Edarbi tablets 80mg, No. 28

Essential hypertension

EdarbiЃ is taken orally once a day, regardless of the meal time. The recommended starting dose is 40 mg once a day. If an additional decrease in blood pressure is required, the dose of the drug can be increased to a maximum of -80 mg once a day.
The maximum daily dose is 80 mg.
In case of inadequate control of blood pressure in monotherapy with EdarbiЃ, it is possible to use it simultaneously with other antihypertensive drugs, including diuretics (chlorthalidone and hydrochlorothiazide) and dihydropyridine blockers of 'slow' calcium channels (amlodipine).
The duration of the course of treatment
EdarbiЃ should be taken daily, without interruption. In case of termination of treatment, the patient must inform the doctor about it.
Skipping a dose
If the next dose is missed, the patient should take the next dose at the usual time. Do not take a double dose of EdarbiЃ.
Special groups
Elderly patients (65 years and older)
No adjustment of the initial dose of EdarbiЃ is required in elderly patients. However, in patients over the age of 75 years, a dose of 20 mg can be considered as the initial dose (the risk of arterial hypotension increases).
Patients with impaired renal function
There is no clinical experience with the use of EdarbiЃ in patients with hypertension with severe renal impairment and end-stage renal failure, therefore, the drug should be used with caution in this category of patients.
No dosage adjustment is required in patients with mild to moderate renal impairment.
Patients with impaired liver function It is
not recommended to use the drug in patients with severe liver impairment due to lack of clinical experience (see section Contraindications ).
Due to the limited experience of using EdarbiЃ in patients with mild and moderate hepatic dysfunction, it is recommended to start treatment with a dose of 20 mg 1 time per day and carry it out under close supervision.
Decreased circulating blood volume (BCC)
The drug EdarbiЃ should be prescribed to patients with a decrease in BCC and / or hyponatremia (for example, patients with prolonged vomiting, diarrhea, or taking large doses of diuretics) only under strict medical supervision. It is also recommended to start treatment with a dosage of 20 mg once a day.
Heart failure
Due to the lack of clinical experience, Edarbi should be used with caution in hypertensive patients with severe chronic heart failure (NYHA functional class IV).
Negroid race
No dose adjustment is required in black patients. As in the case of other angiotensin II receptor antagonists (AT1) and ACE inhibitors, in patients of the Negroid race, there is a smaller decrease in blood pressure compared to the rest of the population. In this regard, for adequate control of blood pressure in patients of the Negroid race, an increase in the dose of Edarbi and complex therapy may be necessary more often than in other patients.

1 tablet 80 mg contains:
Active substance: azilsartan medoxomil potassium 85.36 mg corresponds to azilsartan medoxomil 80 mg
Excipients: mannitol 191.26 mg, fumaric acid 4 mg, sodium hydroxide 1.38 mg, hyprolose 10.8 mg, croscarmellose sodium 27.6 mg, microcrystalline cellulose 36 mg, magnesium stearate 3.6 mg.

- hypersensitivity to the active substance and other components of the drug;

- pregnancy;

- simultaneous administration of aliskiren in patients with diabetes mellitus;

- age up to 18 years (efficacy and safety have not been established);

- severe liver dysfunction (more than 9 points on the Child-Pugh scale) (no experience of use).

Carefully:

- severe chronic heart failure (NYHA functional class IV);

- severe renal failure (creatinine clearance <30 ml / min);

- bilateral stenosis of the renal arteries and stenosis of the artery of the only functioning kidney;

- ischemic cardiomyopathy;

- ischemic cerebrovascular diseases;

- condition after kidney transplantation;

- conditions accompanied by a decrease in the volume of circulating blood (BCC) (including vomiting, diarrhea), as well as in patients on a diet with restricted salt;

- when used simultaneously with large doses of diuretics;

- primary hyperaldosteronism;

- hyperkalemia;

- stenosis of the aortic and mitral valves;

- hypertrophic obstructive cardiomyopathy (GOKMP);

- over 75 years of age.

If you have one of the listed diseases, be sure to consult your doctor before taking EdarbiЃ.

Tradename:

EdarbyЃ

International Non-Proprietary Name (INN):

azilsartan medoxomil

Dosage form:

pills.

