Hydrochlorothiazide, Telmisartan | Telpres Plus tablets 80 mg + 25 mg 28 pcs.

Pharmacological action

Pharmacotherapeutic group: Hypotensive drug combined (angiotensin II receptors telantharmaceuticals sulpharmacin plus antagonist drugs + ) and hydrochlorothiazide - a thiazide diuretic. The simultaneous use of these components leads to a more pronounced antihypertensive effect than the use of each of them separately.

Taking Telpres Plus once a day leads to a significant gradual decrease in blood pressure (BP).

Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (type AT1) that is effective when taken orally. It has a high affinity for the AT 1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. Displaces angiotensin II from the connection with the receptor, not possessing the action of an agonist in relation to this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptors. Communication is long lasting. It has no affinity for other receptors, including the AT2 receptor and other less studied angiotensin receptors. The functional significance of these receptors, as well as the effect of their possible excessive stimulation with angiotensin II, the concentration of which increases with the appointment of telmisartan, has not been studied. Reduces the concentration of aldosterone in the blood, does not inhibit renin in blood plasma and does not block ion channels. Telmisartan does not inhibit the angiotensin converting enzyme (kininase II) (an enzyme that also breaks down bradykinin). Therefore, amplification of the side effects caused by bradykinin is not expected.

In patients with arterial hypertension, telmisartan at 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 oral administration of telmisartan. The effect of the drug persists for 24 hours and remains significant up to 48 hours. A pronounced antihypertensive effect usually develops 4 weeks after regular use of the drug.

In patients with arterial hypertension, telmisartan lowers systolic and diastolic blood pressure (BP), without affecting heart rate (HR).

In the case of abrupt cancellation of telmisartan, blood pressure gradually returns to its original level without the development of withdrawal syndrome.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect the reabsorption of electrolytes in the renal tubules, directly increasing the excretion of sodium and chlorides (approximately in equivalent amounts). The diuretic effect of hydrochlorothiazide leads to a decrease in the volume of circulating blood (BCC), an increase in plasma renin activity, an increase in the secretion of aldosterone, followed by an increase in urine potassium and hydrogen carbonates and, as a result, a decrease in potassium in blood plasma. With simultaneous administration with telmisartan, there is a tendency to stop the loss of potassium caused by these diuretics, presumably due to the blockade of the renin-angiotensin-aldosterone system (RAAS). After oral administration, diuresis increases after 2 hours, and the maximum effect is observed after about 4 hours. The diuretic effect of the drug persists for approximately 6-12 hours.

Long-term use of hydrochlorothiazide reduces the risk of complications of cardiovascular disease and mortality from them.

The maximum antihypertensive effect of Telpres Plus is usually achieved 4-8 weeks after the start of treatment.

Pharmacokinetics:

The combined use of telmisartan and hydrochlorothiazide does not affect the pharmacokinetics of each of the components of the drug.

Telmisartan:

Absorption

When taken orally, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 50%. When taken simultaneously with food, the decrease in 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). 3 hours after ingestion, the concentration in the blood plasma is leveled regardless of the meal.

Distribution of

Communication with plasma proteins - 99.5%, mainly with albumin and alpha-1 glycoprotein. The average value of the apparent volume of distribution in equilibrium concentration is 500 l.

Metabolism

Metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive.

Withdrawal

Elimination half-life (T1 / 2) - more than 20 hours. It is excreted through the intestine unchanged, excretion by the kidneys - less than 2% of the dose taken. The total plasma clearance is high (900 ml / min) compared with hepatic blood flow (about 1500 ml / min).

Pharmacokinetics in special patient groups

Gender differences

There is a difference in plasma concentrations in men and women. Cmax (maximum concentration) and AUC were approximately 3 and 2 times, respectively, higher in women compared with men without a significant effect on effectiveness. Dose adjustment is not required.

