Treatment should be performed by a doctor who has experience in treating hemophilia.
The dose and duration of substitution therapy depends on the severity of the deficiency of the coagulation factor VIII, the localization and severity of bleeding, and the clinical condition of the patient.
The number of units of factor VIII administered is measured in international units (ME), which corresponds to the current standard of the World Health Organization (WHO) for preparations containing coagulation factor VIII. The activity of factor VIII in plasma is expressed as a percentage (relative to normal human plasma) or in ME (relative to the International Standard for Factor VIII Content in Plasma).
One ME activity of factor VIII is equivalent to the amount of factor VIII in one milliliter of normal human plasma.
Calculation of the required dose factor VIII is based on an empirically revealed regularity, according to which 1 ME factor VIII per kilogram of body weight increases the activity of plasma factor VIII by approximately 2% of normal activity (or 2 IU / dl). The required dose is calculated using the following formula:
Required number of units = body weight [kg] x required increase in factor VIII [% or IU / dL] x 0.5.
The dose and frequency of the administration should always be calculated taking into account the clinical effectiveness in each individual case.
In the cases of bleeding described in the table below, the activity of factor VIII for the relevant period should not be lower than the plasma activity level indicated in the table (in % from the normal level or in ME / dL).
Table of calculation of doses of the drug for bleeding and in surgical practice:
| Severity of bleeding / type of surgical procedure | Required level of factor VIII (% or IU / dl) | Frequency of doses (hours) / duration of therapy (days) |
| Bleeding: |
|
|
| Early hemarthrosis, muscle or mouth bleeding | 20 - 40 | Repeated infusion of the drug every 12-24 hours. At least 1 day, until the bleeding stops (according to pain) or healing occurs. |
| More massive bleeding, muscle bleeding or bruising | 30-60 | Repeated infusions of the drug every 12-24 hours for 3-4 days or more, until the pain syndrome or severe disability disappears. |
| Life-threatening bleeding | 60-100 | Repeated infusions every 8-24 hours to eliminate the threat to life. |
| Surgery: |
|
|
| Small, including tooth extraction | 30-60 | Every 24 hours, at least 1 day, until healing takes place. |
| Large | 80-100 (before and after surgery) | Repeated infusions every 8-24 hours until adequate wound healing, then therapy for at least 7 days to maintain the activity of factor VIII at a level of 30-60% (ME / dL). |
During the course of treatment, it is recommended to determine the level of factor VIII in order to calculate the administered dose and the frequency of infusions. With extensive surgical intervention, monitoring of substitution therapy with coagulation analysis (activity of plasma factor VIII) is mandatory. There is a significant individual variability in the response to treatment with factor VIII, in vivo demonstrating different recovery rates and half-lives.
With the long-term prophylaxis of bleeding in patients with severe hemophilia A, factor VIII is normally administered at a dose of 20-40 IU / kg with an interval of 2-3 days.
In some cases, especially in young patients, shorter intervals and higher doses may be required.
Calculation of the doses of the drug is based on body weight, so when determining the doses in children, the same calculation formulas are used as in adults. When determining the frequency of drug administration, clinical efficacy in each individual case must be considered. There is some experience in treating children younger than 6 years.
It is necessary to monitor the production of factor VIII inhibitors in patients. If the expected level of factor VIII activity is not achieved with the preparation or if bleeding is stopped when the calculated dose is administered, an analysis should be carried out for the presence of factor VIII inhibitors. In patients with a high content of inhibitors, factor VIII therapy may not be effective, and in such cases alternative treatment should be considered. The management of such patients should be carried out by physicians with experience in the treatment of patients with hemophilia.
Instructions for preparing a solution
General instructions:
1. The reconstituted lyophilizate solution varies from clear to slightly opalescent. After filtration and before administration, it is recommended to visually check the reconstituted product for the presence of particles and discoloration. Do not use a cloudy solution or solution containing sediment and / or inclusions.
2. The solution is reconstituted and uncorked in aseptic conditions.
3. Remains of the drug and packaging after use should be disposed of in accordance with local requirements.
Solution recovery:
Heat the solvent to room temperature. Make sure that the caps from the bottles with the solvent and the preparation are removed, the plugs are treated with an antiseptic solution and dried before opening the device for adding a solvent with a built-in filter *.
1. Open the blister pack of the device for adding solvent with the built-in filter by removing the top part of the package. Do not remove the device from the blister pack!
2. Place the solvent vial on a flat, clean surface and hold the vial tightly.Take the device for adding the solvent with the built-in filter together with the blister packing and the sharp core of the blue part of the device pierce the stopper of the vial with the solvent, pressing vertically downwards.
3. Carefully remove the blister pack from the solvent addition device by holding it by the edges and pulling it vertically upwards. Make sure that you have removed only the blister pack, not the device itself.
4. Place the vial on the drug on a firm, level surface. Turn over the solvent bottle together with the solvent addition device attached to it and with the sharp rod of the transparent part of the device, pierce the stopper of the vial with the drug, pressing vertically downwards. The solvent will automatically move into the vial with the drug.
5. With one hand firmly holding the device for adding the solvent from the side of the vial with the drug, and the other hand - from the side of the vial from the solvent, gently unfold the device in two parts. Flask from the solvent with the blue part of the device should be thrown away.
6. Carefully twist the vial of the drug with the attached transparent part of the device until the lyophilizate is completely dissolved. Do not shake the bottle.
7. Insert air into an empty sterile syringe and, while holding the vial of the drug in the upright position, attach the syringe to the Luer tip on the solvent addition device with the built-in filter. Enter the air into the vial with the drug solution.
Fence and disposal of the drug
8. By pressing the plunger of the syringe, flip the bottle together with the syringe, and then, slowly pulling the plunger of the syringe, dial into it the reconstituted solution of the preparation.
9. After the reconstituted drug solution is recruited into the syringe, grasp the syringe barrel (holding the syringe down with the piston) and detach the transparent part of the device for adding the solvent from the syringe.
* The device for adding a solvent with a built-in filter is intended for single use; Do not use the device in the event of damage to the package and after the expiry date indicated on the paper part of the blister package as follows: "EXP.year-month"
For injections of Beriaté® it is recommended to use disposable plastic syringes, since the solution can remain on the glass walls of the all-glass syringes.The drug should be heated to room temperature or body temperature before administration. The drug should be administered slowly intravenously at a rate that does not cause discomfort to the patient, after making sure that the blood does not enter the syringe with the drug. The rate of drug administration should not exceed 2 ml per minute.
It should be carefully monitored for the patient to develop an allergic reaction of an immediate type. If the patient has a reaction that can be caused by the introduction of Beriathe®, it is necessary to reduce the rate of drug administration or to stop the administration depending on the clinical state of the patient.
The reconstituted solution remains chemically and physically stable for 8 hours at a temperature of 25 ° C. However, in terms of biological stability, the reconstituted solution should be administered immediately after dilution. Storage of the reconstituted solution should not exceed 8 hours at room temperature.