Active substanceAbciximabAbciximab
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  • ReoPro®
    solution in / in 
    Eli Lilly East SA     Switzerland
  • Dosage form: & nbspsolution for intravenous administration
    Composition:

    Each vial contains:

    active ingredient: abciximab 10 mg;

    auxiliary components: sodium hydrophosphate 6.75 mg, sodium dihydrogen phosphate monohydrate 1.65 mg, sodium chloride 43.83 mg, polysorbate 80 0.05 mg, water for injection q.s. up to 5 ml.

    Description:

    A clear, colorless solution, may contain a small amount of translucent protein particles.

    Pharmacotherapeutic group:Antiaggregant agent
    ATX: & nbsp

    B.01.A.C   Inhibitors of platelet aggregation (excluding heparin)

    B.01.A.C.13   Abciximab

    Pharmacodynamics:

    RyoPro is Fab-Fragment of chimeric monoclonal antibodies 7EZ, blocks glycoprotein (GP) IIb/IIIa (αIIbβ3) receptors located on the surface of human platelets.

    ReoPro inhibits platelet aggregation by preventing the binding of fibrinogen, von Willebrand factor and other adhesion molecules to the site (GP) IIb/IIIbut a receptor on activated platelets. ReoPro also blocks vitronectin (αvβ3) -receptors on the surface of platelets and endothelial cells. Vitronectin receptors determine the procoagulant properties of platelets and the proliferative properties of vascular wall endothelial cells and smooth muscle cells.

    In humans, a single intravenous bolus injection of ReoPro at a dose of 0.15-0.30 mg / kg leads to a rapid dose-dependent inhibition of platelet function (determined by aggregation of platelets ex vivo in response to adenosine diphosphate (ADP) or to increase the time of bleeding). Two hours after the administration of doses: 0.25 and 0.30 mg / kg, the drug blocks more than 80% of the receptors GP IIb/IIIa.

    An intravenous bolus dose of 0.25 mg / kg followed by continuous intravenous infusion at a rate of 10 μg / min for 12-96 hours causes a persistent severe blockade GP IIb/IIIa - receptors (> 80%) and inhibition of platelet function (platelet aggregation ex vivo in response to 5-20 μM ADP is reduced to less than 20 % from the initial, and the bleeding time increases more than up to 30 minutes) throughout the infusion. Low levels of blockade GP IIb/IIIa - receptors persist for 10 days after stopping the infusion, but platelet function returns to normal after 24-48 hours, although abciximab can circulate in the blood in a platelet-related condition for 15 days or more.

    Intravenous bolus injection of ReoPro at a dose of 0.25 mg / kg followed by continuous infusion at a rate of 10 μg / min (or 0.125 μg / kg / min with a maximum10 μg / min) creates a relatively constant level of free drug in the blood plasma throughout the entire infusion period. After the end of infusion, the concentration of free drug in the blood plasma decreases within 6 hours, after which the decrease occurs more slowly.

    Pharmacokinetics:

    After intravenous bolus administration of abciximab, the concentration of free drug in the blood plasma rapidly decreases. The initial half-life is less than 10 minutes, and in the second phase - about 30 minutes, which is caused by rapid binding of the drug with GP IIb/IIIa - receptors of platelets.

    Special patient groups

    Use in children.

    Safety and effectiveness of the drug in children is not established.

    Pathology of the kidneys and peripheral vessels.

    The positive effect of using the drug may be less in patients with kidney and peripheral vascular pathology.


    Indications:

    - Prophylaxis of myocardial ischemia in patients undergoing percutaneous transluminal coronary angioplasty (balloon angioplasty, atherectomy and stent implantation).

    - Short-term (1 month) prevention of myocardial infarction in patients with unstable angina, resistant to standard therapy,which is scheduled for percutaneous coronary angioplasty within 24 hours.

    Contraindications:

    - Continuing internal bleeding;

    - Violations of cerebral circulation (including during the last 2 years);

    - Recent (within 2 months) intracranial and intraspinal surgery or trauma;

    - A recent (within 2 months) extensive surgical operation;

    - Recent (within 6 weeks) clinically significant bleeding of the gastrointestinal tract or urogenital system;

    - Intracranial neoplasm, arteriovenous malformation or aneurysm;

    - Established hemorrhagic diathesis;

    - Severe uncontrolled hypertension;

    - Previous thrombocytopenia;

    - Vasculitis;

    - Hypertensive or diabetic retinopathy;

    - Pronounced impairment of kidney and / or liver function;

    - The established sensitivity to abciximab, to any of the components of the drug or to murine monoclonal antibodies;

    - Residual effects after cerebrovascular accident with neurological deficit;

    - Pregnancy, lactation;

    - Age to 18 years.

