-blockers in combination with ACE inhibitors, and the efficacy of candesartan did not depend on whether one considers the patient the optimal dose of ACE inhibitor or not. In patients with chronic heart failure and reduced left ventricular systolic function (LVEF ≤ 40%), receiving candesartan helped reduce the PR and the capillary pressure in the lungs, increasing the activity of renin and angiotensin II concentrations in plasma, as well as lower levels of aldosterone.
Pharmacokinetics
Absorption and distribution
Candesartan tsileksetil is a prodrug for oral administration.
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