Telprez Plus, tablets 80 mg+25 mg 98 pcs

Pharmacotherapeutic group:

Hypertensive combined 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 (angiotensin II receptor antagonist) and hydrochlorothiazide, a thiazide diuretic. Simultaneous use of these components leads to a more pronounced antihypertensive effect than the use of each of them separately.

Telprez Plus once daily leads to a significant gradual decrease in blood pressure (BP).

Telmisartan

Telmisartan is a specific angiotensin II receptor antagonist (AT1 type) 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. It displaces angiotensin II from binding to the receptor, having no agonist effect against this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptor. The binding is long-lasting. It has no affinity for other receptors, including AT2 receptor and other less studied angiotensin receptors. The functional significance of these receptors and the effect of their possible overstimulation by angiotensin II, the concentration of which increases with telmisartan administration, has not been studied. It reduces the blood concentration of aldosterone, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kinininase II) (an enzyme that also degrades bradykinin). Therefore, an increase in bradykinin-induced side effects 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 action 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.

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

In case of abrupt telmisartan withdrawal BP gradually returns to baseline levels without development of “withdrawal” syndrome.

Hydrochlorothiazide

Hydrochlorothiazide is a thiazide diuretic. Thiazide diuretics affect electrolyte reabsorption in the renal tubules by directly increasing sodium and chloride excretion (approximately equivalent amounts). Diuretic effect of hydrochlorothiazide leads to decreased circulating blood volume (CBC), increased plasma renin activity, increased secretion of aldosterone, with a subsequent increase in urinary potassium and hydrocarbonates and, as a consequence, decreased plasma potassium content. When concomitantly administered with telmisartan, there is a tendency to stop potassium loss caused by these diuretics, presumably due to 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. Diuretic effect of the drug lasts for about 6-12 hours.

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

The maximum antihypertensive effect of Telprez Plus is usually achieved 4 to 8 weeks after treatment initiation.

Pharmacokinetics:

The co-administration of telmisartan and hydrochlorothiazide has no effect on the pharmacokinetics of either component of the drug.

Telmisartan:

Intake

If taken orally, it is rapidly absorbed from the gastrointestinal tract. Bioavailability is about 50%. When taken concomitantly with food, the decrease in AUC (area under the curve “concentration-time”) ranges from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). Three hours after ingestion, plasma concentrations level off regardless of food intake.

Distribution

The binding to plasma proteins is 99.5%, mainly to albumin and alpha-1 glycoprotein. Average apparent volume of distribution at equilibrium concentration is 500 l.

Metabolism

Metabolized by conjugation with glucuronic acid. The metabolites are pharmacologically inactive.

Elimination

The elimination half-life (T1/2) is more than 20 hours. Excretion is through the intestine unchanged, renal excretion is less than 2% of the administered dose. 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 those in younger patients. No dose adjustment is required.

Patients with impaired renal function

In patients with mild to moderate impaired renal function, no dose adjustment of telmisartan is required.

In patients with severe renal impairment and patients on hemodialysis, a lower starting dose of 20 mg daily is recommended. Telmisartan is not excreted by hemodialysis.

Patients with hepatic impairment

Pharmacokinetic studies in patients with hepatic impairment have shown an increase in the absolute bioavailability of telmisartan to almost 100%. In hepatic insufficiency the T1/2 is not changed. 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 administration of the drug Telprez Plus the maximum concentrations of hydrochlorothiazide in plasma are reached within 1-3 hours. Absolute bioavailability, based on total renal excretion, is about 60%. Plasma proteins bind 64% of hydrochlorothiazide, 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. T1L of hydrochlorothiazide is 10-15 hours. There is a difference in plasma concentrations in men and women. In women telmisartan plasma concentration is 2-3 times higher than in men, also in women there is a tendency for increased plasma concentration of hydrochlorothiazide clinically insignificant.

Patients with impaired renal function

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

Studies performed in patients with a creatinine clearance (CK) of 90 ml/min have shown that the T1/2 of hydrochlorothiazide is increased. In patients with decreased renal function, the T1/2 is about 34 hours.

Indications

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

Pharmacological effect

Pharmacotherapeutic group:

Combined antihypertensive agent (angiotensin II receptor antagonist + diuretic agent)

ATX:

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

Pharmacodynamics:

Telpres Plus is a combination of telmisartan (angiotensin II receptor antagonist) 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 (AT1 type), 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 its connection with the receptor, without having an agonist effect on this receptor. Telmisartan binds only to the AT1 subtype of angiotensin II receptors. The connection is long-term. 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 by angiotensin II, the concentration of which increases with the administration 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 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 observed within 3 hours after the first oral administration of telmisartan. The effect of the drug lasts 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 suffering from arterial hypertension, telmisartan reduces systolic and diastolic blood pressure (BP) without affecting heart rate (HR).

In 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 circulating blood volume (CBV), an increase in the activity of plasma renin, an increase in the secretion of aldosterone, with a subsequent increase in the content of potassium and bicarbonates in the urine and, as a consequence, a decrease in the content of potassium in the blood plasma. When taken concomitantly with telmisartan, there is a tendency to stop the potassium loss caused by these diuretics, presumably due to blockade of the renin-angiotensin-aldosterone system (RAAS). After oral administration, diuresis increases after 2 hours, and the maximum effect is observed after approximately 4 hours. The diuretic effect of the drug lasts for approximately 6-12 hours.

Long-term use of hydrochlorothiazide reduces the risk of 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 component of the drug.

Telmisartan:

Suction

When taken orally, it is quickly absorbed from the gastrointestinal tract. Bioavailability is about 50%. When taken simultaneously with food, the reduction 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). 3 hours after administration, the concentration in the blood plasma levels out regardless of food intake.

Distribution

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

Metabolism

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

Removal

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

Pharmacokinetics in special groups of patients

Gender differences

There is a difference in plasma concentrations between men and women. Cmax (maximum concentration) and AUC were approximately 3-fold and 2-fold, respectively, higher in women compared to men, with no significant effect on efficacy. No dose adjustment is required.

Elderly patients

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

Patients with impaired renal function

In patients with mild to moderate renal impairment, no dose adjustment of telmisartan is required.

For patients with severe renal failure and patients on hemodialysis, a lower initial dose of 20 mg per day is recommended. Telmisartan is not eliminated by hemodialysis.

Patients with liver dysfunction

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

Hydrochlorothiazide:

After oral administration of Telpres Plus, maximum plasma concentrations of hydrochlorothiazide are achieved within 1-3 hours. Absolute bioavailability based on total renal excretion is approximately 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 an oral dose is eliminated within 48 hours. Renal clearance is about 250-300 ml/min. T1L of hydrochlorothiazide – 10 – 15 hours. There is a difference in plasma concentrations between 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, which is 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 (CC) 90 ml/min showed that T1/2 of hydrochlorothiazide increases. In patients with reduced renal function, T1/2 is about 34 hours.

Special instructions

Liver dysfunction

The use of Telpres Plus is contraindicated in patients with cholestasis, biliary obstruction or severe liver dysfunction (Child-Pugh class C) (see section “Contraindications”), since telmisartan is mainly excreted in the bile. It is assumed that in such patients the hepatic clearance of telmisartan is reduced. In patients with mild or moderate liver dysfunction (class A and B according to the Child-Pugh classification), Telpres Plus should be used with caution (see section “With caution”).

Renovascular hypertension

When treated with drugs acting on the RAAS, in patients with bilateral arterial stenosis or arterial stenosis of a single functioning kidney, the risk of severe arterial hypotension and renal failure increases.

Renal dysfunction and kidney transplantation

When using the drug Telpres Plus in patients with impaired renal function, periodic monitoring of potassium and creatinine levels in the blood plasma is recommended. There is no clinical experience with the use of 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, especially after the first dose of Telpres Plus, may occur in patients with low blood volume and/or sodium content in the blood plasma due to previous treatment with diuretics, restriction of salt intake, diarrhea or vomiting. Such conditions (fluid and/or sodium deficiency) must be eliminated before starting Telpres Plus.

