Treatment should be carried out by a doctor who has experience in the treatment of hemophilia.
The dose and duration of substitution therapy depend on the extent of factor IX deficiency; localization and severity of bleeding, as well as the clinical state of the patient.
The amount of factor IX administered is expressed in international units (ME), which comply with the current WHO standard for preparations containing coagulation factor IX. The activity of factor IX in the blood plasma is expressed either as a percentage (corresponds to normal human blood plasma), or in international units (corresponds to the International Standard for factor IX in blood plasma).
One international unit (ME) of factor IX activity is equivalent to the same amount of factor IX in one milliliter of normal human plasma. The calculation of the required dose of factor IX is based on the results of empirical studies showing that the administration of 1 IU of factor IX per kg of body weight increases the activity of this factor in blood plasma by 1.0% of its normal activity.
The required dose of the drug is calculated by the following formula:
Required number of units of the preparation = body weight (kg) x desired level of increase in the activity of factor IX [% or ME / dL] x 1.0 *
* is the reciprocal of the observed restoration.
When determining the amount of factor IX to be prescribed, the choice of the route of administration, and the frequency of drug administration, one should always be guided by the therapeutic effect of the drug in each individual case. With bolus administration of factor IX, its administration is rarely required more than 1 time per day.
If the bleeding events listed below develop, the activity of factor IX should not decrease below the established level of activity in blood plasma (in% of normal activity or ME / dL) for the relevant period.
Recommendations for dosing regimens for bleeding episodes and surgical interventions are given in the following Tables 1 and 2.
Table 1. Single intravenous injection
| Severity of bleeding / Type of surgical procedure | Required factor level IX (% or IU / dl) | Frequency of drug administration (hours) / Duration of treatment (days) |
| Bleeding | | |
| Early hemarthrosis, muscle or oral bleeding | 20-40 | Repeated administration every 24 hours. For at least 1 day, until bleeding stops (based on pain syndrome) or healing. |
| More extensive hemarthrosis, muscle bleeding or bruising | 30-60 | Repeated infusions every 24 hours for 3-4 days or more until the disappearance of pain and recovery of work capacity. |
| Life-threatening bleeding | 60-100 | Repeated infusions every 8-24 hours until the threat to life disappears. |
| Surgical interventions | | |
| Small surgical interventions, including tooth extraction | 30-60 | Every 24 hours, at least 1 day, until healing. |
| Large surgical interventions | 80-100 (pre- and postoperative period) | Repeated infusions every 8-24 hours until a sufficient degree of wound healing is achieved, then treatment is continued, at least,for 7 days to maintain the activity of factor IX in the range of 30% to 60% (IU / dL). |
Table 2. Long-term infusions in the performance of surgical interventions
| Desirable levels of factor IX to provide hemostasis | 40-100% (or IU / dl) |
| To achieve the desired level of factor IX, the initial loading dose | Single bolus injection 90 ME per kilogram (range 75-100 IU / kg) of body weight or dosing based on pharmacokinetic parameters of the preparation. |
| Frequency of drug administration | Continuous intravenous infusion, depending on the clearance and the established values of the level of factor IX. |
| Duration of treatment | Up to 5 days. Depending on the type of surgery, longer treatment may be required. |
During the course of treatment, in order to establish the necessary dose of the drug and the frequency of repeated infusions, it is recommended that the levels of factor IX in the blood be appropriately determined. In particular, with extensive surgical interventions, it is necessary to carefully monitor the replacement therapy by means of a blood coagulation assay (factor IX activity in the blood plasma).In individual patients, the response to factor IX therapy may differ, but they achieve different recovery rates activity of the drug in vivo, and there is a different duration of the period elimination half-life.
For long-term prophylaxis of bleeding in patients with severe hemophilia B the usual dose is 20-40 IU of factor IX per kg of body weight at intervals of 3-4 days. In some cases, especially in young patients, it may be necessary to reduce the duration of the intervals between administration of the drug or the use of higher doses.
