Composition, form of production and packaging
Lyophilizate for solution for infusion 1 fl.
anti-inhibitory coagulant complex * 500 units **
Excipients: sodium citrate dihydrate, sodium chloride.
Solvent: water d / and - 20 ml.
Vials (1) complete with a solvent (1 pc.) And a kit for dissolution and administration (needle-adapter, airway needle, needle-filter, disposable syringe, needle-butterfly for transfusion, disposable needle) packs cardboard.
Lyophilizate for solution for infusion 1 fl.
anti-inhibitory coagulant complex * 1000 ED **
Excipients: sodium citrate dihydrate, sodium chloride.
Solvent: water d / and - 20 ml.
Vials (1) complete with a solvent (1 pc.) And a kit for dissolution and administration (needle-adapter, airway needle, needle-filter, disposable syringe, needle-butterfly for transfusion, disposable needle) packs cardboard.
* - contains Factors II, IX and X mainly in non-activated form, as well as activated factor VII; Coagulant Factor VIII antigen (FVIII C: Ag) is present at concentrations up to 0.1 ED per 1 unit of drug activity.
** - a solution containing 1 ED shortens the activated partial thromboplastin time (APTT) of the plasma with an inhibitor to factor VIII to 50% compared to the control.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Hemostatic drug. Although its activity, bypassing inhibitors to factor VIII, has been demonstrated both in vitro and in vivo, the mechanism of action of the drug is still the subject of scientific discussions. Nevertheless, recent scientific studies indicate the role of specific components of the activated prothrombin complex, prothrombin (factor II) as a zymogen and activated factor X (factor Xa) in providing the mechanism of action of the drug Feib.
PHARMACOKINETICS
Because the mechanism of action has not been finally established, it is not possible to draw a conclusion about the pharmacokinetic properties of Feib's 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 coagulopathies due to inhibitors to factors VIII, IX and XI;
- for long-term therapy with IIT (programs for induction of immune tolerance) with a concentrate of factor VIII in order to avoid the development of bleeding.
DOSING MODE
The dose and duration of treatment depend on the severity of hemostasis, localization and intensity of bleeding, as well as the clinical condition of the patient. When choosing the dose and frequency of administration should be guided by clinical effectiveness in each case.
It is recommended to administer 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 units / kg of body weight, and a daily dose of 200 units / kg of 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 Feib's therapy.
Spontaneous bleeding
Hemorrhages in the joints, muscles and soft tissues
In cases of bleeding of low and medium intensity, doses of 50 to 75 U / kg body weight are recommended every 12 hours. Treatment should be continued until clear signs of clinical improvement are obtained: pain disappearance, joint mobility restoration, reduction of its volume.
In cases of extensive hemorrhages in the muscles and soft tissues, for example, 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 of body weight is recommended every 6 hours with close observation of the patient (bleeding area condition, hematocrit dynamics). If bleeding does not stop, a single dose can be increased to 100 U / kg body weight, but do not exceed the maximum daily dose of 200 units / kg body weight / day.
Other severe bleeding
Severe hemorrhages, such as CNS hemorrhages, are effectively stopped by administering the drug at a single dose of 100 U / kg body weight every 12 hours. In some cases, the Feiba preparation can be administered at 6-hour intervals until a clear clinical improvement is achieved, but not exceeding the maximum daily dose 200 units / kg of body weight / day.
Surgical interventions
The recommended single dose of the drug is 50-100 ED / kg body weight every 6 hours, not exceeding the maximum daily dose of 200 units / kg body weight.
Prevention of hemorrhage in patients with inhibitory forms of hemophilia A during induction of immunotolerance (IIT) programs or in the inability of IIT
Patients with high-responders and frequent haemorrhage in the history of Feiba can be administered in combination with factor VIII concentrates at a single dose of 50 to 100 U / kg body weight every 12 hours until the level of the factor VIII inhibitor decreases to 1 BU (1 BU - Bethesda Unit 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 В° C).
If during the IIT programs high doses of factor VIII can not achieve immune tolerance, then for prevention of bleeding can be shown monotherapy with a single dose of Feib in a single dose of 50 to 100 units / kg body weight 3 times a week.
Rules of preparation and use of the drug
The drug solution is prepared immediately before administration. The prepared solution should be immediately used (the drug does not contain preservatives).
The prepared solution is injected iv slowly at a rate of no more than 2 U / kg of body weight / min.
Turbulent solutions or solutions with a suspension should not be used. All unused solutions must be disposed of properly.
Preparation of concentrate solution
1. Closed vial with solvent (water for injection), heat to room temperature (not above 37 В° C).
2. Remove the protective caps from the vials with lyophilizate and solvent and disinfect the rubber stoppers on both vials.
3. Rotate and then remove the protective packaging from one end of the supplied adapter needle. Pierce this end of the needle with a rubber stopper bottle with a solvent.
4. Carefully remove the protective packaging from the other end of the adapter needle, without touching the exposed end of the needle.
5. Turn the vial with solvent and pierce the rubber stopper of the vial with lyophilizate with the free end of the needle-adapter. 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. For a faster dissolution of the lyophilisate, the vial can be gently rotated and shaken.
7. After the lyophilizate is completely dissolved, insert the supplied airway needle into the flask to precipitate the formed foam. Remove the airway needle after the foam settles.
The chemical and physical stability of the finished solution is 3 hours at a temperature of 20 В° -25 В° C. From a microbiological point of view, the Feiba preparation should be used immediately after dissolution. Do not store the finished solution in the refrigerator.
Injection / Infusion
1. Rotate and then remove the protective package from the filter needle and install it on a sterile disposable syringe. Draw the solution into the syringe.
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 (in / in the drip introduction) should use a disposable system for transfusions with a filter.
Do not exceed the injection rate of 2 U / kg body weight / min.
SIDE EFFECT
The following side effects were noted in post-marketing studies. During the clinical trials, these side effects were not noted. The incidence of side effects was evaluated based on the following criteria: very frequent (> 1/10), frequent (> 1/100; <1/10), infrequent (> 1/1000; <1/100), rare (> 1/10 000; <1/1000) and very rare (<1/10 000).
All of the following side effects reflect the types of reactions that may occur with the use of the drug Feib.
The incidence of side effects is <1/10 000, i.e. very rare.
From the coagulation system of blood: disseminated intravascular coagulation, thromboembolic disorders.
From the cardiovascular system: myocardial infarction, marked decrease in blood pressure.
Allergic reactions: anaphylaxis, hypersensitivity reactions, rash.
From the side of the central nervous system: numbness of the face and limbs (hypoesthesia).
Other: acute pain.
Rapid IV administration can cause acute pain, numbness of the face and limbs, as well as a marked decrease 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, conduct standard anti-shock therapy.
CONTRAINDICATIONS
The following contraindications can be considered relative or absolute, depending on the possibility of using alternative therapies.
- Hypersensitivity to the active ingredient or to excipients.
In the following situations, the Feiba preparation can be used only when the use of the appropriate coagulation factor concentrates is obviously ineffective, for example, with a high titer of inhibitors:
- Disseminated intravascular coagulation: with laboratory and / or clinical signs clearly indicating liver damage, because due to the slowdown in the clearance of activated clotting factors, such patients are at increased risk of developing DIC syndrome;
- myocardial infarction, acute thrombosis and / or embolism: in patients with a presumed or established diagnosis of IHD, as well as with acute thrombosis and / or embolism, the use of Feib's preparation is indicated only with life-threatening bleeding.
PREGNANCY AND LACTATION
The safety of the use of the drug Feib during pregnancy and during lactation is not established. Experiments on animals do not allow us to judge the safety of the drug in terms of effects on reproductive function, embryo or fetus development, pregnancy and peri- and postnatal period. Due to the increased risk of thrombosis during pregnancy, the preparation of Feiba should be prescribed only in the absence of alternative methods of treatment and subject to careful medical control.
