Active substanceWillebrand factorWillebrand factor
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  • Wilfactin
    lyophilizate in / in 
    LSE Biomedication     France
  • Dosage form: & nbsplyophilizate for the preparation of a solution for intravenous administration
    Composition:

    1 bottle contains:

    Lyophilizate:

    active substance: von Willebrand factor human 1000 ME (FV: RK) *;

    Excipients: human albumin 100 mg, arginine hydrochloride 1.90 mmol, glycine 0.67 mmol, sodium citrate dihydrate 0.1 mmol, calcium chloride dihydrate 0.01 mmol.

    Solvent:

    water for injection 10 ml.

    * Activity (ME) von Willebrand factor is determined by the method of dosing the ristocetin cofactor "FV: RCO" relative to the international standard for the concentrate of von Willebrand factor (WHO). Prior to the addition of albumin, the specific activity of the preparation Vilfaktin is greater than or equal to 50 ME FV: RK / mg protein.

    The residual coagulant activity of human factor VIII contained in the preparation of Wilfactin is usually less than or equal to 10 IU / 100 ME FV: RK.

    Description:

    Lyophilizate: gigroscopic powder or amorphous mass of white or pale yellow color.

    Solvent: Pcolorless liquid

    Pharmacotherapeutic group:Hemostatic agent
    ATX: & nbsp

    B.02.B.D.10   Coagulation factor of von Willebrand

    Pharmacodynamics:

    The introduction of von Willebrand factor allows to correct hemostatic deviations in patients with a deficiency of this factor (von Willebrand disease) at two levels:

    - The von Willebrand factor restores the adhesion of platelets to the vascular subendothelium at the injury site (can bind to the subendothelium and platelet membrane), providing primary hemostasis, which is manifested in a decrease in bleeding time. This effect appears immediately and depends to a large extent on the level of multimerization of the active substance.

    - The von Willebrand factor contributes to the delayed correction of the concomitant deficiency of factor VIII (produced by the patient's body), stabilizes the content of this factor, preventing its rapid degradation.

    Replacement therapy with von Willebrand factor normalizes the factor of coagulation factor VIII after the first injection. This effect is prolonged and persists during subsequent injections of a single Wilfactin.

    Pharmacokinetics:

    A study of the pharmacokinetics of the preparation of Vilfaktin was carried out in 8 patients with type 3 von Willebrand disease by the dosing of the ristocetin cofactor (FV: RCO). The maximum concentration of the drug was noted 30-60 minutes after administration. The mean recovery is 2.1 IU / dL / IU / kg of the solution administered.

    With a single administration of Wilfactin at a dose of 100 IU / kg, the area under the concentration-time curve (AUC0-∞) is 3444 IU / hour. The average clearance is 3.0 ml / h / kg. The half-life of the drug is in the range of 8 to 14 hours (an average of 12 hours).

    With the introduction of the preparation Vilfaktin increase in the content of the factor FVIII: C occurs gradually and reaches normal values ​​after 6-12 hours. The content of FVIII: C increases by an average of 6% (6 IU / dL) per hour. Therefore, even in patients with an initial level of ΦVIII:C below 5% (5 IU / dl), from the 6th hour, the FVIII: C level reached about 40% (40 IU / dL) and was maintained for 24 hours.

    Indications:

    Prevention and treatment of bleeding (including use before planned and emergency surgical or invasive interventions to reduce blood loss) in patients with Willebrand disease.

    Contraindications:

    The drug Vilfaktin should not be used in the treatment of hemophilia A because of the low content of factor VIII.

    Age to 6 years (use of the drug in children younger than 6 years has not been studied in clinical studies).

    Pregnancy and lactation:

    Controlled studies of the drug Vilfaktin in pregnant women have not been conducted. Data on the reproductive toxicity of the preparation Vilfaktin and its intake in the milk of animals are absent.The safety of the drug Vilfaktin for pregnant women is not established, so it is not recommended to use it during pregnancy and during breastfeeding, except when the potential benefit to the mother significantly exceeds the possible risk to the fetus and the baby.

    Dosing and Administration:

    Vilfaktin is for intravenous administration only!

    Treatment with the drug Vilfaktin should be conducted under the supervision of a doctor with experience in the treatment of bleeding disorders.

