General Information

Praxbind (idarucizumab) is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran.

Praxbind is specifically indicated in patients treated with Pradaxa when reversal of the anticoagulant effects of dabigatran is needed: For emergency surgery/urgent procedures and /or in life-threatening or uncontrolled bleeding.

Praxbind is supplied as a solution for intravenous injection. The recommended dose of is 5 g, provided as two separate vials each containing 2.5 g/50 mL idarucizumab. There is limited data to support administration of an additional 5 g of Praxbind.

Mechanism of Action

Praxbind (idarucizumab) is a humanized monoclonal antibody fragment (Fab) derived from an IgG1 isotype molecule, whose target is the direct thrombin inhibitor dabigatran. It binds to dabigatran and its acylglucuronide metabolites with higher affinity than the binding affinity of dabigatran to thrombin, neutralizing their anticoagulant effect.

Clinical Trial Results

The FDA approval of Praxbind was based on a single cohort case series trial with dabigatran-treated patients who had life-threatening or uncontrolled bleeding, or who required emergency surgery or urgent procedure (RE-VERSE AD). The patients received 5 g idarucizumab administered to patients treated with dabigatran who presented with dabigatran-related lifethreatening or uncontrolled bleeding (Group A) or who required emergency surgery or urgent procedures (Group B). The primary endpoint was the maximum percentage reversal of the pharmacodynamic anticoagulant effect of dabigatran within 4 hours after the administration of idarucizumab, based on central laboratory determination of dTT or ECT. Data are from an Interim analysis for 123 patients: 66 patients with serious bleeding (Group A) and 57 requiring an urgent procedure (Group B). Approximately 67% of patients in Group A and 63% of patients in Group B had been treated with dabigatran 110 mg BID. Among the 90 patients with available data, the median maximum reversal of the pharmacodynamic anticoagulant effect of dabigatran as measured by ECT or dTT in the first 4 hours after administration of 5 g idarucizumab was 100%, with most patients (>89%) achieving complete reversal. Reversal of the pharmacodynamics effects was evident immediately after administration. Results for Groups A and B were similar. In a limited number of patients, between 12 and 24 hours after administration of 5 g idarucizumab, elevated coagulation parameters (e.g., aPTT or ECT) have been observed.