Continuous infusion of recombinant activated factor VII: stability in infusion pump systems

Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) has a half life of 2.8 h in vivo, necessitating frequent dosing to maintain haemostasis where administration is by bolus injection. Continuous infusion would avoid this frequent dosing and potentially reduce the amount of rFVIIa used and the cost of treatment. We investigated the stability of reconstituted rFVIIa solutions alone and with the addition of heparin, low-molecular-weight heparin (LMWH, enoxaparin) and saline solution. Recombinant FVIIa was stable in the infusion pump for several days at room temperature and for 24 h at body temperature. Addition of heparin at pH 7 and LMWH and saline did not significantly affect the activity of rFVIIa for periods of 2 h, 72 h and 30 min, respectively. Recombinant FVIIa continuous infusion systems prepared under strict aseptic conditions remained free from significant microbiological contamination for 24 h.