Telmisartan-Teva of the tab. of 80 mg No. 28

Pharmacological properties

Pharmacodynamics. telmisartan is a peroral specific antagonist of receptors of ii angiotensin (at1 type). with high affinity telmisartan substitutes ii angiotensin in places of its linking with a kind of at1-receptors through which effect of ii angiotensin is mediated. telmisartan does not show any partial agonistic influence on an at1-receptor.

Telmisartan selectively contacts AT ₁ - a receptor for a long time, without having on it even partial agonistic impact. Binding is long-term.

Telmisartan has no relationship to other receptors, including AT ₂ - receptors and other AT receptors. The functional role of these receptors is not found out, as well as effect of their possible stimulation by angiotensin II which levels increase telmisartany. Telmisartan reduces Aldosteronum level in blood plasma, does not block ion channels and does not reduce renin level in blood plasma. It does not lead to inhibition of angiotensin-converting enzyme (kininaza of II), enzyme which also splits bradykinin. Therefore the side effect mediated by bradykinin is not expected.

At the person the dose in 80 mg telmisartan almost completely slows down the increase in the ABP caused by angiotensin II. The inhibitory effect remains within a day and the Pharmacokinetics is defined up to 48 h

. Telmisartan is quickly absorbed, but amount of medicament which is absorbed, unequally. The average bioavailability of a telmisartan is about 50%.

At use of a telmisartan with food AUC for a telmisartan from about 6% (dose of 40 mg) to about 19% (dose of 160 mg) decreases. In 3 h after reception the concentration in blood plasma becomes the same, as well as at use of a telmisartan without food. It is considered that insignificant reduction of AUC does not reduce therapeutic effectiveness of drug. There is no linear dependence between a dose and level in blood plasma. The C _max and to a lesser extent AUC increase disproportionally at doses higher than 40 mg.

Telmisartan substantially contacts proteins of blood plasma (more than 99.5%), mainly albumine and α ₁ - an acid glycoprotein. The average volume of distribution (the V _ss ) in equilibrium state is about 500 l.

Telmisartan is metabolized by

by conjugation in a glucuronide of initial connection which has no pharmacological activity.

Telmisartan is characterized by a biexponentsionalny pharmacokinetic curve with terminal T _½ more 20th Part C _max in blood plasma and to a lesser extent AUC increases disproportionately a dose. At use of a telmisartan in the recommended doses of clinically significant cumulation it is not revealed. Concentration in blood plasma was higher at women, than at men, without the corresponding influence on efficiency.

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After reception (and in / c) introductions telmisartan it is almost completely removed with a stake, mainly in not changed look. Cumulative excretion with urine is less than 1% of the accepted dose. The general clearance of blood plasma (the CL _tot ) high (about 1000 ml/min.) in comparison with a blood flow through a liver (about 1500 ml/min.).

Special categories of patients

Children. The pharmacokinetics of two doses of a telmisartan was estimated as the secondary purpose for hypertensive patients (n=57) aged from 6 up to 18 years after reception of a telmisartan in a dose of 1 or 2 mg/kg of body weight during 4 weeks of treatment. The pharmacokinetic purposes included determination of levels of a telmisartan in a stable state at children and teenagers and a research of the distinctions connected with age. Though children had an insufficient for reliable assessment of pharmacokinetics research aged up to 12 years, results 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 patients of advanced age and 65 years are younger.

Patients with a renal failure. At patients with moderate, average and heavy degree of a renal failure noted increase twice in concentration in blood plasma. However at the patients with a renal failure who are subject to dialysis the low concentration in blood plasma is revealed. Telmisartan has high affinity to proteins of plasma at patients 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. Pharmacokinetic researches at patients with disturbances of a liver showed increase in bioavailability approximately to 100%. At patients with a liver failure of T _½ does not change.

Indication

Ag. treatment essential ag at adults.

Prevention of cardiovascular diseases. Decrease in incidence of cardiovascular nozologiya at patients with:

• significant manifestations of an aterotrombotichesky cardiovascular disease (an ischemic heart disease, a stroke or diseases of peripheral arteries in the anamnesis);
• diabetes of the II type with the diagnosed damage of target organs.

Use

should apply Telmisartan-tev's

1 time a day inside with enough liquid, irrespective of meal.

