Edarbi 40 mg tab 28 pc

Description

Composition
Active substance:
1 tablet contains: potassium azilsartana medoxomil 21.34 mg corresponding to 20 mg azilsartana medoksomilu or potassium azilsartana medoxomil 42.68 mg corresponding to 40 mg azilsartana medoksomilu or potassium azilsartana medoxomil 85.36 mg azilsartana medoksomilu corresponds to 80 mg.
Excipients:
Mannitol, fumaric acid, sodium hydroxide, giproloza, croscarmellose sodium, microcrystalline cellulose, magnesium stearate.
Description:
20 mg Tablets:
White to almost white round biconvex tablets with “of ASL” engraved on one side and “20” on the other.
40 mg Tablets:
White to almost white round biconvex tablets with “of ASL” engraved on one side and “40” on the other.
80 mg Tablets:
White to almost white round biconvex tablets with “of ASL” engraved on one side and “80” on the other.
Product form:
Tablets 20 mg, 40 mg and 80 mg. To 14 tablets per blister AL PE with a built in desiccant layer. 1, 2, 3, 4 or 7 blister together with instructions for use placed into cardboard pack.
Contraindications
Hypersensitivity to the active substance and other ingredients; pregnancy; simultaneous administration of drugs containing aliskiren in patients with diabetes or impaired renal function (glomerular filtration rate
Precautions: severe chronic heart failure (IV NYHA functional class classifying); severe renal insufficiency (creatinine clearance
If you have one of these diseases, before taking Edarbi® sure to consult with your doctor.
Dosage
40 mg
Indications
Essential hypertension.
Interaction with other drugs
Lithium: it was noted reversible increase the concentration of lithium in blood serum and expression of toxicity during the simultaneous application of drugs lithium and lithium ACE inhibitors and drugs with antagonists of angiotensin II receptors. Therefore, the simultaneous use azilsartana medoxomil in combination with lithium therapy is not recommended (see. Specific guidance section). If necessary, use appropriate combination therapy recommended regular monitoring of serum lithium content.
Nonsteroidal anti-inflammatory drugs (NSAIDs), while the application of angiotensin II antagonists and NSAIDs (e.g., COX-2 (cyclooxygenase-2), acetylsalicylic acid (more than 3 g / day) and nonselective NSAIDs) may weaken the antihypertensive effect. With simultaneous use of angiotensin II antagonists and NSAIDs may increase the risk of renal impairment and increased potassium content in the blood serum. Therefore, at the beginning of treatment is recommended for patients receiving regular enough fluid and monitoring of renal function.
potassium Preparations and potassium-sparing diuretics, heparin: the simultaneous use of potassium-sparing diuretics, potassium preparations salt substitute containing potassium and other drugs (e.g., heparin) with azilsartana medoksomilom may lead to an increase in the potassium content in the blood serum (see Specific guidance.). Patients during combination therapy should be monitored content of potassium in the blood serum.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): dual blockade of the RAAS receptor antagonists of angiotensin II, ACE inhibitors, or preparations containing aliskiren, associated with increased risk of arterial hypotension, hyperkalemia, and renal dysfunction (including acute renal failure) compared with monotherapy. Not recommended simultaneous application with ACE inhibitors and drugs containing aliskiren.
Additional information about the interaction azilsartana medoxomil: not observed pharmacokinetic interactions while applying azilsartana azilsartana medoxomil and amlodipine, antacids (aluminum hydroxide and magnesium), chlorthalidone, digoxin, fluconazole, glibenclamide, ketoconazole, metformin and warfarin. Azilsartana medoxomil is converted into a pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the enzyme karboksimetilenbutenolidazy in the gut and liver. In vitro studies have shown that interactions based on the inhibition of enzymes, are unlikely
Diuretics and other hypotensive drugs: antihypertensive effect of therapy azilsartana medoksomilom can be enhanced by the combined use with other antihypertensive agents including diuretics (hydrochlorothiazide and chlorthalidone), and dihydropyridine blockers “slow” calcium channel (amlodipine).
Overdose
Previous applications Edarbi® adults in doses up to 320 mg / day for 7 days shows that the drug was well tolerated.
