Edarbi pills 40mg, 28pcs

Composition

1 tablet contains:

Active ingredient:

azilsartan medoxomil potassium 42.68 mg, which corresponds to azilsartan medoxomil-40 mg,

excipients:

mannitol;

fumaric acid;

sodium hydroxide;

hyprolose;

croscarmellose sodium;

MCC;

magnesium stearate.

Pharmacological action

Pharmacodynamics

Azilsartan medoxomil, the Active ingredient of Edarbi, is a specific angiotensin II type 1 (AT1) receptor antagonist. Azilsartan medoxomil is an oral prodrug. Azilsartan medoxomil is rapidly converted to the active molecule 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 the renin-angiotensin-aldesterone system (RAAS) with effects including vasoconstriction, cardiac stimulation, stimulation of aldosterone synthesis and 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 resulting increase in plasma renin activity and circulating angiotensin II levels 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. A reduction in blood pressure (BP) after ingestion of a single dose is usually achieved within a few hours and persists for 24 hours.

“Withdrawal” syndrome (a sharp increase in blood pressure after drug withdrawal) after sudden withdrawal after prolonged therapy (for 6 months) with Edarbi was not observed.

The safety and efficacy of the drug do not depend on the age of patients, but a greater sensitivity to lowering blood pressure in some elderly patients cannot be excluded. As with other angiotensin II receptor antagonists and angiotensin converting enzyme (ACE) inhibitors, the antihypertensive effect is less pronounced in black patients (usually a population with low plasma renin activity).

Concomitant use of Edarbi 40 mg and 80 mg with dihydropyridine slow calcium channel blockers (amlodipine) or thiazide diuretics (chlortalidone) leads to an additional decrease in blood pressure compared to antihypertensive agents used in monotherapy.

Influence on repolarization processes

The potential of Edarbi to increase the QT/QTc interval was evaluated in healthy volunteers during the QT/QTc study. When using a dose of 320 mg of Edarbi, no increase in the QT/QTc interval was observed.

QTc — corrected (relative to heart rate) value of the QT interval, relative value.

Since the duration of the QT interval depends on the heart rate (lengthening when it slows down), it must be adjusted relative to the heart rate for evaluation.

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 fatal cardiac arrhythmias.

Pharmacokinetics

Suction

Azilsartan medoxomil is a prodrug. After oral use, it is converted to the pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the enzyme carboxymethylenebutenolidase in the intestine and liver.

The estimated absolute oral bioavailability of azilsartan medoxomil is approximately 60% based on the plasma concentration profile. The maximum concentration (Cmax) of azilsartan in blood plasma is reached on average within 1.5 – 3 hours after oral use. Food intake does not affect the bioavailability of azilsartan.

Distribution

The volume of distribution of azilsartan is about 16 liters. Azilsartan binds to plasma proteins (more than 99%), mainly to plasma albumins. The association with plasma proteins remains constant when the concentration of azilsartan in blood plasma is significantly higher than the range achieved with the recommended doses.

Data on the use of the drug during pregnancy and lactation are not available. Azilsartan passes through the placenta of pregnant rats and is excreted in the milk of lactating rats. Studies on animals with radioactive labels have shown that the amount of azilsartan that penetrates the blood-brain barrier is minimal.

Metabolism

Azilsartan is metabolized to two primary metabolites primarily in the liver. The main metabolite in blood plasma is formed by O-dealkylation and is designated as the M-II metabolite, the secondary metabolite is formed by decarboxylation and is designated as the M-I metabolite. The AUC values (areas under the concentration-time pharmacokinetic curve) 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 Edarbi. The main enzyme involved in the metabolism of azilsartan is the isoenzyme CYP2C9.

Deduction

Azilsartan and its metabolites are eliminated from the body, both through the intestines and by the kidneys. Studies have shown that after oral use of azilsartan medoxomil, about 55% (mainly in the form of the M-I metabolite) is detected in the feces and about 42% (15% in the form of azilsartan,19% in the form of the M – II metabolite) – in the urine. 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 blood plasma does not occur with a single daily application.

