Pharmacological properties

Pharmacodynamics. action mechanism. telmisartan — the specific and effective antagonist of receptors of ii angiotensin (type at1). telmisartan with very high affinity substitutes ii angiotensin in places of its binding on subtype receptors at1, responsible for activity of ii angiotensin. telmisartan does not show any partial agonistic impact on an at1-receptor. telmisartan selectively ties an at1-receptor. binding is long-term.

Telmisartan does not show affinity to other receptors, including AT ₂ and another, less studied AT-receptors. The functional role of these receptors is unknown as the effect of their possible "hyper stimulation" by angiotensin II which level increases under the influence of a telmisartan is unknown. Telmisartan reduces Aldosteronum level in blood plasma. Telmisartan does not inhibit renin in blood plasma of the person, does not block an ion channel. Telmisartan does not inhibit angiotensin-converting enzyme (kininaza of II), also destroys bradykinin. Therefore it is not necessary to expect potentiation of bradikininsoprovozhdayushchy side effects.

At the person telmisartan in a dose of 80 mg is almost completely inhibited by increase in the ABP called by angiotensin II. The blocking effect remains during 24 h and there is notable up to 48 h

a Pharmacokinetics

Absorption. Absorption of a telmisartan fast though the adsorbed quantity differs. The average absolute bioavailability of a telmisartan is about 50%.

When telmisartan is accepted at meal time, decrease in AUC for a telmisartan varies approximately from 6% (40 mg) to 19% (160 mg). In 3 h after introduction the concentration in blood plasma is identical irrespective of it, is accepted telmisartan on an empty stomach or with food.

Linearity/nonlinearity. It is considered that small decrease in AUC does not cause decrease in therapeutic effectiveness. There is no linear dependence between a dose and level in blood plasma. With _max and to a lesser extent AUC increase disproportionally at doses higher than 40 mg.

Distribution. Telmisartan actively contacts proteins of blood plasma (99.5%), mainly albumine and alfa-1 an acid glycoprotein. The volume of distribution (Vss) is about 500 l.

Metabolism. Telmisartan is metabolized by conjugation with a glucuronide. The pharmacological activity of a conjugate is not established.

Removal. Telmisartan is characterized by biexponentsialny pharmacokinetics with terminal in T _½ 20 h. With _max and AUC increase disproportionately a dose. There are no data on clinically significant cumulation of a telmisartan at use in the recommended doses. Concentration in blood plasma were higher at women, than at men, without the corresponding influence on efficiency.

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After oral introduction telmisartan it is almost completely removed with a stake generally in not changed look. Cumulative renal excretion is 1% of a dose. The general clearance in blood plasma (Cl _tot ) high (about 1000 ml/min.) if to compare to hepatic circulation (about 1500 ml/min.).

Special categories of patients

Children. Results of researches of pharmacokinetics at children in general correspond to the data obtained for adults and confirm nonlinearity of a telmisartan, in particular for the C _max .

Floor. The C _max and AUC at women approximately in 3 and 2 times is respectively higher, than at men.

Patients of advanced age. The pharmacokinetics of a telmisartan does not differ at people of advanced age and persons aged up to 65 years.

Patients with a renal failure. At patients with moderate, average and heavy degree of a renal failure the increase twice in concentration in blood plasma was observed. However at the patients with a renal failure who are subject to dialysis the low concentration in blood plasma was observed. Telmisartan has high affinity to proteins of blood plasma at persons with a renal failure and cannot be brought by dialysis. At patients with a renal failure of T _½ does not change.

Patients with abnormal liver functions. In pharmacokinetic researches at patients with disturbances of a liver the increase in bioavailability approximately up to 100% is revealed. At patients with a liver failure of T _½ does not change.

Indication

Ag: treatment of essential hypertensia at adults.

Prevention of cardiovascular diseases at patients with:

• manifest aterotrombotichesky cardiovascular disease (ischemic heart disease, stroke or damages of peripheral arteries in the anamnesis);
• diabetes of the II type with the documented damage of target organs.

