Index of drugs

Treatment and prophylaxis of bleeding in patients with haemophilia A (congenital factor VIII deficiency). The preparation does not contain von Willebrand factor and is therefore not used in the treatment of von Willebrand disease. The drug is indicated for use in adults, adolescents and children of all ages.

1 vial contains nominally 250 IU, 500 IU, 1000 IU, 2000 IU. or 3000 IU human coagulation factor VIII (octocog alfa) obtained by recombinant DNA in kidney cells of young hamsters. The specific activity of the preparation is approximately 4000 IU / mg of protein.

The product contains recombinant blood coagulation factor VIII (octocog alfa). Vol. VIII, after administration to a patient with haemophilia, binds in the patient's circulation with the von Willebrand factor. Activated part VIII accelerates the conversion of parts X to activated part X. Activated part X transforms prothrombin into thrombin, and this converts fibrinogen to fibrin, which makes it possible to form a clot. The degree and duration of normalization of partial thromboplastin time after activation (APTT) observed after the use of the preparation is similar to the values ​​achieved after administration of factor VIII obtained from plasma. After administration of the preparation, peak activity of VIII decreased through a two-phase exponential distribution with an average final T_0,5 about 15 hours, the same is true for VIII obtained from plasma, whose average final T_0,5 is about 13 h. The average duration of drug presence in the body is 22 h, the clearance is about 160 ml / h.

Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to mouse protein or hamster protein.

The generation of neutralizing antibodies should be monitored. VIII (inhibitors), through appropriate clinical observation and laboratory tests. The risk of inhibitor formation correlates with the exposure time of anthemophilic part VIII, as well as genetic factors, being the highest during the first 20 days of exposure. The inhibitors occur less frequently during the first 100 days of exposure. There were cases of re-emergence of the inhibitor (low titre) following the change of one recombinant preparation. VIII for another preparation in patients previously exposed for more than 100 days and who had an inhibitor in the past. The drug should be discontinued if an allergic or anaphylactic reaction occurs; in case of shock, appropriate treatment should be used. If the medicine is administered in a continuous infusion, Heparin may be used to prevent thrombophlebitis at the injection site. If a device for central venous access (CVAD) is required, the risk of complications associated with CVAD, including local infections, bacteraemia and thrombosis at the catheter introduction site, should be considered.

There are no studies on the effect of the medicine on reproduction in animals. Lack of experience in the use of the preparation in pregnant and breastfeeding women - use only in the case of obvious indications.

Common: creating an inhibitor of cz. VIII (reported in previously untreated patients and patients treated minimally in clinical trials), infusion site reaction, skin-related hypersensitivity reactions (pruritus, urticaria, rash). Uncommon: the formation of an inhibitor of cz. VIII (reported in previously treated patients in clinical trials and post-marketing studies). Rarely: pyrexia-associated febrile reaction, systemic hypersensitivity reactions (nausea, abnormal blood pressure, dizziness, anaphylactic reaction). Very rare: taste disorders.

Administration of the drug should be initiated under the supervision of a physician experienced in the treatment of haemophilia. International unit (IU) part VIII is equivalent to the number of parts VIII in 1 ml of normal human plasma. The necessary dose of factor VIII is determined using the following formula: the required dose (IU) = body weight (kg) x desired factor VIII (%) or 0.5 mg, based on the formula: expected factor VIII increase (% of normal) = 2 x number of given IU : body weight (kg).Substitution treatment. The dose, frequency of administration and duration of substitution therapy must be adjusted individually to the patient's needs (body weight, severity of hemostasis disorders, site and rate of bleeding, the presence of the inhibitor and the desired level of factor VIII). The recommendations for individual minimum levels are given below. VIII in the blood in various types of bleeding. Early bleeding into the joints, muscles or the oral cavity - required level of VIII is 20-40 (% or IU / dL): repeat the infusion every 12-24 h, at least 1 day, until the bleeding resolves, as indicated by the resolution of pain or healing. More severe bleeding to the joints, muscles or hematoma - required level of VIII is 30-60 (% or IU / dL): repeat the infusion every 12-24 h, for 3-4 days or longer, until the pain and recovery are relieved. Life-threatening hemorrhages such as intracranial bleeding, sore throat or severe abdominal bleeding - required level of VIII is 60-100 (% or IU / dL): repeat the infusion every 8-24 h until the hazard disappears. Small surgical procedures, including tooth extraction - required level of VIII is 30-60 (% or IU / dl): repeat the infusion every 24 hours, at least 1 day, until healing. Major surgical procedures - required level of VIII is 80-100 (% or IU / dL), in the pre- and postoperative period: a. Injection as a bolus - repeat the infusion every 8-24 h until the wound is adequately healed, then continue treatment for at least 7 consecutive days, in order to maintain the activity of cz. VIII within 30-60%; b. continuous infusion - increase the activity of VIII preoperatively, initial injection as a bolus and immediately continue with continuous infusion (in IU / kg / h), adjusted to the patient's daily clearance and the required level of VIII, for at least 7 days. The dose and frequency of administration should each time be adjusted to clinical effectiveness in an individual case. Under certain circumstances, the required dose may be greater than the calculated dose, particularly for the initial dose. During the treatment, it is recommended to correctly determine the levels of VIII, to determine the dose and frequency of infusion repeat. In particular, during major surgical procedures, it is necessary to closely monitor the substitution treatment through coagulological studies (plasma activity of part VIII).Prevention. For long-term bleeding prophylaxis, doses of 20-40 IU are usually used in patients with severe haemophilia. preparation / kg body at intervals of 2 to 3 days. In some cases, especially in younger patients, it may be necessary to shorten the intervals between doses or to use higher doses.Patients with inhibitors. If the inhibitor concentration does not exceed 10 units of Bethesda (J.B.) / ml, administration of an additional amount of recombinant part. Coagulation of VIII may neutralize the inhibitor and ensure continuous clinically effective treatment with the preparation. However, if the inhibitor is present, the required doses are variable and must be adapted to the clinical response and monitored activity of VIII in plasma. In the group of patients with titers of inhibitors exceeding 10 U.B. or a high response in an antigenic stimulus, the use of an activated prothrombin complex concentrate or preparations of recombinant activated part should be considered. VII. The above therapeutic procedures should be carried out under the supervision of a physician experienced in the treatment of patients with haemophilia.
Way of giving. For preparation and administration, use only the solvents and components provided by the manufacturer (powder vial with Bio-Set kit, pre-filled syringe containing solvent and venipuncture set) and follow the manufacturer's instructions. After reconstitution, the drug should be used immediately; do not put the prepared solution in the refrigerator. The drug should be administered intravenously over several minutes. The speed of administration should be adjusted to the patient's comfort level (maximum infusion rate: 2 ml / min). The drug can be administered in a continuous infusion. The infusion dose should be calculated based on the clearance and the required level of VIII, according to the formula: infusion rate (in jm./kg/h) = clearance (in ml / h / kg) × required level of VIII (in int. / Ml); where 100% level of VIII is 100 IU / dl, i.e. 1 IU / ml. Higher infusion rates may be required under accelerated clearance conditions during severe bleeding or extensive tissue damage during surgical interventions.After the initial 24 hours of continuous infusion, the clearance should be recalculated daily using the equation for the state of dynamic equilibrium with the measured level of VIII and the infusion rate using the following equation: clearance = infusion rate / current level of VIII. During continuous infusion, the infusion bags should be changed every 24 hours. Stability for continuous infusion, clinical stability andin vitrousing outpatient pumps with a PVC reserve tank. The preparation contains a small amount of polysorbate 80 as an excipient that is known to increase DEHP extractions from polyvinyl chloride materials, which should be considered when infusing continuous infusions.
The safety and efficacy of the medicine in children of all ages have been determined.