Candesartan FT tablets 8mg №10×3

Name:
Candesartan FT.
Description:
Candesartan FT 8 mg: Round, biconvex, pink, scored tablets on one side. The presence of marbling and inclusions is allowed. On the surface, the presence of marbling of a more intense color is allowed. The tablet may be divided according to risk into 2 equal doses. Candesartan FT 16 mg: Round, biconvex, pink tablets scored on one side. The presence of marbling and inclusions is allowed. On the surface, the presence of marbling of a more intense color is allowed. The tablet may be divided according to risk into 2 equal doses. Candesartan FT 32 mg: Round, biconvex, pink tablets scored on one side. The presence of marbling and inclusions is allowed. On the surface, the presence of marbling of a more intense color is allowed. The tablet may be divided according to risk into 2 equal doses. Pharmacotherapeutic group Means that affect the renin-angiotensin system. Angiotensin II receptor antagonists. ATX code: S09CA06 Release form 10 tablets in a blister pack made of polyvinyl chloride film or rigid PVC film and flexible packaging based on aluminum foil. Each 3 blister packs, together with the leaflet, are placed in a pack of cardboard. DosageSpecial instructionsDouble blockade of the renin-angiotensin-aldosterone system (RAAS) It has been shown that the combined use of drugs from the ACE inhibitor groups, angiotensin II receptor blockers (ARB II) or aliskiren increases the risk of developing hypotension, hyperkalemia and decreased kidney function (including can lead to development of acute renal failure). Therefore, dual blockade of the RAAS by the co-administration of an ACE inhibitor, angiotensin II receptor blockers, or aliskiren is not recommended. When absolutely indicated, therapy with a double blockade of the RAAS should be carried out under the supervision of a specialist and with careful monitoring of renal function, electrolyte balance and blood pressure. An ARB II and an ACE inhibitor should not be co-administered to patients with diabetic nephropathy. Co-administration with an ACE inhibitor in patients with heart failure Co-administration of candesartan cilexetil and an ACE inhibitor may increase the risk of adverse reactions, especially hypotension, hyperkalemia and deterioration of renal function, up to the development of acute renal failure. A triple combination of an ACE inhibitor, a mineralocorticoid receptor antagonist, and candesartan cilexetil is also not recommended. When using these combinations, specialist supervision and careful monitoring of renal function, electrolyte balance and blood pressure are necessary. Angiotensin II receptor blockers and ACE inhibitors should not be co-administered to patients with diabetic nephropathy. Impaired renal function As with other medicinal products that inhibit the RAAS, renal function may be altered in predisposed patients when taking candesartan cilexetil. When using candesartan cilexetil in hypertensive patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended. There is limited experience with candesartan cilexetil in patients with severe or end-stage renal impairment (creatinine clearance < 15 mL/min). In such patients, Candesartan FT should be used with caution and dose titration should be under close monitoring of blood pressure. Assessment of patients with heart failure should include periodic monitoring of renal function, especially in elderly patients ≥ 75 years of age and in patients with impaired renal function. During titration of the dose of the drug, it is also recommended to monitor the levels of serum creatinine and potassium. Clinical trials did not include patients with heart failure who had a serum creatinine level > 265 µmol/L (> 3 mg/dL). Use in children with impaired renal function The use of candesartan cilexetil in children with GFR < 30 ml/min/1.73 m2 has not been studied. Hemodialysis During dialysis, blood pressure may be more sensitive to blockade of AT1 receptors as a result of a decrease in plasma volume and activation of the RAAS. Therefore, dose titration of candesartan cilexetil should be done carefully with close monitoring of blood pressure in patients on hemodialysis. Renal artery stenosis Drugs that affect the RAAS, including angiotensin II receptor blockers, may increase serum urea and creatinine in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. Renal transplantation There is no experience with candesartan cilexetil in patients who have recently undergone kidney transplantation. Hypotension Hypotension may occur in patients with heart failure during treatment with medicinal products