Expiration date: 06/2025
Composition:
1 tablet contains:
active substance: candesartan in tsileksetil was 8.0 mg/mg 16,0/32,0 mg;
auxiliary substances: starch pregelatinization 3.75 mg/7.5 mg/15,0 mg; poloxamer 188 0.5 mg/1.0 mg/2.0 mg; povidone-COA 4.0 mg/8.0 mg/16,0 mg; colorant iron oxide red (E172) 0.075 mg/0.15 mg/0.3 mg; calcium carmellose of 1.65 mg/3.3 mg/6.6 mg; microcrystalline cellulose 17.5 mg/35,0 mg/70,0 mg; lactose monohydrate 43,725 mg/87,45 mg/174,9 mg; magnesium stearate 0.8 mg/1.6 mg/3,2 mg.
Description:
Tablets 8 mg. Pink capsulorraphy tablets scored on both sides and engraved "8" on one side and "8" on the other side of the tablet.
Tablets 16 mg. capsulorraphy Pink pill with line on one side and engraved "s|s" on the different parties of the risks on the other side of the tablet is engraved "16".
Tablets 32 mg. capsulorraphy Pink pill with line on one side and engraved "s|s" on the different parties of the risks on the other side tablets engraved "32".
Pharmacotherapeutic group:
angiotensin II receptor antagonist
Pharmacodynamics:
Angiotensin II is the main hormone of the renin-angiotensin-aldosterone system (RAAS), which plays an important role in the pathogenesis of hypertension, congestive heart failure and other cardiovascular diseases. The major physiological effects of angiotensin II are vasoconstriction, stimulation of aldosterone production, regulation of water and electrolyte status and stimulation of cell growth. Effects mediated by interaction of angiotensin II with angiotensin receptors type 1 (AT1 receptors).
Candesartan is a selective AT1 antagonist-angiotensin II receptor, does not inhibit angiotensin converting enzyme (ACE) involved in the conversion of angiotensin I to angiotensin II, which destroys bradykinin, does not lead to accumulation of bradykinin or substance p. In the blocking AT1-receptors of angiotensin II occurs a dose-dependent increase in the content of renin, angiotensin I, angiotensin II and reduced concentration of aldosterone in blood plasma.
When candesartan in comparison with ACE inhibitors the development of cough was less frequent in patients treated with candesartan.
Candesartan is not associated with other hormone receptors and does not block ion channels involved in the regulation of the functions of the cardiovascular system.
Pharmacokinetics:
Absorption and distribution. When absorption from the gastrointestinal tract (GIT) of candesartan in has tsileksetil through the ethereal hydrolysis is rapidly converted to the active substance candesartan, is strongly associated with AT1-receptor and slowly dissociates, has the properties of the agonist.
The absolute bioavailability of candesartan in after intake of about 40%. The relative bioavailability of tablets compared to an oral solution is approximately 34%. Thus, the estimated absolute bioavailability of a tablet form of the drug is 14%. Food intake has no significant effect on area under the curve "concentration-time" (AUC), i.e., food does not significantly affect the bioavailability of the drug.
The maximum concentration in plasma (Cmax) is reached 3-4 hours after taking a tablet form of the drug. With increasing doses within the recommended limits of concentration of candesartan in increases linearly. The candesartan in binding with blood plasma proteins - 99%. Plasma volume of distribution (Vd) of candesartan in is 0.1 l/kg.
Pharmacokinetic parameters of candesartan in do not depend on the sex of the patient.
Metabolism and excretion.
Candesartan mainly excreted by the kidneys and through the intestines unchanged and only slightly metabolized in the liver.
The elimination half-life (T1/2) of candesartan in approximately 9 h. drug Accumulation in the body is not observed.
Total clearance of candesartan in is around 0,37 ml/min/kg, with renal clearance of about 0.19 ml/min/kg of candesartan in Renal excretion is by glomerular filtration and active tubular secretion.
Ingestion of radioactively-labeled candesartan in about 26% of the administered amount is excreted by the kidneys in the form of candesartan in, and 7% as an inactive metabolite, whereas in the feces is detected 56% of the administered amount in the form of candesartan in, and 10% as the inactive metabolite.
Pharmacokinetics in special clinical cases
Pharmacokinetic parameters of candesartan in do not depend on the sex of the patient.
