Theseo - instructions for use, dose, side effects, contraindications

auxiliary substances: meglumine - 12,000 mg, sorbitol - 162,200 mg, sodium hydroxide - 3,400 mg, povidone 25 - 20,000 mg, magnesium stearate - 2,400 mg.

Each 80 mg tablet contains:

active substance: telmisartan - 80,000 mg;

Excipients: meglumine - 24,000 mg, sorbitol - 324,400 mg, sodium hydroxide - 6,800 mg, povidone 25 - 40,000 mg, magnesium stearate - 4,800 mg.

Description:

Tablets 40 mg: oblong, biconvex tablets from almost white to yellowish color with a risk on both sides.

Tablets 80 mg: oblong, biconvex tablets from almost white to yellowish color with engraving "80" on one side.

Pharmacotherapeutic group:angiotensin II receptor antagonist

ATX: & nbsp

C.09.C.A.07 Telmisartan

Pharmacodynamics:

Telmisartan is a specific antagonist of angiotensin II receptors (APAII) (a type AT₁), effective at ingestion. Telmisartan has a very high affinity for AT₁-receptors, through which the action of angiotensin II is realized. It displaces angiotensin II from the receptor binding, without the action of an agonist for this receptor. Telmisartan binds only to a subtype AT₁receptors of angiotensin II. Communication is stable. Telmisartan has no affinity for other receptors, including AT₂-receptor and other, less studied receptors of angiotensin. The functional significance of these receptors, as well as the effect of their possible excessive stimulation with angiotensin II, whose concentration increases with the appointment of telmisartan, have not been studied. Telmisartan reduces the concentration of aldosterone in the blood plasma, does not reduce the activity of renin and does not block the ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) (kininase II), which also catalyzes the destruction of bradykinin. This avoids the side effects associated with the action of bradykinin (eg, dry cough).

Essential hypertension

Patients telmisartan in a dose of 80 mg completely blocks the hypertensive effect of angiotensin II. The onset of antihypertensive action is noted within 3 hours after the first administration of telmisartan. The effect of the drug persists for 24 hours and remains clinically significant until 48 hours. The pronounced antihypertensive effect usually develops 4-8 weeks after regular administration.

In patients suffering from hypertension, telmisartan reduces systolic and diastolic blood pressure (BP), without affecting the heart rate (heart rate).

In the case of a sharp discontinuation of telmisartan, blood pressure gradually returns to the baseline within a few days without the development of the withdrawal syndrome.

As shown by the results of comparative clinical studies, the antihypertensive effect of telmisartan is comparable to the antihypertensive effect of drugs of other classes (amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril).

The incidence of dry cough was significantly lower with telmisartan compared with ACE inhibitors.

Prevention of cardiovascular diseases

In patients aged 55 years and older with ischemic heart disease, stroke, transient ischemic attack, peripheral arterial disease, or type 2 diabetes complications (eg, retinopathy, left ventricular hypertrophy, macro- or microalbuminuria) in an anamnesis at risk of cardiovascular events, telmisartan had an effect similar to the effect of ramipril on reducing the combined endpoint: cardiovascular mortality from a myocardial infarction without a fatal outcome, a stroke without a fatal outcome, and hospitalization due to chronic heart failure.

Telmisartan was also effective, as was ramipril in terms of reducing the frequency of secondary points: cardiovascular mortality, myocardial infarction myocardial without a fatal outcome or a stroke without a fatal outcome. Dry cough and angioedema were less often described in the background of taking telmisartan in contrast to ramipril, with arterial hypotension more likely to occur when taking telmisartan.

Patients of childhood and adolescence

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

Pharmacokinetics:

Suction

Ingestion telmisartan quickly absorbed from the gastrointestinal tract. Bioavailability - 50%. At reception simultaneously with food decrease AUC (the area under the concentration-time curve) ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). After 3 hours after taking the concentration in the blood plasma levels, regardless, was taken telmisartan simultaneously with the ingestion of food or not. There is a difference in plasma concentrations in men and women. FROM_max (maximum concentration) and AUC were approximately 3 and 2 times, respectively, higher in women than in men without significant effect on efficacy.

There was no linear relationship between the dose of the drug and its plasma concentration. FROM_m_Oh and, to a lesser extent, AUC increase disproportionately to a higher dose when doses above 40 mg per day are used.

Distribution

Telmisartan binds strongly to blood plasma proteins (> 99.5%), mainly with albumin and alpha-1 acidic glycoprotein. Average apparent volume of distribution (Vd_SS) in the equilibrium state is approximately 500 liters.

Metabolism

Metabolized by conjugation with glucuronic acid. The conjugate does not have pharmacological activity.

