Drug Interaction Report

MONITOR: Coadministration of concizumab with recombinant factors VIII (rFVIII), IX (rFIX), or with bypassing agents recombinant factor VIIa (rFVIIa) or activated prothrombin complex concentrates (aPCC) may have synergistic effects on thrombin generation and increase the risk of thrombosis. Interaction studies with concizumab in vitro and ex vivo demonstrated additive effects when coadministered with rFVIIa, aPCC, rFVIII or rFIX, with a synergistic effect accounting for up to 40% of the total observed effect.

MANAGEMENT: Caution and monitoring are recommended with the concomitant use of concizumab with rFVIIa, aPCC, rFVIII, or rFIX. The manufacturer recommends that treatment with rFVIIa should be discontinued at least 12 hours before, factor VIII or factor IX at least 24 hours before, and aPCC at least 48 hours before the initiation of concizumab therapy. In addition, a cautious approach is advised in the treatment of bleeds in patients on prophylactic therapy with concizumab, taking into consideration the risk of thromboembolic events. Use of replacement products or bypassing agents at the lowest effective approved dose should be considered. The product labeling of the hemostatic agent(s) and/or local clinical guidelines should be consulted for dosage guidance.