Atacand® (Atacand®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceCandesartanCandesartan
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    • Dosage form: & nbsppills
    Composition:

    1 tablet contains:

    active substance: candesartan cilexetil 32 mg;

    auxiliary substances:cellulose carboxymethylcellulose (carmellose calcium salt) 11.0 mg, giprolase 8.0 mg, iron stain red oxide E 172 0.52 mg; lactose monohydrate 163.0 mg, magnesium stearate 0.8 mg, corn starch 40.0 mg, macrogol 5.2 mg.

    Description:
    Pink round biconvex tablet with a notch and an engraving on one side and 032 on the other.
    Pharmacotherapeutic group:Angiotensin II receptor antagonist
    ATX: & nbsp

    C.09.C.A.06   Candesartan

    Pharmacodynamics:

    Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system, which plays an important role in the pathogenesis of arterial hypertension, heart failure and other cardiovascular diseases.The main physiological effects of angiotensin II are vasoconstriction, stimulation of aldosterone production, regulation of water-electrolyte homeostasis and stimulation of cell growth. All these effects are mediated by the interaction of angiotensin II with angiotensin type 1 receptors (AT1 receptors).

    Candesartan is a selective antagonist of angiotensin II receptor type 1 (AT1 receptors). Candesartan does not inhibit the angiotensin-converting enzyme (ACE), which converts angiotensin I into angiotensin II and breaks down bradykinin; does not affect the ACE and does not lead to the accumulation of bradykinin or substance P. When comparing candesartan with ACE inhibitors, the development of cough was less common in patients who received candesartan cilexetil. Candesartan does not bind to the receptors of other hormones and does not block the ion channels involved in the regulation of the functions of the cardiovascular system. As a result of blocking AT1 receptors of angiotensin II, a dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in aldosterone in the blood plasma.

    Arterial hypertension

    With arterial hypertension candesartan causes a dose-dependent long-term reduction in blood pressure (BP). The antihypertensive effect of the drug is due to a decrease in the general peripheral vascular resistance, without changing the heart rate (heart rate). There were no cases of severe arterial hypotension after taking the first dose of the drug, as well as withdrawal syndrome ("ricochet" syndrome) after discontinuation of therapy. The onset of antihypertensive action after taking the first dose of candesartan cilexetil usually develops within 2 hours. Against the background of ongoing therapy with the drug in a fixed dose, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists throughout the treatment. Candesartan tsileksetil, appointed once a day, provides an effective and smooth decrease in blood pressure within 24 hours with minor fluctuations of blood pressure in the intervals between the doses of the next dose of the drug. The use of candesartan cilexetil together with hydrochlorothiazide leads to an increased antihypertensive effect. The combined use of candesartan cilexetil and hydrochlorothiazide (or amlodipine) is well tolerated.

    The effectiveness of the drug does not depend on the age and sex of patients.

    Candesartan cilexetil increases renal blood flow and does not change or increases the rate of glomerular filtration, whereas renal vascular resistance and filtration fraction decrease. The use of candesartan cilexetil in a dose of 8-16 mg for 12 weeks does not adversely affect the glucose concentration and lipid profile in patients with hypertension and type 2 diabetes. The clinical effect of candesartan cilexetil on morbidity and mortality at 8-16 mg (mean dose 12 mg) once daily was studied in a randomized clinical trial involving 4937 elderly patients (age 70 to 89 years, 21% of patients in age 80 years and older) with mild to moderate arterial hypertension who are receiving candesartan cilexetil therapy for an average of 3.7 years (SCOPE is a study of cognitive function and prognosis in elderly patients). Patients received candesartan cilexetil or placebo, if necessary, in combination with other antihypertensive agents.Both regimens showed an effective reduction in systolic and diastolic blood pressure (from 166/90 to 145/80 mm Hg in the group of patients who received candesartan, and from 167/90 to 149/82 mm Hg. in the control group) against a background of good tolerability. Cognitive function and quality of life were maintained at a good level in both groups of patients. There were no statistically significant differences in the incidence of cardiovascular events between these two groups of patients (cardiovascular mortality, the incidence of nonfatal myocardial infarction and nonfatal stroke).

