Hyposart, pills 32mg 28pcs

Composition

of 1 tab. candesartan cilexetil 32 mg. Auxiliary substances: lactose monohydrate,174 mg, corn starch – 40 mg hyprolose (viscosity, water,25°C (5%) 75-150 GPA) of 4 mg of hyprolose (viscosity, water,25°C (5%) 1500-3000 SDR) – 4 mg, macrogol 6000 – 5.2 mg, magnesium stearate – 0.8 mg.

Pharmacological action

Angiotensin II receptor antagonist. Angiotensin II is the main RAAS enzyme involved in the pathogenesis of arterial hypertension, heart failure, and other cardiovascular diseases.

Candesartan is a selective angiotensin II receptor antagonist, subtype 1 (AT1receptors). It does not exhibit agonist properties (it does not affect ACE and does not lead to the accumulation of bradykinin or substance P, it does not bind to the receptors of other hormones, and it does not affect the state of ion channels involved in regulating the activity of the cardiovascular system). As a result of blocking AT₁-receptors of angiotensin II, there is a compensatory dose-dependent increase in the activity of renin, the concentration of angiotensin I, angiotensin II, and a decrease in the concentration of aldosterone in blood plasma.

Arterial hypertension

Oral use of candesartan provides a dose-dependent, smooth decrease in blood pressure due to a decrease in OPSS without a reflex increase in heart rate. There are no data on the development of severe hypotension after the first dose or on the development of withdrawal syndrome after discontinuation of therapy.

The onset of antihypertensive action after taking the first dose of the drug usually develops within 2 hours, the duration of the effect is 24 hours. Against the background of continuing therapy with candesartan in a fixed dose, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists throughout treatment. The addition of the thiazide diuretic hydrochlorothiazide to candesartan enhances its antihypertensive effect.

The patient’s age and gender do not affect the effectiveness of the drug. Candesartan increases renal blood flow and does not alter or increase glomerular filtration rate, while renal vascular resistance and filtration fraction are reduced. Candesartan has a less pronounced antihypertensive effect in patients of the black race (a population with predominantly low plasma renin activity).

There are no data on the effect of candesartan on the progression of diabetic nephropathy. In patients with arterial hypertension and type 2 diabetes mellitus, candesartan does not have a negative effect on blood glucose concentration and lipid profile.

Heart failure

Candesartan therapy reduces the mortality rate and hospitalization rate in patients with chronic heart failure (CHF), regardless of age, gender, and concomitant therapy, and leads to a decrease in the NYHA functional class of CHF.

Candesartan is effective in patients taking concomitant beta-blockers in combination with ACE inhibitors; however, its effectiveness does not depend on the dose of an ACE inhibitor. In patients with CHF and reduced left ventricular systolic function (left ventricular ejection fraction (LVEF) less than 40%), candesartan reduces OPSS and pulmonary capillary jamming pressure.

Indications

-arterial hypertension;

– chronic heart failure and impaired left ventricular systolic function (LVEF < 40%) as adjunctive therapy to ACE inhibitors or in case of intolerance to ACE inhibitors.

Use during pregnancy and lactation

The drug Hyposart is contraindicated for use during pregnancy, because it has a direct effect on the RAAS and can cause fetal development disorders (especially in the second and third trimesters of pregnancy) or have a negative effect on the newborn, up to a fatal outcome, if the drug was used during pregnancy. It is known that therapy with angiotensin II receptor antagonists (ARA II) can cause fetal developmental disorders (impaired renal function, oligohydramnios, slowing of ossification of the skull bones) and the development of complications in the newborn (renal failure, hypotension, hyperkalemia). When determining the fact of pregnancy, the drug Hyposart should be discontinued as soon as possible. When planning pregnancy, it is necessary to transfer the patient to an adequate alternative therapy. It is not known whether candesartan is excreted in breast milk, but it is known to enter the milk of lactating rats. During treatment with Hyposart, breastfeeding should be discontinued. Newborns whose mothers took Hyposart during pregnancy should be under close medical supervision due to the likelihood of developing hypotension.

Recommendations for use

The drug is taken orally,1 time/day, regardless of the time of food intake.

Arterial hypertension

The recommended initial and maintenance dose of Hyposart is 8 mg 1 time / day. If necessary, the dose can be increased to 16 mg 1 time/day. The maximum antihypertensive effect is achieved within 4 weeks of therapy. The maximum daily dose is 32 mg 1 time/day.

If adequate blood pressure control is not achieved against the background of the maximum daily dose, it is recommended to add a thiazide diuretic (for example, hydrochlorothiazide) to therapy. This may increase the antihypertensive effect of Hyposart.

In patients at risk of developing arterial hypotension (including patients with reduced BCC), therapy is recommended to start with a dose of 4 mg.

