Universal reference book for medicines
Name of the preparation: EDARBI ® CLO (EDARBI CLO)

Active substance: azilsartan medoxomil, chlorthalidone

Type: Antihypertensive drug

Manufacturer: TAKEDA PHARMACEUTICALS USA, Inc.
(USA) manufactured by TAKEDA PHARMACEUTICAL COMPANY (Japan)
Composition, form of production and packaging

The tablets covered with a film membrane of a pale pink color, round, biconcave, with the written in gray ink inscriptions "A / C" and "40 / 12.5" on one side.
1 tab.
azilsartan medoxomil potassium 42.68 mg,
which corresponds to the content of azilsartan medoxomil 40 mg
Chlorthalidone 12.5 mg
Excipients: mannitol - 211.23 mg, microcrystalline cellulose - 54 mg, fumaric acid - 2 mg, sodium hydroxide - 0.69 mg, giprolose - 10.8 mg, crospovidone - 22.5 mg, magnesium stearate - 3.6 mg.
The composition of the film sheath: hypromellose 2910 - 7.8 mg, talc 1.2 mg, titanium dioxide 0.99 mg, iron oxide red oxide 0.01 mg, macrogol 8000 0.18 mg, gray ink F1 cleaned for labeling - trace amounts.
7 pcs. - blisters aluminum (4) - packs cardboard.
The tablets, covered with a film coat of grayish-pink color, are round, biconcave, with inscriptions "A / C" and "40/25" on one side with gray ink.
1 tab.
azilsartan medoxomil potassium 42.68 mg,
which corresponds to the content of azilsartan medoxomil 40 mg
chlorthalidone 25 mg
Excipients: mannitol - 198.73 mg, microcrystalline cellulose - 54 mg, fumaric acid - 2 mg, sodium hydroxide - 0.69 mg, giprolose - 10.8 mg, crospovidone - 22.5 mg, magnesium stearate - 3.6 mg.
The composition of the film sheath: hypromellose 2910-7.8 mg, talc 1.2 mg, titanium dioxide 0.94 mg, iron oxide red oxide 0.06 mg macrogol 8000 0.18 mg, gray ink F1 cleaned for labeling - trace amounts.
7 pcs. - blisters aluminum (4) - packs cardboard.
* Gray ink F1 cleaned for labeling contain: shellac - 26%, iron dye oxide black - 10%, butyl alcohol - 38%, ethanol - 26%.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Combined antihypertensive drug. The composition of the drug Edarby ® Clot includes an antagonist of angiotensin II receptors (azilsartan medoxomil) and a thiazide-like diuretic (chlorthalidone). Simultaneous application of two active substances leads to a more pronounced decrease in blood pressure as compared with the reception of each of them in monotherapy. When taking the drug 1 time / day, an effective BP reduction is achieved within 24 hours.
Azilsartan medoxomil is a specific antagonist of angiotensin II receptor type 1 (AT 1 ). Angiotensin II is formed from angiotensin I in a reaction catalyzed by the angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the main vasoconstrictor of RAAS, its action includes vasoconstriction, stimulation of synthesis and secretion of aldosterone, an increase in heart rate and the reabsorption of sodium by the kidneys.
Azolsartan medoxomil is a prodrug for oral administration. Rapidly turns into an active molecule of azilsartan, which selectively inhibits the development of the effects of angiotensin II by blocking its binding to the AT 1 receptor in various tissues, for example, in smooth muscles of blood vessels and adrenal glands. Therefore, its effect is not related to the pathway of biosynthesis of angiotensin II. The AT 2 receptor is also found in many tissues, but it is not involved in the regulation of cardiovascular activity. The affinity of azilsartan to the AT 1 receptor is 10,000 times higher than that of the AT 2 receptor.
The inhibition of RAAS activity by ACE inhibitors that inhibit the formation of angiotensin II from angiotensin I is widely used in the treatment of 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 the activity of bradykinin. Azilsartan does not bind to other receptors or ion channels, which play an important role in the regulation of the cardiovascular system, and does not block them.
Azilsartan dose-dependently suppresses the vasoconstrictive effects of angiotensin II infusion. A single dose of azilsartan at a dose equivalent to 32 mg of azilsartan medoxomil suppressed the maximum vasoconstrictive effect of angiotensin II by approximately 90% at the time of highest concentration, and approximately 60% at 24 hours after administration. In healthy volunteers, the concentrations of angiotensin I and angiotensin II and renin activity in the blood plasma increased and the aldosterone concentration decreased after a single oral intake and after repeated doses of azilsartan medoxomil; there was no clinically significant effect on the potassium or sodium content in the blood serum. In general, the pharmacodynamic properties of azilsartan medoxomil are consistent with the blocking of AT 1 receptors.
