Edarbi tablets 80mg №14×2

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Edarbi tab. 80mg in bl. in pack. No. 14×2 The main active ingredient Azilsartan medoxomil Release form tablets Dosage 80 mg Special instructions and precautions for use Activated renin-angiotensin-aldosterone system congestive heart failure, severe renal failure, or renal artery stenosis), treatment with drugs that act on this system, such as angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists, has been associated with the development of acute arterial hypotension, azotemia, oliguria, or, in rare cases, , acute renal failure. The possibility of developing such effects cannot be ruled out when Edarbi is used. Caution should be exercised when prescribing the drug Edarbi to patients with arterial hypertension and severe renal failure, congestive heart failure or renal artery stenosis, since there is no clinical experience in the treatment of such patients (see section “Dosage regimen and route of administration” and “Pharmacokinetic properties”). A sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular disease can lead to the development of myocardial infarction or stroke. Double blockade of the renin-angiotensin-aldosterone system (RAAS) There is evidence that the simultaneous use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the risk of hypotension, hyperkalemia and decreased renal function (including acute renal failure). Therefore, dual blockade of the RAAS by concomitant administration of ACE inhibitors, angiotensin II receptor antagonists or aliskiren is not recommended (see section “Interactions with other medicinal products” and “Pharmacodynamic properties”). If a double blockade is absolutely necessary, it should be carried out only under the supervision of a specialist, subject to strict control of renal function, electrolyte levels and blood pressure. ACE inhibitors and angiotensin II receptor antagonists should not be co-administered in patients with diabetic nephropathy. Kidney transplantation At the moment, there is no clinical experience with the use of the drug Edarbi in patients who have recently undergone kidney transplantation. Impaired liver function Clinical experience with the use of the drug Edarbi in patients with severe liver dysfunction is absent, therefore, the use of the drug by patients from this category is not recommended (see section “Dosage regimen and route of administration” and “Pharmacokinetic properties”). Arterial hypotension in patients with dehydration and / or sodium loss In patients with a significant decrease in circulating blood volume and / or a decrease in sodium content (for example, in patients with vomiting, diarrhea, or taking high doses of diuretics), symptomatic hypotension. Before starting therapy with Edarbi, hypovolemia should be corrected or therapy should be started under strict medical supervision. Primary hyperaldosteronism Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that inhibit the renin-angiotensin system. In this regard, the drug Edarbi is not recommended for such patients. Hyperkalemia Clinical experience with other drugs that affect the renin-angiotensin-aldosterone system shows that the simultaneous use of Edarbi with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase the content of potassium in the blood (for example, heparin), may lead to an increase in potassium levels in patients with arterial hypertension (see section “Interactions with other medicinal products”). In elderly patients, patients with renal insufficiency, diabetes mellitus and / or patients with other concomitant diseases, the risk of developing hyperkalemia, which can be fatal, is increased. Strict monitoring of potassium levels is necessary. Stenosis of the aortic and mitral valve, obstructive hypertrophic cardiomyopathy When prescribing the drug to patients with stenosis of the aortic and mitral valve, or obstructive hypertrophic cardiomyopathy (OHCM), special care should be taken. Pregnancy Angiotensin II receptor antagonists should not be administered during pregnancy. Unless continued therapy with angiotensin II receptor antagonists is considered life-saving, patients planning pregnancy should be switched to alternative antihypertensive therapy with an established safety profile for pregnant women. Immediately after confirmation of pregnancy, angiotensin II receptor antagonists should be discontinued and, if necessary, alternative therapy should be started (see section “Contraindications” and “Fertility, pregnancy and lactation”). Lithium As with other angiotensin II receptor antagonists, the simultaneous use of a combination of lithium and Edarbi is not recommended (see section “Interactions with other drugs”). Pharmacological properties Pharmacodynamics Mechanism of action and pharmacological effect Azilsartan medoxomil is a pro-drug for oral administration, which is rapidly converted into the active azilsartan molecule, which selectively prevents the development of the effects of angiotensin II by blocking its binding to AT1 receptors in various tissues (see section “Pharmacokinetic properties” ). Angiotensin II is the primary vasoactive hormone of the renin-angiotensin system, its effects include vasoconstriction, stimulation of aldosterone synthesis and release, cardiac stimulation, and renal sodium reabsorption. Blockade of AT1 receptors inhibits the negative rebound effect of angiotensin II on renin secretion, however, the resulting increase in plasma renin activity in plasma and the level of circulating angiotensin II does not overcome the antihypertensive effect of azilsartan. Essential Hypertension A total of 5941 patients were enrolled in seven double-blind controlled trials (3672 on Edarbi, 801 on placebo, 1468 on the active comparator). 