Excretion

The half-life (T_1/2) is more than 20 hours. It is excreted through the intestine in an unchanged form, excretion by the kidneys - less than 1%. The total plasma clearance is high (about 1000 ml / min) compared with the "hepatic" blood flow (about 1500 ml / min).

Special populations of patients

Elderly patients

The pharmacokinetics of telmisartan in elderly patients over the age of 65 do not differ from young patients. Dose correction is not required.

Patients with impaired renal function

In patients with mild to moderate renal dysfunction, dosage adjustment for telmisartan is not required. Patients with severe renal failure and patients on hemodialysis are recommended a lower initial dose of 20 mg per day (see section "Special instructions").

Telmisartan is not excreted by hemodialysis.

Patients with impaired hepatic function

In patients with mild and moderate impairment of liver function (class A and B according to the Child-Pugh classification), the daily dose of the drug should not exceed 40 mg.

Indications:

Esisial hypertension.

FROMMortality and frequency of cardiovascular disease in adult patients:

- with cardiovascular diseases of atherothrombotic genesis (ischemic heart disease, stroke or peripheral arterial disease in history);

- with type 2 diabetes mellitus with damage to target organs.

Contraindications:

- Hypersensitivity to the active substance or any excipients of the drug;

- pregnancy and the period of breastfeeding;

- obstructive diseases of the biliary tract;

- severe hepatic impairment (Child-Pugh class C);

- combined use with aliskiren in patients with diabetes mellitus or severe renal dysfunction (glomerular filtration rate [GFR] less than 60 ml / min / 1.73 m² body surface area) (see the sections "Interaction with other drugs" and "Special instructions");

- hereditary intolerance to fructose (due to the presence of sorbitol in the tablet);

- concurrent use with angiotensin-converting enzyme (ACE inhibitors) in patients with diabetic nephropathy (see "Interaction with other drugs" and "Special instructions");

- age to 18 years (efficacy and safety not established).

Carefully:

The preparation TEZEO® should be administered with caution under the following conditions / diseases:

- bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney;

- impaired renal function;

- mild and moderate liver dysfunction;

- decrease in the volume of circulating blood (BCC) on the background of previous intake of diuretics, restriction of consumption of table salt, diarrhea or vomiting;

- hyponatremia;

- hyperkalemia;

- condition after kidney transplantation (no experience of application);

- severe chronic heart failure;

- stenosis of the aortic and mitral valve;

- hypertrophic obstructive cardiomyopathy;

- primary hyperaldosteronism (efficacy and safety not established);

- the use of Negroid race in patients.

Pregnancy and lactation:

Pregnancy

At present, there is no reliable information on the safety of telmisartan in pregnant women. In animal studies, the reproductive toxicity of the drug was identified. The use of TESEO® is contraindicated during pregnancy (see section "Contraindications").

If long-term treatment with TESEO is necessary, patients planning a pregnancy should choose an alternative antihypertensive drug with a proven safety profile during pregnancy. After establishing the fact of pregnancy, treatment with TESEO® should be stopped immediately and, if necessary, started an alternative treatment.

As the results of clinical observations have shown, the use of APAII during the second and third trimesters of pregnancy has a toxic effect on the fetus (impaired renal function, oligohydramnion, delayed ossification of the skull) and newborn (kidney failure, arterial hypotension and hyperkalemia). With the use of APAII Ultrasound examination of the kidneys and fetal skull is recommended during the second trimester of pregnancy.

Children whose mothers took ARAII during pregnancy, should be carefully monitored for arterial hypotension.

Breastfeeding period

Information on the use of telmisartan during breastfeeding is absent. The use of TESEO® during breastfeeding is contraindicated (seesection "Contraindications"), an alternative hypotensive drug with a more favorable safety profile should be used, especially when feeding a newborn or premature baby.

Dosing and Administration:

The preparation TEZEO ® is taken orally once a day, washed down with a liquid, regardless of the food intake.

Arterial hypertension

The initial recommended dose of TESEO® is 1 tablet (40 mg) once a day. In some patients, 20 mg per day can be effective. A dose of 20 mg can be obtained by dividing the tablet 40 mg in half by the risk. In cases where the therapeutic effect is not achieved, the recommended dose of TESEO® can be increased to a maximum of 80 mg once daily. Alternatively, the preparation of Teseo® can be taken in combination with thiazide diuretics, for example hydrochlorothiazide, which, when combined, has an additional antihypertensive effect. When deciding whether to increase the dose, it should be taken into account that the maximum antihypertensive effect is usually achieved within 4-8 weeks after the start of treatment.

