Instruction for use: Coagulation Factor VIII + Willebrand factor

Trade name of the drug – Vilate, Hfemate P

Pharmacological group:

Coagulants (including coagulation factors), hemostatics

Model clinical-pharmacological article 1

Characteristic. The effectiveness of coagulation factor VIII is determined based on the International Standard for Concentrate (FVIII: C), the effectiveness of von Willebrand factor is determined based on the determination of the efficacy of the ristocetin cofactor (FV: RK), based on the International Standard for Concentrate in accordance with the European Pharmacopeia. Specific activity of the preparation is not less than 60 ME FVIII: C / mg and not less than 53 ME PV: RK / mg total protein. The number of units of the coagulation factor VIII is expressed in ME corresponding to the WHO standards for these drugs. Activity is expressed either as a percentage (relative to the normal content of the factor in the plasma), or in International Units (relative to the International Standard for coagulation factor VIII in plasma). 1 ME of the coagulation factor VIII is equivalent to the amount of clotting factor VIII in 1 ml of normal human plasma.

Pharmacotherapy. The clotting factor of VTH binds to the von Willebrand factor; The activated factor VS is a cofactor to the activated factor IX, accelerating the transition of the coagulation factor X into the active form; The activated factor X activates the transition of prothrombin to thrombin, thrombin, in turn activates the transition of fibrinogen to fibrin, followed by the formation of thrombus. The drug contains vWF, which is a normal component of human plasma and acts in the same way as endogenous, and corrects hemostasis disorders in patients with Willebrand's disease: restores platelet adhesion to vascular subendothelium at the site of vascular injury (attached to the vascular subendothelium and to the platelet membrane, provides Primary hemostasis, reduces clotting time, with the effect manifested immediately and depends on the degree of polymerization of the protein); Normalizes the concomitant deficiency of factor VIII (with the in / in the introduction binds the endogenous factor VH and stabilizes it, slowing its rapid degradation), restores the level of factor VIII: C to normal. Substitution therapy in patients with hemophilia A increases the content of the clotting factor VH, providing a temporary correction of the deficit factor and reducing the risk of bleeding. In addition, von Willebrand factor promotes adhesion of platelets in the area of vascular damage and plays a significant role in the process of platelet aggregation.

Pharmacokinetics. Disease of von Willebrand type 3: mean recovery of PV: RK and FV: Ar - 68-99% respectively, which corresponds to an average increase in plasma concentration by 1.5 and 2.1% per replaced ME / kg body weight. T1 / 2 FV: RC - 17.5 h, ground clearance - 3.9 ml / h / kg. Hemophilia A: concentration of factor VIII: C-80-120% of the estimated. T1 / 2 VIII: C - 14.8 h, which corresponds to the biological T1 / 2, the clearance is 2.9 ml / h / kg.

Indication. Treatment and prevention of bleeding in patients with von Willebrand's disease (with quantitative and / or qualitative Willebrand factor deficiency), congenital hemophilia A, or acquired coagulation factor deficiency VIII.

Contraindications. Hypersensitivity, age to 6 years (efficacy and safety not established).

Carefully. Pregnancy, lactation.

Dosing. IV, after dissolution with the applied solvent; The resulting solution contains 90 IU of the clotting factor VIII and 80 IU of vWF in 1 ml.

Von Willebrand disease: the dose and duration of replacement therapy depends on the clinical condition of the patient, the type and severity of bleeding, the level of FVIII: C and FV: PK.

The ratio between FVIII: C and FV: RK 1: 1, an average of 1 IU / kg. FVIII: C and FV: RK increase the plasma level by 1.5-2% of the normal activity of the corresponding protein. The usual dose of the drug is 20-50 IU / kg, which increases the level of FVIII: C and FV: RK to 30-100%. The initial dose can be increased to 50-80 IU / kg, especially in patients with type 3 vWD, with gastrointestinal bleeding.

For the prevention of bleeding, it is necessary to start the preparation 30 minutes before the beginning of the surgical procedure. In case of planned surgical intervention, the drug is administered for 12-24 hours and 1 hour before the beginning of the surgical procedure, with the expected concentration of PV: 60 IU / dL or more (60% or more) and FVIII: C 50 IU / dL and more (50% or more). The dose is administered every 12-24 hours. Continuous treatment may cause an excessive increase in the level of FVIII: C. After 24-48 hours of treatment, in order to avoid an excessive increase in the level of FVIII: C, it is necessary to reduce the dose, or to increase the interval between administrations.

