Edarbi (azilsartan medoxomil) tablets 80 mg. №28

Description

Edarbi 80 mg Composition
active substance: azilsartan medoxomil;

1 40 mg Edarbitm tablet contains 42.68 mg of azilsartan medoxomil potassium, which is equivalent to 40 mg of azilsartan medoxomil;

Edarbi excipients: mannitol (E 421) fumaric acid; sodium hydroxide hydroxypropyl cellulose; croscarmellose sodium; microcrystalline cellulose, magnesium stearate, purified water.

Edarbi 80 mg Dosage form
Pills.

Edarbi 80 mg Basic physical and chemical properties:

40 mg tablets: white or off-white tablets, engraved with “ASL” on one side and “40” on the other;

Pharmacotherapeutic group
Drugs affecting the renin-angiotensin system, angiotensin II receptor antagonists, are simple. ATX code С09С А09.

Pharmacodynamics
Azilsartan medoxomil is an active precursor of a medicinal substance intended for oral administration. The precursor is rapidly converted into an active molecule of azilsartan, which, by blocking the binding of angiotensin II to AT1 receptors in many tissues, acts as a selective antagonist of the effects of angiotensin II (see section “Pharmacokinetics”).

Angiotensin II is the main blocking agent of the renin-angiotensin system; the effects of angiotensin II include vasoconstriction, stimulation of the synthesis and release of aldosterone, stimulation of the heart, and stimulation of sodium reabsorption in the kidneys.

Blocking of AT1 receptors leads to suppression of the negative feedback effect of angiotensin II on renin secretion, but an increase in renin activity in the blood plasma and an increase in the level of angiotensin II in the systemic circulation, which arise as a result of blocking the receptors, do not prevent the development of the antihypertensive effect of azilsartan.

Edarbi 80 mg Pharmacokinetics
After oral administration, azilsartan medoxomil is rapidly hydrolyzed in the digestive tract and / or during absorption of the active substance (azilsartan).

In vitro studies show that the enzyme carboxymethylene butenolidase is involved in the hydrolysis processes in the intestine and liver. Plasma esterases are also involved in the hydrolysis of azilsartan medoxomil to azilsartan.

Absorption. Based on plasma concentrations of azilsartan, the calculated absolute oral bioavailability of azilsartan medoxomil is approximately 60%. After taking azilsartan medoxomil, the maximum concentration of azilsartan in plasma (Cmax) is reached after 1.5-3 hours (see section “Dosage and Administration”). Food does not affect the bioavailability of azilsartan.

Distribution. The volume of distribution of azilsartan is approximately 16 liters. Azilsartan intensively (> 99%) binds to plasma proteins, mainly albumin. Plasma protein binding does not change over a range of concentrations significantly exceeding those achieved when used in recommended doses.

Metabolism. The metabolic degradation of azilsartan leads to the formation of two main metabolites. The main metabolite in plasma is formed by o-dealkylation, it is designated as metabolite M-II. A minor metabolite that is formed as a result of decarboxylation is referred to as the MI metabolite. The levels of systemic exposure of the major and minor metabolites in humans were approximately 50% and less than 1% of the exposure level of azilsartan, respectively. M-I and M-II have no additional effect on the pharmacological action of azilsartan medoxomil. Azilsartan metabolism is mainly due to the CYP2C9 enzyme.

Excretion. After taking azilsartan medoxomil, labeled with a radioactive isotope 14C, approximately 55% of the radioactivity was excreted from the body in the feces and approximately 42% in the urine. Approximately 15% of the drug was excreted in the urine in unchanged form of azilsartan. The half-life of azilsartan from blood plasma is about 11 hours, and the renal clearance is about 2.3 ml / min. The equilibrium concentration of azilsartan develops within 5 days and during repeated administration of the drug once a day, accumulation in the plasma does not occur.

Linearity / non-linearity. In the dose range of azilsartan medoxomil from 20 to 320 mg after taking single or multiple doses, the dependence of the exposure of azilsartan on the dose taken was established.

Characteristics in special patient subgroups.

Children. The pharmacokinetics of azilsartan in children (under the age of 18) have not been studied.

Elderly patients. There were no significant differences in the pharmacokinetics of azilsartan in young people (18-45 years old) and elderly patients (65-85 years old).

Impaired renal function. In patients with mild, moderate and severe renal impairment, the total azilsartan exposure (AUC) increased by 30%, 25% and 95%, respectively. In patients with end-stage renal failure on dialysis, no increase in exposure was observed (+ 5%). At the same time, there is no clinical experience of using the drug in patients with severe renal impairment or end-stage renal failure. Azilsartan is not excreted from the system.

Liver dysfunction. Treatment with Edarbi in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) liver dysfunction for no more than 5 days led to a slight increase in azilsartan exposure (an increase in AUC of 1.3-1.6 times). The use of Edarbi for the treatment of patients with severely impaired liver function has not been studied.

Floor. There were no significant differences in the pharmacokinetics of azilsartan in men and women. There is no need for dose adjustment depending on the patient’s gender.

Racial affiliation. There were no significant differences in the pharmacokinetics of azilsartan in white and black patients. There is no need for dose adjustment depending on the race of the patient.

Indications
Treatment of essential hypertension in adults.

Contraindications
Hypersensitivity to the active substance or other components of the drug.
Pregnant women or women planning to become pregnant (see section “Use during pregnancy or lactation”).
Patients with diabetes mellitus or impaired renal function (GFR <60 ml / min / 1.73 m2) should not use Edarbi with drugs containing aliskiren.
Interaction with other medicinal products