Edarbi pills 80mg, 28pcs

Composition

of 1 tab. :

– azilsartan medoxomil 40 mg or 80 mg

Auxiliary substances:

Ingredients: mannitol,

fumaric acid,

sodium hydroxide,

hydroxypropylcellulose,

sodium croscarmellose,

microcrystalline cellulose,

magnesium stearate.

Pharmacological action

Angiotensin II receptor antagonist. Azilsartan medoxomil is an oral active prodrug that is rapidly converted to active azilsartan by blocking its binding to AT1 receptors in various tissues. Angiotensin II is the main pressor substance of the renin-angiotensin system with effects including vasoconstriction, stimulation of aldosterone synthesis and release, stimulation of cardiac activity and renal sodium reabsorption.

Blockade of AT1 receptors inhibits the reverse suppressive effect of angiotensin II on renin secretion, but the subsequent increase in the activity of circulating plasma renin and angiotensin II concentrations does not overlap the antihypertensive effect of azilsartan.

When using Edarbi™ in the treatment of arterial hypertension, the typical dynamics of blood pressure is as follows: the average systolic blood pressure reduced by 12.2 mm Hg. St. when taking 20 mg,13.4–13.5 mm Hg. St. when receiving 40 mg,14.5-14.6 mm Hg. St. when receiving 80 mg; and office systolic blood pressure reduced by 14.3 mm Hg. St. when taking 20 mg,14.5-16.4 mm Hg. St. when receiving 40 mg,16.7-17.6 mm Hg. St. when receiving 80 mg.

The antihypertensive effect of Edarbi™ is maintained for 24 hours after use.

After discontinuation of therapy, rebound hypertension is not observed.

Concomitant use of Edarbi 40 and 80 mg with calcium channel blockers (amlodipine) or thiazide diuretics (chlortalidone) resulted in an additional reduction in blood pressure compared to other antihypertensive agents as monotherapy. Dose-dependent side effects, including dizziness, hypotension, and increased serum creatinine concentrations, were more common when co-administered with diuretics compared to Edarbi™ as monotherapy, and hypokalemia was less common compared to diuretic monotherapy.

Effect on cardiac repolarization:

When taking Edarbi™ at a dose of up to 320 mg / day. There were no signs of prolongation of QT/QTc intervals.

Pharmacokinetics:

 After oral use of azilsartan, medoxomil is rapidly hydrolyzed to active azilsartan in the gastrointestinal tract and/or during absorption. Based on in vitro studies, it has been established that carboxymethylene butenolidase is involved in hydrolysis in the intestine and liver. In addition, plasma esterases are involved in the hydrolysis of azilsartan medoxomil to azilsartan.

The estimated absolute bioavailability of azilsartan medoxomil based on plasma concentrations of azilsartan is about 60%. After oral use of azilsartan medoxomil, the Cmax of azilsartan in plasma is reached within 1.5-3 hours. Food does not affect the bioavailability of azilsartan.

The Vd of azilsartan is about 16 l. Azilsartan is highly bound to plasma proteins (>99%), mainly to serum albumin. Protein binding is constant at plasma concentrations of azilsartan significantly exceeding the range achieved at recommended doses. Css of azilsartan is achieved within 5 days and with repeated doses of 1 time/day. there is no accumulation in the plasma.

Dose proportionality in exposure was established for azilsartan at a dose of azilsartan medoxomil from 20 mg to 320 mg after a single or multiple dose.

Azilsartan is metabolized to two major metabolites. The main metabolite in plasma is formed by O-dealkylation and is called the M-II metabolite, the second metabolite M-I is formed in a lower concentration by decarboxylation. The systemic effect of both metabolites in humans is approximately 50% and less than 1% of azilsartan itself, respectively. M-I and M-II are not involved in the pharmacological activity of Edarbi™. The main enzyme responsible for the metabolism of azilsartan is CYP2C9.

