Edarbi Clo pills 40mg+12.5mg, 28pcs

Composition

film-coated tablets 1 tab.

azilsartan medoxomil potassium 42.68 mg, which corresponds to the content of azilsartan medoxomil 40 mg

chlortalidone 12.5 mg

Auxiliary substances:

mannitol – 211.23 mg,

microcrystalline cellulose-54 mg,

fumaric acid-2 mg,

sodium hydroxide-0.69 mg,

hyprolose-10.8 mg,

crospovidone-22.5 mg,

magnesium stearate-3.6 mg.

Composition of the film shell:

hypromellose 2910-7.8 mg, talc-1.2 mg, titanium dioxide-0.99 mg, iron oxide red dye-0.01 mg, macrogol 8000-0.18 mg, grey F1 ink cleaned for marking trace amounts*.

Pharmacological action

Edarby® Clo is a combination drug that includes an angiotensin II receptor antagonist (ARAII — azilsartan medoxomil) and a thiazide-like diuretic (chlortalidone). The simultaneous use of two active substances leads to a more pronounced decrease in blood pressure compared to that when taking each of them in monotherapy. When taking the drug once a day, an effective reduction is achieved Blood pressure for 24 hours.

Azilsartan medoxomil is one of the active ingredients of Edarbi® Clo — is a specific angiotensin II type 1 (AT1) receptor antagonist. Angiotensin II is formed from angiotensin I in an ACE-catalyzed reaction (kininase II). Angiotensin II is the main vasoconstrictor of RAAS, its action includes vasoconstriction, stimulation of aldosterone synthesis and secretion, increased heart rate and sodium reabsorption by the kidneys. 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, such as vascular smooth muscle and the adrenal glands. Therefore, its action is not associated with the pathway of angiotensin II biosynthesis.

The AT2 receptor is also found in many tissues, but it is not involved in the regulation of CCC activity. The affinity of azilsartan for the AT1 receptor is 10,000 times higher than for the AT2 receptor.

Inhibition of RAAS activity by ACE inhibitors, which inhibit the formation of angiotensin II from angiotensin I, is widely used in the treatment of arterial hypertension. ACE inhibitors also inhibit the breakdown of bradykinin, which is catalyzed by ACE. Since azilsartan does not inhibit ACE(kininase II), it should not affect bradykinin activity. Azilsartan does not bind to other receptors or ion channels that play an important role in the regulation of CVS, and does not block them.

Azilsartan dose-dependently suppresses the vasoconstrictive effects of angiotensin II infusion. A single dose of azilsartan equivalent to 32 mg of azilsartan medoxomil suppressed the maximum vasoconstrictor effect of angiotensin II by approximately 90% at the time of highest concentration, and by approximately 60% 24 hours after use. In healthy volunteers, plasma angiotensin I and angiotensin II concentrations and renin activity increased, while aldosterone concentrations decreased after a single oral dose and after repeated doses of azilsartan medoxomil; no clinically significant effect on serum potassium or sodium levels was found. In general, the pharmacodynamic properties of azilsartan medoxomil are consistent with blocking the AT1 receptor.

The antihypertensive effect of azilsartan medoxomil develops during the first 2 weeks of use, with the maximum therapeutic effect achieved after 4 weeks. Decline Blood pressure after ingestion of a single dose is usually reached within a few hours and persists for 24 hours

. Chlortalidone-a thiazide-like diuretic-suppresses the active reabsorption of sodium ions in the renal tubules (the initial part of the distal convoluted tubule of the nephron), increasing the excretion of sodium and chlorine ions and increasing diuresis. In addition, chlortalidone increases the excretion of potassium, magnesium and bicarbonate ions, detains calcium ions and uric acid. The antihypertensive effect of chlortalidone is associated with the elimination of fluid and sodium from the body. The diuretic effect develops 2-3 hours after oral use of chlortalidone and persists for 2-3 days.

The antihypertensive effect of chlortalidone develops gradually, with the maximum therapeutic effect reaching 2-4 weeks after the start of therapy.

In the conducted clinical trials, the combination of azilsartan medoxomil + chlortalidone was more effective than the combination of azilsartan medoxomil with hydrochlorothiazide or the combination of olmesartan medoxomil + hydrochlorothiazide, despite the fact that a higher proportion of study participants in the comparison group required an increase in the dose due to insufficient blood pressure control.

In a double-blind study with a planned increase in the dose of 12 weeks, the combination of azilsartan medoxomil + chlortalidone at a dose of 40 + 25 mg was statistically significantly superior to the combination of olmesartan medoxomil + hydrochlorothiazide 40 + 25 mg in reducing sBP in moderate and severe arterial hypertension. Similar results were obtained in all subgroups of patients, regardless of age, gender, or race. The combination of azilsartan medoxomil + chlortalidone reduced blood pressure more effectively than the combination of olmesartan medoxomil + hydrochlorothiazide in every hour of the 24-hour interval between doses of drugs, according to ABPM (daily blood pressure monitoring).

Indications

Essential hypertension (patients who are indicated for combination therapy).

Contraindications

• hypersensitivity to the active substances and other components of the drug;
• refractory hypokalemia;
• anuria;
• simultaneous reception of aliskiren and iliskilendirmesi drugs in patients with diabetes, or moderate or severe renal impairment (glomerular filtration rate less than 60 ml/min/1.73 m 2);
• a severe form of diabetes,
• disorders of liver function severe (more than 9 points on a scale child-Pugh) (no experience);
• renal failure severe (Cl creatinine less than 30 ml/min) (no experience);
• pregnancy and breast-feeding (see “pregnancy and breast-feeding);
• the age of 18 years (effectiveness and safety not established).
• With caution:  severe chronic heart failure (NYHA functional Class IV); impaired renal function (creatinine clearance greater than 30 ml/min); mild to moderate hepatic impairment (5-9 points on the Child-Pugh scale); bilateral renal artery stenosis and artery stenosis of the only functioning kidney; ischemic cardiomyopathy; ischemic cerebrovascular diseases; post-kidney transplantation conditions; conditions accompanied by a decrease in BCC (including vomiting, diarrhea, high-dose diuretics), as well as a diet with a restriction of table salt; primary hyperaldosteronism; hyperuricemia and gout; bronchial asthma; systemic lupus erythematosus; aortic and mitral valve stenosis; hypertrophic obstructive cardiomyopathy (HOCMP); age over 75 years; hypokalemia. If the patient has one of the listed diseases, before taking Edarbi® Clo should consult your doctor.

Side effects

Combination of azilsartan medoxomil and chlortalidone

Blood and lymphatic system disorders:  infrequently-anemia.

Nervous system disorders:  often — dizziness, postural vertigo; infrequently-syncope (syncope), paresthesia.

From the side of blood vessels:  often — a marked decrease in blood pressure.

From the gastrointestinal tract:  often — diarrhea, nausea; infrequently-vomiting.

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

Musculoskeletal and connective tissue disorders:  infrequently-muscle spasms.

From the side of metabolism and nutrition:  often-hyperuricemia; infrequently-hypokalemia, increased potassium content, hyponatremia, exacerbation of gout.

Influence on the results of laboratory and instrumental studies:  very often-increased creatinine concentration; often-increased urea concentration; infrequently-increased glucose concentration.

General violations:  often — increased fatigue, peripheral edema.

Azilsartan medoxomil (monotherapy)

Nervous system disorders:  often — dizziness; infrequently-headache.

From the side of blood vessels:  infrequently — a marked decrease in blood pressure.

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

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

Musculoskeletal and connective tissue disorders:  infrequently-muscle spasms.

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

General violations:  infrequently — increased fatigue, peripheral edema.

Chlortalidone (monotherapy)

Nervous system disorders:  rarely-headache.

From the side of the heart:  rarely-arrhythmia.

From the side of blood vessels:  often — a marked decrease in blood pressure.

From the digestive system: often — loss of appetite, gastrointestinal disorders; rarely-constipation, abdominal pain; very rarely-pancreatitis.

Skin and subcutaneous tissue disorders: often — urticaria; rarely-photosensitization, cutaneous vasculitis.

Respiratory, thoracic and mediastinal disorders: rarely-allergic pulmonary edema.

Liver and biliary tract disorders: rarely-intrahepatic cholestasis or jaundice.

From the side of the kidneys and urinary tract: rarely-allergic interstitial nephritis.

Blood and lymphatic system disorders: rarely-thrombocytopenia, leukopenia, agranulocytosis, eosinophilia.

From the side of metabolism and nutrition: very often-hyperlipidemia, hypokalemia; often-hypomagnesemia; rarely-hypercalcemia, glucosuria, decompensation of existing diabetes mellitus; very rarely-hypochloremic alkalosis.

General violations: often-a decrease in potency.

Description of individual adverse reactions

When azilsartan medoxomil is co-administered with chlortalidone, the frequency of adverse reactions is significantly reduced Blood pressure and increased creatinine concentration-increases in frequency: from infrequent to frequent. This is due to a more effective reduction in blood pressure compared to azilsartan medoxomil 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.

Increased uric acid concentration when using Edarbi® Clo is caused by its constituent chlorthalidone and depends on the dose of the diuretic. Reports of gout development were infrequent even with long-term therapy.

When azilsartan medoxomil is co-administered with chlortalidone, the incidence of an adverse reaction, such as hypokalemia, is reduced.

If any of the side effects listed in the instructions get worse or the patient notices any other side effects that are not listed in the instructions, you should inform your doctor.

Interaction

Lithium. Reversible increases in serum lithium concentrations and toxicity were observed during concomitant use of lithium and diuretics and lithium preparations with ARAII. Therefore, the simultaneous use of Edarbi® Clo in combination with lithium preparations is not recommended (see “Special instructions”). If appropriate combination therapy is required, regular monitoring of serum lithium concentrations is recommended.

NSAIDs, including selective COX-2 inhibitors. In elderly patients and patients with reduced BCC (including those receiving diuretics) or with impaired renal function, the simultaneous use of ARAII and NSAIDs can lead to deterioration of renal function up to the development of acute renal failure. Therefore, at the beginning of treatment, patients are recommended to regularly take sufficient fluids and monitor kidney function. Concomitant use of ARAII and NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs may weaken the antihypertensive effect.

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

Cardiac glycosides. Concomitant use of cardiac glycosides and a diuretic may exacerbate the effects of hypokalemia, such as cardiac arrhythmias.

Additional information on the interaction of azilsartan medoxomil

No PCI was observed when azilsartan medoxomil or azilsartan was co-administered with amlodipine, antacids (aluminum and magnesium 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.

Additional information on the interaction of chlortalidone

Chlortalidone enhances the action of curare-like muscle relaxants and antihypertensive agents (including guanethidine, methyldopa, beta-blockers, vasodilators, BCC), MAO inhibitors.

Concomitant use of chlortalidone with allopurinol may increase the incidence of hypersensitivity reactions to allopurinol.

Chlortalidone may increase the risk of amantadine-related adverse reactions.

Anticholinergic drugs (for example, atropine, biperiden) can increase the bioavailability of chlortalidone, reducing gastrointestinal motility and gastric evacuation.

The hypokalemic effect of chlortalidone is enhanced when used concomitantly with corticosteroids, ACTH, amphotericin, beta-2-blockers, and carbenoxolone. Patients should monitor their serum potassium levels during combination therapy.

It may be necessary to adjust (reduce or increase) the dose of hypoglycemic agents for oral use and insulin.

The pharmacological effects of calcium and vitamin D salts may increase to clinically significant levels when co-administered with chlortalidone.

Concomitant use with cyclosporine may increase the risk of hyperuricemia and complications such as gout.

Colestyramine disrupts the absorption of chlortalidone. It is possible to reduce the pharmacological effect of chlortalidone.

Concomitant use of chlortalidone with methotrexate and cyclophosphamide may lead to potentiation of the pharmacological effect of antitumor drugs.

How to take, course of use and dosage

Inside,1 time a day, regardless of the meal time.

Recommended starting dose of Edarbi® Clo is 40 mg of azilsartan medoxomil + 12.5 mg of chlortalidone 1 time per day. If an additional reduction is required AD dose of Edarbi®Clo can be increased to the maximum — 40 mg of azilsartan medoxomil + 25 mg of chlortalidone 1 time per day.

Duration of treatment. Edarbi®preparation Clo should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor.

Special patient groups

Elderly patients (65 years and older). No adjustment of the initial dose of Edarbi®is required Clo in elderly patients.

Impaired renal function. No clinical experience with Edarbi® Clo in patients with arterial hypertension (AH) with severe renal impairment (creatinine clearance less than 30 ml / min), so it is not recommended to use the drug in this category of patients (see “Contraindications”). No dosage adjustment is required in patients with mild to moderate renal impairment (creatinine clearance greater than 30 ml / min).

Impaired liver function. It is not recommended to use the drug in patients with severe hepatic impairment due to lack of clinical experience (see “Contraindications”). Due to limited experience, Edarbi®should be used with caution Clo in patients with mild to moderate hepatic impairment (less than 9 points on the Child-Pugh scale), since even small violations of the water-electrolyte balance when taking diuretics can provoke a hepatic coma. It is recommended to actively monitor the condition of such patients.

BCC reduction. It is necessary to replace fluid and electrolyte losses in patients with reduced BCC before starting Edarbi® Clo (see “Special instructions”).

Heart failure. Due to the lack of clinical experience, Edarbi®should be used with caution Clo in patients with hypertension and severe CHF (NYHA functional class IV).

The Negroid race. No dose adjustment is required, because the antihypertensive effect of Edarbi® Clo in black patients is similar to its effect in patients of other races.

Skipping a dose

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 ® Clo. Withdrawal syndrome (a sharp increase in Blood pressure) was not observed after sudden discontinuation of azilsartan medoxomil after prolonged therapy (for 6 months). However, discontinuation of Edarbi® Clo should be performed as gradually as possible after prolonged treatment.

Overdose

Azilsartan medoxomil (monotherapy)

Experience with the use of azilsartan medoxomil in adults at 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 pronounced decrease in blood pressure, give the patient a supine position, lift the legs, take measures to increase the BCC; symptomatic therapy. Azilsartan is not eliminated from the systemic circulation by dialysis.

Chlortalidone (monotherapy)

Symptoms: nausea, weakness, dizziness, impaired water and electrolyte balance.

Treatment: there is no specific antidote. With a marked decrease in blood pressure, flush the stomach, take measures to normalize the water-electrolyte balance (infusion therapy); symptomatic therapy.

Special instructions

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 low-salt diet) may develop clinically significant hypotension after starting Edarbi Clo therapy. Hypovolemia and water-electrolyte balance should be adjusted before starting treatment. Transient arterial hypotension is not a contraindication to further treatment, which can be continued after blood pressure stabilizes.

Impaired renal function

In patients with impaired renal function (creatinine clearance greater than 30 ml / min), the drug should be used with caution. It is recommended to regularly monitor the potassium content and serum creatinine concentration. Such patients require careful dose selection with constant monitoring and control of blood pressure. Increased creatinine concentrations are more common in patients with moderate to severe renal impairment.

Chlortalidone can cause azotemia.

In case of progressive deterioration of renal function (increased blood urea nitrogen), temporary discontinuation of diuretic therapy or their complete cancellation is recommended.

Double blockade of the RAAS

Patients whose vascular tone and renal function depend to a large extent on the activity of the RAAS (for example, patients with severe CHF-NYHA functional class IV, severe renal insufficiency, or renal artery stenosis), treatment with drugs acting on the RAAS, such as ACE inhibitors and ARAII, 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 when using Edarbi® Clo.

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

Data on the use of Edarbi® Clo is absent in patients who have recently undergone kidney transplantation.

Impaired liver function

Data on clinical experience with Edarbi® There are no Clos in patients with severe hepatic impairment, so the use of the drug in this category of patients is not recommended (see “Contraindications”). Due to limited experience, Edarbi®should be used with caution Clo in patients with mild to moderate hepatic impairment (less than 9 points on the Child-Pugh scale), since even small violations of the water-electrolyte balance when taking diuretics can provoke a hepatic coma. It is recommended to actively monitor the condition of such patients.

Primary hyperaldosteronism

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

Hypokalemia

Hypokalemia may occur during chlortalidone therapy. It is necessary to regularly monitor the content of potassium in the blood serum. In patients taking cardiac glycosides, hypokalemia may predispose to arrhythmia.

Aortic or mitral valve stenosis, HOCMP

When prescribing Edarbi® Clo patients with aortic or mitral stenosis or HOCMP should be treated with caution.

Lithium

As with other ARAII, concomitant use of lithium and Edarbi® Clo is not recommended.

Influence on the ability to drive vehicles and work with mechanisms. Care should be taken when driving vehicles and working with mechanisms that require increased attention and reaction speed — the risk of dizziness and increased fatigue.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C in the original packaging.

Shelf

life is 3 years.

Active ingredient

Azilsartan medoxomil, Chlortalidone

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Hypertension