Hypoart - instructions for use, dose, side effects, contraindications

Excipients: lactose monohydrate - 98.95 mg maize starch - 20.00 mg, giproloza * - 2.00 mg, giproloza ** - 2.00 mg macrogol 6000 - 2.60 mg magnesium stearate - 0.40 mg, dye iron oxide red E 172 - 0.05 mg.

1 tablet (8 mg) contains:

Active substance: candesartan cilexetil - 8.00 mg.

Excipients: Lactose monohydrate - 197.90 mg, maize starch - 40.00 mg, giproloza * - 4.00 mg, giproloza ** - 4.00 mg macrogol 6000 - 5.20 mg magnesium stearate - 0.80 mg ferric oxide red oxide E 172-0.10 mg.

1 tablet (16 mg) contains:

Active substance: candesartan cilexetil - 16.00 mg.

Excipients: Lactose monohydrate - 87.00 mg maize starch - 20.00 mg, giproloza * - 2.00 mg, giproloza ** - 2.00 mg macrogol 6000 - 2.60 mg magnesium stearate - 0.40 mg.

1 tablet (32 mg) contains:

Active substance: candesartan cilexetil 32.00 mg.

Excipients: lactose monohydrate - 174.00 mg, corn starch - 40.00 mg, giprolase * - 4.00 mg, giprolase ** - 4.00 mg, macrogol 6000 - 5.20 mg, magnesium stearate - 0.80 mg.

* - viscosity, water, 25 ° C (5%) 75-150 cps

** - viscosity, water, 25 ° С (5%) 1500 - 3000 спз

Description:

For tablets 4 mg:

Round, flat tablets with a facet on both sides, with a dividing risk on the one hand, light pink, small inclusions are allowed.

For tablets 8 mg:

Round, biconvex tablets with dividing risk on one side and engraving "8" on the other hand, small inclusions are allowed.

For tablets 16 mg:

Round, biconvex tablets with a dividing risk on one side, white.

For tablets 32 mg:

Round flat tablets with a facet on both sides, with a dividing risk on one side and with engraving "32" on the other hand, white.

Pharmacotherapeutic group:Angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.06 Candesartan

Pharmacodynamics:

Angiotensin II is the main enzyme of the renin-angiotensin-aldosterone system (RAAS), which takes part in the pathogenesis of arterial hypertension (AH), heart failure and other cardiovascular diseases.

Candesartan is a selective antagonist of angiotensin II receptors, subtype 1 (AT₁receptors). Does not manifest the properties of the agonist (does not affect the angiotensin-converting enzyme (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 cardiovascular activity. As a result of blocking AT₁-receptor angiotensin II compensatory dose-dependent increase in renin activity, angiotensin I concentration, angiotensin II, and a decrease in aldosterone in the blood plasma.

Arterial hypertension

Taking candesartan inside provides a dose-dependent, smooth decrease in blood pressure (BP) by reducing the total peripheral vascular resistance (OPSS) without reflex increase in the heart rate (heart rate). There is no data on the development of severe arterial hypotension after taking the first dose or about the development of the "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 continued therapy with candesartan in a fixed dose, the maximum reduction in blood pressure is usually achieved within 4 weeks and persists throughout the treatment. Adding a thiazide diuretic hydrochlorothiazide to candesartan enhances its antihypertensive effect.

Age and sex of the patient do not affect the effectiveness of the drug. Candesartan increases renal blood flow and does not change or increases the rate of glomerular filtration, while renal vascular resistance and filtration fraction decrease. Candesartan has a less pronounced antihypertensive effect in patients of the Negroid race (a population with predominantly low renin activity in the blood plasma).

There is 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 adversely affect the concentration of glucose in the blood and the lipid profile.

Heart failure

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

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

Pharmacokinetics:

Candesartan cilexetil is a prodrug. Kandesartan tsileksetil after intake quickly turns into an active substance - candesartan, by means of ether hydrolysis. When absorbed from the digestive tract, it binds firmly to the AT₁receptors and dissociates slowly, does not have the properties of an agonist.

Suction and distribution

The absolute bioavailability of candesartan is approximately 40% after oral administration. The relative bioavailability is approximately 34%.