Reduction of mortality and incidence of cardiovascular diseases

The recommended dose of TESEO® is 80 mg once a day.

In the initial period of treatment it is recommended to monitor the level of blood pressure (BP), correction of hypotensive therapy may be required.

Special populations of patients

Patients with impaired renal function

The experience with telmisartan in patients with severe renal failure or patients on hemodialysis is limited. These patients are recommended a lower initial dose of 20 mg per day (see section "Special care"). For patients with mild to moderate renal dysfunction, dose adjustment is not required.

The concomitant use of the preparation TEZEO® with aliskiren is contraindicated in patients with renal insufficiency (GFR less than 60 ml / min / 1.73 m body surface area) (see section "Contraindications").

Simultaneous use of TESEO® with ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section "Contraindications").

Patients with impaired hepatic function

TESEO® is contraindicated in patients with severe hepatic impairment (Child-Pugh class C) (see "Contraindications").In patients with mild to moderate hepatic insufficiency (class A and B according to the Child-Pugh classification, respectively), the drug is administered with caution, the dose should not exceed 40 mg once daily (see the section "With caution").

Elderly patients

For elderly patients, dose adjustment is not required.

Children and adolescence

The use of TESEO® in children and adolescents younger than 18 years is contraindicated due to a lack of safety and efficacy data (see "Contraindications").

Side effects:

According to the World Health Organization (WHO), the undesirable effects are classified according to the frequency of their development as follows: very often (≥1/10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1,000 to <1/100), rarely (from ≥1 / 10,000 to <1 / 1,000), very rarely (<1 / 10,000); frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

Within each group according to the incidence of adverse reactions are presented in descending order of severity.

Infectious and parasitic diseases

infrequently: Urinary tract infections, including cystitis, upper respiratory tract infections, including pharyngitis and sinusitis;

rarely: sepsis, including fatal.

Violations of the blood and lymphatic system

infrequently: anemia;

rarely: eosinophilia, thrombocytopenia.

Immune system disorders

rarely: anaphylactic reaction, hypersensitivity.

Disorders from the metabolism and nutrition

infrequently: hyperkalemia;

rarely: hypoglycemia (in patients with diabetes mellitus).

Onimpairment from the psyche:

infrequently: insomnia, depression;

rarely: anxiety.

Disturbances from the nervous system

infrequently: fainting;

rarely: drowsiness.

Disturbances on the part of the organ of sight

rarely: visual disorders.

Hearing disorders and labyrinthine disorders

infrequently: vertigo.

Heart Disease

infrequently: bradycardia;

rarely: tachycardia.

Vascular disorders

infrequently: marked decrease in blood pressure, orthostatic hypotension.

Disturbances from the respiratory system, organs of the chest and mediastinum

infrequently: shortness of breath, cough;

rarely: interstitial lung disease.

Disorders from the gastrointestinal tract

infrequently: abdominal pain, diarrhea, indigestion, flatulence, vomiting;

rarely: dry mouth, discomfort in the stomach, a violation of taste.

Disturbances from the liver and bile ducts

rarely: a violation of liver function / liver damage.

Disturbances from the skin and subcutaneous tissues

infrequently: pruritus, hyperhidrosis, rash;

rarely: angioedema, also fatal, eczema, erythema, urticaria, drug rash, toxic skin rash.

Disturbances from musculoskeletal and connective tissue

infrequently: back pain (ischialgia), muscle spasms, myalgia;

rarely: arthralgia, pain in the extremities, pain in the tendons (tendenitis-like syndrome).

Disorders from the kidneys and urinary tract

infrequently: impaired renal function, including acute renal failure.

General disorders and disorders at the site of administration

infrequently: chest pain, asthenia (weakness);

rarely: flu-like syndrome.

Impact on the results of laboratory and instrumental studies

infrequently: increase in the concentration of creatinine in the blood plasma;

rarely: reduction of hemoglobin, increase of uric acid in the blood plasma, increased activity of "liver" enzymes and creatine phosphokinase (CK).

Overdose:

Symptoms: the most pronounced manifestations of an overdose were a marked decrease in blood pressure and tachycardia, also reported bradycardia, dizziness, increased serum creatinine and acute renal failure.

Treatment: telmisartan is not excreted by hemodialysis. Patients should be monitored carefully and symptomatic, as well as supportive, treatment. The approach to treatment depends on the time elapsed after taking the drug, and the severity of the symptoms. Recommended measures include provoking vomiting and / or gastric lavage, it is advisable to take activated charcoal. The content of electrolytes and creatinine in the blood plasma should be regularly monitored. If there is a marked decrease in blood pressure, the patient should take a horizontal position with raised legs, while the volume of bcc and electrolytes must be quickly replenished.

Interaction:

Double blockade of the renin-angiotensin-aldosterone system (RAAS)

Concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR less than 60 ml / min / 1.73 m² body surface area) and is not recommended for other patients.

Simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section "Contraindications").

Clinical studies have shown that the double blockade of RAAS due to the combined use of ACE inhibitors, APAII or aliskiren is associated with an increased incidence of adverse events such as hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of only one drug acting on RAAS.

The risk of developing hyperkalemia may increase when combined with other medicines that can cause hyperkalemia (potassium-containing dietary supplements and salt substitutes containing potassium, potassium-sparing diuretics (for example, spironolactone, eplerenone, triamterene or amiloride), non-steroidal anti-inflammatory drugs (NSAIDs, including selective inhibitors of cyclooxygenase-2 (COX-2)), heparin, immunosuppressants (ciclosporin or tacrolimus), and trimethoprim).If necessary, against the background of documented hypokalemia, joint use of drugs should be carried out with caution and regularly monitor the potassium content in the blood plasma.

Digoxin

With the joint administration of telmisartan with digoxin, an average increase FROM_maxdigoxin in the blood plasma by 49% and the minimum concentration by 20%. At the beginning of the treatment, when choosing a dose and stopping telmisartan treatment, the concentration of digoxin in the blood plasma should be carefully monitored for its maintenance within the therapeutic range.

Potassium-sparing diuretics or potassium-containing food additives

Angiotensin II receptor antagonists, such as telmisartan, reduce the diuretic-induced loss of potassium. Potassium-sparing diuretics, for example, spironolactone, eplerenone, triamterene or amiloride, potassium-containing dietary supplements or salt substitutes can lead to a significant increase in potassium levels in the blood plasma. If concomitant use is indicated, since there is documented hypokalemia, they should be used with caution and against a background of regular monitoring of potassium in the plasmablood.

Lithium preparations

When co-administration of lithium preparations with ACE inhibitors and APAII, including telmisartan, there was a reversible increase in the concentration of lithium in the blood plasma and its toxic effect. If it is necessary to use this combination of drugs, it is recommended to carefully monitor the concentration of lithium in the blood plasma.

Non-steroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (i.e. acetylsalicylic acid in doses used for anti-inflammatory treatment, COX-2 inhibitors and non-selective NSAIDs) can attenuate the antihypertensive effect of APAII. In some patients with impaired renal function (eg, patients with dehydration, elderly patients with impaired renal function), joint application of APAII and drugs depressing cyclooxygenase-2, can lead to further deterioration of renal function, including the development of acute renal failure, which is usually reversible. Therefore, joint use of drugs should be done with caution, especially elderly patients. Proper fluid intake should also be ensured, in addition, at the beginning of the joint application and periodically the kidney function should be monitored periodically thereafter.

Diuretics (thiazide or "loop")

Previous treatment with high doses of diuretics, such as furosemide (looped diuretic) and hydrochlorothiazide (thiazide diuretic), can lead to hypovolemia and the risk of developing arterial hypotension at the beginning of telmisartan treatment.

Other antihypertensives

The effect of telmisartan may be enhanced by the joint use of other antihypertensive drugs.

Based on the pharmacological properties of baclofen and amifostine, it can be assumed that they will enhance the therapeutic effect of all antihypertensive agents, including telmisartan. In addition, orthostatic hypotension may increase with the use of alcohol, barbiturates, drugs or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids weaken the action of telmisartan.

Special instructions:

Impaired liver function

The use of TESEO® is contraindicated in patients with cholestasis, bile duct obstruction, or severe liver dysfunction (Child-Pugh class C) (see "Contraindications"), since telmisartan mostly excreted with bile.It is suggested that in these patients the hepatic clearance of telmisartan is reduced. In patients with mild to moderate liver failure (class A and B according to the Child-Pugh classification), the TEZEO® preparation should be used with caution (see "With caution").

Renovascular hypertension

When treating with RAAS-acting drugs, patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single functioning kidney are at increased risk for severe arterial hypotension and renal insufficiency.

Impaired renal function and kidney transplantation

When using TESEO® in patients with impaired renal function, periodic monitoring of potassium and creatinine in the blood plasma is recommended. The experience of clinical use of the preparation TEZEO® in patients who have recently undergone kidney transplantation is absent.

Reduction of the volume of circulating blood (BCC)

Symptomatic arterial hypotension, especially after the first dose of TESEO®, may occur in patients with reduced BCC and / or sodium in the blood plasma on the background of previous treatment with diuretics, restriction of salt intake, diarrhea, or vomiting.

