Edarbi Clos pills 40mg + 12,5mg №28

Indications

- Essential hypertension (to patients who are shown combination therapy).

Dosage and administration

Drug Edarbi ^® Clot is ingested 1 time / day, regardless of meal times.

The recommended initial dose of the drug Edarbi^® Clo is 40 mg of azilsartan medoxomil + 12.5 mg of chlorthalidone 1 time / day.

If necessary, further reduction in blood pressure dose of the drug Edarbi^® Clos can be increased to a maximum of 40 mg of azilsartan medoxomil + 25 mg of chlorthalidone 1 time / day.

Drug edarbi^® Clos should be taken daily, without interruption. In case of termination of treatment, the patient must inform the doctor.

In case of skipping the next dose, the next dose should be taken at the usual time. Do not take a double dose of Edarbi^® Clos.

Withdrawal when a sudden discontinuation of azilsartan medoxomil after prolonged therapy (for 6 months) was not observed. However, the abolition of the drug Edarbi^® Clos after prolonged treatment should be carried out, if possible, gradually.

Have elderly patients no adjustment of the initial dose of the drug is required.

No clinical experience with the drug Edarbi^® Clos in patients with hypertension with severe renal dysfunction (CC less than 30 ml / min)therefore, it is not recommended to use the drug in this category of patients. Have patients with impaired renal mild and moderate severity (CC more than 30 ml / min) correction of the mode of dispensing is not required.

It is not recommended to use the drug in patients with severe hepatic impairmentbecause no clinical experience of use. Due to limited experience, Edarbi should be used with caution.^® Clo patients with impaired mild and moderate liver function (less than 9 points on the Child-Pugh scale)Because even small violations of water and electrolyte balance when taking diuretics can provoke hepatic coma. It is recommended to actively monitor the condition of such patients.

In patients with reduced BCC before starting to use the drug Edarbi^® Clos need to compensate for the loss of fluid and electrolytes.

In patients with arterial hypertension with severe chronic heart failure (class IVHA, class IVHA), Edarbi should be used with caution.^® Clos due to lack of clinical experience.

In patients of the Negroid race, dose adjustment is not required, since antihypertensive effect of the drug Edarbi^® Clo in this category of patients is similar to its effect in patients of other races.

Adverse effects

The frequency of adverse reactions was determined in accordance with the 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; unspecified frequency (frequency cannot be calculated from available data).

Hemic and lymphatic: infrequently - anemia.

Nervous system: often - dizziness, postural dizziness; infrequently - syncope, paresthesia.

Cardiovascular: often - excessive decrease in blood pressure.

Gastrointestinal: often - diarrhea, nausea; infrequently - vomiting.

Dermatological: infrequently - rash, itching.

Musculoskeletal system: infrequently - muscle spasms.

Metabolism: often - hyperuricemia; infrequently - hypokalemia, hyperkalemia, hyponatremia, exacerbation of the course of gout.

From the laboratory and instrumental studies: very often - an increase in the concentration of creatinine; often - increase in concentration of urea; infrequently - an increase in glucose concentration.

Allergic reactions: rarely - angioedema.

Other: often - increased fatigue, peripheral edema.

Azilsartan medoxomil (monotherapy)

Nervous system: often - dizziness; infrequently - headache.

Cardiovascular: infrequently - excessive decrease in blood pressure.

Gastrointestinal: often - diarrhea; infrequently - nausea.

Dermatological: infrequently - rash, itching.

Musculoskeletal system: infrequently - muscle spasms.

From the laboratory and instrumental studies: often - increased activity of CPK; infrequently - an increase in the concentration of creatinine, hyperuricemia.

Allergic reactions: rarely - angioedema.

Other: infrequently - increased fatigue, peripheral edema.

Chlorthalidone (monotherapy)

Hemic and lymphatic: rarely - thrombocytopenia, leukopenia, agranulocytosis, eosinophilia.

Nervous system: rarely a headache.

Cardiovascular: often - excessive decrease in blood pressure; rarely - artimia.

Respiratory: rarely - allergic pulmonary edema.

Gastrointestinal: often - loss of appetite, gastrointestinal disorders; rarely, constipation, abdominal pain, intrahepatic cholestasis, or jaundice; very rarely - pancreatitis.

Urogenital: rarely, allergic interstitial nephritis.

Dermatological: rarely - photosensitivity, cutaneous vasculitis.

Metabolism: very often - hyperlipidemia, hypokalemia; often - hypomagnesemia; rarely - hypercalcemia, glycosuria, decompensation of existing diabetes; very rarely - hypochloremic alkalosis.

Allergic reactions: often - urticaria.

Other: often - reduced potency.

Description of individual adverse reactions

With simultaneous use of azilsartan medoxomil with chlorthalidone, the frequency of adverse reactions — an excessive decrease in blood pressure and an increase in the concentration of creatinine — increases in frequency of occurrence: from “infrequently” to “often”. This is associated with a more effective reduction in blood pressure compared with azilsartan monotherapy with medoxomil.Most of these effects were short-term or not progressive, while patients continued therapy. After discontinuation of the drug, most cases of an increase in the concentration of creatinine that were not treated during treatment were reversible.

Increasing the concentration of uric acid when using the drug Edarbi^® Clos is due to chlortalidone in its composition and depends on the dose of diuretic. Reports of gout development have been infrequent, even with prolonged therapy.

With the simultaneous use of azilsartan medoxomil with chlorthalidone, the incidence of hypokalemia decreases.

If any of the side effects indicated in the instructions are aggravated or any other side effects that are not indicated in the instructions appear, the patient should be informed about this by the doctor.

Contraindications

- refractory hypokalemia;

- anuria;

- simultaneous use of aliskiren and aliskiren-containing drugs in patients with diabetes mellitus or moderate or severe renal impairment (GFR less than 60 ml / min / 1.73 m²);

- severe forms of diabetes;

- abnormal liver function (more than 9 points on the Child-Pugh scale), because no experience of use;

- renal failure severe (CC less than 30 ml / min), because no experience of use;

- age up to 18 years (efficiency and safety have not been established);

- pregnancy;

- lactation period (breastfeeding);

- hypersensitivity to the drug.

Carefully:

- severe chronic heart failure (NYHA functional class IV);

- impaired renal function (CC more than 30 ml / min);

- dysfunction of the liver of mild and moderate degree (5-9 points on the Child-Pugh scale);

- bilateral renal artery stenosis and arterial stenosis of the only functioning kidney;

- Ischemic cardiomyopathy;

- ischemic cerebrovascular diseases;

- condition after kidney transplantation;

- conditions accompanied by a decrease in BCC (including vomiting, diarrhea, the use of diuretics in high doses), as well as in patients on a diet with restriction of table salt;

- primary hyper aldosteronism;

- hyperuricemia, gout;

- bronchial asthma;

- Systemic lupus erythematosus;

- Aortic and mitral valve stenosis;

- hypertrophic obstructive cardiomyopathy (GOKMP);

- age over 75 years;

- hypokalemia.

Use during pregnancy and lactation

Experience the use of the drug Edarbi^® Clos in pregnant women is absent. The use of the drug during pregnancy and during breastfeeding is not recommended.

Newborns whose mothers received azilsartan medoxomil may develop hypotension, and therefore newborns should be under close medical supervision.

Chlorthalidone penetrates the placental barrier into umbilical cord blood and can cause fetal or newborn jaundice, thrombocytopenia, and also other undesirable reactions noted in adults.

Immediately after confirmation of pregnancy should stop using the drug Edarbi^® Clo and, if necessary, switch to the use of drugs with proven safety of use during pregnancy.

There is no information in relation to a person about the ability of azilsartan and / or its metabolites to be excreted in breast milk. AT experimental studies in animals it was revealed that azilsartan and its metabolite M-II are excreted in milk of lactating rats.

Chlorthalidone is excreted in breast milk.

If necessary, use the drug Edarbi^® Clos during lactation must stop breastfeeding, or stop taking the drug. Preferably the use of drugs with a proven safety profile.

Application for violations of the liver

It is not recommended to use the drug in patients with severe hepatic impairment due to lack of clinical experience.

Due to limited experience, Edarbi should be used with caution.^® Clo patients with impaired mild and moderate liver function (less than 9 points on the Child-Pugh scale)Because even small violations of water and electrolyte balance when taking diuretics can provoke hepatic coma. It is recommended to actively monitor the condition of such patients.

Application for violations of kidney function

No clinical experience with the drug Edarbi^® Clos in patients with hypertension with severe renal dysfunction (CC less than 30 ml / min)therefore, it is not recommended to use the drug in this category of patients. Have patients with impaired renal mild and moderate severity (CC more than 30 ml / min) correction of the mode of dispensing is not required.

Use in children

The drug is contraindicated at the age of 18 years (efficacy and safety have not been established).

Use in elderly patients

Elderly patients do not require correction of the initial dose of the drug.

With caution should appoint the drug to patients over the age of 75 years.

special instructions

Arterial hypotension on the background of impaired water and electrolyte balance

Patients with reduced BCC and / or hyponatremia (as a result of vomiting, diarrhea, use of diuretics in large doses, or following a diet with restricted salt intake) may develop clinically significant hypotension after starting treatment with Edarbi^® Clos. Hypovolemia and water-electrolyte balance should be adjusted before starting treatment. Transient hypotension is not a contraindication to further treatment, which can be continued after stabilization of blood pressure.

Renal dysfunction

In patients with impaired renal function (CC more than 30 ml / min), the drug should be used with caution. It is recommended to regularly monitor the content of potassium 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 and severe renal impairment.

Chlorthalidone may cause azotemia.

In the case of progressive deterioration of kidney function (increase in blood urea nitrogen (BUN), it is recommended to temporarily stop diuretic therapy or cancel them completely.

Double blockade of RAAS

Patients whose vascular tone and kidney function depend to a large extent on the activity of the RAAS (for example, in patients with severe chronic heart failure (class IVHA functional class IV), severe renal failure or renal artery stenosis). for RAAS, such as ACE inhibitors and ARA II, is associated with the possibility of developing acute arterial hypotension, azotemia, oliguria, or, in rare cases, acute renal failure . The possibility of the development of these effects can not be excluded when using the drug Edarbi^® Clos.

A sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases may lead to the development of myocardial infarction or stroke.

Kidney transplantation

Data on the use of the drug Edarbi^® Clos in patients who have recently had a kidney transplant are absent.

Liver dysfunction

Data on the clinical experience of the drug Edarbi^® Klo in patients with severely impaired liver function are absent, therefore, the use of the drug in this category of patients is not recommended. Due to limited experience, Edarbi should be used with caution.^® Klo in patients with impaired liver function of mild and moderate degree (less than 9 points on the Child-Pugh scale), since even small violations of water and 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 antihypertensive medication therapy that affects the RAAS. In this regard, the drug Edarbi^® Clo is not recommended to appoint such patients.

Hypokalemia

When therapy with chlorthalidone may develop hypokalemia. It is necessary to regularly monitor the content of potassium in the serum. In patients taking cardiac glycosides, hypokalemia may predispose to arrhythmias.

Aortic or mitral valve stenosis, hypertrophic obstructive cardiomyopathy

When prescribing the drug Edarbi^® Patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy should be treated with caution.

Influence on ability to drive motor transport and control mechanisms

Care must be taken when driving and working with mechanisms that require increased attention and responsiveness, because when using the drug there is a risk of dizziness and fatigue.

Overdose

Azilsartan medoxomil (monotherapy)

The experience with azilsartan medoxomil in adults in doses up to 320 mg / day for 7 days shows that the drug is well tolerated.

Symptoms: excessive decrease in blood pressure, dizziness.

Treatment: in case of an excessive decrease in blood pressure, the patient should be placed in a horizontal position with a low head; It is recommended that measures to increase the BCC and symptomatic therapy. Azilsartan is not excreted from the systemic circulation through dialysis.

Chlorthalidone (monotherapy)

Symptoms: nausea, weakness, dizziness, disturbances of water and electrolyte balance.

Treatment: there is no specific antidote. With an excessive decrease in blood pressure should be flushing the stomach; It is recommended to take measures for the normalization of water and electrolyte balance (infusion therapy) and symptomatic therapy.

Drug interaction

There was a reversible increase in serum lithium concentration and toxicity during simultaneous use of lithium preparations and diuretics and lithium preparations with angiotensin II receptor antagonists (APA II). Therefore, the simultaneous use of the drug Edarbi^® Clo in combination with lithium preparations is not recommended. If necessary, the use of appropriate combination therapy is recommended to regularly monitor the concentration of lithium in the serum.

In elderly patients and patients with reduced BCC (including receiving diuretics) or with impaired renal function, the simultaneous use of ARA II and NSAIDs can lead to impaired renal function up to the development of acute renal failure. Therefore, at the beginning of treatment, patients are recommended to regularly take a sufficient amount of fluid and monitor renal function. With the simultaneous use of ARA II and NSAIDs, including selective COX-2 inhibitors, Acetylsalicylic acid (more than 3 g / day) and non-selective NSAIDs, the antihypertensive effect may be weakened.

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

The simultaneous use of cardiac glycosides and a diuretic may aggravate the effects of hypokalemia, such as cardiac arrhythmias.

Additional Information on Azilsartan Medoxomil Interaction

No pharmacokinetic interaction was observed with simultaneous use of azilsartan medoxomil or azilsartan with Amlodipine, antacid preparations (aluminum and Magnesium hydroxide), chlorthalidone, Digoxin, Fluconazole, glibenclamide, Ketoconazole, Metformin and Warfarin .

Azilsartan medoxomil is converted to the pharmacologically active metabolite azilsartan during absorption from the gastrointestinal tract under the action of the enzyme carboxymethylene butenolidase in the intestine and liver. In vitro studies have shown that interaction based on enzyme inhibition is unlikely.

Additional Information on Chlorthalidone Interaction

Chlorthalidone enhances the action of curare-like muscle relaxants and antihypertensive drugs (including guanethidine, methyldopa, beta-blockers, vasodilating agents, slow Calcium channel blockers), MAO inhibitors .

The simultaneous use of chlorthalidone with Allopurinol may lead to an increase in the frequency of hypersensitivity reactions to allopurinol.

Chlorthalidone may increase the risk of side effects caused by amantadine.

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

The hypokalemic effect of chlortalidone is enhanced with simultaneous use with corticosteroids, adrenocorticotropic hormone, amphotericinin, beta₂-adrenoblockers, carbenoxolone. Patients during combination therapy should monitor the content of potassium in the serum.

It may be necessary to correct (decrease or increase) the dose of hypoglycemic agents for oral administration and insulin .

The pharmacological effects of calcium and vitamin D salts may increase to a clinically significant level while being used with chlorthalidone.

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

Kolestiramine interferes with the absorption of chlorthalidone. Perhaps a decrease in the pharmacological effect of chlorthalidone.

The simultaneous use of chlorthalidone with Methotrexate and cyclophosphamide can lead to a potentiation of the pharmacological effect of anticancer drugs.

Terms and conditions of storage

The drug should be stored in its original packaging out of the reach of children, dry, protected from light, at a temperature of above 25 ° C.