Use

Lecheniye ag. the usual effective dose makes 40 mg/days to some patients can be rather daily dose of 20 mg. in cases when the desirable effect is not reached, the dose of a telmisartan can be raised to 80 mg of 1 times a day. alternatively telmisartan it is possible to appoint in a combination with thiazide diuretics, such as hydrochlorothiazide which showed additional decrease hell at use with telmisartany. when the question of increase in a dose is considered, it is necessary to take into account that the maximum antihypertensive effect in general is reached in 4–8 weeks from an initiation of treatment.

Prevention of cardiovascular diseases. The recommended dose makes 80 mg of 1 times a day. The efficiency of a telmisartan in doses less than 80 mg at prevention of cardiovascular diseases is unknown.

telmisartany for the purpose of prevention of cardiovascular diseases recommends to carry out

In an initiation of treatment monitoring of the ABP and, in case of need, to adjust doses of the medicaments lowering the arterial blood pressure.

Special groups of patients

Renal failure. Experience of treatment of patients with a renal failure or the patients who are on a hemodialysis is limited. Such patients are recommended to begin treatment with a low dose of 20 mg (see. Special INSTRUCTIONS). Patients with a renal failure easy and moderate severity do not require dose adjustment.

Simultaneous use of a telmisartan and aliskiren for patients with diabetes or with renal failures (the glomerular filtration rate (GFR) of 60 ml/min. / 1.73 to m ² ) it is contraindicated to

(see CONTRAINDICATIONS).

Abnormal liver function. Hipotel is contraindicated to patients with a heavy abnormal liver function. For patients with slight or moderate abnormal liver functions the daily dose should not exceed 40 mg of 1 times a day (see. Special INSTRUCTIONS).

Patients of advanced age. Dose adjustment for patients of advanced age is not required.

Route of administration. Hipotel to accept 1 time a day with enough liquid, irrespective of meal.

to store

Tablet in the tight blister for protection against moisture. Tablets should be taken out from the blister just before use.

Contraindication

Hypersensitivity to medicament components; the period of pregnancy and to women of reproductive age who, perhaps, are pregnant (see use during pregnancy and feeding by a breast); obstructive biliary disturbances; heavy abnormal liver functions.

Simultaneous use of a telmisartan and aliskiren for patients with diabetes or with renal failures (SKF of 60 ml/min. / 1.73 m ² ) is contraindicated (see USE, SPECIAL INSTRUCTIONS, INTERACTIONS).

Side effects

Infection and invasion: upper respiratory tract infections, including pharyngitis and sinusitis, urinary tract infections, including cystitis; sepsis, including with a lethal outcome.

from the system of blood and lymphatic system: anemia, thrombocytopenia, eosinophilia.

from the immune system: hypersensitivity, anaphylactic reactions.

from a metabolism: a hyperpotassemia, a hypoglycemia (at patients with diabetes).

Mental disorders: depression, insomnia, concern.

from nervous system: to a syncope, drowsiness.

from an organ of sight: disorder of vision.

from an organ of hearing, a vestibular mechanism: vertigo.

from heart: bradycardia, tachycardia.

from vessels: arterial hypotension, orthostatic hypotension.

from the respiratory system, bodies of a thorax and mediastinum: dispnoe, cough, interstitial pulmonary disease.

from digestive system: an abdominal pain, diarrhea, dyspepsia, a meteorism, vomiting, discomfort in a stomach, dryness in a mouth.

from a gepatobiliarny system: dysfunction of a liver / hepatic disorders.

from skin and hypodermic cellulose: the increased sweating, an itching, rashes, an erythema, a Quincke's disease (including with a lethal outcome), medicamentous dermatitis, toxic dermatitis, eczema, a small tortoiseshell.

from the musculoskeletal system and connective tissue: myalgia, dorsodynia (for example sciatica), myotonia, arthralgia, extremity pain, sinew pain (symptoms similar to a tendinitis).

from an urinary system: a renal failure, including OPN.

General disturbances: stethalgia, asthenia (weakness), symptoms similar to flu.

Datas of laboratory: increase in creatinine in blood, increase in uric acid in blood, increase in hepatic enzymes, increase in the KFK level in blood, decrease in hemoglobin.

Special instructions

Pregnancy. during pregnancy it is impossible to begin treatment by antagonists of receptors of ii angiotensin. if continuation of therapy by antagonists of receptors of ii angiotensin is not extremely necessary for the patient planning pregnancy, it has to pass to alternative antihypertensive therapy which has the established safety profile for use during pregnancy. at pregnancy establishment the treatment by antagonists of receptors of ii angiotensin needs to be stopped immediately and if necessary to begin alternative treatment (see contraindications and use during pregnancy and feeding with a breast).

Liver failure. Hipotel it is impossible to appoint the patient with a cholestasia, obstructive diseases of bile ducts and a liver failure of heavy degree (see CONTRAINDICATIONS) as telmisartan it is removed mainly with bile. At such patients it is possible to expect decrease in hepatic clearance of a telmisartan.

Hipotel should appoint

with care the patient with a liver failure of moderate and average degree.

Renovascular hypertensia. There is an increased risk of serious arterial hypotension and renal failure if patients with a bilateral renal artery stenosis or a stenosis of an artery of the only kidney are treated medicaments which influence the renin-angiotensin-aldosteronovuyu system (RAAS).

Renal failure and transplantation of a kidney. When Hipotel appoint to patients with impaired renal function, periodic monitoring of level of potassium and creatinine in blood plasma is recommended. There is no experience of use of a telmisartan for patients with recent transplantation of a kidney.

Reduction of intravascular volume of liquid. Symptomatic hypotension, especially after the first dose of the medicament Hipotel, can arise at patients with reduced OCK and/or level of sodium which result from therapy by diuretics, restrictions of the salt arriving with food, diarrheas or vomitings. Before Hipotel's reception it is necessary to adjust such states, especially decrease in intravascular volume and/or level of sodium.

Double blockade of RAAS. Use of a telmisartan in a combination with aliskireny at patients with diabetes or with renal failures (SKF of 60 ml/min. / 1.73 m ² ) is contraindicated (see CONTRAINDICATIONS).

As a result of braking of RAAS at more sensitive patients noted arterial hypotension, a syncope, a hyperpotassemia and changes of function of kidneys (including OPN), especially if the medicines influencing this system were a part of combination therapy. Therefore double blockade of RAAS (for example use of a telmisartan with other blockers of RAAS) is not recommended. In need of simultaneous use the careful monitoring of function of kidneys is recommended.

Other states demanding stimulation of RAAS. At patients who have a vascular tone and function of kidneys depend mainly on activity of RAAS (for example at patients with heavy stagnant heart failure or the profound disease of kidneys, including a renal artery stenosis), reception of a telmisartan with other medicines influencing RAAS can lead to acute arterial hypotension, a hyperazotemia, an oliguria, is rare — with OPN (see. Side EFFECTS).

Primary hyper aldosteronism. Patients with primary hyper aldosteronism in general do not react to the antihypertensive medicaments operating by blockade system renin-angiotenzinovoy. Therefore purpose of a telmisartan is not recommended to them.

Stenosis of an aorta and mitral valve, subaortic hypertrophic stenosis. As well as other vazodilatator, with extra care appoint medicament to patients for whom the stenosis of an aorta, the mitral valve or a subaortic hypertrophic stenosis is diagnosed.

Patients with diabetes who are treated by insulin or anti-diabetic medicines. During treatment telmisartany at such patients the hypoglycemia can develop. It is necessary to consider need of the corresponding control of level of glucose for blood at such patients. According to indications the dose adjustment of insulin or antidiabetic medicines can be required.

At patients with diabetes, with cardiovascular risks (patients with diabetes, with associated diseases of coronary arteries) risk of developing a myocardial infarction with a lethal outcome and a sudden cardiovascular lethal outcome can be higher at treatment by antihypertensive drugs, such as antagonists of receptors of angiotensin II and APF inhibitors. Patients with diabetes can have an asymptomatic course of associated diseases of coronary arteries and therefore they can be not diagnosed. Patients with diabetes should be examined carefully, for example stressful testing to reveal and treat associated diseases of coronary arteries before prescribing of drug.

