Inhibitor treatment: state of the art

The treatment of hemophilic patients with inhibitors presents many challenges. Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) is a new therapeutic option for this patient population. Optimization of dosing regimens may be achieved by considering (1) individual pharmacokinetics (especially in the pediatric population); (2) high-dose bolus regimens; (3) continuous infusion (CI) including high-dose CI; (4) early treatment with NovoSeven in the course of a bleeding event; and (5) use of NovoSeven as a prophylactic therapy. The literature involving these issues is reviewed here. Institution of early therapy has been shown to decrease total NovoSeven requirement while increasing efficacy. Pediatric patients may require a higher dose of NovoSeven due to the higher clearance rate and shorter half-life demonstrated by this population. Therefore, the patient's age and/or individual pharmacokinetics and clearance rate should be considered when calculating doses and CI rates. High-dose NovoSeven has been shown to be effective in some patient populations without increased reported adverse events. Despite its short half-life, prophylactic use of NovoSeven has been reported in a small number of patients, with an apparent decrease in bleeding episodes experienced. There has been significant interest in administration of NovoSeven by CI, particularly in patients requiring prolonged treatment, and it has been shown to be successful, although the optimal target factor VII activity has yet to be established and some authors have recommended the use of concomitant antifibrinolytics.