Telpres Plus pills 40mg+12.5mg, 98pcs

Composition

Each 12.5 mg + 80 mg tablet contains:

active ingredients:

hydrochlorothiazide-12.50 mg,

telmisartan-80.00 mg;

excipients:

mannitol – 327,70 mg,

povidone-To 25 – mg 21,60,

crospovidon – 40,0 mg,

magnesium stearate – of 8.50 mg,

meglumin – 24,00 mg,

sodium hydroxide – of 6.70 mg,

lactose monohydrate – 49,84 mg,

microcrystalline cellulose – of 32.00 mg,

hypromellose – 3,00 mg,

carboximetilkrahmal sodium type a – 2,00 mg,

iron oxide red (E 172) and 0.17 mg.

Pharmacological properties

Pharmacotherapeutic group:

Combined antihypertensive agent (angiotensin II receptor antagonist + diuretic)

ATX:

C. 09. D. A. 07 Telmisartan in combination with diuretics

Pharmacodynamics :

Telpres Plus is a combination of telmisartan (an angiotensin II receptor antagonist) and a hydrochlorothiazide-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), effective when taken orally. It has a high affinity for the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized. Displaces angiotensin II from binding to the receptor, without having an agonist effect on this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptors. The relationship is long-term. It has no affinity for other receptors, including the AT2 receptor and other less well-studied angiotensin receptors. The functional significance of these receptors, as well as the effect of their possible overstimulation with angiotensin II, the concentration of which increases with the appointment of telmisartan, have not been studied. Reduces the concentration of aldosterone in the blood, does not inhibit renin in the 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, an increase in 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 use of telmisartan. The effect of the drug persists for 24 hours and remains significant for up to 48 hours. A pronounced antihypertensive effect usually develops 4 weeks after regular use of the drug.

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

In the case of abrupt withdrawal 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 chloride (in approximately 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 aldosterone secretion, followed by an increase in the content of potassium and bicarbonates in the urine and, as a result, a decrease in the content of potassium in the blood plasma. When taken concomitantly with telmisartan, there is a tendency to stop the loss of potassium caused by these diuretics, presumably due to blockade of the renin-angiotensin-aldosterone system (RAAS). After oral use, 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 developing complications of cardiovascular diseases 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:

Suction

When taken orally, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 50%. When taken simultaneously with food, the decrease in AUC (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 ingestion, the concentration in the blood plasma is equalized regardless of food intake.

Distribution

The relationship with plasma proteins is 99.5%, mainly with albumin and alpha-1 glycoprotein. The average apparent volume of distribution at equilibrium concentration is 500 liters.

Metabolism

It is metabolized by conjugation with glucuronic acid. The metabolites are pharmacologically inactive.

Deduction

The half-life (T 1/2) is more than 20 hours. It is excreted through the intestines in unchanged form, excretion by the kidneys – less than 2% of the dose taken. Total plasma clearance is high (900 ml / min) compared to “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 higher in women compared to men, respectively, with no significant effect on efficacy. No dose adjustment is required.

Elderly patients

The pharmacokinetics of telmisartan in elderly patients do not differ from young patients. No dose adjustment is required.

Patients with impaired renal function

No dose adjustment of telmisartan is required in patients with mild to moderate renal impairment.

A lower initial dose of 20 mg / day is recommended for patients with severe renal insufficiency and patients undergoing hemodialysis. Telmisartan is not eliminated by hemodialysis.

Patients with impaired liver function

Pharmacokinetic studies in patients with hepatic insufficiency have shown an increase in the absolute bioavailability of telmisartan to almost 100%. With hepatic insufficiency, T 1/2 does not change. In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), the daily dose of the drug should not exceed 40 mg.

Hydrochlorothiazide:

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

Patients with impaired renal function

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

Studies conducted in patients with creatinine clearance (creatinine clearance) of 90 ml / min showed that T 1/2 of hydrochlorothiazide increases. In patients with reduced renal function, T 1/2 is about 34 hours.

