Dose optimization of recombinant factor VIIa in the treatment of acute bleeding in haemophilia-associated inhibitors.
Recombinant coagulation factor VIIa (rFVIIa; NovoSeven) represents an important advance in the therapy for haemophilia patients with inhibitors. Since licensure, the standard dosing has been perceived as 90-120 microg/kg every 2-3 h until cessation of bleeding. There has been an accumulation of anecdotal experience with the use of higher, less frequent dosing of rFVIIIa, and a controlled clinical trial is underway to assess the safety and efficacy of the current dosing recommendation and a single dose of 270 microg/kg. Furthermore, a post-licensure database is being analysed to evaluate the current dosing in acute bleeding episodes. Treatment, efficacy, and safety data from haemophilia patients with inhibitors treated with rFVIIa in a variety of contexts, including the on-demand treatment of acute bleeding, were entered into the registry. Data from patients treated with bolus infusion of rFVIIa were analysed and bleeding episodes were grouped according to total rFVIIa dose administered. Registry data suggest that rFVIIa is both safe and effective at doses > 200 microg/kg and that efficacy improves with increased dose. The database is currently being analysed to determine if increasing dose is associated with an elimination of the need for repeat dosing.
Novo Nordisk Pharmaceuticals, Inc., Princeton, New Jersey 08540, USA. sest@novonordisk.com
Stephanie
S
Seremetis
D000208:Acute Disease; D001779:Blood Coagulation Factors / Q000627:therapeutic use; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005167:Factor VII / Q000008:administration & dosage* / Q000627:therapeutic use; D005169:Factor VIII / Q000037:antagonists & inhibitors / Q000276:immunology; D015942:Factor VIIa; D006467:Hemophilia A / Q000150:complications* / Q000276:immunology; D006470:Hemorrhage / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D015337:Multicenter Studies as Topic; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D012042:Registries; D012449:Safety; D014481:United States
D001779:Blood Coagulation Factors; D007518:Isoantibodies; D011994:Recombinant Proteins; D005167:Factor VII; D005169:Factor VIII; C103587:recombinant FVIIa; C065655:anti-inhibitor coagulant complex; D015942:Factor VIIa