SPECIAL INSTRUCTIONS
Particular attention should be paid to patients on a low-salt diet. the amount of sodium in the maximum daily dose of the drug may exceed 200 mg.
Do not exceed single doses of 100 U / kg and daily doses of 200 U / kg. Patients receiving single doses of 100 U / kg should be monitored for possible development of DIC syndrome and / or symptoms of acute coronary ischemia. High doses of the Feiba preparation should be given only for the time it takes to stop the bleeding.
In the event of clinically pronounced violations of blood pressure and pulse rate, difficulty breathing, pain in the chest and cough, the drug should be immediately discontinued and appropriate diagnostic and therapeutic measures initiated. Laboratory signs of DIC syndrome are fibrinogen reduction, a decrease in the number of platelets and / or the presence of fibrin / fibrinogen degradation products. Other signs are significant lengthening of thrombin time, prothrombin time or APTT.
Patients with acquired coagulopathies due to inhibitors of coagulation factors can have both a tendency to bleeding and an increased risk of thrombosis.
The results of tests conducted to monitor the effectiveness of in vitro treatment, such as APTT, coagulation time and thromboelastogram, may not correlate with clinical improvement. Therefore, attempts to achieve the normalization of these indicators by increasing the doses of the drug Feiba may not only be unsuccessful, but also increase the risk of developing DIC syndrome as a result of an overdose.
Because for the implementation of the action of the drug Feib required the presence of a significant number of fully functional platelets, in the case of an inadequate response to treatment with the drug recommended control of the number of platelets.
Within this expiration date, patients can store the Feiba preparation at room temperature (no higher than 25 В° C) for 6 months. The date of storage at room temperature should be marked on the package.
A warning
Feiba is made from human plasma. When using medicines prepared from human blood or plasma, it is impossible to completely eliminate the risk of transmission of infectious diseases. This also applies to pathogens of unknown origin. However, the risk of transmission of infections is maximally reduced as a result of:
- careful selection of donors by screening and laboratory screening of individual plasma doses and plasma pools for HBsAg, anti-HIV and anti-HCV antibodies;
- testing of plasma pools on the genomic sequences of HIV-1 and HIV-2, HAV, HBV, HCV and parvovirus B19;
- technological stages for the removal and inactivation of viruses and pathogens in the production process. The effectiveness of these technologies is confirmed for HIV-1, HIV-2, HAV, HBV and HCV.
The drug is susceptible to double antiviral treatment.
The techniques used to remove and inactivate can be limited in effectiveness against certain non-enveloped viruses, such as, for example, parvovirus B19. Infection with parvovirus B19 can be dangerous for pregnant women (infection of the fetus) and patients with immunodeficiency or increased disintegration of erythrocytes (eg, in hemolytic anemia).
Patients receiving coagulation factor concentrate therapy are recommended to vaccinate against hepatitis A and B.
In the interests of patients, it is recommended that the name and number of the drug series be fixed each time a Feib preparation is administered.
Impact on the ability to drive vehicles and manage mechanisms
Not noted.
OVERDOSE
An overdose of the drug Feiba increases the risk of developing thromboembolism, DIC syndrome, myocardial infarction (see section "Special instructions").
DRUG INTERACTION
Like other concentrates of coagulation factors, the Feiba preparation should not be mixed with other medicinal products, tk. this can affect the effectiveness and safety of the drug. It is advisable to wash the general venous access with isotonic sodium chloride solution before and after the introduction of Feib's preparation.
It is not recommended to use antifibrinolytic drugs such as epsilonaminocaproic acid in combination with the preparation of Feib. If it is necessary to use combination therapy with antifibrinolytic drugs and the preparation of Feib, the interval between their administration should be at least 6 hours.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of 2 В° to 8 В° C. Do not freeze. Shelf life - 2 years. Do not use after expiry date.