Lecheniye AG. The recommended dose makes 40 mg/days. For some patients the dose of 20 mg/days will be sufficient. If the ABP level does not decrease to desirable figures, then it is possible to raise a dose as much as possible to 80 mg of 1 times a day. It is possible to appoint Telmisartan-Tev in a combination with thiazide diuretics, such as hydrochlorothiazide which show additional effect on decrease in the ABP when assigning together with telmisartany. At the solution of a question of increase in a dose it must be kept in mind that the maximum hypotensive effect occurs in 4–8 weeks from an initiation of treatment.

Prevention of cardiovascular diseases. The recommended dose makes 80 mg of 1 times a day. It is unknown whether the dose of a telmisartan of 80 mg for decrease in level of cardiovascular incidence is effective.

telmisartany for the purpose of reduction of risk of cardiovascular diseases recommends to carry out

In an initiation of treatment careful control of the ABP. There can be a need for the corresponding correction of schemes of use of the medicaments lowering the arterial blood pressure.

Renal failure. Patients with a renal failure easy or have no moderate severity of need for dose adjustment. There is a limited experience of use for patients with a renal failure or on a hemodialysis. For these patients the recommended low initial dose makes 20 mg.

Abnormal liver function. For patients with an abnormal liver function of easy and average degree the dose should not exceed 40 mg/days. Drug is contraindicated to patients with heavy abnormal liver functions.

Sick advanced age. Dose adjustment is not required.

Contraindication

Hypersensitivity to active ingredient or any of medicament excipients.

Pregnant women or women who are going to become pregnant (see Use during pregnancy or feeding by a breast). Obstructive diseases of bile ducts. Heavy abnormal liver functions. Children's age up to 18 years. Contraindicated simultaneous use of a telmisartan and aliskirensoderzhashchy medicaments for patients with diabetes or a renal failure (glomerular filtration rate of 60 ml/min. / 1.73 m ² ) (see INTERACTIONS and PHARMACOLOGICAL PROPERTIES).

Side effects

Serious by-effects including anaphylactic reactions and a Quincke's disease are possible

in some cases, was also observed opn.

Infectious diseases and invasions: infectious diseases of upper airways (including pharyngitis and sinusitis), infectious diseases of an uric path (including cystitis), sepsis (including with a lethal outcome) ¹ .

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

Disturbance from the immune system: hypersensitivity, anaphylactic reactions.

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

Mental disorders: depression, insomnia, concern.

Neurologic disorders: faints, drowsiness.

Disturbance from an organ of sight: disorders of vision.

Disturbance from an organ of hearing and a vestibular mechanism: vertigo.

Disturbance from a cardiovascular system: bradycardia, tachycardia, arterial hypotension ² , orthostatic hypotension.

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

Cases of an interstitial pulmonary disease noted

temporarily at use of a telmisartan during post-marketing observations. However the causal interrelation is not established.

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

Disorder of a gepatobiliarny system: dysfunction of liver/disorder of function of a liver. It was reported that patients of the Japanese nationality are more subject to these side reactions.

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

Disturbance from a musculoskeletal system and connective tissue: myalgia, dorsodynia (for example sciatica), muscular spasms, arthralgia, extremity pain, sinew pain (tendinitopodobny symptoms).

Disturbance from an urinary system: renal failures, including OPN.

General disturbances: stethalgia, asthenia (weakness), grippopodobny symptoms.

Laboratory indicators: increase in level of creatinine in blood, increase in level of uric acid in blood, increase in level of liver enzymes, increase in the KFK level in blood, decrease in level of hemoglobin.

Description of separate side reactions

Sepsis. It was reported that at the patients accepting telmisartan higher frequency of cases of sepsis in comparison with those who received placebo is revealed. It can be both accident, and sign of process which essence is still unknown.

Hypotension. This side reaction was noted often at patients with the controlled ABP who were treated telmisartany for decrease in cardiovascular diseases in addition to standard therapy.

Dysfunction of a liver / hepatic disorders. According to post-marketing data, the majority of cases of dysfunctions of a liver / hepatic disorders noted at patients of the Japanese nationality. Patients of the Japanese nationality are more subject to these side reactions.

