Telsartan N, tablets 12.5 mg+80 mg 28 pcs.

Pharmacodynamics

Telsartan® H is a combination of telmisartan (angiotensin II receptor antagonist) and hydrochlorothiazide, a thiazide diuretic. Simultaneous use of these components leads to a greater antihypertensive effect than the use of each of them separately.

Administration of Telsartan® H once daily results in a significant gradual decrease in blood pressure (BP).

Telmisartan

Telmisartan is a specific angiotensin receptor antagonist (ARA) II, effective when taken orally. It has high affinity to the AT1 subtype of angiotensin II receptors, through which the action of angiotensin II is realized.

It displaces angiotensin II from binding to the receptor without exhibiting agonist properties against this receptor. Telmisartan binds only to the AT1 subtype of the 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 as well as the effect of their possible overstimulation by angiotensin II, the concentration of which increases with telmisartan administration, has not been studied.

Telmisartan reduces plasma aldosterone concentration, does not inhibit plasma renin and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (kininase II), which also catalyzes bradykinin degradation. 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 effects of angiotensin II. The onset of antihypertensive action is observed within 3 hours after the first oral administration of telmisartan.

The action of the drug lasts for 24 hours and remains significant up to 48 hours. Expressed antihypertensive effect usually develops 4 weeks after regular drug intake.

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

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

The study with telmisartan evaluated cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke or hospitalization due to chronic heart failure.

It has been shown to reduce cardiovascular morbidity and mortality in patients at high cardiovascular risk (with coronary artery disease, stroke, peripheral artery disease or diabetes with concomitant target organ damage such as retinopathy, left ventricular hypertrophy, macro- or microalbuminuria in the history) over 55 years of age.

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 a decrease in circulating blood volume (RBC), increased plasma renin activity, increased secretion of aldosterone with a subsequent increase in urinary potassium and hydrocarbonates and, consequently, a decrease in plasma potassium.

In concomitant administration with telmisartan there is a tendency to stop potassium loss caused by these diuretics, presumably due to blockade of renin-angiotensin-aldosterone system (RAAS).

After oral administration 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 hydrochlorthiazide reduces the risk of cardiovascular complications and mortality from them.

Maximum antihypertensive effect of Telsartan® N is usually achieved 4 weeks after the start of treatment.

Pharmacokinetics

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

Telmisartan

When taken orally, it is rapidly absorbed from the gastrointestinal tract.

Bioavailability is approximately 50%. Concentration peaks after about 0.5-1.5 hours. Administration with food decreases area under pharmacokinetic curve “concentration-time” (AUC) from 6% (with a dose of 40 mg) to 19% (with a dose of 160 mg). In 3 hours after oral administration, plasma concentrations level off regardless of food intake.

There is a difference in plasma concentrations of telmisartan in men and women. Maximum plasma concentrations (Cmax) are approximately 3 times and AUC approximately 2 times higher in women compared to men with no significant effect on efficacy. Nevertheless, increase of hypotensive effect is not observed in women.

The binding to plasma proteins is significant (more than 99.5%), mainly to albumin and alpha1-acid glycoprotein. The volume of distribution is approximately 500 liters.

Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive. The elimination half-life (T1/2) is more than 20 hours. It is excreted unchanged in the intestine, renal excretion is less than 2%. Total plasma clearance is high (about 900 ml/min).

Elderly patients

Pharmacokinetics of telmisartan in elderly patients does not differ from younger patients. No dose adjustment is required.

Patients with renal impairment

No change in telmisartan dose is required in patients with renal impairment, including patients on hemodialysis. Telmisartan is not eliminated by hemodialysis.

Patients with hepatic impairment

Pharmacokinetic studies in patients with hepatic impairment have shown increased absolute bioavailability to nearly 100%. In patients with hepatic insufficiency the T1/2 is not changed (see section “Dosage and administration”).

Hydrochlorothiazide

After oral administration of Telsartan® H, the maximum plasma concentrations of hydrochlorothiazide are reached within 1-3 hours. Absolute bioavailability is about 60% (based on total renal excretion). 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. T1/2 of hydrochlorothiazide is 10-15 hours.

There is a difference in plasma concentrations in men and women. In women telmisartan plasma concentrations are 2-3 times higher than in men; also in women there is a tendency for clinically insignificant increase in plasma concentrations of hydrochlorothiazide.

Patients with renal impairment

In patients with impaired renal function the excretion rate of hydrochlorothiazide is reduced.
Studies conducted with patients with a creatinine clearance of 90 ml/min have shown that the T1/2 of hydrochlorothiazide is increased. In patients with decreased renal function, the T1/2 is approximately 34 hours.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

Special Instructions

Contraindications

Side effects

Overdose

Pregnancy use

Similarities