Teveten plus 600mg tablets, No. 28

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen. The oral dose for the fixed combination of eprosartan + hydrochlorothiazide is 600 mg / 12.5 mg 1 time / day.

Film-coated tablets, yellow-brown, oval, biconvex, engraved with '5147' on one side; at the break of a white tablet.

In 1 tablet:

eprosartan mesylate 735.8 mg, which corresponds to the content of eprosartan 600 mg

hydrochlorothiazide 12.5 mg

Severe renal failure (CC <30 ml / min); severe liver failure (more than 9 points on the Child-Pugh scale); cholestasis and obstruction of the biliary tract; hemodynamically significant bilateral renal artery stenosis or severe arterial stenosis of a single functioning kidney; treatment-resistant hypokalemia or hypercalcemia; refractory hyponatremia; symptomatic hyperuricemia or gout; simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (CC less than 60 ml / min); pregnancy, lactation (breastfeeding); age under 18; hypersensitivity to eprosartan, hydrochlorothiazide, and other sulfonamide derivatives.

With caution: severe and chronic heart failure (IV FC according to NYHA classification), bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, a decrease in BCC, a violation of the water and electrolyte balance of the blood (due to the intake of diuretics in high doses, repeated vomiting, prolonged diarrhea, salt-free diet), mild or moderate hepatic impairment (less than 9 points on the Child-Pugh scale without a history of cholestasis), diabetes mellitus, stenosis of the aortic and mitral valves, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, coronary artery disease (limited experience), acute myopathy secondary angle-closure glaucoma, SLE.

pharmachologic effect

Combined antihypertensive drug containing an angiotensin II receptor antagonist eprosartan and a diuretic hydrochlorothiazide.

Eprosartan is an antagonist of angiotensin II receptors, selectively acts on AT1 receptors located in the vessels, heart, kidneys and adrenal cortex, forms a strong bond with them with subsequent slow dissociation. Prevents the development or weakens the effects of angiotensin II, inhibits the activity of the RAAS. It has a vasodilating, hypotensive and diuretic effect. Reduces arterial vasoconstriction, OPSS, pressure in the pulmonary circulation, reabsorption of water and sodium in the proximal segment of the renal tubules, secretion of aldosterone. With prolonged use, it suppresses the proliferative effect of angiotensin II on vascular and myocardial smooth muscle cells. The antihypertensive effect after taking a single oral dose develops within 24 hours,and a stable therapeutic effect develops with regular ingestion after 2-3 weeks without affecting heart rate. Does not cause the development of orthostatic hypotension in response to the first dose of the drug.

Increases renal blood flow and glomerular filtration rate, reduces the excretion of albumin (nephroprotective effect), while maintaining renal self-regulation, regardless of the severity of renal failure. Does not affect lipid, carbohydrate and purine metabolism. On discontinuation of treatment, it does not cause withdrawal symptoms.

Less often than ACE inhibitors, it causes effects associated with the activity of bradykinin (including dry persistent cough).

Hydrochlorothiazide is a thiazide diuretic, the diuretic effect of which is associated with impaired reabsorption of sodium, chlorine, potassium, magnesium, water in the distal nephron; delays the excretion of calcium ions, uric acid. Has antihypertensive properties; the hypotensive effect develops due to the expansion of arterioles. Has practically no effect on the normal level of blood pressure.

The diuretic effect develops within about 2 hours after administration, the maximum effect is achieved in 3-6 hours and lasts for 6-12 hours. The antihypertensive effect is achieved within 3-4 days of treatment and lasts for 1 week after the end of the drug intake. With long-term treatment, a decrease in blood pressure is achieved using smaller doses than those required for a diuretic effect. A decrease in blood pressure is accompanied by a slight increase in the glomerular filtration rate, vascular resistance of the renal bed and renin activity in the blood plasma.