Symptoms: marked reduction of blood pressure, dizziness.
Treatment: In marked decrease in blood pressure make a patient to “lying” leg lift, carry out measures to increase circulating blood volume (CBV); monitor vital signs; symptomatic therapy. Azilsartan not output from the systemic circulation by dialysis.
pharmachologic effect
Pharmacological group:
Angiotensin II receptor antagonist.
Pharmacodynamics:
Azilsartana medoxomil – active substance Edarbi® preparation – is a specific antagonist of the angiotensin II type 1 (AT1) receptor. Azilsartana medoxomil – is a prodrug for oral administration. Azilsartana medoxomil is rapidly converted into the active molecule azilsartana which selectively prevents the development 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-aldesteronovoy system (RAAS) with effects including vasoconstriction, cardiac stimulation, stimulation of synthesis and release of aldosterone, and as a consequence, renal reabsorption of sodium. Blockade of the AT1-receptor inhibits the negative regulatory response of angiotensin II on renin secretion, but the resulting increase in plasma renin activity and circulating levels of angiotensin II not suppress azilsartana antihypertensive effect. Antihypertensive effect azilsartana medoxomil develops within the first 2 weeks of treatment with achieving maximal therapeutic effect after 4 weeks. Lowering blood pressure (BP) after oral administration of a single dose is usually achieved within a few hours and stored for 24 hours. Syndrome “cancel” (a sharp increase in blood pressure after discontinuation of the drug) after abrupt withdrawal after long-term treatment (6 months) drug Edarbi® not observed. The safety and efficacy of the drug does not depend on the age of the patient, but bolshaya sensitivity to lower blood pressure in some older patients can not be ruled out. As with other angiotensin II receptor antagonists and angiotensin converting enzyme (ACE) inhibitors, antihypertensive effect is less pronounced in patients blacks (usually population with low renin activity in blood plasma). Patients with diabetic nephropathy and should not be used simultaneously angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists. Simultaneous application Edarbi® 40 mg and 80 mg dihydropyridine blockers “slow” calcium channel (amlodipine) or thiazide diuretics (chlorthalidone) leads to an additional reduction in blood pressure compared with the antihypertensive agents used in monotherapy (see. Section Interaction with other drugs) .
The effect on the processes of repolarization
Assessing the potential Edarbi® increase the interval QT / QTc was conducted in healthy volunteers in the study, QT / QTc. When applying the dose of 320 mg Edarbi® increasing interval not observed QT / QTc. QTc –corrected (with respect to heart rate (HR)), the value of the interval QT, relative value. Since QT interval duration depends on the heart rate (lengthening when deceleration) to estimate it should be ‘corrected with respect to heart rate. QT prolongation reflects the heterogeneity of ventricular repolarization of the myocardium, and is regarded as an independent indicator, indicating the possibility of occurrence of fatal cardiac arrhythmias.
Pharmacokinetics:
Suction
Azilsartana medoxomil is a prodrug. Upon ingestion it is converted into a pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the enzyme karboksimetilenbutenolidazy in the gut and liver. The calculated absolute bioavailability azilsartana medoxomil ingestion of about 60% according to the profile of plasma concentrations. The maximum concentration (Cmax) in plasma azilsartana average reached within 1.5-3 hours after ingestion of the drug. Eating does not affect the bioavailability azilsartana.
Distribution
Azilsartana volume of distribution is approximately 16 liters. Azilsartan binds to plasma proteins (99%), mostly to albumin in blood plasma. Communication with plasma proteins remains constant at azilsartana plasma concentrations greatly exceeding the range can be achieved with recommended doses. the use of these drugs during pregnancy and lactation are not available. Azilsartan cross the placenta of pregnant rats and excreted into the milk of lactating rats (see. Section Use during pregnancy and lactation). Animal studies with radiolabeled showed that the number azilsartana penetrating the blood-brain barrier is minimal.
Metabolism
Azilsartan metabolized to two primary metabolites, primarily in the liver. The major metabolite in plasma is formed and the O-dealkylation metabolite designated as M-II, a secondary metabolite is formed by decarboxylation, and is denoted as a metabolite of M-I. The values ​​of AUC (area under the curve “concentration-time”) for these metabolites in humans is 50% and less than 1% compared to azilsartanom. M-I and M-II do not affect the pharmacological activity Edarbi®. The main enzyme providing azilsartana metabolism is isoenzyme CYP2C9
breeding
Azilsartan and its metabolites are excreted from the body as through the intestines, and kidneys. Studies have shown that after oral administration azilsartana medoxomil, about 55% (predominantly in the form of a metabolite of M-I) detected in the stool and about 42% (15% – as azilsartana, 19% – as a metabolite of M-II) – in urine . Azilsartana half-life is about 11 hours and renal clearance – about 2.3 mL / min. Azilsartana equilibrium concentration is reached within 5 days and its accumulation in the blood plasma does not occur with single daily application.
Linearity / Non-linearity
Pharmacokinetics in azilsartana azilsartana medoksomile proportional dosage in a dose range from 20 mg to 320 mg after single or repeated ingestion.
Pharmacokinetics in special groups
Children
Azilsartana pharmacokinetics in children under the age of 18 years have not been studied.
Elderly patients
Pharmacokinetics azilsartana in young (18-45 years) and elderly (65-85 years) of the patients were not significantly different.
kidney failure
In patients with mild, moderate and severe renal insufficiency AUC was increased by + 30%, + 25% and + 95% respectively. Increase (+ 5%) AUC in patients with end stage renal failure, hemodialysis, was not observed. Clinical data on pharmacokinetics in patients with severe or end-stage renal disease are not available. Azilsartan not output from the systemic circulation by hemodialysis.
Liver failure
Application Edarbi® over 5 days in patients with mild (Class A scale Chayld- Pugh) or moderate (Class B of Child-Pugh) liver failure severity leads to a small increase in AUC (1.3-1.6 times, respectively). Edarbi® pharmacokinetics in patients with severe patients (class C by Child-Pugh) the degree of hepatic impairment has not been studied.
sexual identity
Pharmacokinetics azilsartana men and women were not significantly different. No dose adjustment based on gender is necessary.
Ethnicity
Pharmacokinetics azilsartana depending on the race of patients was not significantly different. No dose adjustment based on race is required.
Pregnancy and breast-feeding
Use during pregnancy
In animal studies revealed that azilsartan and M-II cross the placental barrier. Patients planning a pregnancy should begin therapy alternative antihypertensive drugs with established safety profile for pregnant women. Immediately after the confirmation of pregnancy should stop taking the drug Edarbi® and, if necessary, start a course of treatment drugs permitted for use during pregnancy. As with any other drug that influences on the renin-angiotensin aldesteronovuyu system (RAAS), there may be damage to the fetus (renal failure, oligohydramnios, delay skull ossification) in second and third trimester of pregnancy. If use of the drug occurred in the second and third trimester of pregnancy, it is recommended to conduct ultrasound examination of the skull and fetal renal excretory function. Neonates whose mothers were treated Edarbi® may develop hypotension, renal failure, hyperkalemia, and therefore, the newborn should be under close medical supervision.
Breast-feeding
No information on the ability azilsartana and / or its metabolites into breast milk. In animal studies revealed that azilsartan and M-II allocated into milk of lactating rats. Due to lack of experience with Edarbi® in women during breast-feeding is not recommended its use in these patients. Preferably, the use of drugs with the most studied safety profile, especially during the care of newborn or prematurely born child.
fertility
Edarbi® exposure data on fertility in humans. Preclinical studies have shown no effect on male or female fertility in rats.
Conditions of supply of pharmacies
Prescription.
side effects
The frequency of adverse reactions was determined in accordance with the recommendations of the World Health Organization: very common (> 1/10); common (> 1/100, 1/1000, 1/10 000,
Disorders of the nervous system: often, dizziness
Violations by vessels: Infrequent, marked reduction in blood pressure
Disorders of the gastrointestinal tract: often, diarrhea; infrequently-nausea
Violations of the skin and subcutaneous tissue disorders: rarely, rash, pruritus, rarely, angioedema
Violations by musculoskeletal and connective tissue disorders: muscle cramps, infrequently
Effect on results of laboratory and instrumental investigations: often increase creatine phosphokinase activity-infrequently-creatinine concentrations, hyperuricemia
General disorders: rare, fatigue, peripheral edema
The description of adverse reactions
With simultaneous use of chlorthalidone Edarbi® frequency of adverse reactions – marked reduction of blood pressure and increased concentration of Creatinine – increases in frequency of occurrence: with occasional to frequent. When applied simultaneously with amlodipine Edarbi® frequency unwanted reactions – peripheral edema – increases with occasional to frequent, but occurs less frequently than with amlodipine monotherapy. Rarely observed angioedema including swelling of the face, lips and periorbital edema. As well as the application of other angiotensin II receptor antagonists and ACE inhibitors, the simultaneous application Edarbi® drug with diuretic (e.g., chlorthalidone) leads to increased rates of increase in creatinine concentration. Increased creatinine concentration while the application Edarbi® diuretics bolshim connected with blood pressure reduction compared to a monotherapy Edarbi®. Most of these effects are transient or progressive as patients continued therapy. After discontinuation of the drug most cases, increasing the concentration of creatinine are not held during treatment were reversible. creatinine concentration in most patients returned to the value at baseline, or values ​​that are close to the baseline. When treating Edarbi® observed a slight increase in the concentration of uric acid in the serum (10.8 mmol / l) compared to placebo (4.3 mol / l). Just as the use of other RAAS inhibitor monotherapy was a slight decrease in hemoglobin and hematocrit (average decreased by about 3 g / l and 1 vol.%, Respectively). If any of these instructions side effects are compounded, or if you notice any other side effects not mentioned in the instructions, tell your doctor.
special instructions
Activated renin-angiotensin-aldosterone system: patients whose vascular tone and renal function depends to a large extent on the activity of the RAAS (e.g., in patients with severe chronic heart failure patients (IV functional class NYHA classification), severe renal insufficiency or stenosis of renal артерий), лечение лекарственными средствами, действующими на РААС, такими как ингибиторы АПФ и антагонисты рецепторов ангиотензина II, связано с возможностью развития острой артериальной гипотензии, аз �темии, олигурии или редко острой почечной недостаточности. Возможность развития перечисленных эффектов не может быть исключена и при применении Эдарби®. Резкое снижение АД у пациентов с ишемической кардиомиопатией или ишемическими цереброваскулярными заболеваниями может приводить к развитию инфаркта миокарда или инсульта.
Трансплантация почки: данные о применении Эдарби® у пациентов, недавно перенесших трансплантацию почки, отсутствуют.
Нарушение функции печени: данные о клиническом опыте применения Эдарби® у пациентов с тяжелой степенью нарушения функции печени отсутствуют, поэтому применение препарата у данной категории пациентов не рекомендуется.
Артериальная гипотензия на фоне нарушения водно-электролитного баланса: у больных со сниженным ОЦК и/или с гипонатриемией (в результате рвоты, диареи, приема больших доз диуретиков или соблюдения диеты с ограничением приема поваренной соли) может развиваться клинически значимая артериальная гипотензия после начала терапией Эдарби®. Гиповолемию следует скорректировать перед началом лечения препаратом Эдарби® или начать лечение с дозировки 20 мг.
Первичный гиперальдостеронизм: пациенты с первичным гиперальдостеронизмом обычно резистентны к терапии гипотензивными препаратами, влияющими на РААС. В связи с этим Эдарби® не рекомендуется назначать таким пациентам.
Гиперкалиемия: клинический опыт применения других препаратов, влияющих на РААС, показывает, что одновременное назначение Эдарби® с калийсберегающими диуретиками, препаратами калия или заменителями солей, содержащими калий, или другими препаратами, которые могут увеличить содержание калия в крови (например, гепарин), может привести к гиперкалиемии у пациентов с артериальной гипертензией. У пожилых пациентов, пациентов с почечной недостаточностью, сахарным диабетом и/или у пациентов с другими сопутствующими заболеваниями увеличивается риск развития гиперкалиемии, которая может быть фатальной. У таких пациентов рекомендуется контролировать содержание калия в сыворотке крови.