Interstitial pulmonary disease. Cases of an interstitial pulmonary disease were observed temporarily at use of a telmisartan during post-marketing observations. However the causal interrelation is not established.

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¹ It was reported about increase in frequency of cases of sepsis at treatment telmisartany in comparison with that at placebo use. This phenomenon can be accidental manifestation or connected with the mechanism which operation is unknown now.

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² It was reported how often arising at the patients with the controlled ABP receiving treatment telmisartany for decrease in cardiovascular incidence in addition to standard therapy.

Special instructions

Pregnancy. during pregnancy it is impossible to begin treatment by antagonists of receptors of ii angiotensin. if continuation of therapy cannot be considered necessary extremely for the patient who plans pregnancy, it should 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 or feeding with a breast).

Liver failure. Telmisartan-Tev should not be applied at patients with a cholestasia, obstructive diseases of a bilious system and a heavy liver failure as telmisartan it is generally removed with bile. At patients with these diseases the hepatic clearance of a telmisartan decreases. It is necessary to apply with care Telmisartan-Tev at patients with a liver failure of easy and average degree.

Renovascular hypertensia. There is a risk of developing of serious arterial hypotension and renal failure at patients with a bilateral renal artery stenosis or a renal artery stenosis of the only kidney at treatment by the medicaments influencing renin-angiotensin-aldosteronovuyu a system.

Renal failure and transplantation of a kidney. At use of medicament for patients with renal failures it is recommended to control periodically the level of potassium and creatinine in blood plasma. There is no experience of use of medicament for patients after transplantation of kidneys.

Decrease in intravascular volume of liquid. Symptomatic arterial hypotension, especially after the first dose of drug, can arise at patients with the reduced OCK or a hyponatremia which arose owing to intensive diuretic care, a diet with restriction of salt or diarrhea and vomiting. Such states should be adjusted before medicament use. Before an initiation of treatment it is necessary to normalize the level of sodium and volume of intravascular liquid.

Double blockade system renin-angiotensin-aldosteronovoy. There are proofs that simultaneous use of APF inhibitors, blockers of receptors of angiotensin II or an aliskiren increases risk of hypotension, a hyperpotassemia and reduces renal function (including OPN).

Therefore double blockade system renin-angiotensin-aldosteronovoy at addition of APF inhibitor to the antagonist of receptors of angiotensin II) it is not recommended to p. If double blockade is considered necessary absolutely, it has to take place only under observation of the expert and on condition of continuous careful monitoring of function of kidneys, electrolytes and the ABP.

APF Inhibitors and blockers of receptors of angiotensin II should not be used by

at the same time at patients with a diabetic nephropathy.

Other states which are followed by stimulation system renin-angiotensin-aldosteronovoy. In patients whose tone of vessels and function of kidneys substantially depend on activity system renin-angiotensin-aldosteronovoy (for example at patients with heavy stagnant heart failure or the profound disease of kidneys, including a renal artery stenosis) the treatment with medicaments which also influence this system, can cause acute arterial hypotension, a hyperazotemia, an oliguria or is more rare — OPN.

Primary aldosteronism. Usually patients with primary aldosteronism do not react to the antihypertensive medicaments suppressing renin-angiotenzinovuyu a system therefore it is not recommended to appoint telmisartan the patient in such state.

Stenosis of mitral and aortal valves, subaortic hypertrophic stenosis. As well as at use of other vazodilatator, it is necessary to appoint with care medicament sick with a mitral and aortal stenosis or a subaortic hypertrophic stenosis.

Hyperpotassemia. Use of the medicaments influencing renin-angiotensin-aldosteronovuyu a system can cause a hyperpotassemia. At patients of advanced age, patients with a renal failure, the hyperpotassemia can lead patients with diabetes, patients who at the same time receive other medicaments capable to increase potassium level and/or at patients with intercurrent diseases to a lethal outcome.

Before simultaneous use of the medicaments suppressing renin-angiotensin-aldosteronovuyu a system should estimate a ratio of advantage and risk.