containing candesartan cilexetil. Also, such a risk exists in patients with a reduced volume of circulating blood, for example, when taking high doses of diuretics. Caution should be exercised when initiating therapy with candesartan cilexetil and an attempt should be made to correct hypovolemia. In children with a possible decrease in circulating blood volume (for example, during diuretic therapy, especially in children with impaired renal function), treatment with candesartan cilexetil should begin with the lowest initial dose under close medical supervision. Anesthesia and surgery Hypotension may occur during anesthesia and surgery in patients treated with angiotensin II receptor blocker drugs due to blockade of the RAAS. In very rare cases, hypotension may be so severe that intravenous fluids or vasoconstrictive drugs may be required. Stenosis of the aorta and mitral valve (obstructive hypertrophic cardiomyopathy) As with other drugs with a vasodilatory effect, special care is required in patients with hemodynamically significant stenosis of the aorta, mitral valve or with obstructive hypertrophic cardiomyopathy when using candesartan cilexetil. Primary hyperaldosteronism In general, patients with primary hyperaldosteronism do not respond to antihypertensive drugs that act by inhibiting the RAAS. The use of candesartan cilexetil in this group of patients is not recommended. Hyperkalemia When treating patients with hypertension, concomitant use of candesartan cilexetil with potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, medicinal products containing potassium, or other medicinal products that may increase serum potassium levels (eg, heparin) may result in an increase in the level of potassium in the blood serum. Serum potassium levels should be properly monitored. Hyperkalemia may occur when candesartan cilexetil is used in patients with heart failure. Periodic monitoring of serum potassium levels is recommended. A triple combination of ACE inhibitors, potassium-sparing diuretics (eg, spironolactone) and candesartan cilexetil should not be used. Such a combination of drugs is possible only with a careful assessment of the potential benefits and risks. General guidelines In patients in whom vascular tone and renal function depend primarily on RAAS activity (eg, in patients with severe congestive heart failure or kidney disease, including renal artery stenosis), treatment with other drugs that affect the RAAS , accompanied by the development of hypotension, azotemia, oliguria or, in rare cases, acute renal failure. The possibility of developing such effects is not excluded during therapy with angiotensin II receptor blockers. When treated with any antihypertensive drug, excessive lowering of blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular disease can lead to the development of myocardial infarction or stroke. The antihypertensive effect of candesartan cilexetil may be enhanced by the concomitant use of medicinal products with antihypertensive activity, regardless of the indication for which they were prescribed. Pregnancy During pregnancy, treatment with angiotensin II receptor antagonists should not be started. Patients planning pregnancy should be given an alternative antihypertensive treatment with a proven safety profile when used during pregnancy, unless continued use of angiotensin II receptor antagonists is considered absolutely necessary. If pregnancy is detected, treatment with angiotensin II receptor antagonists should be stopped immediately and, if necessary, alternative therapy should be initiated. In patients of childbearing potential, the possibility of pregnancy should be regularly assessed. To prevent the risk of adverse effects of candesartan cilexetil during pregnancy, it is necessary to provide the patient with appropriate information and take other possible measures to prevent the use of candesartan cilexetil during pregnancy. Auxiliary components The drug Candesartan FT contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take Candesartan FT. Pharmacodynamic properties Mechanism of action Angiotensin II is the main vasoactive hormone of the renin-angiotensin-aldosterone system and plays a role in the pathophysiology of arterial hypertension, heart failure and other diseases of the cardiovascular system. Angiotensin II also plays a role in the pathogenesis of hypertrophy and target organ damage. The main physiological effects of angiotensin II, such as vasoconstriction, stimulation of aldosterone secretion, regulation of salt and water homeostasis, stimulation of cell growth, are mediated through effects