Telpres plus tablets 40 + 12.5mg, No. 98

- arterial hypertension (in the absence of the effectiveness of monotherapy with telmisartan or hydrochlorothiazide).

The drug is taken orally 1 time / day with a liquid, regardless of food intake.

Patients whose blood pressure cannot be properly controlled with telmisartan or hydrochlorothiazide monotherapy should take the drug. Before switching to a fixed dose combination, individual dose titration of each of the components is recommended. In some clinical situations, a direct transition from monotherapy to fixed-dose combination therapy may be considered.

The drug, 80 mg + 12.5 mg, can be used 1 time / day in patients whose blood pressure cannot be properly controlled when taking telmisartan at a dose of 80 mg / day.

No dose adjustment is required in patients with mild or moderate renal impairment (CC more than 30 ml / min). Periodic monitoring of renal function indicators is recommended.

The concomitant use of telmisartan with aliskiren is contraindicated in patients with renal insufficiency (GFR less than 60 ml / min / 1.73 m2).

Contraindicated in patients with impaired liver function.

For elderly patients (over 70 years), dose adjustment is not required.

Contraindicated for use in children and adolescents under the age of 18 due to the lack of safety and efficacy data.

Active substance:

telmisartan

hydrochlorothiazide

- cholestasis and obstructive diseases of the biliary tract;

- liver dysfunction;

- severe renal dysfunction (CC less than 30 ml / min);

- simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or renal failure (GFR less than 60 ml / min / 1.73 m2);

- simultaneous use with ACE inhibitors in patients with diabetic nephropathy;

- refractory hypokalemia, hypercalcemia;

- hereditary fructose intolerance (contains sorbitol).

- pregnancy;

- the period of breastfeeding;

- age up to 18 years (effectiveness and safety have not been established);

- hypersensitivity to the active substance or any excipients of the drug and to other derivatives of sulfonamides.

With caution, the drug should be prescribed for bilateral renal artery stenosis or stenosis of an artery of a single kidney, severe renal dysfunction; a decrease in BCC against the background of previous diuretic therapy, restriction of salt intake, diarrhea or vomiting; hyperkalemia; condition after kidney transplantation (no experience of use); chronic heart failure III-IV FC according to NYHA classification; stenosis of the aortic and mitral valves; idiopathic hypertrophic subaortic stenosis; hypertrophic obstructive cardiomyopathy; Ischemic heart disease and cerebrovascular diseases; diabetes mellitus; primary hyperaldosteronism; gout; violations of water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia); hyperuricemia;angle-closure glaucoma (due to the presence of hydrochlorothiazide in the composition); systemic lupus erythematosus; in patients of the black race; elderly patients (over 70 years old).

The experience of use in patients with renal insufficiency (CC more than 30 ml / min) is limited, but does not confirm the development of side effects from the kidneys, dose adjustment is not required.

Pharmacological action is a combination of telmisartan (angiotensin II receptor antagonist (ARA II)) and hydrochlorothiazide (thiazide diuretic). The combination of these components provides a more pronounced antihypertensive effect, while the level of blood pressure decreases more than against the background of monotherapy with these components.

The drug, used 1 time / day in therapeutic doses, effectively and gradually reduces blood pressure.

Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (AT1 subtype), effective when taken orally. Telmisartan has a high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. Telmisartan displaces angiotensin II from binding to the receptor, without exhibiting the properties of an AT1 receptor agonist. Telmisartan selectively and stably binds to the AT1 receptor. Telmisartan has no affinity for other receptors, including AT2 and other less studied AT receptors. The functional role of these receptors, as well as the effect of their possible increased stimulation by angiotensin II, the concentration of which increases under the action of telmisartan, have not been studied. Telmisartan reduces the concentration of aldosterone in the blood plasma, does not inhibit renin and does not block ion channels. Telmisartan does not inhibit ACE (kininase II),which also destroys bradykinin. This avoids the side effects associated with the action of bradykinin.

In healthy people, telmisartan 80 mg almost completely blocks the hypertensive effect of angiotensin II. The suppressive effect lasts more than 24 hours and lasts up to 48 hours.

The onset of antihypertensive action is observed within the first 3 hours after taking telmisartan inside. The duration of the therapeutic effect of the drug is more than 24 hours and includes the last 4 hours before taking the next dose according to daily monitoring of blood pressure. This is confirmed by measurements taken at the time of maximum effect and immediately before taking the next dose (the ratio of the residual effect to the maximum is above 80% for dosages of 40 and 80 mg telmisartan in placebo-controlled studies). The maximum antihypertensive effect develops after 4-8 weeks of regular telmisartan administration and persists during long-term therapy.

In patients with arterial hypertension, telmisartan reduces both systolic and diastolic pressure without affecting heart rate. According to the results of clinical studies, the effectiveness of the antihypertensive action of telmisartan is comparable to the therapeutic effect of drugs of other classes, such as amlodipine, atenolol, enalapril, hydrochlorothiazide and lisinopril. In the case of abrupt cessation of treatment with telmisartan, blood pressure gradually returns to baseline values, without the development of a 'withdrawal' syndrome.

The incidence of dry cough was significantly lower with the use of telmisartan, in contrast to ACE inhibitors.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the reabsorption of electrolytes in the renal tubules, thereby increasing the excretion of sodium and chloride ions in approximately equivalent amounts. The diuretic effect of hydrochlorothiazide leads to a decrease in the BCC, an increase in plasma renin activity, an increase in the production of aldosterone, followed by an increase in the content of potassium and bicarbonates in the urine and a decrease in the content of potassium in the blood plasma. The simultaneous use of telmisartan helps to reduce the loss of potassium caused by this diuretic, probably due to the blockade of the RAAS. After taking hydrochlorothiazide, diuresis increases after 2 hours, the maximum effect develops after about 4 hours, the effect lasts about 6-12 hours.

Epidemiological studies have found that long-term hydrochlorothiazide therapy reduces the risk of cardiovascular morbidity and mortality.

Pediatric and adolescent patients

The safety and effectiveness of telmisartan in children and adolescents under 18 years of age has not been established.

Indications

- arterial hypertension (in the absence of the effectiveness of monotherapy with telmisartan or hydrochlorothiazide).

Contraindications

- cholestasis and obstructive diseases of the biliary tract;

- liver dysfunction;

- severe renal dysfunction (CC less than 30 ml / min);

- simultaneous use with drugs containing aliskiren in patients with diabetes mellitus or renal failure (GFR less than 60 ml / min / 1.73 m2);

- simultaneous use with ACE inhibitors in patients with diabetic nephropathy;

- refractory hypokalemia, hypercalcemia;

- hereditary fructose intolerance (contains sorbitol).

- pregnancy;

- the period of breastfeeding;

- age up to 18 years (effectiveness and safety have not been established);

- hypersensitivity to the active substance or any excipients of the drug and to other derivatives of sulfonamides.

With caution, the drug should be prescribed for bilateral renal artery stenosis or stenosis of an artery of a single kidney, severe renal dysfunction; a decrease in BCC against the background of previous diuretic therapy, restriction of salt intake, diarrhea or vomiting; hyperkalemia; condition after kidney transplantation (no experience of use); chronic heart failure III-IV FC according to NYHA classification; stenosis of the aortic and mitral valves; idiopathic hypertrophic subaortic stenosis; hypertrophic obstructive cardiomyopathy; Ischemic heart disease and cerebrovascular diseases; diabetes mellitus; primary hyperaldosteronism; gout; violations of water and electrolyte balance (including hypokalemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia); hyperuricemia;angle-closure glaucoma (due to the presence of hydrochlorothiazide in the composition); systemic lupus erythematosus; in patients of the black race; elderly patients (over 70 years old).

The experience of use in patients with renal insufficiency (CC more than 30 ml / min) is limited, but does not confirm the development of side effects from the kidneys, dose adjustment is not required.

Application during pregnancy and lactation

Pregnancy

Treatment of ARA II during pregnancy is contraindicated. The use of ARA II is not recommended in the first trimester of pregnancy and is contraindicated in the second and third trimesters of pregnancy.

Telmisartan

There is no adequate data on the use of the drug telmisartan in pregnant women. Animal studies have shown reproductive toxicity. Epidemiological evidence of the risk of teratogenicity after taking ACE inhibitors in the first trimester of pregnancy was not convincing, however, this risk cannot be excluded. Until data from controlled epidemiological studies are available regarding the risk of ARA II, a similar risk may exist for this class of drugs. Except for the urgent need for long-term treatment of ARA II, patients planning a pregnancy should choose an alternative antihypertensive drug with a proven safety profile for use during pregnancy.After establishing the fact of pregnancy, treatment with ARA II should be stopped immediately and, if necessary, alternative treatment should be started.

Treatment of ARA II in the II and III trimesters of pregnancy has a toxic effect on the fetus (deterioration of renal function, oligohydramnios, delayed ossification of the skull) and the newborn (renal failure, arterial hypotension and hyperkalemia). When using ARA II from the second trimester of pregnancy, ultrasound of the kidneys and fetal skull is recommended. Children whose mothers took ARA II should be carefully examined for arterial hypotension.

Hydrochlorothiazide

The experience of using hydrochlorothiazide during pregnancy, especially in the first trimester, is limited. Hydrochlorothiazide penetrates the BBB. Based on the pharmacological mechanism of action of hydrochlorothiazide, its use in the II and III trimesters can impair placental blood flow and cause jaundice, imbalance in water and electrolyte balance and thrombocytopenia in the fetus / newborn. Hydrochlorothiazide should not be used for the treatment of edema of pregnant women, hypertension of pregnant women or preeclampsia due to the risk of a decrease in the BCC and deterioration of placental blood flow without a proper therapeutic effect on the course of the disease.

Do not use hydrochlorothiazide for the treatment of essential hypertension in pregnant women, except in rare cases when no other treatment is possible.

Breastfeeding period

Taking the drug during breastfeeding is contraindicated; alternative treatment with more favorable safety profiles should be used.

Fertility

The study of the effect of the combination of telmisartan and hydrochlorothiazide on human fertility has not been conducted.

special instructions

Liver dysfunction

The use of the drug is contraindicated in patients with cholestasis, obstruction of the biliary tract and / or impaired liver function, since telmisartan is mainly excreted in the bile. There is reason to believe that these patients have decreased hepatic clearance of telmisartan.

Renovascular hypertension

When treating with drugs acting on the RAAS, in patients with bilateral renal artery stenosis or stenosis of an artery of a single functioning kidney, the risk of a significant decrease in blood pressure and the development of acute renal failure increases.

Double blockade of RAAS

Data on the simultaneous use of ACE inhibitors with ARA II or with drugs containing aliskiren confirm an increased risk of a sharp decrease in blood pressure, the development of hyperkalemia and a decrease in renal function (including acute renal failure). Therefore, the use of this drug combination is contraindicated. If it is necessary to carry out a double blockade of the RAAS, each case should be considered individually and renal function, water-electrolyte balance and blood pressure indicators should be carefully monitored.

In patients with diabetic nephropathy, the use of a combination of ACE inhibitors and ARA II is contraindicated.

Other conditions associated with stimulation of the RAAS

In patients whose vascular tone and renal function depend mainly on the activity of the RAAS (for example, patients with severe chronic heart failure or existing kidney disease, including renal artery stenosis), the use of drugs acting on this system, such as telmisartan , is associated with the occurrence of an acute decrease in blood pressure, hyperazotemia, oliguria, or rarely with the development of acute renal failure.

Primary hyperaldosteronism

In patients with primary hyperaldosteronism, treatment with antihypertensive drugs, the action of which is carried out by inhibition of the RAAS, is usually ineffective. In this regard, the use of Telzap Plus is not recommended.

Kidney dysfunction and kidney transplant

The use of the drug is contraindicated in patients with severe renal impairment (CCЃ Plus in patients with mild and moderate renal impairment is limited, it is recommended to periodically monitor the content of potassium, creatinine and uric acid in the blood plasma, as well as indicators of renal function. with impaired renal function, azotemia associated with the use of thiazide diuretics may occur.

Decrease in BCC

A decrease in blood pressure, especially after the first dose of the drug, can occur in patients with reduced BCC and / or low sodium content in the blood plasma against the background of previous treatment with diuretics, restriction of sodium chloride intake, diarrhea or vomiting. Such conditions (fluid and / or sodium deficiency) must be eliminated prior to taking the drug.

Aortic or mitral valve stenosis, obstructive hypertrophic cardiomyopathy

As with other vasodilators, patients with aortic or mitral stenosis, as well as hypertrophic obstructive cardiomyopathy, need to be especially careful.

Impact on metabolism and endocrine function

The use of hydrochlorothiazide can impair glucose tolerance, while patients with diabetes mellitus may develop hypoglycemia against the background of the simultaneous use of insulin or hypoglycemic agents and telmisartan. Dose adjustment of hypoglycemic agents may be required, incl. insulin. During treatment with thiazides in patients with impaired glucose tolerance, latent diabetes mellitus may manifest. An increase in the concentration of cholesterol and triglycerides in the blood plasma is associated with treatment with thiazide diuretics. However, when using a drug containing 12.5 mg of hydrochlorothiazide, this effect is minimal or absent. Some patients using hydrochlorothiazide may develop hyperuricemia or a sudden flare-up of gout.

Violation of water and electrolyte balance

When using the drug, it is necessary to periodically monitor the content of electrolytes in blood plasma.

Thiazides, including hydrochlorothiazide, can cause disturbances in water and electrolyte balance (hypokalemia, hyponatremia and hypochloremic alkalosis) and changes in the acid-base state. Signs of imbalance in water and electrolyte balance are: dry mouth, thirst, general weakness, lethargy, drowsiness, anxiety, muscle pain or cramps, muscle weakness, decreased blood pressure, oliguria, tachycardia, and gastrointestinal disorders such as nausea and vomiting.

Method of administration and dosage

The drug is taken orally 1 time / day with a liquid, regardless of food intake.

Patients whose blood pressure cannot be properly controlled with telmisartan or hydrochlorothiazide monotherapy should take the drug. Before switching to a fixed dose combination, individual dose titration of each of the components is recommended. In some clinical situations, a direct transition from monotherapy to fixed-dose combination therapy may be considered.

The drug, 80 mg + 12.5 mg, can be used 1 time / day in patients whose blood pressure cannot be properly controlled when taking telmisartan at a dose of 80 mg / day.

No dose adjustment is required in patients with mild or moderate renal impairment (CC more than 30 ml / min). Periodic monitoring of renal function indicators is recommended.

The concomitant use of telmisartan with aliskiren is contraindicated in patients with renal insufficiency (GFR less than 60 ml / min / 1.73 m2).

The drug is contraindicated in patients with impaired liver function.

For elderly patients (over 70 years), dose adjustment is not required.

Contraindicated for use in children and adolescents under the age of 18 due to the lack of safety and efficacy data.

Side effects

The most commonly reported adverse reaction was dizziness. Serious angioedema was rare.

Adverse reactions are divided into systemic organ classes according to MedDRA. The frequency of side effects was determined in accordance with the WHO classification: very often

Infectious and parasitic diseases: rarely - bronchitis, pharyngitis, sinusitis.

—о стороны иммунной системы: редко - усиление симптомов или обострение системной красной волчанки (в ходе пострегистрационного наблюдени¤).

—о стороны обмена веществ и питани¤: нечасто - гипокалиеми¤; редко - гиперурикеми¤, гипонатриеми¤.

ѕсихические нарушени¤: нечасто - тревога; редко - депресси¤.

—о стороны нервной системы: часто - головокружение; нечасто - обморок, парестезии; редко - бессонница, нарушение сна.

—о стороны органа зрени¤: редко - нарушение зрени¤, преход¤щее нарушение четкости зрени¤.

—о стороны органа слуха: нечасто - вертиго.

—о стороны сердечно-сосудистой системы: нечасто - тахикарди¤, аритми¤, артериальна¤ гипотензи¤, ортостатическа¤ гипотензи¤.

—о стороны дыхательной системы: нечасто - одышка; редко - респираторный дистресс-синдром (включающий пневмонит и отек легких).

—о стороны пищеварительной системы: нечасто - диаре¤, сухость во рту, метеоризм; редко - боль в животе, запор, диспепси¤, рвота, гастрит.

—о стороны печени и желчевывод¤щих путей: редко - нарушение функции печени, заболевани¤ печени.

—о стороны кожи и подкожных тканей: редко - ангионевротический отек (также с летальным исходом), эритема, кожный зуд, кожна¤ сыпь, усиленное потоотделение, крапивница.

—о стороны костно-мышечной системы и соединительной ткани: нечасто - боль в спине, мышечные спазмы, миалги¤; редко - боли в суставах, мышечные спазмы, боли в конечност¤х.

—о стороны половых органов и молочной железы: нечасто - эректильна¤ дисфункци¤.

ќбщие расстройства и нарушени¤ в месте введени¤: нечасто - боль в груди; редко - гриппоподобный синдром, боль.

On the part of laboratory and instrumental studies: rarely - an increase in the concentration of creatinine in the blood plasma, an increase in the activity of CPK, an increase in the activity of hepatic transaminases.

Additional information on the individual components

Side effects noted with the use of one of the components, the development of which can be expected with the use of a combination of telmisartan and hydrochlorothiazide.