Treatment of fulminant purpura and coumarin-induced skin necrosis in patients with severe congenital protein C deficiency. In addition, the drug is indicated for short-term prophylaxis in patients with severe congenital protein C deficiency, if at least one of the following conditions applies: threatening / inevitable surgery or invasive treatment; when initiating treatment with a coumarin derivative; if treatment with the coumarin derivative alone is insufficient; if treatment with a coumarin derivative is not feasible.
Composition:
1 vial contains 500 IU Protein C. A solution prepared by reconstituting the powder in 5 ml of water for injections contains approximately 100 IU / ml protein C from human plasma.
Action:
Protein C is a glycoprotein with anticoagulant properties, produced in the liver with the participation of vitamin K. It is obtained from human plasma purified with the help of mouse monoclonal antibodies. Under the influence of the thrombin / thrombomodulin complex, it is converted to activated Protein C (APC) - a serine protease that strongly inhibits blood clotting, especially in the presence of a cofactor - protein S. The APC effect is to inactivate activated forms of coagulation factors V and VIII, which leads to thrombin formation. It was also shown that APC may have a profibrinolytic effect. Intravenous administration of the drug causes an immediate but transient increase in plasma C protein concentration. Substitution therapy in patients with protein C deficiency is aimed at controlling thrombotic complications or in the case of prophylactic treatment - to prevent their occurrence. In people with asymptomatic protein C deficiency, the biological half-life was 4.4-15,8 h, and the recoveryin vivo was 25.9-83.2%. In patients with acute thrombosis, the increase in protein C and the biological half-life can be significantly reduced.
Contraindications:
Hypersensitivity to any of the ingredients of the preparation, to mouse protein or to Heparin, with the exception of use to control life-threatening thrombotic complications.
Precautions:
Due to the possibility of hypersensitivity reactions, the patient should be informed about the early signs of hypersensitivity reactions; if they occur, the drug should be stopped immediately. In case of shock, follow the current procedure for the treatment of shock. When medicines prepared from human blood or plasma are administered, the possibility of transmission of infectious agents can not be completely ruled out. Patients who receive regular or repeated C protein products should consider appropriate vaccination (hepatitis A and B). Due to the trace presence of Heparin in the preparation, the possibility of heparin-induced thrombosis (HIT) masked with symptomatology of the acute phase of protein C deficiency should be expected. In the case of suspected HIT, the platelet count should be determined and discontinued if necessary. There is no experience regarding the treatment of patients with renal or hepatic impairment (special care should be taken).
Pregnancy and lactation:
The safety of using the drug during pregnancy and breastfeeding has not been established. The preparation can only be used if the expected benefits of treatment outweigh the potential risks for the mother and the child.
Side effects:
Hypersensitivity reactions (angioedema, burning, stabbing pain at the injection site, chills, flushing, rash, generalized urticaria, headache, hypotension, lethargy, nausea, restlessness, tachycardia, chest tightness, tingling, vomiting) may occur. and breathing difficulties). In clinical trials, fever, increase in C-reactive protein, pruritus were very rare. After marketing, anxiety, pleural hematoma, hyperhidrosis, increased body temperature, increased catecholamine requirements to maintain blood pressure have been reported. When administering the preparation to patients with severe congenital protein C deficiency, it is possible to produce antibodies that inhibit protein C.
Dosage:
Treatment should be initiated under the supervision of a physician experienced in substitution therapy with coagulation factors / inhibitors, in centers where it is possible to monitor the activity of protein C. The dose should be selected individually based on the evaluation of the results of laboratory tests. Initially, you need to get 100% protein C activity and keep it above 25% during the treatment period. In order to determine the degree of recovery and biological half-life, it is recommended to give an initial dose of 60-80 IU / kg. Before and during treatment with the preparation, it is recommended to establish plasma protein C by determining the C protein activity using a chromogenic substrate. In severe thrombotic conditions, the signs should be taken every 6 hours until the patient's condition is stabilized, and then twice daily and always immediately before the Next administration of the drug. Due to the large discrepancies in the individual response to treatment, the effect of protein C on coagulation parameters should be controlled regularly. In the case of permanent adjustment of prophylactic treatment with oral anticoagulants, administration of protein C can be discontinued only after reaching a stable state of homeostasis. The dosage of anticoagulant should be started at low doses and gradually increased. The preparation is given by injection into a vein at a rate of no more than 2 ml / min. In children about the month <10 kg feed rate can not be higher than 0.2 ml / kg / min.
(C)