Hemophilia A: 1 ME coagulation factor VIII: C / kg increases the plasma factor by 1.5-2% of normal content. Determination of the required dose: body weight (kg) × desired increase in the level of coagulation factor VIII (%) × 0.5 IU / kg.

In the case of bleeding events described below, the activity level of FVIII: C should not fall below the baseline plasma level (% of normal content) at the appropriate time.

Moderate bleeding (early hemarthrosis, IM bleeding, nasal bleeding, mouth cavity bleeding and other minor injuries) is the required concentration of coagulation factor VIII - 20-40 IU / dl (20-40%), the administration is repeated every 12-24 hours, At least for 1 day, until the pain subsides or the source of the bleeding is healed.

More extensive bleeding (IM bleeding or hematoma) is the necessary concentration of clotting factor VIII - 30-60 IU / dl (30-60%) every 12-24 hours for 3-4 days, until the pain subsides and the ability to recover.

Dangerous for life bleeding (intracranial, intraperitoneal, in the neck, with blunt injuries, without a visible source of bleeding) is the necessary concentration of coagulation factor VIII - 60-100 IU / dL (60-100%) every 8-24 hours, until completely disappearing Threats.

Small surgical interventions (including tooth extraction) - the necessary concentration of clotting factor VIII - 30-60 IU / dl (30-60%) every 24 hours for at least 1 day, until healing.

Large surgical interventions - the required level of coagulation factor VIII (before and after surgery) - 80-100 IU / dl (80-100%) every 8-24 hours, until adequate wound healing, then at least 7 days to maintain the activity of coagulation factor VIII At the level of 30-60%.

For prolonged prevention of bleeding in patients with severe hemophilia A, it is necessary to administer 20-40 IU / kg every 2-3 days. In some cases, especially in young patients, it may be necessary to reduce the interval between administrations or increase the dose.

In the absence of the effect of an adequate dose, or if it is not possible to achieve the desired concentration of coagulation factor VIII in the plasma with adequate administration, it is necessary to conduct the Bethesda test for the presence of inhibitory antibodies to coagulation factor VIII. In patients with high levels of inhibitors, treatment with clotting factor VIII may be ineffective, and require other therapeutic interventions.

Side effect. Allergic reactions (urticaria, skin rash, chills, chest tightness, shortness of breath, low blood pressure, rarely anaphylactic shock), burning at the injection site, hyperthermia, hot flashes, headache, drowsiness, apathy, nausea, vomiting, anxiety . The development of inhibitory antibodies to von Willebrand factor - in von Willebrand disease, hemophilia A - to the factor of blood coagulation VIII (usually IgG), which leads to an inadequate clinical response to the drug administration; Inhibitory antibodies can cause precipitation and contribute to the development of anaphylactic reactions.

In patients receiving von Willebrand factor preparations containing coagulation factor VIII, a prolonged increase in the plasma level of factor VIII: C increases the risk of thrombosis (monitoring of patients at risk).

Patients with hemophilia A may develop inhibitory antibodies, with an inadequate clinical response to the administration of the drug.

Interaction. Do not mix with other drugs or enter at the same time, using the same infusion set.

Special instructions. When you administer the drug, you need to carefully monitor the condition of patients. Early signs of a hypersensitivity reaction are urticaria, generalized rash, a feeling of chest tightness, shortness of breath, a decrease in blood pressure and anaphylaxis. If these symptoms occur, discontinue the drug immediately. With the development of anaphylactic reactions, patients should be examined for the presence of inhibitory antibodies.

When using drugs derived from human blood or plasma, the possibility of transmission of infectious agents cannot be completely ruled out, therefore, a preventive vaccination against hepatitis A and B is recommended.

Long-term treatment of patients with Willebrand disease with a drug containing vWF and clotting factor VIII can cause an excessive increase in the clotting factor VIII: C, which increases the risk of thrombus formation (control of the concentration of coagulation factor VIII: C is necessary).

The risk of developing inhibitory antibodies in hemophilia A reaches a maximum within the first 20 days after administration, less often after the first 100 days of use. The possibility of using the drug in the presence of inhibitory antibodies to coagulation factor VIII is not established.

To administer the drug, only the kit for dissolution and intravenous administration should be used. Other devices are able to adsorb clotting factors on their inner surface, leading to a decrease in the effectiveness of treatment.

If a water bath is used to warm the solvent, its temperature should not exceed 37 ° C. It is admissible to use only a clear or slightly opalescent solution, without sediment.