Major factors of risk of a hyperpotassemia which should be taken into account:

• diabetes, renal failure, age (70 years);
• a combination with one or several medicaments influencing renin-angiotensin-aldosteronovuyu a system and/or with the nutritional supplements containing potassium. Medicines or therapeutic classes of medicaments which can provoke a hyperpotassemia include kaliysoderzhashchy substitutes of salt, kaliysberegayushchy diuretics, APF inhibitors, antagonists of receptors of angiotensin II, NPVP (including selection TsOG-2 inhibitors), heparin, immunodepressants (cyclosporine or takrolimus) and Trimethoprimum;
• intercurrent manifestations, in particular dehydration, sharp warm decompensation, metabolic acidosis, renal failure, unexpected aggravation of symptoms of kidneys (for example infectious diseases), killing (for example acute ischemia of extremities, rhabdomyolysis, severe injury).

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recommends careful control of potassium in blood plasma at the patients belonging to risk group.

Sorbite. Drug contains sorbite (E420) therefore it is not necessary to appoint him the patient with hereditary intolerance of fructose.

Ethnic distinctions. As it was revealed when prescribing APF inhibitors, telmisartan and other blockers of receptors of angiotensin are less effective for decrease in the ABP at patients of negroid race in comparison with representatives of other races, it is possible because renin level at patients of negroid race with AG is less, than at representatives of other races.

Others. As well as at use of other antihypertensive drugs, excessive decrease in the ABP at patients with an ischemic heart disease and an ischemic cardiopathy can lead to development of a myocardial infarction or stroke.

Diabetic patients who are treated by insulin or hypoglycemic medicines. Patients who receive insulin or antidiabetic medicaments can have a hypoglycemia. At these patients it is necessary to control glucose level in blood and also it should be considered at dose adjustment of insulin or antidiabetic means.

risk of developing a myocardial infarction with a lethal outcome and a sudden cardiovascular lethal outcome can be higher than

At patients with diabetes, cardiovascular risks (patients with diabetes, associated diseases of coronary arteries) 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 appointing drug.

Use during pregnancy or feeding by a breast

Pregnancy. It is contraindicated to use medicament at the pregnant women or women planning pregnancy. If during treatment the pregnancy is confirmed by medicine, its use should be stopped immediately and if it is necessary, to replace with other medicine allowed for use for pregnant women.

do not have

sufficient data on use of a telmisartan for pregnant women.

Epidemiological justification of risk of teratogenecity as a result of use APF inhibitors in the I trimester of pregnancy were not convincing, however it is impossible to exclude small increase in risk. Though there are no controlled epidemiological data on risk of teratogenecity at use of antagonists of receptors of angiotensin II, similar risks can exist for this class of medicines. When planning pregnancy it is necessary to replace beforehand medicament with other antihypertensive with the established safety profile for use during pregnancy. At pregnancy establishment the treatment by antagonists of receptors of angiotensin II should be stopped immediately and if necessary to begin alternative treatment.

It is known that use of antagonists of receptors of angiotensin II in II and III trimester of pregnancy causes a fetotoksichnost in people (a renal failure, oligogidramnion, a delay of forming of bones of a skull) and neonatal toxicity (renal failure, hypotension, a hyperpotassemia). If use of antagonists of receptors of angiotensin II was begun with the II trimester of pregnancy, it is recommended to carry out ultrasonography of function of kidneys and bones of a skull of a fruit. The condition of newborns whose mothers antagonists of receptors of angiotensin II accepted needs to be controlled carefully on presence of arterial hypotension.

Feeding by a breast. As there is no information concerning use of a telmisartan during feeding by a breast, its use is not recommended and it is necessary to use alternative methods of treatment with the established safety profiles during feeding by a breast, especially newborn or premature babies.

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

Children. The efficiency and safety of use of medicament for children aged up to 18 years were not investigated.

Ability to influence speed of response at control of vehicles or work with other mechanisms. At use of antihypertensive therapy there can sometimes be conditions of dizziness or drowsiness. Therefore if necessary to run vehicles or to work with other mechanisms it is necessary to consider it.

Interaction

Digoksin. at simultaneous use of a telmisartan and digoxin noted average increase in cmax 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 level of digoxin for their maintenance within therapeutic range.

As well as other medicines influencing renin-angiotensin-aldosteronovuyu a system telmisartan can cause a hyperpotassemia. This risk can increase at combination with other medicines which can also provoke a hyperpotassemia (kaliysoderzhashchy substitutes of salt, kaliysberegayushchy diuretics, APF inhibitors, antagonists of receptors of angiotensin II, NPVP (including selection TsOG-2 inhibitors), heparin, immunodepressants (cyclosporine or takrolimus) and Trimethoprimum).

