Azilsartan medoxomil + Chlortalidone (Azilsartani medoxomilum + Chlortalidonum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Angiotensin II receptor antagonists (AT1 subtype)

Diuretics

Included in the formulation
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    Takeda Pharmaceuticals USA, Inc.     USA
    • АТХ:

    C.09.D.A.09   Azilsartan medoxomil and diuretics

    Pharmacodynamics:

    Combined antihypertensive.

    Azilsartan medoxomil

    Blocking the conversion of angiotensin I in angiotensin II, resulting in a decrease in the release of norepinephrine from the endings of sympathetic fibers, the vasoconstrictor effect, the secretion of aldosterone by the adrenal cortex and increases the bradykinin content by reducing its inactivation by the angiotensin-converting enzyme.

    Bradykinin stimulates B2-cinin receptors of the vascular endothelium, which leads to the rapid release of prostacyclin and other vasodilating substances that cause relaxation of smooth muscles.

    Reduces the overall peripheral resistance of blood vessels, without affecting the heart rate.

    Chlorthalidone

    A non-azidic diuretic of medium strength, stimulates the excretion of sodium, chlorine, potassium, magnesium and water ions, preserves calcium ions.Due to the lower sodium content in the vascular wall, the sensitivity of the baroreceptors to vasoconstrictor influences decreases. The duration of the action is from 24 to 48 hours.

    Pharmacokinetics:

    Azilsartan medoxomil

    After oral administration, up to 60% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is achieved after 1.5-3 hours. The connection with plasma proteins is 99%.

    Penetrates through the blood-brain barrier. Metabolism in the liver.

    The half-life is 11 hours. Elimination with feces and kidneys.

    Chlorthalidone

    After ingestion, up to 64% is absorbed in the gastrointestinal tract. The maximum concentration in the blood plasma is reached after 12 hours. The connection with plasma proteins is 75%, including with erythrocytes.

    Metabolism in the liver.

    The half-life is 35-50 hours. Elimination of the kidneys, mostly unchanged.

    Indications:

    It is used for the treatment of hypertensive disease, with secondary hypertensive states.

    ICD-10

    IX.I10-I15.I10   Essential [primary] hypertension

    IX.I10-I15.I15   Secondary Hypertension

    Contraindications:

    Cardiogenic shock, atrioventricular blockade of II-III degree, bradycardia, chronic cardiac insufficiency, resistant to the action of cardiac glycosides,bronchial asthma, renal and hepatic insufficiency, age to 18 years, pregnancy and lactation, individual intolerance.

    Carefully:

    Chronic bronchitis with an asthmatic component, obliterating arterial diseases, atrioventricular blockade of the 1st degree, disturbance of the water-electrolyte balance.

    Pregnancy and lactation:

    Recommendations for FDA - Category D. Contraindicated in pregnancy and lactation.

    Dosing and Administration:

    It is taken orally 1 tablet once a day (in the morning).

    The highest daily dose: 2 tablets.

    The highest single dose: 80 mg (1 tablet) once a day. If necessary, the dose can be doubled.

    The highest daily dose: 160 mg (2 tablets).

    Side effects:

    Azilsartan medoxomil

    Central and peripheral nervous system: headache, dizziness, sleep disorders, paresthesia, confusion.

    Respiratory system: dry cough, shortness of breath, sinusitis, bronchospasm.

    Hemopoietic system: anemia, thrombocytopenia, agranulocytosis, pancytopenia.

    The cardiovascular system: arterial hypotension, tachycardia, rarely - pain in the chest, flushes of blood.

    Digestive system: glossitis, vomiting, diarrhea, constipation, rarely - hepatitis, cholestatic jaundice, pancreatitis.

    Musculoskeletal system: myalgia, cramps of the calf muscles.

    Dermatological reactions: a rash.

    Sense organs: a noise in the ears, a violation of taste perception, blurred vision.

    Urinary system: dysuria, rarely - acute renal failure.

    Reproductive system: erectile disfunction.

    Allergic reactions.

    Chlorthalidone

    Central and peripheral nervous system: headache, dizziness, paresthesia, adynamia, apathy, depression, drowsiness, confusion.

    Hemopoietic system: hemolytic anemia, eosinophilia, agranulocytosis.

    The cardiovascular system: arterial hypotension, orthostatic hypotension, collapse, tachycardia, arrhythmia, decreased circulating blood volume, possible Botallov duct open in preterm.

    Water-electrolyte exchange: hypovolemia, dehydration, hypokalemia, hyponatremia, hypochloraemia, hypomagnesemia, metabolic alkalosis.

    Digestive system: dryness of the oral mucosa, thirst, decreased appetite, nausea, vomiting, constipation or diarrhea, cholestatic jaundice, exacerbation of pancreatitis.

    Musculoskeletal system: myasthenia gravis, calf muscle cramps (tetany).

    Dermatological reactions: skin itching, exfoliative dermatitis, multiform erythema exudative, photosensitivity

    Sense organs: blurred vision, xanthopsia, tinnitus, hearing loss.

    Reproductive system: decreased potency.

    Urinary system: hyperuricemia with exacerbation of gout, acute urinary retention, interstitial nephritis, hematuria, glucosuria, development of nephrocalcinosis and nephrolithiasis in premature infants.

    Allergic reactions.

    Overdose:

    Arrhythmia, convulsions, drowsiness, severe bradycardia, arterial hypotension.

    Treatment. Intravenous 1-2 mg atropine, 2.5 mcg / kg dobutamine, intravenously bolus 10 mg glucagon, intravenously drip 10-20 mcg isoprenaline at a rate of not more than 5 mcg per minute.

    Interaction:

    Azilsartan medoxomil

    Strengthens the hypoglycemic action of insulin and oral hypoglycemic drugs.

    Enhances the toxic effects of lithium preparations.

    Sodium chloride, non-steroidal anti-inflammatory drugs reduce the hypotensive effect of azilsartan medoxomil.

    With simultaneous use with potassium-sparing diuretics (amiloride, triamterene, spironolactone), products with a high content of potassium develops hyperkalemia.

    The risk of developing leukopenia increases with simultaneous use with cytostatics, allopurinol, systemic glucocorticosteroids, procainamide, immunosuppressive drugs.

    With simultaneous use with drugs for general anesthesia and for local anesthesia, it is possible to develop arterial hypotension.

    Chlorthalidone

    Improves the hypotensive effect of ACE inhibitors, theophylline, warfarin, diazoxide.

    Reduces the effect of tubocurarine.

    Weakens the action norepinephrine and antidiabetic drugs.

    Increases the ototoxicity of cisplatin, aminoglycosides, ethacrynic acid.

    With simultaneous use with cardiac glycosides, the risk of hypokalemia, hence, cardiac arrhythmia, increases.

    Indomethacin and sucralfate reduce the effect by inhibiting the synthesis of prostaglandin.

    Probenecid blocks the excretion and increases the content of chlorthalidone in the blood plasma.

    It is not recommended combination of chlorthalidone with cephalosporins, gentamicin, other agents,which have a nephrotoxic effect.

    Special instructions:

    Monitoring of blood pressure, composition of peripheral blood.

    In the treatment it is not recommended to drive vehicles and work with moving mechanisms.

    Instructions
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