VILATE

Active material: human coagulation factor VIII, von Willebrand factor
When ATH: B02BD06
CCF: The drug factors (VIII and Willebrand) clotting
ICD-10 codes (testimony): D66, D68.0, D68.4
When CSF: 20.01.06
Manufacturer: MANIFOLD GROWTH Pharmazeutika Produktionsges m. b. H. (Austria)

Pharmaceutical form, composition and packaging

Valium for drug of a solution for / in in the form of powder or amorphous masses almost white or light yellow in colour.

Excipients: glycine, sucrose, sodium citrate, sodium chloride, calcium chloride.

Solvent: 0.1% r-r polisorbata 80 d/in the water and – 5 ml.

Glass Bottles (1) – packs cardboard; together with the solvent (fl.) and set for the on/in the introduction (a disposable syringe, A two needle, Needle filter, needle-butterfly, 2 des. napkins) in a separate paper cartons.

Valium for drug of a solution for / in in the form of powder or amorphous masses almost white or light yellow in colour.

Excipients: glycine, sucrose, sodium citrate, sodium chloride, calcium chloride.

Solvent: 0.1% r-r polisorbata 80 d/in the water and – 10 ml.

Glass Bottles (1) – packs cardboard; together with the solvent (fl.) and set for the on/in the introduction (a disposable syringe, A two needle, Needle filter, needle-butterfly, 2 des. napkins) in a separate paper cartons.

Pharmacological action

Hemostatic drug. The effectiveness of coagulation factor VIII (FVIII) determined on the basis of the international standard for concentrate (FVIII:C), effectiveness of von Willebrand factor (FV) determined on the basis of the determination of the effectiveness of ristocetinovogo cofactor (FV:RK), based on the international standard for concentrate FV in accordance with the European Pharmacopoeia.

The specific activity of the drug Vilatesostavljaet not less than 60 ME FVIII:C/mg and not less than 53 ME FV:RC/mg total protein.

Von Willebrand Disease

The drug contains Vilate FV, which is a normal component of human plasma and has the same effect, as endogenous FV.

Application of FV corrigiruet Hemostatic disorders in patients with the deficiency of FV as follows:

-FV restores adhesion of platelets to sosudistomu subjendoteliju in the place of damaged vessel (through attachment to sosudistomu and subjendoteliju to the membrane of platelets), providing these primary hemostasis, that is manifested by the reduction of the time. This effect manifests itself immediately and to a great extent depends on the level of protein polymerization.

— Detains a concomitant deficit correction FV FVIII. When in/with the introduction of FV binds endogenous FVIII (contained in the patient's plasma) and stabilizes its, slowing its rapid degradation. Thanks to this, application of pure PV (the drug PV with low content of FVIII) FVIII level is recovers to normal, as a secondary effect. Application Of FV, contains FVIII, immediately restores the level of FVIII:(C) to normal.

Hemophilia A

Complex of FVIII/FV consists of two molecules (FVIII and FV) with different physiological functions. With the introduction of the drug in patients with hemophilia, FVIII binds krovenosnom line with FV, activated FVIII (FVIIIa) acts as a cofactor to activated FIX (FIXa), accelerating the transition factor out X in the active form (FHa). FHa activates transition protrombina in trombin. Thrombin, in turn, activates transition Fibrinogen in fibrin, with the subsequent formation of a blood clot. Hemophilia A, concatenated with the floor, – an inherited clotting disorder, due to the reduced level of FVIII:FROM, that manifests itself in the form of profuzhnykh hemorrhage into joints, muscles or internal organs, as spontaneous, and as a result of trauma or surgical interventions. Hormone replacement therapy can increase plasma FVIII, providing the temporary deficit correction factor and decreasing the tendency to bleeding.

In addition to the role of FVIII-stores protein, FV promotes adhesion of platelets in the zone of damage to blood vessels and plays a significant role in the process of aggregation of platelets.

Pharmacokinetics

Von Willebrand Disease

The product contains human FV, which is a normal component of human plasma and has the same effect, as endogenous FV.

The average recovery of FV:RK and FV:AG in patients with von Willebrand disease 3 type varies between 68 and 99% respectively. These values correspond to the average increase level in plasma 1.5 and 2.1% on zameshhennuju IU/kg body weight. The half-life of FV:RC is about 17.5 no., clearance – 3.9 ml / h / kg.

Hemophilia A

The product contains human FVIII, which is a normal component of human plasma and has the same effect, as endogenous FVIII. After the introduction of the drug level of FVIII:With the plasma reaches 80-120% of the estimated. The half-life of FVIII:With is about 14.8 no, that corresponds to the biological half-life period. Clearance is 2.9 ml / h / kg.

Testimony

-treatment and prevention of bleeding in von Willebrand disease (When quantitative and/or qualitative deficiency of von Willebrand factor);

-treatment and prevention of bleeding in congenital hemophilia a;

is the treatment and prevention of bleeding in patients with the acquired deficiency of coagulation factor VIII.

Dosage regimen

Dose and duration of treatment depend on the degree of deficiency of coagulation factors, localization and severity of bleeding and the clinical condition of the patient. Treatment should consult doctors with experience of patients with coagulation disorders.

Drug Vilate introducing/in, After the dissolution of the annexed solvent (0.1% solution polisorbata 80 water for injection), the resulting solution contains 90 ME and FVIII 80 ME at PT 1 ml.

Von Willebrand Disease

The ratio between FVIII:With and FV:RK is approximately 1:1, average – 1 IU / kg body weight. FVIII:With and FV:RK increases plasma levels at 1.5-2% from the normal activity of the corresponding protein. Usually to achieve adequate hemostasis requires dose Vilate from 20 to 50 IU / kg body weight, This increases the level of FVIII:With and FV:Of the REPUBLIC of KAZAKHSTAN to 30-100%.

The initial dose of the drug can reach 50-80 IU / kg body weight, especially in patients with von Willebrand disease 3 type, where necessary to maintain plasma levels requires higher doses, than other types of. In addition to this, patients with gastrointestinal bleeding higher source and supporting dose.

Prevention of bleeding in case of surgical procedures or when extensive injury: to prevent bleeding, you must start the preparation for Vilate 30 minutes before the start of surgery. In the case of elective surgery, you must first enter the preparation for 12-24 h and over 1 hours before surgery, at this level should be obtained from the FV:RK ≥ 60 IU/DL (≥ 60%) and FVIII:With ≥ 50 IU/DL (≥ 50%).

The appropriate dose should be every 12-24 no. Dose and duration of therapy depends on the clinical condition of the patient, the type and severity of bleeding, the level of FVIII:With and FV:RK.

When applying the preparations FV, containing FVIII, it should be understood, that prolonged treatment may cause an excessive increase in the level of FVIII:FROM. After 24-48 h treatment to avoid excessive increase of level of FVIII:(C) the need to reduce the dose or increase the interval between wvedeniami.

Hemophilia A

Dose and duration of treatment depend on the degree of deficiency of FVIII, localization and duration of bleeding, clinical status of the patient.

The number of units used FVIII is expressed in international units (ME), relevant standards for drugs FVIII. FVIII activity is expressed as a percentage or (relative to a normal content of factor in human plasma), or in International Units (on the international standard for the plasma FVIII).

1 International Unit (ME) FVIII is equivalent to the number in FVIII 1 ml of normal human plasma.

Calculation of the required doses of FVIII is based on empirically the results, whereby 1 ME FVIII:C/kg body weight increases the level of factor in plasma 1.5-2% from the normal content. The required dose is determined by the following formula:

The required dose = weight (kg) × desired increase the level of FVIII (%) × 0.5 IU / kg

The number and frequency of application of FVIII must comply with clinical efficiency in each individual case. Info, presented in table, can be used for the selection of doses during episodes of bleeding and surgical interventions at the Adult and older children 6 years.

In cases of bleeding, This table, the level of FVIII activity:(C) must not fall below the baseline in plasma (% from the normal content) at the relevant time.

During the treatment it is recommended to determine the level of FVIII:(C) for the regulation and correction of applied dose and frequency of introductions. When conducting a large surgical interventions need to control carried out treatment based on the results of coagulation diagram.

Response to the introduction of the drug in patients is unique, for some patients, there are differences in the level of increase factors in plasma and T values_1/2.

To prolonged prevention of bleeding in severe hemophilia a You must enter a drug dose of Vilatev 20-40 IU / kg of body weight every 2-3 day. In some cases, particularly in young patients, You may need to reduce the interval between wvedeniami or an increase in dose.

Terms of preparation of the solution

1. Solvent (0.1 % solution polisorbata 80 d/in the water and) and valium in the closed bottle to bring to room temperature. If a solvent is used for warming water bath, should closely monitor the, do not allow water to come into contact with rubber Stoppers or lids of vessels. The temperature of the water bath did not exceed 37 ° C..

2. Remove protective caps from bottles with lyophilized powder and solvent, disinfect rubber Stoppers bottles one of disinfectant wipes.

3. The short end of the double ended needle to release from plastic packaging, Pierce them in the Center cap of the vial with the solvent and push down until it stops. Invert the vial with the solvent together with needle, free the long end dvuhkoncevoj needle from the plastic packaging, Pierce them in the center of the Cork of the bottle with liofilizatom and push down until it stops. The vacuum in the vial will draw water with lyophilisate.

5. An empty bottle of solvent separated along with a needle from the vial with liofilizatom. The drug quickly dissolves, To do this, the vial should be gently shake.

To use only clear or slightly Opalescent solution, no sediment.

Terms of administration of the solution

Cooked solution of the drug should be entered directly after dissolution. As prevention should monitor heart rate before the introduction and during the introduction. When expressed increasing pulse rate should suspend the imposition or reduce injection speed.

1. Filter needle pierced the rubber stopper of the vial with lyophilized powder rastvorivshimsja.

2. The other end of the needles coupled with disposable syringe.

3. Turn the bottle and get the solution in the syringe.

4. Disinfect the skin at the injection site.

5. Release syringe with the solution from the filter needle and attach the needle tie.

6. Enter a solution into the vein at a speed 2-3 ml / min.

Any unused solution of the drug should be disposed of in accordance with existing rules.

Side effect

Allergic reactions: possible urticaria, skin rashes, hypersensitivity reactions, accompanied by a decline in AD, a feeling of constriction of the chest, shortness of breath, chills; rarely – anaphylactic shock.

Von Willebrand disease, especially 3 type, the development of ingibitoryh antibodies to FV (accompanied by inadequate clinical response to the introduction of the drug). Inhibitory antibodies can cause pretipitatia and contribute to the development of anaphylactic reactions.

In patients with hemophilia and possibly the development of ingibitornyh FVIII antibody (accompanied by inadequate clinical response to the introduction of the drug).

From the blood coagulation system: There is a risk of thrombotic complications, especially in patients with known clinical and laboratory risk factors.

Patients, receiving drugs FV, containing FVIII, prolonged increased plasma levels of FVIII:(C) increases the risk of thrombotic phenomena.

CNS: headache, drowsiness, apathy, anxiety.

From the digestive system: nausea, vomiting.

Other: Perhaps the sense of stinging in introducing; rarely during the introduction – fever.

Contraindications

- Children up to age 6 years (the lack of data);

-hypersensitivity to coagulation factor VIII, Von Willebrand factor and/or other components of the drug.

Pregnancy and lactation

Use of the drug during pregnancy and lactation is possible only if, the projected benefits of therapy to the mother outweighs the potential risk to the fetus and infant.

Cautions

Possible reactions of hypersensitivity, as with the introduction of other drugs of protein origin. With the introduction of the drug should be carefully monitored patients.

Early signs of hypersensitivity reactions are urticaria, generalized rash, a feeling of constriction of the chest, breathlessness, the decline ad and Anaphylaxis. In case of these symptoms should immediately discontinue administration of the drug. In the case of shock should apply modern methods of antishock therapy.

In the case of the use of drugs, derived from human blood or plasma, the possibility of transmitting infectious agents can not be completely ruled. This also applies to agents currently unknown diseases. The risk of transmission of these infections, Nonetheless, significantly reduced by screening in healthy donors, blood and plasma screening for the presence of hepatitis b virus antigens, antibodies to HIV 1 and 2, hepatitis c virus, analysis of plasma fractions for the presence of hepatitis c virus genetic material, procedures for the inactivation/removal of viruses, included in the manufacturing process, which were confirmed on the viral model. These procedures are highly effective in inactivating/removing viruses hepatitis a, IN, FROM, HIV 1 and 2, but may have limited effectiveness against bezobolochechnyh virus, such as Parvovirus B19. Parvovirus B19 can cause serious reactions in pregnant women (intrauterine infection), as well as in patients with immune deficiency or in certain types of anemia (eg, hemolytic anemia).

We recommend preventive vaccination against hepatitis a and b all patients, using any blood products.

In applying the drug need to monitor the possibility of Vilate patient ingibitornyh FVIII antibody. In the absence of the effect of adequate dose or if it is not possible to attain the desired level of plasma FVIII adequately its introduction, you need to test for the presence of Bethesda ingibitornyh FVIII antibody. In patients with a high level of FVIII therapy inhibitors may be ineffective, This might require other treatment. Treatment of such patients should consult doctors with experience of patients with coagulation disorders. To detect early symptoms of thrombosis risk group patients requires control. Prevention of thrombotic complications should be carried out in accordance with modern requirements.

You should not use other drugs during drug administration Vilate.

For injection Vilate should only be provided by complete set for the dissolution and/introduction. Other devices able to adsorb coagulation factors on its inner surface, the resulting decrease in the effectiveness of treatment.

Von Willebrand Disease

When applying the preparations FV, containing FVIII, the attending physician must be prepared to, that prolonged treatment may cause an excessive increase in the level of FVIII:FROM. Patients, long-term receiving such drugs, requires monitoring of FVIII:FROM, in order to avoid a prolonged increase plasma levels of FVIII:FROM, that may increase the risk of thrombosis.

There is a risk of thrombotic complications in applying drugs FV, containing FVIII, especially in patients with known clinical and laboratory risk factors. Therefore, to detect early symptoms of thrombosis risk group patients requires control. Prevention of thrombotic complications should be carried out in accordance with modern requirements.

In patients with von Willebrand disease, especially 3 type, the development of ingibitoryh antibodies to FV. In this case, noted inadequate clinical response to the introduction of the drug. Inhibitory antibodies can cause pretipitatia and contribute to the development of anaphylactic reactions. Patients develop anaphylactic reactions must be inspected for the presence of ingibitornyh antibodies. In such cases it is advisable to apply to specialized hematology / Haemophilus centers.

Hemophilia A

Ingibitornyh FVIII antibody formation is a well-known complication in patients with hemophilia a. In the case of inadequate clinical response to the introduction of the drug are advised to refer to specialized centres gemofil'nye/hematologic. Usually, inhibitory antibodies are IgG antibodies, against FVIII activity prokoaguljantnoj, and defines the modern methods of research (test Bethesda) the Modified Units Bethesda per ml of plasma. The risk of ingibitornyh antibodies correlate with the appointment of FVIII, reaching a peak during the first 20 days after the appointment of the. Less inhibitory antibodies develop after the first 100 days of the drug. Patients, receiving treatment FVIII, It should be carefully inspected to detect ingibitornyh antibodies. Possibility of the use of the drug in the presence ingibitornyh Vilate antibodies to FVIII in clinical trials is not installed.

Use in Pediatrics

The use of the drug have Vilate children under 6 years cannot be recommended in connection with the insufficient data.

Effects on ability to drive vehicles and management mechanisms

Vilate drug use has no negative impact on the ability to drive or complex machines.

Overdose

The cases of drug overdose not Vilate noted. It is not recommended to exceed the assigned dose.

Drug Interactions

Vilate drug interaction data with other drugs not available.

Drug Vilatene should be mixed with other drugs or enter at the same time, using the same infusion set.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dark place at a temperature of 2 ° to 8 ° C; Do not freeze. Shelf life – 2 year.