Recombinant factor IX (BeneFix^®) by adjusted continuous infusion: a study of stability, sterility and clinical experience

Abstract

The safety and efficacy of adjusted continuous infusion (CI) of recombinant factor IX (FIX; BeneFix) was assessed in vitro and in a clinical study. BeneFix was reconstituted at 100 IU mL-1 with or without unfractionated heparin (4 U mL-1) and stored at either 4 degrees C or room temperature. Reconstituted BeneFix retained at least 90% activity over 14 days if stored at 4 degrees C but stability was reduced at room temperature. BeneFix reconstituted in a sterile pharmacy was free of bacterial contamination. Six patients with haemophilia B received seven CIs of BeneFix to cover routine surgery and severe bleeding episodes. The CIs lasted between 3 and 10 days. In all cases, haemostasis was excellent and the desired therapeutic FIX level was easily maintained. No thrombotic episodes or inhibitor development occurred but two patients developed thrombophlebitis at the infusion site when heparin was not added to the infusion. BeneFix is not currently licensed for CI and we suggest that studies to enable licensing should be established as soon as possible.

Factor IX replacement to cover total knee replacement surgery in haemophilia B: a single‐centre experience, 2000–2010

“…However, these descriptions of thrombosis have been in association with other risk factors, such as sepsis and a central venous catheter, in a neonate [9], radical retropubic prostatectomy [10] and burns with sepsis [11]. The two patients in whom thrombophlebitis was reported achieved resolution of thrombophlebitis following an increase in the rate of 0.9% sodium chloride infusion [8]. There was no evidence of this in any of our patients, whichever concentrate was used.…”

Continuous infusion of coagulation factors: current opinion

“…These studies comprised a total of 50 patients and 59 continuous infusion treatments (55 for major surgery) and provided evidence of an excellent hemostatic effect [35][36][37][38]46]. The initial factor IX (FIX) bolus of 12.4-155 IU was followed by infusion rates ranging between 1.7 and 8.6 IU/kg/h (median 3.9 IU/ kg/h) and aimed at maintenance FIX levels of more than 0.9 IU/ml in all studies but one that targeted FIX levels of 0.5-1.0 IU/ml.…”

Nacionalna priporočila za obravnavo bolnikov s hemofilijo

“…najkasneje v obdobju do največ 96 ur (64,65). Dokazali so nad 90-odstotno stabilnost rekombinantnega FIX na sobni temperaturi 7 dni po pripravi z dodanim standardnim heparinom ali brez (66). V primeru, da se pojavijo znaki tromboflebitisa, je potrebno mesto vstopa v veno takoj zamenjati.…”