Maximum concentration (C_max) in the blood serum is achieved 3-4 hours after ingestion. The concentration in the blood plasma increases linearly with increasing dose in the therapeutic interval (up to 32 mg). The association with plasma proteins is high (more than 99%).The volume distribution of candesartan is 0.13 l / kg. The pharmacokinetic parameters of candesartan do not depend on the age, sex of the patient and on the time of ingestion.

Metabolism and excretion

Candesartan is mainly excreted from the body by the kidneys and through the intestines in unchanged form. It is slightly metabolized in the liver (20-30%) with the participation of isoenzyme CYP2C9 to form an inactive derivative.

The half-life (T_1/2) candesartan is approximately 9 hours. Do not cumulate. The total clearance is about 0.37 ml / min / kg, with the renal clearance of the drug - 0.19 ml / min / kg. After oral administration ¹⁴FROM26% of the dose was excreted by the kidneys in the form of candesartan and 7% in the form of an inactive metabolite, while 56% of the dose was excreted through the intestines with bile in the form of candesartan and 10% in the form of an inactive metabolite. After a single intake within 72 hours, more than 90% of the dose is withdrawn.

Special patient groups

In elderly patients (over 65 years of age) FROM_max and the area under the "concentration-time" curve (AUC) candesartan increase in comparison with patients of young age by approximately 50% and 80% respectively.

However, the response from BP and the possible side effects with candesartan do not depend on the age of the patients.

In patients with mild to moderate renal impairment FROM_max and AUC candesartan increase by approximately 50% and 70%, respectively, while T_1/2 does not change in comparison with patients with preserved renal function.

Pharmacokinetics in patients on hemodialysis is similar to that in patients with severe renal dysfunction.

Have patients with severe renal dysfunction FROM_max and AUC increase by 50% and 110%, respectively, and T_1/2 the drug is increased 2 times.

Have patients with mild or moderate hepatic impairment average value AUC candesartan increases by approximately 20% in one study and 80% in another study. No experience in patients with severe impairment of liver function.

Indications:

Arterial hypertension.

Chronic heart failure and impaired systolic function of the left ventricle (LVEF ≤ 40%) - as an additional therapy for ACE inhibitors or intolerance to ACE inhibitors.

Contraindications:

Hypersensitivity to candesartan or other components of the drug. Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome.

Pregnancy and the period of breastfeeding.

Children and adolescents under 18 years of age (efficacy and safety not established).

Severe liver dysfunction and / or cholestasis.

Simultaneous use with aliskiren and aliskirenoderzhaschimi drugs in patients with diabetes mellitus or impaired renal function (the glomerular filtration rate is less than 60 ml / min).

Carefully:

Severe renal impairment (creatinine clearance less than 30 mL / min), hemodialysis, bilateral stenosis of the renal arteries or stenosis of the single kidney, hemodynamically significant stenosis of the aortic and / or mitral valve, hypertrophic obstructive cardiomyopathy (GOCMP), condition after kidney transplantation , cerebrovascular disorders of ischemic origin and coronary heart disease (IHD), hyperkalemia in patients with reduced circulating blood volume (BCC), general anesthesia and surgical interventions in (the risk of developing arterial hypotension due to the blockade of RAAS), primary hyperaldosteronism.

Pregnancy and lactation:

Pregnancy

The drug Giposart is contraindicated for use during pregnancy, tk. it has a direct effect on RAAS and can cause fetal developmental disorders (in especially in the second and third trimesters of pregnancy) or to have a negative impact on the newborn, up to a lethal outcome, if the drug was used during pregnancy.

It is known that therapy with angiotensin II receptor antagonists (ARAII) can cause fetal development disorders (renal dysfunction, oligohydramnion, slowing ossification of the bones of the skull) and development of complications in the newborn (kidney failure, arterial hypotension, hyperkalemia).

When establishing the fact of pregnancy, the drug Giposart must be canceled as soon as possible.

When planning pregnancy, it is necessary to transfer the patient to adequate alternative therapy.

Breastfeeding period

It is not known whether the candesartan in breast milk, but it is known that it penetrates the milk of lactating rats.

During treatment with Giposart, breastfeeding should be discontinued. Newborns, whose mothers took during pregnancy Giposart,should be under careful medical supervision because of the likelihood of developing arterial hypotension.

Dosing and Administration:

Inside, 1 time per day, regardless of the time of food intake.

Arterial hypertension

The recommended initial and maintenance dose of the drug 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 the background of the maximum daily dose does not achieve adequate control of blood pressure, it is recommended to add a thiazide diuretic to therapy.

Patients with reduced BCC

In patients at risk of developing arterial hypotension, therapy should be started with an initial dose of 4 mg.

Patients with impaired renal function

In patients with mild or moderate renal dysfunction (KK 30-80 ml / min / 1.73 m² body surface area), including patients on hemodialysis, the initial dose of the drug is 4 mg. Dose titrated depending on the therapeutic effect. Clinical experience in the use of the drug in patients with severe renal dysfunction or terminal stage of renal failure (QC less than 15 ml / min) is limited (see section "Special instructions".)

Patients with impaired hepatic function

The initial daily dose of the drug in patients with liver disease of mild and moderate severity is 4 mg. It is possible to increase the dose if necessary. Clinical experience of the drug in patients with severe impairment of liver function and / or cholestasis is not available (see Contraindications section).

Concomitant therapy

The use of the drug Hyposartum simultaneously with thiazide diuretics (for example, hydrochlorothiazide) can enhance the antihypertensive effect of the drug.

Chronic heart failure

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

Special patient groups

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

Application in children and adolescents

Safety and effectiveness of the drug Hyposart in children and adolescents under the age of 18 years have not been established.

Concomitant therapy

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

Side effects:

Classification of the frequency of development of side effects of the World Health Organization (WHO): very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10 000, <1/1000); very rarely (<1/10 000), including individual messages.

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 respiratory system: often - respiratory infections, pharyngitis, rhinitis, cough.

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

From the genitourinary system: often - a violation of kidney function, including renal failure in predisposed patients.

On the part of the hematopoiesis and lymphatic system: very rarely - leukopenia, neutropenia, thrombocytopenia and agranulocytosis.

From the digestive system: very rarely - nausea.

From the hepatobiliary system: very rarely - increased activity of "liver" transaminases, a violation of liver function or hepatitis.

From the side of the musculoskeletal system: very rarely - back pain, arthralgia, myalgia.

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

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

Other: exacerbation of gout, "hot flashes" of blood to the skin of the face.

Overdose:

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

Treatment: with a pronounced decrease in blood pressure, move the patient to the "lying" position on the back, lift the legs; further measures should be taken to increase bcc (introduction of 0.9% sodium chloride solution intravenously).

If necessary, sympathomimetic preparations may be prescribed. Symptomatic therapy under the control of vital body functions. Hemodialysis is ineffective.

Interaction:

The use of candesartan concomitantly with preparations containing aliskiren, is contraindicated in patients with diabetes mellitus or moderate or severe renal insufficiency (GFR less than 60 mL / min / 1.73 m² ) (see the section "Contraindications").

The simultaneous use of candesartan with hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol / levonorgestrel), glibenclamide, nifedipine, and enalapril has been studied; clinically significant pharmacokinetic interaction was not observed.

Candesartan is slightly metabolized in the liver (using isoenzyme CYP2C9). No effect on isozymes CYP2C9 and CYP3A4; The effect on other cytochrome P450 isoenzymes is currently unknown.

Hypotensive drugs potentiate the antihypertensive effect of candesartan. The experience of using other drugs acting on 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 capable of increasing potassium levels in the blood serum (eg, heparin) may lead to the development of hyperkalemia.

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

With the simultaneous use of ARAII and non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of cyclooxygenase-2 (COX-2) and nonselective NSAIDs, for example, acetylsalicylic acid more than 3 g / day, may reduce the antihypertensive effect candesartan.

Double blockade of RAAS

As in the case of ACE inhibitors, the simultaneous use of APAII and NSAIDs increase the risk of reducing kidney function, up to the development of renal failure, leading to hyperkalemia in patients with impaired renal function. This combination should be used with caution, especially in elderly patients. All patients should receive a sufficient amount of fluid; it is necessary to monitor the function of the kidneys at the beginning of therapy and in the future.

Special instructions:Ethnic Features

The antihypertensive effect of candesartan in patients of the Negroid race is less pronounced compared with 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 drugs. Impaired renal function

The experience of using the drug in patients with severe renal failure or end-stage renal failure (QC less than 15 ml / min) is limited. Such patients need a strict selection of the dose of the drug Hyposart under the careful control of blood pressure.

In patients with CHF, especially older than 75 years, and in patients with impaired renal function, it is necessary to periodically monitor kidney 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 in CHF

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

Hemodialysis

During hemodialysis, blood pressure may be particularly sensitive to blockade of AT₁ receptors as a result of reduction of bcc and activation of RAAS. Therefore, patients on hemodialysis need control of blood pressure and individual selection of the dose of HypoSart.

Stenosis of the renal artery

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 to a solitary kidney. A similar effect may develop with the use of ARAII.

Kidney Transplantation

The experience of using the drug in patients who have recently undergone kidney transplantation is absent.

Arterial hypotension

In patients with CHF, receiving the drug Hyposart, may develop an arterial hypotension. It is also possible to develop arterial hypotension in patients with reduced BCC, for example, receiving large doses of diuretics. At the beginning of therapy, care must be taken and, if necessary, compensated for BCC.

General anesthesia / surgery

When conducting surgical interventions under general anesthesia in patients taking ARAII, arterial hypotension may develop as a result of RAAS blockade. Very rarely arterial hypotension can be pronounced and require intravenous fluid and / or vasopressors.

Stenosis of aortic and / or mitral valves, GOKMP

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

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are resistant to antihypertensive drugs that affect RAAS; therefore, such patients are not recommended to use HypoSart.

Hyperkalemia

The simultaneous use of Hyposart and potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, or other agents capable of increasing the potassium content in the serum (eg, heparin) can lead to the development of hyperkalemia in patients with arterial hypertension.

Hyperkalemia can develop in patients with CHF who are taking Giposart. Against the background of therapy with the drug Hyposart in patients with CHF it is recommended to conduct periodic monitoring of potassium in the blood serum,especially with simultaneous use of ACE inhibitors and potassium-sparing diuretics (spironolactone, eplerenone, triamterene, amiloride).

Are common

Patients in whom vascular tone and renal function predominantly depend 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 through RAAS may be accompanied by the development of arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. This can not be ruled out for angiotensin II receptor antagonists. Excessive reduction in blood pressure in patients with ischemic heart disease or cerebrovascular diseases of ischemic origin can lead to the development of myocardial infarction or stroke.

Double blockade of RAAS in the use of drugs containing aliskiren

It is not recommended double blocking of RAAS by simultaneous application of candesartan and aliskiren, in view of the increased risk of arterial hypotension, hyperkalemia and renal dysfunction.

The use of the drug simultaneously with aliskirenom and aliskirenoderzhaschimi drugs in patients with diabetes mellitus orimpaired renal function (GFR less than 60 mL / min / 1.73 m²) (see the section "Contraindications").

Effect on the ability to drive transp. cf. and fur:

The influence of the drug Giposart on the management of vehicles and work with complex mechanisms has not been studied, but the pharmacodynamic properties of the drug indicate that such an effect is absent.

Care must be taken when driving vehicles and engaging in potentially hazardous activities that require a high concentration of attention and speed of psychomotor reactions due to the risk of dizziness.

Form release / dosage:

Tablets 4 mg, 8 mg, 16 mg, 32 mg.

Packaging:

For 14 tablets in a foil blister Al / PVC / PVDC.

1, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002665

Date of registration:20.10.2014

Expiration Date:20.10.2019

The owner of the registration certificate:Pharmaceutical factory "POLFARMA" JSCPharmaceutical factory "POLFARMA" JSC Poland

Manufacturer: & nbsp

Pharmaceutical Works POLPHARMA, S.A. Poland

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp24.04.2017

Illustrated instructions

Instructions

Hypoarthritis (HYPOSART)