Description
Pharmacological action
Specific angiotensin II receptor antagonist type 1 (AT1). Azilsartan medoxomil is a prodrug. It quickly turns into an active molecule of azilsartan, which selectively inhibits 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 RAAS with effects including vasoconstriction, cardiac stimulation, stimulation of synthesis and release of aldosterone, and, as a result, renal reabsorption of sodium.
AT1 receptor blockade inhibits the negative regulatory response of angiotensin II to renin secretion, but the resulting increase in plasma renin activity and the level of circulating angiotensin II does not inhibit the antihypertensive effect of azilsartan.
The antihypertensive effect of azilsartan medoxomil develops during the first 2 weeks of use with maximum therapeutic effect after 4 weeks. A decrease in blood pressure after oral administration of a single dose is usually achieved within a few hours and persists for 24 hours.
Discontinuation syndrome after a sudden cessation of admission with prolonged therapy (for 6 months) with Edarbi ® was not observed.
Safety and efficacy of the drug are independent of the age of the patients, but greater sensitivity to lowering blood pressure in some elderly patients cannot be ruled out. As with other angiotensin II receptor antagonists and ACE inhibitors, the antihypertensive effect is less pronounced in patients of the Negroid race (usually a population with low plasma renin activity). The simultaneous use of Edarbi ® 40 mg and 80 mg with dihydropyridine blockers of slow calcium channels (amlodipine) or thiazide diuretics (chlortalidone) leads to an additional decrease in blood pressure compared with the antihypertensive drugs used in monotherapy.
Effect on repolarization processes
Evaluation of the potential of the drug Edarbi ® to increase the QT / QTc interval was carried out in healthy volunteers during the QT / QTc study. When using the drug Edarbi ® at a dose of 320 mg, an increase in the QT / QTc interval was not noted. QTc – corrected (relative to heart rate) QT interval value, relative value. Because the duration of the QT interval depends on the heart rate (lengthening when it slows down), to assess it must be corrected for heart rate. The lengthening of the QT interval reflects the heterogeneity of the ventricular myocardial repolarization processes, and is regarded as an independent indicator indicating the possibility of fatal cardiac arrhythmias.
Indications
essential hypertension.
Contraindications
severe hepatic impairment (more than 9 Child-Pugh scores) (no experience gained)
pregnancy
concurrent administration of aliskiren in patients with diabetes
age under 18 years (efficacy and safety not established)
increased active substance and other components of the drug.
Precautions should be used in patients with severe chronic heart failure (NYHA class IV functional class) severe renal failure (CC <30 ml / min) bilateral renal artery stenosis and artery stenosis of the only functioning kidney ischemic cardiomyopathy ischemic cerebrovascular disease condition after kidney transplantation conditions accompanied by a decrease in BCC (including vomiting, diarrhea), as well as in patients on a diet with a restriction of salt while diuretics in high doses of primary hyperaldosteronism hyperkalemia hypertrophic stenosis of aortic and mitral valves hypertrophic obstructive cardiomyopathy (in GOKMP) in patients over 75 years old. Special instructions Patients in whom vascular tone and renal function depend to a large extent on RAAS activity (e.g. in patients with severe chronic heart failure (NYHA class IV functional class), severe renal failure, or renal artery stenosis), treatment with drugs acting 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 developing these effects cannot be excluded with the use of Edarbi ®. 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. Data on the use of the drug Edarbi ® in patients who have recently undergone kidney transplantation are not available. Data on the clinical experience with the use of the drug Edarbi ® in patients with severe hepatic impairment are not available, therefore, the use of the drug in this category of patients is not recommended. Patients with reduced BCC and / or hyponatremia (vomiting, diarrhea, high-dose diuretics, or diets that restrict salt intake) may develop clinically significant arterial hypotension after starting treatment with Edarbi ®. Hypovolemia should be adjusted before starting treatment with Edarbi ® or starting treatment with a dosage of 20 mg. Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect RAAS. In this regard, the drug Edarbi ® is not recommended for such patients. Clinical experience with other drugs that affect RAAS suggests that concurrent administration of Edarbi ® with potassium-sparing diuretics, potassium preparations, or salt substitutes containing potassium, or other drugs that can increase blood potassium (e.g., heparin) lead to hyperkalemia in patients with arterial hypertension. Elderly patients, patients with renal failure, diabetes mellitus and / or patients with other concomitant diseases have an increased risk of developing hyperkalemia, which can be fatal. In such patients, it is recommended that serum potassium levels be monitored. Caution must be exercised when using Edarbi ® in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy. As with other angiotensin II receptor antagonists, the simultaneous use of lithium and Edarbi ® is not recommended. Influence on the ability to drive vehicles and control mechanisms Based on the pharmacodynamic properties, it is expected that azilsartan medoxomil will slightly affect the ability to drive vehicles and control mechanisms. Caution must be exercised, as with any antihypertensive drug (risk of dizziness and increased fatigue). Composition Composition 1 tablet: Active ingredient: medoxomil azilsartan – 20 mg (medoxomil potassium azilsartan – 21.34 mg) Excipients: mannitol – 47.815 mg, fumaric acid – 1 mg, sodium hydroxide – 0.345 mg 2.7 mg, croscarmellose sodium – 6.9 mg, microcrystalline cellulose – 9 mg, magnesium stearate – 0.9 mg. Dosage and administration The drug is taken orally 1 time / day, regardless of food intake. Recommended starting dose is 40 mg 1 time / day. If necessary, additional reduction in blood pressure, the dose of the drug can be increased to a maximum of 80 mg 1 time / day. The maximum daily dose is 80 mg. In case of inadequate blood pressure control when using Edarbi ® as a monotherapy, it can be used simultaneously with other antihypertensive drugs, including diuretics (chlortalidone and hydrochlorothiazide) and dihydropyridine slow calcium channel blockers (amlodipine). Edarbi ® should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor. If you miss the next dose, the patient should take the next dose at the usual time. Do not take a double dose of Edarbi ®. No adjustment is required for the initial dose of Edarbi ® in elderly patients. However, in patients over the age of 75 years, a dose of 20 mg can be considered as the initial (increased risk of developing arterial hypotension). Dosage adjustment is not required in patients with impaired renal function of mild to moderate severity. There is no clinical experience with the use of Edarbi ® in patients with severe renal impairment and end-stage renal failure, therefore, the drug should be used in this category of patients with caution. Due to the limited experience with the use of the drug Edarbi ® in patients with impaired liver function of mild to moderate severity, it is recommended to start treatment with a dose of 20 mg 1 time / day and conduct it under close supervision. The use of the drug in patients with severe liver dysfunction is not recommended due to lack of clinical experience. Edarbi ® should be prescribed to patients with a decrease in BCC and / or hyponatremia (for example, patients with prolonged vomiting, diarrhea, or taking diuretics in large doses) only under strict medical supervision. It is recommended to start treatment with a dosage of 20 mg 1 time / day. Due to the lack of clinical experience, the Edarbi ® preparation should be used with caution in patients with severe chronic heart failure (functional class IV according to NYHA classification). No dose adjustment is required in patients of the Negroid race. As with other angiotensin II receptor antagonists (AT1) and ACE inhibitors, patients of the Negroid race have a lower 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, it may be necessary to increase the dose of Edarbi ® and complex therapy more often than in other patients. Side effects The frequency of adverse reactions was determined in accordance with WHO recommendations: very often (> 1/10) often (> 1/100, <1/10) infrequently (> 1/1000, <1/100) rarely (> 1/10 000, <1/1000) is very rare (<1/10 000), including individual messages of unspecified frequency (the frequency cannot be calculated from the available data). From the nervous system: often – dizziness. From the cardiovascular system: infrequently – a pronounced decrease in blood pressure. From the digestive system: often – diarrhea infrequently – nausea. From the skin and subcutaneous tissues: infrequently – rash, itching rarely – angioedema. From the musculoskeletal system: infrequently – muscle cramps. On the part of laboratory and instrumental studies: often – increased CPK activity infrequently – increased creatinine concentration, hyperuricemia. Other: infrequently – fatigue, peripheral edema. Description of individual adverse reactions With the simultaneous use of the drug Edarbi ® with chlortalidone, the frequency of adverse reactions – a pronounced decrease in blood pressure and an increase in creatinine concentration – increases in frequency with infrequently to often. With the simultaneous use of Edarbi ® with amlodipine, the frequency of an undesirable reaction – peripheral edema – increases from infrequent to frequent, but is less common than with amlodipine monotherapy. Angioedema is rare, including swelling of the face, lips, and periorbital edema. As with other angiotensin II receptor antagonists and ACE inhibitors, the simultaneous use of Edarbi ® with diuretics (for example, chlortalidone) leads to more frequent cases of increased creatinine concentration. An increase in creatinine concentration while the use of Edarbi ® with diuretics is associated with a more pronounced decrease in blood pressure compared with monotherapy with Edarbi ®. Most of these effects were short-term or non-progressive while patients continued therapy. After discontinuation of the drug, most cases of an increase in creatinine concentration that did not pass during treatment were reversible. Creatinine concentration in most patients returned to the values located on the baseline, or values ² ¹ ² ¹close to the baseline. During treatment with Edarbi ®, there was a slight increase in the concentration of uric acid in the blood serum (10.8 Ñmol / L) compared with placebo (4.3 Ñmol / L). As with other RAAS inhibitors, when Edarbi ® was used as monotherapy, a slight decrease in hemoglobin and hematocrit was observed (on average, decreased by about 3 g / l and 1 vol.%, respectively). If any of the side effects indicated in the instructions are aggravated, or the patient notes other side effects not listed in the instructions, you should inform your doctor. Storage conditions 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. Expiration 3 years. Active ingredient azilsartan medoxomil drugstore terms drugstore Dosage form tablets