Hydrochlorothiazide in a single dose in high doses leads to a decrease in plasma volume, glomerular filtration rate, renal blood flow and mean blood pressure. With long-term administration in low doses, the blood plasma volume remains reduced, while the minute volume and glomerular filtration rate return to the initial level prior to the start of treatment. Mean blood pressure and systemic vascular resistance remain reduced. Thiazide diuretics can interfere with breast milk production.

Eprosartan + hydrochlorothiazide. In patients with elevated systolic blood pressure, eprosartan provides a statistically significant decrease. The addition of 12.5 mg hydrochlorothiazide to a single daily dose (600 mg or 1200 mg) of eprosartan provides an additional statistically significant decrease in systolic blood pressure compared to the daily intake of eprosartan alone. The combined use of eprosartan with hydrochlorothiazide reduces the loss of potassium associated with the diuretic effect of hydrochlorothiazide. The diuretic effect when using this combination develops within the first 2 hours, and reaches a maximum - 4 hours after ingestion. A stable antihypertensive effect usually develops after 2-3 weeks of treatment.

Indications of the active substances of TevetenЃ Plus

Arterial hypertension (if necessary, combined therapy with eprosartan and hydrochlorothiazide).

Dosage regimen

The method of application and dosage regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. It is necessary to strictly observe the compliance of the used dosage form of a particular drug with the indications for use and the dosage regimen. The oral dose for the fixed combination of eprosartan + hydrochlorothiazide is 600 mg / 12.5 mg 1 time / day.

Side effect

From the hematopoietic system: infrequently - leukopenia; very rarely - hemolytic anemia; frequency unknown - agranulocytosis, thrombocytopenia, aplastic anemia.

From the immune system: infrequently - hypersensitivity reactions; frequency unknown - anaphylactic reactions.

From the side of metabolism and nutrition: often - hyperglycemia; infrequently - hyperuricemia, exacerbation of the course of gout, hyponatremia, hypokalemia, hypochloremia, hypercholesterolemia; frequency unknown - hypercalcemia, hypomagnesemia, hypertriglyceridemia, anorexia.

From the side of the psyche: infrequently - depression, anxiety, insomnia, nervousness, libido disorders; frequency unknown - concern.

From the nervous system: very often - headache (11%), often - dizziness, paresthesia.

From the side of the organ of vision: the frequency is unknown - acute myopia, secondary angle-closure glaucoma.

On the part of the organ of hearing and balance: infrequently - vertigo.

From the side of the cardiovascular system: often - a marked decrease in blood pressure, orthostatic hypotension; frequency unknown - necrotizing angiitis.

From the respiratory system: often - rhinitis; rarely, respiratory distress syndrome (including pneumonitis and noncardiogenic pulmonary edema).

From the digestive system: often - nonspecific gastrointestinal disorders (nausea, vomiting, diarrhea); infrequently - constipation; rarely - pancreatitis.

Liver and biliary tract disorders: frequency unknown - jaundice, incl. intrahepatic cholestatic jaundice.

On the part of the skin and subcutaneous tissues: often - allergic skin reactions (skin rash, itching); infrequently - angioedema; frequency unknown - toxic epidermal necrolysis, photosensitivity reactions.

From the musculoskeletal system: infrequently - muscle spasms; frequency unknown - systemic lupus erythematosus.

From the urinary system: the frequency is unknown - interstitial nephritis, renal failure, impaired renal function in patients at risk (renal artery stenosis), glucosuria.

From the genital organs: infrequently - sexual dysfunction.

General disorders: often - asthenia; infrequently - hyperthermia.

Contraindications for use

Severe renal failure (CC <30 ml / min); severe liver failure (more than 9 points on the Child-Pugh scale); cholestasis and obstruction of the biliary tract; hemodynamically significant bilateral renal artery stenosis or severe arterial stenosis of a single functioning kidney; treatment-resistant hypokalemia or hypercalcemia; refractory hyponatremia; symptomatic hyperuricemia or gout; simultaneous use with aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (CC less than 60 ml / min); pregnancy, lactation (breastfeeding); age under 18; hypersensitivity to eprosartan, hydrochlorothiazide, and other sulfonamide derivatives.

With caution: severe and chronic heart failure (IV FC according to NYHA classification), bilateral stenosis of the renal arteries, stenosis of the artery of a single kidney, a decrease in BCC, a violation of the water and electrolyte balance of the blood (due to the intake of diuretics in high doses, repeated vomiting, prolonged diarrhea, salt-free diet), mild or moderate hepatic impairment (less than 9 points on the Child-Pugh scale without a history of cholestasis), diabetes mellitus, stenosis of the aortic and mitral valves, hypertrophic obstructive cardiomyopathy, primary hyperaldosteronism, coronary artery disease (limited experience), acute myopathy secondary angle-closure glaucoma, SLE.

Application during pregnancy and lactation

Use during pregnancy and lactation (breastfeeding) is contraindicated.

special instructions

In patients whose renal function depends on the activity of the RAAS (for example, in severe chronic heart failure of functional class IV according to the NYHA classification), oliguria and / or progressive azotemia may develop during treatment with ACE inhibitors, and, in rare cases, acute renal failure. These phenomena are most likely in patients taking diuretics at the same time. Due to the lack of experience in the use of angiotensin II receptor antagonists in patients with severe chronic heart failure IV FC according to the NYHA classification, renal dysfunction cannot be ruled out against the background of the use of a combination of eprosartan + hydrochlorothiazide due to inhibition of the RAAS activity. Due to the increased risk of severe arterial hypotension and renal failure in such patients,renal function should be closely monitored.

Before starting treatment with a combination of eprosartan + hydrochlorothiazide in patients with renal insufficiency and, periodically, during treatment, renal function, potassium and uric acid levels in the blood serum should be monitored. If during this period there is a deterioration in renal function, treatment with the combination should be discontinued.

In patients with impaired renal function, hydrochlorothiazide-associated azotemia may occur.

Eprosartan should be used with caution in the treatment of patients with mild to moderate hepatic impairment due to the limited clinical experience of using the drug in such patients.

Due to the possibility of intrahepatic cholestasis, hydrochlorothiazide should be used with caution in the treatment of mild to moderate hepatic impairment.

Changes in fluid and electrolyte balance can cause hepatic coma.

Hydrochlorothiazide is able to reduce glucose tolerance, which may require dose adjustment of hypoglycemic agents and insulin. Latent diabetes mellitus can manifest itself during treatment with this combination.

The use of hydrochlorothiazide can lead to a violation of the water-electrolyte balance of the blood (hypokalemia, hyponatremia, hypercalcemia, hypomagnesemia and hypochloremic alkalosis).

All patients receiving diuretics, including hydrochlorothiazide, should periodically monitor serum electrolytes.

With severe hyponatremia or a decrease in BCC (for example, during treatment with diuretics in high doses, repeated vomiting, prolonged diarrhea, salt-free and low-salt diet), taking this combination can cause a sharp decrease in blood pressure. Correction of hyponatremia and / or BCC is necessary and, if possible, the withdrawal of diuretics before starting treatment with this combination.

Hydrochlorothiazide, being a sulfonamide, can cause idiosyncrasy, expressed in acute transient myopia and an attack of acute angle-closure glaucoma. Symptoms, which include a sharp decrease in visual acuity or pain in the eye, usually develop within hours to several weeks after starting the drug. Lack of treatment for acute angle-closure glaucoma can lead to irreversible loss of vision. The primary treatment is to withdraw hydrochlorothiazide as quickly as possible. Urgent medical or surgical treatment may be required if intraocular pressure remains uncontrolled. Risk factors for the development of an attack of acute angle-closure glaucoma may be a history of allergic reactions to sulfonamide or penicillin.

In patients with primary hyperaldosteronism, the use of antihypertensive drugs that inhibit the RAAS is usually ineffective. In this regard, the use of this combination in this category of patients is not recommended.

