Composition, form of production and packaging
Lyophilizate for the preparation of a solution for intravenous administration in the form of a porous mass or a white or almost white powder; the prepared solution is transparent or slightly opalescent, from colorless to light yellow in color.
1 ml of ready-made r- 1 fl.
highly purified concentrate of the blood coagulation factor IX of the human 50 IU 500 IU
[PRING] L-Lysine monohydrochloride, glycine, trisodium citrate, citric acid, sodium hydrogen phosphate dihydrate, sodium chloride.
Vials of colorless glass (1) complete with a sterile filter needle - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
Hemostatic drug. It is a highly purified concentrate of the human blood coagulation factor IX, isolated from the blood of carefully selected donors tested for HIV, hepatitis B and C viruses, also specially treated to remove the above and other possible viruses. It is a chain of a glycoprotein with a molecular mass of about 68,000 Da.
Replenishes the deficiency of coagulation factor IX and, thus, eliminates hypocoagulation in patients with its deficiency. The drug injected into the blood increases the level of K-dependent coagulation factors (II, VII, IX, X) in the plasma.
In the process of blood coagulation, it is converted into activated factor IX (factor IXa), which in combination with factor VIII transforms factor X into the active form of Xa. Under the influence of the latter there is a transition of prothrombin to thrombin, which converts fibrinogen into fibrin, as a result of which a fibrin clot is formed.
T 1/2 after intravenous administration of the drug in patients with hemophilia B is about 1 day.
- treatment and prevention of bleeding in patients with hemophilia B, acquired by the coagulation factor deficiency IX.
Treatment should be carried out under the supervision of a doctor who has the necessary experience of therapy for patients with hemophilia B. The dose and duration of treatment depend on many factors and are evaluated by the attending physician.
Drugs of factor IX rarely require administration more than 1 time / day.
The amount of factor IX administered is expressed in IU, which corresponds to the generally accepted WHO standard for preparations containing 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).
1 MU of factor IX activity is equivalent to the same amount of factor IX in 1 ml 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 Replenin-VF preparation per kg of body weight increases the level of factor IX in blood plasma by 1.3% of normal activity.
The dose of the drug is calculated by the following formula:
the required number of units of the drug = body weight (kg)? required level of factor IX activity increase (%)? 0.8
The table below gives an approximate estimate of the required dose for different situations.
Severity of bleeding / Type of surgical procedure Therapeutically necessary level of factor IX in blood plasma (%) Multiplicity of administration / duration of treatment
Early hemarthrosis, cerebral hemorrhage or oral cavity 20-40 Repeat administration every 24 hours, at least 1 time / day until relief of bleeding, pain or before recovery.
More extensive hemarthrosis, muscle hemorrhage or hematoma 30-60 Repeated administration every 24 hours for 3-6 days until pain and discomfort ceases.
Hemorrhages threatening life (including intracranial, intra-abdominal, gastrointestinal) 60-100 Repeat injections every 8-24 hours until the threat to the life of the patient is eliminated.
Minor (including extraction of the tooth) 30-60 Repeat the administration every 24 hours, at least 1 time / day before the onset of recovery.
Extensive surgical interventions (pre and postoperative period) 80-100 Repeat administration every 8-24 hours until the required level of wound healing is achieved, then therapy for at least the next 7 days to maintain factor IX activity at 30-60%
In certain circumstances, especially when determining the initial dose, a greater dose of the drug may be required than the one calculated above. In particular, with extensive surgical interventions, substitution therapy should be monitored through a blood coagulation assay (factor IX activity in the patient's blood plasma).
During the first few days after the operation, the concentration of plasma factor IX should be monitored and, if necessary, repeated administration of Replenin-VF every 12-24 hours. After a few days, the dose and multiplicity of administration can be reduced. Treatment is usually continued for 10 days or more.
If the concentration of factor IX does not reach the desired level or decreases more rapidly than expected (within 12 hours), the presence of factor IX inhibitors should be suspected and necessary studies should be carried out to determine these inhibitors.
In children, a dose of 1 IU / kg may result in a smaller increase in factor IX activity. At present, there is insufficient data on the use of Replenin-VF in children younger than 6 years of age.
The prepared drug solution should be injected iv slowly (at a rate of approximately 3 ml / min).
To administer the drug, you should attach a suitable needle (for example, a "butterfly" needle) to the syringe. Despite the low probability of side effects, the dose of the drug (especially the first one) should be administered slowly (at a rate of approximately 3 ml / min). If you need to enter the contents of more than 1 vial of the drug, you should collect the contents of the required number of vials in a 1 syringe of a suitable volume, transferring the solution from each vial through a separate sterile needle with a filter.
Preparation of injection solution
To prepare a solution for injection, water for injection should be used. The preparation and a bottle of water for injection are warmed to a temperature of 20 В° to 30 В° C. Remove flips from the flasks and wipe the plugs with a swab dipped in alcohol.
Further for the preparation of solution for injection, one of the following methods is used:
1. Using a sterile needle and syringe (which is destroyed after use), you should inject into the syringe water for injection and transfer it to the vial with the drug. After puncturing the stopper of the vial with the preparation, the water itself flows into the vial, since vacuum vacuum is created therein. It is necessary to pay special attention to the fact that the supplied needle with the filter can not be used for water transfer for injections.
2. Remove the protective tip from one end of the two-pointed needle and insert it through the stopper into the water injection bottle. Remove the tip from the other end of the needle, place a vial of water over the vial of the drug and insert the free end of the needle through the stopper into the vial with the drug. After puncturing the stopper of the vial with the preparation, the water itself flows into the vial. In the bottle with water for injection will remain a small amount of water. Pay special attention to the fact that if the water does not flow into the bottle with the drug, the leaktightness of the package has been violated and the drug can not be used.
Then you should proceed as follows: remove the syringe from the needle, remove the needle from the vial with the drug. Or, separate the 2 vials by removing the needle first from the vial of water, then from the vial with the drug.
Carefully rotate the vial with the drug between the palms to dissolve the drug. For no more than 5 minutes, a clear or slightly opalescent liquid should form. If you need more than 1 bottle to get the required dose, the contents of the required number of vials should be drained together.
After the preparation of the drug solution, wipe the stopper of the vial with a tampon moistened with alcohol. The dissolved preparation should be transferred from the vial to the plastic "portable filter" through the supplied needle with a sterile filter to release the solution from the tiny undissolved particles that may be present in it.
The solution should be applied within no more than 1 hour after preparation. If the diluted product forms a gel or clots, if there is flakes in the solution or a precipitate has fallen out, the drug can not be used. On such facts, as well as the fact of violation of the integrity (tightness) of the package should be reported to the manufacturer.
From the digestive system: rarely - nausea, jaundice, lack of appetite, bloating.
From the side of the central nervous system: rarely - headache, confusion.
From the cardiovascular system: rarely - tachycardia, postoperative thrombosis.
Allergic reactions: rarely - fever, chills, fever, urticaria, anaphylactic reactions.
Other: rarely - loss of body weight, tingling sensations in the body, back pain, malaise, fever, reduced resistance to infectious diseases, the appearance of antibodies to factor IX in the blood.
severe hepatic impairment;
- hypersensitivity to factor IX or other components of the drug.
It is not recommended to use the drug in patients who have inhibitors of coagulation factor VIII, as well as to correct disorders of coagulation factors in patients with liver disease, with the abolition of oral anticoagulants.
Caution should be used in children.
PREGNANCY AND LACTATION
When using Repenin-VF during pregnancy and during breastfeeding, no complications were noted. However, the use of the drug in pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus and newborn.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated use of the drug in severe violations of liver function.
Caution should be used to correct the correction of coagulation factors in patients with liver disease.
APPLICATION FOR CHILDREN
Caution should be used in children.
To dilute the drug, use sterile water for injection.
When injecting drugs prepared from human plasma, the risk of infection with known or unknown viruses can not be completely ruled out. To reduce the risk of infection, strict monitoring is carried out when blood donors are selected.
In addition, during the production of Replenin-VF, two special stages are carried out for the removal of viruses:
1. Solvent / detergent treatment destroying HIV, hepatitis B virus, hepatitis C virus.
2. Special viral filtration to remove viruses such as hepatitis A virus and parvoviruses.
However, human blood products can not be completely guaranteed against the presence of these viruses, so the manufacturer recommends that before the treatment start the patient should be vaccinated against hepatitis A and hepatitis B.
When using preparations of factor IX of low purification (concentrate of prothrombin complex), there were cases of thromboembolism. To date, clinical experience shows that with the use of high-purity factor IX preparations, which is Replenin-VF, this risk is significantly reduced. However, this potential risk should be considered when prescribing Replenin-VF to patients with heart disease, liver disease, after recent surgery, if there have been cases of thrombosis or thromboembolism or whether there are reasons to fear the formation of thrombi or extensive hematomas.
In case of allergic reactions or anaphylactic reactions, the drug should be discontinued immediately and if necessary, anti-shock therapy should be performed.
Some patients with congenital factor IX deficiency may receive antibodies to it after the course of treatment. This can lead to ineffective drug use. If there is a suspicion of the presence of antibodies to factor IX, tests should be performed to identify them, especially before the proposed operation.
It is necessary to check the level of factor IX in the blood before and after the course of treatment, especially during the first course.
Use in Pediatrics
Special care should be taken to prescribe the drug to children.
Impact on the ability to drive vehicles and manage mechanisms
It is not known about the effect of the drug on the ability to drive a vehicle or any other mechanisms.
No reports of cases of drug overdose have been reported.
Until now, there have been no drug interactions with other drugs.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, protected from light at a temperature of 2 В° to 8 В° C; Do not freeze. Shelf life - 3 years.