The antihypertensive effect of azilsartan medoxomil develops during the first 2 weeks of use with the maximum therapeutic effect achieved after 4 weeks. Reduction of blood pressure after ingestion of a single dose is usually achieved within a few hours and persists for 24 hours.
Chlortalidone is a thiazide-like diuretic that 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 enhancing diuresis. In addition, chlortalidone increases the excretion of potassium, magnesium and bicarbonate ions, delays calcium ions and uric acid. The antihypertensive effect of chlorthalidone is associated with the excretion of liquid and sodium from the body. Diuretic effect develops 2-3 hours after chlorthalidone intake and remains for 2-3 days.
The antihypertensive effect of chlorthalidone develops gradually with the achievement of maximum therapeutic effect in 2-4 weeks after the initiation of therapy.
In clinical trials, the combination of azilsartan medoxomil / chlorthalidone was more effective than the combination of azilsartan medoxomil with hydrochlorothiazide or a combination of olmesartan medoxomil / hydrochlorothiazide, although a higher proportion of participants in the comparison group required an increase in dose due to insufficient blood pressure control.
In a double-blind study with a planned dose increase of 12 weeks, the combination of azilsartan medoxomil / chlorthalidone at a dose of 40 mg / 25 mg statistically significantly exceeded the combination of olmesartan medoxomil / hydrochlorothiazide 40 mg / 25 mg in reducing systolic blood pressure with moderate and severe degree of hypertension. Similar results were obtained in all subgroups of patients, regardless of age, gender or race. The combination of azilsartan medoxomil / chlorthalidone lowered blood pressure more efficiently than the combination of olmesartan medoxomil / hydrochlorothiazide at each hour of the 24-hour interval between doses of the drugs, according to the BPM (daily BP monitoring).
PHARMACOKINETICS
Azilsartan medoxomil
Suction
After taking the drug inside C max azilsartan in blood plasma, on average, is achieved within 3 hours.
The pharmacokinetic parameters (T max , Cmax , AUC value) of azilsartan are similar both when it is co-administered with chlorthalidone and without it.
Distribution
V d of azilsartan is about 16 liters. Azilsartan binds to blood plasma proteins (more than 99%), mainly with albumins.
Metabolism
Azilsartan is metabolized to two primary metabolites, mainly in the liver. The main metabolite in the blood plasma is formed by O-dealkylation and is referred to as the M-II metabolite, the secondary metabolite is formed by decarboxylation and is referred to as the M-I metabolite. The values ​​of AUC for these metabolites in humans are 50% and less than 1%, respectively, compared with azilsartan. The main enzyme that provides the metabolism of azilsartan is the isoenzyme CYP2C9.
Excretion
Azilsartan and its metabolites are excreted from the body both through the intestine and by the kidneys. T 1/2 of azilsartan is about 12 hours. Studies have shown that after ingestion of azilsartan medoxomil, about 55% (mainly in the form of metabolite M-I) is found in the feces and about 42% (15% in the form of azilsartan, 19% in form metabolite M-II) - in the urine.
Pharmacokinetics in specific patient groups
The pharmacokinetics of azilsartan in young (18-45 years) and elderly (65-85 years) patients is not significantly different.
In patients with mild, moderate and severe renal failure, the AUC was increased by 30%, 25% and 95%, respectively. Increases (by 5%) of AUC in patients with terminal stage of renal failure on hemodialysis were not observed. Clinical data on pharmacokinetics in patients with severe degree or terminal stage of renal failure are absent. Azilsartan is not excreted from the systemic blood flow through hemodialysis.
The use of azilsartan medoxomil for more than 5 days in patients with hepatic insufficiency is mild (less than 5 on the Child-Pugh scale) or an average (less than 9 on the Child-Pugh scale), leading to a slight increase in AUC (1.3-1.6 times, respectively). The pharmacokinetics of azilsartan in patients with severe hepatic insufficiency (more than 9 on the Child-Pugh scale) has not been studied.
The pharmacokinetics of azilsartan in men and women is not significantly different. Correction of dose depending on sex is not required.
The pharmacokinetics of azilsartan, depending on the race of the patients, is not significantly different. Correction of dose depending on race is not required.
Chlorthalidone
Suction
After taking the drug inside chlortalidone is absorbed from the digestive tract by 60%. C max chlorthalidone in blood plasma is achieved on average within 12 hours.
The value of AUC of chlorthalidone is similar to that when it is co-administered with azilsartan medoxomil, and without it. However, C max is 47% higher when it is co-administered with azilsartan medoxomil as part of the Edarby ® Clo preparation. Eating does not have a clinically significant effect on the bioavailability of the drug.
Distribution
In whole blood chlortalidone is associated, mainly, with the carbonic anhydrase of erythrocytes. In blood plasma, approximately 75% of chlorthalidone is associated with blood plasma proteins, with 58% with albumin.
Metabolism and excretion
Chlortalidone is mainly excreted unchanged. There are no data on the comparative amounts of chlorthalidone, which is excreted unchanged and in the form of metabolites.
Chlortalidone is mainly excreted by the kidneys unchanged. T 1/2 chlortalidone is 40-50 hours. As a thiazide-like diuretic, chlortalidone is excreted in breast milk.
Pharmacokinetics in specific patient groups
In elderly patients, chlorthalidone is excreted more slowly than in young patients, presumably due to age-related changes in renal function and leads to an increase in T 1/2 . Reduction of elimination is not clinically significant.
With renal failure, it is possible to accumulate chlorthalidone.
There is no data on the pharmacokinetics of chlorthalidone in liver failure.
Data on the differences in pharmacokinetics in men and women are not available.
There are no data on the differences in pharmacokinetics depending on race.
INDICATIONS
- Essential hypertension (patients who are shown combined therapy).
DOSING MODE
Edarby ® Clos are taken orally 1 time / day, regardless of the time of ingestion.
The recommended initial dose of Edarbi ® Clo is 40 mg of azilsartan medoxomil + 12.5 mg chlorthalidone 1 time / day.
If it is necessary to further reduce blood pressure, the dose of Edarbi ® Clo can be increased to a maximum of 40 mg of azilsartan medoxomil + 25 mg chlorthalidone 1 time / day.
Edarby ® Clos should be taken daily, without interruption. In the event of discontinuation of treatment, the patient should inform the physician about this.
If you miss a dose, the patient should take the next dose at the usual time. Do not take a double dose of the drug Edarby ® Clos.
The withdrawal syndrome with a sudden discontinuation of azilsartan medoxomil after prolonged therapy (for 6 months) was not observed. However, the elimination of the drug Edarby ® Clo after prolonged treatment should be carried out, if possible, gradually.
Older patients (65 years and older) do not need to adjust the initial dose of the drug.
There is no clinical experience with the use of Edarbi ® Clo in patients with hypertension with impaired renal function of severe degree (QC less than 30 ml / min) , therefore it is not recommended to use the drug in this category of patients. In patients with impaired renal function of mild and moderate severity (QC greater than 30 ml / min) , dosage regimen correction is not required.
It is not recommended to use the drug in patients with severe hepatic dysfunction ; there is no clinical experience of application (see section Contraindications). Due to limited experience with use, Edarby ® Clo should be used with caution in patients with mild or moderate liver function impairment (less than 9 on the Child-Pugh scale) , since even small disturbances of the electrolyte balance can be triggered by diuretics when administered to the hepatic coma. It is recommended to actively monitor the condition of such patients.
In patients with reduced BCC, before starting the use of the Edarbi ® Clo drug, it is necessary to compensate for fluid and electrolyte losses.
In patients with arterial hypertension with severe chronic heart failure (IV NYHA), caution should be applied to Edarby ® Clo because of the lack of clinical experience.
In patients of the Negroid race, dose adjustment is not required, because The antihypertensive effect of the drug Edarby ® Clo in this category of patients is similar to its effect in patients of other races.
SIDE EFFECT
Determination of the frequency of adverse reactions in accordance with 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 can not be calculated by available data).
