Telsartan AM Tablets 5 mg+80 mg, 28 pcs.

Pharmacodynamics

Combination drug, contains two hypotensive agents with complementary action, which allows to control blood pressure (BP) in patients with arterial (essential) hypertension: The angiotensin II receptor antagonist (ARA II) – telmisartan, and the “slow” calcium channel blocker (CMCB), a dihydropyridine derivative – amlodipine.
The combination of these substances has an additive antihypertensive effect, reducing BP to a greater extent than each individual component. The combination of amlodipine and telmisartan, taken once daily, leads to an effective and sustained BP reduction within 24 hours.

Amlodipine

Amlodipine is a dihydropyridine derivative and belongs to the BMCC class. It inhibits transmembrane entry of calcium ions into cardiomyocytes and vascular smooth muscle cells. The mechanism of antihypertensive action of amlodipine is associated with direct relaxant effect on vascular smooth muscle cells, which leads to reduction of peripheral vascular resistance and BP.

In patients with arterial hypertension once daily use of amlodipine provides clinically significant BP reduction for 24 hours.
Orthostatic arterial hypotension is not typical during amlodipine use due to slow onset of drug action.

In patients with arterial hypertension and normal renal function, amlodipine at therapeutic doses resulted in decreased renal vascular resistance, increased glomerular filtration rate and effective renal blood flow, without changes in filtration or proteinuria.

Amlodipine does not lead to any metabolic adverse effects or changes in plasma lipid content and is therefore suitable for use in patients with bronchial asthma, diabetes and gout. Use of amlodipine in patients with heart failure is not accompanied by negative inotropic effect (it does not reduce exercise tolerance, left ventricular ejection fraction).

Telmisartan

Telmisartan is a specific ARA II (type AT1) effective when taken orally. It has high affinity for 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 agonist effect on this receptor.

Telmisartan binds only to the AT1-receptor subtype of angiotensin II. The binding is long lasting. It has no affinity to other receptors, including AT2-receptor. Reduces aldosterone concentration in blood, does not inhibit plasma renin activity and does not block ion channels. Telmisartan does not inhibit angiotensin-converting enzyme (ACE) or kininase II, an enzyme that also degrades bradykinin. Therefore, an increase in bradykinin-induced adverse reactions is not expected.

At a dose of 80 mg, telmisartan completely blocks the hypertensive effects of angiotensin II. The onset of antihypertensive action is observed within 3 hours after the first telmisartan administration. The action of the drug persists for 24 hours and remains significant up to 48 hours. A pronounced antihypertensive effect usually develops in 4-8 weeks after regular use.
Telmisartan reduces systolic and diastolic BP in patients with arterial hypertension without affecting heart rate (HR).

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

Pharmacokinetics

The rate and degree of absorption of the combined drug amlodipine and telmisartan are equivalent to the bioavailability of telmisartan and amlodipine when used as separate tablets.

Amlodipine

absorption

After oral administration of amlodipine at therapeutic doses, Cmax in plasma is reached after 6-12 h. Absolute bioavailability ranges from 64% to 80%. Food intake has no effect on the bioavailability of amlodipine.

Distribution

Distribution volume of amlodipine is approximately 21 l/kg. In vitro studies have shown that in patients with arterial hypertension approximately 97.5% of circulating amlodipine is bound to plasma proteins.

Metabolism

Amlodipine is largely (approximately 90%) metabolized in the liver to form inactive metabolites.

Excretion

Excretion of amlodipine from blood plasma is biphasic. The elimination half-life (T1/2) is approximately 30-50 hours. Stable plasma concentrations are achieved after continuous drug administration for 7-8 days. Amlodipine is excreted by kidneys both as unchanged (10%) and as metabolites (60%).

Telmisartan

absorption
When taken orally, it is rapidly absorbed from the gastrointestinal tract (GIT). Bioavailability is 50%. Administration with food decreases area under pharmacokinetic curve “concentration-time” (AUC) from 6% (at a dose of 40 mg) to 19% (at a dose of 160 mg). Three hours after oral administration, plasma concentrations level off regardless of ingestion.

Distribution

Binding to plasma proteins is 99.5%, mainly to albumin and alpha-1 glycoprotein. Mean apparent volume of distribution in equilibrium is 500 l.

Metabolism

Telmisartan is metabolized by conjugation with glucuronic acid. Metabolites are pharmacologically inactive.

Elimation

T1/2 is greater than 20 h. The maximum plasma concentration (Cmax) and, to a lesser extent, AUC increase disproportionately to the dose. There is no evidence of clinically significant cumulation of telmisartan. It is excreted unchanged in the intestine, renal excretion is less than 2%. Total plasma clearance is high (900 ml/min) compared to hepatic blood flow (approximately 1500 ml/min).

Special patient groups

There is a difference in plasma concentrations of telmisartan in men and women. Cmax and AUC were approximately 3 and 2 times higher in women compared to men, respectively, with no significant effect on efficacy.

Elderly

Telmisartan pharmacokinetics in elderly and younger patients do not differ. Amlodipine clearance tends to decrease in elderly patients, resulting in increased AUC and T1/2.

Renal dysfunction

In patients with renal impairment, telmisartan T1/2 is not altered and lower plasma telmisartan concentrations are observed. Amlodipine pharmacokinetics in patients with impaired renal function is not significantly altered. Amlodipine and telmisartan are not eliminated by hemodialysis.

Hepatic impairment

Pharmacokinetic studies conducted in patients with hepatic impairment have shown that the absolute bioavailability of telmisartan is increased to almost 100%. T1/2 in patients with hepatic impairment does not change. In patients with hepatic impairment the clearance of amlodipine was decreased, resulting in an increase in AUC of approximately 40-60%.