    In the group of patients who received candesartan, there were 26.7 cases of cardiovascular complications per 1000 patient-years, compared with 30.0 cases per 1000 patient-years in the control group (relative risk = 0.89, 95% confidence interval 0.75-1, 06, p = 0.19).

    The table below shows the results of the assessment of the primary endpoint (cardiovascular complications) and its components.

    Number of patients with primary event

    Relative

    risk (95% CI)

    R

    Candesartana

    cilexetil *

    (N = 2477)

    Control*

    (N = 2460)

    Cardiovascular complications:

    242

    268

    0,89 (0,75-1,06)

    0,19

    Cardiovascular mortality

    145

    152

    0,95 (0,75-1,19)

    0,63

    Non-fatal stroke

    68

    93

    0,72 (0,53-0,99)

    0,04

    Non-fatal myocardial infarction

    54

    47

    1,14 (0,77-1,68)

    0,52

    * Prior to randomization, any previous antihypertensive therapy was standardized to hydrochlorothiazide at a dose of 12.5 mg once daily.

    Another antihypertensive agent was added to the double-blind study drug (candesartan cilexetil 8-16 mg or placebo once a day) if systolic blood pressure remained ≥160 mm Hg and / or diastolic blood pressure ≥ 90 mmHg. 49% and 66% of patients in the candesartan cilexetil group and control group received this additional therapy, respectively.

    Heart failure

    According to the results of the study CHARM (Candesartan in chronic heart failure - Assessment of Decrease in Mortality and Morbidity), the use of candesartan cilexetil led to a reduction in the incidence of deaths and the need for hospitalization for chronic heart failure and improved systolic function of the left ventricle.

    Patients with chronic heart failure in addition to the main therapy received candesartan tsileksetil in a dose of 4 - 8 mg per day with increasing doses up to 32 mg per day or up to the maximum tolerable therapeutic dose (the 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 take candesartan cilexetil (89%), received a therapeutic dose of 32 mg.

    In another CHARM-Alternative study (n = 2028) patients with a reduced left ventricular ejection fraction (LVEF) ≤40% who did not receive an ACE inhibitor because of intolerance (mainly due to a cough - 72%) participated; the rates of deaths from cardiovascular diseases and the first hospitalization for chronic heart failure were significantly lower in the group of patients who received candesartan compared with the placebo group (risk ratio = 0.77, 95% confidence interval 0.67-0.89, p <0.001). The relative risk reduction was 23%. Statistically, in this study, 14 patients were required to be treated throughout the study period to prevent one death from cardiovascular complications or hospitalization for chronic heart failure. The combined indicator, which included the frequency of deaths regardless of their causes, and the rate of first hospitalization for chronic heart failure, was also significantly lower in the group of patients who received candesartan (risk ratio = 0.80, 95% confidence interval 0.70-0.92, p = 0.001). In this case, the positive effect of candesartan on each of the components of this combined criterion - the rate of deaths and incidence (the frequency of hospitalizations for chronic heart failure) was noted. The use of candesartan cilexetil led to an improvement in the functional class of chronic heart failure according to NYHA classification (p = 0.008).

    In the CHARM-Added study (n = 2548) in patients with reduced LVEF <40% who received ACE inhibitors, the combined test, including the mortality from cardiovascular disease and the first hospitalization for chronic heart failure, was significantly lower in the group of patients who received candesartan, compared with the placebo group (risk ratio = 0.85, 95% confidence interval 0.75-0.96, p = 0.011), which corresponded to a 15% relative risk reduction. In this study, to prevent one death from cardiovascular complications or hospitalization for chronic heart failure, it was necessary to treat 23 patients throughout the study period.The value of the combined efficacy index, which included an estimate of the frequency of deaths regardless of their cause or frequency of first hospitalization for chronic heart failure, was significantly lower in the group of patients receiving candesartan (risk ratio = 0.87, 95% confidence interval 0.78-0.98, p = 0.021), which also indicated a positive effect with candesartan. The use of candesartan cilexetil led to an improvement in the functional class of chronic heart failure according to the NYHA classification (p = 0.020).

