Index of drugs

Treatment and prophylaxis of bleeding in patients with von Willebrand disease with quantitative and / or qualitative von Willebrand factor deficiency when treatment with DDAVP (1-deamino-8-D-arginine vasopressin / desmopressin) is ineffective or contraindicated. The main indications are: treatment and prophylaxis of bleeding, prevention and treatment of bleeding during minor and major surgical procedures. Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency) and prevention and treatment of bleeding during minor and major surgical procedures.

1 vial contains 450 IU human coagulation factor VIII and 400 IU von Willebrand factor. 1 vial contains 900 IU. human coagulation factor VIII and 800 IU. von Willebrand factor.

The combination of coagulation factors factor VIII and von Willebrand factor are the physiological components of human plasma that behave like endogenous components. Administration of von Willebrand factor allows correction of hemostasis disorders occurring in patients with von Willebrand factor deficiency at two levels: von Willebrand factor restabilizes platelet adhesion to the endothelium of the vessel at the site of vessel damage (it joins both the endothelium and the platelet membrane) resulting in primary hemostasis, which is manifested by a shortening of the bleeding time (the effect of action occurs immediately and is dependent to a large extent on the level of protein polymerization); von Willebrand factor causes a delayed increase in coexisting factor VIII deficiency, intravenous von Willebrand factor binds to endogenous factor VIII (which is synthesized in the patient), stabilizing this factor prevents its rapid disintegration. For this reason, the administration of pure von Willebrand factor (a preparation of the von Willebrand factor with low factor VIII content) restores the normal level of factor VIII as a secondary effect after the first infusion. When administered intravenously in patients with haemophilia, factor VIII is combined with von Willebrand factor in the patient's circulation. The active factor VIII (VIlla) acts as a cofactor of active factor IX (IXa), accelerating the conversion of factor X to active factor X (Xa). The active factor X transforms prothrombin into thrombin. The thrombin then converts fibrinogen into a fibrin that allows clot formation. In patients with type 3 von Willebrand disease, the calculated mean recovery for VWF: RCo and VWF: Ag was 68 and 99%, respectively. These values ​​correspond to mean plasma increments of 1.5 and 2.1% after administration of IU. per kg of body weight. In patients with haemophilia A, after injection, approximately 2/3 to 3/4 of factor VIII remains in the circulation. The level of factor VIII activity achieved in plasma should be between 80% and 120% of the predicted factor VIII activity. Plasma factor VIII activity decreases in the biphasic two-phase distribution. In the initial phase, distribution between endovascular and other compartments (body fluids) occurs with a plasma elimination half-life of 3 to 6 h. In the Next, slower phase, which probably reflects the consumption of factor VIII, the half-life is from 8 to 18 h, average 15 h.

Hypersensitivity to the active substances or to any of the excipients.

Allergic type hypersensitivity reactions are possible. Patients should be informed of the early signs of hypersensitivity reactions including rash, generalized urticaria, tightness in the chest, wheezing, hypotension and anaphylaxis. Standard measures to prevent infection resulting from the use of preparations obtained from human blood or plasma rely on the selection of donors, the study of individual donations and pools of plasma for specific markers of infection and effective stages of the production process aimed at inactivation / removal of viruses. Nevertheless, the transmission of infectious agents when administering preparations obtained from human blood or plasma can not be fully ruled out. This also applies to unknown or emerging viruses and other pathogens.The methods used are considered effective against enveloped viruses such as HIV, HBV and HCV as well as non-enveloped HAV. The methods used may have limited efficacy compared to non-enveloped viruses such as parvovirus B19. Appropriate vaccination (anti-hepatitis A and B) should be considered for patients receiving treatment regularly or when treatment is repeated using preparations containing human coagulation factor VIII and human von Willebrand factor. During treatment with factor VIII von Willebrand preparations, it can lead to excessively elevated levels of factor VIII in plasma; plasma factor VIII levels should be monitored to avoid excessively high plasma levels that increase the risk of thrombotic complications. This risk of thrombotic complications especially exists in patients with known clinical or laboratory risk factors; patients at increased risk should be monitored for early signs of thrombosis. Patients with von Willebrand disease, mainly type 3, may develop neutralizing antibodies (inhibitors) von Willebrand factor. If the expected level of von Willebrand's plasma activity is not reached or if bleeding can not be controlled with a suitable dose, a diagnosis should be made to check for the possible presence of von Willebrand factor inhibitor. In patients with high levels of inhibitor, treatment with von Willebrand factor may not be effective and another treatment should be considered. The development of neutralizing antibodies (inhibitors) of factor VIII is a known complication during the course of treatment of patients with haemophilia A; patients should be closely monitored for the formation of inhibitors through appropriate clinical observation and laboratory testing. The medicine contains up to 2.55 mmol sodium (58.7 mg) at a dose of 450 IU. factor VIII and 400 IU von Willebrand factor per vial and up to 5.1 mmol sodium (117.3 mg) at a dose of 900 IU. factor VIII and 800 IU von Willebrand factor per vial; this should be taken into account in patients on a sodium restricted diet.

There is no experience in using the drug during pregnancy and breastfeeding. The drug should be used during pregnancy or breastfeeding in women with von Willebrand factor deficiency, if this is strictly indicated, taking into account the fact that childbirth presents an increased risk of bleeding in these patients. Due to the rare occurrence of haemophilia A in women, there is no experience in the use of factor VIII during pregnancy and breastfeeding; drug used during pregnancy and breastfeeding only if it is strictly indicated.

Uncommon: hypersensitivity reactions. Rare: fever, Factor VIII inhibitors. Very rare: anaphylactic shock, von Willebrand factor inhibitors (inhibitors may lead to anaphylactic reactions). There is a risk of thrombotic complications, especially in patients with known clinical or laboratory risk factors.

Intravenously. Treatment should be started under the supervision of a physician experienced in the treatment of coagulation system diseases. The amount of medicine (IU) to be used per kg of body weight (body weight) should be calculated based on the factor VIII activity given.Von Willebrand's disease. The ratio between FVIII: C and VWF: RCo is approx. 1: 1. Overall, 1 IU / kg FVIII: C and VWF: RCo causes an increase in plasma activity of 1.5 to 2% of normal protein activity. Typically, about 20 to 50 IU / kg. is enough to achieve the expected hemostasis. This causes an increase in FVIII: C and VWF: RCo in patients by about 30 to 100%. The starting dose is usually 50 to 80 IU / kg, mainly in patients with von Willebrand type 3 disease, where higher doses are required to maintain adequate plasma levels compared to other types of von Willebrand disease.Prevention of hemorrhage during surgery or serious injuries: the drug should be administered 1 to 2 h before surgery. VWF levels: RCo ≥60 IU / d (≥60%) and FVIII: C ≥ 40 IU / d (≥40%) should be achieved. The appropriate dose should be repeated every 12 to 24 hours of treatment. Dosage and duration of treatment depends on the patient's clinical status, location and extent of bleeding, and FVIII: C and VWF: RCo levels.Prophylactic treatment: 20 to 40 IU / kg, 2 to 3 times a weekHemophilia A. The dosage and length of substitution treatment depends on the level of factor VIII deficiency, the location and intensity of bleeding and the clinical condition of the patient.1 international unit (IU) of factor VIII activity is equivalent to the amount of factor VIII in 1 ml of normal human plasma. The calculation of the required dose of factor VIII is based on 1 IU / kg body weight. factor VIII increases the activity of plasma factor VIII by 1.5 to 2% of normal activity. The required dose is calculated on the basis of the following formula: required units (IU) = body weight (kg) x required increase in factor VIII activity (%) (IU / dl) x 0.5 IU / kg body weightBleeding and surgery. Adults and children> 6 y.Bleeding with low intensity (early bleeding into the joints, muscles, nose, mouth and other minor injuries): the required level of factor VIII is 20-40 IU / dl, repeat every 12 to 24 hours for at least 1 day until the pain caused by bleeding or healing of the wound.More severe bleeding to the joints, muscles or hematoma: the required level of factor VIII is 30-60 IU / dl, repeat administration every 12 to 24 h, for 3-4 days or more until pain and recovery are relieved.Bleeds that threaten life (bleeding to o.u.n., blunt trauma without visible bleeding, heavy bleeding into the abdominal cavity, respiratory tract, throat): required level of factor VIII is 60-100 IU / day, the administration should be repeated every 8 to 24 h until the risk disappears.Operations: smaller (including tooth extraction) - the required level of factor VIII is 30-60 IU / dl, repeat administration every 24 h for at least 1 day, until healing;bigger - the required level of factor VIII is 80-100 IU / dl, repeat administration every 8 to 24 h until appropriate wound healing, then continue therapy for at least 7 consecutive days in order to maintain the factor's activity at 30-60 IU / dl .Prophylactic treatment. Long-term prophylaxis of bleeding in patients with severe haemophilia A should be administered at a dose of 20 to 40 IU / kg. at intervals of 2 to 3 days. In some cases, especially in younger patients, it may be necessary to administer the drug at shorter intervals or at higher doses. Continuous infusion: the initial infusion dose can be calculated using the following formula: infusion dose (IU / kg / h) = clearance (ml / kg / h) x required stable level. After initial infusion for 24 h, clearance should be recalculated every day using a stationary equation using the labeled level and the known infusion dose.
The rate of injection or infusion of the drug should not exceed 2-3 ml / min.