The combination of azilsartan medoxomil and chlorthalidone
Frequency Adverse Reactions
On the part of the hematopoiesis system
Infrequent Anemia
From the nervous system
Often Dizziness Postural dizziness
Infrequently Syncope (syncope) Paresthesia
From the side of the cardiovascular system
Often marked decrease in blood pressure
From the digestive system
Often Diarrhea Nausea
Infrequently Vomiting
From the skin and subcutaneous tissues
Infrequent Skin rash, itching
Allergic reactions
Rarely Angioedema
From the musculoskeletal system
Infrequently Muscle Cramps
From the side of metabolism
Often Hyperuricemia
Infrequently Hypokalemia Increased potassium content Hyponatremia Exacerbation of gout
Laboratory indicators
Very often Increased creatinine concentration
Often Increased urea concentration
Infrequent Increase in glucose concentration
General reactions
Often Increased fatigue Peripheral edema
Azilsartan medoxomil (monotherapy)
Frequency Adverse Reactions
From the nervous system
Often Dizziness
Infrequently Headache
From the side of the cardiovascular system
Infrequent pronounced decrease in blood pressure
From the digestive system
Frequently Diarrhea
Infrequently Nausea
From the skin and subcutaneous tissues
Infrequent Skin rash, itching
Allergic reactions
Rarely Angioedema
From the musculoskeletal system
Infrequently Muscle Cramps
Laboratory indicators
Often Increased activity of CK
Infrequent Increase in creatinine concentration Hyperuricemia
General reactions
Infrequently Increased fatigue Peripheral edema
Chlortalidone (monotherapy)
Frequency Adverse Reactions
From the nervous system
Rarely Headache
From the side of the cardiovascular system
Often marked decrease in blood pressure
Rarely arrhythmia
From the digestive system
Often Loss of appetite Gastrointestinal disorders
Rarely Constipation Abdominal pain Intrahepatic cholestasis or jaundice
Very rarely Pancreatitis
From the skin and subcutaneous tissues
Rarely Photosensitivity Skin Vasculitis
Allergic reactions
Often Urticaria
From the respiratory system
Rarely allergic pulmonary edema
From the urinary system
Rarely allergic interstitial nephritis
On the part of the hematopoiesis system
Rarely Thrombocytopenia Leukopenia Agranulocytosis Eosinophilia
From the side of metabolism
Very often Hyperlipidemia Hypokalemia
Often Hypomagnesemia
Rarely Hypercalcemia Glucosuria Decompensation of existing diabetes mellitus
Very rarely Hypochloremic alkalosis
Other
Often Decreased potency
Description of individual adverse reactions
With the simultaneous use of azilsartan medoxomil with chlorthalidone, the incidence of adverse reactions - a marked decrease in blood pressure and an increase in creatinine concentration - increases in the frequency of occurrence: from "infrequently" to "often." This is due to a more effective decrease in blood pressure compared with the monotherapy of azilsartan medoxomil. Most of these effects were transient or non-progressive, as long as patients continued therapy. After drug withdrawal, the majority of cases of increase in creatinine concentration that did not pass during treatment were reversible.
The increase in the concentration of uric acid with the use of the drug Edarbi ® Clo is due to the chlorothalide in its composition and depends on the dose of the diuretic. Reports of gout development were infrequent even with prolonged therapy.
With simultaneous use of azilsartan medoxomil with chlorthalidone, the incidence of an adverse reaction, such as hypokalemia, decreases.
If any of the above side effects are aggravated or any other side effects occur, the patient should inform the physician about it.
CONTRAINDICATIONS
- hypersensitivity to 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 dysfunction (GFR less than 60 ml / min / 1.73 m 2 );
- severe forms of diabetes mellitus;
- violations of liver function severe (more than 9 points on the scale Child-Pugh), tk. no experience of use;
- renal failure of severe degree (QC less than 30 ml / min), because no experience of use;
- age under 18 years (effectiveness and safety not established);
- Pregnancy and the period of breastfeeding.
Carefully:
- severe chronic heart failure (IV NYHA class IV);
- impaired renal function (QC more than 30 ml / min);
- impaired liver function of mild to moderate degree (5-9 points on the Child-Pugh scale);
- bilateral stenosis of the renal arteries and stenosis of the artery of a single functioning kidney;
- ischemic cardiomyopathy;
- ischemic cerebrovascular disease;
- condition after kidney transplantation;
- state, accompanied by a decrease in the bcc (including vomiting, use of diuretics at higher doses) as well as in patients with a diet restriction salt;
- primary aldosteronism;
- hyperuricemia, gout;
- hypokalemia;
- bronchial asthma;
- systemic lupus erythematosus;
- stenosis of the aortic and mitral valve;
- hypertrophic obstructive cardiomyopathy (GOKMP);
- age over 75 years.
PREGNANCY AND LACTATION
Experience with the drug Edarbi ® Clo pregnant offline. Use of the drug is not recommended during pregnancy and lactation.
Neonates whose mothers were treated azilsartanom medoksomilom may develop hypotension, and therefore infants should be kept under close medical supervision.
