Pharmacotherapeutic group: antihaemorrhagics, blood coagulation factors II, VII, IX and X in combination
ATC code: B02B D01
The coagulation factors II, VII, IX and X, which are synthesised in the liver with the help of vitamin K, are commonly called the prothrombin complex. In addition to the coagulation factors Beriplex contains the vitamin K dependent coagulation inhibitors Protein C and Protein S.
Factor VII is the zymogen of the active serine protease factor VIIa by which the extrinsic pathway of blood coagulation is initiated. The tissue thromboplastin factor-factor VIIa complex activates coagulation factors IX and X, whereby factor IXa and Xa are formed. With further activation of the coagulation cascade, prothrombin (factor II) is activated and transformed to thrombin. By the action of thrombin, fibrinogen is converted to fibrin, which results in clot formation. The normal generation of thrombin is also of vital importance for platelet function as a part of the primary haemostasis.
Isolated severe deficiency of factor VII leads to reduced thrombin formation and a bleeding tendency due to impaired fibrin formation and impaired primary haemostasis. Isolated deficiency of factor IX is one of the classical haemophilias (haemophilia B). Isolated deficiency of factor II or factor X is very rare but in severe form they cause a bleeding tendency similar to that seen in classical haemophilia.
The further ingredients, the coagulation inhibitors Protein C and Protein S, are also synthesized in the liver. The biological activity of Protein C is enforced by the cofactor Protein S.
Activated Protein C inhibits the coagulation by inactivating the coagulation factors Va and VIIIa. Protein S as cofactor of Protein C supports the inactivation of the coagulation. Protein C deficiency is associated with an increased risk of thrombosis.
Acquired deficiency of the vitamin K-dependent coagulation factors occurs during treatment with vitamin K antagonists. If the deficiency becomes severe, a severe bleeding tendency results, characterised by retroperitoneal or cerebral bleeds rather than muscle and joint haemorrhage. Severe hepatic insufficiency also results in markedly reduced levels of the vitamin K-dependent coagulation factors and a clinical relevant bleeding tendency. However this is often complex due to a simultaneously ongoing low-grade intravascular coagulation, low platelet levels, deficiency of coagulation inhibitors and disturbed fibrinolysis.
The administration of human prothrombin complex provides an increase in plasma levels of the vitamin K-dependent coagulation factors, and can temporarily correct the coagulation defect of patients with deficiency of one or several of these factors.
⚠️ Warnings
Method of administration
General instructions
- The solution should be clear or slightly opalescent. After filtering/withdrawal (see below) reconstituted product should be inspected visually for particulate matter and discoloration prior to administration.
- Do not use solutions that are cloudy or have deposits.
- Reconstitution and withdrawal must be carried out under aseptic conditions.
Reconstitution
Bring the solvent to room temperature. Ensure product and solvent vial flip caps are removed and the stoppers are treated with an antiseptic solution and allowed to dry prior to opening the Mix2Vial package.
1. Open the Mix2Vial package by peeling off the lid. Do
not
remove the Mix2Vial from the blister package!
2. Place the
solvent vial
on an even, clean surface and hold the vial tight. Take the Mix2Vial together with the blister package and push the spike of the
blue
adapter end
straight down
through the solvent vial stopper.
3. Carefully remove the blister package from the Mix2Vial set by holding at the rim, and pulling
vertically
upwards. Make sure that you only pull away the blister package and not the Mix2Vial set.
4. Place the
product vial
on an even and firm surface. Invert the solvent vial with the Mix2Vial set attached and push the spike of the
transparent
adapter end
straight down
through the product vial stopper.
The solvent will automatically flow into the product vial.
5. With one hand grasp the product-side of the Mix2Vial set and with the other hand grasp the solvent-side and unscrew counterclockwise the set carefully into two pieces.
Discard the solvent vial with the blue Mix2Vial adapter attached.
6. Gently swirl the product vial with the transparent adapter attached until the substance is fully dissolved. Do not shake.
7. Draw air into an empty, sterile syringe. While the product vial is upright, connect the syringe to the Mix2Vial's Luer Lock fitting by screwing clockwise. Inject air into the product vial.
Withdrawal and application
8. While keeping the syringe plunger pressed, turn the system upside down and draw the solution into the syringe by pulling the plunger back slowly.
9. Now that the solution has been transferred into the syringe, firmly hold on to the barrel of the syringe (keeping the syringe plunger facing down) and disconnect the transparent Mix2Vial adapter from the syringe by unscrewing counterclockwise.
Care should be taken that no blood enters the syringe filled with product, as there is a risk that the blood could coagulate in the syringe and fibrin clots could therefore be administered to the patient.
In case more than one vial of Beriplex is required, it is possible to pool several vials of Beriplex for a single infusion via a commercially available infusion device.
The Beriplex solution must not be diluted.
The reconstituted solution should be administered intravenously (not more than 8 ml/min*).
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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