Such conditions (deficiency of fluid and / or sodium) should be eliminated before starting the TESEO® preparation.

Double blockade of the renin-angiotensin-aldosterone system

The concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal insufficiency (GFR less than 60 mL / min / 1.73 m² body surface area) (see section "Contraindications").

Simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy (see section "Contraindications").

As a result of the oppression of RAAS, arterial hypotension, syncope, hyperkalemia and impaired renal function (including acute renal failure) were noted in patients who were predisposed to this, especially when several drugs were used together, also acting on this system. Therefore, the double blockade of RAAS (for example, against the background of taking telmisartan with other antagonists of RAAS) is not recommended.

In cases of vascular tone and kidney function, mainly from RAAS activity (for example, in patients with chronic heart failure or kidney disease, including,with stenosis of the renal arteries, or stenosis of the artery of a single kidney), the administration of drugs that affect this system can be accompanied by the development of acute arterial hypotension, hyperazotemia, oliguria, and in rare cases acute renal failure.

Primary hyperaldosteronism

In patients with primary hyperaldosteronism, treatment with antihypertensive drugs, which are effected by inhibition of RAAS, is usually ineffective. Therefore, the use of TESEO® is not recommended.

Stenosis of aortic and mitral valves, hypertrophic obstructive cardiomyopathy

As with other vasodilators, patients with aortic or mitral stenosis, as well as hypertrophic obstructive cardiomyopathy, should be especially careful when using TESEO®.

Patients with diabetes who received insulin or hypoglycemic agents for oral administration

Against the background of treatment with TESEO®, hypoglycemia can occur in these patients. In such patients, glycemic control should be strengthened,since it may be necessary to adjust the dose of insulin or hypoglycemic agent.

Hyperkalemia

The intake of medicines acting on RAAS can cause hyperkalemia. In elderly patients, patients with renal insufficiency or diabetes mellitus, patients also taking medications that promote increased levels of potassium in the blood plasma, and / or patients with concomitant diseases, hyperkalemia can be fatal.

When deciding on the concomitant use of drugs acting on RAAS, it is necessary to assess the risk-benefit ratio. The main risk factors for the development of hyperkalemia, which should be considered, are:

- diabetes mellitus, renal failure, age (patients older than 70 years);

- combination with one or more drugs acting on RAAS, and / or potassium-containing food additives. Drugs or therapeutic classes of medications that can cause hyperkalemia include salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists,non-steroidal anti-inflammatory drugs (NSAIDs, including selective inhibitors of COX-2), heparin, immunosuppressants (ciclosporin or tacrolimus) and trimethoprim;

- intercurrent diseases, especially dehydration, acute heart failure, metabolic acidosis, impaired renal function, cytolysis syndrome (eg, acute limb ischemia, rhabdomyolysis, extensive trauma).

Patients at risk should carefully monitor potassium levels in the blood plasma (see section "Interaction with other drugs").

Sorbitol

This medication contains sorbitol (E420). Patients with a rare hereditary intolerance to fructose should not take the TESEO® preparation.

Ethnic differences

As noted for ACE inhibitors, telmisartan and other ARAII, appear to be less effective in lowering arterial pressure in patients of the Negroid race than in representatives of other races, possibly due to a greater predisposition to a decrease in renin activity in the population of these patients.

Other

As with the use of other antihypertensive drugs,excessive reduction in blood pressure in patients with ischemic cardiomyopathy or coronary heart disease can lead to myocardial infarction or stroke.

Effect on the ability to drive transp. cf. and fur:

Special clinical studies to study the effect of the drug on the ability to drive a car and mechanisms were not conducted. When driving and working with mechanisms that require increased concentration of attention, you should be careful, as against the background of taking the drug TEZEO^®seldom there may be dizziness and drowsiness.

Form release / dosage:

Tablets, 40 mg and 80 mg.

Packaging:

For 10 tablets in a blister of OPA / Alu / PVC / Alu.

For 3, 6 or 9 blisters are placed in a pack of cardboard along with instructions for use.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date shown on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003545

Date of registration:01.04.2016

Date of cancellation:2021-04-01

The owner of the registration certificate:Zentiva c.s.Zentiva c.s. Czech Republic

Manufacturer: & nbsp

ZENTIVA SAGLIK URUNLERI SANAYI VE TICARET, A.S. Turkey

Representation: & nbspZENTIVA PHARMA, LLCZENTIVA PHARMA, LLC

Information update date: & nbsp13.06.2016

Illustrated instructions

Instructions

Theseo® (Tezeo®)