    Typically, 1 IU / kg von Willebrand factor increases the level of PV: RQo in blood plasma at 0.02 IU / ml (2%). In order to ensure hemostasis, it is usually recommended to administer 40-80 IU / kg von Willebrand factor. We should strive to achieve PV levels: RQ> 0.6 IU / ml (60%) and factor VIII:C > 0.4 IU / ml (40%), because content of the factor VIII:C, equal to 0.4 IU / ml (40%), is usually sufficient to provide hemostasis.

    1. Prevention of bleeding before routine or emergency surgical interventions and treatment of bleeding (spontaneous or due to trauma).

    In the case of urgent surgical interventions, the preparation of Wilfactin should be administered one hour before the beginning of the operation.

    For planned surgical interventions, the preparation of Wilfactin should be administered 12-24 hours before the operation, then re-enter the drug 1 hour before the operation. In such a case, simultaneous administration of the coagulation factor VIII preparation is not required, since endogenous factor VIII:C to the beginning of the operation already reaches 0.4 IU / ml (40%). Nevertheless, each patient should determine the content of the factor VIII:C.

    With the introduction of a single von Willebrand factor, the content of factor VIII: C in the blood plasma increases gradually and reaches a maximum after 6-12 hours. Administration of the preparation Vilfaktin does not lead to an immediate increase in the concentration of the factor VIII:C. Therefore, if the initial level of the factor VIIT.C in plasma is below critical, and urgent correction of hemostasis is required (for example, in cases of treatment of bleeding, severe injuries or urgent surgery), then a preparation of the factor of blood coagulation VIII should be administered simultaneously with the preparation of Wilfactin in order to achieve the activity of the factor VIII:C, providing hemostasis.

    If there is no need for an urgent increase in the content of factor VIII: C (for example, in planned operations),or if the initial activity of factor VIII: C in the plasma is sufficient to provide hemostasis, the physician may decide not to use the coagulation factor VIII preparation together with the first administration of the preparation Vilfaktin.

    The dose and duration of therapy depend on the clinical condition of the patient, the type and severity of bleeding and the content of von Willebrand factor.

    The dosage regimen in children is calculated taking into account the body weight, that is, it is based on the same principles as in adults. The frequency of administration of the drug Vilfaktin should always depend on the clinical effectiveness in each individual case.

    The first injection

    For the treatment of bleeding or in severe injuries, the preparation Vilfaktin is administered in doses of 40 to 80 IU / kg in combination with the required amount of coagulation factor VIII to achieve an adequate level of activity factor VIII:C. The preparation of coagulation factor VIII is administered immediately before the operation or as soon as possible after bleeding or trauma; The dose of coagulation factor VIII is determined by its initial content in the blood plasma.

    In some cases, the preparation of Wilfactin should be administered at an initial dose of 80 IU / kg, in particular in patients with type 3 von Willebrand disease,in which maintaining adequate levels of vWF can require higher doses than with other types of von Willebrand disease.

    Follow-up treatment

    If necessary, treatment should be continued with a suitable dose of Wilfactin 40-80 IU / kg per day, in one or two injections, for one or several days. The dose and frequency of injections should always correspond to the nature of the surgical intervention, the clinical condition of the patient, the content of PV: RV and FVIII: C in the blood plasma, and the type and severity of bleeding.

    2. Prevention of spontaneous bleeding in patients with von Willebrand disease.

    Vilfaktin can be used as a long-term prophylaxis in doses individually selected for each patient. The introduction of the drug Vilfaktin in doses from 40 to 60 IU / kg 2-3 times a week can reduce the number of bleeding.

    Instructions for preparing a solution

    Wilfactin is a lyophilizate, which is dissolved immediately before use with water for injection.

    Wilfactin is administered only intravenously, as a single dose, immediately after dissolution, at a rate of no more than 4 ml per minute.

    Preparation of the solution

    Observe the usual rules of asepsis.

    1. If necessary, bring two vials (lyophilizate and solvent) to a temperature not higher than 25 ° C.

    2. Remove the plastic caps from the vials. Disinfect the surface of both plugs.

    3. Remove the protective film from the adapter.

    The bottle with the solvent is installed vertically, attach the blue side of the adapter to the vial and press the adapter all the way. The adapter must be securely connected to the vial.