Composition:

1 tablet 20 mg contains:
Active substance: azilsartan medoxomil potassium 21.34 mg corresponds to azilsartan medoxomil 20 mg
Excipients: mannitol 47.815 mg, fumaric acid 1 mg, sodium hydroxide 0.345 mg, hyprolose 2.7 mg, croscarmellose sodium 6.9 mg , microcrystalline cellulose 9 mg, magnesium stearate 0.9 mg.
1 tablet 40 mg contains:
Active substance: azilsartan medoxomil potassium 42.68 mg corresponds to azilsartan medoxomil 40 mg
Excipients: mannitol 95.63 mg, fumaric acid 2 mg, sodium hydroxide 0.69 mg, hyprolose 5.4 mg, croscarmellose sodium 13.8 mg, microcrystalline cellulose 18 mg, magnesium stearate 1.8 mg.
1 tablet 80 mg contains:
Active ingredient:azilsartan medoxomil potassium 85.36 mg corresponds to azilsartan medoxomil 80 mg
Excipients: mannitol 191.26 mg, fumaric acid 4 mg, sodium hydroxide 1.38 mg, hyprolose 10.8 mg, croscarmellose sodium 27.6 mg, microcrystalline cellulose 36 mg , magnesium stearate 3.6 mg.

Pharmacotherapeutic group:

angiotensin II receptor antagonist.

Description
Tablets 20 mg:
White to off-white round biconvex tablets engraved with 'ASL' on one side and '20' on the other.
Tablets 40 mg:
White to off-white round, biconvex tablets engraved with 'ASL' on one side and '40' on the other.
Tablets 80 mg:
White to off-white round, biconvex tablets engraved with 'ASL' on one side and '80' on the other.

Pharmacological properties

Pharmacodynamics
Azilsartan medoxomil - the active ingredient of the drug EdarbiЃ - is a specific antagonist of angiotensin II type 1 (AT1) receptors. Azilsartan medoxomil is an oral prodrug. Azilsartan medoxomil is rapidly converted into the active molecule of azilsartan, which selectively prevents the development of the effects of angiotensin II by blocking its binding to AT1 receptors in various tissues. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldesterone system (RAAS) with effects including vasoconstriction, cardiac stimulation, stimulation of aldosterone synthesis and release, and, as a consequence, renal sodium reabsorption.
Blockade of AT1 receptors inhibits the negative regulatory response of angiotensin II to renin secretion, but the resulting increase in plasma renin activity and circulating angiotensin II level does not suppress the antihypertensive effect of azilsartan.
The antihypertensive effect of azilsartan medoxomil develops during the first 2 weeks of use, with the maximum therapeutic effect being achieved after 4 weeks. A decrease in blood pressure (BP) after oral administration of a single dose is usually achieved within a few hours and persists for 24 hours.
The syndrome of 'withdrawal' (a sharp increase in blood pressure after drug withdrawal) after sudden withdrawal after prolonged therapy (within 6 months) with EdarbiЃ was not observed.
The safety and efficacy of the drug does not depend on the age of the patients, but a greater sensitivity to lowering blood pressure in some elderly patients cannot be ruled out. As with the use of other angiotensin II receptor antagonists and angiotensin-converting enzyme (ACE) inhibitors, the antihypertensive effect is less pronounced in black patients (usually a population with low plasma renin activity). The simultaneous use of EdarbiЃ 40 mg and 80 mg with dihydropyridine blockers of 'slow' calcium channels (amlodipine) or thiazide diuretics (chlorthalidone) leads to an additional decrease in blood pressure compared to antihypertensive drugs used in monotherapy (see section Interaction with other drugs ) ...
Impact on repolarization processes
Evaluation of the potential of EdarbiЃ to increase the QT / QTc interval was carried out in healthy volunteers during the QT / QTc study. When using a dose of 320 mg
Edarbi, no increase in the QT / QTc interval was observed.
QTc - corrected (relative to the heart rate (HR)) value of the QT interval, relative value.
Since the duration of the QT interval depends on the heart rate (lengthening as it slows down), it must be corrected relative to the heart rate for assessment.
Prolongation of the QT interval reflects the heterogeneity of the processes of repolarization of the ventricular myocardium, and is regarded as an independent indicator indicating the possibility of fatal cardiac arrhythmias.

Pharmacokinetics
Absorption
Azilsartan medoxomil is a prodrug. After oral administration, it is converted to the pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the action of the enzyme carboxymethylene butenolidase in the intestine and liver.
The estimated absolute bioavailability of azilsartan medoxomil when taken orally is approximately 60% according to the plasma concentration profile. The maximum concentration (Cmax) of azilsartan in blood plasma, on average, is achieved within 1.5 - 3 hours after taking the drug inside. Food intake does not affect the bioavailability of azilsartan.
Distribution
The volume of distribution of azilsartan is about 16 liters. Azilsartan binds to blood plasma proteins (more than 99%), mainly to blood plasma albumin. The connection with blood plasma proteins remains constant when the concentration of azilsartan in blood plasma significantly exceeds the range achieved when taking the recommended doses.
There are no data on the use of the drug during pregnancy and during breastfeeding. Azilsartan crosses the placenta of pregnant rats and is excreted in the milk of lactating rats (see section Use during pregnancy and breastfeeding ).
Studies in animals with radioactive labels have shown that the amount of azilsartan that crosses the blood-brain barrier is minimal.
Metabolism
Azilsartan is metabolized to two primary metabolites predominantly in the liver. The main metabolite in blood plasma is formed by O-dealkylation and is designated as the M-II metabolite, the minor metabolite is formed by decarboxylation and is designated as the M-I metabolite. The AUC (area under the concentration-time pharmacokinetic curve) for these metabolites in humans is 50% and less than 1%, respectively, compared with azilsartan. ћ-I and ћ-II do not affect the pharmacological activity of EdarbiЃ. The main enzyme providing the metabolism of azilsartan is the CYP2C9 isoenzyme.
Withdrawal
Azilsartan and its metabolites are excreted from the body both through the intestines and by the kidneys. Studies have shown that after oral administration of azilsartan medoxomil, about 55% (mainly in the form of the M-I metabolite) is found in the feces and about 42% (15% - in the form of azilsartan, 19% - in the form of the M-II metabolite) - in the urine ... The half-life of azilsartan is about 11 hours and the renal clearance is about 2.3 ml / min. The equilibrium concentration of azilsartan is reached within 5 days and its accumulation in blood plasma does not occur with a single daily use.
Linearity / Non-linearity The
pharmacokinetics of azilsartan in azilsartan medoxomil are proportional to the dosage in the dose range from 20 mg to 320 mg after a single or multiple oral administration.
Pharmacokinetics in special groups
Children
The pharmacokinetics of azilsartan in children under the age of 18 has not been studied.
Elderly patients The
pharmacokinetics of azilsartan in young (18-45 years old) and elderly (65-85 years old) patients does not differ significantly.
Renal failure
In patients with mild, moderate and severe renal failure, the AUC was increased by + 30%, + 25% and + 95%, respectively. There was no increase (+ 5%) in AUC in patients with end-stage renal failure on hemodialysis. There are no clinical data on pharmacokinetics in patients with severe or end-stage renal disease.
Azilsartan is not cleared from the systemic circulation by hemodialysis.
Liver failure
The use of EdarbiЃ for more than 5 days in patients with mild (class A on the Child-Pugh scale) or moderate (class B on the Child-Pugh scale) severity of liver failure leads to a slight increase in AUC (1.3 - 1.6 times, respectively). The pharmacokinetics of EdarbiЃ in patients with severe (class C on the Child-Pugh scale) degree of liver failure has not been studied.
Gender The
pharmacokinetics of azilsartan do not differ significantly in men and women. No dose adjustment depending on gender is required.
Race The
pharmacokinetics of azilsartan do not differ significantly depending on the race of patients. No dose adjustment is required based on race.

Indications for use

Essential hypertension

Contraindications

- hypersensitivity to the active substance and other components of the drug;

- pregnancy;

- simultaneous administration of aliskiren in patients with diabetes mellitus;

- age up to 18 years (efficacy and safety have not been established);

- severe liver dysfunction (more than 9 points on the Child-Pugh scale) (no experience of use).

Carefully:

- severe chronic heart failure (NYHA functional class IV);

- severe renal failure (creatinine clearance <30 ml / min);

- bilateral stenosis of the renal arteries and stenosis of the artery of the only functioning kidney;

- ischemic cardiomyopathy;

- ischemic cerebrovascular diseases;

- condition after kidney transplantation;

- conditions accompanied by a decrease in the volume of circulating blood (BCC) (including vomiting, diarrhea), as well as in patients on a diet with restricted salt;

- when used simultaneously with large doses of diuretics;

- primary hyperaldosteronism;

- hyperkalemia;

- stenosis of the aortic and mitral valves;

- hypertrophic obstructive cardiomyopathy (GOKMP);

- over 75 years of age.

If you have one of the listed diseases, be sure to consult your doctor before taking EdarbiЃ.

Application during pregnancy and during breastfeeding

Application during pregnancy
In animal studies, it was found that azilsartan and M-II penetrate the placental barrier.
Patients planning a pregnancy should begin therapy with alternative antihypertensive drugs with an established safety profile for pregnant women. Immediately after confirmation of pregnancy, you should stop taking EdarbiЃ and, if necessary, start a course of treatment with drugs approved for use during pregnancy.
In newborns whose mothers received EdarbiЃ therapy, arterial hypotension may develop, and therefore, newborns should be under close medical supervision.
Breast-feeding
There is no information on the ability of azilsartan and / or its metabolites to pass into breast milk. In animal studies, it was found that azilsartan and M-II are excreted in the milk of lactating rats.
Due to the lack of experience with the use of EdarbiЃ in women during breastfeeding, its use in this category of patients is not recommended. It is preferable to use drugs with the most studied safety profile, especially during the period of caring for a newborn or premature baby.
Fertility There is no
data on the effect of EdarbiЃ on fertility in humans. Preclinical studies have shown no effect on male or female fertility in rats.

Method of administration and dosage

EdarbiЃ is taken orally once a day, regardless of the meal time. The recommended starting dose is 40 mg once a day. If an additional decrease in blood pressure is required, the dose of the drug can be increased to a maximum of -80 mg once a day.
The maximum daily dose is 80 mg.
In case of inadequate control of blood pressure in monotherapy with EdarbiЃ, it is possible to use it simultaneously with other antihypertensive drugs, including diuretics (chlorthalidone and hydrochlorothiazide) and dihydropyridine blockers of 'slow' calcium channels (amlodipine).
The duration of the course of treatment
EdarbiЃ should be taken daily, without interruption. In case of termination of treatment, the patient must inform the doctor about it.
Skipping a dose
If the next dose is missed, the patient should take the next dose at the usual time. Do not take a double dose of EdarbiЃ.
Special groups
Elderly patients (65 years and older)
No adjustment of the initial dose of EdarbiЃ is required in elderly patients. However, in patients over the age of 75 years, a dose of 20 mg can be considered as the initial dose (the risk of arterial hypotension increases).
Patients with impaired renal function
There is no clinical experience with the use of EdarbiЃ in patients with hypertension with severe renal impairment and end-stage renal failure, therefore, the drug should be used with caution in this category of patients.
No dosage adjustment is required in patients with mild to moderate renal impairment.
Patients with impaired liver function It is
not recommended to use the drug in patients with severe liver impairment due to lack of clinical experience (see section Contraindications ).
Due to the limited experience of using EdarbiЃ in patients with mild and moderate hepatic dysfunction, it is recommended to start treatment with a dose of 20 mg 1 time per day and carry it out under close supervision.
Decreased circulating blood volume (BCC)
The drug EdarbiЃ should be prescribed to patients with a decrease in BCC and / or hyponatremia (for example, patients with prolonged vomiting, diarrhea, or taking large doses of diuretics) only under strict medical supervision. It is also recommended to start treatment with a dosage of 20 mg once a day.
Heart failure
Due to the lack of clinical experience, Edarbi should be used with caution in hypertensive patients with severe chronic heart failure (NYHA functional class IV).
Negroid race
No dose adjustment is required in black patients. As in the case of other angiotensin II receptor antagonists (AT1) and ACE inhibitors, in patients of the Negroid race, there is a smaller decrease in blood pressure compared to the rest of the population. In this regard, for adequate control of blood pressure in patients of the Negroid race, an increase in the dose of Edarbi and complex therapy may be necessary more often than in other patients.

Overdose

ќпыт применени¤ ЁдарбиЃ у взрослых в дозах до 320 мг/сутки на прот¤жении 7 дней показывает, что препарат хорошо переноситс¤.
—имптомы:
выраженное снижение ј?, головокружение.
Ћечение:
ѕри выраженном снижении ј? придать пациенту положение Ђлежаї, ноги приподн¤ть, проводить меропри¤ти¤ по увеличению объема циркулирующей крови (ќ? ); симптоматическа¤ терапи¤.
јзилсартан не выводитс¤ из системного кровотока посредством диализа.

¬заимодействие с другими лекарственными средствами

Ћитий
Ѕыло отмечено обратимое повышение концентрации лити¤ в сыворотке крови и про¤вление токсичности во врем¤ одновременного применени¤ препаратов лити¤ и ингибиторов јѕ‘ и препаратов лити¤ с антагонистами рецепторов ангиотензина II. ѕоэтому одновременное применение азилсартана медоксомила в комбинации с препаратами лити¤ не рекомендуетс¤ (см. раздел ќсобые указани¤). ѕри необходимости применени¤ соответствующей комбинированной терапии рекомендуетс¤ регул¤рный контроль содержание лити¤ в сыворотке крови.
Ќестероидные противовоспалительные препараты (Ќѕ¬ѕ)
ѕри одновременном применении антагонистов ангиотензина II и Ќѕ¬ѕ (например, селективных ингибиторов ?ќv-2 (циклооксигеназы-2), ацетилсалициловой кислоты (более 3 г/сутки) и неселективных Ќѕ¬ѕ) возможно ослабление антигипертензивного эффекта. ѕри одновременном применении антагонистов ангиотензина II и Ќѕ¬ѕ может возрастать риск нарушени¤ функции почек и увеличени¤ содержани¤ кали¤ в сыворотке крови. ѕоэтому в начале лечени¤ пациентам рекомендуетс¤ регул¤рный прием достаточного количества жидкости и контроль функции почек.
ѕрепараты кали¤ и калийсберегающие диуретики, гепарин
ќдновременное применение калийсберегающих диуретиков, препаратов кали¤, заменителей солей, содержащих калий и других лекарственных средств (например, гепарина) с азилсартана медоксомилом может привести к увеличению содержани¤ кали¤ в сыворотке крови (см. раздел ќсобые указани¤). ѕациентам во врем¤ комбинированной терапии следует контролировать содержание кали¤ в сыворотке крови.
?война¤ блокада ренин-ангиотензин-альдостероновой системы (–јј—)
?война¤ блокада –јј— антагонистами рецепторов к ангиотензину II, ингибиторами јѕ‘, или алискиреном св¤зана с повышенным риском развити¤ артериальной гипотензии, гиперкалиемии, и нарушением функции почек (включа¤ острую почечную недостаточность) по сравнению с монотерапией.
?ополнительна¤ информаци¤ по взаимодействию азилсартана медоксомила
Ќе наблюдалось фармакокинетических взаимодействий при одновременном применении азилсартана медоксомила или азилсартана с амлодипином, антацидными препаратами (магни¤ и алюмини¤ гидроксидом), хлорталидоном, дигоксином, флуконазолом, глибенкламидом, кетоконазолом, метформином и варфарином.
јзилсартана медоксомил превращаетс¤ в фармакологически активный метаболит азилсартан во врем¤ абсорбции из желудочно-кишечного тракта под действием фермента карбоксиметиленбутенолидазы в кишке и печени. »сследовани¤ in vitro показали, что взаимодействи¤, основанные на ингибировании ферментов, ¤вл¤ютс¤ маловеро¤тными.
?иуретики и другие гипотензивные средства
јнтигипертензивный эффект от терапии азилсартана медоксомилом может быть усилен при комбинированном применении с другими гипотензивными средствами, включа¤ диуретики (хлорталидон и гидрохлоротиазид), и дигидропиридиновые блокаторы Ђмедленныхї кальциевых каналов (амлодипин).

ќсобые указани¤

јктивированна¤ ренин-ангиотензин-альдостеронова¤ система
ѕациенты, у которых сосудистый тонус и функци¤ почек завис¤т в большой степени от активности –јј— (например, у пациентов с т¤желой хронической сердечной недостаточностью (IV функциональный класс по классификации NYHA), т¤желой степенью почечной недостаточности или стенозом почечных артерий), лечение лекарственными средствами, действующими на –јј—, такими как ингибиторы јѕ‘ и антагонисты рецепторов ангиотензина II, св¤зано с возможностью развити¤ острой артериальной гипотензии, азотемии, олигурии или редко острой почечной недостаточности. ¬озможность развити¤ перечисленных эффектов не может быть исключена и при применении ЁдарбиЃ.
–езкое снижение ј? у пациентов с ишемической кардиомиопатией или ишемическими цереброваскул¤рными заболевани¤ми может приводить к развитию инфаркта миокарда или инсульта.
“рансплантаци¤ почки
?анные о применении ЁдарбиЃ у пациентов, недавно перенесших трансплантацию почки, отсутствуют.
Ќарушение функции печени
?анные о клиническом опыте применени¤ ЁдарбиЃ у пациентов с т¤желой степенью нарушени¤ функции печени отсутствуют, поэтому применение препарата у данной категории пациентов не рекомендуетс¤.
јртериальна¤ гипотензи¤ на фоне нарушени¤ водно-электролитного баланса
” больных со сниженным ќ?  и/или с гипонатриемией (в результате рвоты, диареи, приема больших доз диуретиков или соблюдени¤ диеты с ограничением приема поваренной соли) может развиватьс¤ клинически значима¤ артериальна¤ гипотензи¤ после начала терапией ЁдарбиЃ. vиповолемию следует скорректировать перед началом лечени¤ препаратом ЁдарбиЃ или начать лечение с дозировки 20 мг.
ѕервичный гиперальдостеронизм
ѕациенты с первичным гиперальдостеронизмом обычно резистентны к терапии гипотензивными препаратами, вли¤ющими на –јј—. ¬ св¤зи с этим ЁдарбиЃ не рекомендуетс¤ назначать таким пациентам.
vиперкалиеми¤
 линический опыт применени¤ других препаратов, вли¤ющих на –јј—, показывает, что одновременное назначение ЁдарбиЃ с калийсберегающими диуретиками, препаратами кали¤ или заменител¤ми солей, содержащими калий, или другими препаратами, которые могут увеличить содержание кали¤ в крови (например, гепарин), может привести к гиперкалиемии у пациентов с артериальной гипертензией. ” пожилых пациентов, пациентов с почечной недостаточностью, сахарным диабетом и/или у пациентов с другими сопутствующими заболевани¤ми увеличиваетс¤ риск развити¤ гиперкалиемии, котора¤ может быть фатальной. ” таких пациентов рекомендуетс¤ контролировать содержание кали¤ в сыворотке крови.
—теноз аортального или митрального клапанов, гипертрофическа¤ обструктивна¤ кардиомиопати¤
ѕри назначении ЁдарбиЃ пациентам с аортальным или митральным стенозом или гипертрофической обструктивной кардиомиопатией необходимо соблюдать осторожность.
Ћитий
 ак и в случае других антагонистов рецепторов ангиотензина II, не рекомендуетс¤ одновременное применение препаратов лити¤ и препарата ЁдарбиЃ (см. раздел ¬заимодействие с другими лекарственными средствами).

¬ли¤ние на способность управл¤ть автотранспортными средствами и механизмами

Ќа основании фармакодинамических свойств ожидаетс¤, что азилсартана медоксомил будет незначительно вли¤ть на способность к вождению автотранспорта и управлению механизмами. Ќеобходимо соблюдать осторожность, как и при применении любых гипотензивных средств (риск развити¤ головокружени¤ и повышенной утомл¤емости).

‘орма выпуска

Tablets 20 mg, 40 mg and 80 mg.
14 tablets per AL blister with a desiccant built into the PE layer. 1, 2, 3, 4 or 7 blisters, together with instructions for use, are placed in a cardboard box.

Shelf life

3 years.
Do not use after the expiration date printed on the package.

Storage conditions

Store in its original packaging to protect from light and moisture at a temperature not exceeding 25 ? C.
Keep out of the reach of children.

Vacation conditions

Prescription