Stability and antimicrobial effectiveness of treprostinil sodium in Sterile Diluent for Flolan.

Summary Introduction:  Long-term intravenous infusion of epoprostenol and treprostinil for treatment of pulmonary arterial hypertension (PAH) via a central venous catheter is associated with the risk of bloodstream infection (BSI). While several potential explanations exist for possible differences in BSI incidence among intravenous prostanoids, one hypothesis suggests that the alkaline pH of epoprostenol in Sterile Diluent for Flolan (SDF) has greater antimicrobial activity compared with the neutral pH of other common diluents such as sterile saline or water, which have been used for treprostinil. Methods:  The chemical stability and antimicrobial activity of 4 μg/ml and 130 μg/ml treprostinil in SDF were assessed according to United States and European Pharmacopeia. Results:  At both concentrations, treprostinil in SDF remained stable after incubation at 40 °C and ambient relative humidity for up to 52 h. Solution pH also remained stable (range 10.4–10.6), and the solutions were essentially free of particulate at all time points examined. Antimicrobial activity was measured using an antimicrobial effectiveness test after inoculation with five species of bacteria, yeast and mould. The antimicrobial activity of both concentrations of treprostinil met United States Pharmacopeia requirements. Further, the antimicrobial activity of treprostinil in SDF against gram-negative bacteria (> 4 log10 reductions) exceeded that previously described for treprostinil in sterile saline. Conclusion:  These results suggest that dilution of treprostinil with the alkaline solution SDF may reduce the risk of infection from inadvertent patient contamination compared with dilution of treprostinil in sterile saline.