    4. Remove the protective cover from the other side of the adapter.

    5. Turn the adapter connected to the solvent bottle, push it with a transparent part onto the vial with lyophilizate and secure the adapter to the stop. The solvent moves automatically into the powder vial. While holding the connected vials together, stir the solution with gentle rotational movements until the drug dissolves completely.

    6. While holding the vial with a soluble drug in one hand and a bottle of solvent in the other, unscrew the blue part of the device together with the solvent bottle.

    Usually the powder dissolves immediately, it must completely dissolve in less than 10 minutes. The resulting solution should be clear or slightly opalescent, colorless or pale yellow.Do not use a cloudy solution or solution containing a precipitate.

    7. While holding the vial vertically with the dissolved preparation, twist the sterile syringe to the device Mix2Vial. Slowly dial the drug into the syringe.

    After typing the drug into the syringe, holding it (piston down), unscrew the device Mix2Vial and replace it with an intravenous or epicranial needle.

    Remove air from the syringe, and after disinfecting the skin, insert the needle into the vein.

    Enter intravenously, slowly and without interruption, immediately after dissolving the drug, at a rate of no more than 4 ml / minute.

    From the point of view of microbiology, the drug should be used immediately after dissolution. However, he demonstrated the physicochemical stability after 24 hours storage at a temperature of 25 ° C. Any amount of unused product or remaining material must be disposed of in accordance with existing regulations.

    Side effects:

    WHO classification of unwanted drug reactions by frequency of occurrence:

    Very frequent - 1/10 appointments (≥ 10%)

    Frequent - 1/100 appointments (≥ 1%, but <10%)

    Infrequent - 1/1000 appointments (≥ 0.1%, but <1%)

    Rare - 1/10000 appointments (≥ 0.01%, but <0.1%)

    Very rare - less than 1/10000 prescriptions (<0.01%)

    The frequency is unknown - can not be set based on the available data.

    The following are undesirable drug reactions according to the classification MedDRA:

    From the immune system: infrequently - hypersensitivity reactions or allergic reactions; In very rare cases, severe anaphylactic reactions (Quincke's edema or anaphylactic shock) can develop.

    Disorders of the psyche: infrequently - anxiety.

    From the central nervous system: infrequently - a headache, drowsiness.

    From the heart: infrequently - a tachycardia.

    From the side of the vessels: infrequently - hypotension, hot flashes.

    From the respiratory, thoracic and mediastinal organs: infrequently - shortness of breath.

    From the gastrointestinal tract: infrequently - nausea, vomiting.

    From the skin and subcutaneous tissues: infrequently - a rash, generalized urticaria, skin itch, a feeling of "crawling creepy."

    General disorders and reactions at the site of administration: infrequent - burning or tingling at the injection site, chills, a feeling of restraint of breathing; rarely - a fever.

    Other: very rarely - the formation of neutralizing antibodies (inhibitors) to the von Willebrand factor, especially in patients with type 3 von Willebrand disease.

    In a clinical study of Wilfactin in 62 patients, of whom 23 were of the third type of vWD, no formation of neutralizing antibodies was observed after the administration of Wilfactin. The presence is manifested in the form of an inadequate clinical response (the expected level of EF: RBC in the blood plasma is not achieved, or bleeding is difficult to control with an adequate dose of the drug) and may be associated with an increased risk of anaphylactic reactions.

    Overdose:

    No cases of an overdose of the drug Vilfaktin have been reported.

    Possible development of thromboembolic complications in the case of a significant overdose of the drug.

    Interaction:

    Wilfactin should not be mixed with other medications.

    Only polypropylene injection / infusion products should be used, since the adsorption of human plasma proteins on the internal surfaces of some infusion materials may result in ineffective treatment.

    Clinically significant interactions of the drug Vilfaktin with other drugs are not known.

    Special instructions:

    The use of the drug Vilfaktin in patients who have not previously received von Willebrand factor therapy has not been studied in clinical studies.

    In cases of bleeding in patients at the initial stage of treatment, it is recommended to enter factor VIII simultaneously with Wilfactin.

    Patients should be monitored throughout the period of drug administration to identify early signs of allergic or anaphylactic reactions. Patients should be informed of early manifestations of hypersensitivity reactions, including pruritus, urticaria, chest tightness, dyspnoea, hypotension and anaphylactic reactions. If such symptoms appear, discontinue the drug immediately. With anaphylactic shock treatment is conducted in accordance with current recommendations.

    There is a risk of thromboembolic complications, especially in patients with risk factors. Therefore, patients from the risk group should be observed to identify early signs of thrombosis. Prevention of venous thromboembolism should be carried out in accordance with current recommendations.

    After correcting the lack of von Willebrand factor, due to the possible risk of thrombosis, early signs of thrombosis or disseminated intravascular coagulation should be identified andprevent thromboembolic complications in accordance with current recommendations.

    In patients with von Willebrand disease, especially type 3, neutralizing antibodies (inhibitors) to the von Willebrand factor can be formed. The presence of inhibitors manifests itself in the form of an inadequate clinical response (the expected level of EF: RBC in the blood plasma is not achieved, or bleeding is difficult to control an adequate dose of the drug). If the expected EF: plasma in the plasma is not reached, or if bleeding is difficult to control with an adequate dose, laboratory tests should be conducted to determine the presence of PV inhibitors. In patients with a high level of inhibitors, the use of the drug Vilfaktin may not be effective enough and other therapeutic options should be considered. Treatment of such patients should be performed by a doctor with experience in the treatment of blood clotting disorders.

    The presence of inhibitory antibodies to von Willebrand factor may be associated with an increased risk of anaphylactic reactions. Therefore, in all patients with anaphylactic reactions or in case of ineffective treatment, it is necessary to conduct appropriate biological studies to determine the presence of inhibitors.

    Standard measures to prevent the risk of transmission of infectious agents through drugs prepared from human blood or plasma include: clinical selection of donors, screening of individual blood samples and batches of plasma for specific markers of infections. Procedures for inactivation and removal of viruses are included in the production process. However, when using drugs made from human blood or plasma, the risk of transmission of infectious agents can not be completely ruled out. This also applies to unknown or only detectable viruses or other types of infectious agents.

    The drug is effectively protected against enveloped viruses: HIV, hepatitis B and C. There is no full guarantee of protection against non-enveloped viruses - hepatitis A and parvovirus B19. Parvovirus B19 is most dangerous for pregnant women (fetal infection), for people with immunodeficiency and for patients with hemolytic anemia.

    Patients who are systematically receiving therapy with coagulation factors are advised to undergo the necessary vaccination against hepatitis A and B. It is strongly recommended that, at each injection of the drug, register its serial number indicated on the vial,to monitor the relationship between the patient and the drug used.

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

    Vilfaktin does not affect the ability to drive vehicles and engage in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

    Form release / dosage:

    Lyophilizate for the preparation of a solution for intravenous administration of 1000 IU / complete with a solvent - water for injection.

    Packaging:

    By 1000 ME human von Willebrand factor in a vial of transparent colorless glass type I (Hebrew F) with a capacity of 30 ml, sealed with a halobutyl rubber stopper, crimped on top with an aluminum cap with an orange plastic lid to control the first opening.

    10 ml of solvent - water for injection - into a bottle of transparent colorless glass type II (Hebrew F.) with a capacity of 10 ml, sealed with a halobutyl rubber stopper, crimped from above with an aluminum cap with a blue plastic lid for monitoring the first opening.

    1 adapter for bottles "MIX2VIAL™ "made of polycarbonate plastic, equipped with a filter with a nominal pore diameter of 50 μm, in an individual transparent polyethylene cell packaging, covered with a film of PEVD (Tyvek®).

    1 vial with lyophilizate and 1 vial with a solvent, 1 cell pack with a vial adapter, together with the instruction for use, will be prevented in a cardboard box.

    Storage conditions:

    Store in a consumer package, protected from light, at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Do not freeze.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-002093
    Date of registration:04.06.2013
    Expiration Date:04.06.2018
    The owner of the registration certificate:LSE BiomedicationLSE Biomedication France
    Manufacturer: & nbsp
    Representation: & nbspRAYFARM, LLCRAYFARM, LLC
    Information update date: & nbsp15.02.2017
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