on receptors (AT1) to angiotensin. Pharmacodynamic effects Candesartan cilexetil is an oral prodrug. The substance is quickly transformed into the pharmacologically active substance candesartan by ether hydrolysis, which occurs during its absorption from the lumen of the gastrointestinal tract. Candesartan is an angiotensin II receptor blocker (ARB II), selective for the AT1 receptor, with which the substance binds closely and slowly dissociates from bonds. Candesartan does not have a stimulating effect on receptors. Candesartan does not inhibit the angiotensin-converting enzyme, which converts angiotensin I to angiotensin II and cleaves bradykinin. There is no effect on ACE and potentiation of bradykinin and substance P in candesartan. In controlled clinical trials comparing the effects of candesartan and ACE inhibitors, the incidence of cough was less in patients taking candesartan cilexetil. Candesartan does not bind or block receptors for other hormones or ion channels that play an important role in the regulation of the cardiovascular system. The blocking effect on AT1 receptors of angiotensin II leads to a dose-dependent increase in plasma renin levels, angiotensin I and angiotensin II levels, as well as a decrease in plasma aldosterone concentration. Clinical efficacy and safety Arterial hypertension In the treatment of arterial hypertension, candesartan cilexetil causes a dose-dependent and long-term decrease in blood pressure. The antihypertensive effect is due to a decrease in total peripheral resistance without a reflex increase in heart rate. When using candesartan cilexetil, there is no serious or pronounced arterial hypotension after taking the first dose, and there is no "rebound effect" after its withdrawal. After a single dose of candesartan cilexetil, the onset of the antihypertensive effect usually occurs within 2 hours. With constant use of the drug, most of the antihypertensive effect is observed within 4 weeks and persists throughout the entire period of treatment. According to the meta-analysis, when the dose was increased from 16 mg 1 time per day to 32 mg 1 time per day, the total antihypertensive effect was small. Given intra-individual variability, some patients may experience a greater response than the average population. Once-daily administration of candesartan cilexetil provides an effective and mild reduction in blood pressure after 24 hours with minimal difference between the maximum and minimum effects in the dosing interval. The antihypertensive effect and tolerability of candesartan cilexetil and losartan were compared in 2 randomized, double-blind studies involving 1268 patients with mild to moderate arterial hypertension. The minimum decrease in blood pressure was 13.1/10.5 mm Hg. Art. (SBP / DBP, respectively) when taking candesartan cilexetil at a dose of 32 mg 1 time per day and 10.0 / 8.7 mm Hg. Art. when taking losartan potassium at a dose of 100 mg 1 time per day (difference in pressure reduction 3.1 / 1.8 mm Hg, p <0.0001 / p <0.0001). When candesartan cilexetil was co-administered with hydrochlorothiazide, the effect of lowering blood pressure was summed up. An enhanced antihypertensive effect has also been observed with the co-administration of candesartan cilexetil with amlodipine and felodipine. Blockers of the renin-angiotensin-aldosterone system, including candesartan cilexetil, have a less pronounced antihypertensive effect in patients of the Negroid race, a feature of which is a low level of renin in the blood compared to patients of other races. This fact was proven in an open clinical study in which 5156 patients with diastolic arterial hypertension took part, as a result of which it was found that the decrease in blood pressure was less intense in patients of the black race compared with patients of other races (14.4/10.3 mmHg vs 19.0/12.7 mmHg, p<0.0001/p<0.0001). Candesartan cilexetil increases renal blood flow and does not affect the glomerular filtration rate (GFR), or increases GFR while reducing renal vascular resistance and filtration fraction. In a 3-month clinical study in patients with hypertension and type 2 diabetes mellitus and microalbuminuria, antihypertensive treatment with candesartan cilexetil reduced microalbuminuria (albumin/creatinine ratio, mean 30%, 95% confidence interval 15-42 %). There are currently no data on the effect of candesartan cilexetil on the progression of diabetic nephropathy. The effect of candesartan cilexetil at doses of 8-16 mg (median dose 12 mg) on once daily cardiovascular morbidity and mortality. Patients received candesartan cilexetil or placebo in combination with other antihypertensive drugs, which were introduced into the treatment regimen as needed. Arterial pressure decreased from 166/90 to 145/80 mm Hg. Art. in the candesartan cilexetil group and from 167/90 to 149/82 mm Hg. Art. in the control group. There was no statistically significant difference in the primary end points, major CV events (cardiovascular death, and non-fatal stroke and myocardial infarction). In the candesartan cilexetil group, there were 26.7 cardiovascular events per 1000 person-years and in the control group - 30.0 per 1000, respectively. Two large randomized trials (ONTARGET and VA NEPHRON-D) investigated the combination of an ACE inhibitor and ARB II: - The ONTARGET study included patients with cardiovascular or cerebrovascular disease, type 2 diabetes mellitus, complicated target organ damage. - Patients with diabetes mellitus and diabetic nephropathy took part in the VA NEPHRON-D study. The results of these studies did not show a significant benefit of using a combination of drugs from different groups related to RAAS inhibitors in terms of renal status and / or cardiovascular outcomes. However, the use of this combination resulted in an increased risk of hyperkalemia, acute kidney injury and/or hypotension compared with monotherapy. Given the similar pharmacodynamic properties, these results are also consistent with other ACE inhibitors and ARBs II. Therefore, co-administration of ACE inhibitors and ARB II drugs in patients with diabetic nephropathy is not allowed. The ALTITUDE study evaluated the benefits of adding aliskiren to standard therapy with an ACE inhibitor or ARB II in patients with type 2 diabetes and chronic kidney disease and/or cardiovascular disease. The study was terminated early due to an increased risk of adverse outcomes. Cardiovascular mortality and stroke rates were significantly higher in the aliskiren group than in the placebo group. Also, other serious adverse reactions, such as hyperkalemia, hypotension, and impaired renal function, occurred significantly more often in the aliskiren group compared to placebo. Children The antihypertensive effect of candesartan cilexetil was evaluated in children with arterial hypertension aged 1 to <6 6="" 17="" 2-="" 4="" :="" br=""> – 93 children with arterial hypertension aged from 1 to 6 years were randomized depending on doses. Children received candesartan cilexetil in the form of a suspension at doses of 0.05 mg/kg, 0.20 mg/kg and 0.40 mg/kg 1 time per day. SBP and DBP decreased in a dose-dependent manner from 6.0/5.2 to 12.0/11.1 mm Hg. Art. from the original level. However, given the fact that there was no placebo group in the study, the true fluctuations in blood pressure values remain undetermined, making it difficult to definitively assess the benefit-risk ratio in this age group. – 240 children aged 6 to <17 1:2:2:2="" 50="" 2="" 8="" 16="" 1="">50 kg doses of candesartan cilexetil were 4, 16 or 32 mg 1 time per day. According to the results of the combined assessment, SBP decreased by 10.2 mm Hg. Art., DBP – by 6.6 mm Hg. Art. compared to the original values. Despite a significant placebo effect, each dose of candesartan cilexetil (as well as the combined result of all doses) was significantly higher than placebo. The maximum response in reducing blood pressure in children weighing below and above 50 kg was achieved at doses of 8 mg and 16 mg. Of all the children who participated in the study, 47% were black and 29% were female. Mean age was 12.9 +/- 2.6 years. In children aged 6 to <17 br=""> Heart failure Treatment with candesartan cilexetil reduced mortality, reduced hospitalizations for worsening heart failure, and improved symptoms in patients with impaired left ventricular systolic function as found in the CHARM program. The program was a double-blind, placebo-controlled program in patients with chronic heart failure with NYHA functional class II to IV. The program consisted of 3 studies: – The first study (CHARM-Alternative) involved patients (n=2028) with heart failure, whose left ventricular ejection fraction (LVEF) ≤ 40%. The treatment of these patients did not include ACE inhibitors, due to their intolerance (mainly due to cough). – The second study (CHARM-Added) included patients (n=2548) with heart failure who had an LVEF ≤ 40%. These patients were treated with ACE inhibitors. – The third study (CHARM-Preserved) included patients (n=3023) with heart failure with an LVEF >40%. Patients were randomized to receive either candesartan cilexetil (dose titrated from 4 mg once daily or 8 mg once daily to 32 mg once daily or maximum tolerated dose; median dose was 24 mg) or placebo followed by approximately 37.7 months of follow-up. After 6 months of treatment, 63% of patients who were still on candesartan cilexetil (89%) reached the target dose of 32 mg. In the CHARM-Alternative study, the composite endpoint (CV mortality, first hospitalization for chronic heart failure) was significantly reduced in the candesartan cilexetil groups compared to the placebo groups. An absolute difference of 7% regarding the occurrence of events attributable to the combined endpoint was determined in the candesartan cilexetil group (33%) and in the placebo group (40%). In 14 patients there was a need for additional treatment during the study: in order to prevent death in 1 patient and in the rest to carry out therapy due to the worsening course of heart failure. An absolute difference of 6% regarding the occurrence of events attributable to the combined endpoint was determined in the candesartan cilexetil group (36.6%) and in the placebo group (42.7%). Both components (mortality and hospitalization due to worsening heart failure) of the combined endpoint contributed to the evidence for the efficacy of candesartan cilexetil compared with the placebo group. In addition, treatment with candesartan cilexetil resulted in an improvement in NYHA functional class. In the CHARM-Added study, the composite endpoint consisted of cardiovascular death or first hospitalization for worsening heart failure. Treatment with candesartan cilexetil resulted in a significant reduction in these events compared with placebo. An absolute difference of 4.4% regarding the occurrence of events attributable to the combined endpoint was determined in the candesartan cilexetil group (37.9%) and in the placebo group (42.3%). In 23 patients there was a need for additional treatment during the study: in order to prevent death in 1 patient and in the rest to carry out therapy due to the worsening course of heart failure. The composite endpoint of all-cause mortality or first hospitalization for worsening heart failure was also lower in the candesartan cilexetil group compared with placebo. An absolute difference of 3.9% regarding the occurrence of events attributable to the combined endpoint was determined in the candesartan cilexetil group (42.2%) and in the placebo group (46.1%). Both components (mortality and hospitalization due to worsening heart failure) of the combined endpoint contributed to the evidence for the efficacy of candesartan cilexetil compared with the placebo group. Also, treatment with candesartan cilexetil led to an improvement in NYHA functional class. The CHARM-Preserved study found no statistically significant difference in reduction in mortality or first hospitalization due to worsening heart failure. The positive effect of candesartan cilexetil did not depend on age, gender and concomitant therapy. Candesartan cilexetil was also effective in patients taking concomitant ACE inhibitors and β-blockers. In patients with heart failure and reduced left ventricular function (LVEF ≤ 40%), candesartan cilexetil reduced systemic vascular resistance and pulmonary capillary wedge pressure, renin activity and plasma angiotensin II concentration, and also reduced aldosterone levels. Pharmacokinetic properties Absorption and distribution Following oral administration of candesartan, cilexetil is converted to the active pharmaceutical ingredient candesartan. The absolute bioavailability of candesartan is approximately 40% after oral administration of candesartan cilexetil. The relative bioavailability of candesartan tablets compared to oral solution is about 34% with very low variability. The estimated absolute bioavailability of tablets is 14%. The maximum concentration (Cmax) of candesartan is reached approximately 3-4 hours after taking candesartan cilexetil in the form of tablets. Serum concentrations of candesartan increase linearly with dose within therapeutic doses. There were no differences in pharmacokinetics depending on gender. Food intake did not change the area under the concentration-time curve (AUC) of candesartan. Candesartan is more than 99% bound to plasma proteins. The volume of distribution of candesartan was 0.1 L/kg. The bioavailability of candesartan was not altered by food. Metabolism and excretion Candesartan is mainly excreted unchanged in the urine and bile (with stools) and only a small part of it is metabolized in the liver using the CYP 2C9 isoenzyme of the cytochrome P450 system. Available interaction studies have shown no effect on CYP 2C9 and CYP 3A4. Based on in vitro data, no in vivo interaction is expected with drugs whose metabolism is dependent on the cytochrome P450 system (namely CYP 1A2, CYP 2A6, CYP 2C9, CYP 2C19, CYP 2D6, CYP 2E1, CYP 3A4 isoenzymes). The elimination half-life of candesartan is approximately 9 hours. When taking repeated doses, there is no accumulation of the substance. The total plasma clearance is 0.37 ml / min / kg, renal clearance is about 0.19 ml / min / kg. Renal excretion of candesartan occurs through glomerular filtration and active tubular secretion. Following oral administration of 14C-labeled candesartan cilexetil, approximately 26% of the dose as candesartan and 7% as the inactive metabolite is excreted in the urine, with stools approximately 56% of the administered dose as candesartan and 10% as the inactive metabolite. Special groups of patients Elderly patients In patients over the age of 65, Cmax and AUC of candesartan are increased by approximately 50% and 80%, respectively, compared with younger patients. However, the antihypertensive effect and incidence of adverse reactions in older and younger patients are similar. Patients with impaired renal function In patients with mild to moderate renal impairment, the Cmax and AUC of candesartan increase during repeated doses by approximately 50% and 80%, respectively, but the elimination half-life does not change compared with patients with normal renal function. Changes in Cmax and AUC in patients with acute renal impairment were approximately 50% and 110%, respectively, and the elimination half-life doubled in these patients. The AUC of candesartan in patients undergoing hemodialysis was similar to that in patients with acute renal failure. Patients with hepatic impairment In 2 studies that included patients with mild to moderate hepatic impairment, an increase in candesartan AUC of approximately 20% was observed in one study and approximately 80% in another study. There is no experience with candesartan cilexetil in patients with acute hepatic impairment. Children The pharmacokinetic parameters of candesartan were evaluated in children with arterial hypertension aged 1 to <6 6="" 17="" 2-="" br=""> 10 children aged 1 to < 6 years weighing from up to < 25 kg received a single dose of candesartan cilexetil at a dose of 0.2 mg/kg in the form of an oral suspension. In children of different ages and with different body weights, there were no differences in Cmax and AUC values. Clearance data for candesartan have not been evaluated, so the likelihood of clearance being affected by body weight and age in this population is unknown. 22 children aged 6 to <17 16="" cmax="" auc="" br=""> Children over 6 years of age were exposed to the same exposure as adults who received the same dose. The pharmacokinetics of candesartan has not been studied in children under 1 year of age. Preclinical data No evidence of systemic or target organ toxicity has been found for candesartan at doses consistent with therapeutic doses. In preclinical safety studies conducted in mice, rats, dogs and monkeys, candesartan cilexetil had an effect on the kidneys and red blood counts at higher doses. Candesartan cilexetil caused a decrease in red blood parameters such as red blood cell count, hemoglobin, and hematocrit. Effects on the kidneys (interstitial nephritis, tubular dilation, basophilic infiltration of the tubules, increased plasma urea and creatinine concentrations) were secondary due to hypotension, which led to impaired renal perfusion. Moreover, candesartan cilexetil induced hyperplasia and hypertrophy of the cells of the juxtaglomerular apparatus. These changes were caused by the pharmacological action of candesartan. At doses of candesartan cilexetil recommended for therapeutic use in humans, hyperplasia and hypertrophy of cells of the juxtaglomerular apparatus are not characteristic. In preclinical studies in neonatal and juvenile rats with normal blood pressure, candesartan cilexetil caused a decrease in body weight and heart weight in animals. In adult rats, these effects were due to the pharmacological action of candesartan, with exposure to the lowest dose in rats of 10 mg/kg being 12 to 78 times greater than exposure to candesartan cilexetil (0.2 mg/kg dose) in children aged 1 to < 6 years, and 7-54 times the exposure to candesartan cilexetil (16 mg dose) in children aged 6 to <17 -="" noel="" br=""> Fetal toxicity with candesartan cilexetil was observed in the later stages. Data from standard in vitro and in vivo genotoxicity studies indicated that candesartan cilexetil was not mutagenic or clastogenic at therapeutic doses. There was no evidence of carcinogenicity of candesartan