Universal reference book for medicines
Name of the preparation: EDARBI ® (EDARBI)

Active substance: azilsartan medoxomil

Type: Angiotensin II receptor antagonist

Manufacturer: TAKEDA GLOBAL RESEARCH & DEVELOPMENT CENTER (EUROPE) (UK) manufactured by TAKEDA PHARMACEUTICAL COMPANY (Japan) packed by TAKEDA IRELAND (Ireland)
Tablets from white to almost white, round, biconcave, with engraving "ASL" on one side and "20" on the other.
1 tab.
azilsartan medoxomil potassium 21.34 mg,
which corresponds to the content of azilsartan medoxomil 20 mg
Excipients: mannitol - 47.815 mg, fumaric acid - 1 mg, sodium hydroxide - 0.345 mg, giprolose - 2.7 mg, croscarmellose sodium - 6.9 mg, microcrystalline cellulose 9 mg, magnesium stearate 0.9 mg.
14 pcs. - blisters aluminum (1) - packs cardboard.
14 pcs. - blisters aluminum (2) - packs cardboard.
14 pcs. - blisters aluminum (3) - packs cardboard.
14 pcs. - blisters aluminum (4) - packs cardboard.
14 pcs. - blisters aluminum (7) - packs cardboard.
Tablets from white to almost white, round, biconcave, engraved "ASL" on one side and "40" on the other.
1 tab.
azilsartan medoxomil potassium 42.68 mg,
which corresponds to the content of azilsartan medoxomil 40 mg
Excipients: mannitol - 95.63 mg, fumaric acid - 2 mg, sodium hydroxide - 0.69 mg, giprolase - 5.4 mg, croscarmellose sodium - 13.8 mg, microcrystalline cellulose - 18 mg, magnesium stearate - 1.8 mg.
14 pcs. - blisters aluminum (1) - packs cardboard.
14 pcs. - blisters aluminum (2) - packs cardboard.
14 pcs. - blisters aluminum (3) - packs cardboard.
14 pcs. - blisters aluminum (4) - packs cardboard.
14 pcs. - blisters aluminum (7) - packs cardboard.
Tablets from white to almost white, round, biconcave, engraved "ASL" on one side and "80" on the other.
1 tab.
azilsartan medoxomil potassium 85.36 mg,
which corresponds to the content of azilsartan medoxomil 80 mg
Excipients: mannitol - 191.26 mg, fumaric acid - 4 mg, sodium hydroxide - 1.38 mg, giprolose - 10.8 mg, croscarmellose sodium - 27.6 mg, microcrystalline cellulose - 36 mg, magnesium stearate - 3.6 mg.
14 pcs. - blisters aluminum (1) - packs cardboard.
14 pcs. - blisters aluminum (2) - packs cardboard.
14 pcs. - blisters aluminum (3) - packs cardboard.
14 pcs. - blisters aluminum (4) - packs cardboard.
14 pcs. - blisters aluminum (7) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Specific antagonist of angiotensin II receptor type 1 (AT 1 ). Azolsartan medoxomil is a prodrug. Rapidly turns into an active molecule of azilsartan, which selectively prevents the development of the effects of angiotensin II by blocking its binding to AT 1 receptors in various tissues. Angiotensin II is the primary vasoactive hormone RAAS with effects including vasoconstriction, cardiac stimulation, synthesis stimulation and aldosterone 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 total increase in plasma activity of renin and the level of circulating angiotensin II 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 achieved after 4 weeks. Reduction of blood pressure 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) with Edarby ® was not observed.
The safety and effectiveness of the drug do not depend on the age of the patients, but a greater sensitivity to lowering blood pressure in some elderly patients can not be ruled out. As with the use of 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 renin activity in the blood plasma). The simultaneous use of Edarby ® 40 mg and 80 mg with dihydropyridine blockers of slow calcium channels (amlodipine) or thiazide diuretics (chlorthalidone) leads to an additional reduction in blood pressure as compared with antihypertensive therapy used in monotherapy.
Influence on repolarization processes
Evaluation of the potential of the Edarb® preparation to increase the QT / QT interval was performed in healthy volunteers during the QT / QT c study. When using the drug Edarby ® at a dose of 320 mg increase in the QT / QT c interval was not observed. QT c - corrected (relative to the heart rate) value of the QT interval, relative value. Because the duration of the QT interval depends on the heart rate (lengthening when it slows down), for evaluation it should be corrected for the heart rate. The 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 the occurrence of fatal cardiac arrhythmias.
PHARMACOKINETICS
Suction
Estimated absolute bioavailability of azilsartan medoxomil for oral administration is approximately 60% according to the profile of concentrations in the blood plasma. With max of azilsartan in blood plasma is achieved on average within 1.5-3 h after ingestion. Eating 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 single or multiple oral administration.
V d of azilsartan is about 16 liters. Azilsartan binds to blood plasma proteins (more than 99%), mainly with albumins. The association with blood plasma proteins remains constant at a concentration of azilsartan in the blood plasma, which is significantly higher than the range achieved when taking in the recommended doses. C ss of azilsartan is reached within 5 days, its cumulation in the blood plasma with a daily application 1 time / day does not occur.
Studies on animals with radioactive labels showed that the amount of azilsartan penetrating through the BBB is minimal.
Metabolism
After ingestion during absorption from the gastrointestinal tract of azilsartan, medoxomil is converted into the pharmacologically active metabolite azilsartan under the action of the enzyme carboxymethylenebutenolidase in the intestine and liver. Azilsartan is metabolized to two primary metabolites, mainly in the liver. The main metabolite in the blood plasma is formed by O-dealkylation and is referred to as the M-II metabolite, the secondary metabolite is formed by decarboxylation and is referred to as the MI metabolite. The AUC values ​​for these metabolites in humans are 50% and less than 1%, respectively, compared to azilsartan. MI and M-II do not affect the pharmacological activity of the Edarb® preparation. The main enzyme that provides the metabolism of azilsartan is the isoenzyme CYP2C9.
Excretion
Azilsartan and its metabolites are excreted from the body, both through the intestine, and by the kidneys. Studies have shown that after ingestion of azilsartan medoxomil, about 55% (mainly as a metabolite MI) is found in the feces and about 42% (15% in the form of azilsartan, 19% in the form of a metabolite M-II) - in the urine. T 1/2 of azilsartan is about 11 hours, the renal clearance is about 2.3 ml / min.
Pharmacokinetics in specific patient groups
The pharmacokinetics of azilsartan in children and adolescents under the age of 18 years has not been studied.
The pharmacokinetics of azilsartan in young patients (18-45 years) and elderly patients (65-85 years) is not significantly different.
In patients with mild, moderate and severe renal failure, the AUC was increased by 30%, 25% and 95%, respectively. An increase in AUC (5%) in patients with terminal stage of renal failure on hemodialysis was not observed. Clinical data on pharmacokinetics in patients with severe degree or terminal stage of renal failure are absent. Azilsartan is not excreted from the systemic blood flow through hemodialysis.
The use of EDARBY ® 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 the Edarb® preparation in patients with severe (grade C on the Child-Pugh scale) degree of hepatic insufficiency has not been studied.
The pharmacokinetics of azilsartan in men and women is not significantly different. Correction of dose depending on sex is not required.
The pharmacokinetics of azilsartan depending on the race of patients is not significantly different. Dose adjustments are not required depending on the race.
INDICATIONS
essential hypertension.
DOSING MODE
The drug is taken orally 1 time / day, regardless of food intake.
The recommended initial dose is 40 mg 1 time / day. If it is necessary to further reduce blood pressure, the dose of the drug can be increased to the maximum - 80 mg 1 time / day. The maximum daily dose is 80 mg.
In case of inadequate control of BP with the use of Edarb® as a monotherapy, it can be used simultaneously with other antihypertensive drugs, including diuretics (chlorthalidone and hydrochlorothiazide) and dihydropyridine blockers of slow calcium channels (amlodipine).
The drug Edarby ® should be taken daily, without interruption. If the treatment is discontinued, the patient should be informed about this by the doctor.
If you miss a dose, the patient should take the next dose at the usual time. Do not take a double dose of Edarb®.
It is not necessary to correct the initial dose of Edarb® in elderly patients . However, in patients older than 75 years, a dose of 20 mg can be considered as an initial (increases the risk of developing arterial hypotension).
There is no need for correction of the dosing regimen in patients with impaired renal function of mild and moderate severity . There is no clinical experience with the use of Edarby ® in patients with impaired renal function and severe end-stage renal disease , so use the drug in this category of patients should be cautious.
Due to the limited experience of using Edarb® in patients with mild to moderate liver function disorders, it is recommended to start treatment at a dose of 20 mg once a day and monitor it carefully. It is not recommended to use the drug in patients with impaired hepatic function due to lack of clinical experience.
The Edarby ® drug should be given to patients with reduced BCC and / or hyponatremia (eg, patients with prolonged vomiting, diarrhea, or receiving diuretics in high 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 Edarb® drug should be used with caution in patients with severe chronic heart failure (IV functional class according to the NYHA classification).
Do not require dose adjustment in patients of the Negroid race. As with the use of other antagonists of angiotensin II (AT 1 ) receptors and ACE inhibitors, a decrease in blood pressure is observed in patients of the Negroid race in comparison with the rest of the population. In this regard, for an adequate control of blood pressure in patients of the Negroid race, an increase in the dose of Edarb® and complex therapy may be required more often than in other patients.
SIDE EFFECT
The incidence 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); very rarely (<1/10 000), including individual messages; frequency (frequency can not be calculated from available data).
From the nervous system: often - dizziness.
From the side of the cardiovascular system: infrequent - a pronounced decrease in blood pressure.
On the part of the digestive system: often - diarrhea; infrequently - nausea.
From the skin and subcutaneous tissues: infrequently - rash, itching; rarely - angioedema.
From the musculoskeletal system: infrequently - muscle spasms.
From laboratory and instrumental studies: often - increased activity of CK; infrequently - increased concentration of creatinine, hyperuricemia.
Other: infrequent - increased fatigue, peripheral edema.
Description of individual adverse reactions
With the simultaneous use of the drug Edarby ® with chlorthalidone, the frequency of adverse reactions - a marked decrease in blood pressure and an increase in creatinine concentration - increases in the frequency of occurrence from "infrequently" to "often."
With simultaneous use of the drug Edarby ® with amlodipine, the frequency of the undesirable reaction - peripheral edema - increases from infrequent to frequent, but is less common than with monotherapy with amlodipine.
Rarely angioedema is observed, including edema of the face, lips and periorbital edema.
As with the use of other angiotensin II receptor antagonists and ACE inhibitors, concomitant use of Edarb® with diuretics (eg, chlorthalidone) leads to increased rates of increase in creatinine concentration. An increase in the concentration of creatinine with the simultaneous use of the drug Edarb® with diuretics is associated with a more pronounced decrease in blood pressure as compared to monotherapy with Edarb®. Most of these effects were transient or non-progressive, as long as patients continued therapy. After drug withdrawal, the majority of cases of increase in creatinine concentration that did not pass during treatment were reversible. The creatinine concentration in most patients returned to values ​​on the baseline, or values ​​close to the baseline.
When treated with Edarby ® , a slight increase in serum uric acid concentration (10.8 μmol / L) was observed compared to placebo (4.3 μmol / L).
As with other RAAS inhibitors, a small reduction in hemoglobin and hematocrit was observed as monotherapy with the Edarb® preparation (on average they decreased by about 3 g / l and 1% by volume, respectively).
If any of the side effects indicated in the manual are aggravated, or the patient notices other side effects not listed in the instructions, you should inform your doctor.
CONTRAINDICATIONS
- severe violations of the liver (more than 9 points on the scale Child-Pugh) (no experience of use);
- Pregnancy;
- simultaneous administration of aliskiren in patients with diabetes mellitus;
- age under 18 years (effectiveness and safety not established);
- Hypersensitivity to the active substance and other components of the drug.
Caution should be applied to the drug in severe chronic heart failure (IV functional class according to the NYHA classification); renal failure of severe degree (CK <30 ml / min); bilateral stenosis of the renal arteries and stenosis of the artery of a single functioning kidney; ischemic cardiomyopathy; ischemic cerebrovascular diseases; condition after kidney transplantation; Conditions accompanied by a decrease in BCC (including vomiting, diarrhea), as well as in patients who follow a diet with restriction of table salt; with simultaneous use with diuretics in high doses; primary hyperaldosteronism; hyperkalemia; stenosis of the aortic and mitral valves; hypertrophic obstructive cardiomyopathy (GOKMP); in patients over the age of 75 years.
PREGNANCY AND LACTATION
Pregnancy
In animal studies, it has been found that azilsartan and M-II penetrate the placental barrier.
Patients planning a pregnancy should be treated with alternative antihypertensive drugs with an established safety profile for pregnant women. Immediately after confirmation of pregnancy, you should stop taking Edarb® and, if necessary, begin treatment with drugs approved for use in pregnancy.
In newborns whose mothers received therapy with Edarby ® , arterial hypotension may develop, and therefore newborns should be under careful medical supervision.
Lactation period
There is no information on the ability of azilsartan and / or its metabolites to enter breast milk. In animal studies, it has been found that azilsartan and M-II are secreted from the milk of activated rats.
Due to the lack of experience with the use of Edarb® 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
There are no data on the effect of Edarb® on fertility in humans. Preclinical studies showed no effect on male or female fertility in rats.
APPLICATION FOR FUNCTIONS OF THE LIVER
There is no need for correction of the dosing regimen in patients with impaired renal function of mild and moderate severity . There is no clinical experience with the use of Edarby ® in patients with impaired renal function and severe end-stage renal disease , so use the drug in this category of patients should be cautious.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Due to the limited experience of using Edarb® in patients with mild to moderate liver function disorders, it is recommended to start treatment at a dose of 20 mg once a day and monitor it carefully. It is not recommended to use the drug in patients with impaired hepatic function due to lack of clinical experience.
APPLICATION FOR CHILDREN
Contraindicated use of the drug in children and adolescents under the age of 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
It is not necessary to correct the initial dose of Edarb® in elderly patients . However, in patients older than 75 years, a dose of 20 mg can be considered as an initial (increases the risk of developing arterial hypotension).
SPECIAL INSTRUCTIONS
Patients with 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 (IV functional class NYHA classification), severe renal insufficiency or renal artery stenosis), treatment with drugs acting on the RAAS, such as ACE inhibitors and angiotensin II receptor antagonists, due to the possibility of an acute hypotension, azotemia, oliguria or, rarely, acute renal failure . The ability of these effects can not be excluded and the application Edarbi ® .
The sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases can lead to myocardial infarction or stroke.
Data on the use of the drug Edarbi ® in patients who have recently had a kidney transplant, no.
Data on the clinical experience with the drug Edarbi ® in patients with severe hepatic dysfunction are absent, so the use of the drug in these patients is not recommended.
In patients with reduced BCC and / or hyponatremia (resulting in vomiting, diarrhea, diuretics in high doses or dieting limited reception salt) may develop clinically significant hypotension after initiation of therapy with Edarbi ® . Hypovolemia should be adjusted before the start of treatment with Edarbi ® or initiate treatment with a dosage of 20 mg.
Patients with primary hyperaldosteronism generally resistant to treatment with antihypertensive drugs that affect the RAAS. In connection with this drug Edarbi ® not recommended in such patients.
Clinical experience with other drugs affecting RAAS shows that co-administration of drug Edarbi ®potassium-sparing diuretics, preparations or potassium salt substitutes containing potassium, or other drugs that may increase the content of potassium in the blood (e.g., heparin) can cause hyperkalemia in hypertensive patients. Elderly patients, patients with renal insufficiency, diabetes mellitus, and / or in patients with other underlying medical conditions increases the risk of hyperkalemia, which can be fatal. In these patients, it is recommended to control the content of potassium in the blood serum.
In applying the drug Edarbi ® in patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy be careful.
As with other angiotensin II receptor antagonists without the simultaneous application of drugs lithium and Edarbi preparation ® .
Impact on the ability to drive vehicles and manage mechanisms
Based on the pharmacodynamic properties it is expected that azilsartana medoxomil will slightly affect the ability to drive vehicles and management mechanisms. Care must be taken, as well as the application of any antihypertensive drugs (risk of dizziness and fatigue).
OVERDOSE
Previous applications Edarbi preparation ® 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 of the patient should be transferred to a horizontal position with a low headboard; It recommended to introduce measures to increase BCC and symptomatic therapy. Hemodialysis is ineffective.
DRUG INTERACTION
It was noted reversible increase in the concentration of lithium in blood serum and expression of toxicity while applying 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. If necessary, use of the combination is recommended lithium regular monitoring of serum.
With simultaneous use of angiotensin II antagonists and NSAIDs (e.g., the selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / d) and nonselective NSAIDs) may weaken the antihypertensive effect. With simultaneous use of the angiotensin II antagonist and the NSAID 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.
The simultaneous use of potassium-sparing diuretics, potassium preparations salt substitute containing potassium and other drugs (e.g., heparin) with azilsartana medoksomilom may cause an increase in potassium in serum. Patients during combination therapy should be monitored content of potassium in the blood serum.
Dual RAAS blockade of angiotensin II receptor antagonists, ACE inhibitors or aliskiren is associated with increased risk of arterial hypotension, hyperkalemia, and renal failure (including acute renal failure) as compared with monotherapy.
There was no 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 intestine by the enzyme karboksimetilenbutenolidazy in the intestine and liver. In vitro studies have shown that interactions based on the inhibition of the enzymes are unlikely.
The antihypertensive 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).
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The preparation should be stored in their original packaging to protect it from light and moisture, the reach of children at a temperature not higher than 25 ° C. Shelf life - 3 years.
The information is provided for your information, do not self-medicate, it is dangerous for your health.
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