Hyperpotassemia. During the entire period of use of the medicines influencing RAAS there can be a hyperpotassemia.

At patients of advanced age, patients with a renal failure, diabetes, at the patients in parallel accepting other medicines which can cause increase in level of potassium, and/or patients with associated diseases a hyperpotassemia the lethal outcome can have

.

Before the accompanying use of medicines, the oppressing RAAS, it is necessary to estimate a ratio of advantage and risk.

Major factors of risk of development of a hyperpotassemia to which it is necessary to pay attention:

• diabetes, a renal failure, age is more senior than 70 years;
• combination therapy with one or several other medicaments influencing RAAS and/or potassium additives. The salt substitutes containing potassium, kaliysberegayushchy diuretics, APF inhibitors, antagonists of receptors of angiotensin II, NPVP (including selection TsOG-2 inhibitors), heparin, immunodepressants (cyclosporine or takrolimus) and Trimethoprimum belong to medicaments or therapeutic groups of medicines which can provoke a hyperpotassemia;
• associated diseases, especially dehydration, a sharp warm decompensation, a metabolic acidosis, a renal failure, sharp aggravation of symptoms of kidneys (for example owing to infectious diseases), cellular lysis (for example owing to acute ischemia of extremities, acute necrosis of skeletal muscles, an extensive injury).

Sick risk groups needs to undergo careful control of plasma potassium concentration (see INTERACTIONS).

Ethnic distinctions. As well as all other antagonists of receptors of angiotensin II, telmisartan is less effective for decrease in the ABP at patients of negroid race, than at representatives of other races. Perhaps, it has a talk big distribution of low reninovy states at patients of negroid race with AG.

Others. As well as at use of any other antihypertensive drug, considerable decrease in the ABP at patients with an ischemic cardiopathy or an ischemic cardiovascular disease can lead to a myocardial infarction or a stroke.

Use during pregnancy or feeding by a breast. Pregnancy. Antagonists of receptors of angiotensin II should not appoint pregnant women or women who, perhaps, are pregnant (see CONTRAINDICATIONS). If pregnancy is confirmed during treatment by this drug, its use should be stopped immediately and if necessary to begin alternative treatment.

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It was reported about lethal outcomes at a fruit and the newborn, an oligoamnios, hypotension at a fruit and the newborn, a renal failure, a hyperpotassemia, a hypoplasia of a skull, a contracture of extremities / cerebral, craniofacial deformation / a pulmonic dysplasia, perhaps, caused by an oligoamnios in the pregnant patients receiving antagonists of receptors of angiotensin II in II or III trimester of pregnancy.

Patient, the receiving antagonists of receptors of angiotensin II and planning pregnancy have to pass to antihypertensive medicines which have the established safety profile for use during pregnancy.

Feeding by a breast. Due to the lack of information on use of a telmisartan during feeding by a breast Hipotel is not recommended for use. Preference should be given to alternative treatment with better the studied safety profile, especially when feeding by a breast of the newborn or premature child.

Fertility. During preclinical trials the influence of a telmisartan on fertility of men and women is not revealed.

Children. Hipotel is contraindicated to children because of limited information on safety and efficiency of medicament at this category of patients.

Ability to influence speed of response at control of vehicles or work with other mechanisms. When driving and mechanisms it is necessary to consider possibility of dizziness or a hypersomnia at antihypertensive therapy, including the medicament Hipotel.

Interaction

Double blockade raas. the combination of a telmisartan and an aliskiren is contraindicated for patients with diabetes and a renal failure (skf 60 ml/min. / 1.73 to sq.m) and is not recommended for patients of other groups (see contraindications, special instructions).

Digoksin. At simultaneous use of a telmisartan and digoxin noted average increase in peak concentration of digoxin in blood plasma (for 49%) and the minimum concentration (for 20%). At the beginning of reception in case of dose adjustment and the termination of reception of a telmisartan it is necessary to conduct monitoring of levels of digoxin for their maintenance within therapeutic range.

As well as other medicaments which suppress RAAS telmisartan can provoke a hyperpotassemia (see. Special INSTRUCTIONS). The risk can increase in case of treatment in a combination with other means which can also lead to a hyperpotassemia (the salt substitutes containing potassium, kaliysberegayushchy diuretics, APF inhibitors, antagonists of receptors of angiotensin II, NPVP including selection TsOG-2 inhibitors), heparin, immunodepressants (cyclosporine or takrolimus) and Trimethoprimum.

Cases of a hyperpotassemia depend on the related risk factors. The risk increases at the therapeutic combinations given above. The risk at a combination with kaliysberegayushchy diuretics is especially high and in combination with the salt substitutes containing potassium. The combination with APF or NPVP inhibitors, for example, is less risky on condition of accurate observance of precautionary measures at use.

Simultaneous use is not recommended to

Kaliysberegayushchy diuretics or potassium additives. Such antagonists of receptors of angiotensin II, as telmisartan, soften the potassium loss caused by diuretics. Kaliysberegayushchy diuretics, for example Spironolactonum, eplerenon, Triamterenum or amiloride, potassium additives or substitutes of salt containing potassium can cause substantial increase of potassium concentration in blood plasma. If simultaneous use is shown in view of documentary confirmed hypopotassemia, it is necessary to take medicaments with caution, often controlling potassium level in blood plasma.

Lities. Cases of reversible increase in concentration of lithium in blood plasma and toxicity at the accompanying intake of lithium with APF inhibitors are known and antagonists of receptors of angiotensin II, including telmisartan. If purpose of this combination is considered necessary, during simultaneous use it is necessary to control attentively lithium level in blood plasma.

Simultaneous use demands care

NPVP. NPVP (that is acetylsalicylic acid in anti-inflammatory doses, TsOG-2 inhibitors and non-selective NPVP) can reduce antihypertensive action of antagonists of receptors of angiotensin II.

combined reception of antagonists of receptors of angiotensin II and the means braking COG can lead

At some patients with deterioration in function of kidneys (for example patients with dehydration of an organism or at elderly people with deterioration have functions of kidneys) to further deterioration in function of kidneys, including possible OPN which usually is reversible. Therefore it is necessary to appoint this combination with care, especially to elderly people. Patients should provide appropriate hydration; besides, after the beginning of combination therapy and also periodically further it is necessary to control function of kidneys. 0-24 and the C _max a ramipril and the ramiprilat Are p>

. The clinical importance of this observation is unknown.

Diuretics (thiazide or loopback diuretics). The previous treatment by high doses of such diuretics as furosemide (loopback diuretic) and a hydrochlorothiazide (thiazide diuretic), can lead to loss of OCK and risk of arterial hypotension if to begin treatment telmisartany.

Should be taken into account at simultaneous use

Other antihypertensive drugs. The ability of a telmisartan lower the arterial blood pressure can be increased by the accompanying use of other antihypertensive drugs.

can expect

On the basis of pharmacological properties of Baclofenum and an amifostin that these medicines can strengthen hypotensive effect of all antihypertensive drugs, including a telmisartan. Besides, orthostatic hypotension can be strengthened by alcohol, barbiturates, medicaments and antidepressants.

Corticosteroids (system use). Reduction of expressiveness of antihypertensive action.

Overdose

Information on overdose at people is insufficient

.

Symptoms. Arterial hypotension and tachycardia were considerable manifestations at overdose of a telmisartan; also it was reported about bradycardia, dizziness, increase in concentration of creatinine in blood plasma and OPN.

Therapy. Telmisartan is not brought by a hemodialysis.

Patients have to be under stringent control and receive symptomatic and maintenance therapy. Therapy depends on time which passed after administration of medicament and weight of symptoms. The recommended measures include calling of vomiting and/or gastric lavage. At therapy of overdose it is possible to apply activated carbon. It is necessary to check often the level of electrolytes and creatinine in blood plasma. When developing arterial hypotension of the patient it is necessary to lay on a back and to help, directed to fast completion of volume of liquid and salt in an organism.

Storage conditions

At a temperature not above 25 °C in original packing.