Universal reference book for medicines
Name of the preparation: ORDISS ® (ORDISS)

Active ingredient: candesartan

Type: Angiotensin II receptor antagonist

Manufacturer: Teva Pharmaceutical Industries (Israel)
Composition, form of production and packaging
Tablets of
pink color, capsule-shaped, with a risk on both sides and engraved "8 | C" on one side and "C | 8" on the other side of the tablet.

1 tab.

candesartan cilexetil 8 mg

Auxiliary substances: pregelatinized starch - 3.75 mg, poloxamer 188 - 0.5 mg, povidone K30 - 4 mg, iron dye red oxide (E172) - 0.075 mg, carmellose calcium - 1.65 mg, microcrystalline cellulose 17.5 mg, lactose monohydrate 43.725 mg, magnesium stearate - 0.8 mg.

5 pieces.
- blisters (6) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
Tablets of pink color, capsule-shaped, with risk on one side and engraving "C | C" on opposite sides of the risk, on the other side of the tablet - engraving "16".

1 tab.

candesartan cilexetil 16 mg

Auxiliary substances: pregelatinized starch - 7.5 mg, poloxamer 188 - 1 mg, povidone K30 - 8 mg, iron dye red oxide (E172) 0.15 mg, calcium carmellose 3.3 mg, microcrystalline cellulose 35 mg, lactose monohydrate 87.45 mg, magnesium stearate - 1.6 mg.

5 pieces.
- blisters (6) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
Tablets of pink color, capsule-shaped, with a risk on one side and engraving "C | C" on opposite sides of the risk, on the other side of the tablet - engraving "32".

1 tab.

candesartan cilexetil 32 mg

Auxiliary substances: pregelatinized starch - 15 mg, poloxamer 188 - 2 mg, povidone K30 - 16 mg, iron oxide red (E172) 0.3 mg, calcium carbellose - 6.6 mg, microcrystalline cellulose - 70 mg, lactose monohydrate - 174.9 mg, magnesium stearate - 3.2 mg.

5 pieces.
- blisters (6) - packs of cardboard.
10 pieces.
- blisters (3) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.

Description of the drug approved by the manufacturer for the printed edition of 2017.

PHARMACHOLOGIC EFFECT

Antihypertensive drug, angiotensin II receptor antagonist.
Angiotensin II is the main hormone of RAAS, which plays an important role in the pathogenesis of arterial hypertension, heart failure and other cardiovascular diseases. The main physiological effects of angiotensin II are vasoconstriction, stimulation of aldosterone production, regulation of the water-electrolyte state and stimulation of cell growth. The effects are mediated by the interaction of angiotensin II with angiotensin receptor type 1 (AT 1 receptors).
Candesartan is a selective antagonist of AT 1 -receptor angiotensin II, does not inhibit ACE that converts angiotensin I into angiotensin II, which destroys bradykinin, does not lead to accumulation of bradykinin or substance P. Blocking of AT 1 -receptors of angiotensin II results in a dose-dependent increase in renin content, angiotensin I, angiotensin II, and a decrease in aldosterone in the blood plasma.

When comparing candesartan with ACE inhibitors, the development of cough was less common in patients receiving candesartan.

Candesartan does not bind to the receptors of other hormones and does not block the ion channels involved in the regulation of cardiovascular functions.

PHARMACOKINETICS

Suction and distribution

When sucked from the gastrointestinal tract of candesartan, cilexitil through ether hydrolysis rapidly turns into an active substance - candesartan, binds firmly to AT 1-receptors and dissociates slowly, does not have the properties of an agonist.
The absolute bioavailability of candesartan after oral administration is about 40%. The relative bioavailability of the tablet form compared to the oral solution is approximately 34%. Thus, the calculated absolute bioavailability of the tablet form of the drug is 14%. Eating does not have a significant effect on AUC, i.e. food does not significantly affect the bioavailability of the drug.
C max in blood plasma is achieved 3-4 hours after taking the drug in tablet form.
When the dose is increased within the recommended limits, the concentration of candesartan rises linearly.
The binding of candesartan to plasma proteins is more than 99%.
Plasma V d candesartan is 0.1 l / kg.
Metabolism and excretion

Candesartan, in general, is excreted from the body by the kidneys and through the intestine in an unchanged form and only marginally metabolized in the liver.
T 1/2 is approximately 9 hours. Cumulation of candesartan in the body is not observed.
The total clearance of candesartan is about 0.37 ml / min / kg, with a kidney clearance of about 0.19 ml / min / kg.
Renal excretion of candesartan is carried out by glomerular filtration and active tubular secretion.
When administered radically-labeled candesartan, about 26% of the administered amount is excreted with kidneys in the form of candesartan and 7% in the form of an inactive metabolite, whereas in feces 56% of the administered amount in the form of candesartan and 10% in the form of an inactive metabolite is detected.

Pharmacokinetics in special clinical cases

The pharmacokinetic parameters of candesartan do not depend on the sex of the patient.

In patients older than 65 years, C max and AUC of candesartan increase by 50% and 80%, respectively, compared with younger patients.
However, the hypotensive effect and incidence of side effects with candesartan do not depend on the age of the patients.
In patients with mild to moderate renal dysfunction, C max and AUC of candesartan increased by 50% and 70%, respectively, whereas T 1/2 did not change as compared to patients with normal renal function.

Candesartan increased by 50% and 110%, respectively, in patients with severe renal dysfunction and / or on hemodialysis, and T 1/2 increased 2-fold.

In patients with mild and moderate impairment of liver function, AUC of candesartan was increased by 23%.

INDICATIONS

- arterial hypertension;

- chronic heart failure and a violation of left ventricular systolic function (left ventricular ejection fraction (LVEF) not more than 40%) as an additional therapy with ACE inhibitors or with intolerance to ACE inhibitors.

DOSING MODE

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

Arterial hypertension

The recommended initial dose of Ordiss ® is 8 mg 1 time / day.
Patients who require a further reduction in blood pressure, it is recommended to increase the dose to 16 mg 1 time / day. The maximum antihypertensive effect is achieved within 4 weeks from the start of treatment. The maximum daily dose is 32 mg / day. In the event that, against the background of treatment with Ordiss®, adequate blood pressure control is not achieved, it is recommended to add a thiazide diuretic to therapy.
In patients with reduced BCC, there is a risk of developing arterial hypotension, so you should start treatment with the drug at a dose of 4 mg / day (1/2 tablet 8 mg).

In elderly patients, there is no need to adjust the initial dose of the drug.

When used in patients with mild to moderate severe renal insufficiency (GFR not less than 30 ml / min / 1.73 m 2 body surface area), the initial dose is 4 mg / day (1/2 tablet 8 mg).
The clinical experience of using the drug in patients with severe renal failure (GFR less than 30 ml / min / 1.73 m 2 body surface area) islimited. In these cases, you should consider starting treatment with a dose of 4 mg / day (1/2 tablet 8 mg).
When using the drug in patients with a malfunction of the liver of mild and moderate severity , an initial dose of 2 mg / day (1/4 tablet of 8 mg) is recommended.
If necessary, it is possible to increase the dose. The clinical experience of the drug in patients with severe impairment of liver function and / or cholestasis is limited.
Ordisse ® can be used in conjunction with thiazide diuretics (for example, hydrochlorothiazide), which leads to increased antihypertensive effect.

Chronic heart failure (CHF)

The recommended initial dose of Ordiss ® is 4 mg 1 time / day (1/2 tablet 8 mg).
An increase in the dose to 32 mg 1 time / day or up to the maximum tolerated dose is carried out by doubling it at intervals of not less than 2 weeks.
Ordisse ® can be used in conjunction with other drugs used for CHF, for example, with ACE inhibitors, beta-adrenoblockers, diuretics and cardiac glycosides.

Older patients, patients with renal insufficiency or liver dysfunction, do not need to change the initial dose of the drug.

SIDE EFFECT

The incidence of adverse events is classified according to WHO recommendations: very often (? 10%), often (? 1%, but <10%);
infrequently (? 0.1%, but <1%); rarely (? 0.01%, but <0.1%), very rarely (<0/01%, including single messages).
From the hemopoietic system: very rarely - leukopenia, neutropenia, thrombocytopenia, agranulocytosis.

From the immune system: very rarely - skin rash, itching, urticaria, angioedema.

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

On the part of the respiratory system: often - respiratory infections, pharyngitis, rhinitis.

From the side of the digestive system: very rarely - nausea.

From the liver and bile ducts: very rarely - increased activity of liver transaminases, a violation of liver function, hepatitis.

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

From the osteomuscular system and connective tissue: very rarely - back pain, arthralgia, myalgia.

From the urinary system: often - a violation of kidney function.

Laboratory indicators: very rarely - hyperkalemia, hyponatremia, increase in creatinine concentration, hyperuricemia, decrease in hemoglobin.

Other: very rarely - exacerbation of the gout, the "tides" of blood to the face.

CONTRAINDICATIONS

- hypersensitivity to candesartan and other components of the drug;

severe liver dysfunction and / or cholestasis;

- Pregnancy;

- the period of breastfeeding;

- children and adolescence under 18;

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

- simultaneous use with aliskiren (direct renin inhibitor) in patients with diabetes mellitus and / or renal dysfunction (GFR less than 60 ml / min / 1.73 m 2 body surface area).

With caution: hemodynamically significant stenosis of the aortic and mitral valves, cerebrovascular disease, coronary artery disease, hypertrophic obstructive cardiomyopathy, condition after kidney transplantation, bilateral stenosis of the renal arteries or stenosis of the single kidney artery, primary hyperaldosteronism, severe renal insufficiency (<30 ml / min), hemodialysis, hyperkalemia;
patients with reduced BCC, general anesthesia and surgical interventions (risk of arterial hypotension, due to RAAS blockade).
PREGNANCY AND LACTATION

The drug Ordiss ® is contraindicated for use in pregnancy because candesartan has a direct effect on RAAS, can cause fetal developmental disorders or have a negative impact on the newborn, up to a lethal outcome.

If pregnancy is detected during treatment with Ordiss ® , it is necessary to immediately cancel the drug.
When planning pregnancy, it is necessary to transfer the patient to adequate therapy, permitted for use in pregnancy.
Newborns whose mothers took Ordiss® during pregnancy should be under medical supervision because of the likelihood of developing arterial hypotension.

It is not known whether candesartan is excreted in breast milk.
Do not use Ordiss ® during breastfeeding. If it is necessary to use the drug during lactation, breastfeeding should be stopped.
SPECIAL INSTRUCTIONS

Simultaneous use of ACE inhibitors, ARA II or aliskiren increases the risk of arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure).Double blockade of RAAS with the use of ACE inhibitors, ARA II or aliskiren is not recommended.

If a double blockade of RAAS is considered absolutely necessary, then treatment should be carried out only under the supervision of a doctor and with regular monitoring of kidney function, electrolyte content and blood pressure.
ACE inhibitors and ARA II should not be used simultaneously in patients with diabetic nephropathy.
Impaired renal function

Against the backdrop of the use of Ordiss®, as in the case of other drugs that oppress RAAS, in some cases, kidney function may develop.

When using Ordiss ® in patients with arterial hypertension and severe renal insufficiency (KC less than 30 ml / min), it is recommended to regularly monitor the potassium content and serum creatinine concentration.
The clinical experience of using the drug in patients with terminal stage of renal failure (QC less than 15 ml / min) is limited. When using Ordiss ® in such patients, it is necessary to select the dose of Orissit ® under the control of blood pressure.
Patients with CHF need to periodically monitor kidney function, especially in patients over the age of 75 years and patients with impaired renal function.
When increasing the dose, it is also recommended to monitor the potassium content and serum creatinine concentration.
There are no data on the use of Ordiss ® in patients with CHF with a creatinine concentration greater than 265 μmol / L (more than 3 mg / ml).

Hemodialysis

During hemodialysis, blood pressure may be particularly sensitive to blockade of AT 1 -receptors as a result of a decrease in bcc and activation of RAAS.
Therefore, patients on hemodialysis need to monitor blood pressure and individually adjust the dose of Ordiss ® in accordance with the indices of blood pressure.
Simultaneous use with ACE inhibitors in CHF

With simultaneous use with ACE inhibitors, the risk of side effects increases, especially renal dysfunction and hyperkalemia.
It is necessary to monitor the clinical status of patients and the corresponding laboratory parameters.
Stenosis of the renal artery

Drugs that affect RAAS (eg, ACE inhibitors) may lead to an increase in serum urea and creatinine in patients with bilateral renal artery stenosis or stenosis of the artery of a single kidney.
A similar effect can be expected with angiotensin II receptor antagonists.
Kidney Transplantation

The experience of using Ordiss® in patients who have recently undergone kidney transplantation is not available.

Arterial hypotension

In patients with CHF in the use of the drug Ordiss ® may develop arterial hypotension.
It is also possible to develop arterial hypotension in patients with BCC deficiency, for example, when using diuretics in high doses. In this case, before applying Ordiss®, it is necessary to correct the BCC.
General anesthesia and / or surgery

Patients receiving angiotensin II antagonists may develop arterial hypotension as a result of RAAS blockade during general anesthesia and during surgical interventions.
In rare cases, arterial hypotension can be pronounced, requiring intravenous fluid and / or vasopressor substances.
Stenosis of aortic and / or mitral valves, GOKMP.

Care should be taken when using Ordiss ® in patients with GOKMP or hemodynamically significant stenosis of the aortic or mitral valves.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect RAAS, so it is not recommended to use Ordiss ® in the patient group category.

Hyperkalemia

The simultaneous use of Ordiss ® with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase serum potassium levels (eg, heparin) can lead to hyperkalemia in patients with hypertension.

Hyperkalemia can also develop in patients with CHF who are taking Ordiss®.
On the background of therapy with Ordiss ® in patients with CHF it is recommended to carry out periodic monitoring of potassium content in blood serum, especially with simultaneous use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene, amiloride).
Are common

Patients who have vascular tone and renal function preferentially depend on RAAS activity (for example, patients with severe chronic heart failure, kidney disease, including renal artery stenosis) are particularly sensitive to drugs acting on RAAS.
The use of such drugs is accompanied in these patients by severe arterial hypotension, azotemia, oliguria and, more rarely, acute renal failure. The possibility of developing these effects is not excluded even when angiotensin II receptor antagonists are used. A sharp decrease in blood pressure in patients with ischemic cardiopathy, cerebrovascular disease of ischemic genesis with the use of any antihypertensive drugs, can lead to the development of myocardial infarction or stroke.
Use in Pediatrics

The safety and efficacy of Ordiss ® in children and adolescents under the age of 18 years have not been established.

Impact on the ability to drive vehicles and manage mechanisms

When there are undesirable effects from the central nervous system during therapy with Ordiss ® , caution should be exercised when performing actions requiring an increased concentration of attention and speed of psychomotor reactions.

OVERDOSE

Symptoms: an analysis of the pharmacological properties of the drug suggests that the main manifestation of an overdose may be a clinically pronounced decrease in blood pressure, dizziness.
Individual cases of drug overdose (up to 672 mg candesartan), which resulted in the recovery of patients without severe consequences, were described.
Treatment: with the development of clinically pronounced blood pressure lowering, it is necessary to carry out symptomatic treatment and monitor the patient's condition.
Lay the patient on his back and raise his legs. If necessary, increase bcc, for example, by iv injection of 0.9% sodium chloride solution. If necessary, you can apply sympathomimetic drugs. Withdrawal of candesartan by hemodialysis ineffective.
DRUG INTERACTION

With simultaneous use of candesartan hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinylestradiol / levonorgestrel), glibenclamide, nifedipine and enalapril clinically significant drug interactions have been identified.
With simultaneous use of candesartan with ACE inhibitors, other antagonists of angiotensin II, aliskiren increases the risk of hyperkalemia, the sharp reduction in blood pressure, renal dysfunction, including acute renal failure that requires careful monitoring of blood pressure, as well as indicators of renal function, fluid and electrolyte balance .
The simultaneous use of candesartan with aliskiren in patients with diabetes and renal impairment (creatinine clearance less than 60 mL / min) is not recommended.
Candesartan is metabolized in the liver to a small extent with the assistance of isoenzyme CYP2C9. Studies on the interaction of the drug showed no effect on CYP2C9 and CYP3A4, effects on other isozymes of the cytochrome P450 system has not been studied.
The simultaneous use of candesartan with other antihypertensive agents enhances the antihypertensive effect.
Experience with other drugs acting on the RAAS reveals that concomitant treatment by potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, and other means which increase the content of potassium in the serum (e.g., heparin) can lead to the development of hyperkalemia.
With simultaneous use of drugs lithium and ACE inhibitors occurs reversible increase in the concentration of lithium in blood serum and the development of toxic reactions. Similar reactions can occur when applying and angiotensin II receptor antagonists, and therefore it is recommended to control blood serum lithium content.
The simultaneous use of NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / d) and non-selective NSAIDs may reduce the antihypertensive effect of candesartan and also increase the risk of renal function, including to the development of acute renal failure, and to improve the content of potassium in the blood serum. Caution is advised to use a combination of these drugs, especially in elderly patients.
TERMS OF RELEASE FROM PHARMACY

The drug is released by prescription.

CAN-RU-00026-DOK
TERMS AND CONDITIONS OF STORAGE

The drug should be stored out of reach of children, dry place at a temperature of no higher than 25 ° C.
Shelf life - 2 years.
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