Hyposart, tablets 32 mg 28 pcs

An 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 (AT₁ receptors). It does not exhibit agonist properties (does not affect ACE and does not lead to accumulation of bradykinin or substance P, does not bind to receptors of other hormones, does not affect ion channels involved in the regulation of cardiovascular activity).

As a result of blocking AT₁-receptors of angiotensin II there is a compensatory dose-dependent increase of renin activity, angiotensin I, angiotensin II concentration and decrease of plasma aldosterone concentration.

Arterial hypertension

The oral administration of candesartan provides a dose-dependent, smooth decrease in BP by reducing PPS without a reflex increase in HR. There are no data on the development of significant arterial hypotension after the first dose or on the development of withdrawal syndrome after discontinuation of therapy.

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

The patient’s age and gender have no effect on the efficacy of the drug. Candesartan increases renal blood flow and does not alter or increase glomerular filtration rate, whereas renal vascular resistance and filtration fraction decrease. Candesartan has a less pronounced antihypertensive effect in patients of non-hypertensive 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 has no adverse effect on blood glucose concentration and lipid profile.

Heart failure

Therapy with candesartan decreases mortality and hospitalization rate in patients with chronic heart failure (CHF) regardless of age, sex, and concomitant therapy, leading to a decrease in NYHA functional class of CHF.

Candesartan is effective in patients taking simultaneously beta-adrenoblockers in combination with ACE inhibitors, and its effectiveness is independent of ACE inhibitor dose. In patients with CHF and reduced left ventricular systolic function (left ventricular ejection fraction (LVEF) less than 40%), candesartan reduces PFS and congestion pressure in the pulmonary capillaries.

Indications

– Arterial hypertension;

Chronic heart failure and impaired left ventricular systolic function (LVEF ≤40%) as additional therapy to ACE inhibitors or when ACE inhibitors are intolerant.

Active ingredient

Composition

Interaction

The use of candesartan concomitantly with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or moderate to severe renal impairment (FFR < 60 ml/min/1.73 m2).

Candesartan has been studied concomitantly with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol/levonorgestrel), glibenclamide, nifedipine and enalapril; no clinically significant pharmacokinetic interaction was noted.

Candesartan is slightly metabolized in the liver (via CYP2C9 isoenzyme). No effect on CYP2C9 and CYP3A4 isoenzymes has been found; the effect on other cytochrome P450 isoenzymes is currently unknown.

Hypotensive agents potentiate the antihypertensive effect of candesartan. Experience with other drugs acting on the RAAS shows that concomitant use of the drug and potassium-saving diuretics (spironolactone, eplerenone, triamterene, amiloride), potassium preparations, salt substitutes containing potassium, or other agents capable of increasing serum potassium concentration (e.g., heparin) may lead to hyperkalemia.

In concomitant use of lithium and ACE inhibitors, there have been cases of transient increase in serum lithium concentration and development of toxic effects. A similar effect is possible with concomitant use of lithium and angiotensin II receptor antagonists, which requires periodic monitoring of serum lithium concentration when combining these drugs.

The simultaneous use of APA II and NSAIDs, including selective COX-2 inhibitors and non-selective NSAIDs (e.g., acetylsalicylic acid over 3 g/day) may decrease the antihypertensive effect of candesartan.

Double RAAS blockade

As with ACE inhibitors, concomitant use of APA II and NSAIDs increases the risk of reduced renal function, up to and including 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 get enough fluids; renal function should be monitored at the beginning of therapy and thereafter.

Directions for use

The drug is taken orally, once daily, regardless of the time of meals.

Arterial hypertension

The recommended starting and maintenance dose of Hyposart is 8 mg once daily. If necessary, the dose may be increased to 16 mg once daily. The maximum antihypertensive effect is reached within 4 weeks of therapy. The maximum daily dose is 32 mg once daily.

If adequate BP control is not achieved at the maximum daily dose, it is recommended to add a thiazide diuretic (e.g., hydrochlorothiazide) to therapy. This may increase the antihypertensive effect of Hyposart.

In patients at risk of arterial hypotension (including patients with decreased blood pressure), it is recommended to start therapy with a dose of 4 mg.

In patients with mild to moderate renal dysfunction (CKD 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 with the drug in patients with severe renal dysfunction or end-stage renal failure (CKR less than 15 ml/min) is limited.

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 liver dysfunction and/or cholestasis.

Chronic heart failure

The recommended starting dose of Hyposart is 4 mg once daily. Increase to a maximum daily dose of 32 mg once daily or to a maximum tolerated dose by doubling the dose at intervals of at least 2 weeks.

Patients who are elderly and patients with renal or hepatic impairment do not require adjustment of the initial dose of the drug.

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

Companion therapy

Hyposart may be concomitantly used with other drugs for treatment of CHF, including ACE inhibitors, beta-adrenoblockers, diuretics, cardiac glycosides, or combinations of these drugs.

Special Instructions

Ethnicity

The antihypertensive effect of candesartan is less pronounced in patients of the Negro race compared to patients of other races, which often requires an increased dose of Hyposart and combination with other hypotensive agents.

Renal dysfunction

The experience with the drug in patients with severe or end-stage renal impairment (CK < 15 ml/min) is limited. In such patients, careful selection of the dose of Hyposart is necessary under strict control of BP.

In patients with CHF, especially those over 75 years of age, and in patients with impaired renal function, renal function should be monitored periodically. Serum creatinine and potassium concentrations should be monitored during dosing of Hyposart.

Combined therapy with ACE inhibitor in CHF

Hyposart in combination with an ACE inhibitor may increase the risk of side effects: impaired renal function and hyperkalemia. In these cases close monitoring and control of relevant laboratory parameters is necessary.

Hemodialysis

During hemodialysis, BP may be particularly sensitive to AT1-receptor blockade as a result of decreased RBC and activation of the RAAS. Therefore, patients on hemodialysis require BP monitoring and individual selection of the dose of Hyposart.

Renal artery stenosis

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

Kidney transplantation

There is no experience with the drug in patients who have recently undergone a kidney transplant.

Arterial hypotension

Hyposart patients receiving Hyposart may develop arterial hypotension. Hypotension is also possible in patients with decreased blood pressure, e.g., those receiving high-dose diuretics. At the beginning of therapy, caution should be exercised and the blood pressure should be compensated if necessary.

Common anesthesia/surgery

In general anesthesia surgical procedures patients taking APA II may experience arterial hypotension due to RAAS blockade. Very rarely, arterial hypotension may be severe and require intravenous administration of fluids and/or vasopressors.

Aortic and/or mitral valve stenosis, GOCMP

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

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs affecting the RAAS, so the use of Hyposart is not recommended in these patients.

Hyperkalemia

. Concomitant use of Hyposart and potassium-saving diuretics, potassium preparations, salt substitutes containing potassium, or other agents capable of increasing serum potassium concentration (e.g., heparin) may lead to hyperkalemia in patients with arterial hypertension. Hyperkalemia may also develop in patients with CHF taking Hyposart. During therapy with Hyposart in patients with CHF it is recommended to perform periodic monitoring of serum potassium concentration, especially during simultaneous use of ACE inhibitors and potassium-saving diuretics (spironolactone, eplerenone, triamterene, amiloride).

General

Patients in whom vascular tone and renal function are predominantly dependent on RAAS activity (e.g., patients with severely decompensated CHF or concomitant renal disease, including unilateral stenosis.including unilateral renal artery stenosis), therapy with other drugs affecting the RAAS can be accompanied by the development of arterial hypotension, azotemia, oliguria and, rarely, acute renal failure. It also cannot be excluded for angiotensin II receptor antagonists. Excessive BP reduction in patients with CHD or cerebrovascular disease of ischemic genesis may lead to myocardial infarction or stroke.

Double RAAS blockade with drugs containing aliskiren

Double RAAS blockade by concomitant use of candesartan and aliskiren is not recommended because of increased risk of arterial hypotension, hyperkalemia, and renal function impairment.

Influence on driving and operating machinery

The effect of Hyposart on driving and operating complex machinery has not been studied, but pharmacodynamic properties of the drug indicate that this effect is absent. Caution should be exercised while driving motor transport and engaging in potentially hazardous activities requiring high concentration and quick psychomotor reactions due to risk of dizziness.

Contraindications

– hypersensitivity to candesartan or other components of the drug;

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

– pregnancy;

– breastfeeding period;

– children and adolescents under 18 years of age (efficacy and safety not established);

– severe hepatic dysfunction and/or cholestasis;

– simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes or impaired renal function (GFR less than 60 ml/min).

With caution: Severe renal dysfunction (CKF less than 30 ml/min), hemodialysis, bilateral renal artery stenosis or artery stenosis of the sole kidney, hemodynamically significant aortic and/or mitral valve stenosis, hypertrophic obstructive cardiomyopathy (HCMP), kidney transplantation, cerebrovascular disorders of ischemic genesis and CHD, hyperkalemia in patients with decreased blood circulation, general anesthesia and surgical interventions (risk of arterial hypotension due to RAAS blockade), primary hyperaldosteronism.

Side effects

Classification of the incidence of side effects: very common (≥1/10); common (≥1/100, < 1/10); infrequent (≥1/1000, < 1/100); rare (≥1/10 000, < 1/1000); very rare (< 1/10 000), including individual reports. Side effects of candesartan are mild and transient. The frequency of side effects is independent of the drug dose and patient age.

Nervous system disorders:often dizziness, headache, weakness.

Cardiovascular system disorders:often – marked decrease in BP.

As for the respiratory system: often – respiratory infections, pharyngitis, rhinitis, cough.

Digestive system disorders: very rarely – nausea, increased liver transaminase activity, impaired liver function or hepatitis.

In the urinary system: frequently – impaired renal function, including renal failure in predisposed patients.

Muscular system disorders: very rarely – back pain, arthralgia, myalgia.

Hematopoietic system: very rarely – leukopenia, neutropenia, thrombocytopenia and agranulocytosis.

Laboratory findings: very rarely – hyperkalemia, hyponatremia, increased blood creatinine concentration, hyperuricemia, slight decrease in hemoglobin.

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

Others: acute course of gout, “rushes” of blood to the skin of the face.

Overdose

Symptoms:excessive BP decrease, dizziness, tachycardia. Individual cases of overdose of the drug (up to 672 mg of candesartan cilexetil) have been described, which ended with recovery of patients without severe consequences.

Treatment:In case of marked BP decrease the patient should be transferred to the supine position with legs elevated; then there should be measures to increase the blood circulation (administration of 0.9% sodium chloride solution intravenously). If necessary, sympathomimetic drugs may be prescribed. Symptomatic therapy under control of vital body functions is recommended. Hemodialysis is ineffective.

Pregnancy use

Similarities