ÈáÓñ«ßá½® 40

General characteristics. Structure:

Kernel:

Active ingredient: medoksomit an olmesartan - 40,00 mg.

Excipients: cellulose microcrystallic, a hypro rod (with low extent of substitution), lactoses monohydrate, a hypro rod (viscosity of 6-10 MPas • c), magnesium stearate.

Cover: titanium dioxide (Е 171), talc, gipromelloz (viscosity of 5 MPas • с).

Pharmacological properties:

Pharmacodynamics. Olmesartana medoksomit - active ingredient of the drug Кардосал® 10 - is a specific antagonist of receptors of angiotensin II (AT1 type) for intake. Angiotensin II is primary vasoactive hormone renin-angiotensin-aldosteronovoy of system and plays a significant role in a pathophysiology of arterial hypertension by means of AT1 receptors. It is supposed what олмесартан blocks all effects of angiotensin II mediated by AT1 receptors irrespective of a source and a way of synthesis of angiotensin II.

At arterial hypertension олмесартан causes a dozozavisimy long lowering of arterial pressure (ABP). There are no data on development of arterial hypotension after reception of the first dose of drug and about development of a syndrome of "cancellation" (sharp increase in the ABP after drug withdrawal).

Reception of an olmesartan of a medoksomil provides effective and soft decrease in the ABP during 24 h once a day, and the effect after a single dose is similar to effect of administration of drug twice a day in the same daily dose. Hypotensive action of an olmesartan develops, as a rule, already in 2 weeks, and the maximum effect develops approximately in 8 weeks after the beginning of therapy.

Pharmacokinetics. Absorption and distribution: medoksomit an olmesartan is pro-medicine. It quickly turns into pharmacological active metabolite олмесартан under the influence of enzymes in a mucous membrane of intestines and in portal blood during absorption from digestive tract. Olmesartana medoksomit in not changed look in a blood plasma it was not found. Bioavailability of an olmesartan averages 25,6%. The maximum concentration (Cmax) of an olmesartan in a blood plasma is on average reached in 2 h after reception of an olmesartan of a medoksomil inside and increases approximately linearly with increase in a single dose up to 80 mg.

Meal does not exert considerable impact on bioavailability of an olmesartan therefore medoksomit an olmesartan it is possible to accept irrespective of meal. Clinically significant distinctions in pharmacokinetic indicators of an olmesartan depending on a floor are not revealed.

Olmesartan contacts proteins of a blood plasma (99,7%), but the potential for clinically significant shift of size of linkng with proteins at interaction of an olmesartan with other high-communicating and at the same time applied medicines is low (confirmation to that serves lack of clinically significant interaction between olmesartany and warfarin). Communication of an olmesartan with blood cells is insignificant.

Metabolism and removal: the general plasma clearance usually makes 1,3 l/h (coefficient of variation - 19%) and is rather low in comparison with a hepatic blood-groove (about 90 l/h). Renal removal makes about 40%, with bile - about 60%. Intra hepatic circulation of an olmesartan is minimum. As the most part of an olmesartan is removed through a liver, its use for patients with obstruction of biliary tract is contraindicated (see the section of the Contraindication).

The elimination half-life of an olmesartan makes 10-15 h after multiple dose inside. The significant effect of therapy is reached after reception of the first several doses of drug, and after 14 days of repeated use further cumulation is not observed. The renal clearance makes about 0,5-0,7 l/h and does not depend on a drug dose.

At patients with a renal failure the area under a curve "concentration time" (AUC) at the established (steady) state was increased approximately by 62, 82 and 179% in case of an easy, moderate and heavy renal failure, respectively, in comparison with healthy volunteers.

After a single dose in AUC value for an olmesartan were for 6 and 65% is higher at patients with easy and moderate degree of an abnormal liver function, respectively, in comparison with healthy volunteers. The untied fraction of an olmesartan in 2 h after reception of a dose of drug at healthy volunteers, at patients with the easy and moderated degrees of an abnormal liver function made 0,26, 0,34 and 0,41% respectively.

Indications to use:

Essential hypertensia.