Linearity / Non-Linearity

The pharmacokinetics of azilsartan in azilsartan medoxomil are proportional to the dosage in the dose range from 20 mg to 320 mg after a single or multiple oral use.

Pharmacokinetics in special groups

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 do not differ significantly.

Kidney failure

In patients with mild, moderate and severe renal insufficiency, AUC was increased by + 30%, + 25% and + 95%, respectively. No increase (+ 5%) in AUC was observed in patients with end-stage renal failure undergoing hemodialysis. There are no clinical data on the pharmacokinetics in patients with severe or end-stage renal insufficiency. Azilsartan is not eliminated from the systemic circulation by hemodialysis.

Liver failure

The use of Edarbi for more than 5 days in patients with mild (Child-Pugh class A) or moderate (Child-Pugh Class B) severity of hepatic insufficiency leads to a slight increase in AUC (1.3-1.6 times, respectively). The pharmacokinetics of Edarbi® in patients with severe (Child-Pugh class C) hepatic insufficiency have not been studied.

Gender

The pharmacokinetics of azilsartan in men and women do not differ significantly. No gender-specific dose adjustment is required.

Race The

pharmacokinetics of azilsartan did not differ significantly from patient to patient. No dose adjustment is required depending on the race.

Indications

Essential hypertension.

Use during pregnancy and lactation

Use during pregnancy

Animal studies have shown that azilsartan and M-II penetrate the placental barrier.

Patients planning pregnancy should start therapy with alternative antihypertensive drugs with an established safety profile for pregnant women. Immediately after confirmation of pregnancy, you should stop taking Edarbi and, if necessary, start a course of treatment with drugs approved for use during pregnancy.

Newborns whose mothers have received Edarbi therapy may develop hypotension, and therefore, newborns should be under close medical supervision.

Breast-feeding

There are no data on the ability of azilsartan and / or its metabolites to pass into breast milk. Animal studies have shown that azilsartan and M-II are excreted in the milk of lactating 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. It is preferable to use drugs with the most studied safety profile, especially during the care of a newborn or premature baby.

Fertility

There are no data on the effects of Edarbi on human fertility. Preclinical studies have shown no effect on male or female fertility in rats.

Contraindications

• Hypersensitivity to the Active ingredient and other components of the drug;
• pregnancy;
• simultaneous use of aliskiren in patients with diabetes mellitus;
• age up to 18 years (efficacy and safety have not been established);
• severe liver function disorders (more than 9 points on the Child-Pugh scale) (no experience of use).

With caution:

• Severe chronic heart failure (NYHA functional Class IV);
• severe renal insufficiency (creatinine clearance < 30 ml / min);
• bilateral renal artery stenosis and artery stenosis of the only functioning kidney;
• ischemic cardiomyopathy;
• ischemic cerebrovascular disease;
• condition after kidney transplantation;
• state, accompanied by a decrease in the volume of circulating blood (BCC) (including vomiting, diarrhea), and in patients who are on a diet with restriction of salt;
• while the use of high doses of diuretics; primary aldosteronism;
• hyperkalemia;
• stenosis of the aortic and mitral valves;
• hypertrophic obstructive cardiomyopathy (HACMP);
• age older than 75 years.

If you have any of these conditions, be sure to consult your doctor before taking Edarbi®.

Side effects

From the nervous system: often – dizziness.

Vascular disorders: infrequently-marked decrease in blood pressure.

From the gastrointestinal tract: often – diarrhea; infrequently-nausea.

Skin and subcutaneous tissue disorders: infrequently-rash, pruritus; rarely-angioedema.

Musculoskeletal and connective tissue disorders: infrequently-muscle spasms.

Influence on the results of laboratory and instrumental studies: often-increased creatine phosphokinase activity; infrequently-increased creatinine concentration, hyperuricemia.

General disorders: infrequently-increased fatigue, peripheral edema.

Description of individual adverse reactions

With simultaneous use of Edarbi with chlortalidone, the frequency of adverse reactions – a pronounced decrease in blood pressure and an increase in creatinine concentration – increases in frequency: from infrequent to frequent.

When Edarbi is co-administered with amlodipine, the frequency of adverse reactions – peripheral edema-increases from infrequent to frequent, but is less common than with amlodipine monotherapy.

Rarely there is angioedema, including swelling of the face, lips and periorbital edema.

As with other angiotensin II receptor antagonists and ACE inhibitors, concomitant use of Edarbi with diuretics (for example, chlortalidone) leads to an increase in creatinine concentrations. An increase in creatinine concentration with concomitant use of Edarbi with diuretics is associated with a greater decrease in blood pressure compared to Edarbi monotherapy. Most of these effects were short-lived or did not progress as long as patients continued therapy. After discontinuation of the drug, most cases of increased creatinine concentrations that did not go away during treatment were reversible. The creatinine concentration in most patients returned to values that are at the baseline, or values that are close to the baseline.

Edarbi treatment showed a slight increase in serum uric acid concentrations (10.8 mmol / l) compared to placebo (4.3 mmol/L).

As with other RAAS inhibitors, a slight decrease in hemoglobin and hematocrit was observed in monotherapy (on average, they decreased by about 3 g/l and 1 vol.%, respectively).

If any of the side effects listed in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Interaction

Lithium

Reversible increases in serum lithium concentrations and toxicity were observed during concomitant use of lithium preparations with ACE inhibitors and lithium preparations with angiotensin II receptor antagonists. Therefore, concomitant use of azilsartan medoxomil in combination with lithium preparations is not recommended. If appropriate combination therapy is required, regular monitoring of serum lithium levels is recommended.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Concomitant use of angiotensin II antagonists and NSAIDs (for example, selective COX-2 inhibitors (cyclooxygenase-2), acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs) may weaken the antihypertensive effect. Concomitant use of angiotensin II antagonists and NSAIDs may increase the risk of impaired renal function and increased serum potassium. Therefore, at the beginning of treatment, patients are recommended to regularly take sufficient fluids and monitor kidney function.

Potassium preparations and potassium-sparing diuretics, heparin

Concomitant use of potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium and other medications (for example, heparin) with azilsartan medoxomil may lead to an increase in serum potassium. Patients should monitor their serum potassium levels during combination therapy.

Double blockade of the renin-angiotensin-aldosterone system (RAAS)

Dual blockade of the RAAS with angiotensin II receptor antagonists, ACE inhibitors, or aliskiren is associated with an increased risk of hypotension, hyperkalemia, and impaired renal function (including acute renal failure) compared to monotherapy.

Additional information on the interaction of azilsartan medoxomil

No pharmacokinetic interactions were observed when azilsartan medoxomil or azilsartan was co-administered with amlodipine, antacids (magnesium and aluminum hydroxide), chlortalidone, digoxin, fluconazole, glibenclamide, ketoconazole, metformin and warfarin. Azilsartan medoxomil is converted to the pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the enzyme carboxymethylenebutenolidase in the intestine and liver. In vitro studies have shown that interactions based on enzyme inhibition are unlikely.

Diuretics and other antihypertensive agents

The antihypertensive effect of azilsartan medoxomil therapy may be enhanced when combined with other antihypertensive agents, including diuretics (chlortalidone and hydrochlorothiazide), and dihydropyridine slow calcium channel blockers (amlodipine).

How to take, course of use and dosage

Edarbi is taken orally once a day, regardless of the time of meal. The recommended starting dose is 40 mg once a day. If you need an additional reduction in blood pressure, the dose of the drug can be increased to a maximum of 80 mg once a day.

The maximum daily dose is 80 mg.

In case of inadequate blood pressure control in monotherapy with Edarbi, it may be used simultaneously with other antihypertensive agents, including diuretics (chlortalidone and hydrochlorothiazide) and dihydropyridine slow calcium channel blockers (amlodipine).

Duration of treatment

Edarbi should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor.

If you forgot to apply the drug

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.

Elderly patients (65 years and older)

There is no need to adjust the initial dose of Edarbi in elderly patients. However, in patients over 75 years of age, a dose of 20 mg may be considered as an initial dose (increased risk of hypotension).

Patients with impaired renal function

There is no clinical experience of using Edarbi in patients with hypertension with severe renal impairment and end-stage renal failure, so the drug should be used with caution in this category of patients. No dosage adjustment is required in patients with mild to moderate renal impairment.

Patients with impaired liver function

It is not recommended to use the drug in patients with severe hepatic impairment due to lack of clinical experience. Due to the limited experience of using Edarbi in patients with mild to moderate hepatic impairment, it is recommended to start treatment with a dose of 20 mg once a day and conduct it under close supervision.

Decreased circulating blood volume (BCC)

Edarbi should only be prescribed to patients with reduced BCC and / or hyponatremia (for example, patients with prolonged vomiting, diarrhea, or taking large doses of diuretics) under strict medical supervision. It is also recommended to start treatment with a dosage of 20 mg once a day.

Heart failure

Due to the lack of clinical experience, Edarbi should be used with caution in patients with hypertension and severe chronic heart failure (NYHA functional Class IV).

The Negroid race

No dose adjustment is required in black patients. As with other angiotensin II (AT1) receptor antagonists and ACE inhibitors, patients of the black race show a smaller decrease in blood pressure compared to the rest of the population. In this regard, for adequate blood pressure control in black patients, an increase in the dose of Edarbi and complex therapy may be necessary more often than in other patients.

Overdose

Experience with the use of Edarbi in adults in doses up to 320 mg/day for 7 days shows that the drug is well tolerated.

Symptoms: marked decrease in blood pressure, dizziness.

Treatment: with a marked decrease in blood pressure, give the patient a “lying down” position, lift the legs, take measures to increase the volume of circulating blood (BCC); symptomatic therapy.

Azilsartan is not eliminated from the systemic circulation by dialysis.

Special instructions

Activated renin-angiotensin-aldosterone system

In patients whose vascular tone and renal function are highly dependent on RAAS activity (for example, in patients with severe chronic heart failure (NYHA functional Class IV), severe renal insufficiency, 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 can not be excluded with the use of Edarbi. A sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases can lead to the development of myocardial infarction or stroke.

Kidney transplantation

There are no data on the use of Edarbi in patients who have recently undergone kidney transplantation.

Impaired liver function

There are no data on clinical experience with Edarbi in patients with severe hepatic impairment, so the use of the drug in this category of patients is not recommended.

Arterial hypotension on the background of impaired water-electrolyte balance

Patients with reduced BCC and / or hyponatremia (as a result of vomiting, diarrhoea, high-dose diuretics, or a salt-restricted diet) may develop clinically significant hypotension after starting Edarby therapy. Hypovolemia should be corrected before starting treatment with Edarbi or starting treatment with a dosage of 20 mg.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism are usually resistant to therapy with antihypertensive drugs that affect the RAAS. In this regard, Edarbi is not recommended for such patients.

Hyperkalemia

Clinical experience with other drugs that affect the RAAS shows that concomitant use of Edarbi with potassium-sparing diuretics, potassium preparations or salt substitutes containing potassium, or other drugs that can increase the potassium content 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 have an increased risk of developing hyperkalemia, which can be fatal. In such patients, it is recommended to monitor the content of potassium in the blood serum.

Aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy

Caution should be exercised when prescribing Edarbi to patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy.

Lithium

As with other angiotensin II receptor antagonists, the concomitant use of lithium and Edarbi is not recommended.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Based on its pharmacodynamic properties, it is expected that azilsartan medoxomil will have a minor effect on the ability to drive vehicles and operate mechanisms. Caution should be exercised, as with any antihypertensive agents (risk of dizziness and fatigue).

Form of production

Tablets

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.

Shelf

life is 3 years.

Active ingredient

Azilsartan medoxomil

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension