Ordiss tablets 16mg, No. 30

Arterial hypertension; chronic heart failure and impaired systolic function of the left ventricle (decrease in LVEF <40%) as adjunctive therapy to ACE inhibitors or in case of intolerance to ACE inhibitors.

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

Arterial hypertension. The recommended initial dose of OrdissЃ is 8 mg once a day. Patients who require a further decrease in blood pressure are advised to increase the dose to 16 mg once a day. The maximum antihypertensive effect is achieved within 4 weeks from the start of treatment. The maximum daily dose is 32 mg / day. If, during treatment with OrdissЃ, adequate control of blood pressure is not achieved, it is recommended to add a thiazide diuretic to the therapy.

In patients with reduced BCC there is a risk of arterial hypotension, therefore, treatment with the drug should be started with a dose of 4 mg / day (1/2 table. 8 mg).

In patients with renal impairment. When used in patients with mild or moderate renal impairment (GFR not less than 30 ml / min / 1.73 m2), the initial dose is 4 mg / day (1/2 table. 8 mg).

Clinical experience with the use of the drug in patients with severe renal failure (GFR less than 30 ml / min / 1.73 m2) is limited. In these cases, you should consider starting treatment with a dose of 4 mg / day (1/2 table. 8 mg).

In patients with impaired liver function. When using the drug in patients with mild and moderate hepatic dysfunction, an initial dose of 4 mg / day is recommended (1/2 table. 8 mg). The dose may be increased if necessary. Clinical experience with the drug in patients with severe liver dysfunction and / or cholestasis is limited (see 'Contraindications').

The drug OrdissЃ can be used in conjunction with thiazide diuretics (for example, hydrochlorothiazide), which leads to an increase in the hypotensive effect.

Chronic heart failure (CHF). The recommended initial dose of the drug OrdissЃ is 4 mg once a day (1/2 table. 8 mg).

Increasing the dose to 32 mg 1 time per day or to the maximum tolerated dose is carried out by doubling it at intervals of at least 2 weeks.

OrdissЃ can be used in conjunction with other drugs used in CHF, such as ACE inhibitors, beta-blockers, diuretics and cardiac glycosides.

Special patient groups. Elderly patients, patients with renal insufficiency or impaired liver function do not need to change the initial dose of the drug.

Active ingredient: candesartan cilexetil

hypersensitivity to candesartan and other components of the drug;

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

severe liver dysfunction and / or cholestasis;

simultaneous use with a direct renin inhibitor - the drug aliskiren or aliskiren-containing drugs in patients with diabetes mellitus and / or impaired renal function (glomerular filtration rate (GFR) less than 60 ml / min / 1.73 m2 body surface area);

pregnancy;

breastfeeding period;

children under 18 years of age.

With caution: hemodynamically significant stenosis of the aortic and mitral valves, cerebrovascular diseases, coronary artery disease (CHD), hypertrophic obstructive cardiomyopathy (GOKMP), condition after kidney transplantation, bilateral renal artery stenosis or arterial stenosis, severe kidney failure, primary hyperaldosteric degree (Cl creatinine - less than 30 ml / min), hemodialysis, hyperkalemia; patients with reduced BCC, general anesthesia and surgical interventions (risk of arterial hypotension due to RAAS blockade).

Clinical and pharmacological group: Angiotensin II receptor antagonist

Pharmaco-therapeutic group: Angiotensin II receptor antagonist

pharmachologic effect

Antihypertensive agent, angiotensin II receptor antagonist. Blocks AT1 receptors, which leads to a decrease in the biological effects of angiotensin II (mediated by this type of receptor), incl. vasoconstrictor action, stimulating effect on the release of aldosterone, regulation of salt and water homeostasis and stimulation of cell growth. The antihypertensive effect is due to a decrease in the systemic vascular resistance without a reflex increase in heart rate.

Does not inhibit ACE. Does not interact or block other hormone receptors or ion channels, which are important for the regulation of the functions of the cardiovascular system.

Pharmacokinetics

Cmax in blood plasma is reached 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%. It is 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 cumulate. The total clearance is 0.37 ml / min / kg, while the renal clearance is about 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 of age), Cmax and AUC increase by 50% and 80%, respectively, compared with young patients.

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

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

In patients with mild to moderate liver dysfunction, an increase in AUC was observed by 23%.

Indications

Arterial hypertension; chronic heart failure and impaired systolic function of the left ventricle (decrease in LVEF <40%) as adjunctive therapy to ACE inhibitors or in case of intolerance to ACE inhibitors.

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen.

It is taken internally. The dose and regimen of administration are set individually, depending on the indications and response to therapy.

Side effect

Infectious diseases: often - respiratory infections.

From the hematopoietic system: very rarely - leukopenia, neutropenia, agranulocytosis.

From the side of metabolism: rarely - hyperkalemia, hyponatremia.

From the nervous system: infrequently - dizziness / vertigo, headache.

From the side of the cardiovascular system: often - a pronounced decrease in blood pressure.

From the digestive system: very rarely - nausea.

From the liver and biliary tract: very rarely - an increase in the level of liver enzymes, impaired liver function, hepatitis.

From the respiratory system: very rarely - cough.

On the part of the skin and subcutaneous tissues: itching.

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

From the musculoskeletal system: infrequently - back pain; very rarely - arthralgia, myalgia.

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

On the part of laboratory parameters: it is possible - a slight decrease in hemoglobin, an increase in the concentration of creatinine and urea, an increase in the content of potassium and a decrease in the content of sodium.

General reactions: often - weakness.

Contraindications for use

Hypersensitivity to candesartan; pregnancy, breastfeeding period; severe liver dysfunction and / or cholestasis; age up to 18 years (efficacy and safety have not been established). The use of candesartan in combination with drugs containing aliskiren in patients with diabetes mellitus and / or with moderate or severe renal impairment (GFR less than 60 ml / min / 1.73 m2 body surface area). Concomitant use with ACE inhibitors in patients with diabetic nephropathy.

With care: severe renal dysfunction (creatinine clearance less than 30 ml / min); bilateral stenosis of the renal arteries or stenosis of an artery of a solitary kidney; hemodynamically significant stenosis of the aortic and / or mitral valves; a history of conditions after a kidney transplant; hemodialysis; cerebrovascular disorders of ischemic origin and ischemic heart disease; hyperkalemia; in patients with reduced BCC; primary hyperaldosteronism; hypertrophic obstructive cardiomyopathy.

Application during pregnancy and lactation

Candesartan is contraindicated during pregnancy and lactation (breastfeeding).

Application for violations of liver function

Contraindicated in severe liver dysfunction and / or cholestasis.

Application for impaired renal function

Contraindicated for use in patients with moderate or severe renal impairment (glomerular filtration rate less than 60 ml / min / 1.73 m2 body surface area). Use with caution in patients with impaired renal function (creatinine clearance less than 30 ml / min); with bilateral stenosis of the renal arteries or stenosis of an artery of a single kidney; with primary hyperaldosteronism; conditions after kidney transplant in history; hemodialysis.

When used in patients with renal insufficiency, the level of potassium and creatinine in the blood plasma should be periodically monitored.

Application in children

Contraindicated for use in children and adolescents under the age of 18 years.

Use in elderly patients

Caution should be given to elderly patients in order to avoid worsening of the course of concomitant diseases. Renal function should be monitored periodically, especially in patients aged 75 and over.

special instructions

When using candesartan in patients with arterial hypertension and severe renal impairment (CC less than 30 ml / min), it is recommended to periodically monitor the potassium content and serum creatinine concentration. Patients with CC less than 15 ml / min should carefully select the dose under close control of blood pressure.

In patients with chronic heart failure, it is necessary to periodically monitor renal function, especially in patients aged 75 years and older, as well as in patients with impaired renal function.

When the dose of candesartan is increased, it is recommended to control the potassium content and the concentration of creatinine.