cilexetil. The renin-angiotensin-aldosterone system plays a key role in the development of fetal kidneys (in utero). Suppression of the renin-angiotensin-aldosterone system results in impaired renal development in very young mice. The administration of drugs that have a direct effect on the renin-angiotensin-aldosterone system may interfere with the normal development of the kidneys. Therefore, children under the age of 1 year should not take candesartan cilexetil. Indications for use The drug Candesartan FT is indicated for: – treatment of essential arterial hypertension in adults; – treatment of arterial hypertension in children and adolescents aged 6 to 18 years; – treatment of adult patients with heart failure and impaired systolic function of the left ventricle (with an ejection fraction of the left ventricle ≤ 40%): with intolerance to drugs from the group of angiotensin-converting enzyme inhibitors (ACE inhibitors) or as an additional therapy to treatment with drugs from the ACE inhibitor group in patients with symptoms of heart failure, despite optimal therapy, in case of intolerance to mineralocorticoid receptor antagonists. Method of administration and doses For oral administration. Candesartan FT should be taken once daily with or without food (meal does not affect the bioavailability of candesartan). The tablet should be swallowed with a small amount of water. If possible, the tablets should be taken at the same time each day. Candesartan FT 8 mg, 16 mg and 32 mg tablets can be divided into 2 equal doses. In this case, the tablet should be placed with the risk up on a horizontal surface and press with the thumb and forefinger of one hand on each of the halves of the tablet so that the fracture can pass along the risk. Usually this method allows you to divide the pill at risk. Arterial hypertension Dosing regimen Adults The recommended starting dose and standard maintenance dose of candesartan cilexetil is 8 mg once daily. Most of the antihypertensive effect that the drug is able to provide is achieved within 4 weeks from the start of treatment. In patients who fail to achieve adequate control of blood pressure, the dose may be increased to 16 mg 1 time per day or up to 32 mg 1 time per day (32 mg is the maximum daily dose). Therapy should be adjusted according to the blood pressure (BP) response. Candesartan FT may be co-administered with other antihypertensive agents. It has been shown that hydrochlorothiazide, when combined with candesartan cilexetil, causes an additional decrease in blood pressure. Children Children and adolescents 6 to 18 years of age The recommended starting dose is 4 mg once daily. – For children and adolescents weighing < 50 kg: if adequate control of arterial hypertension is not achieved, the dose may be increased to a maximum of 8 mg 1 time per day (8 mg is the maximum daily dose for this group of patients). - For children and adolescents weighing ≥ 50 kg: if adequate control of arterial hypertension is not achieved, the dose may be increased to 8 mg 1 time per day, then, if necessary, up to 16 mg 1 time per day. Doses greater than 32 mg of candesartan cilexetil have not been studied in the pediatric population. For children with possible reduced blood volume (eg, patients taking diuretics, in particular those with impaired renal function), treatment with candesartan cilexetil should be started under close medical supervision. At the beginning of treatment, it may be necessary to prescribe a lower dose than those recommended above. The use of candesartan cilexetil in children with a glomerular filtration rate (GFR) < 30 ml/min/1.73 m2 has not been studied. Children of the Negroid race The antihypertensive effect is less pronounced than in children of other races. Children under 6 years The safety and efficacy of candesartan cilexetil in children under 6 years of age has not been studied. No dosage recommendations can be given for candesartan cilexetil in this age group. The use of candesartan cilexetil in children under 6 years of age is contraindicated. Special groups of patients Use in elderly patients Adjustment of the initial dose is not required in elderly patients. Use in patients with reduced circulating blood volume (CBV) In patients with hypovolemia who are at risk of arterial hypotension, an initial dose of 4 mg should be considered. Use in patients with impaired renal function The initial dose of candesartan cilexetil for patients with impaired renal function, including patients on hemodialysis, is 4 mg. The dose should be adjusted depending on the response to treatment. Limited experience with candes