In patients older than 65 years Cmax and AUC of candesartan in increase by 50% and 80%, respectively, compared to the young patients. However, the hypotensive effect and the incidence of side effects when using candesartan in do not depend on the age of the patients.
In patients with slight and moderate impaired renal function Cmax and AUC of candesartan in increased PA 50% and 70%, respectively, whereas T1/2 of the drug is not changed in comparison with patients with normal function nights.
In patients with severe impairment of renal function and/or hemodialysis, the Cmax and AUC of candesartan in increased by 50% and 110%, respectively, while T1/2 of the drug increased in 2 times.
In patients with easy and moderate hepatic impairment there was an increase in the AUC of candesartan in 23%.
Indications:
Hypertension.
Chronic heart failure and systolic dysfunction of the left ventricle (ejection fraction of the left ventricle (FULI) not more than 40%) as adjunctive therapy with ACE inhibitors or intolerance to ACE inhibitors.
Contraindications:
Hypersensitivity to candesartan and other components of the drug; lactose intolerance; lactase deficiency; syndrome of glucose-galactosyl malabsorption; severe hepatic impairment and/or cholestasis; pregnancy; lactation; children up to age 18 years; concurrent use with aliskiren in patients with diabetes and impaired renal function (KK less 60 ml/min).
With caution:
Gemodinamicheski signicant stenosis of the aortic and mitral valves, cerebrovascular disease, coronary heart disease (CHD), hypertrophic obstructive cardiomyopathy (HACMP), condition after kidney transplantation, bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, primary aldosteronism, renal insufficiency, severe (creatinine clearance (CC) less than 30 ml/min), hemodialysis, hyperkalemia; in patients with a reduced volume of circulating blood (BCC), General anaesthesia and surgical interventions (risk of hypotension due to blockade of the RAAS).
Pregnancy and lactation:
The drug Ordiss® is contraindicated during pregnancy due to the fact that candesartan has a direct impact on the RAAS can cause abnormalities of fetal development or to have a negative impact on the newborn, including death. If pregnancy is detected during treatment with the drug, Ordiss®, you should immediately stop the drug. When planning a pregnancy it is necessary to translate the patient on appropriate therapy, approved for use during pregnancy.
Newborns whose mothers had received during pregnancy, the drug, Ordiss®, should be under medical supervision because of the likelihood of hypotension.
It is unknown whether candesartan penetrates in breast milk. NS should use the drug, Ordiss® during breastfeeding. Should stop breastfeeding if necessary, use of the drug in the mother.
Method of application and dose:
Inside, regardless of meals, 1 time per day.
Hypertension the recommended initial dose of the drug, Ordiss® is 8 mg 1 times per day. Patients requiring further reduction in blood pressure (BP), it is recommended to increase the dose to 16 mg 1 time per day. The maximum antihypertensive effect is achieved within 4 weeks of starting treatment. The maximum daily dose of 32 mg/day. If on the background of drug treatment, Ordiss® not achieved adequate blood pressure control, it is recommended to add to the therapy thiazide diuretic.
Patients pressure age, it is not necessary initial dose adjustment of the drug.
In patients with reduced BCC, there is a risk of hypotension, so you should begin the treatment with a dose of 4 mg/day (1/2 tablet of 8 mg).
In patients with renal insufficiency. When used in patients with mild or moderate renal insufficiency (QC of not less than 30 ml/min/1.73 m2 of the body surface area) initial dose of 4 mg/day (1/2 tablet of 8 mg).
Clinical experience with the drug in patients with severe renal failure (KK less 30 ml/min/1.73 m2 of body surface) is restricted. In these cases, you should consider beginning treatment with a dose of 4 mg/day (1/2 tablet of 8 mg).
In patients with impaired liver function. In applying the drug in patients with hepatic impairment mild and moderate severity recommended initial dose is 2 mg/day (1/4 tablet 8 mg). If needed, may increase doses. Clinical experience with the drug in patients with severely impaired liver function and/or cholestasis is limited (see section "Contraindications").
The drug Ordiss® can be used in conjunction with thiazide diuretics (e.g. hydrochlorothiazide), which leads to increased hypotensive action.
Chronic heart failure (CHF)
The recommended initial dose of the drug, Ordiss® is 4 mg of 1 times a day (1/2 tablet of 8 mg). Increase the dose to 32 mg 1 time per day or until maximum tolerated dose is held by doubling at intervals of not less than 2 weeks.
The drug Ordiss® can be used in conjunction with other drugs used in CHF, for example, with ACE inhibitors, beta-adrenoblokatorami, dioretikami and cardiac glycosides.
Special groups of patients
Elderly patients, patients with renal insufficiency or impaired liver function should not need to change the initial dose of the drug.
Side effects:the incidence of adverse effects classified according to the recommendations of the world health organization: very often - not less than 10%; often - at least 1% but less than 10%; rarely, at least 0.1% but < 1%; rare - not less than 0.01%, but less than 0.1%; very rare - less than 0.01%, including individual messages.
The blood and lymphatic system: very rarely - leukopenia, neutropenia, thrombocytopenia, agranulocytosis.
The immune system: very rarely - skin rash, itching, hives, angioedema.
From the nervous system: often - dizziness, headache, weakness.
The respiratory system: often - respiratory infection, pharyngitis, rhinitis.
Gastrointestinal: very rarely - nausea.
Of the cardiovascular system: often- expressed lower AD.
The liver and biliary tract: rarely - increased activity of "liver" transaminases, abnormal liver function, hepatitis.
On the part of the musculoskeletal system and connective tissue: very rare back pain, arthralgia, myalgia.
The kidneys and urinary tract: often - violation of the kidney (see section "Special instructions").
The laboratory parameters: very rarely - hyperkalemia, hyponatremia, increased creatinine concentration, hyperuricemia, a decrease in hemoglobin.
Other: very rarely - exacerbation of gout, "tides" of blood to the face.
Overdose:
Symptoms: analysis of pharmacological properties of the drug suggests that the main manifestation of an overdose may be clinically significant decrease in blood pressure, dizziness. Described isolated cases of overdose (up to 672 mg candesartan in), and ended with the recovery of patients without severe consequences.
Treatment: with the development of clinically expressed lower AD should be symptomatic treatment and monitor the patient's condition. To lay the patient on his back and lift his legs. If necessary, increase the BCC, for example, by on/in the introduction 0.9% solution of sodium chloride. If necessary, you can apply a sympathomimetic means. The excretion of candesartan in with the use of hemodialysis is ineffective.
Interaction:While the use of candesartan in hydrochlorothiazide, warfarin, digoxin, oral contraceptives (ethinyl estradiol/levonorgestrel), glibenclamide, nifedipine and enalapril clinically significant drug interactions have been identified.
While the use of candesartan in with ACE inhibitors, other receptor antagonists to angiotensin II, aliskiren increases the risk of hyperkalemia, a sharp decline in blood pressure, impaired renal function, including acute renal failure, which requires careful control of blood pressure and indices of renal function and water and electrolyte balance.
Concurrent use of candesartan in with aliskiren in patients with diabetes and impaired renal function (YUS less than 60 ml/min) is not recommended. Candesartan metabolized in the liver to a small extent with the participation of izofermenta CYP2C9. The study on the interaction showed no effect of candesartan in the isozymes CYP2C9 and CYP3A4, the effect on other isoenzymes of cytochrome P450 have not been studied.
Concurrent use of candesartan in with other antihypertensives increases the antihypertensive effect.
Experience of application of other drugs acting on the RAAS, indicates that concomitant therapy potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium and other drugs that increase potassium in the blood serum (e.g. heparin) may lead to the development of hyperkalemia.
With simultaneous use of drugs lithium and ACE inhibitors occurs reversibly increase the concentration of lithium in the blood serum and the development of toxic reactions. Such a reaction can also occur in the use of receptor antagonists of angiotensin II, therefore it is recommended to monitor the lithium content in the blood serum.
Concurrent use of nonsteroidal anti-inflammatory drugs (NSAIDs), including selective cyclooxygenase-2 inhibitors (COX-2), acetylsalicylic acid (>3 g/day), and nonselective NSAIDs may reduce the antihypertensive effect of candesartan in, and can also lead to an increased risk of renal dysfunction, including the development of acute renal failure and to increase the amount of potassium in the blood serum. Be careful to use a combination of these drugs, especially in elderly patients.
Special instructions:
The impairment of renal function. On the background of the drug, Ordiss®, as the use of other drugs, oppressive RAAS, in some cases, may develop renal dysfunction.
In applying the drug, Ordiss® in patients with hypertension and renal failure, severe (CC less than 30 ml/min) is recommended to regularly monitor the content of potassium and creatinine concentration in blood serum. Clinical experience with the drug in patients with end-stage renal failure (KK less 15 ml/min) is limited. In applying the drug, Ordiss® in such patients it is necessary to adjust the dose of the drug, Ordiss® under the control of AD.
In patients with khsp is necessary to periodically monitor renal function, especially in patients older than 75 years and patients with impaired renal function. At higher doses it is also recommended to monitor potassium and creatinine concentration in blood serum.
No data on the use of the drug, Ordiss® at HSN with the concentration of creatinine more than 265 µmol/l (>3 mg/ml).
Hemodialysis. During hemodialysis the blood pressure can be particularly sensitive to the blockade of AT1-receptors by reducing the volume and activate the RAAS. Therefore, patients undergoing hemodialysis, it is necessary to supervise a blood pressure and to carry out individual selection of doses of the drug, Ordiss® in accordance with the indicators of AD.
The simultaneous use of ACE inhibitors in CHF. While the use of ACE inhibitors increases the risk of side effects, especially impaired renal function, and hyperkalemia. Should monitor the clinical condition of patients and appropriate laboratory parameters.
Renal artery stenosis. Drugs that affect the RAAS (e.g., ACE inhibitors) may lead to the increase of urea and creatinine in blood serum in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney. The same effect can be expected in the application of antagonists of angiotensin II receptors.
Kidney transplantation. The experience of the drug, Ordiss® in patients who recently had kidney transplant, is missing.
Hypotension. In patients with CHF using the drug, Ordiss® may develop hypotension. It is also possible the development of arterial hypotension in patients with a deficit BCC, for example, when using large doses of diuretics. In this case, before using the product, Ordiss® it is necessary to make correction of the BCC.
General anesthesia and/or surgery. Patients receiving antagonist of angiotensin II during General anesthesia and during surgery may develop hypotension due to the blockade of RAAS. In rare cases, hypotension may be severe, requiring intravenous fluid and/or vasopressors.
Stenosis of the aortic and/or mitral valves, HOKE. In applying the drug, Ordiss® in patients with HACMP or hemodynamically significant stenosis of the aortic or mitral valves should be used with caution.
Primary hyperaldosteronism. Patients with primary hyperaldosteronism is usually resistant to treatment, antihypertensive drugs, affecting the RAAS, therefore, to use the drug, Ordiss® in this group of patients is not recommended. Hyperkalemia. The simultaneous use of the drug, Ordiss® with potassium-sparing diuretics, potassium supplements or salt substitutes containing potassium, or other drugs that can increase potassium level in the serum (e.g. heparin) may lead to the development of hyperkalemia in patients with hypertension.
Hyperkalemia may develop in patients with chronic heart failure taking the drug, Ordiss®. On the background of drug therapy, Ordiss® in patients with CHF, it is recommended to periodically control the content of potassium in the blood serum, especially with simultaneous use of ACE inhibitors and potassium-sparing diuretics (spironolactone, triamterene, amiloride).
Common. Patients in whom vascular tone and renal function depend predominantly on the activity of the RAAS (e.g., patients with severe chronic heart failure, renal disease, including renal artery stenosis), are particularly sensitive to drugs acting on the RAAS. The use of such drugs is accompanied in these patients, abrupt hypotension, azotemia, oliguria and rarely acute renal failure. The possibility of the development of the listed effects are not excluded in the application of antagonists of angiotensin II receptors. A sharp decrease in blood pressure in patients with ischemic cardiomyopathy, cerebrovascular diseases ischemic when using any antihypertensives, can lead to the development of myocardial infarction or stroke.
Use in Pediatrics. The safety and efficacy of the drug, Ordiss® under the age of 18 years not installed.
The impact on the ability to manage transp. Ms. and fur.:
If you experience unwanted effects from the CNS during therapy with the drug, Ordiss® use caution when performing actions that require high concentration and psychomotor speed reactions.
Storage conditions:
Store in a dry place at temperatures not above 25 °C.
Keep out of reach of children.
Expiration date:
2 years.
Do not use after expiration date.