Patients should be monitored for the formation of factor IX inhibitors. If the expected level of activity of factor IX in the blood plasma can not be achieved or if there is no control over bleeding against the recommended dose, an analysis should be performed to determine the inhibitors of factor IX. In patients with a high concentration of a factor IX inhibitor, treatment may be ineffective, in which case other methods of treatment should be considered.
Observation of such patients should be carried out by physicians,who have experience in the treatment of patients with hemophilia.
Special patient groups
Children
Safety and efficacy of Mononain® in children with prolonged infusion have not been studied. In this regard, the possibility of using a prolonged infusion of Mononain® in children and adolescents should be considered only if received before surgery pharmacokinetic data for calculating the dose (i.e., the degree of recovery and clearance) and with careful monitoring of the concentration of Factor IX in the perioperative period.
Instructions for preparing a reconstituted drug solution
General Instructions
- Restoration of the preparation and extraction of the finished solution from the vial should be carried out under aseptic conditions.
- Typically, the reconstituted solution is colorless or slightly opalescent. After filtration, the solution or extract, and also before its introduction reconstituted preparation should be visually observed pas presence of particulate matter and discoloration. Do not use turbid solutions or solutions containing a precipitate (precipitate and / or particles).
Recovery
Bring the solvent to room temperature.Ensure that the lids from the vials with the solvent and the preparation are removed, the plugs are treated with an antiseptic solution and dried before opening the package with a device for adding a solvent with a built-in filter *.
Attention! The packaging of Mononain® can contain two types of device for adding a solvent with a built-in filter Mix2VialTM 20/13 or Mix2VialTM20/20.
Depending on the device you are using, follow the instructions below.
If using a device for adding a solvent with a built-in 15 μm filter Mix2 Vial ™ 20/13:
1. After removing the lid, open the blister pack with the device for adding the solvent with the built-in filter.
2. Caution, without touching the tip of both ends of the double-ended needle, remove the device from the package. Place the solvent bottle on a flat and clean surface and squeeze tightly in your hand. Puncture the blue end of the device with a flask of solvent.
3. Place the vial with lyophilizate on a flat surface. Turn the solvent flask over with the solvent addition device attached to it, and then pierce the stopper of the vial with the lyophilizate on the transparent part of the device. The solvent will automatically move into the vial with lyophilizate.
4. Without separating the vials, gently rotate the vial with the lyophilizate to ensure that the lyophilizate is completely dissolved. Do not shake the bottle.
5. Unscrew the device for adding the solvent with the built-in filter into two parts, compressing the end of the system in one hand, attached to a vial with a dissolved preparation, and in the other hand - the end of the system attached to a bottle of the solvent.
Collect air into an empty sterile syringe. While holding the bottle upright in a vertical position, attach the syringe to the device for adding the solvent. Enter the air into the vial with the drug solution.
Extraction and application.
6. Pressing the plunger of the syringe, flip the bottle together with the syringe and then, slowly pulling the syringe piston, dial into it the reconstituted solution of the preparation.
7. After the reconstituted solution of the drug is dialed into the syringe, detach the transparent part of the device to add the solvent from the syringe while holding the syringe down with the piston.
* Device for adding a solvent with a built-in filter Mix2VialTM 20/13 is intended for single use only; Do not use the device in case of damage.packaging and after the expiry date indicated on the paper part of the blister pack as follows: "EXP.year-month".
In the case of using a device for the addition of a solvent with a built-in 15 μm filter Mix2Vial™ 20/20:
1. Open the blister pack of the solvent adding device with the built-in filter by removing the top of the package. Do not remove the device for adding the solvent with the built-in filter 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 edge and pulling it vertically upwards. Make sure that you have removed only the blister pack, not the device itself.
4. Place the preparation vial on a hard, level surface and flip a solvent vial over it with the solvent addition device attached to it andwith a sharp core of the transparent part of the device for adding the solvent, 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, grasp the device for adding a solvent from the side of the vial with the drug, the other from the side of the vial with the solvent and gently unfold the device into two parts. The solvent bottle with the blue part of the device for adding the solvent should be discarded.
6. Carefully twist the vial with the drug and attached to it a transparent part of the device to add the solvent until the drug 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.
Extraction and application
8. Pressing the plunger of the syringe, flip the bottle together with the syringe and then, gradually pulling the syringeaboutsyringe, add a reconstituted solution of the drug into it.
9. After the reconstituted solution of the drug is dialed into the syringe, detach the transparent part of the device to add the solvent from the syringe, while holding the syringe with the piston down.
* Device for adding a solvent with a built-in filter Mix2Vial™ 20/20 is intended for single use only; 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."
Method of administration
Restore the drug according to the above instructions for preparing a reconstituted solution of the drug.
The drug Mononain® should be heated to room temperature or body temperature before administration.
The drug Mononain® should be administered intravenously slowly to detect allergic reactions of immediate type. If any potentially drug-related reaction occurs during the administration, the infusion rate should be reduced until the drug is discontinued depending on the clinical condition of the patient.
Single intravenous injection
Perform venipuncture using a suitable set for intravenous administration.Enter intravenously slowly with a patient comfortable for the patient (maximum injection rate 2 ml / min).
Prolonged infusion
The drug Mononain® should be reconstituted with water for injection according to the above instructions for preparing a reconstituted drug solution. After recovery, the drug Mononain® can be used as a continuous infusion undiluted with the help of an infusomat or ergusor (syringe pump for long infusions).
The activity of the undiluted reduced Mononain® preparation is approximately 100 IU / ml.
The diluted solution is obtained as follows:
- dilute the reconstituted filtered solution by transferring the appropriate amount of the preparation to the desired volume of the isotopic solution under aseptic conditions;
- in solutions diluted to a ratio of 1:10 (factor IX concentration 10 IU / ml), the activity of factor IX remains stable up to 24 hours;
- at higher dilutions the activity of factor IX may decrease. To maintain the required level of factor IX in the blood, it is necessary to monitor its activity.
Example for breeding 500 ME reconstituted Mononain® solution:
| The target activity of the diluted solution | 10 IU / ml | 20 IU / ml |
| Scope restored preparation Mononain® | 5.0 ml | 5.0 ml |
| The required volume of 0.9% sodium chloride solution | 45.0 ml | 20.0 ml |
| Received breeding | 1:10 | 1:5 |
Example for breeding 1000 ME reconstituted Mononain® solution:
| The target activity of the diluted solution | 10 IU / ml | 20 IU / ml |
| Scope restored preparation Mononain® | 10.0 ml | 10.0 ml |
| Required volume 0.9% solution of sodium chloride | 90.0 ml | 40.0 ml |
| Received breeding | 1:10 | 1:5 |
- for intravenous administration of the drug is recommended to use infusion bags and tubes made of polyvinyl chloride (PBX);
- carefully mix and check if the infusion bag is leaking;
- It is recommended that every 12-24 hours replace the infusion bags with freshly diluted Mononain® solution.
Recommended rate of administration of the Mononain® preparation for long-term infusion to maintain a stable level of factor IX (approximately 80%) is 4 IU / kg body weight / hour, but may depend on the pharmacokinetic profile of the drug in the patient and the desired target level of activity.For patients in whom factor IX clearance is known, the infusion rate can be calculated individually.
Rate of administration (IU / mg body weight / hour) = Clearance (mL / h / kg body weight) × required increase in factor IX activity (IU / mL).
The reconstituted drug solution should be used immediately, taking into account microbiological safety. However, the reconstituted solution is physically and chemically stable for 24 hours at a temperature of no higher than 25 ° C.
The reconstituted drug solution Mononain® after dilution to a ratio of 1:10 is stable for 24 hours.