Azilsartan medoxomil (Azilsartani medoxomilum)

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)

Included in the formulation
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    Takeda Global Research and Development Sente (Europe) Limited     United Kingdom
    • АТХ:

    C.09.C.A.09   Azilsartan medoxomil

    Pharmacodynamics:

    Specifically blocks the angiotensin receptors II 1-st type. Azolsartan medoxomil is a prodrug. 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 receptors1 in various tissues. Inhibits such effects of angiotensin as cardiac stimulation, vasoconstriction, stimulation of aldosterone release and synthesis, and, consequently, renal sodium reabsorption.

    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.

    Pharmacokinetics:

    Eating does not affect the bioavailability of the drug,absolute bioavailability is approximately 60%. Penetration through the blood-brain barrier is minimal. Vd azilsartan is about 16 liters. Azilsartan binds to blood plasma proteins (more than 99%), mainly with albumins. After ingestion during absorption from the digestive tract azilsartan medoxomil is converted into the pharmacologically active metabolite azilsartan under the action of the enzyme carboxymethylenebutenolidase in the intestine and liver. 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 metabolite M-II, the secondary metabolite is formed by decarboxylation and is referred to as the metabolite M-I. Metabolized mainly by isoenzyme CYP2C9, the main pharmacologically active metabolite is azylsartan. Excreted by the gastrointestinal tract and kidneys. Azilsartan and its metabolites are excreted from the body both through the intestine and by the kidneys. Studies have shown that after ingestion of azilsartan medoxomil, about 55% (predominantly in the form of metabolite M-I) is found in the feces and about 42% (15% in the form of azilsartan, 19% in the form of metabolite M-II) - in the urine. The half-life is 11 hours.

    Indications:

    Essential hypertension.

    ICD-10

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

    Contraindications:

    - ghypersensitivity;

    - age to 18 years;

    - bVariability;

    - aboutsimultaneous reception with aliskiren in patients with diabetes mellitus;

    - severe violations of the liver (more than 9 points on the scale Child-Pugh) (no experience of use).

    Carefully:

    Severe renal insufficiency (clearance creatinine <30 ml / min); chronic heart failure (IV functional class by classification NYHA), bilateral stenosis of the renal arteries and stenosis of the artery of a single functioning kidney; state, accompanied by a decrease volume of circulating blood (including vomiting, diarrhea), as well as in patients observing a diet with restriction of table salt; condition after kidney transplantation; ischemic cerebrovascular disease, ischemic cardiomyopathy, with simultaneous use with large doses of diuretics; primary hyperaldosteronism, hyperkalemia; stenosis of the aortic or mitral valves; a diet low in salt, age over 75 years, hypertrophic obstructive cardiomyopathy.

    Pregnancy and lactation:

    Category FDA - D. In animal studies, it has been found that azilsartan and M-II penetrate the placental barrier. Patients planning a pregnancy should begin therapy with alternative antihypertensive drugs with an established safety profile for pregnant women. Immediately after confirmation of pregnancy, stop taking the drug and, if necessary, begin treatment with drugs that are approved for use during pregnancy.

    In newborns, whose mothers received therapy, hypotension may develop, and therefore newborns should be under careful medical supervision.

    There is no information on the ability of azilsartan and / or its metabolites to enter breast milk. In animal studies, it has been found that azilsartan and M-II are secreted into the milk of lactating rats.

    Due to the lack of experience in women during breastfeeding, its use in this category of patients is not recommended. Preferably the use of drugs with the most studied safety profile, especially during the care of a newborn or premature baby.

    Dosing and Administration:

    Orally, regardless of the time of food intake, once a day, the initial dose - 40 mg, the maximum daily dose - 80 mg.

    Duration of treatment. The drug should be taken daily, without interruption. In the event of discontinuation of treatment, the patient should inform the physician about this.

    Skipping the dose. 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.

    Side effects:

    From the musculoskeletal system: muscle spasms.

    From the nervous system: dizziness.

    From the gastrointestinal tract: nausea, diarrhea.

    From the skin: itching, rash.

    From the cardiovascular system: marked reduction in blood pressure.

    Other: peripheral edema, increased fatigue, increased activity of creatine kinase, hyperuricemia, increased concentration of creatinine.

    Overdose:

    Dizziness, lowering blood pressure. Treatment: with a pronounced decrease blood pressure give the patient a prone position, raise his legs, carry out measures to increase the volume of circulating blood; symptomatic therapy.

    Azilzartan is not excreted from the systemic blood flow through dialysis.

    Interaction:

    With the simultaneous use of the drug with chlorthalidone, the frequency of adverse reactions is a marked decrease blood pressure and increasing the concentration of creatinine - increases.

    With the simultaneous use of azilsartan medoxomil with amlodipine, the frequency of the undesirable reaction - peripheral edema - increases from infrequent to frequent, but is less common than with monotherapy with amlodipine.

    Potassium-sparing diuretics, potassium preparations, heparin - simultaneous use of potassium-sparing diuretics, potassium preparations, salt substitutes containing potassium and other medicines (eg, heparin) with azilsartan medoxomil may lead to an increase in serum potassium.

    Nonsteroidal anti-inflammatory drugs - a risk of impaired renal function.

    Lithium preparations - increasing the concentration of lithium in the blood.

    Double blockade renin-angiotensin-aldosterone system receptor antagonists to angiotensin II, inhibitors ACE, or aliskirenom is associated with an increased risk of developing arterial hypotension, hyperkalemia,and impaired renal function (including acute renal failure) compared with monotherapy.

    Special instructions:

    A sharp decline blood pressure in patients with ischemic cardiomyopathy or ischemic cerebrovascular disease can lead to the development of myocardial infarction or stroke.

    Impact on the ability to drive vehicles and manage mechanisms

    Slight, be careful.

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