After an oral dose of 14C-labeled azilsartan medoxomil, about 55% of radioactivity is detected in the feces and about 42% in the urine,15% of this dose is excreted in the urine as azilsartan. T 1/2 of azilsartan is approximately 11 hours, and the renal clearance is approximately 2.3 ml / min

. Pharmacokinetics in special patient groups:

The pharmacokinetics of azilsartan in young (age 18-45 years) and elderly (age 65-85 years) patients do not differ significantly. No increase (+5%) in exposure was observed in patients with end-stage renal disease on dialysis. However, there is no clinical experience of its use in patients with severe renal insufficiency or end-stage renal disease. Hemodialysis does not remove azilsartan from the systemic circulation.

use of Edarbi™ for up to 5 days in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic insufficiency resulted in a slight increase in azilsartan exposure (AUC increased 1.3-1.6 times). The pharmacokinetics of Edarbi™ in patients with severe hepatic insufficiency have not been studied.

The pharmacokinetics of azilsartan in men and women do not differ significantly. No gender-specific dose adjustment is required.

Indications

treatment of essential hypertension in adults.

Use during pregnancy and lactation

You should not start taking angiotensin II receptor antagonists during pregnancy. Unless continuation of previously initiated therapy with angiotensin II receptor antagonists is considered important, patients planning pregnancy should be replaced with an alternative antihypertensive drug that is safe to use during pregnancy. If pregnancy is established, treatment with angiotensin II receptor antagonists should be stopped immediately, and alternative therapy should be initiated if necessary.

Since there is no information about the use of Edarbi™ during lactation, the use of the drug is not recommended, and alternative treatment methods with better proven safety characteristics during lactation are preferred, especially during the feeding of a newborn or premature baby.

Contraindications

-hypersensitivity to the Active ingredient or to any of the excipients of the drug Edarbi;- combined use of aliskiren and azilsartan in patients with diabetes mellitus;— pregnancy; – lactation period; – children and adolescents under 18 years of age.

Side effects

When taking Edarbi™, side effects may be mild to moderate. Gender and age do not affect the frequency of side effects.

The frequency of side effects of the drug is estimated as follows: very often (≥1/10), often (≥1/100, Often: dizziness, diarrhea, increased blood creatinine clearance.

Infrequently: hypotension, fatigue, peripheral edema*, increased blood creatinine, increased uric acid concentration in the blood/hyperuricemia.

Rarely: angioedema, including edema of the perioral and periorbital regions, decreased hemoglobin and hematocrit concentrations.

* – when Edarbi™ was co-administered with amlodipine, the incidence of peripheral edema increased, but was lower than with amlodipine alone.

Interaction

Not recommended combinations:

Dual blockade of the renin-angiotensin system with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren is associated with an increased risk of hypotension, hyperkalemia, and changes in renal function (including acute renal failure). compared to monotherapy.

With simultaneous use of lithium and ACE inhibitors, a reversible increase in the concentration of lithium in the blood serum and its toxicity was recorded. A similar effect can occur with angiotensin II receptor antagonists. Due to the lack of experience with the simultaneous use of azilsartan medoxomil and lithium, their combination is not recommended. If this combination is necessary, careful monitoring of serum lithium concentrations is recommended.

Combinations that require caution:

NSAIDs (including selective COX-2 inhibitors, acetylsalicylic acid >3 g / day, and non-selective NSAIDs) may reduce the antihypertensive effect when taken concomitantly with angiotensin II receptor antagonists. In addition, concomitant use of angiotensin II receptor antagonists and NSAIDs may lead to an increased risk of worsening renal function and increased serum potassium concentrations. Therefore, adequate hydration and monitoring of renal function is recommended at the beginning of treatment.

Concomitant use of potassium-sparing diuretics, potassium supplements, potassium-containing salt substitutes, or other medications (such as heparin) may increase potassium concentrations. Serum potassium should be monitored as necessary.

Additional information:

No clinically significant interaction of azilsartan medoxomil or azilsartan with amlodipine, antacids, chlortalidone, digoxin, fluconazole, glibenclamide, ketoconazole, metformin and warfarin was reported. Azilsartan medoxomil is rapidly hydrolyzed to active azilsartan by esterases in the gastrointestinal tract and/or upon absorption of the drug. In vitro studies have shown that interactions based on esterase inhibition are unlikely.

How to take it, course of use and dosage

Tablets should be taken orally regardless of food intake.

The recommended starting dose is 40 mg once a day. The dose can be increased to the maximum (80 mg 1 time / day.) in patients whose blood pressure is not properly controlled at lower doses.