    In the CHARM-Preserve study (n = 3023), in patients with preserved systolic function (LVEF> 40%), there was no statistically significant difference in the value of the combined efficacy index, which included the incidence of fatal outcomes and the frequency of first hospitalization for chronic heart failure, in the groups candesartan and placebo (risk ratio = 0.89, 95%, confidence interval 0.77 - 1.03, p = 0.118). A small numerical decrease in this criterion was due to a decrease in the frequency of hospitalizations for chronic heart failure.In this study, the effect of candesartan on the incidence of fatal outcomes was not shown.

    In a separate analysis of the results of 3 studies of the CHARM program, there was no significant difference in the incidence of fatal outcomes in the candesartan and placebo groups. However, the death rate was assessed in the combined CHARM-Alternative and CHARM-Added studies and in all 3 studies (risk ratio = 0.91, 95% confidence interval 0.83-1.00, p = 0.055). Decrease in the frequency of deaths and frequency of hospitalizations for chronic heart failure in the context of candesartan therapy did not depend on age, sex and concomitant therapy. Candesartan was also effective in patients taking beta-blockers in combination with ACE inhibitors, while the effectiveness of candesartan did not depend on whether the patient was taking the optimal dose of an ACE inhibitor or not.

    In patients with chronic heart failure and reduced left ventricular systolic function (LVEF ≤ 40%), candesartan administration contributed to a reduction in overall peripheral vascular resistance and capillary pressure in the lungs, increased renin activity and angiotensin II concentration in blood plasma, and a decrease in aldosterone levels.

    Pharmacokinetics:

    Suction and distribution

    Candesartan cilexetil is a prodrug for oral administration. Quickly turns into an active substance - candesartan through ether hydrolysis when absorbed from the digestive tract, firmly binds to the AT1- receptors and slowly dissociates, does not have the properties of an agonist. Absolute bioavailability of candesartan after ingestion of a solution of candesartan cilexetil is about 40%. The relative bioavailability of the tablet preparation as compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. The maximum concentration in the blood serum (C max) is achieved 3-4 hours after taking the tablet form of the drug. With an increase in the dose of the drug within the recommended range candesartan increases linearly. The pharmacokinetic parameters of candesartan do not depend on the sex of the patient. Food intake does not have a significant effect on the area under the concentration-time curve (AUC), i.e. simultaneous intake of food does not significantly affect the bioavailability of the drug. Candesartan actively binds to blood plasma proteins (> 99%). The volume distribution of candesartan is 0.1 l / kg.

    Metabolism and excretion from the body

    Candesartan, basically, is excreted from the body by the kidneys and bile in unchanged form and only marginally metabolized in the liver. The half-life of candesartan is approximately 9 hours. Cumulation in the body is not observed.

    The total clearance of candesartan is about 0.37 ml / min / kg, with a kidney clearance of about 0.19 ml / min / kg. Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion. When ingestion of radio-labeled candesartan cilexetil, about 26% of the administered amount is excreted by the kidneys in the form of candesartan and 7% in the form of an inactive metabolite, whereas in the stool 56% of the administered amount as candesartan and 10% in the form of an inactive metabolite is detected.

    In elderly patients (over 65 years), C max and AUC of candesartan increase by 50% and 80%, respectively, compared with young patients. However, the hypotensive effect and incidence of side effects when using Atacanda do not depend on the age of the patients.

    In patients with mild to moderate renal dysfunction, Cmax and AU candesartan increased by 50% and 70%, respectively, whereas the half-life of the drug did not change compared to patients with normal renal function. In patients with severe renal dysfunction, Cmax and AUC of candesartan increased by 50% and 110%, respectively, and the half-life of the drug increased 2-fold. Patients on hemodialysis were found to have the same pharmacokinetic parameters of candesartan as in patients with severe renal dysfunction.

    In patients with mild and moderate impairment of liver function, AUC of candesartan was increased by 23%.

    Indications:

    Arterial hypertension.

    Chronic heart failure and impaired systolic function of the left ventricle (reduced LVEF ≤ 40%) as adjunctive therapy to angiotensin-converting enzyme (ACE) inhibitors or with intolerance to ACE inhibitors (see section "Pharmacodynamics").

    Contraindications:

    Hypersensitivity to candesartan cilexetil or other components that make up the drug.

    Pregnancy and the period of breastfeeding (see section "Application during pregnancy and during breast-feeding").

    Severe liver dysfunction and / or cholestasis.

    Lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

    The use of candesartan cilexetil in combination with preparations containing anskilen, in patients with diabetes mellitus (type 1 or type 2) or with moderate or severe renal failure (glomerular filtration rate <60 ml / min / 1.73 m2).

    Carefully:

    In patients with severe renal insufficiency (creatinine clearance less than 30 ml / min), bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, with hemodynamically significant stenosis of the aortic and mitral valve, after a kidney transplant in anamnesis, in patients with cerebrovascular disease and coronary heart disease (IHD), hyperkalemia, in patients with reduced circulating blood volume, primary hyperaldosteronism (there is insufficient data on clinical studies), hypertrophy Coy obstructive cardiomyopathy.

    Pregnancy and lactation:

    Pregnancy

    The use of Atacand® during pregnancy is contraindicated (see the section "Contraindications").

    Patients taking Atacand ® should be warned about this before planning a pregnancy so that they can discuss alternative therapies with their doctor. In the case of pregnancy, therapy with Atacand® should be immediately discontinued and, if necessary, an alternative treatment is prescribed.

    Drugs that have a direct effect to renin-angiotensin-aldosterone system, can cause violations develop a fetus or have a negative action on the newborn, up to lethal outcome, when applied drug during pregnancy.

    It is known that antagonist therapy receptors of angiotensin II may cause impaired development of the fetus kidney function, oligohydramnion, Deceleration of ossification of the skull bones) and development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

    Breastfeeding period

    Currently not known, penetrates whether candesartan in breast milk. In connection with possible undesirable effect on infants, Atacand® should not be used during breastfeeding.

    Dosing and Administration:

    Atacand® should be taken once a day, regardless of food intake. For the following mode dosing of Atacand® in a dosage form is possible tablets of 8 and 16 mg.

    Arterial hypertension

    The recommended initial and maintenance dose of Atacanda® for arterial hypertension is 8 mg once a day. Patients who did not manage to sufficiently lower arterial pressure after 4 weeks of receiving Atakanda® at a dose of 16 mg per day, it is recommended to increase the dose to 32 mg once a day.

    In the event that therapy with Atacand® does not lead to a decrease blood pressure to optimal level, it is recommended to change the scheme treatment.

    TTherapy should be accordance with the level of arterial pressure.

    The maximum antihypertensive effect is achieved within 4 weeks from the start of treatment.

    Elderly patients

    In elderly patients, there is no need to adjust the initial dose of the drug.

    Patients with impaired renal function

    In patients with mild or moderate renal impairment (creatinine clearance 30-80 ml / min), including patients on hemodialysis, the initial dose of the drug is 4 mg (1/2 tablet of 8 mg). The dose should be titrated depending on the therapeutic effect of the drug.

    Clinical experience of the drug in patients with severe renal dysfunction or terminal stage of renal failure (creatinine clearance less than 15 ml / min) is limited (see section "Special instructions").

    Patients with impaired hepatic function

    The initial daily dose of the drug in patients with impaired liver function of mild and moderate severity is 4 mg (1/2 tablet of 8 mg). It is possible to increase the dose if necessary.

    Atacand® is contraindicated in patients with severe impairment of liver function and / or cholestasis (see "Contraindications").

    Concomitant therapy

    The use of Atakand® together with thiazide type diuretics (for example, hydrochlorothiazide) can enhance the antihypertensive effect of Atakand®.

    Hypovolemia

    The recommended initial dose of the drug Atacand® is 4 mg (1/2 tablets of 8 mg) once a day.

    Heart failure

    The recommended initial dose of Atakand is 4 mg (1/2 tablet of 8 mg) once a day. Increasing the dose to 32 mg once a day or up to the maximum tolerated dose is done by doubling it at intervals of not less than 2 weeks (see section "Special instructions").

    Special Groups patients

    Older patients and patients with impaired renal, hepatic or hypovolemic function do not need to change the initial dose of the drug.

    Application in children and adolescents

    The safety and efficacy of Atacand® in children and podsotkov (under the age of 18 years) have not been established.

    Concomitant therapy

    Atakand® can be administered jointly by other agents used in the therapy of chronic heart failure, for example, ACE inhibitors, beta-blockers, diuretics and cardiac glycosides (see section "Specific guidance", "Pharmacodynamics").

    Side effects:

    Arterial hypertension

    Side effects in clinical trials were mild and transient and were comparable in frequency with the placebo group.The overall incidence of side effects associated with Atacanda® was independent of the dose and age of the patient. The incidence of discontinuation due to side effects was similar when using candesartan cilexetil (2.4%) and placebo (2.6%).

    During the analysis of the data of the conducted studies, the following side effects were reported, often (> 1/100) occurring against the background of the reception of candesartan cilexetil. The described side effects were observed with a frequency of at least 1% more than in the placebo group.

    From the central nervous system: dizziness, weakness, headache.

    From the musculoskeletal system, connective tissue: backache.

    Infections: Respiratory infections.

    Laboratory indicators: In general, no clinically significant changes in standard laboratory parameters were observed with Atacanda®. As with other inhibitors of the renin-angiotensin-aldosterone system, there may be a slight decrease in hemoglobin concentration. There was an increase in the creatinine, urea or potassium content and a decrease in the sodium content.The increase in ALT levels was noted somewhat more frequently with Atacanda® compared with placebo (1.3% instead of 0.5%). When using Atacanda®, there is usually no need for regular monitoring of laboratory indicators. However, in patients with impaired renal function, it is recommended to periodically monitor the level of potassium and creatinine in the serum.

    Chronic heart failure

    The side effects found in the background of Atakanda® in patients with chronic heart failure corresponded to the pharmacological properties of the drug and depended on the patient's condition. In the clinical trials of CHARM, Atakand® was compared in doses up to 32 mg (n = 3803) with placebo (n = 3796), 21% of patients in the group of patients receiving candesartan cilexetil, and 16.1% of patients in the placebo group discontinued treatment due to adverse reactions.

    The most common side effects (≥1 / 100, <1/10):

    From the side of the cardiovascular system: marked decrease in blood pressure.

    From the side of the urinary system: impaired renal function.

    Laboratory changes: increase in the level of creatinine, urea and potassium. It is recommended to monitor the level of creatinine and potassium in the blood serum.

    The following side effects during post-marketing use of the drug were reported very rarely (<1 / 10,000):

    From the side of the blood and lymphatic system: leukopenia, neutropenia and agranulocytosis.

    Disturbance of metabolism and diseases caused by metabolic disorders: hyperkalemia, hyponatremia.

    From the nervous system: dizziness, weakness, headache.

    From the gastrointestinal tract: nausea.

    From the liver and biliary tract: increased activity of "liver" enzymes, a violation of liver function or hepatitis.

    Allergic reactions: angioedema, skin rash, hives, itching.

    From the musculoskeletal system, connective tissue: back pain, arthralgia, myalgia.

    From the side of the urinary system: impaired kidney function, including renal failure in predisposed patients.

    Overdose:

    Symptoms

    Analysis of pharmacological data of the drug suggests that the main manifestation of an overdose may be a clinically pronounced decrease in blood pressure and dizziness. Individual cases of drug overdose (up to 672 mg of candesartan cilexetil), which resulted in the recovery of patients without severe consequences, were described.

    Treatment

    With the development of a clinically pronounced decrease in blood pressure, it is necessary to carry out symptomatic treatment and monitor the patient's condition. Lay the patient on his back, raise his legs. If necessary, increase the volume of circulating blood plasma, for example, by iv injection of 0.9% sodium chloride solution. If necessary, sympathomimetic preparations may be prescribed. Candesartan is not excreted by hemodialysis.

    Interaction:

    The use of candesartan cilexetil in combination with drugs containing aliskiren, is contraindicated in patients with diabetes mellitus (type 1 or type 2) or with moderate or severe renal insufficiency (glomerular filtration rate <60 ml / min / 1.73 m2) and is not recommended for other patients (see the sections "Contraindications" and "Special instructions").

    In pharmacokinetic studies, the combined use of Atacand® with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol / levonorgestrel), glibenclamide, nifedipine, and enalapril was studied. Clinically significant pharmacokinetic interaction was not revealed.

    Candesartan is metabolized in the liver to an insignificant extent (isoenzyme CYP2C9). The conducted studies on the interaction did not reveal the effect of the drug on the isoenzymes CYP2C9 and CYP3A4, the effect on other isoenzymes of the cytochrome P450 system has not been studied. The simultaneous use of Atacand® with other antihypertensive drugs potentiates the antihypertensive effect.

    The experience with other drugs acting on the renin-angiotensin-aldosterone system shows that concomitant therapy with potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other agents that can increase serum potassium (for example, heparin) can lead to the development of hyperkalemia.

    When combined prescription of lithium preparations with ACE inhibitors, a reversible increase in the concentration of lithium in serum and the development of toxic reactions were reported. Similar reactions can occur with the use of angiotensin II receptor antagonists, and therefore it is recommended to monitor the concentration of lithium in the serum when combined with these drugs.

    With the combined use of angiotensin II receptor antagonists and non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2, acetylsalicylic acid, hypotensive effect may decrease.

    As with the use of ACE inhibitors, the combined use of angiotensin II receptor antagonists and NSAIDs may increase the risk of renal dysfunction, including acute renal failure, an increase in serum potassium, especially in patients with reduced renal function.

    Caution should be exercised in the joint use of these drugs, especially in elderly patients and in patients with reduced circulating blood volume. Patients need to compensate for fluid loss and regularly monitor kidney function after initiating combination therapy and periodically against such therapy.

    The bioavailability of candesartan is not dependent on food intake.

    Special instructions:

    Impaired renal function

    Against the background of therapy with Atacand®, as with other agents that affect or act on the renin-angiotensin-aldosterone system, some patients may have impaired renal function.

    When using Atakand® in patients with arterial hypertension and severe renal failure (creatinine clearance less than 30 ml / min), it is recommended to periodically monitor the potassium content and serum creatinine concentration. The clinical experience of using the drug in patients with severe renal dysfunction or terminal stage of renal failure is limited (creatinine clearance less than 15 ml / min). Such patients should be cautioned titrate the dose of Atacand ® under careful control of blood pressure.

    Patients with chronic heart failure need periodic monitoring of kidney function, especially in patients aged 75 years and older, as well as in patients with impaired renal function. When the dose of Atakand® is increased, it is also recommended to monitor the potassium content and creatinine concentration.

    Clinical studies of Atacand® in patients with chronic heart failure did not include patients with a concentration of more than 265 μmol / L (> 3 mg / dl).

    Co-administration with ACE inhibitors in chronic heart failure

    When applying candesartan in combination with ACE inhibitors, the risk of side effects may increase, especially kidney and hyperkalemia (see "Side effect" section). In these cases, careful monitoring and monitoring of laboratory indicators is necessary.

    Stenosis of the renal artery

    In patients with bilateral renal artery stenosis or stenosis of the single kidney artery, drugs that affect the renin-angiotensin-aldosterone system, in particular ACE inhibitors, can cause an increase in the concentration of urea and creatinine in the serum. Similar effects can be expected with the appointment of angiotensin II receptor antagonists.

    Kidney transplantation

    Clinical experience of Atakand® in patients who underwent kidney transplantation is limited.

    Arterial hypotension

    In patients with chronic heart failure against the background of therapy with Atacand®, hypotension may develop. As with the use of other drugs that affect the renin-angiotensin-aldosterone system, the cause of the development of arterial hypotension in patients with arterial hypertension can be a decrease in the volume of circulating blood, as observed in patients receiving high doses of diuretics.Therefore, at the beginning of therapy, care should be taken and, if necessary, correct hypovolemia.

    Double blockade of the renin-angiotensin-aldosterone system when applied preparations containing aliskiren

    The double blockade of the renin-angiotensin-aldosterone system is not recommended by combining candesartan cilexetil and aliskiren, in view of the increased risk of arterial hypotension, hyperkalemia, and renal function changes.

    The use of candesartan cilexetil in combination with aliskiren is contraindicated in patients with diabetes mellitus (type 1 or type 2) or with moderate or severe renal failure (GFR <60 mL / min / 1.73 m2) (see the section "Contraindications").

    General anesthesia and surgery

    Patients receiving angiotensin II antagonists may develop arterial hypotension as a result of blockade of the renin-angiotensin-aldosterone system during general anesthesia and during surgical interventions. Very rarely there can be cases of severe arterial hypotension, requiring intravenous administration of plasma-substituting solutions and / or vasopressors.

    Stenosis of the aortic and mitral valve or hypertrophicobstructive cardiomyopathy

    Care should be taken when administering Atacand®, as well as other vasodilators, to patients with hypertrophic obstructive cardiomyopathy or hemodynamically significant stenosis of the aortic or mitral valve.

    Primary hyperaldosteronism

    Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the renin-angiotensin-aldosterone system. In this regard, Atacand® is not recommended for such patients.

    Hyperkalemia

    The clinical experience of using other drugs that affect the renin-angiotensin-aldosterone system shows that simultaneous administration of Atacand® with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase the potassium content in the blood (for example, heparin), can lead to the development of hyperkalemia in patients with arterial hypertension.

    In patients with chronic heart failure against the background of therapy with Atacand®, hyperkalemia can develop.When administering Atakand® to patients with chronic heart failure, regular monitoring of potassium in the blood is recommended, especially when co-administered with ACE inhibitors and potassium-sparing diuretics.

    Are common

    Patients with vascular tone and kidney function are primarily dependent on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis) are particularly sensitive to drugs acting on the renin-angiotensin-aldosterone system. The appointment of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. The possibility of developing these effects can not be ruled out when angiotensin II receptor antagonists are used. A sharp decrease in blood pressure in patients with coronary heart disease or cerebrovascular diseases of atherosclerotic genesis with the use of any antihypertensive drugs can lead to the development of myocardial infarction or stroke.

    Effect on the ability to drive transp. cf. and fur:

    Influence on the ability to drive a car or work with machinery has not been studied, but the pharmacodynamic properties of the drug indicate that such an effect is absent.

    When driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions, it should be taken into account that when using the drug, dizziness and fatigue can occur.

    Form release / dosage:

    Tablets of 32 mg.

    Packaging:

    For 14 tablets in a blister of PVC / PVDC / aluminum, 2 blisters per cardboard pack with instructions for use.

    Storage conditions:Store at a temperature not exceeding 30 ° C, out of the reach of children.
    Shelf life:3 years. Do not use after the expiration date.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-001353/08
    Date of registration:29.02.2008 / 22.12.2015
    Expiration Date:Unlimited
    The owner of the registration certificate:AstraZeneca ABAstraZeneca AB Sweden
    Manufacturer: & nbsp
    Representation: & nbspAstraZeneca Pharmaceuticals Ltd.AstraZeneca Pharmaceuticals Ltd.
    Information update date: & nbsp09.10.2017
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