Feiba® (Feiba®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAnti-inhibitory coagulant complexAnti-inhibitory coagulant complex
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  • Feiba®
    lyophilizate d / infusion 
    Baxter AG     Austria
    • Dosage form: & nbsplyophilizate for solution for infusion
    Composition:

    In 1 bottle of the drug contains:

    Active substance: antiinhibitory coagulant complex - 500 ED * or 1000 ED *. Excipients: sodium citrate dihydrate - 80 mg, sodium chloride - 160 mg. Solvent: water for injection - 20 ml.

    * A solution containing 1 unit of Feiba® shortens the activated partial thromboplastin time (APTT) of plasma with an inhibitor to factor VIII to 50% compared to the control.

    The preparation of Feiba® contains Factors II, IX and X predominantly in the non-activated form, as well as the activated factor VII; coagulant antigen of factor VIII (FVIII C:Ag) is present at a concentration of up to 0.1 ED per 1 unit of Feiba®. The preparation may contain traces of factors of the kallikrein-kinin system or not contain them at all.

    Description:

    Powder or brittle solid mass of white, almost white or pale green color.

    Pharmacotherapeutic group:Hemostatic agent
    ATX: & nbsp

    B.02.B.D   Coagulation factors

    Pharmacodynamics:

    Although the Feiba® preparation was created in the early 1970s and its activity shunting the inhibitors to factor VIII was demonstrated as in vitro and in vivo, The mechanism of action of the drug is still the subject of scientific discussions.

    Recent scientific studies indicate the role of specific components of the activated prothrombin complex - prothrombin (FII) as a zymogen and an activated factor X (FXa) - in providing the mechanism of action of the drug Feiba®.

    Pharmacokinetics:

    Since the mechanism of action antiingibitornogo coagulant complex is still not completely established, to conclude that the pharmacokinetic properties of Feyba® not possible preparation.

    Indications:

    Treatment and prevention of bleeding in patients with an inhibitory form of hemophilia A;

    Treatment and prevention of bleeding in patients with an inhibitory form of hemophilia B;

    Treatment and prevention of bleeding in patients with acquired coagulopathy due inhibitors to factors VIII, IX and XI.

    Feyba® The drug is also used in combination with Factor VIII concentrate for long-term therapy to prevent the development of bleeding with the PIT (program immune tolerance induction).

    Contraindications:

    Given hereinafter contraindications can assume relative or absolute, depending on the possibility of using alternative methods of treatment.

    - Hypersensitivity to the active substance or to excipients.

    In the following situations, the Feiba® preparation can be used only when the use of the appropriate coagulation factor concentrates is notoriously ineffective, for example, with a high titer of inhibitors:

    - Disseminated intravascular coagulation (ICE): with laboratory and / or clinical signs that clearly indicate liver damage, because due to the slowdown in the clearance of activated clotting factors, such patients are at increased risk of developing ICE;

    - Myocardial infarction, acute thrombosis and / or embolism: in patients with a suspected or established diagnosis of coronary heart disease, as well as with acute thrombosis and / or embolism, the use of the Feiba ® preparation is indicated only for life-threatening bleeding.

    Carefully:


    Pregnancy and lactation:

    The safety of using Feiba® during pregnancy and lactation has not been established. The doctor should evaluate the potential risk and prescribe the drug in case of obvious need, taking into account,that during pregnancy and in the puerperium the risk of thromboembolic complications increases, as well as some complications of pregnancy, which are associated with an increased risk of developing ICE. Studies of reproductive function in animals with the preparation of Feiba® were not conducted. The effect of the drug on fertility in controlled clinical trials has not been established.

    Dosing and Administration:

    For intravenous injection or infusion.

    The rate of drug administration should not exceed 2 units / kg of body weight / min.

    Doses

    The dose and duration of treatment depend on the severity of hemostasis, localization and intensity of bleeding, as well as the clinical state of the patient. When choosing the dose and frequency of administration should be guided by clinical efficacy in each individual case.

    It is recommended to use the drug Feiba in a dose of 50 to 100 units / kg body weight. In this case, do not exceed a single dose of 100 U / kg body weight and a daily dose of 200 U / kg body weight. Coagulation tests, such as coagulation time, thromboelastogram and APTT, usually show a slight reduction in relevant indicators and do not correlate with clinical improvement.For this reason, these tests are of limited importance for the monitoring of Feiba® therapy.

    1. Spontaneous bleeding

    Hemorrhages in the joints, muscles and soft tissues

    In cases of moderate to moderate bleeding, a dose of Feiba® from 50 to 75 U / kg body weight is recommended every 12 hours. Treatment should continue until clear signs of clinical improvement: the disappearance of pain, restore joint mobility, reduce its volume.

    In cases of extensive hemorrhages in the muscles and soft tissues, in particular, with retroperitoneal hematomas, the recommended dose is 100 units / kg body weight every 12 hours.

    Bleeding from the mucous membranes

    A dose of 50 U / kg body weight is recommended every 6 hours, with careful monitoring of the patient (bleeding area condition, hematocrit dynamics). If the bleeding does not stop, a single dose can be increased to 100 U / kg of body weight, without exceeding the maximum daily dose of 200 U / kg of body weight.

    Other severe bleeding

    Severe hemorrhages, such as hemorrhages in the CNS, are effectively stopped by administering the drug in a single dose of 100 U / kg of body weight every 12 hours.In some cases, the Feiba® preparation can be administered at an interval of 6 hours until a clear clinical improvement is achieved, without exceeding the maximum daily dose of 200 U / kg body weight.

    2. Surgical interventions

    The recommended single dose is 50-100 U / kg body weight every 6 hours, not exceeding the maximum daily dose of 200 U / kg body weight. Doses of the drug, intervals between administrations and the duration of treatment during and after surgery depend on the type of surgery, the general condition of the patient and the clinical effectiveness in each case.

    Preventive treatment

      1. To prevent bleeding in patients with high inhibitor titers and frequent bleeding after failure to induce immune tolerance (IIT) or when IIT not conducted the recommended dose is 70-100 U / kg of body weight every other day. If necessary, the dose may be increased to 100 U / kg body weight per day or may be gradually reduced.
      2. For prevention of bleeding in patients with high inhibitor titers during induction of immune tolerance (IIT), the Feiba® preparation can be administered concomitantly with factor VIII at a dosage range of 50-100 U / kg body weight twice a day until the inhibitor titer decreases to <2 BU1

    [1] BU (Bethesda Unit) - unit Bethesda; is defined as the amount of antibody that inhibits 50% of the activity of factor VIII in fresh standard human plasma after incubation for 2 hours at 37 ° C.

    Monitoring

    If there is an inadequate clinical response to treatment with Feiba®, it is recommended to determine the number of platelets, since the realization of the clinical effect requires a sufficient number of functionally complete platelets.

    Because of the complex mechanism of action, there is no direct monitoring of active components. The values ​​of coagulation tests, such as coagulation time, thromboelastogram (r value) and partial activated thromboplastin time, usually show a slight decrease, which does not necessarily correlate with the clinical effect. Therefore, these tests play only an auxiliary role in monitoring therapy with the drug Feiba®.

    Mode of application

    The preparation of Feiba® does not contain preservatives. The drug solution should be prepared immediately before administration with strict adherence to aseptic conditions and used immediately after preparation.

    The solution must be thoroughly mixed and inspected for complete dissolution of the preparation.Otherwise, the active substance will not pass through the device filter. Before use, the solution should be checked for solids and discoloration. Do not use a turbid solution or solution with a slurry.

    If different devices are used to administer the Feiba® device, be sure to use an adequate filter.

    The prepared solution is administered intravenously slowly by injection or infusion at a rate of no more than 2 U / kg body weight / min.

    All unused solutions must be properly disposed of.

    Preparation of the solution

    1. Closed bottle with solvent (water for injections) heat to room temperature (not above +37 ° C).
    2. Remove the protective caps from the vials with lyophilizate and solvent (Figure 1) and disinfect the rubber stoppers on both vials.
    3. Rotate and then remove the protective packaging from one end of the supplied adapter needle (Figure 2). Pierce this end of the needle with a rubber stopper of the vial with a solvent (Figure 3).
    4. Carefully remove the protective packaging from the other end of the adapter needle without touching the surface of the needle.
    5. Turn the solvent bottle and pierce the rubber stopper of the vial with lyophilizate (Fig. 4) with the free end of the adapter needle. Due to the vacuum, the solvent will flow into the vial with the lyophilizate.
    6. Disconnect the vials by removing the needle-adapter from the vial with lyophilizate (Fig. 5). For a faster dissolution of the lyophilisate, the vial can be gently rotated and shaken.
    7. After completely dissolving the lyophilizate, insert the supplied airway needle into the vial (Figure 6) to precipitate the formed foam. Remove the airway needle after the foam settles.

    Before and after the administration of Feiba, it is advisable to wash the total venous access with isotonic sodium chloride solution.

    Coagulation factors derived from human blood plasma can be adsorbed on the inner surface of a certain type of injector or infusion device, which can lead to ineffective therapy. Therefore, only authorized plastic infusion devices can be used to dissolve and administer the Feiba® preparation.

    The chemical and physical stability of the finished solution is 3 hours at a temperature of +20 ° С - +25 ° С.From a microbiological point of view, the preparation of Feiba® should be used immediately after dissolution. Do not store the finished solution in the refrigerator.

    Injection / Infusion

    1. Turn and then remove the protective packaging from the filter needle and install it on a sterile disposable syringe. Draw the solution into the syringe (Figure 7).

    2. Disconnect the needle filter from the syringe, insert the attached butterfly needle for transfusion or a disposable needle for injection and inject the solution intravenously slowly.

    When infusion (intravenous drip introduction) should be used one-time system for transfusions with a filter.

    Do not exceed the rate of administration of 2 units of Feiba® / kg of body weight / min!

    Side effects:

    Hypersensitivity reactions of the allergic type

    The preparation of Feiba® can cause hypersensitivity reactions of the allergic type, in particular, urticaria, Quincke's edema, gastrointestinal manifestations, bronchospasm and hypotension. These reactions can be very serious and of a systemic nature (in particular, anaphylaxis with hives and Quinck edema, bronchospasm, and anaphylactic shock). Other infusion reactions, such as chills, hyperthermia and hypertension, were also noted with the drug.

    The following side effects were observed in postmarketing studies and two studies of the use of the drug for the treatment of bleeding in adult patients and children with hemophilia A or B and inhibitors to factors VIII or IX. One study also included patients acquired hemophilia with inhibitors to factor VIII (2 of 49 patients).

    The frequency of side effects was assessed based on the following criteria: very frequent (> 1/10), frequent (> 1/100; <1/10), infrequent (> 1/1000; <1/100), rare (> 1/10000 ; <1/1000) and very rare (<1/10000).

    All of the following side effects reflect the types of reactions that may occur with the use of the Feiba preparation.

    Violations of the blood and lymphatic system

    Disseminated intravascular coagulation, an increase in inhibitor titer (anamnestic response)

    Disorders from the cardiovascular system

    Myocardial infarction, tachycardia

    Thrombosis, venous thrombosis, arterial thrombosis, arterial hypotension, arterial hypertension, flushes of blood to the skin of the face

    Immune system disorders

    Hypersensitivity reactions (including allergic), urticaria, anaphylactic reactions

    Disturbances from the nervous system

    Paresthesia, hypoesthesia, ischemic stroke, embolic stroke, headache, drowsiness, dizziness, taste perversion

    Disturbances from the respiratory system, chest and mediastinal organs

    Pulmonary embolism, bronchospasm, wheezing, cough, shortness of breath

    Disorders from the gastrointestinal tract

    Vomiting, diarrhea, abdominal discomfort, nausea

    Disturbances from the skin and subcutaneous tissues

    Feeling numbness of the face, angioedema, itching, rash

    General disorders and disorders at the site of administration

    Pain at the injection site, malaise, fever, chills, fever, chest pain, chest discomfort

    Surveys

    Positive titer of antibodies to the surface antigen of the hepatitis B virus.

    Class-specific reactions

    Other symptoms of hypersensitivity reactions to drugs derived from plasma include lethargy and anxiety.

    The rapid intravenous administration of Feiba® can cause acute pain, numbness in the face and limbs, and a drop in blood pressure.

    It was found that myocardial infarction was noted at doses exceeding the recommended maximum daily doses, and / or with prolonged use, and / or in the presence of risk factors for thromboembolism.

    When the hypersensitivity reaction develops, the introduction of Feiba® must be discontinued.

    To stop light reactions, it is sufficient to prescribe antihistamines. In the case of shock, standard anti-shock therapy should be performed.

    Overdose:

    High doses of Feiba ® increase the risk of thromboembolic complications (DVS, myocardial infarction, venous thrombosis and pulmonary embolism). Some of the complications occurred when the drug was administered at doses above 200 U / kg body weight or in patients with other risk factors for thromboembolic complications.

    Interaction:

    Adequate and well-controlled studies of the combined or sequential use of Feiba® and recombinant factor Vila or antifibrinolytic agents were not performed. When combined with the preparation of Feiba® systemic antifibrinolytic agents, such as tranexamic and aminocaproic acids, the possibility of thrombus formation should be considered.

    If combined antifibrinolytic use is required, do not use within 6 to 12 hours after the administration of Feiba®.

    In the case of the concomitant use of a recombinant factor Vila, It is impossible to exclude a possible drug interaction similar to that observed in clinical studies and experiments in vitro.

    Like other coagulation factor concentrates, the Feiba® preparation should not be mixed with other drugs, as this can affect the efficacy and safety of the drug.

    Special instructions:

    When treating with Feiba®, special attention should be given to patients on a low-salt diet, since the maximum daily dose of sodium in the drug may exceed 200 mg.

    Control during treatment

    Do not exceed a single dose of 100 U / kg body weight and a daily dose of 200 U / kg body weight.

    Patients receiving a single dose of 100 U / kg should be closely monitored, including for possible development of ICE and / or symptoms of acute coronary ischemia. High doses of Feiba® should be given only for the time it takes to stop bleeding.

    In the case of the appearance of clinically pronounced violations of blood pressure and heart rate,difficulty breathing, chest pain and coughing, the drug should be immediately discontinued and appropriate diagnostic and treatment measures initiated. Laboratory signs of ICE include fibrinogen reduction, a decrease in the number of platelets and / or the presence of fibrin / fibrinogen degradation products (PDF). Other signs are significant lengthening of thrombin time, prothrombin time or APTT.

    At the first signs or symptoms of an infusion reaction or a hypersensitivity reaction, the introduction of Feiba® should be discontinued and the necessary medical care should be started.

    When considering the re-use of Feiba in patients with known or suspected hypersensitivity, the expected benefit and risk of re-exposure should be carefully weighed against the known or suspected hypersensitivity of the patient (allergic or non-allergic), including the possibility of prophylactic treatment or use alternative therapies.

    Risk of thrombosis and thromboembolic complications

    When treating patients with congenital and acquired hemophilia, one should always remember the presence of risk factors for thrombosis and thromboembolic complications.

    The risk of developing such complications (including ICE, myocardial infarction, venous thrombosis and pulmonary embolism) may increase with the use of high doses of Feiba®, as well as in patients with DIC syndrome, atherosclerosis, massive traumatic lesions, sepsis, or concomitant treatment with a recombinant factor VII. Patients with a risk of developing ICE, arterial or venous thrombosis, the drug should be administered with extreme caution (see the section "Contraindications").

    With Feiba therapy, thromboses and thromboembolic complications were observed, including ICE, venous thrombosis, pulmonary embolism, myocardial infarction, and strokes. Some of these complications developed with doses above 200 U / kg / day or in patients with other risk factors for thromboembolic complications.

    If the severity of bleeding does not justify the use of higher doses, a single dose of 100 U / kg body weight and a daily dose of 200 IU / kg body weight should not be exceeded.Patients receiving Feiba® in doses above 100 U / kg body weight should be observed for possible development of ICE, acute coronary ischemia, and symptoms of other thrombotic or thromboembolic complications.

    When the first signs or symptoms of thrombosis or thromboembolic complications should immediately stop the infusion and take the necessary measures for diagnosis and treatment of the patient.

    Patients with acquired coagulopathy

    Patients with acquired coagulopathies due to inhibitors of coagulation factors can have both a tendency to bleeding and an increased risk of thrombosis.

    Laboratory analysis and clinical efficacy

    Test results in vitro, Conducted to monitor the effectiveness of treatment, such as APTT, whole blood coagulation time and thromboelastogram may not correlate with the clinical condition of the patient. Therefore, attempts to achieve the normalization of these indicators by increasing the dose of Feiba® can not only be unsuccessful, but also increase the risk of developing an internal combustion engine as a result of an overdose.

    The value of controlling the number of platelets

    Since the realization of the action of the Feib preparation requires the presence of a sufficient number of functionally complete platelets, in the case of an inadequate response to treatment with the drug, it is recommended to check the number of platelets and, if necessary, to correct it.

    When used to stop bleeding, the drug should be used only as long as it is absolutely necessary to achieve the goal of therapy.

    Due to the individual characteristics of the patient, the response to the use of drugs with a shunt mechanism of action may be different, and in a particular bleeding situation, a patient with an inadequate response to one drug may respond to another drug. In case of insufficient response to one drug, you should consider using another drug.

    The administration of Feiba® to patients with inhibitors may lead to an initial "anamnestic" increase in the content of the inhibitor. The results of clinical studies and published data indicate that the effectiveness of the preparation of Feiba® in the anamnestic reaction is not reduced.With continued use of the Feiba® preparation, the inhibitor content decreases with time. The temporary increase in the level of passively tolerated antibodies to the surface antigen of the hepatitis B virus, observed after the use of high doses of Feiba®, may lead to false positive serological results.

    Use in children

    The reports on the cases of application and the data of several clinical studies allow to judge the possibility of using the drug in children under six years of age. The experience of using Feiba ® in children under six years is not enough. The dosing regimen designed for adult patients should be adapted according to the clinical situation.

    WARNINGS

    The preparation of Feiba® is made from human plasma.

    When using drugs prepared from human blood or plasma, it is impossible to completely exclude the risk of transmission of infectious diseases, including those caused by unknown viruses or other pathogens. The risk of transmission of infections is reduced as a result of:

    1. careful screening of donors by screening and laboratory screening of individual plasma doses and plasma pools HBsAg, antibodies to HIV and HCV;
    2. testing of plasma pools on the genomic sequences of HIV-1 and HIV-2, HAV, HBV, HCV and parvovirus B19;
    3. technological stages for the removal and inactivation of viruses-pathogens and virus-models in the production process. The effectiveness of these technologies is confirmed for HIV-1, HIV-2, HAV, HBV and HCV.

    The drug was subjected to a double antiviral treatment.

    Applied technologies for the removal and inactivation of pathogens can be limitedly effective against some non-enveloped viruses, parvovirus B19 in particular. Infection with parvovirus B19 can be dangerous for pregnant women (infection of the fetus) and patients with immunodeficiency or increased disruption of erythrocytes (in particular, in hemolytic anemia).

    Appropriate vaccination (against hepatitis A and B) can be recommended to patients who receive regular therapy with drugs produced from blood plasma, including the preparation of Feiba®.

    Every time you introduce Feiba®, it is strongly recommended that you write down the name of the drug series number in order to be able to track the association between the administration of the drug and the patient's condition.

    Within this expiration date, patients can store the Feiba® preparation at room temperature (not above + 25 ° C) for 6 months. The date of starting the storage of the drug at room temperature should be marked on the package. If the drug was stored at room temperature for 6 months, it is either administered to the patient or disposed of. Subsequent storage in the refrigerator is unacceptable.


    Effect on the ability to drive transp. cf. and fur:

    Effects on the ability to drive a car or other mechanisms are not noted.

    Form release / dosage:Lyophilizate for the preparation of a solution for infusions of 500 ED and 1000 units.
    Packaging:

    Liofilizate for the preparation of a solution for infusions of 500 ED and 1000 ED (bottles) complete with a solvent - water for injection (bottles) 20 ml and a set for dissolution and administration - needle-adapter, airway needle, needle-filter, disposable syringe, needle- "butterfly" for transfusion, disposable needle for injection.

    1 vial with the drug, 1 bottle of solvent, kit for dissolving and administering the drug and instructions for use are placed in a cardboard box.

    Storage conditions:

    Store at a temperature of +2 ° C to +8 ° C. Do not freeze!

    Keep out of the reach of children.

    Shelf life:2 of the year.

    Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N013644 / 01
    Date of registration:04.05.2008
    The owner of the registration certificate:Baxter AGBaxter AG Austria
    Manufacturer: & nbsp
    Representation: & nbspBaxter Baxter USA
    Information update date: & nbsp28.08.2014
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