Dual blockade of the renin-angiotensin-aldosterone system

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

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

Primary aldosteronism

In patients with primary aldosteronism, treatment with antihypertensive drugs that act by inhibiting the RAAS is usually ineffective.

Aortic and mitral valve stenosis, hypertrophic obstructive cardiomyopathy

Caution must be exercised when using Telpres Plus (as well as other vasodilators) in patients with aortic or mitral stenosis, as well as hypertrophic obstructive cardiomyopathy.

Acute myopia and secondary angle-closure glaucoma

Hydrochlorothiazide, being a sulfonamide derivative, can cause an idiosyncratic reaction in the form of acute transient myopia and acute angle-closure glaucoma. Symptoms of these disorders include a sudden decrease in visual acuity or eye pain, which typically occurs within a few hours to several weeks after starting to use the drug. If left untreated, acute angle-closure glaucoma can lead to vision loss. The main treatment is to discontinue hydrochlorothiazide as quickly as possible. It is important to keep in mind that if intraocular pressure remains uncontrolled, emergency medical or surgical treatment may be required. Risk factors for the development of acute angle-closure glaucoma include a history of allergies to sulfonamides or penicillin.

Effect on metabolism and function of endocrine glands

In patients with diabetes mellitus, changes in the dose of insulin or oral hypoglycemic agents may be required. During therapy with thiazide diuretics, latent diabetes mellitus may manifest.

In some cases, when using thiazide diuretics, hyperuricemia and exacerbation of gout may develop.

Water-electrolyte imbalance

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 fluid and electrolyte balance and acid-base status (hypokalemia, hyponatremia and hypochloremic alkalosis). Warning signs for these disorders are dryness of the oral mucosa, a feeling of thirst, general weakness, drowsiness, anxiety, myalgia or convulsive twitching of the calf muscles (cramps), muscle weakness, a marked decrease in blood pressure, oliguria, tachycardia and gastrointestinal disorders such as nausea or vomiting.

When using thiazide diuretics, hypokalemia may develop, but concomitantly used telmisartan may increase the potassium level in the blood. The risk of hypokalemia increases most in patients with cirrhosis of the liver, with increased diuresis, while following 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 antagonism to angiotensin II receptors (AT1 subtype). Although clinically significant hyperkalemia has not been reported with Telpres Plus, it should be taken into account that 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 diuretic-induced hyponatremia. 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 hidden hyperparathyroidism. Before assessing parathyroid function, thiazide diuretics should be discontinued.

Thiazide diuretics have been shown to increase renal excretion of magnesium, which may lead to hypomagnesemia.

In patients with coronary heart disease, the use of any antihypertensive drug, in case of excessive reduction in 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 that binds to serum proteins without showing signs of thyroid dysfunction; There is information about cases of the development of photosensitivity reactions when taking thiazide diuretics. If a photosensitivity reaction occurs during treatment, it is recommended to suspend treatment. If it is decided that it is necessary to resume taking a diuretic, it is necessary to protect areas of the body that may be exposed to sunlight or ultraviolet A rays and avoid sun exposure; hydrochlorothiazide may increase the concentration of cholesterol and triglycerides in the blood; hydrochlorothiazide may give a positive result during doping control.

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

Ethnic differences

ACE inhibitors, telmisartan, and other ARBs appear to be less effective in lowering blood pressure in blacks than in other races, possibly due to a greater predisposition to decreased renin activity in these patient populations.

Other

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

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

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

Active ingredient

Hydrochlorothiazide, Telmisartan

Composition

Each 25 mg + 80 mg tablet 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,

meglumine – 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.

Contraindications

– Hypersensitivity to the active substances or auxiliary components of the drug or other sulfonamide derivatives;

– Pregnancy;

– Breastfeeding period;

– Obstructive diseases of the biliary tract;

– Severe liver dysfunction (class C according to the Child-Pugh classification);

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

– Refractory hypokalemia, hypercalcemia;

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

– Simultaneous 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 have not been established).