The antihypertensive effect is manifested at the 2nd week and the maximum effect is achieved by the 4th week of use.

If blood pressure is not properly controlled with Edarbi™ monotherapy alone, additional blood pressure reduction may be achieved when Edarbi™ is co-administered with other antihypertensive medications, including diuretics (such as chlortalidone and hydrochlorothiazide) and calcium channel blockers (such as amlodipine).

In elderly patients, no special dose selection of Edarbi™ is required, although attention should be paid to the 20 mg dose as the initial dose in very elderly individuals (>75 years) who are likely to be at risk of hypotension.

Caution should be exercised in patients with severe renal insufficiency and end-stage renal disease, as there is no experience of using Edarbi™ in such patients. Hemodialysis does not remove azilsartan from the circulation. No dose adjustment is required in patients with mild or moderate renal insufficiency.

In patients with severe hepatic insufficiency, the effect of Edarbi™ has not been studied, so its use in this group of patients is not recommended. Since the experience of using Edarbi™ in patients with mild to moderate hepatic insufficiency is limited, careful monitoring of such patients is recommended.

In patients with a possible decrease in BCC or salt depletion (for example, patients with vomiting, diarrhea, or taking high-dose diuretics), Edarbi™ should be started under close medical supervision and only after normal BCC has been restored.

Caution should be exercised in patients with hypertension and congestive heart failure, as there is no experience of using Edarbi™ in such patients.

Overdose

In patients taking Edarbi™ 320 mg / day. within 7 days, there were no signs of overdose.

Symptoms: hypotension and dizziness.

Treatment: if hypotension occurs, then symptomatic therapy should be initiated and vital functions monitored. Hemodialysis is not effective.

Special instructions

Activated RAAS:

In patients whose vascular tone and renal function depend primarily on RAAS activity (for example, in patients with congestive heart failure, severe renal impairment, or renal artery stenosis), treatment with drugs that affect this system, such as ACE inhibitors and angiotensin II receptor antagonists, has been associated with acute hypotension, azotemia, oliguria, or less often with acute renal failure. The probability of such effects cannot be excluded in Edarby.

Caution should be exercised in patients with severe renal impairment, congestive heart failure, or renal artery stenosis, as there is no experience of using Edarbi™ in these patients.

Excessive lowering of blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular disease can lead to myocardial infarction or stroke.

Kidney transplantation:

Currently, there is no experience of using Edarbi™ in patients who have recently undergone kidney transplantation.

Liver damage:In patients with severe hepatic insufficiency, the effect of Edarbi™ has not been studied, and therefore it is not recommended to use it in this group of patients.

Hypotension in patients with water or salt depletion:

Patients with significantly reduced BCC and salt depletion (for example, patients with vomiting, diarrhea, or taking high-dose diuretics) may experience symptomatic hypotension after starting treatment with Edarbi™. Hypovolemia should be corrected before starting Edarbi™, or treatment should be initiated under close medical supervision.

Primary hyperaldosteronism:Patients with primary hyperaldosteronism usually do not respond to antihypertensive drugs that act by inhibiting the renin-angiotensin system. Therefore, the use of Edarbi™ in these patients is not recommended. Hyperkalemia:Based on experience with other medications that affect the RAAS, concomitant use of Edarbi™ with potassium-sparing diuretics, potassium-containing supplements, potassium-containing salt substitutes, or other medications that increase the potassium content (for example, heparin) may lead to an increase in the concentration of potassium in the blood serum of patients. In the elderly, in patients with renal insufficiency, in patients with diabetes mellitus and/or in patients with other concomitant diseases, the risk of hyperkalemia increases, which can be fatal. Potassium concentrations should be monitored as needed.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy:Special precautions are recommended in patients with aortic or mitral valve stenosis or hypertrophic obstructive cardiomyopathy.

Lithium:As with other angiotensin II receptor antagonists, the combination of lithium and Edarbi™ is not recommended.

Influence on the ability to drive motor vehicles and manage mechanisms:

Based on the pharmacodynamic properties, azilsartan medoxomil is expected to have a minor effect on the ability to drive a car and work with mechanisms. However, when taking any antihypertensive medications, it should be borne in mind that sometimes dizziness or fatigue may occur.

Form of production

Pills.

Active ingredient

Azilsartan medoxomil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension