Edarby 80 mg tablets № 28

EDARBI instruction manual

Composition

active ingredient: azilsartan medoxomil;

One 20 mg Edarbi tablet contains 21.34 mg of potassium medoxomil azilsartan, equivalent to 20 mg of azilsartan medoxomil;

1 Edarbi 40 mg tablet contains 42.68 mg of azilsartan medoxomil potassium, equivalent to 40 mg of azilsartan medoxomil;

One 80 mg Edarbi tablet contains 85.36 mg of potassium medoxomil, which is equivalent to 80 mg of azilsartan medoxomil.

auxiliary substances: mannitol (E 421) fumaric acid; sodium hydroxide hydroxypropyl cellulose; sodium croscarmellose;cellulose microcrystalline magnesium stearate water purified.

Dosage form

Pills.

Basic physical and chemical properties:

tablets of 20 mg: white or almost white tablets, engraved with "ASL" on one side and "20" on the other;

tablets of 40 mg: white or almost white tablets, engraved with "ASL" on one side and "40" on the other;

tablets of 80 mg: white or almost white tablets, engraved "ASL" on one side and "80" on the other side.

Pharmacological group

Angiotensin II antagonists are direct action. ATC code: C09C A09.

Pharmacological properties

Pharmacodynamics . Azilsartan medoxomil is an active precursor of a medicinal substance intended for oral administration. The precursor is rapidly converted into an active molecule of azilsartan, which by blocking the binding of angiotensin II to the AO1 receptors in many tissues is a selective antagonist of the effects of angiotensin II. Angiotensin II - the main blocking agent of the renin-angiotensin system; to the effects of angiotensin II include narrowing of the vessels, stimulation of synthesis and release of aldosterone, stimulation of the heart and stimulation of sodium reabsorption in the kidneys.

Blocking of AT 1 receptors leads to suppression of the negative feedback effect of angiotensin II on renin secretion, but an increase in renin activity in the blood plasma and an increase in the level of angiotensin II in the systemic bloodstream that result from receptor blocking do not hinder the development of antihypertensive effects of azilsartan.

Pharmacokinetics . After oral administration of azilsartan, medoxomil rapidly hydrolyzes in the digestive tract and / or upon absorption to the active substance (azilsartan).

In vitro studies show that the enzyme carboxymethylene butenolidase participates in hydrolysis in the intestinal tract and liver. Also, plasma esterases are involved in the hydrolysis of azosartan medoxomil to azilsartan.

Absorption. Based on the concentrations of azilsartan in blood plasma, the calculated absolute oral bioavailability of azilsartan medoxomil is approximately 60%. After taking medication with azilsartan medoxomil, the maximum concentration of azilsartan in plasma (C max) is reached after 1.5 - 3:00. Food does not affect the bioavailability of azilsartan.

Distribution. The volume of distribution of azilsartan is approximately 16 liters. Azilsartan is intensively (> 99%) bound to plasma proteins, mainly with albumin. The binding to plasma proteins does not change in a range of concentrations that are significantly higher than those achieved when administered at the recommended doses.

Metabolism. Metabolic digestion of azilsartanu leads to the formation of two major metabolites. The main metabolite in plasma is formed by O-dealkylation, it is referred to as the M-II metabolite. The secondary metabolite, which is formed as a result of decarboxylation, is referred to as the MI metabolite. The level of system exposure of the primary and secondary metabolites in humans was approximately 50% and less than 1% of the exposure level of azilsartan, respectively. M-I and M-II do not exert additional influence on the pharmacological action of Edarby. Metabolism of azilsartan is mainly due to the enzyme CYP2C9.

Conclusion. After taking medication with azilsartan medoxomil, labeled with a radioactive isotope 14 C, approximately 55% of radioactivity was excreted from the body with feces and about 42% - with urine. Approximately 15% of the drug was excreted in the urine in the unmodified form of azilsartan. The half-life of azilsartanu from the blood plasma is about 11:00, and the renal clearance is about 2.3 ml / min. The equilibrium concentration of azilsartan develops within 5 days, and during repeated administration of the drug once daily, no accumulation occurs in the plasma.

Linearity / nonlinearity. In the dose range of azilsartan medoxomil from 20 to 320 mg after taking single or multiple doses, the exposure of the azillartanum to the dose was determined.

Characteristics in special subgroups of patients.

Children. The pharmacokinetics of azilsartan in children (under the age of 18 years) were not investigated.

Patients of advanced age. There were no significant differences in the pharmacokinetics of azilsartan in young people (aged 18-45 years) and in elderly patients (65-85 years).

Impaired renal function. In patients with mild, moderate and severe renal dysfunction, the total exposure to azilsartan (AUC) increased by 30%, 25% and 95%. In patients with terminal renal failure on dialysis, no increase in exposure was observed (+ 5%). At the same time, clinical experience of the drug in patients with severe renal dysfunction or terminal stage of renal failure is absent. Azilsartan is not excreted from the systemic circulation during hemodialysis.

Violation of the function of the liver. Treatment of Edarbi in patients with a lung (class A in Child-Pugh) or moderate (class B in Child-Pugh), a violation of liver function for not more than 5 days resulted in a slight increase in exposure to azilsartan (AUC growth 1.3-1.6 times ). The use of the Edarbi drug for the treatment of patients with severe impairment of liver function has not been investigated.

Floor. There were no significant differences in the pharmacokinetics of azilsartan in men and women. There is no need to adjust the dose depending on the patient's sex.

Race affiliation. There were no significant differences in the pharmacokinetics of azilsartan in white and black patients.There is no need to adjust the dose depending on the race of the patient.

Indications

Treatment of essential hypertension in adults.

Contraindications

Hypersensitivity to the active substance or other components of the drug.

Pregnant women or women planning to become pregnant (see section "Use during pregnancy or lactation").

Do not use Edarby with preparations containing aliskiren, patients with diabetes mellitus or renal dysfunction (GFR <60 ml / min / 1.73 m 2).

Interaction with other drugs and other interactions

Combinations are not recommended.

Lithium. With simultaneous use of lithium drugs and ACE inhibitors, a reversible increase in serum lithium concentrations and a reversible increase in toxicity were observed. With angiotensin II receptor blockers, a similar effect can be observed. In connection with the lack of experience in the simultaneous use of azilsartan medoxomil and lithium preparations, this combination of drugs is not recommended. If it is necessary to simultaneously prescribe these drugs, it is recommended to carefully monitor the level of lithium in the blood serum.

Combinations should be used with caution.

Non-steroidal anti-inflammatory drugs (NSAIDs), including selective inhibitors of COX-2, acetylsalicylic acid at a dose> 3 g / day and nonselective NSAIDs.

With the simultaneous use of NSAIDs (ie, selective inhibitors of COX-2, for example, acetylsalicylic acid at doses> 3 g / day and nonselective NSAIDs) and angiotensin II receptor blockers, the hypotensive effect of the latter may be weakened. In addition, the simultaneous use of angiotensin II receptor blockers and NSAIDs can lead to an increased risk of impaired renal function and an increase in serum potassium levels. Thus, it is recommended at the beginning of treatment to provide adequate hydration of the patient and control of kidney function.

Potassium-sparing diuretics, potassium supplements, salt substitutes with potassium and other substances that can raise the level of potassium in the blood.

Potassium-sparing diuretics, potassium-containing supplements, salt substitutes with potassium and other drugs (eg, heparin), when used at the same time, can raise the level of potassium in the blood. If necessary, monitor potassium levels in serum.

Additional Information.

Clinical studies have shown that the double blockade of renin-angiotensin (RAAS) with the combined use of ACE inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of arterial hypotension, hyperkalemia, impaired renal function (including acute renal failure) compared with monotherapy with the active agent of RAAS (see the sections "Contraindications" and "Features of application").

In studies with the use of azilsartan medoxomil or azilsartan in combination with amlodipine, antacid preparations, chlorthalidone, digoxin, fluconazole, glyburide, ketoconazole, metformin and warfarin, no clinically significant interactions of medications have been reported.

Azilsartan medoxomil is rapidly hydrolyzed by esterases in the digestive tract and / or during absorption to the active substance of azilsartan. In vitro studies indicate a low probability of interactions based on oppression of esterases.

Application features

Renin-angiotensin is activated. Patients whose vascular tone and renal function are dependent primarily on the activity of renin-angiotensin (eg, patients with congestive heart failure, severe renal failure or renal artery stenosis), treatment with drugs that affect the renin-angiotensin-aldosterone system (for example, ACE inhibitors and angiotensin II receptor blockers) was associated with the onset of acute hypotension, azotemia, oliguria, or, in rare cases, acute renal failure. It is impossible to exclude the occurrence of such phenomena when using Edarby.

Caution should be used with EDARBI for the treatment of patients with hypertension and severe renal impairment, congestive heart failure or renal artery stenosis, since there is no experience of using the drug to treat such patients.

Too much reduction in blood pressure in patients with ischemic cardiomyopathy or cerebrovascular disorders of an ischemic nature can lead to myocardial infarction or to a stroke.

Double blockade of renin-angiotensin (RAAS). Joint use of ACE inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of arterial hypotension, hyperkalemia and impaired renal function (including acute renal failure).Therefore, the double blockade of RAAS due to the combined use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is not recommended (see Section "Interaction with Other Drugs and Other Interactions"). In case of need for double blockade therapy, it should be performed under the supervision of a doctor and monitoring the kidney function, electrolyte level and blood pressure. Patients with diabetic nephropathy should not use ACE inhibitors together with angiotensin II receptor blockers.

Kidney transplantation. To date, the experience of using Edarbi for the treatment of patients who have recently undergone kidney transplantation is not available.

Violation of the function of the liver. The use of Edarbi for the treatment of patients with severe impairment of liver function has not been investigated, so this drug is not recommended for patients of this group.

Hypotension in patients with circulating volume deficiency and / or salt depletion. In patients with severe circulatory volume deficiency and / or salt exhaustion (eg, patients with diarrhea, vomiting, or patients receiving large doses of diuretics) symptomatic hypotension may occur after the initiation of Edarby's treatment. Before the start of treatment, it is necessary to take measures to compensate for hypovolemia or to begin treatment under close supervision. You should also consider the possibility of an initial dose of 20 mg.

Primary hyperaldosteronism. In patients with primary hyperaldosteronism, there is usually no response to treatment with antihypertensive drugs, the mechanism of action of which is to suppress the renin-angiotensin system. Thus, the use of Edarby in such patients is not recommended.

Hyperkalemia. Based on the experience of using other medications that affect the renin-angiotensin-aldosterone system, the simultaneous use of Edarby together with potassium-sparing diuretics, potassium supplements, salt substitutes with potassium or other medications that are capable of increasing the level of potassium in the blood (for example, heparin ), can lead to an increase in the level of potassium in the blood of patients with hypertension. In elderly patients, patients with renal insufficiency, patients with diabetes and / or patients with other concomitant diseases, the risk of hyperkalemia (which can be lethal) increases. If necessary, monitor potassium levels.

Stenosis of aortic and mitral valves, obstructive hypertrophic cardiomyopathy. Treatment of patients with stenosis of the aortic or mitral valve or with hypertrophic obstructive cardiomyopathy requires extreme caution.

Lithium. As for other angiotensin II receptor blockers, Edarby should not be given concomitantly with lithium preparations.

Use during pregnancy or lactation

Pregnancy. The drug should not be used by pregnant women or women who plan to become pregnant. If pregnancy is confirmed during treatment, its use should be immediately stopped and replaced with another medication approved for use in pregnant women.

Data on the application of Yodarbi to pregnant women are not available. Studies in animals have shown reproductive toxicity.

Epidemiological data do not indicate a risk of teratogenicity resulting from the exposure of ACE inhibitors during the first trimester of pregnancy, however, a slight increase in risk can not be ruled out. Due to the lack of controlled epidemiological data on the risk associated with angiotensin II receptor blockers, this risk can not be excluded for this class of drugs. Patients planning a pregnancy should switch to alternative antihypertensive therapy, have a more researched safety profile for use by pregnant women.

Therapy with angiotensin II receptor blockers in women in the second and third trimesters of pregnancy can lead to fetotoxicity (decreased kidney function, oligohydramnion, delayed ossification of the skull bones) and neonatal toxicity (renal failure, arterial hypotension, hyperkalemia).

If the drug was used in the II trimester of pregnancy, an ultrasound is recommended to determine the function of the kidneys and ossification of the skull bones in the fetus.

Care should be taken to monitor infants whose mothers used angiotensin II receptor blockers for the development of arterial hypotension (see Sections "Contraindications" and "Features of Use").

Lactation . The drug is not recommended for use during breastfeeding due to the lack of relevant data. During breastfeeding, it is advisable to begin an alternative treatment with a more researched safety profile, especially during the feeding of a newborn or premature baby.

Fertility. Data on the impact of Yodarbi on human reproductive function are absent. According to the results of preclinical studies, azilsartan did not affect the reproductive function of female and male rats.

The ability to influence the reaction rate when driving vehicles or other mechanisms

Taking into account the pharmacodynamic characteristics of the drug, azilsartan medoxomil may have a negligible effect on the reaction rate when driving vehicles or working with other mechanisms. At the same time, when taking any antihypertensive drug, you should know about the possible occurrence of dizziness or fatigue.

Dosing and Administration

Edarby is intended for oral use, tablets can be taken regardless of food intake.

The recommended initial dose is 40 mg once a day.

For patients in whom this dose does not adequately control blood pressure, the dose can be increased to the maximum recommended dose of 80 mg once a day.

A stable antihypertensive effect is achieved within 2 weeks of treatment. The maximum effect is achieved after 4 weeks of therapy with the drug.