Hypersensitivity reactions to hydrochlorothiazide are most likely in patients with a history of allergies, incl. with hypersensitivity to sulfonamide derivatives.

Hydrochlorothiazide can be positive when tested for drug control.

The combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with the separate use of drugs acting on the RAAS. In this regard, the double blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended. If double blockade is necessary, then it should be carried out strictly under the supervision of a specialist and with constant monitoring of renal function, electrolyte content and blood pressure.

The combined use of ACE inhibitors and angiotensin II receptor antagonists is not recommended for patients with diabetic nephropathy.

Influence on the ability to drive vehicles and mechanisms

During the period of treatment with this combination, the patient should be careful when driving and engaging in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions, due to the possibility of dizziness and weakness.

Drug interactions

The combined use of ACE inhibitors and angiotensin II receptor antagonists in patients with diabetic nephropathy is not recommended.

The combined use of aliskiren with an ACE inhibitor or an angiotensin II receptor blocker is contraindicated in patients with type 2 diabetes mellitus or renal failure (CC less than 60 ml / min).

Eprosartan + hydrochlorothiazide

A reversible increase in the serum lithium content and an increase in toxicity were noted with the combined use of lithium preparations with ACE inhibitors and, in rare cases, with angiotensin II receptor antagonists. In addition, thiazides reduce the renal clearance of lithium and therefore may increase the risk of its toxic effects. In this regard, this combination with lithium preparations is not recommended. If combination therapy is necessary, regular monitoring of the concentration of lithium in the blood serum should be carried out.

Baclofen - Possible increased antihypertensive action.

The combined use of angiotensin II receptor antagonists and NSAIDs may increase the risk of developing renal dysfunction, including the possibility of developing acute renal failure and an increase in serum potassium, especially in patients with pre-existing reduced renal function. Such combinations should be used with caution, especially in elderly patients.

Amifostine - an increase in the antihypertensive effect is possible.

Other antihypertensive drugs - the antihypertensive effect of this combination may be enhanced when used simultaneously with other antihypertensive drugs.

Ethanol, barbiturates, anesthetics, or antidepressants - Orthostatic hypotension may occur.

Eprosartan

Clinical study data have shown that double blockade of the RAAS through the combined use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is associated with an increased incidence of adverse events such as arterial hypotension, hyperkalemia and renal dysfunction (including acute renal failure) compared with the use of drugs alone. acting on the RAAS.

Hydrochlorothiazide

The hypokalemic effect of hydrochlorothiazide may be enhanced with the simultaneous administration of other drugs leading to the excretion of potassium and hypokalemia (for example, other potassium-sparing diuretics, laxatives, corticosteroids, glycyrrhizic acid (contained in licorice root), adrenocorticotropic hormone (for v / ), carbenoxolone, penicillin G (sodium salt) or salicylic acid derivatives). Therefore, the use of this combination is not recommended.

Thiazide diuretics can increase serum calcium due to a decrease in its excretion. If it is necessary to use calcium preparations or calcium-saving drugs (for example, vitamin D), it is necessary to control the calcium content in the blood serum and adjust its dose accordingly.

The absorption of hydrochlorothiazide decreases with the simultaneous use of anion exchange resins, incl. cholestyramine or colestipol.

Cardiac glycosides - hypokalemia or hypomagnesemia caused by thiazide diuretics contributes to the development of arrhythmias.

Medicines whose effects are affected by hypokalemia - cardiac glycosides and antiarrhythmic drugs, as well as drugs that can cause polymorphic ventricular tachycardia of the 'pirouette' type (ventricular tachycardia) - class IA antiarrhythmic drugs (for example, quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (eg, amiodarone, dofetilide, ibutilide) and sotalol; some antipsychotics (for example, thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol); other drugs (eg, bepridil, cisapride, diphemanil, IV erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, IV vincamine).

Non-depolarizing muscle relaxants (eg tubocurarine) - hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants.