azilsartan medoksomyl, Hlortalydon | Edarbi Clough tablets coated. 40 mg + 25 mg 28 pcs. pack

Packing

28 capsules.

Indications

Essential hypertension (patients who are shown combination therapy).

Contraindications

hypersensitivity to the active substances and other components of the drug

refractory hypokalemia

anuria

simultaneous administration of aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or moderate or severe renal impairment (glomerular filtration rate less than 60 ml / min / 1.73 m2)

severe diabetes mellitus

severe liver function impairment (more than 9 Child-Pugh score) (no experience with use)

severe renal failure (creatinine Cl less than 30 ml / min) (no experience with use)

pregnancy and lactation period (see. lactation and lactation)

age up to 18 years (efficacy and safety not established).

Caution: severe chronic heart failure (NYHA class IV functional class) impaired renal function (creatinine Cl more than 30 ml / min) mild to moderate hepatic impairment (5–9 Child-Pugh score) bilateral renal artery stenosis and artery stenosis functioning kidney ischemic cardiomyopathy ischemic cerebrovascular disease condition after kidney transplantation conditions, accompanied by a decrease in BCC (including vomiting, diarrhea, taking high doses of diuretics), as well as a diet with ogre deficiency of table salt primary hyperaldosteronism hyperuricemia and gout bronchial asthma systemic lupus erythematosus aortic and mitral valve stenosis hypertrophic obstructive cardiomyopathy (GOKMP) age over 75 years of hypokalemia. If the patient has one of these diseases, consult with your doctor before taking Edarbi® Clo.

Use during pregnancy and lactation

There is no experience with the use of the drug Edarbi® Klo in pregnant women. Taking the drug during pregnancy and during breastfeeding is not recommended.

In newborns whose mothers received azilsartan medoxomil therapy, arterial hypotension may develop, and therefore newborns should be closely monitored. Chlortalidone crosses the placental barrier into the umbilical cord blood and can cause fetal or newborn jaundice, thrombocytopenia, and also other adverse reactions seen in adults. Immediately after confirmation of pregnancy, you should stop taking the drug Edarbi® Klo and, if necessary, switch to the use of drugs with proven safety during pregnancy.

There is no information on a person regarding the ability of azilsartan and / or its metabolites to pass into breast milk. Animal studies have revealed that azilsartan and its metabolite MII are excreted in the milk of lactating rats. Chlortalidone crosses the placental barrier and is detected in umbilical cord blood, fetal blood, and breast milk. If it is necessary to use the drug Edarbi® Klo during lactation, it is necessary to stop breastfeeding or taking the drug. The use of drugs with a proven safety profile is preferred.

Special instructions

Arterial hypotension in patients with impaired water-electrolyte balance

In patients with reduced BCC and / or hyponatremia (as a result of vomiting, diarrhea, taking large doses of diuretics, or following a diet that restricts salt intake), clinically significant arterial hypotension may develop after starting treatment with EdarbiВ® Clough. 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 stabilization of blood pressure.

Impaired renal function

In patients with impaired renal function (Cl creatinine greater than 30 ml / min), the drug should be used with caution. It is recommended that you regularly monitor the potassium content and serum creatinine concentration. Such patients require careful dose selection with constant monitoring and control of blood pressure. An increase in creatinine concentration is more often observed in patients with moderate and severe renal impairment.

Chlortalidone may cause azotemia.

In case of progressive deterioration in renal function (increased blood urea nitrogen, temporary suspension of diuretic therapy or their complete withdrawal is recommended.

Double blockade of RAAS

Patients in whom vascular tone and renal function depend to a large extent on RAAS activity (for example, patients with severe heart failure - Functional class IV according to NYHA classification, severe renal failure or renal artery stenosis), treatment of drugs acting on RAAS, such as ACE inhibitors and ARAII, is associated with the possibility of developing I acute hypotension, azotemia, oliguria, or rarely - acute renal failure. The possibility of developing these effects cannot be excluded with the use of the drug EdarbiВ® Klo.

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.

Kidney transplantation

There are no data on the use of the drug EdarbiВ® Klo in patients who have recently undergone kidney transplantation.

Impaired liver function

Data on the clinical experience with the use of the drug EdarbiВ® Clo in patients with severe liver dysfunction are not available, therefore, the use of the drug in this category of patients is not recommended (see "Contraindications"). Due to limited experience, EdarbiВ® Clough should be used with caution in patients with mild to moderate hepatic impairment (less than 9 points on the Child-Pugh scale), since even small disturbances in the water-electrolyte balance when taking diuretics can provoke 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 RAAS. In this regard, the drug EdarbiВ® Klo is not recommended for such patients.

Hypokalemia

Hypokalemia may occur with 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 arrhythmias.

Aortic or mitral valve stenosis, GOKMP

Caution must be exercised when prescribing EdarbiВ® Clo to patients with aortic or mitral stenosis or GOKMP.

Lithium

As with other ARAII, the simultaneous use of lithium and EdarbiВ® Cloe is not recommended.

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

Composition

1 tab. contains: Active substances: azilsartan medoxomil potassium - 42.68 mg, which corresponds to the content of azilsartan medoxomil 40 mg

chlortalidone 25 mg

Excipients: mannitol - 198.73 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 coat: hypromellose 2910 - 7.8 mg, talc - 1.2 mg, titanium dioxide - 0.94 mg, dye iron oxide red - 0.06 mg, macrogol 8000 - 0.18 mg, gray ink F1 purified for marking - trace amounts.

Dosage and Administration

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

The recommended starting dose of Edarbi® Cloe is 40 mg of azilsartan medoxomil + 12.5 mg of chlortalidone once a day. If it is necessary to further reduce blood pressure, the dose of Edarbi®Klo can be increased to a maximum of 40 mg of azilsartan medoxomil + 25 mg of chlortalidone once a day.

Duration of treatment. Edarbi® Clough 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 correction of the initial dose of Edarbi®Klo in elderly patients is required.

Impaired renal function. There is no clinical experience with the use of the drug Edarbi® Clo in patients with arterial hypertension (AH) with severe renal impairment (creatinine Cl less than 30 ml / min), therefore, it is not recommended to use the drug in this category of patients (see "Contraindications"). Correction of the dosage regimen is not required in patients with impaired renal function of mild to moderate severity (Cl creatinine more than 30 ml / min).

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

Decrease in bcc. It is necessary to compensate for the loss of fluid and electrolytes in patients with reduced BCC before starting to use the drug Edarbi® Klo (see "Special Instructions").

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

Negroid race. Dose adjustment is not required because the antihypertensive effect of the drug Edarbi® Clo in patients of the Negroid race is similar to its effect in patients of other races.

Skip dose

If you skip taking the next dose, the patient should take the next dose at the usual time. Do not take a double dose of Edarbi® Clough. Withdrawal syndrome (a sharp increase in blood pressure) after a sudden withdrawal after prolonged therapy (for 6 months) with azoxartan medoxomil was not observed. Nevertheless, discontinuation of the drug Edarbi® Klo after prolonged treatment should be carried out gradually if possible.

Side effects

Combination of azilsartan medoxomil and chlortalidone

From the blood and lymphatic system: infrequently - anemia.

From the nervous system: often - dizziness, postural dizziness infrequently - fainting (syncope), paresthesia.

From the vessels: often - a pronounced decrease in blood pressure.

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

From the skin and subcutaneous tissues: infrequently - skin rash, itching rarely - angioedema.

From the side of musculoskeletal and connective tissue: infrequently - muscle cramps.

From the side of metabolism and nutrition: often - hyperuricemia infrequently - hypokalemia, increased potassium, hyponatremia, exacerbation of the course 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 disorders: often - fatigue, peripheral edema.

Azilsartan medoxomil (monotherapy)

From the nervous system: often - dizziness infrequently - headache.

From the vessels: infrequently - a pronounced decrease in blood pressure.

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

From the skin and subcutaneous tissues: infrequently - skin rash, itching rarely - angioedema.

From the side of musculoskeletal and connective tissue: infrequently - muscle cramps.

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

General disorders: infrequently - fatigue, peripheral edema.

Chlortalidone (monotherapy)

From the nervous system: rarely - headache.

From the side of the heart: rarely - arrhythmia.

From the vessels: often - a pronounced decrease in blood pressure.

From the digestive system: often - loss of appetite, gastrointestinal upset rarely - constipation, abdominal pain is very rare - pancreatitis.

From the skin and subcutaneous tissues: often - urticaria rarely - photosensitivity, skin vasculitis.

From the respiratory system, chest and mediastinal organs: rarely - allergic pulmonary edema.

From the liver and biliary tract: rarely - intrahepatic cholestasis or jaundice.

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

From the blood and lymphatic system: 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 is very rare - hypochloremic alkalosis.

General disorders: often - a decrease in potency.

Description of individual adverse reactions

With the simultaneous use of azilsartan medoxomil with chlortalidone, the frequency of adverse reactions - a marked decrease in blood pressure and an increase in creatinine concentration - increases in frequency: from infrequently to often. This is due to a more effective reduction in blood pressure compared with monoxysilane azilsartan medoxomil. 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.

An increase in the concentration of uric acid when using the drug Edarbi® Cloe is due to chlortalidone included in its composition and depends on the dose of the diuretic. Reports of gout development were infrequent even with prolonged therapy.

With the simultaneous use of azilsartan medoxomil with chlortalidone, the incidence of an adverse reaction, such as hypokalemia, is reduced.

If any of the side effects indicated in the instructions are aggravated or the patient has noticed any other side effects, not specified in the instructions, you should inform your doctor.

Drug Interactions

Lithium. A reversible increase in serum lithium concentration and toxicity were observed during the simultaneous use of lithium preparations and diuretics and lithium preparations with ARAII. Therefore, the simultaneous use of the drug Edarbi® Klo in combination with lithium preparations is not recommended (see "Special instructions"). If appropriate combination therapy is needed, regular monitoring of serum lithium concentration 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 advised to regularly take a sufficient amount of fluid and monitor renal function. With the simultaneous use of ARAII and NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs, a weakening of the antihypertensive effect is possible.

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

Cardiac glycosides. The simultaneous use of cardiac glycosides and a diuretic may exacerbate the effects of hypokalemia, such as heart rhythm disturbances.

Additional information on the interaction of azilsartan medoxomil

No PKF was observed with the simultaneous use of azilsartan medoxomil or azilsartan with amlodipine, antacids (aluminum and magnesium hydroxide), chlortalidone, digoxin, fluconazole, glibenclamidamine, ketone.

Azilsartan medoxomil is converted to the pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract by the action of the carboxymethylenebutenolidase enzyme 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 curariform muscle relaxants and antihypertensive drugs (including guanethidine, methyldopa, beta-blockers, vasodilating agents, CCB), MAO inhibitors.

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

Chlortalidone may increase the risk of adverse reactions due to amantadine.

Anticholinergics (such as atropine, biperiden) can increase the bioavailability of chlortalidone, reducing gastrointestinal motility and gastric evacuation.

The hypokalemic effect of chlortalidone is enhanced with concurrent use with corticosteroids, ACTH, amphotericin, beta2-blockers, carbenoxolone. Patients during combination therapy should monitor the serum potassium content.

May require correction (decrease or increase) in the dose of hypoglycemic agents for oral administration and insulin.

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

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

Colestyramine disrupts the absorption of chlortalidone. A decrease in the pharmacological effect of chlortalidone is possible.

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

Overdose

Azilsartan medoxomil (monotherapy)

The experience 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: in case of a pronounced decrease in blood pressure, give the patient a lying position, raise his legs, carry out measures to increase the BCC symptomatic therapy. Azilsartan is not excreted in the systemic circulation by dialysis.

Chlorthalidone (monotherapy)

Symptoms: nausea, weakness, dizziness, impaired electro-electrolyte balance.

Treatment: There is no specific antidote. In case of marked decrease in blood pressure, wash the stomach, carry out measures to normalize the water-electrolyte balance (infusion therapy) symptomatic therapy.

Storage conditions

Dry, protected from light at a temperature not exceeding 25 РC in the original package.

Shelf life

3 years.

Conditions of release from drugstores

Prescription of pdroro1pf1690 Terms and conditions of vocational

dosage form

tab heel

Possible Product Names

Edarby Clough tablets film 40 mg + 25 mg 28 pcs.

Takeda GmbH, Japan