Composition, form of production and packaging
Lyophilizate for the preparation of a solution for intravenous administration from white to almost white in the form of powder or loose solid mass.
1 f.
octokog alpha (recombinant antihemophilic factor) 1000 IU
[PRING] human albumin, sodium chloride, histidine, macrogol 3350, calcium chloride dihydrate, hydrochloric acid, sodium hydroxide.
Solvent: water d / u - 10 ml.
Vials (1) complete with a solvent (fl.), A plastic syringe, a needle with a filter, a double-sided needle, a d / inf. System, 2 napkins, and 2 plasters-packs of cardboard.
Lyophilizate for the preparation of a solution for intravenous administration from white to almost white in the form of powder or loose solid mass.
1 f.
octokog alpha (recombinant antihemophilic factor) 250 IU
[PRING] human albumin, sodium chloride, histidine, macrogol 3350, calcium chloride dihydrate, hydrochloric acid, sodium hydroxide.
Solvent: water d / u - 10 ml.
Vials (1) complete with a solvent (fl.), A plastic syringe, a needle with a filter, a double-sided needle, a d / inf. System, 2 napkins, and 2 plasters-packs of cardboard.
Lyophilizate for the preparation of a solution for intravenous administration from white to almost white in the form of powder or loose solid mass.
1 f.
octokog alpha (recombinant antihemophilic factor) 500 IU
[PRING] human albumin, sodium chloride, histidine, macrogol 3350, calcium chloride dihydrate, hydrochloric acid, sodium hydroxide.
Solvent: water d / u - 10 ml.
Vials (1) complete with a solvent (fl.), A plastic syringe, a needle with a filter, a double-sided needle, a d / inf. System, 2 napkins, and 2 plasters-packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
The recombinant acts like an endogenous factor VIII. Factor VIII is an important component in the process of blood clotting. As a cofactor for factor XI, it accelerates the activation of factor X. Activated factor X converts prothrombin to thrombin, which in turn converts fibrinogen to fibrin, which leads to the formation of a clot. The activity of factor VIII is significantly reduced in patients with hemophilia A, therefore they need appropriate replacement therapy.
In toxicity studies conducted on laboratory animals, the administration of doses exceeding several times the recommended dosages for humans showed no toxic effects. In studies on mutagenic activity in vitro, no reversible mutations, chromosomal aberrations or an increase in the number of micronuclei in polychromatic erythrocytes of the bone marrow have been identified.
PHARMACOKINETICS
Pharmacokinetic studies showed that in previously treated patients, T 1/2 Recombinant was 14.6 В± 4.9 hours, which was not statistically different from that of plasma anti-hemophilic factor (human), Hemophil M (pAGH), which were 14.7 В± 5.1 h. However, the level of Recombinate after infusions of 50 IU / kg in plasma was 123.9 В± 47.7 IU / 100 ml, which is significantly higher than the level of Hemophilus M 101.7 В± 31.6 IU / 100ml. However, the calculated plasma level (ie 2% increase in the activity of factor VIII 1 ME antihemophilic factor / kg body weight) for Recombinant (121.2% В± 48.9%) was comparable to that for Hemophil M (123.4% В± 16.4%).
INDICATIONS
- treatment and prevention of bleeding in patients with hemophilia A (congenital factor VIII deficiency), incl. in surgical operations in patients with hemophilia A.
DOSING MODE
Dosing regimen and duration of treatment depends on the severity of hemostasis disorder, as well as the clinical condition of the patient. Treatment should be conducted under the supervision of a specialist and regular monitoring of the concentration of antihemophilic factor in the patient's plasma. The expected peak in the increase in the level of the recombinant is expressed in IU / 100 ml of plasma or% (percentage) of the normal value, can be determined by multiplying by 2 administered doses per kg of body weight (IU / kg).
Careful monitoring of the therapy is especially necessary in the case of surgical interventions or life-threatening hemorrhages. It is recommended to regularly monitor the level of antihemophilic factor in the plasma of patients to monitor the achievable AHF indices. If it is not possible to reach the calculated level of AGP in the plasma, or bleeding is not controlled by the introduction of adequate doses of the drug, then the presence of inhibitory antibodies should be suspected. In laboratory tests, the presence of inhibitory antibodies can be detected and quantified in neutralized ME antihemophilic factor in each ml of plasma (Bethesda units) or in the total volume of plasma. If the inhibitor is determined in less than 10 units of Bethesda per ml, the administration of an additional dose of an anti-hemophilic factor may neutralize the action of the inhibitor. Thus, the administration of an additional dose of the drug should improve the expected effect. In such a situation, careful laboratory monitoring of the level of antihemophilic factor is necessary. The inhibitor titer of more than 10 units of Bethesda per ml can lead to a loss of control over hemostasis when an anti-hemophilic factor is introduced or impossible or difficult to control, high doses of the drug are required.
Recommendations on the dosage regimen in children and adults are given in Table 1. The dosage and multiplicity of drug administration should always be correlated with clinical efficacy in each case. The recombinant can be used for the prevention of bleeding (short or long course of therapy), if the attending physician considers it necessary. In this case, it is worthwhile to focus on the peak activity of anti-hemophilic factor in patients with known half-life of factor VIII. If necessary, the peak activity should be measured within 30 minutes after drug administration. For patients with a short half-life of factor VIII, an increase in the dose and / or frequency of administration of the drug may be necessary. On each vial with a recombinant anti-hemophilic factor (Recombinant), the activity of the anti-hemophilic factor is expressed in the ME per vial, which is due to the requirements and WHO standards for the factor VIII concentrate. Studies have shown that to achieve accurate levels of activity, quantification should be performed using plastic tubes and pipettes, as the substrate contains normal levels of von Willebrand factor.
Mode of application
The drug should be administered iv after preparation. It is recommended to infuse the drug no later than 3 hours from the time of preparation. After preparation, the solution can not be stored in the refrigerator. The drug should be administered at a rate of up to 10 ml / min. It is necessary to monitor the patient's pulse before and during the introduction of the Recombinate. If a significant tachycardia occurs, the rate of administration should be reduced or the drug should be temporarily discontinued, which usually leads to rapid relief of symptoms.
Table 1. Schemes of introduction
Severity of bleeding / Type of surgery Required level of factor VIII (% of normal or IU / for plasma) Frequency of administration (h) / Duration of administration (days)
Initial signs of hemarthrosis or hemorrhages in the muscles, or bleeding in the oral cavity 20-40 Repeated infusions every 12 to 24 hours for at least 1 day until the complete relief of episodes of bleeding, as evidenced by the absence of pain or healing
Hemarthroses and hemorrhages in the muscles of moderate severity or hematomas 30-60 Repeated infusions every 12 to 24 hours for 3-4 days or more until complete relief of pain and recovery of motor activity
Life-threatening bleeding, such as pharyngeal bleeding, bleeding into the abdominal cavity, hemothorax, as well as with surgical interventions on the head 60-100 Repeated infusions every 8-24 hours until the bleeding ceases completely
Small surgical interventions, including tooth extraction 60-80 A single infusion of the drug and oral antifibrinolytic therapy for 1 h is usually sufficient for 70% of cases
Large surgical interventions 80-100 Repeated infusions every 8-24 h until adequate wound healing, then therapy for at least 7 days to maintain the activity of factor VIII at 30-60% (IU / 100 ml)
Preparation of the solution
1. Bring the temperature of the lyophilized powder and the solvent (water for injection) to room temperature (15-25 В° C).
2. Remove the protective caps from the vials.
3. Disinfect the surface of the caps with an antiseptic solution.
4. Remove the protective cap from one side of the double-sided needle supplied in the kit and puncture the stopper of the vial with the solvent. Then remove the second protective cap from the needle, turn the bottle with the solvent so that it is above the powder bottle. Puncture the stopper of the vial with the powder with the free end of the needle. The solvent under the action of vacuum will flow into the vial of powder.
5. Disconnect the vials by removing the needle first from the vial with the solvent, and then from the vial with the Recombinant. Easy stirring will accelerate the dissolution process. Make sure that the powder is completely dissolved.
6. After preparation of the Recombinate solution, the preparation should not be stored in the refrigerator. The drug should be used for 3 hours, at a temperature not exceeding 15-25 В° C
Solution administration
It is recommended to inject the solution no later than 3 hours from the moment of its preparation. The resulting solution can not be stored in the refrigerator. Before administration, the solution should be visually assessed for undissolved particles or discoloration. The solution should be from colorless to slightly yellowish color.
1. Attach the filter needle to the syringe and draw air into it.
2. Insert the needle into the vial with a recombinant anti-hemophilic factor.
3. Insert air from the syringe into the vial, then draw the solution into the syringe.
4. Remove the needle from the vial and disconnect from the syringe. Type in / in. The rate of administration should not exceed 10 ml / min. It is necessary to monitor the pulse of the patient during the injection. If a significant tachycardia occurs, the rate of administration should be reduced or the drug should be temporarily discontinued, which usually leads to rapid relief of symptoms.
5. The needle filter should be used only once.
SIDE EFFECT
As with the use of other protein-containing drugs, side effects may occur when using Recombinant.
The following side effects are possible with the administration of the drug: nausea, a feeling of heat, mild fatigue, rash, bruising, sweating, itching, tremor, fever, leg pain, cold extremities, dry throat, inflammatory ear diseases and hearing loss.
Rarely, allergic side effects (hives, rash, dyspnoea, cough, chest pain, decreased blood pressure and anaphylactic condition) were noted. It is necessary to warn the patient about possible signs of allergic reactions and at their occurrence to stop application of a preparation. Particular care should be taken in patients with known allergies to the components of the drug.
The production of neutralizing antibodies, inhibitors of factor VIII, is a common complication in the treatment of patients with hemophilia A. These antibodies are one of the immunoglobulin G fractions. The activity of neutralizing antibodies is expressed in units of Bethesda per ml of plasma. The risk of developing such a complication correlates with the administration of antihemophilic factor VIII. this risk is greatest during the first 20 days of drug administration. In studies among patients with haemophilia A with a high risk of producing inhibitory antibodies (previously untreated patients), the level of antibodies to recombinant plasma derived antihemophilic factor. Patients treated with a recombinant anti-hemophilic factor should be carefully monitored for the formation of inhibitory antibodies by special laboratory tests.
CONTRAINDICATIONS
- allergy to proteins of cattle, mice or hamsters;
- Hypersensitivity to any component of the drug.
With caution: with a high risk of thrombosis, thromboembolism, myocardial infarction, DIC-syndrome, pregnancy and lactation.
PREGNANCY AND LACTATION
Studies of the effect of recombinate on reproductive performance of laboratory animals have not been conducted. It is not known whether the Recombinant can have any effect on the fetus. Therefore, the use of the drug for women during pregnancy is possible only if no other therapy is possible.
Take with caution during lactation.
APPLICATION FOR CHILDREN
The recombinant can be used in children of any age, including newborns (corresponding studies on safety and efficacy were conducted in previously treated and previously untreated children).
SPECIAL INSTRUCTIONS
In some cases, when a recombinant anti-hemophilic factor was introduced, allergic reactions developed. Therefore, care should be taken when applying the drug to patients who are hypersensitive to the proteins of cattle, mice and hamsters.
Allergic reactions of severe degree are a contraindication to the introduction of the Recombinate. If an anaphylactic reaction occurs, discontinue the drug immediately and start using conventional anti-shock measures. If, after the administration of the necessary doses of the drug, the levels of the anti-hemophilic factor do not reach the calculated values, blood samples should be examined for the presence of inhibitors of the anti-hemophilic factor.
The recombinant can be used in children of any age, including newborns (corresponding studies on safety and efficacy were conducted in previously treated and previously untreated children).
Since the preparation contains only recombinant VIII factor, it is not intended for the treatment of patients with von Willebrand disease.
Impact on the ability to drive vehicles and manage mechanisms
The use of this drug does not affect the ability to drive a car or any other mechanisms.
OVERDOSE
Symptoms of drug overdose are not revealed.
DRUG INTERACTION
No reactions of drug interaction were detected.
Recombinant should not be confused with other medical products.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored out of reach of children at a temperature of 2 В° to 8 В° C. Do not freeze.
Within the indicated shelf life for 6 months can be stored at a temperature of 15-25 В° C. Shelf life - 2 years.