Route of administration and doses:

It is recommended to accept Кардосал® 40 inside every day at the same time it is not dependent on meal of 1 times a day. The maximum daily dose - 40 mg.

Features of use:

Symptomatic arterial hypotension, especially after reception of the first dose of drug, can occur at patients with a reduced volume of the circulating blood and/or reduced level of sodium owing to an intensive care diuretics, restrictions of consumption of salt with food at dietary food, and also owing to diarrhea or vomiting. The corresponding factors should be eliminated prior to use of the drug Кардосал® 40.

At patients who have a vascular tone and function of kidneys depend to a large extent on activity system renin-angiotensin-aldosteronovoy (for example, at patients with heavy chronic heart failure or a renal failure, including a stenosis of renal arteries), treatment by other medicines operating on this system is connected with a possibility of development of acute arterial hypotension, an azotemia, an oliguria or, in rare instances, of an acute renal failure. The possibility of similar action cannot be excluded at use of antagonists of receptors of angiotensin II.

There is an increased risk of development of heavy arterial hypotension and renal failure if the patient with a bilateral stenosis of renal arteries or a stenosis of an artery of the only functioning kidney receives therapy by the medicines influencing renin-angiotensin-aldosteronovuyu system.

At use of the drug Кардосал® 40 for patients with a renal failure it is recommended to carry out periodic control of level of potassium and creatinine in blood serum. Experience of use of the drug Кардосал® 40 for patients with recently carried out transplantation of a kidney or at patients with the last stage of a renal failure (for example, KK less than 12 ml/min.) is absent.

As well as in case of other antagonists of receptors of angiotensin II and APF inhibitors, at treatment by the drug Кардосал® 40 the hyperpotassemia can develop if the patient suffers from a renal failure and/or chronic heart failure (see the section Interaction with other medicines). At patients of this risk group control of level of potassium in blood serum is recommended.

As well as in case of other antagonists of receptors of angiotensin II, the combination of drugs of lithium and the drug Кардосал® 40 is not recommended (see the section Interaction with other medicines).

As well as in case of other antagonists of receptors of angiotensin II, at the patients of negroid race having arterial hypertension efficiency of therapy by the drug Кардосал® 40 is slightly lower, than at patients of other races.

As in case of any anti-hypertensive means, excessive decrease in the ABP at patients with coronary heart disease or cerebrovascular insufficiency can lead to a myocardial infarction or a stroke.

Influence on ability to driving of motor transport and to control of mechanisms

Influence of the drug Кардосал® 40 on ability to driving of motor transport and to control of mechanisms was not studied therefore during treatment by the drug Кардосал® 40 it is necessary to be careful during the driving of motor transport and occupations potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions (dizziness and weakness are possible).

Side effects:

Possible side effects are given below on the descending emergence frequency: very often (> 1/10); often (> 1/100 <1/10); sometimes (> 1/1000, <1/100); seldom (> 1/10000, <1/1000); very seldom (<1/10000), including separate messages.

From circulatory and lymphatic systems
 Very seldom: thrombocytopenia.

From the central nervous system
 Sometimes: dizziness.
Very seldom: headache.

From respiratory system
 Often: pharyngitis, rhinitis.
Very seldom: cough, bronchitis.

From a digestive tract
 Often: diarrhea, dyspepsia, gastroenteritis.
Very seldom: abdominal pain, nausea, vomiting.

From integuments
 Very seldom: skin itch, rash, Quincke's disease, allergic dermatitis,
small tortoiseshell.

From a musculoskeletal system
 Often: dorsodynia, ostealgia, arthralgia, arthritis.
Very seldom: myotonia, mialgiya.

From an urinary system
 Often: hamaturia, infection of uric ways.
Very seldom: acute renal failure.

From laboratory indicators
 Very seldom: increase in level of creatinine and urea in blood serum, increase
 activities of enzymes of a liver.

From cardiovascular system
 Seldom: excess decrease in the ABP.
Sometimes: stenocardia, tachycardia.

From a metabolism
 Often: increase in level of a kreatinfosfokinaza, gipertriglitseridemiya, hyperuricemia.
Seldom: hyperpotassemia.

Other disturbances
 Often: thorax pain, grippopodobny symptoms, peripheral hypostases.
Very seldom: adynamy, fatigue, indisposition, drowsiness.

Interaction with other medicines:

Combined use with kaliysberegayushchy diuretics, potassium drugs, substitutes of the salts containing potassium or other medicines capable to increase potassium level in blood serum (for example, heparin) is not recommended, it can lead to increase in level of potassium in blood serum (see the section Special instructions).

The anti-hypertensive effect of therapy olmesartany can be strengthened at the combined use with other antihypertensives.

Non-steroidal anti-inflammatory drugs (NPVP), including acetylsalicylic acid in doses more than 3 g/days, and also inhibitors of cyclooxygenase-2 (TsOG-2), and antagonists of receptors of angiotensin II can synergistically work, reducing glomerular filtering. At simultaneous use of NPVP and antagonists of receptors of angiotensin II there can be a risk of development of an acute renal failure therefore control of function of kidneys in an initiation of treatment, and also regular reception of enough liquid is recommended. At the same time simultaneous treatment can reduce anti-hypertensive action of antagonists of receptors of angiotensin II, leading to partial loss of their therapeutic effectiveness. At simultaneous use with antacids (magnesium and aluminum hydroxide) perhaps moderate decrease in bioavailability of an olmesartan.

There are messages on reversible increase in concentration of lithium in blood serum and manifestation of toxicity during simultaneous use of drugs of lithium with inhibitors of the angiotensin-converting enzyme (ACE) and with antagonists of receptors of angiotensin II therefore use of an olmesartan of a medoksomil in a combination with drugs of lithium is not recommended (see the section Special instructions). In case of need uses of the corresponding combination therapy regular control of level of lithium in blood serum is recommended.

Contraindications:

• hypersensitivity to active ingredient or to any of the excipients which are a part of drug (see the section Structure);
• obstruction of biliary tract;
• renal failure (clearance of creatinine (CC) less than 20 ml/min.), state
 after transplantation of a kidney (there is no experience of a clinical use);
• pregnancy, lactation period;
• age up to 18 years (efficiency and safety are not established);
• deficit of lactase, galactosemia or sprue.

With care:
• stenosis of aortal or mitral valves;
• hypertrophic subaortic stenosis;
• primary aldosteronism;
• hyperpotassemia, hyponatremia (risk of dehydration, arterial hypotension, renal failure);
• renal failure (KK more than 20 ml/min.);
• chronic heart failure;
• bilateral stenosis of renal arteries or stenosis of an artery of the only kidney;
• coronary heart disease;
• cerebrovascular diseases;
• advanced age (65 years are more senior);
• abnormal liver function;
• the states which are followed by decrease in volume of the circulating blood (including diarrhea, vomiting), and also at the patients keeping to a diet with sodium restriction;
• at simultaneous use with diuretics.

Use at pregnancy and a lactation

Experience of use of an olmesartan of a medoksomil for pregnant women is absent. However in view of the available messages on heavy teratogenic effect of the medicines operating directly on a renin-angiotenzinovuyu system, as well as any medicine of this class олмесартан it is contraindicated during pregnancy. In case of approach of pregnancy during therapy by the drug Кардосал® 40 drug needs to be cancelled.

There are no data - whether is allocated олмесартан with breast milk therefore in need of use of the drug Кардосал® 40 in the period of a lactation breastfeeding for administration of drug should be stopped.

Overdose:

Symptoms: the expressed decrease in the ABP.

Treatment: at the expressed decrease in the ABP it is recommended to lay the patient on a back, having raised legs. The gastric lavage and/or reception of absorbent carbon, the therapy directed to correction of dehydration and disturbances of a water salt metabolism, completion of volume of the circulating blood is recommended.

Storage conditions:

At a temperature not above 30 °C. To store in the place, unavailable to children! Period of validity 3 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 40 mg.

On 14 tablets in the blister strip packaging (blister) made from
 the laminated film (polyamide / aluminum / PVC) and aluminum foil.

On 1, 2, 4 or 7 blisters together with the application instruction in a cardboard pack.