51% were male, 26% of patients were 65 years of age or older (5% ≥ 75 years); 67% belonged to the Caucasian race, 19% – to the Negroid. Edarbi was compared with placebo and active comparators in two 6-week, randomized, double-blind studies. The levels of blood pressure reduction in both studies, compared with placebo, were derived from mean 24-hour blood pressure readings measured using the ambulatory blood pressure monitoring (AMAD) system and clinical methods, and are summarized in the table below. In addition, the drug Edarbi 80 mg contributed to a significantly more pronounced decrease in systolic blood pressure (SBP) than the maximum allowable dosages of olmesartan medoxomil and valsartan. OLM-M – olmesartan medoxomil, MLS = least squares method, MWRP = last preceding missing value replacement method. * Significant difference compared to placebo at the 0.05 level in a stepwise analysis. § Significant difference compared to comparator(s) at the 0.05 level in a stepwise analysis. # Maximum dose achieved in study 2. Doses were proactively increased at week 2 from 20 to 40 mg and from 40 to 80 mg for Edarbi, and from 20 to 40 mg and from 160 to 320 mg, respectively, for olmesartan medoxomil and valsartan. In these two clinical studies, the most significant and common adverse reactions were dizziness, headache, and dyslipidemia. In the case of Edarbi, olmesartan medoxomil and valsartan, dizziness was observed with a frequency of 3.0%, 3.3% and 1.8%, headache with a frequency of 4.8%, 5.5% and 7.6%, dyslipidemia – 3 .5%, 2.4% and 1.1%, respectively. In studies using the active comparator drug (valsartan or ramipril), the pressure-lowering effect of Edarbi was stable over a long period of treatment. In the Edarbi group, the incidence of cough (1.2%) was lower compared to the ramipril group (8.2%). The antihypertensive effect of the drug Edarbi manifested itself during the first 2 weeks of use, reaching a maximum by 4 weeks. With a sharp cessation of taking Edarbi after 6 months of treatment, rebound arterial hypertension was not observed. Significant differences in the safety and efficacy profile between young and elderly patients were not observed, however, increased sensitivity to lower blood pressure in some elderly patients cannot be ruled out (see section “Dosage regimen and method of application”). As with other angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors, the antihypertensive effect was lower in black patients (generally belonging to a population with low renin levels). The combined use of the drug Edarbi 40 mg or 80 mg and a calcium channel blocker (amlodipine) or a thiazide-like diuretic (chlorthalidone) led to an additional decrease in blood pressure, compared with each individual diuretic antihypertensive agent (chlorthalidone), led to an additional decrease in blood pressure, compared with each individual antihypertensive agent. Dose-dependent adverse reactions, including dizziness, hypotension and increased creatinine levels, were observed more frequently when using Edarbi in combination with a diuretic than when using it in the form of monotherapy, while hypokalemia occurred less frequently compared with the use of a single diuretic. At the moment, the beneficial effects of the drug Edarbi on overall mortality, mortality from cardiovascular diseases and damage to individual target organs have not been established. Influence on the processes of cardiac repolarization A thorough QT/QTc study in healthy patients was conducted to evaluate the ability of Edarbi to prolong the QT/QTc interval. In doses up to 320 mg, Edarbi did not show this effect. Pharmacokinetics After oral administration of azilsartan, medoxomil is rapidly hydrolyzed in the gastrointestinal tract and / or during absorption to the active metabolite of azilsartan. According to the results of in vitro studies, hydrolysis in the intestine and liver takes place with the participation of carboxymethylene butenolidase. Also, plasma esterases are involved in the hydrolysis of azilsartan medoxomil to azilsartan. Absorption The calculated absolute oral bioavailability of azilsartan medoxomil based on the plasma concentration profile is approximately 60%. After oral administration of azilsartan medoxomil, the maximum plasma concentration (Cmax) of azilsartan is reached within 1.5-3 hours. Food intake does not affect the bioavailability of azilsartan (see section “Dosage regimen and method of administration”). Distribution The volume of distribution of azilsartan is about 16 liters. Azilsartan is highly bound to plasma proteins (> 99%), predominantly to serum albumin. Communication with plasma proteins remains constant at a plasma concentration of azilsartan that is significantly higher than the range achieved when taking the recommended doses. Metabolism Azilsartan is metabolized to two primary metabolites. The main metabolite in 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 amount in the systemic circulation of the main and minor metabolite compared with azilsartan in humans was approximately 50% and less than 1%, respectively. Metabolites M-I and M-II do not affect the pharmacological activity of the drug Edarbi. The main enzyme responsible for the metabolism of azilsartan is CYP2C9. Excretion After oral administration of 14C-labeled azilsartan medoxomil, approximately 55% of the radioactivity was found in the feces and approximately 42% in the urine, with 15% of the dose found in the urine as azilsartan. 