In patients with mild to moderate renal impairment (creatinine clearance 30-80 ml/min/1.73 m2), including patients on hemodialysis, the initial dose of the drug is 4 mg. The dose should be titrated depending on the therapeutic effect. Clinical experience of using the drug in patients with severe renal impairment or end-stage renal failure (creatinine clearance less than 15 ml / min) restricted.

The initial daily dose of the drug in patients with mild to moderate liver disease is 4 mg. It is possible to increase the dose if necessary. There is no clinical experience of using the drug in patients with severe hepatic impairment and / or cholestasis.

Chronic heart failure

The recommended initial dose of Hyposart is 4 mg 1 time / day. An increase to the maximum daily dose of 32 mg 1 time/day or to the maximum tolerated dose is carried out by doubling the dose at intervals of at least 2 weeks.

Elderly patients and patients with impaired renal or hepatic function do not need to adjust the initial dose of the drug.

The safety and efficacy of Hyposart in children and adolescents under 18 years of age have not been established.

Concomitant therapy

Hyposart can be used concomitantly with other medications for the treatment of CHF, including ACE inhibitors, beta-blockers, diuretics, cardiac glycosides, or combinations of these medications.

Contraindications

— hypersensitivity to candesartan or other components of the drug;

— lactose intolerance, lactase deficiency, a syndrome of glucose-galactose malabsorption;

— pregnancy;

— the period of breastfeeding;

— children’s and teenage age up to 18 years (efficacy and safety not established);

— severe disturbances of liver function and/or cholestasis;

— simultaneous use with aliskiren and iliskilendirmesi drugs in patients with diabetes mellitus or renal impairment (GFR less than 60 ml/min).

With caution:  severe renal impairment (creatinine clearance less than 30 ml/min), hemodialysis, bilateral renal artery stenosis or stenosis of the artery of a single kidney, hemodynamically significant aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy (HOCMP), post-kidney transplantation, cerebrovascular disorders of ischemic origin and coronary heart disease, hyperkalemia in patients with reduced BCC, general anesthesia and surgical interventions (risk of developing hypotension due to RAAS blockade), primary hyperaldosteronism.

Side effects

Classification of the frequency of side effects: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10 000, <1/1000); very rare ( Side effects of candesartan are mild and transient. The frequency of side effects does not depend on the dose of the drug and the age of the patient.

Nervous system disorders:  often – dizziness, headache, weakness.

From the cardiovascular system:  often – a marked decrease in blood pressure.

Respiratory system disorders:  often – respiratory infections, pharyngitis, rhinitis, cough.

From the digestive system:  very rarely – nausea, increased activity of hepatic transaminases, impaired liver function or hepatitis.

From the urinary system:  often-impaired renal function, including renal failure in predisposed patients.

Musculoskeletal disorders:  very rarely-back pain, arthralgia, myalgia.

From the hematopoietic system:  very rarely – leukopenia, neutropenia, thrombocytopenia and agranulocytosis.

Laboratory parameters:  very rarely-hyperkalemia, hyponatremia, increased creatinine concentration in the blood, hyperuricemia, a slight decrease in hemoglobin.

Allergic reactions:  very rarely – angioedema, skin rash, pruritus, urticaria.

Other services:  exacerbation of gout, “hot flashes” of blood to the skin of the face.

Interaction

Concomitant use of candesartan with aliskiren-containing medications is contraindicated in patients with diabetes mellitus or moderate to severe renal insufficiency (GFR

Concomitant use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol/levonorgestrel), glibenclamide, nifedipine and enalapril was studied; no clinically significant pharmacokinetic interaction was observed.

Candesartan is only slightly metabolized in the liver (via the CYP2C9 isoenzyme). No effect was found on the CYP2C9 and CYP3A4 isoenzymes; the effect on other cytochrome P 450 isoenzymes is currently unknown.

Antihypertensive agents potentiate the antihypertensive effect of candesartan. Experience with other drugs that affect the RAAS shows that the simultaneous use of the drug and potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, or other agents that can increase the concentration of potassium in the blood serum (for example, heparin), can lead to the development of hyperkalemia.

When lithium preparations and ACE inhibitors were used simultaneously, cases of transient increase in the concentration of lithium in the blood serum and the development of toxic effects were noted. A similar effect is possible with the simultaneous use of lithium preparations and angiotensin II receptor antagonists, which requires periodic monitoring of the concentration of lithium in the blood serum with the combined use of these drugs.

Concomitant use of ARA II and NSAIDs, including selective COX-2 inhibitors and non-selective NSAIDs (for example, acetylsalicylic acid at a dose of more than 3 g/day), may reduce the antihypertensive effect of candesartan.

Double blockade of the RAAS

As with ACE inhibitors, concomitant use of ARA II and NSAIDs increases the risk of decreased renal function, up to the development of renal failure, which leads to hyperkalemia in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. All patients should receive sufficient fluids and renal function should be monitored at the beginning of therapy and thereafter.

Overdose

Symptoms: excessive lowering of blood pressure, dizziness, tachycardia. Individual cases of overdose of the drug (up to 672 mg of candesartan cilexetil), which resulted in recovery of patients without serious consequences, are described.

Treatment: with a pronounced decrease in blood pressure, the patient should be transferred to the supine position, raise the legs; then-take measures aimed at increasing the BCC (use of 0.9% sodium chloride solution IV). If necessary, sympathomimetic drugs may be prescribed. It is recommended to conduct symptomatic therapy under the control of vital body functions. Hemodialysis is ineffective.

Special instructions

Ethnic features

The antihypertensive effect of candesartan in patients of the black race is less pronounced compared to patients of other races, and therefore, an increase in the dose of Hyposart is more often required, as well as a combination with other antihypertensive agents.

Impaired renal function

Experience of using the drug in patients with severe renal insufficiency or who are in the end stage of renal insufficiency (CC In such patients, careful selection of the dose of Hyposart is necessary under strict blood pressure control.

In patients with CHF, especially over the age of 75 years, and in patients with impaired renal function, it is necessary to periodically monitor renal function. During the selection of the dose of Hyposart, it is recommended to monitor the concentration of creatinine and potassium in the blood serum.

Combination therapy with an ACE inhibitor for CHF

When using the drug Hyposart in combination with an ACE inhibitor, the risk of side effects may increase: impaired renal function and hyperkalemia. In these cases, careful monitoring and monitoring of appropriate laboratory parameters is necessary.

Hemodialysis

During hemodialysis, blood pressure may be particularly sensitive to AT1-receptor blockade as a result of BCC reduction and RAAS activation. Therefore, patients undergoing hemodialysis need to monitor blood pressure and individually select the dose of Hyposart.

Renal artery stenosis

Drugs that affect the RAAS, such as ACE inhibitors, can cause hyperuricemia and hypercreatininemia in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney. A similar effect can develop with the use of ARA II.

Kidney transplantation

There is no experience of using the drug in patients who have recently undergone kidney transplantation.

Arterial hypotension

Patients with CHF receiving Hyposart may develop hypotension. Hypotension may also occur in patients with reduced BCC, such as those receiving high-dose diuretics. At the beginning of therapy, care should be taken and, if necessary, compensate for BCC.

General anesthesia/surgical procedures

When performing surgery under general anesthesia, patients taking ARA II may develop hypotension due to RAAS blockade. Very rarely, hypotension may be severe and require intravenous fluids and/or vasopressors.

Aortic and/or mitral valve stenosis, HOCMP

Hyposart should be used with caution in patients with hemodynamically significant aortic and/or mitral valve stenosis or with HOCMP.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect the RAAS, so the use of Hyposart is not recommended for such patients.

Hyperkalemia

Concomitant use of Hyposart with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other agents capable of increasing serum potassium concentrations (for example, heparin) may lead to the development of hyperkalemia in patients with arterial hypertension. Hyperkalemia may also occur in patients with CHF who are taking Hyposart. During therapy with Hyposart in patients with CHF, it is recommended to periodically monitor the concentration of potassium in the blood serum, especially with the simultaneous use of ACE inhibitors and potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride).

General information

Patients whose vascular tone and renal function are predominantly dependent on RAAS activity (for example, patients with severe decompensated CHF or concomitant renal disease, including unilateral renal artery stenosis), therapy with other drugs that affect RAAS may be accompanied by the development of arterial hypotension, azotemia, oliguria and, less often, acute renal failure. This cannot be excluded for angiotensin II receptor antagonists. Excessive lowering of blood pressure in patients with CHD or cerebrovascular diseases of ischemic origin can lead to the development of myocardial infarction or stroke.

Double blockade of the RAAS when using drugs containing aliskiren

Double blockade of the RAAS by concomitant use of candesartan and aliskiren is not recommended, due to the increased risk of hypotension, hyperkalemia and impaired renal function.

Influence on the ability to drive motor vehicles and manage mechanisms

The effect of Hyposart on the ability to drive vehicles and work with complex mechanisms has not been studied, but the pharmacodynamic properties of the drug indicate that there is no such effect. Caution should be exercised when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions due to the risk of dizziness.

Form of production

Tablets are white, round, flat, with a chamfer on both sides, with a dividing risk on one side and an engraving “32” on the other side.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Shelf

life is 2 years.

Active ingredient

Candesartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension, Heart Failure