With caution:

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

– Liver dysfunction (class A and B according to the Child-Pugh classification) (see section “Special instructions”);

– Decrease in blood volume due to previous diuretic therapy, restriction of salt intake, diarrhea or vomiting;

– Hyperkalemia;

– Condition after kidney transplantation (no experience of use);

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

– Hypercalcemia;

– Hypercholesterolemia;

– Hypertriglyceridemia;

– Coronary heart disease;

– Progressive liver diseases (risk of developing 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 of hydrochlorothiazide in the composition);

– Use in patients of the Negroid race;

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

– Simultaneous use with ACE inhibitors or aliskiren;

– Simultaneous use with potassium preparations, 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 the 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 breath3).

Cardiac disorders:

arrhythmias3), tachycardia3), bradycardia1).

Vascular disorders:

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

Nervous system disorders:

syncope/fainting3), paresthesia3), sleep disturbances3), insomnia3), dizziness3), increased excitability2), headache2).

Mental disorders:

anxiety3), depression3).

Gastrointestinal disorders:

Diarrhea3), dryness of the oral mucosa3), flatulence3), abdominal pain3), constipation3), vomiting3), gastritis3), decreased appetite2), anorexia2), hyperglycemia2), hypercholesterolemia2), pancreatitis2), dyspepsia1),2),3).

Disorders of the liver and biliary tract:

liver dysfunction3), jaundice (hepatocellular or cholestatic)2).

Disorders of the skin and subcutaneous tissues:

Eczema1), drug rash1),2), toxic epidermal necrosis1),2), erythema3), pruritus3), 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).

Blood and lymphatic system disorders:

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

Renal and urinary tract disorders:

renal failure1),2), including acute renal failure1), interstitial nephritis2), glycosuria2).

Visual disorders:

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

Disorders of the genital organs and breast:

Impotence3).

Infectious and parasitic diseases:

sepsis, including fatal cases1), 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:

increased concentration of creatinine in blood plasma3), increased activity of liver enzymes3), increased activity of creatine phosphokinase3), increased activity of blood uric acid concentration3), hypertriglyceridemia2), hypokalemia2),3), hypomagnesemia2), hyperkalemia1), hyponatremia2),3), hyperuricemia3), decreased blood volume2), hypoglycemia (in patients with diabetes mellitus)1), impaired tolerance to glucose2), decrease in 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), necrotizing vasculitis2), systemic vasculitis2), relapse of systemic lupus erythematosus2), vasculitis2).

General disorders and disorders at the injection site:

flu-like syndrome3), fever2), 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.

Combination use with digoxin, warfarin, hydrochlorothiazide, glibenclamide, ibuprofen, paracetamol, simvastatin and amlodipine does not lead to clinically significant interactions.

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

Concomitant use of telmisartan with aliskiren is contraindicated in patients with diabetes mellitus or renal failure (GFR less than 60 ml/min/1.73 m2 body surface area) and is not recommended in other patients. The simultaneous use of telmisartan and ACE inhibitors is contraindicated in patients with diabetic nephropathy.

Data from clinical studies have shown that dual blockade of the RAAS due to the combined use of ACE inhibitors, ARB II 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 the RAAS.

The risk of developing hyperkalemia may increase when used concomitantly with other drugs that can cause hyperkalemia (potassium-containing dietary supplements and salt substitutes containing potassium and potassium-sparing diuretics (spironolactone, eplerenone, triamterene or amiloride), non-steroidal anti-inflammatory drugs (NSAIDs, including selective cyclooxygenase-2 (COX) inhibitors), 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 potassium content in the blood plasma should be regularly monitored.

Digoxin

When telmisartan was taken together with digoxin, an increase in the average Cmax of digoxin in the blood plasma by 49% and the minimum concentration by 20% was noted. At the beginning of treatment, when selecting a 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 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 may lead to a significant increase in plasma potassium levels. If concomitant use is indicated because hypokalemia is documented, they should be used with caution and in conjunction with regular monitoring of plasma potassium.

Lithium preparations

When lithium preparations were taken together with ACE and ARB II inhibitors, including telmisartan, a reversible increase in the concentration of lithium in the blood plasma and its toxic effect occurred. If it is necessary to use this combination of drugs, it is recommended to carefully monitor lithium concentrations 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), concomitant use of ARB II and drugs that inhibit cyclooxygenase-2 may lead to a 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. Adequate fluid intake should be ensured and renal function should be monitored at the start of co-administration and periodically thereafter.

Diuretics (thiazide or loop diuretics)

Previous treatment with high doses of diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may lead to hypovolemia and the risk of hypotension when starting treatment with telmisartan.

Other antihypertensive drugs

The effect of telmisartan may be enhanced by concomitant 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 be exacerbated by the use of alcohol, barbiturates, narcotics, or antidepressants.

Corticosteroids (for systemic use)

Corticosteroids weaken the effect of telmisartan.

Hydrochlorothiazide

When used simultaneously with:

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

– hypoglycemic agents for oral administration and insulin: dose adjustment of hypoglycemic agents for oral administration and insulin may be required;

– metformin: risk of developing lactic acidosis;

– cholestyramine and colestipol: in the presence of anion exchange resins, the absorption of hydrochlorothiazide is impaired;

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

– pressor amines (for example, norepinephrine): the effect of pressor amines may be weakened;

– non-depolarizing muscle relaxants (for example, tubocurarine chloride): hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants;

– antigout drugs: the concentration of uric acid in the blood serum may increase and therefore changes in the dose of uricosuric drugs may be required. The use of thiazide diuretics increases the incidence of hypersensitivity reactions to allopurinol;

– calcium supplements and vitamin D: thiazide diuretics can increase the calcium level in the blood serum due to a decrease in its excretion by the kidneys. If you need to use calcium supplements, you should regularly monitor the calcium level in the blood and, if necessary, change the dose of calcium supplements;

– beta-blockers and diazoxide: thiazide diuretics may enhance hyperglycemia caused by beta-blockers and diazoxide;

– m-anticholinergic blockers (for example, atropine, biperidine): decreased gastrointestinal motility, increased bioavailability of thiazide diuretics;

– amantadine: the clearance of amantadine may be reduced by hydrochlorothiazide, which leads to an increase in amantadine plasma concentrations and possible toxicity;

– cytotoxic drugs (for example, cyclophosphamide, methotrexate): reducing the renal excretion of cytotoxic drugs and enhancing their myelosuppressive effect;

– NSAIDs: combined use with thiazide diuretics may lead to a decrease in diuretic and antihypertensive effect;

– drugs that lead to potassium excretion and hypokalemia (for example, diuretics that remove potassium; laxatives; glucocorticosteroids, calcitonin, ACTH (adrenocorticotropic hormone), glycyrrhizic acid (found in licorice root), amphotericin B; carbenoxolone; benzylpenicillin; acetylsalicylic acid derivatives acids): increased hypokalemic effect. Hypokalemia caused by hydrochlorothiazide is compensated by the potassium-sparing effect of telmisartan;

– theophylline: increased risk of hypokalemia;

– amiodarone: simultaneous use with thiazide diuretics may lead to an increased risk of arrhythmias associated with hypokalemia;

– potassium-sparing diuretics, potassium preparations, other drugs that can increase potassium levels in the blood serum (for example, heparin) or replacing sodium in table salt with potassium salts can lead to hyperkalemia.

Periodic monitoring of the potassium level in the blood plasma is recommended in cases where Telpres Plus is prescribed together with drugs that can cause hypokalemia, as well as with drugs that can increase the potassium level in the blood serum.

Overdose

Information regarding overdose is limited. Possible symptoms of overdose consist of symptoms from the individual components of the drug. Telmisartan – the most significant – a pronounced decrease in blood pressure and tachycardia, bradycardia, dizziness, an increase in serum creatinine concentration and acute renal failure may also be observed.

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

Treatment: symptomatic therapy, hemodialysis is ineffective. The extent to which hydrochlorothiazide is removed during hemodialysis has not been established. Regular monitoring of electrolytes and creatinine in the blood serum is necessary. Hemodialysis is not effective.

Storage conditions

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

Keep out of the reach of children!

Shelf life

2 years

Manufacturer

Laboratorios Likonsa S.A., Spain