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 the blood plasma does not occur with a single daily use. Linearity/Nonlinearity Linearity of the blood dose/concentration ratio was confirmed for azilsartan in azilsartan medoxomil in the dose range of 20-320 mg after single or multiple oral administration. Pharmacokinetics in special groups of patients Pediatric patients The pharmacokinetics of azilsartan in children under 18 years of age have not been studied. Elderly patients The pharmacokinetics of azilsartan in young (18-45 years) and elderly (65-85 years) patients does not differ significantly. Renal insufficiency In patients with mild, moderate and severe renal insufficiency, the total content in the bloodstream (AUC) of azilsartan was increased by 30%, 25% and 95%, respectively. There was no increase (+5%) in ESRD patients on hemodialysis! However, there is no experience in the treatment of patients with severe or end-stage renal disease (see section “Dosage regimen and route of administration”). Azilsartan is not removed from the systemic circulation by hemodialysis. Liver failure The use of Edarbi for up to 5 days in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) liver failure resulted in a slight increase in the level of azilsartan (AUC increased by 1.3-1, 6 times, see section “Dosage regimen and method of application”). The use of the drug in patients with severe hepatic insufficiency has not been studied. Gender The pharmacokinetics of azilsartan in men and women does not differ significantly. Dose adjustment based on sex is not required. Race The pharmacokinetics of azilsartan in patients of Caucasian and Negroid races does not differ significantly. Dose adjustment based on race is not required. Indications for use The drug Edarbi is intended for the treatment of essential hypertension in adults. Dosage and administration Dosage The recommended initial dose is 40 mg once a day. If the specified dose is not enough for adequate control of blood pressure (BP) in patients, it can be increased to a maximum of 80 mg once a day. The antihypertensive effect close to the maximum appears 2 weeks after the start of therapy and reaches a maximum by 4 weeks. In case of inadequate blood pressure control during monotherapy with Edarbi, it is possible to use it simultaneously with other antihypertensive drugs, including diuretics (such as chlorthalidone and hydrochlorothiazide) and calcium channel blockers (see sections “Contraindications”, “Special instructions and measures precautions”, “Interactions with other drugs” and “Pharmacodynamic properties”). Special groups of patients Elderly patients (65 years and older) Correction of the initial dose of the drug Edarbi in elderly patients is not required (see section “Pharmacokinetic properties”). Renal failure The drug Edarbi should be used with caution in patients with arterial hypertension with concomitant severe renal impairment and end-stage renal failure, since there is no clinical experience with the use of Edarbi in such patients (see section “Special Instructions and Precautions” and “Pharmacokinetic properties”). Azilsartan is not removed from the systemic circulation by hemodialysis. Correction of the dosing regimen in patients with impaired renal function of mild or moderate severity is not required. Hepatic insufficiency The drug Edarbi has not been studied in patients with severe hepatic impairment, so the use of the drug in patients of this category is not recommended (see section “Special instructions and precautions” and “Pharmacokinetic properties”). Due to the limited experience with the use of the drug Edarbi for patients with impaired liver function of mild or moderate severity, careful monitoring is recommended (see section “Pharmacokinetic properties”). Decrease in circulating blood volume Edarbi should only be administered to patients with a potential decrease in circulating blood volume or excessive excretion of sodium chloride from the body (for example, patients with vomiting, diarrhea or taking high doses of diuretics) only under close medical supervision. Heart failure Caution should be exercised when prescribing Edarbi to patients with arterial hypertension with concomitant congestive heart failure, since there is no clinical experience in the treatment of such patients with this drug (see section “Special Instructions and Precautions”). Negroid race Dose adjustment in patients of the Negroid race is not required, although compared with representatives of other races, such patients have a less pronounced decrease in blood pressure (see the section “Pharmacodynamic properties”). In general, this phenomenon is also observed in the case of the use of other angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors. Thus, the need to increase the dose of Edarbi or conduct combination therapy in order to more effectively control blood pressure in the treatment of patients of the black race may occur more often. Children The safety and efficacy of Edarbi in children and adolescents aged 0-18 years has not yet been established. No data available. Method of application The drug Edarbi is intended for oral administration, the tablet can be taken both with food and on an empty stomach (see section “Pharmacokinetic properties”). Application during pregnancy and lactation Pregnancy The use of angiotensin II receptor antagonists during the first trimester of pregnancy (see section “Special instructions and precautions”) is not recommended. The use of angiotensin II receptor antagonists during the second and third trimester of pregnancy is contraindicated (see section “Contraindications” and “Special instructions and precautions”). There is no clinical experience with the use of Edarbi in pregnant women. Reproductive toxicity has been demonstrated in animal studies. Available epidemiological data on the risk of teratogenic effects from the use of angiotensin-converting enzyme inhibitors in the first trimester of pregnancy do not allow a definitive conclusion, however, the possibility of a slight increase in this risk should not be ruled out. Although epidemiological data from controlled studies regarding the risk of using angiotensin II receptor antagonists are not available, a similar risk may exist in the case of this class of drugs. Unless continued therapy with angiotensin II receptor antagonists is considered essential, patients planning pregnancy should be switched to alternative antihypertensive therapy with an established safety profile for pregnant women. Immediately after confirmation of pregnancy, angiotensin II receptor antagonists should be discontinued and, if necessary, alternative therapy should be initiated. It is known that therapy with angiotensin II receptor antagonists during the second and third trimester of pregnancy in humans leads to fetotoxicity (impaired renal function, development of oligohydramnios, delayed ossification of the skull bones) and neonatal toxicity (renal failure, hypotension, hyperkalemia). If an angiotensin II receptor antagonist has been used during the second or third trimester of pregnancy, it is recommended to conduct ultrasound monitoring of the state of the skull and kidney function in the fetus. Strict monitoring is necessary for the detection of arterial hypotension in infants if their mothers took angiotensin II receptor antagonists (see section “Contraindications” and “Special instructions and precautions”). Breastfeeding Since there is no clinical experience with the use of the drug Edarbi during breastfeeding, its appointment during this period is not recommended; it is preferable for breastfeeding mothers to choose an alternative treatment with a better established safety profile. Fertility There are no data on the effect of Edarbi on human fertility. In preclinical studies, azilsartan has been shown to have no effect on male or female fertility in rats. Interaction with other drugs Joint use is not recommended Lithium A reversible increase in the concentration of lithium in the blood serum and the manifestation of toxicity during the simultaneous use of lithium preparations and angiotensin-converting enzyme inhibitors have been noted. Similar effects may occur in the case of simultaneous use of lithium preparations and angiotensin II receptor antagonists. Due to the lack of clinical experience with the combined use of azilsartan medoxomil and lithium, the use of a combination of these drugs is not recommended. If appropriate combination therapy is required, careful monitoring of serum lithium levels is recommended. Caution should be exercised when co-administered Non-steroidal anti-inflammatory drugs (NSAIDs), including COX-2 inhibitors, acetylsalicylic acid at doses > 3 g/day, and non-selective NSAIDs With simultaneous use of angiotensin II receptor antagonists and NSAIDs (i.e., selective COX inhibitors -2, acetylsalicylic acid (> 3 g / day) or non-selective NSAIDs) may weaken the antihypertensive effect. In addition, the combined use of angiotensin II receptor antagonists and NSAIDs may lead to an increased risk of developing impaired renal function and an increase in serum potassium. Therefore, at the beginning of treatment, patients are advised to regularly take a sufficient amount of fluid and monitor kidney function. Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs that may increase potassium levels Concomitant use of Edarbi with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, or other drugs (eg, heparin) that may increase the amount of potassium in the blood, may lead to an increase in potassium levels. Strict monitoring of the level of potassium in the blood serum is necessary (see section “Special Instructions and Precautions”). Additional information Clinical studies have shown that dual RAAS with concomitant use of ACE inhibitors, angiotensin II receptor antagonists or aliskiren increases the incidence of adverse events such as hypotension, hyperkalemia and deterioration of kidney function (including the development of acute renal failure) compared with monotherapy agent that affects the RAAS (see section “Contraindications”, “Special instructions and precautions” and “Pharmacodynamic properties”). In studies of the use of azilsartan medoxomil or azilsartan together with amlodipine, antacids, chlorthalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin and warfarin, no clinically significant interactions were observed. In the gastrointestinal tract and / or during absorption under the action of azilsartan esterases, medoxomil is rapidly hydrolyzed to the active substance azilsartan (see section “Pharmacokinetic properties”). In vitro studies have shown that interactions based on esterase inhibition are unlikely. Contraindications Hypersensitivity to the active substance or to any of the excipients. Second and third trimester of pregnancy (see section “Special instructions and precautions” and “Fertility, pregnancy and lactation”). Simultaneous administration of Edarbi with drugs containing aliskiren is contraindicated in patients with diabetes mellitus or impaired renal function (GFR < 60 ml / min / 1.73 m2) (see section "Interactions with other drugs" and "Pharmacodynamic properties"). Each tablet contains 40 mg or 80 mg of azilsartan medoxomil (42.68 mg or 85.36 mg of azilsartan medoxomil potassium, respectively). A complete list of excipients is given in the "List of excipients" section. OverdoseSymptoms Based on the pharmacological properties of the drug, the main symptoms of overdose are probably symptomatic hypotension and dizziness. In controlled clinical trials involving healthy patients, the drug Edarbi was used once a day at doses up to 320 mg / day for 7 days, such treatment was well tolerated by the study participants. Treatment If symptomatic hypotension develops, supportive therapy should be initiated and vital signs monitored. Azilsartan is not excreted by hemodialysis. Side effect Overview of the safety profile The safety of using the drug Edarbi at a dosage of 20, 40 or 80 mg was evaluated in clinical studies lasting up to 56 weeks. Adverse reactions observed during these clinical studies associated with Edarbi therapy were mostly mild or moderate in nature, and their overall frequency was approximately comparable to that of the placebo group. The most common adverse reaction was dizziness. The frequency of development of adverse reactions when using Edarbi did not depend on gender, age or race. Tabulated list of adverse reactions The classification of adverse reactions is based on a summary analysis of data (40 mg and 80 mg doses) and is given below according to system organ classes and terms of preferred use. In each system organ class, adverse reactions are grouped by frequency of occurrence. The frequency is regarded as follows: very often (? 1/10), often (from ? 1/100 to < 1/10), infrequently (from ? 1/1000 to < 1/100), rarely (from ? 10,000 to < 1/1000), very rarely (<1/10 000), including individual cases. Within each frequency category, adverse reactions are listed in descending order of severity. In one placebo-controlled study, the incidence of adverse reactions in Edarbi therapy at a dose of 20 mg was the same as when using the drug at doses of 40 mg and 80 mg. Description: of individual adverse reactions With the simultaneous use of Edarbi with chlorthalidone, the incidence of increased blood creatinine levels and the development of hypotension increased in frequency of occurrence: from “infrequently” to “often”. With the simultaneous use of Edarbi with amlodipine, the incidence of peripheral edema increased in frequency of occurrence: from "infrequently" to "often", but was lower than with amlodipine monotherapy. Influence on the results of laboratory or instrumental studies Serum creatinine levels In randomized placebo-controlled trials of Edarbi monotherapy, the incidence of increased serum creatinine levels was comparable to that of the placebo group. The simultaneous use of Edarbi with diuretics, such as chlorthalidone, led to an increase in the incidence of increased creatinine levels; this observation is consistent with the results of studies on the use of other angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors. An increase in serum creatinine concentration while using Edarbi with diuretics was associated with a more pronounced decrease in blood pressure compared with monotherapy. Most of these reactions were transient or non-progressive despite continued therapy. After discontinuation of the drug, most cases of increased creatinine concentration that did not resolve during treatment were reversible, while the serum creatinine concentration in most patients returned to the original value or was close to the original values. Uric acid In the treatment of Edarbi, there was a slight increase in the level of uric acid in the blood serum (10.8 µmol/l) compared with placebo (4.3 µmol/l). Hemoglobin and hematocrit A slight decrease in hemoglobin and hematocrit (on average by about 3 g / l and 1 vol.%, respectively) was observed in placebo-controlled studies of Edarbi monotherapy. This effect was also observed with the use of other inhibitors of the renin-angiotensin-aldosterone system. Reporting Suspected Adverse Reactions It is important to report suspected adverse reactions after drug registration. This will allow continuous monitoring of the benefit-risk ratio of the medicinal product. If an adverse reaction occurs that is indicated in this package leaflet or not mentioned in it, patients are advised to contact their doctor. Medical professionals are encouraged to report any suspected adverse drug reactions to the Republican Unitary Enterprise "Center for Expertise and Testing in Health Care" (see section "Send information about adverse reactions to the address"). Storage conditions Store in the original packaging to protect from light and moisture at a temperature not exceeding 25°C. Keep out of the reach of children. Buy Edarbi tablets 80mg No. 14x2 Price for Edarbi tablets 80mg No. 14x2