A new approach to treating breakthrough bleeds when using concomitant aPCC 1

Clinical experience suggests that a drug interaction exists with HEMLIBRA® and aPCC

Cases of TMA and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of aPCC was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis.

No events occurred when aPCC was used for <24 hours.

Five of the 13 treatment instances reported TMA or thrombotic events when using cumulative amounts of aPCC averaging >100 U/kg/24 hours for ≥24 hours.

  • An instance of aPCC treatment was defined as all doses of aPCC received by a patient, for any reason, until there was a 36-hour treatment-free break
  • Synergistic thrombin generation has been shown with aPCC in combination with HEMLIBRA in vitro and in vivo 20
  • aPCC contains coagulation factors that can accumulate with multiple doses and supplies substrates for HEMLIBRA that result in overcorrection of clotting 21

Continue to use your discretion when managing breakthrough bleeds with FVIII or FVIIa

At the time of the primary analyses in the HAVEN trials, no serious adverse events were observed with concomitant use of HEMLIBRA with FVIII or rFVIIa therapy 1

In the HAVEN 3 and HAVEN 4 primary analyses, no serious adverse events were observed with the concomitant use of HEMLIBRA with FVIII therapy. 1,2,20

At the time of the primary analyses in HAVEN 1 and HAVEN 2, no serious adverse events, TMA, or thrombotic events were observed with the concomitant use of HEMLIBRA and rFVIIa therapy. 2,11

Clinical experience was limited and of relatively short duration (median treatment exposure was 42 weeks for HAVEN 1, 29 weeks for HAVEN 2), and cannot exclude the possibility of occurrence of events with rFVIIa when taking HEMLIBRA. 1

Download our guidelines for additional information about treating breakthrough bleeds.

Surgical experience 2,19

Retrospective review of patients undergoing surgeries and procedures in HAVEN trials.

Analysis of the use of additional BPAs (HAVEN 1 and HAVEN 2) or FVIII (HAVEN 3) for surgeries was not an objective of the HAVEN studies, and there is limited experience from the clinical trials. Click here to see retrospective surgery data.

Talk to patients and caregivers about how HEMLIBRA increases coagulation potential 1




*Monitoring includes D-dimer, prothrombin fragment F1+2 (if available), platelet count, serum creatinine, LDH, and peripheral blood smear analysis for schistocytes. For patients who require multiple BPA doses, laboratory monitoring should be performed every 24-48 hours thereafter until 24-48 hours following the last BPA dose administered to treat a given bleed. 22 
aPCC=activated prothrombin complex concentrate; BPA=bypassing agent; FVIII=factor VIII; rFVIIa=activated recombinant factor VII; TMA=thrombotic microangiopathy.

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