    Dosing and Administration:

    RhePro is intended for intravenous administration to adults.

    RheOpro should be used in combination with acetylsalicylic acid and heparin. The recommended dose of ReoPro is: 0.25 mg / kg bolus, followed by intravenous continuous infusion at a rate of 0.125 μg / kg / min (maximum 10 μg / min).

    To stabilize the condition of patients with unstable angina after a bolus dose, continuous infusion is performed, which should be started no more than 24 hours before possible percutaneous coronary angioplasty and completed 12 hours after the procedure.

    To prevent ischemic complications from the heart in patients undergoing percutaneous coronary angioplasty and who are currently not undergoing ReoPro infusion, bolus administration should be performed 10-60 minutes before the procedure followed by intravenous infusion of the drug within 12 hours.

    Instructions for the administration of the drug:

    1. Do not use a solution of ReoPro containing visible mechanical inclusions;

    2. In case of symptoms of an allergic reaction or anaphylaxis, the introduction of ReoPro should be stopped immediately and appropriate antiallergic or symptomatic therapy should be given;

    3. Collect the necessary amount of ReoPro into the syringe for bolus administration.Filter the solution for bolus administration through a sterile, pyrogen-free filter for a syringe with a low protein binding capacity with a pore diameter of 0.2 / 0.22-μm or 5.0 μm. Bolus administration should be performed within one (1) minute;

    4. Collect the amount of ReoPro needed for continuous infusion into the syringe. Transfer the contents of the syringe to a suitable container containing sterile 0.9% saline or 5 % dextrose solution, and begin the infusion with a predetermined rate, using a pump for continuous infusion. The solution for continuous infusion should be filtered before mixing through a sterile, apyrogenic filter for a syringe with a low protein binding capacity with a pore diameter of 0.2 / 0.22 μm or 5.0 μm, or, when administered, use a sterile, pyrogen-free low-pass filter the ability to bind proteins with a pore diameter of 0.2 or 0.22-μm. After the infusion is finished, unused portion of the solution should be poured out.

    5. Despite the fact that there was no incompatibility with liquids for intravenous infusions or with commonly used cardiovascular drugs,It is recommended to inject ReoPro whenever possible through a separate system for intravenous administration and not mix with other medications.

    Concomitant treatment with acetylsalicylic acid and heparin

    RheOpro is prescribed as a supplement to therapy with acetylsalicylic acid and heparin.

    Acetylsalicylic acid.

    It is prescribed orally in a daily dose of at least 300 mg.

    Heparin.

    Percutaneous coronary angioplasty.

    Bolus administration of heparin before percutaneous coronary angioplasty.

    If the activated coagulation time (ACB) is less than 200 seconds before the beginning of percutaneous coronary angioplasty, then heparin is initially administered bolus by creating the arterial access as follows:

    ABC <150 seconds: enter 70 units / kg ABC = 150-199 seconds: enter 50 units / kg.

    The initial bolus dose of heparin should not exceed 7,000 units.

    After bolus administration of heparin, ABC should be checked within two minutes. If ABC is <200 seconds, additional bolus injections of heparin should be given in doses of 20 U / kg. If ABC remains <200 seconds, then bolus injections of heparin should be taken at 20 U / kg until ABC> 200 seconds.

    In situations where there is a clinical need for the administration of higher doses of heparin, despite the increased risk of bleeding, it is recommended that the achieved ABC does not exceed 300 seconds.

    Bolus administration of heparin during percutaneous coronary angioplasty.

    During the percutaneous coronary angioplasty, ABC should be monitored every 30 minutes. If ABC <200 seconds, then you can additionally bolus enter heparin at a dose of 20 U / kg. If ABC remains <200 seconds, then bolus injections of heparin should be taken at 20 U / kg until ABC> 200 seconds. ABC should be monitored before each bolus injection of heparin and at least 2 minutes after injection.

    An alternative to the additional bolus injections of heparin described above can be continuous infusion of heparin at a rate of 7 U / kg / hr initiated upon reaching ABC> 200 seconds after the introduction of the initial heparin bonus and continuing during the procedure of percutaneous coronary angioplasty.

    Infusion of heparin after percutaneous coronary angioplasty.

    It is strongly recommended to stop the administration of heparin immediately after the end of percutaneous coronary angioplasty, followed by removal of the arterial catheter for 6 hours.If a prolonged heparin therapy or later removal of the catheter is planned after percutaneous coronary angioplasty, a heparin infusion with an initial rate of 7 U / kg / h is recommended. In all cases, the administration of heparin should be discontinued no less than 2 hours before removal of the catheter from the artery.

    Stabilization of unstable angina.

    Anti-coagulant therapy should begin with the use of heparin to achieve activated partial thromboplastin time (APTT) 60-85 seconds. During the infusion of RheoPro, it is necessary to continue the infusion of heparin. After the angioplasty, the administration of heparin is carried out according to the scheme described in Section 1 (percutaneous coronary angioplasty).

    Side effects:

    On the part of the organs of hematopoiesis and the system of hemostasis.

    Bleeding during the first 36 hours (ReoPro does not increase the risk of intracranial hemorrhages), thrombocytopenia, anemia, leukocytosis, petechiae.

    From the cardiovascular system.

    Reduction of arterial pressure, pulmonary edema, atrioventricular blockade, supraventricular tachycardia, ventricular tachyarrhythmias, bradycardia,"intermittent claudication", peripheral vascular embolism, pulmonary embolism.

    From the digestive system.

    Constipation or diarrhea, nausea, vomiting, ileus.

    From the nervous system.

    Confusion, dizziness, brain ischemia, hyperesthesia.

    From the urinary system.

    Renal failure, urinary retention.

    Allergic reactions.

    Itching, anaphylactic shock.

    Other.

    Myalgia, phlegmon, fever, pain at the injection site, impaired vision, pleural effusion, pneumonia.

    After 2-4 weeks, it is possible to detect human anti-chimeric antibodies (CHAHA) (usually with a low titer).

    Overdose:

    Symptoms. Profuse bleeding, acute allergic reaction, thrombocytopenia, vascular collapse.

    Treatment. Abolition of the drug, transfusion of platelet mass, symptomatic treatment.

    Interaction:

    Anticoagulants (heparin in a dose of more than 70 units / kg), thrombolytics, antiplatelet drugs (ticlopidine, dipyridamole, low molecular weight dextran) - increase the risk of bleeding.

    The introduction of other monoclonal antibodies increases the risk of allergic reactions.

    Special instructions:

    Before starting treatment with ReoPro, a thorough assessment of the benefit / risk ratio should be carried out. In patients with low risk, but above 65 years, a favorable benefit / risk ratio is not achieved.

    RheOpro should be administered only if the following conditions are met: the availability of experienced specialists and appropriate equipment for transfusion of blood products, the possibility of appropriate care and the conduct of appropriate hematological tests.

    It is recommended to use with caution the preparation of ReoPro in the following cases:

    - reception of oral anticoagulants during the previous 7 days with a decrease in prothrombin time by 1.2 and more compared to baseline;

    - intravenous dextrans before coronary angioplasty;

    - body weight below 75 kg;

    - age over 65;

    - unsuccessful or prolonged (more than 70 min) percutaneous coronary intervention;

    - Coronary angioplasty within 12 hours after the development of acute myocardial infarction.

    Precautions associated with bleeding.

    Treatment of ReoPro is associated with an increase in the frequency of bleeding,in particular at the site of arterial access for insertion of a catheter into the femoral artery. The following are specific recommendations for precautionary measures at the access point.

    Catheterization of the femoral artery

    - Use only arterial access (avoid insertion of the catheter into the vein).

    - Only point the front wall of the vessel.

    - The method of end-to-end approaches for determining the vascular structure is not recommended.

    When a catheter is in the femoral artery

    - Check the location of the catheter insertion and the distal pulse on the corresponding leg (s) every 15 minutes for the first hour, then every hour for 6 hours.

    - The patient should be on the bed with an elevated angle of no more than 30 ° the head end in a state of complete rest.

    - Maintain the corresponding leg (legs) in the extended position with rollers from the sheet or soft immobilization.

    - If necessary, eliminate pain in the back and inguinal area medically.

    - Consult a patient on how to behave after a percutaneous coronary intervention.

    Removal of a catheter from the femoral artery

    - The administration of heparin must be discontinued no less than 2 hours before the removal of the arterial catheter.

    - Before removing the arterial catheter, you need to check the APTT or ABC: do not withdraw the catheter until APTTV is set <50 seconds or ABC <175 seconds.

