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Active ingredients
Azilsartan medoxomil potassium
Release form
Pills
Pharmacological effect
A specific antagonist of type 1 angiotensin ii receptors (at1). azylsartan medoxomil is a prodrug. it quickly turns into an active azilsartan molecule, 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 raas with effects including vasoconstriction, cardiac stimulation, stimulation of synthesis and release of aldosterone, and, as a result, renal reabsorption of sodium. blockade of receptors at1 inhibits the negative regulatory response of angiotensin ii to the secretion of the sodium block. renin and circulating angiotensin ii levels do not suppress the antihypertensive effect of azilsartan. The antihypertensive effect of azilsartan medoxomil develops during 2 weeks of use with the achievement of the maximum therapeutic effect after 4 weeks. A decrease in hell after ingestion of a single dose is usually achieved within a few hours and persists for 24 hours. The withdrawal syndrome after a sudden discontinuation of treatment with prolonged therapy (for 6 months) did not show edarbi. The safety and efficacy of the drug does not depend on the age of the patients , but greater sensitivity to hell reduction in some elderly patients can not be excluded. As with the use of other antagonists of angiotensin ii receptors and APF inhibitors, the antihypertensive effect is less pronounced in patients of the Negroid race (usually a population with low renin activity in plasma). the simultaneous use of edarbi 40 mg and 80 mg with dihydropyridine blockers of slow calcium channels (amlodipine) or thiazide diuretics (chlorthalidone) leads to an additional decrease in hell compared to antihypertensive therapy used in monotherapy. effect on repolarization processes, assessment of the drug preparation Edgar abs scores qtc was performed in healthy volunteers during the qt / qtc study. when using the drug edarbi in a dose of 320 mg, an increase in the qt / qtc interval was not observed.qtc is the corrected (relative to the heart rate) value of the qt interval, the relative value. because the duration of the qt interval depends on the heart rate (lengthening when it is slowed down), for evaluation it must be adjusted relative to the heart rate. prolongation of the qt interval reflects the heterogeneity of the repolarization of the ventricular myocardium, and is regarded as an independent indicator indicating the possibility of the appearance of fatal cardiac rhythm disturbances.
Pharmacokinetics
Absorption The estimated absolute bioavailability of azilsartan medoxomil when administered is approximately 60% according to the concentration profile in the blood plasma. Cmax azilsartan in plasma is on average achieved within 1.5-3 hours after taking the drug inside. Food intake does not affect the bioavailability of azilsartan. Distribution The pharmacokinetics of azilsartan medoxomil is proportional to the dosage in the dose range from 20 mg to 320 mg after a single or multiple ingestion. Vd azilsartan is about 16 liters. Azilsartan binds to plasma proteins (more than 99%), mainly albumin. The bond with plasma proteins is kept constant when the concentration of azilsartan in the blood plasma is much higher than the range achieved when taken in recommended doses. Css of azylsartan is reached within 5 days, its cumulation in blood plasma with daily use of 1 time / day does not occur. Studies on animals with radioactive labels showed that the amount of azilsartan penetrating through the BBB is minimal. Medoxomil is converted to the pharmacologically active metabolite azilsartan by the action of the carboxymethylene butenolidase enzyme in the intestine and liver. Azilsartan is metabolized to two primary metabolites predominantly in the liver. The main metabolite in the blood plasma is formed by O-dealkylation and is designated as the metabolite M-II, the minor metabolite is formed by decarboxylation and is designated as the metabolite M-I. The AUC values for these metabolites in humans are 50% and less than 1%, respectively, compared to azilsartan. 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 the isoenzyme CYP2C9. Excretion Azilsartan and its metabolites are excreted both through the intestines and by the kidneys.Studies have shown that after oral administration of azilsartan medoxomil, about 55% (mostly in the form of metabolite M-I) is found in the feces and about 42% (15% in the form of azilsartan, 19% in the form of metabolite M-II) in urine. T1 / 2 azilsartan is about 11 hours, renal clearance is about 2.3 ml / min. Pharmacokinetics in special groups of patients The pharmacokinetics of azilsartan in children and adolescents under the age of 18 years have not been studied. The pharmacokinetics of azilsartan in young patients (18-45 years) and elderly patients age (65-85 years) is not significantly different. In patients with mild, moderate and severe renal insufficiency, the AUC was increased by 30%, 25% and 95%, respectively. An increase in AUC (5%) in patients with end-stage renal failure on hemodialysis was not observed. Clinical data on pharmacokinetics in patients with severe or terminal stage of renal failure are not available. Azilsartan is not eliminated from systemic blood flow through hemodialysis. Using the Edarbi drug for more than 5 days in patients with mild (grade A on the Child-Pugh scale) or moderate (grade B on the Child-Pugh scale) severity of liver failure leads to a slight increase in AUC (in 1.3-1.6 times, respectively). The pharmacokinetics of the drug Edarbi in patients with severe (class C on the Child-Pugh scale) degree of liver failure has not been studied. The pharmacokinetics of azilsartan in men and women is not significantly different. Dose adjustment based on gender is not required. The pharmacokinetics of azilsartan are not significantly different depending on the race of patients. Dose adjustment depending on race is not required.
Indications
Treatment of essential hypertension in adults.
Contraindications
- hypersensitivity to the active substance or to any of the excipients of the drug Edarbi; - the combined use of aliskiren and azilsartan in patients with diabetes mellitus; - pregnancy; - lactation period; - children and adolescents under 18 years of age.
Precautionary measures
The drug should be stored in its original packaging to protect from light and moisture, out of the reach of children at a temperature not exceeding 25 ° C.
Use during pregnancy and lactation
PregnancyAn animal studies have revealed 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 the Edarbi drug and, if necessary, start a course of treatment with drugs approved for use in pregnancy. Newborns whose mothers received therapy with Edarbi may develop hypotension, and therefore newborns should be under careful medical observation. Lactation period. There is no information about the ability of azilsartan and / or its metabolites to penetrate into breast milk. In animal studies, it has been found that azilsartan and M-II are excreted with milk activating rats. Due to the lack of experience with the use of Edarbi in women during breastfeeding, its use in this category of patients is not recommended. Preferably the use of drugs with the most studied safety profile, especially during the care of a newborn or premature baby. Fertility Data about the effect of Edarbi on fertility in humans are absent. Preclinical studies have shown no effect on male or female fertility in rats.
Side effects
When taking the drug Edarbi side effects can be mild or moderate severity. Gender and age do not affect the frequency of side effects. The frequency of side effects of the drug is as follows: very often (≥1 / 10), often (≥1 / 100, Often: dizziness, diarrhea, elevated blood CPC. Often: hypotension, fatigue, peripheral edema, increased blood creatinine, increased concentration of uric acid in the blood / hyperuricemia. Rarely: angioedema, including edema of the periotic and periorbital regions, decrease in the concentration of hemoglobin and hematocrit.
Overdose
Experience with the use of the drug Edarbi in adults in doses up to 320 mg / day for 7 days shows that the drug is well tolerated. Symptoms: pronounced decrease in blood pressure, dizziness. Treatment: when a pronounced decrease in blood pressure should transfer the patient to a horizontal position with a low headboard; It is recommended that measures to increase the BCC and symptomatic therapy. Hemodialysis is ineffective.
Interaction with other drugs
A reversible increase in serum lithium concentration and manifestation of toxicity were observed with simultaneous use of lithium preparations and ACE inhibitors and lithium preparations with angiotensin II receptor antagonists. Therefore, the simultaneous use of azilsartan medoxomil in combination with lithium preparations is not recommended. If it is necessary to use this combination, regular monitoring of the lithium content in the blood serum is recommended. With simultaneous use of angiotensin II antagonists and NSAIDs (for example, selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs, the antihypertensive effect may be reduced. With simultaneous use of antagonists of angiotensin II and NSAIDs may increase the risk of impaired renal function and an increase in the content of potassium in the blood serum. Therefore, at the beginning of treatment, it is recommended to regularly take a sufficient amount of fluid and monitor kidney function. Simultaneous use of potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium, and other medicines (such as heparin) from azilsartan medoxomil can lead to an increase in serum potassium . Patients during combination therapy should monitor serum potassium. Double RAAS blockade with angiotensin II receptor antagonists, ACE inhibitors or aliskiren is associated with an increased risk of arterial hypotension, hyperkalemia, and impaired renal function (including acute renal failure) compared with monotherapy. No pharmacokinetic interactions were observed with the simultaneous use of azilsartan medoxomil or azilsartan with amlodipine, antacid preparations (mag Ia and aluminum hydroxide), chlorthalidone, digoxin, fluconazole, glibenclamide, ketoconazole, metformin and varfarinom.Azilsartana medoxomil is converted into a pharmacologically active metabolite azilsartan during absorption from the intestine by the enzyme karboksimetilenbutenolidazy in the intestine and liver. Studies in vitro have shown that interactions based on the inhibition of enzymes, are maloveroyatnymi.Antigipertenzivny effect of therapy azilsartana medoksomilom can be enhanced by the combined use with other antihypertensive agents including diuretics (chlorthalidone and hydrochlorothiazide), dihydropyridine calcium channel blockers slow (amlodipine).
special instructions
Patients whose vascular tone and kidney function depend to a large extent on the activity of the RAAS (for example, in patients with severe chronic heart failure (class IVHA functional class IV), severe renal failure or renal artery stenosis). on RAAS, such as ACE inhibitors and angiotensin II receptor antagonists, is associated with the possibility of developing acute arterial hypotension, azotemia, oliguria, or, rarely, acute renal failure . The possibility of the development of these effects can not be excluded when using Edarbi. A drastic decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases may lead to the development of myocardial infarction or stroke. There are no data on the use of Edarbi in patients who have recently had a kidney transplant. about the clinical experience of the use of the drug Edarbi in patients with severe hepatic impairment is absent, therefore, the use of the drug in this category These patients are not recommended. Patients with reduced BCC and / or hyponatremia (as a result of vomiting, diarrhea, taking diuretics in high doses, or following a diet with restricted salt intake) may develop clinically significant hypotension after starting treatment with Edarbi. Hypovolemia should be corrected before starting treatment with Edarbi or starting treatment with a dosage of 20 mg. Patients with primary hyperaldosteronism are usually resistant to treatment with antihypertensive drugs that affect the RAAS. In this regard, the Edarbi drug is not recommended for such patients. Clinical experience with other drugs that affect the RAAS shows that the simultaneous prescription of the Edarbi drug with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that may increase the content potassium in the blood (for example, heparin), can lead to hyperkalemia in patients with arterial hypertension. Elderly patients, patients with renal insufficiency, diabetes mellitus and / or patients with other concomitant diseases increase the risk of developing hyperkalemia, which can be fatal.In such patients, it is recommended to control the content of potassium in the blood serum. When using the Edarbi drug in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy, caution should be taken. Influence on ability to drive motor transport and control mechanisms. On the basis of pharmacodynamic properties it is expected that azilsart Ana Medoxomil will have little effect on the ability to drive and control machinery. Care must be taken as with the use of any antihypertensive drugs (risk of dizziness and increased fatigue).