Feasibility of using recombinant factor VIIa in continuous infusion

Area of Science:

• Pharmacology and Therapeutics
• Hematology

Background:

• Recombinant factor VIIa (rFVIIa) is a hemostatic agent for hemophiliacs with inhibitors.
• Short half-life of rFVIIa necessitates frequent injections, posing a treatment challenge.

Purpose of the Study:

• To evaluate the stability and feasibility of continuous infusion of reconstituted rFVIIa.
• To assess the impact of infusion systems and additives on rFVIIa activity and patient safety.

Main Methods:

• Assessed rFVIIa stability in three infusion systems at room temperature.
• Investigated the effect of heparin and low molecular weight heparin on rFVIIa activity.
• Monitored sterility and bacterial growth in reconstituted rFVIIa.
• Conducted pharmacokinetic evaluations and treated two patients with continuous rFVIIa infusion.

Main Results:

• rFVIIa maintained activity for at least 3 days in infusion systems.
• Heparin reduced rFVIIa activity by 50% within 4 hours; low molecular weight heparin had no effect.
• Infusion systems maintained sterility and did not support significant bacterial growth.
• Continuous infusion was feasible, reduced rFVIIa dosage by 50-75%, and was associated with thrombophlebitis in one patient without heparin.

Conclusions:

• Continuous infusion of rFVIIa using minipumps is a viable and effective treatment strategy.
• This method overcomes the limitations of frequent injections, potentially reducing overall rFVIIa consumption.
• Co-administration with heparin or low molecular weight heparin may mitigate infusion site complications.