Teveten Plus, 12.5mg+600mg 28 pcs.

Eprosartan
Angiotensin II receptor antagonist, acts selectively on ATI receptors located in blood vessels, heart, kidneys and adrenal cortex, forms a strong bond with them with subsequent slow dissociation.

Prevents or attenuates the effects of angiotensin II, inhibits the activity of the renin-angiotensin-aldosterone system (RAAS). It has vasodilatory, hypotensive and mediated diuretic effects.

It decreases arterial vasoconstriction, total peripheral vascular resistance (TPRR), small circle pressure, water and sodium reabsorption in the proximal segment of the renal tubules, aldosterone secretion. With prolonged use it suppresses proliferative effect of angiotensin II on vascular smooth muscle cells and myocardium.

Hypotensive effect after a single oral dose develops within 24 hours, and a stable therapeutic effect develops with regular oral administration – after 2-3 weeks without affecting heart rate (HR). Does not cause development of orthostatic hypotension in response to the first dose of the drug.

It increases renal blood flow and glomerular filtration rate, decreases excretion of albumin (nephroprotective effect), while maintaining renal self-regulation regardless of the severity of renal failure. It has no effect on lipid, carbohydrate and purine metabolism. When discontinuing treatment it does not cause “withdrawal” syndrome.

Less often than angiotensin-converting enzyme (ACE) inhibitors it causes the occurrence of effects associated with bradykinin activity (including dry persistent cough).

Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect electrolyte reabsorption mechanisms in the renal tubule, increasing fluid, sodium and chlorine excretion.

With the diuretic action of hydrochlorothiazide, plasma volume decreases, plasma renin activity increases and aldosterone secretion increases, which causes increased renal excretion of potassium and hydrocarbonates and decreased serum potassium content. The mechanism of hypotensive action of hydrochlorothiazide is a combined diuretic and vasodilator effect.

Teveten® plus
In patients with elevated systolic blood pressure (BP), eprosartan provides a statistically significant reduction in BP. Adding 12.5 mg of hydrochlorothiazide to a single daily dose (600 or 1200 mg) of eprosartan provides an additional statistically significant reduction in systolic BP compared to daily administration of eprosartan alone.

The combined administration of eprosartan with hydrochlorothiazide reduces potassium loss associated with the diuretic effect of hydrochlorothiazide. Diuretic effect of Teveten Plus develops within the first 2 hours, and reaches a maximum of 4 hours after oral administration.

Stable hypotensive effect usually develops after 2-3 weeks of treatment.

Pharmacokinetics

Eprosartan
With oral administration the absolute bioavailability is about 13%. Maximum concentration (Cmax) in blood plasma is determined after 1-2 hours. The binding to plasma proteins is high (98%) and remains constant after reaching therapeutic plasma concentrations. The degree of binding to plasma proteins does not depend on sex, age, liver function of patients and does not change in moderate or mildly expressed renal insufficiency, but may decrease in severe renal insufficiency.

It practically does not cumulate.

The volume of distribution is 13 liters and total clearance is 130 ml/min. When administered orally it is eliminated mainly unchanged – through the intestine (90%), by the kidneys (7%). A small part (less than 2%) is excreted by the kidneys as glucuronides. In elderly patients the values of Cmax and area under the curve “concentration-time” (AUC) increase, on average, by a factor of 2, which, however, does not require dose adjustment, because it has no clinical significance.

In cases of hepatic impairment, the AUC values increase by about 40% on average, which does not require dose adjustment and has no clinical significance.

In patients with moderate chronic renal insufficiency (CKD) (creatinine clearance (CK) from 30 to 59 ml/min) AUC and Cmax are 30% higher, and in patients with severe CKD (CK from 5 to 29 ml/min) – 50% higher compared to healthy volunteers. The pharmacokinetics of eprosartan do not differ in male and female patients.

Hydrochlorothiazide
Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. At least 61% of the oral dose is excreted unchanged within 24 hours. It does not penetrate the blood-brain barrier, but penetrates the placental barrier and is excreted with breast milk.

Teveten Plus
Simultaneous administration of eprosartan and hydrochlorothiazide has no clinically significant effect on the pharmacokinetics of either component. Food intake has no effect on the bioavailability of eprosartan and hydrochlorothiazide, but delays their absorption. Maximum plasma concentrations are reached 4 hours after administration of eprosartan and 3 hours after oral hydrochlorothiazide.

Indications

Arterial hypertension (in monotherapy or in combination with other antihypertensive drugs).

Pharmacological effect

Eprosartan
Angiotensin II receptor antagonist, selectively acts on ATI receptors located in blood vessels, heart, kidneys and adrenal cortex, forms a strong connection with them followed by slow dissociation.

Prevents the development or weakens the effects of angiotensin II, inhibits the activity of the renin-angiotensin-aldosterone system (RAAS). It has a vasodilating, hypotensive and indirect diuretic effect.

Reduces arterial vasoconstriction, total peripheral vascular resistance (TPVR), pressure in the pulmonary circulation, reabsorption of water and sodium in the proximal segment of the renal tubules, and aldosterone secretion. With long-term use, it suppresses the proliferative effect of angiotensin II on vascular and myocardial smooth muscle cells.

The hypotensive effect after taking a single dose orally develops within 24 hours, and a stable therapeutic effect develops with regular oral administration – after 2-3 weeks without affecting the heart rate (HR). 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. When stopping treatment, it does not cause withdrawal syndrome.

Less common than angiotensin-converting enzyme (ACE) inhibitors, it causes effects associated with bradykinin activity (including dry persistent cough).

Hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the mechanisms of electrolyte reabsorption in the renal tubule, increasing the volume of fluid, sodium and chlorine excreted.

Due to the diuretic effect of hydrochlorothiazide, the volume of blood plasma decreases, the activity of renin in the blood plasma increases, and the secretion of aldosterone increases, which causes increased excretion of potassium and bicarbonates by the kidneys and a decrease in the potassium content in the blood serum. The mechanism of the hypotensive effect of hydrochlorothiazide is a combined diuretic and vasodilating effect.

Teveten® plus
In patients with elevated systolic blood pressure (BP), eprosartan provides a statistically significant reduction in blood pressure. The addition of 12.5 mg hydrochlorothiazide to a single daily dose (600 or 1200 mg) of eprosartan provides an additional statistically significant reduction in systolic blood pressure compared to daily administration 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 of Teveten Plus develops during the first 2 hours and reaches its maximum 4 hours after oral administration.

A stable hypotensive effect usually develops after 2-3 weeks of treatment.

Pharmacokinetics

Eprosartan
When taken orally, the absolute bioavailability is about 13%. The maximum concentration (Cmax) in blood plasma is determined after 1-2 hours. The binding to plasma proteins is high (98%) and remains constant after reaching a therapeutic concentration in the blood plasma. The degree of binding to plasma proteins does not depend on the gender, age, or liver function of patients and does not change with moderate or mild renal failure, but may decrease with severe renal failure.

Practically does not accumulate.

The volume of distribution is 13 l, the total clearance is 130 ml/min. When taken orally, it is excreted mainly unchanged – through the intestines (90%), by the kidneys – (7%). A small part (less than 2%) is excreted by the kidneys in the form of glucuronides. In elderly patients, the values ​​of Cmax and area under the concentration-time curve (AUC) increase, on average, 2 times, which, however, does not require dose adjustment, since it has no clinical significance.

In case of liver failure, AUC values ​​increase, on average, by approximately 40%, which does not require dose adjustment and has no clinical significance.

In patients with moderate chronic renal failure (CRF) (creatinine clearance (CR) from 30 to 59 ml/min.), AUC and Cmax are 30% higher, and with severe chronic renal failure (CrCl from 5 to 29 ml/min.) – 50% higher compared to healthy volunteers. The pharmacokinetics of eprosartan do not differ between male and female patients.

Hydrochlorothiazide
Hydrochlorothiazide is not metabolized and is rapidly excreted by the kidneys. At least 61% of the dose taken orally is excreted unchanged within 24 hours. Does not penetrate the blood-brain barrier, but penetrates the placental barrier and is excreted in breast milk.

Teveten plus
Concomitant use of eprosartan and hydrochlorothiazide does not have a clinically significant effect on the pharmacokinetics of both components. Food intake does not affect the bioavailability of eprosartan and hydrochlorothiazide, but delays their absorption. Maximum plasma concentrations are achieved 4 hours after taking eprosartan and 3 hours after taking hydrochlorothiazide orally.

Special instructions

Based on its pharmacodynamic properties, Teveten Plus should not affect the ability to drive a car or use machines and mechanisms.

During the treatment of hypertension, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions, due to the fact that dizziness and weakness may occur.

Active ingredient

Hydrochlorothiazide, Eprosartan

Composition

1 film-coated tablet contains:

Active substances:
eprosartan mesylate – 735.8 mg, which corresponds to 600 mg of eprosartan, hydrochlorothiazide – 12.5 mg.
Excipients:
microcrystalline cellulose – 43.3 mg,
lactose monohydrate – 43.3 mg,
pregelatinized corn starch – 43.3 mg,
crospovidone – 38.5 mg,
magnesium stearate – 7.2 mg,
purified water – 50.9 mg.
Shell:
Opadry II Butterscotch 85F27320 – 39 mg (polyvinyl alcohol – 15.60 mg, macrogol 3350 – 7.88 mg, talc – 5.77 mg, titanium dioxide (E171) – 9.41 mg, iron oxide yellow (E172) – 0.33 mg, iron oxide black (E172) – 0.004 mg).

Contraindications

Hypersensitivity to eprosartan, hydrochlorothiazide and other sulfonamide derivatives and other components of the drug.
Pregnancy and lactation period.
Severe renal failure (creatinine clearance less than 30 ml/min).
Age up to 18 years (efficacy and safety have not been established).
Hemodynamically significant bilateral renal artery stenosis and stenosis of the artery of a single kidney.
Rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome (the drug contains lactose).

With caution
Severe chronic heart failure (IV functional class according to the NYHA classification); bilateral renal artery stenosis, stenosis of the artery of a single kidney, decreased circulating blood volume (CBV), impaired water-electrolyte balance in the blood (due to taking large doses of diuretics, repeated vomiting, prolonged diarrhea, salt-free diet), moderate or severe impaired liver function, diabetes mellitus.

There is no clinical experience with the use of Teveten® plus in the treatment of patients with severe liver dysfunction.

Side Effects

The overall incidence of adverse events reported in patients taking eprosartan is comparable to that observed when taking placebo. These effects were generally mild and short-lived, such that treatment discontinuation was required in only 4.1% of patients treated with eprosartan in placebo-controlled clinical trials (6.5% in the placebo group).

From the side of the central nervous system: rarely – headache, dizziness, asthenia.

From the cardiovascular system: very rarely – decreased blood pressure, incl. postural hypotension.

From the skin and subcutaneous fat: rarely – skin reactions (rash, itching and urticaria); very rarely – facial swelling, angioedema.

Other: rarely – cough.

Interaction

The hypotensive effect may be enhanced when used simultaneously with other antihypertensive drugs.

When used together with oral hypoglycemic agents, it is necessary to adjust their dose, because hydrochlorothiazide may decrease glucose tolerance.

When used simultaneously with lithium preparations, a reversible increase in the concentration of lithium in the blood plasma and an increase in the risk of its toxic effects is possible (careful monitoring of lithium concentrations in patients receiving this combination is necessary).

NSAIDs may reduce the diuretic and hypotensive effect of Teveten Plus.

By reducing potassium levels, hydrochlorothiazide may enhance the effect of cardiac glycosides and some antiarrhythmic drugs.

Hydrochlorothiazide increases the risk of hypokalemia when prescribed together with drugs that cause the body to lose potassium, for example, diuretics with a kaliuretic effect, laxatives, corticosteroids and ACTH.

Hydrochlorothiazide may enhance the effect of non-depolarizing muscle relaxants (for example, tubocurarine). The absorption of hydrochlorothiazide is reduced by co-administration of anion exchange resins (for example, cholestyramine or colestipol).

Overdose

There is currently no data on overdose of Teveten Plus. Among the symptoms, it is possible to assume the following: excessive decrease in blood pressure, dehydration and electrolyte imbalance (hypokalemia, hypochloremia, hyponatremia), manifested in the form of nausea and drowsiness.

Treatment depending on the time elapsed after ingestion, measures taken should include induction of vomiting, gastric lavage and/or administration of activated charcoal.

If there is a sharp decrease in blood pressure, it is recommended to place the patient on his back, raise his legs, and, if necessary, administer plasma-substituting fluids. In case of dehydration and disturbance of the water-salt balance, symptomatic and supportive therapy is recommended. Hemodialysis is not effective.

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Shelf life

3 years

Manufacturer

Mylan Laboratories SAS, France