With the combined use of candesartan with ACE inhibitors in chronic heart failure, the risk of side effects, especially renal dysfunction and hyperkalemia, may increase. In these cases, careful monitoring of the patient and monitoring of laboratory parameters are necessary.

During hemodialysis, blood pressure can be particularly sensitive to blocking AT1 receptors due to a decrease in blood plasma volume and activation of the renin-angiotensin-aldosterone system. In this regard, patients on hemodialysis should carefully titrate the dose of candesartan under close control of blood pressure.

In patients with bilateral renal artery stenosis or stenosis of a solitary kidney artery, drugs that affect the renin-angiotensin-aldosterone system, in particular ACE inhibitors, can cause an increase in serum urea and creatinine concentrations. Similar effects can be expected with the use of angiotensin II receptor antagonists.

Patients with chronic heart failure during therapy with candesartan may develop arterial hypotension. At the beginning of therapy, special care should be taken and, if necessary, hypovolemia should be corrected.

In patients receiving angiotensin II receptor antagonists, during general anesthesia and during surgery, arterial hypotension may develop as a result of blockade of the renin-angiotensin-aldosterone system. Very rarely, there may be cases of severe arterial hypotension requiring intravenous administration of plasma-substituting solutions and / or vasopressors.

Patients whose vascular tone and nocturnal function are predominantly dependent on the activity of the renin-angiotensin-aldosterone system (for example, patients with severe chronic heart failure or kidney disease, including renal artery stenosis) are especially sensitive to drugs acting on the renin-angiotensin-aldosterone system. The appointment of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, less often, acute renal failure. The possibility of the development of these effects cannot be excluded when using angiotensin II receptor antagonists. A sharp decrease in blood pressure in patients with ischemic heart disease or cerebrovascular diseases of atherosclerotic genesis, with the use of any antihypertensive drugs, can lead to the development of myocardial infarction or stroke.

Influence on the ability to drive vehicles and use mechanisms

During the period of candesartan treatment, patients should be careful when driving vehicles and engaging in other activities that require a high concentration of attention and speed of psychomotor reactions, since candesartan can cause dizziness and weakness.

Drug interactions

The simultaneous use of candesartan with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus and / or with moderate or severe renal failure (glomerular filtration rate less than 60 ml / min / 1.73 m2 body surface area) is contraindicated and is not recommended in other patients.

There is evidence that the combined use of ACE inhibitors and angiotensin II receptor antagonists can lead to an increase in adverse reactions such as hypotension, hyperkalemia and renal impairment, in particular in patients with diabetic nephropathy. Therefore, the simultaneous use of angiotensin II receptor antagonists with ACE inhibitors is contraindicated in patients with diabetic nephropathy and is not recommended in other patients.

The simultaneous use of candesartan with other antihypertensive drugs potentiates the antihypertensive effect.

With simultaneous use with potassium preparations, potassium-sparing diuretics, dietary supplements containing potassium, or potassium salt substitutes, hyperkalemia may develop.

Candesartan increases serum lithium concentration and increases the risk of toxic reactions.

With the combined use of angiotensin II receptor antagonists and NSAIDs, incl. selective inhibitors of cyclooxygenase-2, acetylsalicylic acid (more than 3 g per day), there may be a decrease in the antihypertensive effect.

As with the use of ACE inhibitors, the simultaneous use of angiotensin II receptor antagonists and NSAIDs may increase the risk of impaired renal function, including acute renal failure, increased serum potassium concentration, especially in patients with reduced renal function. Caution should be exercised with the simultaneous use of these drugs, especially in elderly patients and in patients with reduced BCC. Patients need to compensate for fluid loss and carefully monitor renal function after starting combination therapy and periodically during such therapy.

Drugs that affect the RAAS can increase the concentration of urea and creatinine in the blood in patients with bilateral renal artery stenosis or an artery of a solitary kidney. Concomitant use of diuretics and other antihypertensive drugs increases the risk of arterial hypotension.

Contacts for inquiries

TEVA (Israel)