Indications

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

Contraindications

– Hypersensitivity to the Active ingredient or auxiliary components of the drug or other derivatives of sulphonamides;

– Pregnancy;

– the Period of breastfeeding;

– Obstructive disease of the biliary tract;

Severe disturbances of liver function (class C classification for child-Pugh);

– Severe renal dysfunction (CC less than 30 ml/min);

Refractory hypokalemia, hypercalcemia;

– Concurrent use of aliskiren in patients with diabetes mellitus and/or impaired renal function (glomerular filtration rate less than 60 ml/min/1.73 m 2);

– Simultaneous use of ACE inhibitors in patients with diabetic nephropathy;

– lactase Deficiency, lactose intolerance, a syndrome of glucose-galactose malabsorption;

– Age under 18 years (effectiveness and safety not established).

With caution:

– Bilateral renal artery stenosis or stenosis of the artery to a solitary kidney (see “Special instructions”);

– violations of the liver function (class A and b according to the classification of child-Pugh) (see “Special instructions”);

– Reduction of BCC as a result of prior diuretic therapy, restriction of salt, diarrhoea, or vomiting;

– Hyperkalemia;

– Condition after kidney transplantation (experience of missing);

– Chronic heart failure III-IV functional class (FC) according to the classification of new York heart Association;

– Hypercalcemia;

– Hypercholesterolemia;

Hypertriglyceridemia;

– Ischemic heart disease

– Progressing liver disease (risk of hepatic coma);

– stenosis of the aortic and mitral valve;

– Idiopathic hypertrophic subaortic stenosis (hypertrophic obstructive cardiomyopathy);

– diabetes mellitus;

Primary hyperaldosteronism;

– Gout, hyperuricemia;

– Systemic lupus erythematosus;

Secondary angle-closure glaucoma (due to the presence in the composition of hydrochlorothiazide);

– Use in patients of the Negroid race;

– Experience in patients with impaired renal (QC more than 30 ml/min) is limited, but does not confirm the development of side effects in the kidneys and dose adjustment is not required;

– concomitant use with ACE inhibitors or aliskiren;

– Simultaneous use with potassium supplements, potassium-sparing diuretics.

Side effects

1) expected based on experience with telmisartan

2) expected based on experience with hydrochlorothiazide

3) side effects that were not observed in clinical studies with simultaneous use of telmisartan and hydrochlorothiazide, but are expected during the use of Telpres Plus

Respiratory system disorders:

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

Cardiac disorders:

arrhythmias 3), tachycardia 3), bradycardia 1).

Vascular disorders:

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

Nervous system disorders:

syncope / syncope 3), paresthesia 3), sleep disorders 3), insomnia 3), dizziness 3), increased excitability 2), headache 2).

Mental disorders:

anxiety 3), depression 3).

Disorders of the gastrointestinal tract:

Diarrhea 3), dry oral mucosa 3), flatulence 3), abdominal pain 3), constipation 3), vomiting 3), gastritis 3), decreased appetite 2), anorexia 2), hyperglycemia 2), hypercholesterolemia 2), pancreatitis 2), dyspepsia 1),2),3).

Liver and biliary tract disorders:

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

Skin and subcutaneous tissue disorders:

Eczema 1), drug rash 1),2), toxic epidermal necrosis 1),2), erythema 3), pruritus 3), rash 3), increased sweating 3), photosensitization reaction 2).

Musculoskeletal and connective tissue disorders:

back pain 3), muscle spasms 3), myalgia 3), arthralgia 3), calf muscle cramps 3), osteoarthritis 1), tendinitis-like symptoms 1), chest pain 3).

Disorders of the blood and lymphatic system:

iron deficiency anemia 1), aplastic anemia 2), hemolytic anemia 2), thrombocytopenia 1), eosinophilia 1), leukopenia 2), neutropenia/agranulocytosis 2), thrombocytopenia 2).

