Ambrisenthan (Ambrisentanum)

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

Other cardiovascular drugs

Included in the formulation
  • Volibrys
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    GlaxoSmithKline Trading, ZAO     Russia
    • АТХ:

    C.02.K.X.02   Ambrisenthan

    Pharmacodynamics:

    Selective antagonist of endothelin receptors type A (ETA).

    Endothelin-1 (ET-1) is a strong autocrine and paracrine peptide. In smooth muscle vessels and in the endothelium, the effects of endothelin-1 are mediated by two types of endothelin receptors - ETA and ETAT. Activation of ETAreceptors causes predominantly vasoconstriction and cell proliferation.

    Pharmacokinetics:

    After oral administration Ambrisenthan absorbed, Cmax is reached in about 2 hours.

    The binding with plasma proteins is high - 99%.

    Half-life Ambrozental is 15 hours. Effective half-life Ambrozental - about 9 hours. The average value of clearance for oral intake is 38 ml per minute and 19 ml per minute in healthy volunteers and in patients with pulmonary arterial hypertension, respectively. It is mainly excreted out of the kidney, but the relative role of metabolism and biliary elimination is insufficiently characterized.

    Indications:

    Treatment of pulmonary arterial hypertension to improve the tolerance of exercise, slowing the progression of clinical symptoms.

    Pulmonary hypertension II-III functional class idiopathic etiology of hereditary etiology (64%) or pulmonary arterial hypertension associated with connective tissue diseases (32%).

    ICD-10

    IX.I26-I28.I27.0   Primary pulmonary hypertension

    Contraindications:

    Idiopathic pulmonary fibrosis with or without secondary pulmonary hypertension, giperchuvstvitelnost to ambrizentanu, lactation, age under 18 years, have come or planned pregnancy, severe hepatic insufficiency (more than 10 points on a scale Child-Pugh), lactose intolerance, lactase deficiency and syndrome of glucose-galactose malabsorption (drug contains lactose), increasing activity of hepatic transaminases ACT and / or ALT more than 3 times from the upper limit of the norm.

    Carefully:Hepatic insufficiency of mild and moderate degree, hematologic disorders, fluid retention, veno-occlusive lung diseases.
    Pregnancy and lactation:

    The FDA class is not defined. Ambrisenthan has a teratogenic effect. The use during pregnancy (either come or is planned) is contraindicated. If it is necessary to use ambrisent during lactation, breastfeeding should be discontinued.

    Dosing and Administration:

    Inside, regardless of food intake, washing down with water.

    Adults should start treatment with a dose of 5 mg once a day. If the dose is well tolerated, 5 mg is allowed to increase to a maximum daily dose of 10 mg once a day.

    Side effects:

    Effects associated with peripheral vasodilation: headache, flushing of the face, palpitations, congestion of the nose, edema of the shins.

    Gastrointestinal disorders: nausea, abdominal pain, constipation; increased level of transaminases.

    Decreased hemoglobin level. The appearance of edema of the shins, as a rule, is associated with the dilatation of arterioles and is not a manifestation of heart failure. They decrease with decreasing dose, however, they often pass without changing the therapy when physical activity is limited.

    Overdose:The maximum daily dose is 10 mg. Application in a dose of more than 10 mg in patients with pulmonary arterial hypertension has not been studied.
    Interaction:Cyclosporine: with multiple simultaneous intake, the bioavailability of ambrisated increased approximately 2-fold in healthy volunteers, so for this combination the dose of ambrisent should be reduced to 5 mg once a day. Eating does not affect bioavailability.
    Special instructions:

    Correction of dose of the drug in patients aged 65 years and older is not required.

    It is not recommended to apply ambrice in patients with clinically significant anemia. If in the course of treatment there is a clinically significant decrease in hemoglobin concentration and other causes of this effect excluded, you should cancel ambrice. Before the start of treatment, after 1 month of treatment and then periodically monitor the concentration of hemoglobin.

    With symptoms of fluid retention, diuretic therapy is used. If the symptoms of fluid retention continue to increase, a survey should be conducted, appropriate therapy, if necessary, cancel ambrice. Decompensation of heart failure requires hospitalization.

    Peripheral edema was more frequent and more severe in elderly patients.

    With the development of veno-occlusive disease of the lungs against the background of ambrisental application, it should be abolished.

    Patients with mild or moderate renal dysfunction do not need dose adjustment.Data on the use in patients with severe impairment of kidney function is not available. The effect of hemodialysis on the distribution of ambrisental has not been studied.

    Data on the use of ambrisent for mild violations of liver function are not available; it should be borne in mind that in such cases it is possible to increase the bioavailability of ambrisent. Ambrisenthan should be abolished, if in the course of treatment there is an increase in the activity of transaminases more than 3 times higher than the upper limit of the norm; an increase in the concentration of bilirubin is more than 2 times higher than the upper limit of the norm or in the presence of symptoms of impaired liver function.

    It can not be ruled out that endothelin receptor antagonists, including ambrice, can have an undesirable effect on spermatogenesis.

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