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 hypotensive agents).

Active ingredient

Composition

1 film-coated tablet contains:

How to take, the dosage

Teveten Plus is taken orally, 1 tablet a day, in the morning, regardless of meals.

Tevetin Plus does not require dosage adjustment in elderly patients, patients with mild to moderate hepatic impairment, and patients with impaired renal function (creatinine Cl over 30 ml/min).

Interaction

The hypotensive effect may increase with concomitant use with other antihypertensive agents.

When used concomitantly with oral hypoglycemic agents, their dose should be adjusted, because hydrochlorothiazide may decrease glucose tolerance.

In concomitant use with lithium preparations, there may be a reversible increase in plasma lithium concentration and an increased risk of its toxic effects (close monitoring of lithium concentration in patients receiving this combination is necessary).

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

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

Hydrochlorothiazide increases the risk of hypokalemia when prescribed with drugs that cause potassium loss, such as diuretics that have a potassiuretic effect, laxatives, GCS, and ACTH.

Hydrochlorothiazide may increase the effect of nondepolarizing myorelaxants (e.g., tubocurarine). Absorption of hydrochlorothiazide is reduced by co-administration of anion-exchange resins (e.g., colestyramine or colestipol).

Special Instructions

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

During treatment of hypertension, caution should be exercised when driving motor vehicles and engaging in potentially hazardous activities requiring increased concentration and rapid psychomotor reactions due to the possibility of dizziness and weakness.

Contraindications

With caution
Severe chronic heart failure (functional class IV according to NYHA classification); Bilateral stenosis of the renal arteries, stenosis of the artery of the only kidney, decreased circulating blood volume (CBC), disrupted electrolyte-water balance of blood (due to large doses of diuretics, repeated vomiting, prolonged diarrhea, salt-free diet), moderate or severe liver function disorder, diabetes.

Teuven® Plus has no clinical experience in the treatment of patients with severe hepatic impairment.

Side effects

The overall incidence of adverse events reported in patients taking eprosartan is comparable to that reported with placebo. These effects were generally mild and of short duration, so that only 4.1% of patients taking eprosartan in placebo-controlled trials (6.5% in the placebo group) needed to discontinue treatment.

CNS disorders: rarely – headache, dizziness, asthenia.

Cardiovascular system disorders: very rarely – decrease of BP, including postural hypotension.

Skin and subcutaneous fatty tissue: rare – skin reactions (rash, itching and urticaria); very rare – facial edema, angioedema.

Others: rare – cough.

Overdose

There are currently no data on overdose of Teveten Plus. Among the symptoms we can assume the following: excessive BP decrease, dehydration and electrolyte imbalance (hypokalemia, hypochloremia, hyponatremia) manifested by nausea and somnolence.

Treatment depending on the time since the meal, measures taken should include stimulation of vomiting, gastric lavage and/or taking activated charcoal.

If there is a sharp decrease in BP, it is recommended that the patient be placed on his back, his legs elevated, and plasma replacement fluids administered if necessary. With dehydration and impaired I-salt balance, symptomatic and supportive therapy is recommended. Hemodialysis is not effective.