Index of drugs

Treatment of primary hypertension in adults. Treatment of hypertension in children and adolescents from 6 to <18 years. Treatment of adult patients with heart failure and impaired left ventricular systolic function (left ventricular ejection fraction ≤40%) when ACE inhibitors are not tolerated or added to an ACE inhibitor in patients with persistent symptoms of heart failure, despite optimal therapy, when Mineralocorticoid receptor antagonists are not tolerated.

1 tabl contains 8 mg, 16 mg or 32 mg candesartan cilexetil. The tablets contain lactose.

Candesartan cilexetil is a pro-drug which, when absorbed from the gastrointestinal tract, is rapidly converted (by ester hydrolysis) to the active form - candesartan. Candesartan is an angiotensin II receptor antagonist that acts selectively on AT receptors₁. It is characterized by strong binding to the receptor and slow unblocking of this connection. There is no agonist activity. It does not reduce ACE (ACE) enzyme activity, thanks to which it does not increase the effects of bradykinin-dependent effects. It does not bind to other receptors or ion channels important for regulation in the circulatory system. In hypertension, candesartan induces a dose-dependent, long-lasting reduction in blood pressure as a result of a reduction in total vascular resistance without reflexive acceleration of the heart rhythm. After a single dose, the antihypertensive effect usually occurs within 2 hours; full antihypertensive effect usually occurs within 4 weeks of treatment. In heart failure, treatment with candesartan reduces mortality, the need for hospitalization for heart failure, and improves the condition of patients with impaired left ventricular systolic function. The maximum concentration of candesartan in the blood occurs after 3-4 hours after administration of the drug. Candesartan is highly bound to plasma proteins (over 99%). It is excreted mainly in unchanged form with urine and bile. T_0.5 is about 9 hours.

Hypersensitivity to candesartan or other ingredients. Severe hepatic impairment and / or cholestasis (cholestasis). Children under 1 year of age Co-administration with aliskiren-containing products in patients with diabetes mellitus or renal impairment (glomerular filtration rate, GFR <60 ml / min / 1.73 m²). II and III trimester of pregnancy.

In patients with hypertension and renal failure, periodic monitoring of serum potassium and creatinine is recommended. Data on the use of the preparation in patients with very severe or end-stage renal disease (creatinine clearance <15 ml / min) are limited. The evaluation of patients with heart failure should include periodic tests of renal function, especially in> 75 years and in patients with impaired renal function. When setting a dose in patients with heart failure, monitoring of potassium and creatinine levels is recommended. Clinical trials on heart failure did not include patients with serum creatinine> 265 μmol / l (> 3 mg / dl). Studies on the use of the preparation in children with a glomerular filtration rate <30 ml / min / 1.73 m² they were not kept. The risk of adverse reactions, especially hypotension, hyperkalemia and worsening of renal function (including acute renal failure) may be increased when candesartan is co-administered with an ACE inhibitor. A three-way combination of an ACE inhibitor, a mineralocorticoid receptor antagonist and candesartan is also not recommended. The use of these connections should be under the supervision of a specialist, and the kidney function, electrolyte concentration and blood pressure of the patient should be closely monitored. At the same time, ACE inhibitors and angiotensin II receptor antagonists should not be used in patients with diabetic nephropathy. In patients on dialysis, AT receptor blockade₁ It can cause significant changes in blood pressure because they have reduced plasma volume and increased activity of the renin-angiotensin-aldosterone system - dose selection in these patients should be prudent and combined with accurate blood pressure control. Angiotensin II receptor antagonists may increase serum urea and creatinine levels in patients with bilateral renal artery stenosis or narrowing of the artery to a single kidney. There are no data on the use of the product in kidney transplant patients. The use of candesartan in patients with heart failure may result in hypotension. Hypotension may also occur in hypertensive patients with decreased intravascular volume, e.g. in patients taking high doses of diuretics. In this group of patients, caution should be exercised when starting treatment and an attempt to compensate for hypovolaemia. In children with possible circulating blood volume reduction (eg in patients treated with diuretics, especially in those with impaired renal function), treatment with candesartan should be initiated under close medical supervision and a lower starting dose should be considered. In patients treated with angiotensin II antagonists during anesthesia and surgery, hypotension may occur due to inhibition of the renin-angiotensin system; very rarely hypotension can be serious and intravenous fluids and / or blood pressure-lowering medicines may be necessary. Special care should be taken in patients with haemodynamically significant aortic or mitral valve stenosis or with hypertrophic cardiomyopathy with narrowing of the left ventricle outflow pathway. Patients with primary hyperaldosteronism generally do not respond to treatment with antihypertensive drugs acting through the inhibition of the renin-angiotensin-aldosterone system - therefore, the use is not recommended in this group of patients. Co-administration of candesartan together with potassium sparing diuretics, potassium supplements, potassium-containing salt substitutes or other drugs that may increase potassium levels (eg heparin) may result in increased serum potassium in hypertensive patients - potassium levels should be monitored serum. In patients with heart failure taking candesartan, hyperkalaemia may occur - periodic monitoring of serum potassium is recommended. Concomitant use of ACE inhibitors, potassium-sparing diuretics (eg spironolactone) and candesartan is not recommended and can only be considered after careful evaluation of the potential benefits and risks. In patients with vascular tone and renal function to a large extent dependent on the activity of the renin-angiotensin-aldosterone system (e.g., in patients with severe congestive heart failure or kidney disease, including renal artery stenosis), treatment with other medicines affecting the this system led to severe hypotension, azotemia, oliguria or, more rarely, severe renal failure. Excessive hypotension when using antihypertensive medicinal products in patients with ischemic heart disease or cerebrovascular disease may result in a myocardial infarction or stroke. The concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalaemia and renal dysfunction (including acute renal failure) - therefore, dual blocking of the RAA system is not recommended by concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren. If the use of a dual RAA blockade is absolutely necessary, it should only be carried out under the supervision of a specialist, and the vital parameters of the patient, such as kidney function, electrolyte concentration and blood pressure should be closely monitored. In patients with diabetic nephropathy, ACE inhibitors and angiotensin II receptor antagonists should not be used concurrently. The safety and efficacy of the medicine in children from 1 to <6 years have not been determined. Due to the lactose content, patients with congenital galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose should not take this preparation.

The use of candesartan in the first trimester of pregnancy is not recommended. Use in the second and third trimester of pregnancy is contraindicated - the drug is toxic to fetal development (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, hypotension, hyperkalemia). In cases where exposure to the drug occurred from the second trimester of pregnancy, ultrasound examination of the fetus skull and kidneys is recommended. Children whose mothers took the drug during pregnancy should be closely monitored for possible hypotension. In patients after the first menstruation, the possibility of pregnancy should be regularly assessed. Candesartan is not recommended during breast-feeding.

Hypertension - often: respiratory tract infections, dizziness / vertigo, headache; very rare: leukopenia, neutropenia, agranulocytosis, hyperkalemia, hyponatremia, cough, nausea, increase in liver enzymes, liver dysfunction or hepatitis, angioedema, rash, urticaria, pruritus, back pain, joint pain, muscle pain, kidney problems (including renal failure in susceptible patients); a slight decrease in hemoglobin was also observed. While the nature and severity of adverse events in children and adolescents are similar to those observed in adult patients, the incidences of all adverse events are higher in children and adolescents, especially with regard to such actions as: headache, dizziness, upper respiratory tract infection , cough, mouth and throat pain (very common); rash, sinus arrhythmia, nasopharyngitis, fever (common); hyperkalemia, hyponatraemia, abnormal liver function (uncommon). The general safety profile of candesartan in pediatric patients is not significantly different from the safety profile of adult patients. Heart failure - often: hyperkalemia, hypotension, renal dysfunction (including renal failure in susceptible patients); very rare: leukopenia, neutropenia, agranulocytosis, hyponatremia, headache and dizziness, nausea, increased liver enzymes, liver dysfunction or hepatitis, angioneurotic edema, rash, urticaria, pruritus, back pain, joint pain, muscle pain.

Orally.Hypertension. Adults. The starting dose and usual maintenance dose is 8 mg once a day. The best antihypertensive effect is achieved within 4 weeks of starting treatment. In patients whose blood pressure is not adequately controlled, the dose may be increased to 16 mg once a day, up to a maximum of 32 mg once a day. The treatment regimen should be determined individually, depending on the patient's response to treatment. Candesartan can be used concomitantly with other antihypertensive drugs. It has been observed that the use of hydrochlorothiazide together with any dose of candesartan causes an additional reduction in blood pressure. There is no need to change the starting dose in elderly patients. In patients at risk of hypotension, such as patients with intravascular volume depletion, a starting dose of 4 mg may be considered. In patients with renal insufficiency (including those undergoing hemodialysis) and in patients with mild or moderate hepatic impairment, the starting dose is 4 mg. Data on the use of this product in patients with very severe or end-stage renal disease (creatinine clearance <15 ml / min) are limited - dose-finding should be prudent and should be accompanied by careful monitoring of blood pressure. In black patients, it may be more necessary to increase the dose and the simultaneous use of other antihypertensive drugs.Children from 6 to <18 years. The recommended starting dose is 4 mg once a day. In patients with insufficient control of blood pressure, the dose may be increased: in patients with an <50 kg to a maximum of 8 mg once a day; in patients with mc. ≥50 kg to 8 mg once daily, followed by up to 16 mg once a day, if indicated. The use of doses exceeding 32 mg has not been studied in children and adolescents. Most of the effects of the antihypertensive effect of the drug are obtained within 4 weeks. In children with the possibility of reducing the volume of circulating blood (e.g.in patients treated with diuretics, especially in those with impaired renal function), treatment with the preparation should be implemented under close medical supervision and a lower starting dose should be considered than the general starting dose given above. Studies on the use of the drug in children with a glomerular filtration rate <30 ml / min / 1.73 m² they were not kept. In pediatric Black patients, the antihypertensive effect of candesartan is less pronounced than in patients of other breeds.Heart failure: the starting dose is 4 mg once a day. This dose can be increased by doubling, at intervals of at least 2 weeks, to the highest dose tolerated by the patient - no more than 32 mg once a day. Candesartan can be co-administered with other medicines used to treat heart failure, including ACE inhibitors, beta blockers, diuretics and digitalis or with the combination of these medicines. The preparation can be given in combination with an ACE inhibitor in patients with persistent symptoms of heart failure despite the use of optimal standard therapy for heart failure when mineralocorticoid receptor antagonists are not tolerated. The concomitant use of an ACE inhibitor, a potassium sparing diuretic and candesartan is not recommended and can only be considered after a thorough benefit and risk assessment. There is no need to change the starting dose in elderly patients or in patients with decreased intravascular volume, renal insufficiency or mild to moderate hepatic impairment. The safety and efficacy of the preparation in children and adolescents <18 years in the treatment of heart failure has not been established.
The tablets should be taken once a day, with or without food.