Drotrekogin alfa (activated) (Drotrecoginum alfa (activatum))

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

Anticoagulants

Included in the formulation
  • Sigris®
    lyophilizate d / infusion 
    Lilly Pharma Fertigung und Distribution GmbH & Co. KG     Germany
    • АТХ:

    B.01.A.D.10   Drotrekalin alpha (activated)

    Pharmacodynamics:

    Anticoagulant of indirect action. Activated protein C has an antithrombotic effect by inhibiting the Va and VIIIa coagulation factors, in vitro has an indirect profibrinolytic effect due to its ability to inhibit the inhibitor of the plasminogen-1 activator and to limit the production of the activated thrombin-activated fibrinolysis inhibitor. In addition, it has an anti-inflammatory effect due to suppression of tumor necrosis factor, synthesized by monocytes, blocking of adhesion of leukocytes to selectins, as well as restriction of thrombin-induced inflammatory response in the endothelium of the vessels of the microcirculatory bed.

    Pharmacokinetics:

    The equilibrium concentration is achieved after 2 hours of infusion. Biotransformation - inactivation of endogenous plasma protease inhibitors. Clearance - 40 (27-50) l / h.

    Indications:

    Sepsis, accompanied by acute multi-organ failure, with a high risk of death.

    ICD-10

    I.A30-A49.A41   Other septicemia

    I.A30-A49.A40   Streptococcal septicemia

    Contraindications:

    Hypersensitivity, internal bleeding, recently transferred (during the previous 3 months) hemorrhagic stroke, recently transferred (during the previous 2 months) intracranial operation or operation on the spinal cord, severe craniocerebral trauma (including recently transferred); trauma, accompanied by a high risk of life-threatening bleeding; presence of an epidural catheter, intracranial tumors / formation or signs of cerebral hernia, pregnancy, lactation, children's age (under 18 years).

    Carefully:

    Treatment with heparin (at a dose of more than 15 units / kg / h); thrombocytopenia (platelet count is less than 30,000 per μL, even if the platelet count increased after transfusion); prothrombin time - more than 3 minutes; gastrointestinal hemorrhage, recently transferred (during the previous 6 weeks); thrombolytic therapy in the anamnesis (during the previous 3 days), taking (during the previous 7 days) oral anticoagulants or glycoprotein IIb / IIIa inhibitors, taking (during the previous 7 days) acetylsalicylic acid in a dose of more than 650 mg per day or other inhibitors of platelet aggregation; recently transferred (during the previous 3 months) ischemic stroke; intracranial vascular anomalies, aneurysms; hemorrhagic diathesis; severe chronic liver disease; Other conditions in which there is a high risk of bleeding or difficulty in stopping them, due to localization.

    The safety and efficacy of drtrekogin alpha in newborns (gestational age of 38 weeks) and in persons under 18 years of age have not been studied. Data on the efficacy of drtrekogin alpha in adult patients with a high risk of death suffering from severe sepsis can not be extrapolated to children with severe sepsis.

    Pregnancy and lactation:

    Recommendations FDA category C. Adequate well-controlled studies in humans have not been conducted. Studies on animals have not been carried out. Drotrekogin alfa should be used in pregnant women only if necessary.

    There is no information on the penetration of human milk or the ability to be absorbed from the digestive tract. When prescribing drtrekogin alpha not to breastfeed, take into account the need for its use.

    Dosing and Administration:

    The concentration of the resulting solution should be 2 mg / ml.Then, sterile water for injections is slowly added to the contents of the vial. Cautiously, each vial is shaken until the lyophilizate is completely dissolved and further diluted with a sterile 0.9% solution of sodium chloride. Then slowly, the appropriate amount of the drug solution is taken from the vial and added to the dropper container containing 0.9% sodium chloride solution. Before the injection, examine the product for opacities and discoloration

    When using a pump for intravenous administration, the drug solution is usually diluted with a sterile 0.9% solution of sodium chloride to a concentration of 0.1-0.2 mg / ml.

    When using a syringe pump, the drug solution is usually diluted with a sterile 0.9% solution of sodium chloride to a concentration of 0.1-1 mg / ml. When the drug is administered at low concentrations (less than 0.2 mg / ml) at a low rate (less than 5 ml / h), the infusion should be performed for approximately 15 minutes at a rate of about 5 ml / h.

    Enter intravenously at a rate of 24 μg / kg / h, with an infusion time of 96 hours. After interruption of the infusion, the administration should be resumed at a rate of 24 μg / kg / h.Increasing the dose or bolus is not recommended.

    Side effects:

    Bleeding. In clinical studies, 25% of patients had at least one bleeding, mostly in the form of ecchymosis or bleeding from the gastrointestinal tract. Serious bleeding (including intracranial hemorrhage, life-threatening bleeding, bleeding requiring more than three units of erythrocyte mass per day for two consecutive days, or any bleeding assessed as a serious side effect) occurred in 3.5% of patients. With the development of bleeding - to immediately abolish drtrekogin alfa, after stopping bleeding it is possible to resume therapy, after careful discussion.

    Overdose:

    Life threatening bleeding. Treatment: the antidote is unknown, canceling the drotrecohin alpha.

    Interaction:

    Care should be taken when using combinations with other drugs that affect hemostasis.

    Acetylsalicylic acid or other inhibitors of platelet aggregation - the risk of bleeding may outweigh the benefits of using drtrekogin alpha in terms of up to 7 days after the withdrawal of acetylsalicylic acid at a dose of more than 650 mg per day or other antiplatelet agents.

    Heparin sodium - sharing 15 U / kg per hour or more is not investigated and may increase the risk of bleeding.

    Oral anticoagulants or glycoprotein IIb / IIIa inhibitors - the risk of bleeding may outweigh the benefits of using drtrekogin alfa up to 7 days after the abolition of anticoagulants or glycoprotein IIb / IIIa inhibitors.

    Thrombolytic agents - the risk of bleeding may outweigh the benefits when using drotrekogin alfa in terms of up to three days after the administration of thrombolytic.

    Special instructions:

    Each patient should be carefully examined before the start of therapy, and the expected effect of treatment should be compared with the possible risk of using the drug.

    If clinically significant bleeding occurs, discontinue the infusion of the drug immediately and continue using other medications that affect the blood coagulation system, taking special care. At achievement of adequate parameters of a hemostasis the question on continuation of treatment by drotrecohinum alpha can be considered.

    Drotrecohin alpha treatment should be discontinued 2 hours before surgery or other procedures associated with an increased risk of bleeding.When adequate levels of hemostasis are reached, treatment with the drug can be started 12 hours after extensive invasive procedures and surgical operations or after uncomplicated, less invasive interventions are resumed immediately.

    Most patients with severe sepsis have coagulopathy, which is usually associated with an increase activated partial thromboplastin time and prothrombin time. Drotrekogin alfa can increase activated partial thromboplastin time in varying degrees. In connection with this, the value activated partial thromboplastin time It can not be used to assess the severity of coagulopathy during the infusion of drotrecohin alpha. The value of prothrombin time, drotrekogin alpha has minimal effect, so this value can be used to assess the severity of coagulopathy in this category of patients.

    As with the use of other protein drugs, when using drotrekogin alpha there is the potential for potential immunogenicity (not statistically confirmed).

    Since the preparation does not include antibacterial preservatives, it is desirable to use it immediately after the preparation of the solution (it can be stored at room temperature 15-30 ° C for not more than 3 hours). Intravenous administration should be completed within 12 hours of the preparation of the intravenous solution.

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