    - After removing the catheter, firmly press the access site for at least 30 minutes.

    - After reaching the hemostasis, apply a pressure bandage.

    After removal of the catheter from the femoral artery

    - Check for bleeding / hematoma in the groin and distal pulse every 15 minutes for the first hour or until a stable condition is established. Next - every hour for 6 hours after removal of the catheter.

    - Continue to maintain the patient's complete resting state. The patient should continue to be in a state of complete rest on the bed with an elevated angle of at most 30 ° the head of the bed and with elongated legs for 6-8 hours after removal of the catheter from the femoral artery, 6-8 hours after stopping the introduction of ReoPro or 4 hours after stopping the administration of heparin, depending on which procedure will be completed later.

    - Before lifting the patient from bed, it is necessary to remove the pressure bandage.

    Stop bleeding with the formation of a hematoma (or without) at the access point to the femoral artery

    - Lower the head of the bed to 0 °.

    - Press the access site manually or with a pressure device until the bleeding stops.

    - Any hematoma must be measured and controlled to increase it.

    - If necessary, change the pressure bandage.

    - Before the appointment of heparin, it is necessary to measure the APTT and select a dose of heparin. Preserve venous access if the catheter has been removed.

    If, despite these measures, inguinal bleeding continues or the hematoma increases in size during the infusion of ReoPro, the infusion of ReoPro should be stopped immediately and, in accordance with the recommendations outlined above, remove the arterial catheter. After removal of the catheter, the venous access should be maintained until control of the bleeding is restored.

    Uncontrolled bleeding

    In case of serious profuse bleeding or if an emergency surgical procedure is necessary, the introduction of ReoPro should be discontinued. In most patients, bleeding time returns to 12 minutes for 12 hours. If the bleeding time remains longer than 12 minutes, you can enter 10 units of platelet mass. ReoPro can be displaced from endogenous platelet receptors, followed by binding to transfused platelets.However, a single transfusion may be sufficient to reduce the blockade of receptors to 60-70%. With this level of blockade, the function of platelets is restored. To maintain bleeding time at 12 minutes or less, repeated transfusions of platelet mass may be required.

    Possible places of bleeding

    Attention should be paid to all possible bleeding sites, including venous and arterial puncture sites, catheter insertion sites, venesection sites and needle points.

    Retroperitoneal bleeding

    During the introduction of ReoPro, the risk of retroperitoneal bleeding associated with puncture of the femoral vessels increases. The use of femoral catheters should be kept to a minimum, and when establishing vascular access, only the front wall of the arteries or veins should be pointed.

    Pulmonary haemorrhage

    Introduction ReoPro is not often the cause of pulmonary (mainly alveolar) bleeding, which can be accompanied by: hypoxemia, increased alveolar infiltration on the roentgenogram of the chest, hemoptysis, or a decrease in hemoglobin of an unknown etiology.In case of confirmation of bleeding, the introduction of ReoPro, all anticoagulants and antiaggregants should be discontinued.

    Prevention of gastrointestinal bleeding

    To prevent gastrointestinal bleeding, it is recommended to prescribe patients with histamine H antagonists2-receptors or solutions of antacids. If necessary, antiemetics should be prescribed.

    General Nursing Care

    It should be avoided without the need for puncture of arteries and veins, intramuscular injections, routine catheterization of the bladder, nasotracheal intubation, the introduction of a nasogastric tube and the imposition of an automatic pressure cuff. When creating a venous access, non-compressible sites (for example, subclavian or jugular veins) should be avoided. Blood fetuses should be taken from a catheter, for the flushing of which heparin or physiological saline should be used. Puncture sites need to be documented and monitored. When removing the bandages, you need to be extra careful.

    Dynamic monitoring of the patient

    Before the introduction of ReoPro to detect existing disorders of blood clotting, it is necessary to determine the number of platelets, ABC, prothrombin time and APTT.

    Additional platelet counts should be taken 2-4 hours later, and 24 hours after bolus administration. Before the introduction of ReoPro, and also at 12 and 24 hours after the bolus is administered, it is necessary to determine the level of hemoglobin and hematocrit. Before the introduction of the RheoPro bolus, when returning the patient to the ward from the catheterization laboratory and 24 hours after the administration of the RheoPro bolus, a 12-channel ECG should be made. Vital signs (including blood pressure and pulse) should be evaluated every hour for the first 4 hours after the administration of the RheoPro bolus and at 6, 12, 18 and 24 hours after the bolus is administered.

    Recovery of platelet function

    In the event of serious uncontrolled bleeding or the need for emergency surgery, the introduction of ReoPro must be discontinued. In most patients, bleeding time is normalized within 12 hours. In case of prolonged bleeding time, and / or obvious suppression of platelet function, if rapid hemostasis is required, and / or lack of adequate hemostatic recovery, the decision should be based on the recommendation of a hematologist with experience in diagnosing and managing patients with bleeding.If it is necessary to achieve rapid hemostasis, a platelet mass (at least 5.5 x 1011 thrombocytes). There may be a redistribution of ReoPro from the endogenous platelet receptors to the platelets received during transfusion. Single transfusion can reduce blockade of receptors to 60-70% of the level at which the function of platelets is restored. To maintain hemostasis, repeated platelet transfusions may be required.

    Thrombocytopenia

    To reduce the likelihood of thrombocytopenia, the number of platelets should be monitored before treatment, 2-4 hours after the bolus injection of ReoPro and after 24 hours. If the patient shows an acute drop in the number of platelets, it is necessary to conduct an additional determination of the number of platelets. Blood samples for these studies should be collected in three separate tubes containing ethylenediaminetetraacetic acid (EDTA), citrate and heparin, respectively, to exclude pseudothrombocytopenia due to interactions of anticoagulants in vitro. If true thrombocytopenia is confirmed, then ReoPro should be immediately discontinued and appropriate monitoring and treatment performed.The daily number of platelets should be determined as long as their number does not return to normal. If the patient's platelet count drops to 60,000 cells / μl, then heparin and aspirin should be discontinued. If the platelet count falls below 50,000 cells / μl, platelet transfusion should be addressed, especially in case of bleeding and / or current or planned invasive procedure. If the platelet count falls below 20,000 cells / μl, transfusion of platelet mass should be performed. The question of transfusion of platelet mass should be decided on the basis of the clinical picture individually.

    Repeated administration.

    Introduction RheoPro can lead to the formation of human anti-chimeric antibodies (CHAHA), which potentially can cause hypersensitivity and allergic reactions (including, anaphylactic reactions), thrombocytopenia and a decrease in the beneficial effect upon repeated administration. In the Phase III studies, CHAXs usually appeared in low titers in about 5-6% of patients after a single injection of ReoPro. The available data indicate that human antibodies to other monoclonal antibodies cross-react with ReoPro.

    Re-introduction of RheoPro to patients undergoing percutaneous coronary interventions was evaluated in a register that included 1,342 appointments in 1,284 patients. The majority of patients had a second injection of ReoPro, 15% of patients had a third and subsequent administration. The total number of CHAX-positive before reintroduction was 6% and increased to 27 % after repeated administration. No serious allergic and anaphylactic reactions have been reported. Thrombocytopenia was more frequent in studies with repeated administration than in phase III studies with a single administration, suggesting a possible relationship between repeated administration and increased frequency and severity of thrombocytopenia.

    Kidney Diseases

    In patients with kidney disease, the positive effects of RheoPro can be reduced. The decision to use ReoPro in patients with severe renal failure should be taken after a thorough assessment of the risk and benefit. Since the potential risk of bleeding in patients with severe renal disease is elevated, patients should be monitored more carefully for bleeding.In case of serious bleeding, the question of transfusion of platelet mass should be decided. In patients on dialysis, the use of ReoPro is contraindicated.

    Recommendations for transportation and storage.

    RhePro does not contain preservatives and is intended for single use only. Unused portions must be poured. To carry out intravenous infusion, the solution of ReoPro must be prepared immediately before administration.

    When transporting the drug, special containers with cooling elements (coolers 8 MSZ and 4 MC28) should be used to avoid violation of temperature storage conditions.

    Form release / dosage:Solution for intravenous administration of 2 mg / ml in vials.
    Packaging:

    5 ml of the drug in a bottle of neutral glass. One bottle together with the instruction for medical use is placed in a cardboard pack.

    Storage conditions:

    Store at a temperature of 2 ° C - 8 ° C. Do not freeze. Do not shake.

    Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N015367 / 01
    Date of registration:02.04.2011
    Date of cancellation:2016-09-21
    The owner of the registration certificate:Eli Lilly East SAEli Lilly East SA Switzerland
    Manufacturer: & nbsp
    CILAG, AG Switzerland
    Representation: & nbspELI LILLY EAST SA ELI LILLY EAST SA Switzerland
    Information update date: & nbsp22.09.2016
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