If during the monotherapy with the Edarby drug it is not possible to achieve adequate control of blood pressure, an additional reduction in blood pressure can be achieved through combined treatment with other antihypertensive agents, including diuretics (eg chlortalidone and hydrochlorothiazide) and calcium channel blockers.

Elderly patients (65 years) does not need to be corrected initial dose Edarbi. However, for patients older than 75 years with the risk of hypotension should consider the use of the drug at a dose of 20 mg.

Impaired renal function. Should be used with caution Edarbi patients with hypertension and severe renal impairment or end-stage renal failure, since these patients experience with offline preparation. Azilsartan it not derived from the circulatory system in hemodialysis. Patients with mild or moderate renal insufficiency does not require dose adjustments.

Abnormal liver function. Investigations on the use of Edarbi in patients with severe liver functions are not performed, and the drug is not recommended for this group of patients.

Since the experience of Edarbi patients with mild to moderate hepatic impairment limited, should carefully monitor the status of patients and to consider the possibility of the drug in an initial dose of 20 mg.

The deficit in intravascular volume. Patients with possible deficiency of volume or salt depletion (e.g., patients with vomiting, diarrhea or patients who receive high doses of diuretics) Edarbi drug administered under close medical supervision, it should also consider the use of an initial dose of 20 mg.

Heart failure. Should be used with caution preparation Edarbi patients with congestive heart failure because such patients experience with offline preparation.

Patients blacks. The need to adjust the dose No, although these patients have a less pronounced reduction in blood pressure compared with those who belong to other races. Generally this concerns other angiotensin II receptor blockers and ACE inhibitors. For this population may require more frequent dose escalation Edarbi and concomitant therapy drugs.

Children

Data on drug use among children (under 18) are not present.

Overdose

Symptoms. Based on the pharmacological properties it can be expected that the principal manifestation of overdose would be in the form of symptomatic hypotension and dizziness. During controlled clinical studies involving healthy individual participants received Edarbi at doses up to 320 mg once a day for 7 days. These doses were well tolerated by the study participants.

Treatment. With the development of symptomatic hypotension should start replacement therapy and monitor vital signs. Azilsartan it not removed by dialysis.

Adverse Reactions

Side effects by frequency of occurrence is classified in categories: very common (≥ 1/10), common (> 1/100 and <1/10), uncommon (> 1/1000 and <1/100), rarely (> 1 / 10,000 and <1/1000), very rare (<1/10000), including isolated cases.

From the nervous system.

Often dizziness.

On the part of the circulatory system.

Infrequently hypotension.

On the part of the digestive tract.

Often diarrhea.

Infrequent nausea.

Skin and subcutaneous tissue disorders.

Infrequently a rash, itching.

Rarely angioedema.

On the part of the musculoskeletal system and connective tissue.

Infrequently muscle spasms.

General disorders.

Infrequently, fatigue, peripheral edema.

Laboratory research.

Often: increased CPK in the blood.

Uncommon: increased creatinine level in the blood, increased levels of uric acid in the blood / hyperuricemia.

Description of individual adverse reactions.

During joint application Edarbi chlorthalidone and frequency increase in serum creatinine level and hypotension grown from infrequent frequent.

During the joint use of Edarbi and amlodipine incidence of peripheral edema grew by infrequent frequent, but was lower than is typical for amlodipine monotherapy.

Laboratory research.

creatinine level in blood serum. In a randomized, placebo-controlled studies monotherapy frequency increase serum creatinine levels after treatment Edarbi not different from placebo. Simultaneous application Edarbi and diuretics, e.g., chlorthalidone, resulted in a higher frequency increase in serum creatinine. This observation is consistent with the known facts for other angiotensin II receptors and angiotensin-converting enzyme. Increased creatinine level during concomitant use Edarbi and diuretic drugs was associated with a marked reduction of blood pressure as compared to using one of these drugs. Most episodes of increased creatinine levels were of a temporary nature, or did not progress with continued treatment.After cessation of treatment creatinine levels in most cases come to normal or near normal values by yourself.

Uric acid. In applying Edarbi observed a slight increase in the mean levels of uric acid in blood serum when compared to placebo (10.8 .mu.mol / l vs. 4.3 mmol / L).

Hemoglobin and hematocrit. In a placebo-controlled studies, the drug alone was a slight decrease in hemoglobin and hematocrit (about 3 g / l and 1 volume percent, respectively). This effect is also observed when other inhibitors of the renin-angiotensin.

Shelf life

3 years.

Storage conditions

It does not require any special storage conditions. Store in original container. Keep out of the reach of children!

Incompatibility

Not described.

Packaging

For 14 tablets in a blister pack. 1 or 2 or 4 blisters per box.

Category of leave

On prescription.