Elderly patients

The pharmacokinetics of telmisartan in elderly patients are not different from younger patients. Dose adjustment is not required.

Patients with impaired renal function

In patients with mild to moderate impaired renal function, dose adjustment of telmisartan is not required.

Patients with severe renal impairment and those on hemodialysis are recommended a lower initial dose of 20 mg per day. Telmisartan is not excreted by hemodialysis.

Patients with impaired liver function

Pharmacokinetics studies in patients with hepatic impairment showed an increase in the absolute bioavailability of telmisartan to almost 100%. With liver failure, T1 / 2 does not change. In patients with mild to moderate impaired liver function (class A and B on the Child-Pugh scale), the daily dose should not exceed 40 mg.

Hydrochlorothiazide:

After oral administration of Telpres Plus, the maximum plasma concentrations of hydrochlorothiazide are reached within 1-3 hours. Absolute bioavailability based on total kidney excretion is about 60%. It is bound by blood plasma proteins to 64% hydrochlorothiazide, and the distribution volume is 0.8 В± 0.3 l / kg. Hydrochlorothiazide is not metabolized in the body and excreted by the kidneys almost unchanged. About 60% of the dose taken orally is eliminated within 48 hours. Renal clearance of about 250-300 ml / min. T1L hydrochlorothiazide - 10 - 15 hours. There is a difference in plasma concentrations in men and women. In women, the concentration of telmisartan in plasma is 2-3 times higher than in men, and women have a tendency to increase the concentration of hydrochlorothiazide in the blood plasma is clinically insignificant.

Patients with impaired renal function

In patients with impaired renal function, the rate of elimination of hydrochlorothiazide is reduced.

Studies in patients with creatinine clearance (CC) of 90 ml / min showed that T1 / 2 of hydrochlorothiazide is increased. In patients with impaired T1 / 2 renal function, about 34 hours.

Indications

Arterial hypertension (in case of inefficiency of telmisartan or hydrochlorothiazide in monotherapy).

Contraindications

Hypersensitivity to the active ingredients or auxiliary components of the drug or other sulfonamide derivatives

Pregnancy

Breastfeeding period

Obstructive biliary tract disease

Severe liver dysfunction Class C 30 ml / min)

Refractory hypokalemia, hypercalcemia

Concomitant use with aliskiren in patients with diabetes mellitus and / or impaired kidney function (glomerular filtration rate less than 60 ml / min / 1.73 m2)

Concomitant use of ACE inhibitors in patients with diabetic nephropathy

Lactase deficiency, lactose intolerance,

glucose-galactose malabsorption syndrome Age up to 18 years (efficacy and safety not established).

Precautions:

Bilateral renal artery stenosis or stenosis of a single kidney artery (see Special Instructions)

Impaired liver function (Child-Pugh Class A and B) (see Special Instructions)

Decreased BCC due to prior diuretic therapy , restrictions on the intake of salt, diarrhea or vomiting

Hyperkalemia

Condition after kidney transplantation (no experience with use)

Chronic heart failure III-IV functional class (FC) according to the classification of the New York Cardiology Association

Hypercalcemia

Hypercholesterolemia srdlkrd heart disease hepatic coma)

Stenosis of the aortic and mitral valve

Idiopathic hypertrophic subaortic stenosis (hypertrophic obstruction) uctive cardiomyopathy)

Diabetes mellitus

Primary hyperaldosteronism

Gout,

Special instructions

Mental disorders

Mental disorders, seizures, and delirium-like psychoneurological disorders have been reported in patients (mainly children and adolescents) who have received oseltamivir for the treatment of influenza. These cases were rarely accompanied by life-threatening actions. The role of oseltamivir in the development of these phenomena is unknown. Similar neuropsychiatric disorders are also noted in patients with influenza, in patients with bilateral arterial stenosis or arterial stenosis of a single functioning kidney, the risk of severe arterial hypotension and renal failure increases.

Impaired renal function and kidney transplantation

When using Telpres Plus in patients with impaired renal function, periodic monitoring of potassium and creatinine in blood plasma is recommended. There is no clinical experience with Telpres Plus in patients who have recently undergone kidney transplantation.

The use of thiazide diuretics in patients with impaired renal function can lead to azotemia. Periodic monitoring of renal function is recommended.

Decreased circulating blood volume

Symptomatic arterial hypotension, arterial hypotension, fainting, hyperkalemia and impaired renal function (including acute renal failure) in patients predisposed to this, especially when combined with several drugs that also act on this system. Therefore, a double blockade of RAAS (for example, while taking telmisartan with other RAAS antagonists) is not recommended.

In cases of dependence of vascular tone and renal function mainly on RAAS activity (for example, in patients with chronic heart failure or kidney disease, including renal artery stenosis or stenosis of a single kidney artery), prescribing drugs that affect this system, may be accompanied by the development of acute arterial hypotension, hyperazotemia, oliguria, and in rare cases, acute renal failure. alarming against these disorders are dry oral mucosa, thirst, general weakness, drowsiness, anxiety, myalgia or convulsive twitching of the calf muscles (muscle crumps), muscle weakness, marked decrease in blood pressure, oliguria, tachycardia and such gastrointestinal disorders like nausea or vomiting.

Hypokalemia may develop with thiazide diuretics, but telmisartan can increase blood potassium at the same time. The risk of hypokalemia is most increased in patients with cirrhosis, with increased diuresis, with a salt-free diet, as well as in the case of simultaneous use of glucocorticosteroids, calcitonin, ACTH (adrenocorticotropic hormone), glycyrrhizic acid (found in the licorice root), Telmisartan, Before evaluating parathyroid function, thiazide diuretics should be discontinued.

Thiazide diuretics have been shown to increase kidney excretion of magnesium, which can lead to hypomagnesemia.

In patients with coronary heart disease, the use of any antihypertensive agent, in the case of an excessive decrease in blood pressure, can lead to myocardial infarction or stroke.

Requires enhanced monitoring of patients with impaired uric acid metabolism, thiazides can reduce the amount of iodine that binds to serum proteins, without showing signs of impaired thyroid function, there is information about cases of a photosensitivity reaction when taking thiazide diuretics. If a photosensitivity reaction occurs during treatment, it is recommended to suspend treatment.

Other

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

Impact on the ability to drive transp. Wed and fur .:

There have been no special clinical studies evaluating the effect of Telpres Plus on the ability to drive vehicles and work with mechanisms that require increased attention. However, when driving and engaging in potentially hazardous activities, the possibility of developing dizziness and drowsiness should be taken into account, which requires caution. especially after the first administration of Telpres Plus, it can occur in patients with low BCC and / or sodium in blood plasma against the background of previous treatment with diuretics, restriction of salt, diarrhea or vomiting. Such conditions (fluid and / or sodium deficiency) should be eliminated before taking Telpres Plus.

Double blockade of the renin-angiotensin-aldosterone system

The concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (glomerular filtration rate less than 60 ml / min / 1.73 m2) (see section Contraindications).

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

As a result of the oppression of the RAAS, the following were noted:

Effect on metabolism and endocrine gland function

In patients with diabetes, a dose change of insulin or hypoglycemic agents for oral administration may be required. During therapy with thiazide diuretics, latent diabetes mellitus can manifest.

In some cases, with the use of thiazide diuretics, the development of hyperuricemia and exacerbation of the course of gout are possible.

Violations of the water-electrolyte balance

When using Telpres Plus, as in the case of diuretic therapy, periodic monitoring of serum electrolytes is necessary. Thiazide diuretics, including hydrochlorothiazide, can cause disturbances in water-electrolyte balance and acid-base state (hypokalemia, hyponatremia and hypochloremic alkalosis). Signs which is part of Telpres Plus, on the contrary, can lead to hyperkalemia due to antagonism to angiotensin II receptors (subtype AT1). Although clinically significant hyperkalemia has not been reported with the use of Telpres Plus, the risk factors for its development include renal and / or heart failure and diabetes mellitus.

