Hyposart, 16 g tablets 28 pcs

Cmax in plasma is reached within 3-4 hours. Plasma concentrations increase linearly with increasing dose in the therapeutic range (up to 32 mg). Vd – 0.13 l/kg. Binding to plasma proteins – 99.8%. Slightly metabolized in the liver (20-30%) with the participation of CYP2C to form inactive metabolite.

The final T1/2 is 9 h. It does not cumulate. Total clearance is 0.37 ml/min/kg with renal clearance of approximately 0.19 ml/min/kg. Candesartan is excreted by the kidneys (by glomerular filtration and active tubular secretion): 26% as candesartan and 7% as an inactive metabolite; with bile, 56% and 10%, respectively. After a single dose within 72 hours more than 90% of the dose is excreted.

In elderly patients (over 65 years) Cmax and AUC are increased by 50% and 80%, respectively, compared to younger patients.

In patients with mild to moderate renal impairment, Cmax and AUC are increased by 50% and 70%, respectively, whereas the T1/2 of the drug is unchanged compared to patients with normal renal function.

In patients with severe renal impairment, Cmax and AUC are increased by 50% and 110%, respectively, and the T1/2 is doubled.

In patients with mild to moderate hepatic dysfunction, a 23% increase in AUC was observed.

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

Cmax in blood plasma is achieved within 3-4 hours. Plasma concentration increases linearly with increasing dose in the therapeutic range (up to 32 mg). Vd – 0.13 l/kg. Plasma protein binding – 99.8%. Slightly metabolized in the liver (20-30%) with the participation of CYP2C with the formation of an inactive metabolite.

Final T1/2 – 9 hours. Does not accumulate. Total clearance is 0.37 ml/min/kg, while renal clearance is about 0.19 ml/min/kg. Candesartan is excreted by the kidneys (by glomerular filtration and active tubular secretion): 26% – in the form of candesartan and 7% – in the form of an inactive metabolite; with bile – 56% and 10%, respectively. After a single dose, more than 90% of the dose is eliminated within 72 hours.

In elderly patients (over 65 years of age), Cmax and AUC increase by 50% and 80%, respectively, compared to young patients.

In patients with mild to moderate renal impairment, Cmax and AUC increase by 50% and 70%, respectively, while T1/2 of the drug does not change compared to patients with normal renal function.

In patients with severely impaired renal function, Cmax and AUC increase by 50% and 110%, respectively, and T1/2 increases by 2 times.

In patients with mild to moderate hepatic impairment, an increase in AUC of 23% was observed.

Special instructions

Use for liver dysfunction

In the treatment of arterial hypertension, 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.

When treating chronic heart failure, patients with impaired liver function do not require adjustment of the initial dose of the drug. The use of the drug is contraindicated in cases of severe liver dysfunction and/or cholestasis.

Use for renal impairment

In the treatment of arterial hypertension in patients with mild to moderate renal dysfunction (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.

When treating chronic heart failure, patients with impaired renal function do not require adjustment of the initial dose of the drug.

The drug should be prescribed with caution in case of severe renal impairment (CC

Use in children

The use of the drug is contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

Use in elderly patients

Elderly patients do not require adjustment of the initial dose of the drug.

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 use of the drug in patients with severe renal failure or those in end-stage renal failure (CK

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 16 mg.

Excipients:

lactose monohydrate – 87 mg,

corn starch – 20 mg,

hyprolose (viscosity, water, 25°C (5%) 75-150 spz) – 2 mg,

hyprolose (viscosity, water, 25°C (5%) 1500-3000 spz) – 2 mg,

macrogol 6000 – 2.6 mg,

magnesium stearate – 0.4 mg.

Contraindications

– severe liver dysfunction and/or cholestasis;

– simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (GFR lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome);

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

– hypersensitivity to candesartan or other components of the drug.

The drug should be prescribed with caution in case of severe renal impairment (CC

Side Effects

Classification of the frequency of side effects: very often (≥1/10); often (≥1/100). 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 – excessive 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 concomitantly with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or moderate to severe renal impairment (GFR2).

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 blood pressure decreases excessively, the patient should be transferred to a horizontal position with a low headboard; 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.

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