Chlorthalidone crosses the placental barrier in cord blood and may cause fetal or neonatal jaundice, thrombocytopenia and other undesirable reactions marked in adults.
Immediately after the confirmation of pregnancy should stop using the drug Edarbi ®Clough and, if necessary, to switch to the use of drugs with a proven safety profile in pregnancy.
There is no information in respect of a person's ability azilsartana and / or its metabolites into breast milk. In experimental studies in animals revealed that azilsartan and its metabolite M-II allocated into milk of lactating rats.
Chlorthalidone crosses the placental barrier and is detected in umbilical cord blood, fetal blood and breast milk.
If necessary, use Edarbi preparation ® Clo lactation period must discontinue breastfeeding or stop taking the drug. Preferably, the use of drugs with proven safety profile.
APPLICATION FOR FUNCTIONS OF THE LIVER
No clinical experience with the drug Edarbi ® Clo in hypertensive patients with violation severe renal function (creatinine clearance less than 30 mL / min) , therefore, use the drug in these patients is not recommended. In patients with impaired renal mild and moderate severity function (CC 30 ml / min) is required correction mode.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
It is not recommended to use the drug in patients with severe impairment of liver function due to lack of clinical application experience.
Due to the limited experience in the application should be used with caution Edarbi ® Clos in patients with impaired liver function mild to moderate (less than 9 points on a scale Child-Pugh) , since even minor violations of water-electrolyte balance while taking diuretics may provoke a hepatic coma. It is recommended to actively monitor the status of these patients.
APPLICATION FOR CHILDREN
Contraindicated in the use of drugs under the age of 18 years (efficacy and safety not established).
APPLICATION IN ELDERLY PATIENTS
Elderly patients do not require an initial dose adjustment.
Precautions should be prescribed to patients over the age of 75 years.
SPECIAL INSTRUCTIONS
Hypotension to the damage of water-electrolyte balance
in patients with reduced BCC and / or hyponatremia (resulting in vomiting, diarrhea, use of diuretics in high doses or dieting limited reception salt) may develop clinically significant hypotension after initiation of drug therapy Edarbi ® Claw. Hypovolemia and fluid and electrolyte balance should be corrected before treatment. Transient hypotension is not a contraindication to further treatment, which may be continued after the stabilization of blood pressure.
Renal function
Patients with impaired renal function (creatinine clearance of more than 30 ml / min), the drug should be used with caution. It is recommended to regularly monitor potassium and creatinine concentration in the serum. These patients require careful titration with constant supervision and control of blood pressure. Increased creatinine concentration more frequently observed in patients with moderate and severe renal impairment.
Chlorthalidone can cause azotemia.
This progressive deterioration in renal function (increase in blood urea nitrogen (BUN) recommended temporary cessation of therapy with diuretics or their complete cancellation.
Dual blockade of the RAAS
Patients with vascular tone and renal function depends to a large extent on the activity of the RAAS (e.g., in patients with severe chronic heart failure (IV FC by NYHA classification), severe renal insufficiency or renal artery stenosis), treatment with drugs acting on RAAS, such as ACE inhibitors and ARA II, due to the possibility of an acute hypotension, azotemia, oliguria, or in rare cases of acute renal failure. The ability of these effects can not be ruled out when using the drug Edarbi ® Claw.
The sharp decrease in blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular diseases can lead to myocardial infarction or stroke.
Kidney transplantation
Data on the use of the drug Edarbi ® Clos in patients who have recently had a kidney transplant, no.
Impaired liver function
Data on clinical experience of the drug Edarbi ® Clo in patients with impaired liver function severe absent, so the use of the drug in these patients is not recommended (see. The section "Contraindications"). Due to the limited experience of application should be used with caution Edarbi ® Clo in patients with impaired liver function mild to moderate (less than 9 points on the Child-Pugh), since even small violations of water-electrolyte balance when receiving diuretics may provoke hepatic coma. It is recommended to actively monitor the status of these patients.
primary aldosteronism
Patients with primary hyperaldosteronism generally resistant to treatment with antihypertensive drugs affecting RAAS. In connection with this drug Edarbi ® Claw not recommended in such patients.
Hypokalemia
When chlorthalidone therapy may develop hypokalemia. Should regularly monitor the content of potassium in the blood serum. Patients taking cardiac glycosides, hypokalemia may predispose to arrhythmias.
Stenosis of the aortic or mitral valve, hypertrophic obstructive cardiomyopathy
When assigning preparation Edarbi ® Clo patients with aortic or mitral stenosis or hypertrophic obstructive cardiomyopathy be careful.