Стеноз аортального или митрального клапанов, гипертрофическая обструктивная кардиомиопатия: при назначении Эдарби® пациентам с аортальным или митральным стенозом или гипертрофической обструктивной кардиомиопатией необходимо соблюдать осторожность.
Литий: как и в случае других антагонистов рецепторов ангиотензина II, не рекомендуется одновременное применение препаратов лития и препарата Эдарби® (см. раздел Взаимодействие с другими лекарственными средствами)
The effect on the ability to drive vehicles and mechanisms
На основании фармакодинамических свойств ожидается, что азилсартана медоксомил будет незначительно влиять на способность к вождению автотранспорта и управлению механизмами. Необходимо соблюдать осторожность, как и при применении любых гипотензивных средств (риск развития головокружения и повышенной утомляемости).
Storage conditions
Хранить в оригинальной упаковке для защиты от света и влаги при температуре не выше 25 С. Хранить в недоступном для детей месте.
Dosing and Administration
Эдарби® принимают внутрь один раз в сутки независимо от времени приема пищи. Рекомендованная начальная доза – 40 мг 1 раз в сутки. При необходимости дополнительного снижения АД дозу препарата можно увеличить до максимальной – 80 мг 1 раз в сутки. Максимальная суточная доза составляет 80 мг. В случае неадекватного контроля АД в монотерапии препаратом Эдарби® возможно его одновременное применение с другими гипотензивными средствами, включая диуретики (хлорталидон и гидрохлоротиазид) и дигидропиридиновые блокаторы «медленных» кальциевых каналов (амлодипин).
Продолжительность курса лечения
Эдарби® следует принимать ежедневно, без перерыва. В случае прекращения лечения пациент должен сообщить об этом врачу.
Пропуск дозы
В случае пропуска приема очередной дозы пациенту следует принять следующую дозу в обычное время. Не следует принимать двойную дозу препарата Эдарби®.
Особые группы
Пациенты пожилого возраста (65 лет и старше)
Не требуется коррекция начальной дозы препарата Эдарби® у пациентов пожилого возраста. Однако у пациентов в возрасте старше 75 лет доза 20 мг может рассматриваться как начальная (повышается риск развития артериальной гипотензии).
Patients with impaired renal function
Нет клинического опыта применения Эдарби® у пациентов с АГ с нарушением функции почек тяжелой степени и терминальной стадией почечной недостаточности, поэтому применять препарат у данной категории пациентов следует с осторожностью. Необходим мониторинг выделительной функции почек. Не требуется коррекции режима дозирования у пациентов с нарушениями функции почек легкой и умеренной степени тяжести.
Patients with impaired liver function
Не рекомендуется применение препарата у пациентов с нарушениями функции печени тяжелой степени по причине отсутствия клинического опыта (см. раздел Противопоказания). Из-за ограниченного опыта применения Эдарби® у пациентов с нарушениями функции печени легкой и средней степени тяжести рекомендуется начинать лечение с дозы 20 мг 1 раз в сутки и проводить его под тщательным наблюдением.
Снижение объема циркулирующей крови (ОЦК)
Препарат Эдарби® следует назначать пациентам со снижением ОЦК и/или гипонатриемией (например, пациентам с длительной рвотой, диареей, или принимающим большие дозы диуретиков) только в условиях строгого медицинского контроля. Также рекомендуется начинать лечение с дозировки 20 мг 1 раз в сутки
Heart failure
По причине отсутствия клинического опыта следует с осторожностью применять Эдарби® у пациентов с АГ с тяжелой хронической сердечной недостаточностью (IV функциональный класс по классификации NYHA)
Негроидная раса
Не требуется коррекции дозы у пациентов негроидной расы. Как и в случае других антагонистов рецепторов ангиотензина II (AT1) и ингибиторов АПФ, у пациентов негроидной расы наблюдается меньшее снижение АД по сравнению с остальной популяцией. В связи с этим для адекватного контроля АД у пациентов негроидной расы могут быть необходимы увеличение дозы Эдарби® и комплексная терапия чаще, чем у других пациентов.
Information
Appearance may differ from that depicted in the picture. There are contraindications. You need to read the manual or consult with a specialist