Kidney and urinary tract disorders:

renal failure 1),2), including acute renal failure 1), interstitial nephritis 2), glucosuria 2).

Visual disturbances:

visual impairment 3), transient blurred vision 3), xanthopsia 2), acute angle-closure glaucoma 2), acute myopia 2).

Genital and breast disorders:

Impotence 3).

Infectious and parasitic diseases:

sepsis, including fatal cases 1), upper respiratory tract infections (bronchitis, pharyngitis, sinusitis)1),3), urinary tract infections (including cystitis)1), inflammation of the salivary glands 2).

Influence on the results of laboratory and instrumental studies:

increasing the concentration of creatinine in the blood plasma 3), increased activity of “liver” enzymes 3), increased activity of creatine kinase 3), increased activity of uric acid concentration of the blood 3), hypertriglyceridemia 2), hypokalemia 2),3), hypomagnesemia 2), hyperkalemia 1), hyponatremia 2),3), hyperuricemia 3), a decrease in BCC 2), hypoglycemia (in patients with diabetes)1), impaired glucose tolerance 2), decreased hemoglobin in the blood 1).

Immune system disorders:

angioedema (including fatal cases)3), anaphylactic reactions 1),2), lupus-like reactions 2), exacerbation or worsening of symptoms of systemic lupus erythematosus 3), necrotic vasculitis 2), systemic vasculitis 2), relapse of systemic lupus erythematosus 2), vasculitis 2).

General disorders and disorders at the injection site:

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

Interaction

Telmisartan

Telmisartan may increase the antihypertensive effect of other antihypertensive agents. Other types of interactions of clinical significance have not been identified.

Co-use with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine did not result in clinically significant interactions.

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 of body surface area) and is not recommended for other patients. Concomitant use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy.

The clinical trial data has shown that dual blockade of RAAS due to the combined use of ACE inhibitors, ARA II or aliskiren associated with increased frequency of adverse events such as hypotension, hyperkalemia, and impaired renal function (including acute renal failure) compared to using only one drug acting on the RAAS.

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

Digoxin

When telmisartan was co-administered with digoxin, an increase in the average Cmax of digoxin in blood plasma by 49% and the minimum concentration by 20% was noted. At the beginning of treatment, when selecting the dose and stopping treatment with telmisartan, the concentration of digoxin in the blood plasma should be carefully monitored to maintain it within the therapeutic range.

Potassium-sparing diuretics or potassium-containing dietary supplements

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

Lithium preparations

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

Nonsteroidal anti-inflammatory drugs (NSAIDs)

NSAIDs (including acetylsalicylic acid in doses used for anti-inflammatory treatment, COX-2 inhibitors and non-selective NSAIDs) may weaken the antihypertensive effect of ARA II. In some patients with impaired renal function (for example, patients with dehydration, elderly patients with impaired renal function), the combined use of ARA II and drugs that inhibit cyclooxygenase-2 may lead to further deterioration of renal function, including the development of acute renal failure, which is usually reversible. Therefore, the combined use of drugs should be carried out with caution, especially in elderly patients. Proper fluid intake should be ensured, and renal function indicators should also be monitored at the beginning of co-use and periodically thereafter.

Diuretics (thiazide or loop diuretics)

Previous treatment with high-dose diuretics, such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic), may lead to hypovolemia and the risk of hypotension at the start of telmisartan treatment.

Other antihypertensive agents

The effect of telmisartan may be enhanced with the combined 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 drugs, including telmisartan. In addition, orthostatic hypotension may increase with alcohol, barbiturates, narcotic drugs or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids weaken the effect of telmisartan.

Hydrochlorothiazide

With simultaneous use with:

– ethanol, barbiturates, or narcotic analgesics: the risk of orthostatic hypotension;

– hypoglycemic agents for oral use and insulin may require dose adjustment of hypoglycemic agents for oral use of insulin;

– Metformin: risk of lactic acidosis;

colestyramine and colestipol: in the presence of anionic exchange resins absorption of hydrochlorothiazide is broken;

– cardiac glycosides: the risk of hypokalemia or hypomagnesemia caused by thiazide diuretics, the development of arrhythmias caused by receiving cardiac glycosides;

– pressor amines (for example, norepinephrine): it is possible to weaken the effect of pressor amines;

– non-depolarizing muscle relaxants (for example, tubocurarin chloride): hydrochlorothiazide may enhance the effect of non-depolarizing muscle relIt should be borne in mind that if intraocular pressure remains uncontrolled, urgent conservative or surgical treatment may be required. Risk factors for acute angle-closure glaucoma include a history of allergy to sulfonamides or penicillin.

Effects on metabolism and endocrine gland function

In patients with diabetes mellitus, it may be necessary to change the dose of insulin or hypoglycemic agents for oral use. Latent diabetes mellitus may occur during therapy with thiazide diuretics.

In some cases, the use of thiazide diuretics may lead to hyperuricemia and exacerbation of the course of gout.

Violations of the water-electrolyte balance

When using the drug Telpres Plus, as in the case of diuretic therapy, periodic monitoring of the content of electrolytes in the blood serum is necessary. Thiazide diuretics, including hydrochlorothiazide, can cause disturbances in the water-electrolyte balance and acid-base state (hypokalemia, hyponatremia, and hypochloremic alkalosis). Warning signs for these disorders are dryness of the oral mucosa, thirst, general weakness, drowsiness, anxiety, myalgia or convulsive twitching of the calf muscles (crampi), muscle weakness, marked decrease in blood pressure, oliguria, tachycardia, and gastrointestinal disorders such as nausea or vomiting.

Hypokalaemia may occur with thiazide diuretics, but concomitant use of telmisartan may increase blood potassium levels. The risk of hypokalemia is most increased in patients with cirrhosis of the liver, 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 licorice root), Telmisartan, which is part of the drug Telpres Plus, on the contrary, can lead to hyperkalemia due to antagonism to angiotensin II receptors (subtype AT 1). Although no clinically significant hyperkalemia has been reported with Telpres Plus, it should be taken into account that 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 violations of calcium metabolism) a transient and slight increase in the content of calcium in the blood serum. More severe hypercalcemia may be a sign of latent hyperparathyroidism. Thiazide diuretics should be discontinued before evaluating parathyroid function.

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

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

Increased monitoring of patients with impaired uric acid metabolism is required; thiazides can reduce the amount of iodine binding to serum proteins, without showing signs of thyroid dysfunction; there is information about cases of photosensitivity reactions when taking thiazide diuretics. If a photosensitivity reaction occurs during treatment, it is recommended to suspend treatment. If a decision is made to resume taking a diuretic, it is necessary to protect areas of the body that may be exposed to sunlight or ultraviolet rays of type A and 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.

Systemic lupus erythematosus has been reported with thiazide diuretics.

Ethnic differences

ACE inhibitors, telmisartan, and other ARA II drugs appear to be less effective in lowering blood pressure in black patients than in other races, possibly due to a greater predisposition to a decrease in renin activity in the population of these patients.

Other things

As with other antihypertensive agents, excessive lowering of blood pressure in patients suffering from ischemic cardiomyopathy or coronary heart disease can lead to the development of myocardial infarction or stroke.

Influence on the ability to drive vehicles and mechanisms:

No specific clinical studies have been conducted to evaluate the effect of Telpres Plus on the ability to drive vehicles and work with mechanisms that require increased attention. However, when driving vehicles and engaging in potentially dangerous activities, the possibility of dizziness and drowsiness should be taken into account, which requires caution.

Form of production

Tablets

Storage conditions

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

Keep out of reach of children!

Shelf

life is 2 years.

Active ingredient

Hydrochlorothiazide, Telmisartan

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension