BERIPLEX

What it is

Beriplex P/N is a human prothrombin complex presented as a powder for reconstitution with diluent, available in strengths of 250 IU, 500 IU and 1000 IU factor IX. The P/N designation refers to virus inactivation and removal steps comprising pasteurisation and nanofiltration. The product contains human coagulation factors II, VII, IX and X, as well as the vitamin K dependent coagulation inhibitors protein C and protein S.

Approved indications

— Treatment of bleedings in acquired deficiency of the prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists, or in case of overdose of vitamin K antagonists, when rapid correction of the deficiency is required. — Perioperative prophylaxis of bleedings in acquired deficiency of the prothrombin complex coagulation factors, such as deficiency caused by treatment with vitamin K antagonists, or in case of overdose of vitamin K antagonists, when rapid correction of the deficiency is required.

Dosing overview

For bleeding and perioperative prophylaxis during vitamin K antagonist treatment, the dose depends on the International Normalised Ratio (INR) before treatment and the targeted INR. The pre-treatment INR should be measured as close as possible to the time of dosing. For normalisation of INR to approximately 1.3 or less, approximate doses based on factor IX per kilogram body weight are 25 IU/kg for pre-treatment INR of 2.0–3.9, 35 IU/kg for INR of 4.0–6.0, and 50 IU/kg for INR greater than 6.0. For patients weighing more than 100 kg, the maximum single dose should not exceed 2500 IU for an INR of 2.0–3.9, 3500 IU for an INR of 4.0–6.0 and 5000 IU for an INR of greater than 6.0. The correction of vitamin K antagonist-induced impairment of haemostasis is commonly reached approximately 30 minutes after injection.

Key safety warnings

There is a risk of thrombosis or disseminated intravascular coagulation when patients are treated with Beriplex P/N, particularly with repeated dosing. The risk may be higher in treatment of isolated factor VII deficiency. Patients given Beriplex P/N should be observed closely for signs or symptoms of disseminated intravascular coagulation or thrombosis. Close monitoring should be exercised when administering Beriplex P/N to patients with a history of coronary heart disease or myocardial infarction, to patients with liver disease, to patients perioperatively or postoperatively, to neonates, or to patients at risk of thromboembolic phenomena or disseminated intravascular coagulation. Patients receiving a vitamin K antagonist may have an underlying hypercoagulable state and infusion of human prothrombin complex may exacerbate this. Allergic or anaphylactic-type reactions have been uncommonly observed, including severe anaphylactic reactions. Repeated dosing with Beriplex P/N for patients requiring urgent reversal of vitamin K antagonist treatment is not supported by clinical data and therefore not recommended.

Contraindications

Beriplex P/N is contraindicated in hypersensitivity to the active substance or to any of the excipients. In the case of disseminated intravascular coagulation, prothrombin complex preparations may only be applied after termination of the consumptive state. Beriplex P/N is contraindicated in known history of Heparin-Induced Thrombocytopenia (HIT), as Beriplex P/N contains heparin.

Regulatory history

Beriplex P/N 250 IU and 500 IU formulations were first listed on the Australian Register of Therapeutic Goods on 5 February 2010. The 1000 IU formulation was first listed on 5 August 2015. A reformulated product designated BERIPLEX AU in 250 IU, 500 IU and 1000 IU strengths was first listed on 7 July 2020.