Clinical and pharmacological group: & nbsp

Anticoagulants

Included in the formulation
  • Actylase®
    lyophilizate d / infusion 
  • Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

    VED

    АТХ:

    B.01.A.D.02   Alteplase

    Pharmacodynamics:

    Human tissue activator of plasminogen (recombinant): activation of plasminogen, conversion of plasminogen to plasmin, destruction of fibrin, fibrinogen, coagulation factors V and VIII.

    Pharmacological effects

    Thrombolytic.

    Pharmacokinetics:

    Biotransformation occurs in the liver. T1 / 2 - 35 min. Elimination by the kidneys (80% - in the form of metabolites).

    Indications:

    Myocardial infarction (in the first 6-12 hours), acute massive thromboembolism of the pulmonary artery, acute ischemic stroke, peripheral artery thrombosis of lower extremities

    IX.I20-I25.I21   Acute myocardial infarction

    IX.I26-I28.I26   Pulmonary embolism

    Contraindications:

    Hemorrhagic vasculitis, hemorrhagic retinopathy, simultaneous reception of indirect anticoagulants. Severe or dangerous bleeding (ongoing or recent), cerebral circulation (intracranial hemorrhage, hemorrhagic stroke), including during the last 6 months. Neoplasms of the central nervous system and other localization, accompanied by an increased risk of bleeding, aneurysm, intracranial surgery or spinal surgery (in the past 2 months).Severe trauma (within the last ten days), traumatic open heart massage (within the last 10 days). Obstetric delivery (within the last 10 days). Surgery, puncture of blood vessels with low pressure: for example, subclavian or jugular vein (within the last 10 days). Severe uncontrolled AH. Bacterial endocarditis, pericarditis. Stomach ulcer and duodenal ulcer (within 3 months after the onset of exacerbation), acute pancreatitis.

    Arterial or venous malformatsii.Pechenichnaya failure, cirrhosis, portal hypertension, active hepatitis. Varicose veins of the esophagus. The patient's age is over 70 years.

    Carefully:

    Recently suffered minor injuries as a result of biopsy, vascular puncture, intravenous injection, cardiac massage and other conditions, accompanied by a risk of bleeding.

    Pregnancy and lactation:

    Pregnancy

    The category of FDA recommendations is not defined. Controlled studies on humans and animals have not been conducted. It is suggested that thrombolytic agents administered during the first 18 weeks of pregnancy increase the risk of premature placenta separation,because it is attached to the uterus mainly with fibrin.

    Lactation

    There is no information on the penetration of breast milk and complications. In view of the excretion of many drugs with milk, caution should be used to prescribe thrombolytic agents for lactating women.

    Dosing and Administration:

    AMI. For the first 6 hours, intravenously, bolus at a dose of 15 mg for 1-2 minutes, followed by infusion at a dose of 50 mg for 30 minutes and 35 mg for 60 minutes before reaching the maximum dose (100 mg). Patients weighing less than 65 kg - intravenously bolus at a dose of 15 mg and 0.75 mg / kg for 30 minutes (maximum - 50 mg); then - infusion of 0.5 mg / kg for 60 minutes (maximum - 35 mg). After 6-12 hours after the onset of symptoms, the drug is administered intravenously bolus in a dose of 10 mg, and 50 mg - infuzionno during the first hour, and then at a dose of 10 mg for 30 minutes (up to a maximum dose of 100 mg for 3 hours). For patients with a body weight of less than 65 kg, the drug is prescribed in a dose not exceeding 1.5 mg / kg.

    At the same time, acetylsalicylic acid is administered and heparin sodium. Acetylsalicylic acid - 160-300 mg / day after the onset of symptoms for several months; heparin sodium - before the start of thrombolytic therapy intravenously bolus in a dose of 5 thousand ME, then - 1 thousand each.ME / h, taking into account the parameters of APTT (activated partial thromboplastin time), measured several times (the values ​​should be 1.5-2.5 times higher than the initial ones).

    Acute massive thromboembolism of the pulmonary artery in combination with unstable hemodynamics. Intravenous bolus in a dose of 10 mg for 1-2 minutes, then for 90 mg intravenously for 2 hours. The total dose of the drug in patients weighing less than 65 kg should not exceed 1.5 mg / kg. If the PV exceeds the original value by less than 2 times, it is simultaneously assigned heparin sodium (under the control of APTTV). With massive thromboembolism of the pulmonary artery with unstable hemodynamics, the drug acts in the same way as streptokinase. The introduction of alteplase in a total dose of 100 mg for 2 hours is comparable with the action of reteplase, streptokinase at a dose of 1.5 million IU for 2 hours, urokinase at a dose of 1 million ED bolus for 10 min (then - 2 million units intravenously for 2 h) and more effective than the intravenous drip of sodium heparin at 1750 IU / h. In the latter case, side effects often occur.

    Acute ischemic stroke - thrombolysis (including alteplase 0.9 mg / kg to 90 mg in 100 ml of 0.9% sodium chloride, 10% dose in the form of a bolus,the rest - intravenously for 1 hour; alteplase 0.85 mg / kg intravenously for 60 min in the first 90 min and 91-180 min after the onset of the disease); alteplase (recombinant tissue plasminogen activator) 1.1 mg / kg to 100 mg intravenously, 10% dose in the form of a bolus, the rest intravenously for 1 hour;

    With topical application in the case of thrombosis of the peripheral arteries of the lower extremities, the alteplase is superior to urokinase. With thrombosis of the cerebral arteries, the introduction of 2 million units / day of alteplase has advantages over intravenous administration of 60,000 U / day of urokinase for 7 days.

    Use in children

    Efficiency and safety have not been studied.

    With intravascular thrombosis, the drug is administered intravenously strontaneously (in sterile water for injection until a solution with a concentration of 1 mg / ml) or drip (in a 0.9% solution of sodium chloride, until the concentration reaches 200 μg / ml). Do not dilute the drug with dextrose. Newborn drug is administered at 100-500 μg / kg per hour for 3-6 hours; children aged 1 month to 18 years - 100-500 μg / kg per hour for 3-6 hours (maximum daily dose - 100 mg). Before prescribing a second course, ultrasound monitoring of the response to the first course is necessary.

    With occlusion of arteriovenous shunts or catheters for children aged 1-18 months, the drug is injected directly into the catheter in a dose of no more than 2 ml (depending on the type of catheter) of a solution with a concentration of 1 mg / ml; The lysate is aspirated after 4 hours, after which the catheter is washed with 0.9% sodium chloride solution. The use of the drug for thrombosis of the arteries or veins in newborns is not known.

    Side effects:

    Hematologic: bleeding, fatal intracranial bleeding (when applied in the acute period of ischemic stroke). From the cardiovascular system: chest pain, arrhythmias, hypotension, not associated with bleeding or arrhythmia. Hypersensitivity: allergic reactions. Other: fever.

    Overdose:

    Bleeding. Treatment: transfusion of freshly frozen plasma, whole blood, plasma-substituting solutions, synthetic inhibitors of fibrinolysis.

    Interaction:

    The risk of bleeding increases with simultaneous use of coumarin derivatives, antiplatelet agents, heparin and other drugs that inhibit blood clotting.

    Special instructions:

    In acute coronary syndrome, it is advisable to conduct thrombolysis.It helps to reduce mortality and is economically profitable. There were no differences in survival after application of tissue activator plasminogen, streptokinase and anisolated plasminogen-streptokinase complex; the duration and the scheme of thrombolytic therapy is discussed. Additional treatment with anticoagulants and antiaggregants probably increases the effectiveness of thrombolytic therapy.

    The earlier thrombolysis has been performed, the more effective it is. That's why thrombolysis needs to be introduced into the daily practice of medical institutions. It is necessary to take into account the risk of the need for resuscitation related to thrombolysis.

    In outpatient practice, urokinase (bolus injection of tenecteplase or reteplase) is considered the drug of choice, and streptokinase (in the inpatient setting) (except when patients received it earlier). New agents (alteplase) are more expensive and therefore can not be drugs of the first line. The approximate cost of a course of treatment for one patient with the use of a thromboplastin tissue activator inhibitor is $ 2,900, with the use of streptokinase - $ 400, anisolated plasminogen-streptokinase complex - $ 1,900, urokinase - $ 775.

    Heads and administrators of health care, cardiologists of hospitals should promote thrombolysis by general practitioners.

    Coagulogram monitoring (APTT, fibrinogen, fibrin degradation products, thrombin, thrombin time), hematocrit, hemoglobin concentration, platelet count, electrocardiogram (with coronary artery thrombosis); at a thrombosis of vessels of a brain - the control of a mental and neurologic status (before the beginning of treatment and periodically during reception of a preparation). To assess treatment in dynamics, one or more criteria are used; The blood pressure, pulse and respiratory rate are determined regularly.

    The risk of hemorrhagic complications increases with the use of doses of the drug, exceeding 100 mg.

    The potential risk and benefit of using alteplase after recent minor injuries (biopsy, vascular puncture, intramuscular injections, cardiac massage) and in other conditions accompanied by a risk of bleeding during pregnancy during the first 10 days of the postpartum period should be correlated (increased risk of bleeding) , during lactation, in old age and in children.

    Heparin sodium before the thrombolytic therapy is canceled; following administration, and possibly after thrombolysis return indicators thrombin time and / or APTT values ​​to double control and lower (usually after 2-4 hours).

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