There is no evidence that Telpres Plus can reduce or prevent hyponatremia caused by diuretics. Hypochloremia is usually minor and does not require treatment.

Thiazide diuretics can reduce the excretion of calcium by the kidneys and cause (in the absence of obvious disturbances in calcium metabolism) a transient and slight increase in serum calcium. More severe hypercalcemia may be a sign of latent hyperparathyroidism. If a decision is made on the need to resume taking a diuretic, it is necessary to protect areas of the body that can be exposed to sunlight or ultraviolet rays of type A and to avoid exposure to the sun, hydrochlorothiazide can increase the concentration of cholesterol and triglycerides in the blood, hydrochlorothiazide can give a positive result during doping control.

There are reports of the development of systemic lupus erythematosus with thiazide diuretics.

Ethnic differences

ACE inhibitors, telmisartan, and other ARA II seem to lower blood pressure in patients of the Negroid race less effectively than in other races, possibly due to a greater predisposition to lower renin activity in the patient population.

Composition

Each tablet 25 mg + 80 mg contains:

Active ingredients:

Hydrochlorothiazide - 25.00 mg

Telmisartan - 80.00 mg.

Excipients:

Mannitol - 327.70 mg

Povidone-K25 - 21.60 mg

Crospovidone - 20.0 mg

Magnesium stearate - 9.00 mg

Megglumin - 24.00 mg

Sodium hydroxide - 6.70 mg

Lactose monohydrate - 99.67 mg

Microcrystalline cellulose - 64.00 mg

Hypromellose - 6.00 mg

Sodium carboxymethyl starch

Type A - 4.00 mg

Iron oxide yellow (E 172) - 0.33 mg.

Dosage and administration

Inside, regardless of the meal time.

The drug Telpres Plus must be taken once a day.

- Telpres Plus 12, 5/40 mg can be prescribed to patients in whom the use of telmisartan preparations in a dosage of 40 mg or hydrochlorothiazide does not lead to adequate control of blood pressure.

- Telpres Plus 12.5 / 80 mg may be prescribed to patients in whom the use of telmisartan 80 mg or Telpres Plus 12.5 / 40 mg does not lead to adequate blood pressure control.

- Telpres Plus 25/80 mg can be prescribed to patients in whom the use of telmisartan preparations in a dosage of 80 mg or Telpres Plus 12.5 / 80 mg drug does not lead to adequate control of blood pressure, or to patients whose condition has previously been stabilized by telmisartan or hydrochlorothiazide with separate application.

In patients with severe arterial hypertension, the maximum daily dose of telmisartan is 160 mg in combination with hydrochlorothiazide in a daily dose of 12.5-25 mg.

Impaired renal function

Limited experience with Telpres Plus in patients with mild to moderate renal impairment does not require dose changes in these cases. In such patients, renal function should be monitored (with CC less than 30 ml / min, see section Contraindications).

Impaired liver function

In patients with mild to moderate impaired liver function (Child-Pugh Class A and B), the daily dose of Telpres Plus should not exceed 12.5 / 40 mg per day (see Pharmacokinetics section).

Elderly patients

Dosage regimen does not require changes.

Side effects of

1) expected based on experience with telmisartan

2) expected based on experience with hydrochlorothiazide

3) side effects that were not observed in clinical trials when telmisartan and hydrochlorothiazide are used, but are expected during use.

Disorders of the respiratory system:

respiratory distress syndrome (including pneumonia and non-cardiogenic pulmonary edema) 3), dyspnea 3).

Disturbances from the heart:

arrhythmias3), tachycardia3), bradycardia1).