Frequency of cases of a hyperpotassemia depends on the associated risk factors. The risk increases at use of the therapeutic combinations mentioned above. This risk is especially high at combination with the kaliysberegayushchy diuretics and substitutes of salt containing potassium. The combination, for example, to APF or NPVP inhibitors creates smaller risk at strict observance of care at use.

Simultaneous use is not recommended to

With the kaliysberegayushchy diuretics or nutritional supplements containing potassium. Antagonists of receptors of angiotensin II, such as telmisartan, reduce potassium loss which is caused by diuretics. Kaliysberegayushchy diuretics, such as Spironolactonum, eplerenon, can lead Triamterenum or amiloride, nutritional supplements containing potassium or kaliysoderzhashchy substitutes of salt to substantial increase of level of potassium in blood plasma. If simultaneous use owing to the diagnosed hypopotassemia is shown, these medicaments should be used with care with frequent control of potassium in blood plasma.

With lithium. At simultaneous use of lithium with APF inhibitors and antagonists of receptors of angiotensin II, including telmisartan, reversible increase in concentration of lithium in blood plasma and toxicity was noted. If use of such combination is necessary, careful control of level of lithium in blood plasma is recommended.

Simultaneous use demanding care

NPVP. NPVP (for example acetylsalicylic acid in the doses intended for treatment of inflammatory processes, TsOG-2 inhibitors and non-selective NPVP) can reduce antihypertensive effect of antagonists of receptors of angiotensin II.

At some patients with renal failures (for example at patients with dehydration or at patients of advanced age with renal failures) simultaneous use of antagonists of receptors of angiotensin II and means, the oppressing COG, can lead to further deterioration in function of kidneys, including possible OPN which usually is reversible. Therefore such combination should be applied with care, especially at patients of advanced age. Patients need to receive adequate amount of liquid and it is necessary to weigh a possibility of control of function of kidneys after the beginning of simultaneous treatment and periodically after its termination.

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reported about increase almost by 2.5 times of AUC _0-24 also the C _max at simultaneous use with ramiprily and ramiprilaty. The clinical importance of this message is unknown.

Diuretics (thiazide or loopback). Preliminary treatment by high doses of diuretics, such as furosemide (loopback diuretic) and hydrochlorothiazide (thiazide diuretic), can lead to dehydration and risk of developing arterial hypotension in an initiation of treatment telmisartany.

Should be considered at simultaneous use

Other antihypertensive drugs. The effect of a telmisartan — decrease in the ABP — can increase at simultaneous use with other antihypertensive drugs.

Considering pharmacological properties, it is possible to expect that such medicines as Baclofenum, amifostin, can cause hypotensive effects of all antihypertensive drugs, including telmisartan. Also orthostatic hypotension can worsen owing to alcohol intake, use of barbiturates, medicaments or antidepressants.

GKS (system use). Decrease in antihypertensive effect.

Double blockade system renin-angiotensin-aldosteronovoy. It is shown that double blockade system renin-angiotensin-aldosteronovoy at simultaneous use of APF inhibitors, antagonists of receptors of angiotensin II or an aliskiren is characterized by the bigger frequency of development of such side reactions as arterial hypotension, a hyperglycemia, depression of function of kidneys (including OPN), in comparison with monotherapy use.

Overdose

Information on overdose of a telmisartan is limited to

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Most expressed symptoms of overdose of a telmisartan; also it was reported about bradycardia, dizziness, increase in level of creatinine in blood plasma and OPN.

Telmisartan is not brought by

from an organism by means of a hemodialysis. The patient should be under careful observation, and he needs to carry out symptomatic and maintenance therapy. Treatment depends on time which passed after overdose and weight of symptoms. It is recommended to cause vomiting and/or to wash out a stomach. At treatment of overdose it is possible to apply activated carbon. It is necessary to carry out frequent monitoring of level of plasma electrolytes and creatinine. If there is arterial hypotension, the patient should give a dorsal decubitus and to carry out recovery of balance of liquid and salt in an organism.

Storage conditions

does not demand special storage conditions.