Index of drugs

Treatment and prevention of bleeding in patients with haemophilia A (congenital deficiency of coagulation factor VIII). The preparation can be used in adults and children of all ages, including neonates. The product does not contain von Willebrand factor and can not be used to treat von Willebrand disease.

1 vial contains 250 IU, 500 IU, 1000 IU or 2000 IU moroctocog alfa. After reconstitution, 1 ml of solution contains approximately 62.5 IU, 125 IU, 250 IU, respectively. or 500 IU moroctocog alfa. After reconstitution, 1 vial contains 1.23 mmol (29 mg) of sodium.

Anti-haemorrhagic drug, blood coagulation factor VIII. The preparation contains the domain-free recombinant coagulation factor VIII (moroctocog alfa). It is a glycoprotein with a molecular weight of approx. 170,000 Da, made up of 1438 amino acids. The preparation has functional features comparable to those of endogenous factor VIII. Factor VIII infused into a haemophilia patient is associated with the von Willebrand factor present in the patient's circulation. The use of substitution therapy increases the concentration of factor VIII in the plasma, which makes it possible to temporarily reduce the deficiency of the factor and prevent bleeding tendencies.

Hypersensitivity to the active substance or any of the excipients. Hypersensitivity to hamster proteins.

As with other intravenously administered protein preparations, allergic type hypersensitivity reactions are possible. The product contains traces of hamster proteins. In case of allergic or anaphylactic reactions, the drug should be stopped immediately and appropriate treatment should be given. There is a risk of generating neutralizing antibodies (inhibitors) of factor VIII, which are usually IgG immunoglobulins against factor VIII procoagulant activity; this risk is greatest during the first 20 days of exposure. Inhibitors have been detected in previously treated patients receiving factor VIII containing formulations. After switching from one formulation containing recombinant coagulation factor VIII to another, cases of recurrence of inhibitors (low titre) have been observed in previously treated patients with a history of inhibitors who have previously been exposed for more than 100 days. Patients treated with recombinant coagulation factor VIII should be closely monitored for the formation of inhibitors, through clinical observations and laboratory tests. There were cases of no treatment outcome (bleeding to the target joints, bleeding to new joints or subjectively experienced by the patient new start of bleeding) mainly in patients treated prophylactically. When implementing the treatment, it is very important to individually adjust the dosage and control the concentration of the factor in each patient in order to obtain an appropriate therapeutic response. After reconstitution, 1 vial contains 1.23 mmol (29 mg) sodium - this should be taken into account in patients who are controlling the sodium content of the diet.

Due to the rare occurrence of haemophilia A in women and lack of experience in treatment during pregnancy and breastfeeding - the drug can be administered only if it is absolutely necessary.

The occurrence of neutralizing antibodies (inhibitors) factor VIII is a common phenomenon in patients being treated for haemophilia A. Patients should be screened for inhibitors that should be measured in Bethesda units (BJ) using the Nijmegen modification of the Bethesda assay. The formation of inhibitors may appear as an ineffective response to treatment. Very common: occurrence of factor VIII inhibitors - PUPs, vomiting. Common: Factor VIII - PTPs inhibitors, headache, haemorrhage / haemorrhage, nausea, joint pain, asthenia, fever, vascular access complications (including catheter-related complications with permanent vascular access). Uncommon: anaphylactoid reaction, anorexia, neuropathy, dizziness, drowsiness, taste disturbance, angina pectoris, tachycardia, palpitations, hypotension, thrombophlebitis, vasodilatation, hot flushes, cough, shortness of breath, abdominal pain, diarrhea, urticaria, pruritus, rash, sweating, muscle pain, chills / feeling cold, inflammation at the injection site, pain at the injection site, increased ALT and AST, increased bilirubin in the blood, increased creatine phosphokinase in the blood.Occasional hypersensitivity reactions or allergic reactions (which may include angioneurotic edema, burning and burning pain at the infusion site, chills, hot flushes, generalized urticaria, headache, rash, hypotension, lethargy, nausea, restlessness, tachycardia, feeling of tightness in the chest, tingling, vomiting, wheezing), which may in some cases develop into severe anaphylactic reactions, including shock. The preparation may contain traces of hamster protein. The development of anti-hamster antibodies has been observed very rarely, but without clinical sequelae. There was one case of cyst formation in an 11-year-old patient and one case of disorientation in a 13-year-old patient, the occurrence of which could be related to the treatment with the preparation. There was a tendency for a higher incidence of side effects in children aged 7-16 than in adults. Clinical trials evaluating the use of moroctocog alfa (AF-CC) in children under 6 are currently in progress.

Treatment should be started under the supervision of a physician experienced in the treatment of haemophilia A. During treatment, it is recommended to monitor the activity of factor VIII using the method described in the European Pharmacopoeia using a chromogenic substrate. Values ​​of factor VIII plasma activity assays using the chromogenic substrate method are higher than those obtained as a result of a one-stage coagulation assay. In the case of a one-stage coagulation test, it is typical to obtain values ​​20-50% lower than in the case of the chromogenic substrate method. Another preparation containing moroctocog alfa (XYNTHA) released for sale outside of Europe has a different activity, which is determined by means of a manufacturing standard calibrated to the WHO International Standard using a one-stage coagulation test. Because XYNTHA and ReFacto AF preparations used different methods for determining the activity, 1 IU. XYNTHA corresponds to approximately 1.38 IU. ReFacto AF. If a patient receiving XYNTHA is prescribed ReFacto AF, the treating physician should consider dose adjustment based on the average recovery of factor VIII. Based on the current dosing regimen, patients with type A hemophilia should be advised to take with them the appropriate amount of factor VIII sufficient for the intended treatment. Before traveling, patients should consult their physician.
The dosage and duration of substitution treatment depend on the level of factor VIII deficiency, the location and severity of the bleeding, and the clinical condition of the patient. The doses administered should be adjusted to the patient's clinical response. If an inhibitor is present, it may be necessary to administer higher doses or use other appropriate specific measures. The number of units of factor VIII administered is expressed in International Units (IU) that correspond to current WHO standards for factor VIII containing preparations. Factor VIII activity in plasma is expressed either as a percentage (relative to normal human plasma) or in international units (relative to the International Standard for factor VIII in plasma). One square meter factor VIII activity corresponds to the amount of this factor in 1 ml of normal human plasma. The calculation of the required dose of factor VIII is based on the results of previous tests, indicating that the injection of 1 IU factor VIII per kg body weight causes an increase in factor VIII activity in the plasma by 2 IU / day. The required dose is calculated using the following formula: Required units (IU) = body weight (kg) x desired increase in factor VIII activity (% or IU / dL) x 0.5 (IU / kg per IU / dL) where 0, 5 IU / kg / IU / dl represents the inverse of the recovery gain generally observed after the administration of factor VIII. The amount of the preparation administered and the frequency of dosing should always be adjusted individually taking into account clinical efficacy. In case of early bleeding into the joints, muscles or the mouth, the factor VIII level is 20-40% or IU / dl; administration of the drug is repeated every 12-24 h, at least one day, until the bleeding signaled by pain or wound healing resolves. In more severe bleeding to the joints, muscles or hematoma, the required level of factor VIII is 30-60% or IU / dl; the infusion is repeated every 12-24 h for 3-4 days or more until pain and bleeding are resolved.In the case of life-threatening bleeding, the required level of factor VIII is 60-100% or IU / dl, the infusion should be repeated every 8-24 h until the risk disappears. In the case of smaller surgical procedures, eg tooth extraction, the required level of factor VIII is 30-60 (% or IU / dl), the drug is administered every 24 hours for at least 1 day, until the wound heals. In large surgery, the required level of factor VIII is 80-100 (% or IU / dL) before and after the procedure, the infusion is repeated every 8-24 h until the wound heals, and then treatment is continued for at least the Next 7 days in to maintain factor VIII activity at 30-60% or IU / dl. During treatment, it is recommended to perform factor VIII levels to adjust the dosage and frequency of infusion. Particularly in the case of extensive surgical procedures, it is necessary to closely monitor substitution treatment using coagulation system tests (Factor VIII activity assays). Individual patients may differ in their response to factor VIII therapy, achieving different degrees of improvement in conditionsin vivo and different half-lives. In long-term prevention of bleeding in patients with severe haemophilia A, 20 to 40 IU are usually administered. factor VIII per kg body weight, at intervals of 2 to 3 days. In some cases, especially in younger patients, it may be necessary to use shorter intervals between drug administration or higher doses. Patients taking factor VIII replacement therapy should be monitored for factor VIII inhibitors. If the expected plasma factor VIII activity is not obtained in the recipient's plasma or if bleeding can not be stopped using standard doses of the preparation, a test for factor VIII inhibitors should be performed. Data from clinical trials indicate that if the titer of inhibitors is lower than 10 Bethesda units (B.B.), addition of antihaemophilic factor may neutralize the inhibitors. In patients with an inhibitor of more than 10 UB, treatment with factor VIII may be ineffective and other treatments should be considered. Such patients should be under the supervision of a physician experienced in the treatment of patients with haemophilia. No dose adjustment clinical trials have been conducted in patients with renal or hepatic impairment. For treatment of younger children, a higher dose should be considered than for adults and older children. In children under 6 years T_0,5 and recovery was less than that seen in older children and adults. During clinical trials in preventing bleeding in children under the age of 6 an average dose of 50 IU / kg was used. and an average of 6.1 bleeding episodes per year was observed. In older children and adults, an average dose of 27 IU / kg was used to prevent bleeding. and an average of 10 bleeding episodes per year was observed. In the clinical study, the mean dose of the infusion preparation used in the treatment of bleeding in children under 6 years was higher than the average dose for older children and adults (51.3 IU / kg and 29.3 IU / kg, respectively).
The drug is given as a few minutes of intravenous injection after reconstitution of lyophilized powder in a sodium chloride 9 mg / ml (0.9%) solution for injection. The speed of administration must depend on the level of comfort of the patient.