Lithium
As in the case of other ARA II, it is not suitable for the simultaneous use of drugs and drug lithium Edarbi ® Claw.
Impact on the ability to drive vehicles and manage mechanisms
Caution should be exercised when driving and operating machinery that require attention and speed of reaction, because when using the drug there is the risk of dizziness and fatigue.
OVERDOSE
Azilsartana medoxomil (monotherapy)
Experience of azilsartana medoxomil in adults in doses up to 320 mg / day for 7 days shows that the drug was well tolerated.
Symptoms: marked reduction of blood pressure, dizziness.
Treatment: In marked decrease in blood pressure of the patient should be transferred to a horizontal position with a low headboard; It recommended to introduce measures to increase BCC and symptomatic therapy. Azilsartan not output from the systemic circulation by dialysis.
Chlorthalidone (monotherapy)
Symptoms: Nausea, weakness, dizziness, disorders of water and electrolyte balance.
Treatment: there is no specific antidote. In marked decrease in blood pressure should be rinsed stomach; It recommends implementation of measures to normalize the water-electrolyte balance (infusion therapy); symptomatic therapy.
DRUG INTERACTION
It was noted reversible increase in the concentration of lithium in blood serum and expression of toxicity during the simultaneous use of diuretics and drugs lithium and lithium drugs with antagonists of angiotensin II (ARA II). Therefore, the simultaneous use of the drug Edarbi ® Clo in combination with lithium therapy is not recommended (see. The "Special instructions"). If necessary, use appropriate combination therapy recommended regular monitoring of lithium concentrations in serum.
Elderly patients and patients with reduced BCC (including receiving diuretics) or impaired renal function simultaneous use of ARA II and NSAIDs may lead to deterioration of renal function up to the development of acute renal failure. Therefore, at the beginning of treatment is recommended for patients receiving regular enough fluid and monitoring of renal function. With simultaneous use of ARA II and NSAIDs, including selective COX-2 inhibitors, acetylsalicylic acid (more than 3 g / d) and non-selective NSAIDs may weaken the antihypertensive effect.
Dual angiotensin II blockade of the RAAS receptor antagonists, ACE inhibitors or aliskiren is associated with increased risk of arterial hypotension, hyperkalaemia and worsening renal function (including acute renal failure) as compared with monotherapy.
Concomitant use of cardiac glycosides and diuretics can exacerbate the effects of hypokalemia, such as cardiac arrhythmias.
Additional information about the interaction azilsartana medoxomil
were no pharmacokinetic interaction while applying azilsartana azilsartana medoxomil and amlodipine, antacids (aluminum and magnesium hydroxide), chlorthalidone, digoxin, fluconazole, glibenclamide, ketoconazole, metformin and warfarin.
Azilsartana medoxomil is converted into a pharmacologically active metabolite azilsartan during absorption from the intestine by the enzyme karboksimetilenbutenolidazy in the gut and liver. In vitro studies have shown that interactions based on the inhibition of the enzymes are unlikely.
Additional information about the interaction chlorthalidone
chlorthalidone curariform enhances the action of muscle relaxants and anti-hypertensive agents (including guanethidine, methyldopa, beta-blockers, vasodilating agents, calcium channel blockers slow), MAO inhibitors.
The simultaneous use of chlorthalidone with allopurinol can lead to increased incidence of hypersensitivity reactions to allopurinol.
Chlorthalidone may increase the risk of adverse reactions caused by amantadine.
Anticholinergics (e.g., atropine, biperiden) may increase the bioavailability chlorthalidone, decreasing gastrointestinal motility and evacuation of stomach contents.
Chlorthalidone gipokaliemicheskoe effect is enhanced while the use of corticosteroids, ACTH, amphotericin, beta 2 adrenoblokatorami, carbenoxolone. Patients during combination therapy should be monitored content of potassium in the blood serum.
May require correction (reduction or increase) the dose hypoglycemic agents for oral and insulin.
The pharmacological effects of calcium and vitamin D may be increased to a clinically significant level while the use of chlorthalidone.
Concomitant use of cyclosporine may increase the risk of hyperuricemia and complications such as gout.
Kolestiramin violates the absorption of chlorthalidone. May reduce the pharmacologic effect of chlorthalidone.
The simultaneous use of chlorthalidone with methotrexate and cyclophosphamide can lead to a potentiation of pharmacological effect of anticancer drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in the original packaging of the reach of children, dry, dark place at a temperature above 25 ° C. Shelf life - 3 years.
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