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 in case of intolerance to ACE inhibitors.

Pharmacological effect

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

Candesartan is a selective antagonist of angiotensin II receptors, subtype 1 (AT1 receptors). Does not exhibit agonist properties (does not affect ACE and does not lead to the accumulation of bradykinin or substance P, does not bind to receptors of other hormones, does not affect the state of ion channels involved in the regulation of the cardiovascular system).

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

Arterial hypertension

Oral administration of candesartan provides a dose-dependent, smooth decrease in blood pressure due to a decrease in peripheral vascular resistance without a reflex increase in heart rate. There is no data on the development of severe arterial hypotension after taking the first dose or on the development of withdrawal syndrome after cessation 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. With continued therapy with candesartan at 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 change or increases glomerular filtration rate, while renal vascular resistance and filtration fraction are reduced. Candesartan has a less pronounced antihypertensive effect in patients of the Negroid race (a population with predominantly low renin activity in blood plasma).

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 concentrations and lipid profiles.

Heart failure

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

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

Special instructions

Ethnic characteristics

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

Renal dysfunction

Experience with the drug in patients with severe renal failure or those in end-stage renal failure (creatinine clearance < 15 ml/min) is limited. In such patients, careful selection of the dose of Giposart under strict blood pressure control is necessary.

In patients with CHF, especially those over the age of 75 years, and in patients with impaired renal function, renal function should be periodically monitored. During the period of selecting the dose of the drug Giposart, 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 Giposart in combination with an ACE inhibitor, the risk of side effects may increase: impaired renal function and hyperkalemia. In these cases, careful observation and monitoring of relevant laboratory parameters is necessary.

Hemodialysis

During hemodialysis, blood pressure may be especially sensitive to AT1 receptor blockade as a result of a decrease in blood volume and activation of the RAAS. Therefore, patients on hemodialysis need blood pressure monitoring and individual selection of the dose of the drug Giposart.

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 solitary renal artery stenosis. A similar effect can develop with the use of ARA II.

Kidney transplant

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

Arterial hypotension

In patients with CHF receiving Hyposart, arterial hypotension may develop. It is also possible to develop arterial hypotension in patients with reduced blood volume, for example, receiving diuretics in high doses. At the beginning of therapy, care must be taken and, if necessary, compensate for the volume of blood volume.

General anesthesia/surgical procedures

When performing surgical interventions under general anesthesia, patients taking ARA II may develop arterial hypotension due to blockade of the RAAS. Very rarely, hypotension may be severe and require IV fluids and/or vasopressors.

Stenosis of the aortic and/or mitral valves, HOCM

Giposart should be used with caution in patients with hemodynamically significant stenosis of the aortic and/or mitral valves or with HOCM.

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 and potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that can increase serum potassium concentrations (for example, heparin) may lead to the development of hyperkalemia in patients with arterial hypertension. Hyperkalemia can also develop in patients with CHF taking Hyposart. During therapy with Giposart 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

In patients whose vascular tone and renal function primarily depend on the activity of the RAAS (for example, patients with severe decompensated CHF or concomitant kidney disease, including unilateral renal artery stenosis), therapy with other drugs that affect the RAAS may be accompanied by the development of arterial hypotension, azotemia, oliguria and, less commonly, acute renal failure. This cannot be excluded for angiotensin II receptor antagonists. An excessive decrease in blood pressure in patients with coronary artery disease 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 simultaneous use of candesartan and aliskiren is not recommended, due to the increased risk of arterial hypotension, hyperkalemia and renal dysfunction.

Impact on the ability to drive vehicles and operate machinery

The effect of the drug Giposart 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. Care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions due to the risk of dizziness.

Active ingredient

Candesartan

Composition

1 tab.:

candesartan cilexetil 32 mg.

Excipients:

lactose monohydrate – 174 mg,

corn starch – 40 mg,

hyprolose (viscosity, water, 25°C (5%) 75-150 spz) – 4 mg,

hyprolose (viscosity, water, 25°C (5%) 1500-3000 spz) – 4 mg,

macrogol 6000 – 5.2 mg,

magnesium stearate – 0.8 mg.

Pregnancy

The drug Giposart is contraindicated for use during pregnancy, because it has a direct effect on the RAAS and can cause developmental disorders of the fetus (especially in the second and third trimesters of pregnancy) or have a negative effect on the newborn, including death, 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, delayed ossification of the skull bones) and the development of complications in the newborn (renal failure, arterial hypotension, hyperkalemia).

If the fact of pregnancy is established, the drug Giposart must be discontinued as quickly as possible. When planning pregnancy, it is necessary to transfer the patient to adequate alternative therapy.

It is not known whether candesartan is excreted in breast milk, but it is known to be excreted in the milk of lactating rats.
During treatment with Hyposart, breastfeeding should be stopped. Newborns whose mothers took Hyposart during pregnancy should be under close medical supervision due to the likelihood of developing arterial hypotension.

Contraindications

– hypersensitivity to candesartan or other components of the drug;

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

– pregnancy;

– period of breastfeeding;

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

– severe liver dysfunction and/or cholestasis;

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

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

Side Effects

Classification of the frequency of side effects: very often (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000), including isolated reports. 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.

From the nervous system: often – dizziness, headache, weakness.

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

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

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

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

From the musculoskeletal system: very rarely – back pain, arthralgia, myalgia.

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

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

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

Other: exacerbation of gout, “flushes” of blood to the skin of the face.

Interaction

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

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

Candesartan is slightly metabolized in the liver (via the CYP2C9 isoenzyme). There was no effect on the isoenzymes CYP2C9 and CYP3A4; the effect on other cytochrome P450 isoenzymes is currently unknown.

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

With the simultaneous use of lithium preparations and ACE inhibitors, cases of transient increases in the concentration of lithium in the blood serum and the development of toxic effects have been observed. A similar effect is possible with the simultaneous use of lithium drugs and angiotensin II receptor antagonists, which requires periodic monitoring of the concentration of lithium in the blood serum during the combined use of these drugs.

With simultaneous 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), the antihypertensive effect of candesartan may be reduced.

Double blockade of the RAAS

As with ACE inhibitors, simultaneous use of ARB II and NSAIDs increases the risk of decreased renal function, including 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; it is necessary to monitor renal function at the beginning of therapy and thereafter.

Overdose

Symptoms: excessive decrease in blood pressure, dizziness, tachycardia. Isolated cases of drug overdose (up to 672 mg of candesartan cilexetil) have been described, resulting in the recovery of patients without serious consequences.

Treatment: if there is a pronounced decrease in blood pressure, the patient should be placed in a supine position with his legs raised; further – carry out measures aimed at increasing the volume of blood volume (administration of 0.9% sodium chloride solution intravenously). If necessary, sympathomimetic drugs can be prescribed. It is recommended to carry out symptomatic therapy under the control of vital functions of the body. Hemodialysis is ineffective.

Recommendations for use

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

Arterial hypertension

The recommended initial and maintenance dose of Giposart 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 at the maximum daily dose, it is recommended to add a thiazide diuretic (eg, hydrochlorothiazide) to therapy. This may enhance the antihypertensive effect of Giposart.

In patients at risk of developing arterial hypotension (including patients with reduced blood volume), it is recommended to start therapy 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 with the use of the drug in patients with severe renal impairment or end-stage renal failure (creatinine clearance 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 with the use of the drug in patients with severe liver dysfunction and/or cholestasis.

Chronic heart failure

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

Elderly patients and patients with impaired renal or liver function do not require adjustment of the initial dose of the drug.

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

Concomitant therapy

The drug Giposart can be used simultaneously with other drugs for the treatment of CHF, including ACE inhibitors, beta-blockers, diuretics, cardiac glycosides or combinations of these drugs.

Storage conditions

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

Shelf life

2 years.

Manufacturer

Polpharma JSC, Poland