Vascular disorders:

marked decrease in blood pressure (including orthostatic hypotension) 3).

Disorders of the nervous system:

syncope / fainting 3), paresthesia 3), sleep disturbance 3), insomnia 3), dizziness 3), increased irritability 2), headache 2).

Mental disorders:

anxiety3), depression3).

Disorders of the gastrointestinal tract:

Diarrhea3), dry mucous membranes of the oral cavity3), flatulence3), abdominal pain3), constipation3), vomiting3), gastritis3), decreased appetite2), anorexia2), hyperglycemia2), hypercholesterol2) pancreatitis2), dyspepsia1), 2), 3).

Violations of the liver and biliary tract:

impaired liver function 3), jaundice (hepatocellular or cholestatic) 2).

Disorders of the skin and subcutaneous tissue:

Eczema1), drug rash1), 2), toxic epidermal necrosis1), 2), erythema3), skin itch3), rash3), increased sweating3), photosensitivity reaction2).

Musculoskeletal and connective tissue disorders:

back pain3), muscle spasms3), myalgia3), arthralgia3), calf muscle cramps3), arthrosis1), tendonitis-like symptoms1), chest pain3).

Disorders of the blood and lymphatic system:

iron deficiency anemia1), aplastic anemia2), hemolytic anemia2), thrombocytopenia1), eosinophilia1), leukopenia2), neutropenia / agranulocytosis2), thrombocytopenia2).

Disorders of the kidneys and urinary tract:

renal failure1), 2), including acute renal failure1), interstitial nephritis2), glucosuria2).

Visual disturbances:

visual impairment3), transient blurred vision3), xanthopsia2), acute angle-closure glaucoma2), acute myopia2).

Disorders of the genitals and mammary gland:

Impotence 3).

Infectious and parasitic diseases:

sepsis, including fatal cases1), upper respiratory tract infections (bronchitis, pharyngitis, sinusitis) 1), 3), urinary tract infections (including cystitis) 1), salivary gland inflammation 2).

Influence on the results of laboratory and instrumental studies:

increased plasma creatinine concentration 3), increased activity of liver enzymes 3), increased activity of creatine phosphokinase 3), increased activity of blood uric acid concentration 3), hypertriglyceridemia 2), hypokalemia 2), 3), hypomagnesemia 2) ), hyponatremia2), 3), hyperuricemia3), a decrease in BCC2), hypoglycemia (in patients with diabetes mellitus) 1), impaired glucose tolerance2), decreased hemoglobin in the blood1).

Immune system disorders:

angioedema (including fatal cases) 3), anaphylactic reactions1), 2), lupus-like reactions2), exacerbation or worsening of symptoms of systemic lupus erythematosus3), necrotic vasculitis2), systemic vasculitis2), lupus erythematosus 2), vasculitis 2).

General disorders and disorders at the injection site:

flu-like syndrome 3), fever 2), weakness 1), 2).

Overdose

Information on overdose is limited. Possible symptoms of an overdose are composed of symptoms from the individual components of the drug. Telmisartan - the most significant - a marked decrease in blood pressure and tachycardia, bradycardia, dizziness, increased serum creatinine concentration and acute renal failure can also be observed.

Hydrochlorothiazide - a violation of the water-electrolyte balance of the blood (hypokalemia, hypochloremia), a decrease in BCC, which can lead to muscle spasms and / or increase disorders of the cardiovascular system: arrhythmias caused by the simultaneous use of cardiac glycosides or some antiarrhythmic drugs.

Treatment: symptomatic therapy, hemodialysis is ineffective. The degree of removal of hydrochlorothiazide during hemodialysis has not been established. Regular monitoring of serum electrolytes and creatinine is required. Hemodialysis is not effective.

Storage conditions

At a temperature not exceeding 25 РC, in the original packaging.

Keep out of the reach of children!

Expiration

2 years.

Terms and conditions

prescription

Dosage form

tablets