In vitro compatibility of admixture solutions of 5-fluorouracil and khapzory (disodium levofolinate) in a single infusion bag.

Abstract

First-line chemotherapy for metastatic colorectal cancer typically involves a fluoropyrimidine, like 5-fluorouracil (5-FU), along with a folate agent, levoleucovorin. However, calcium-based levoleucovorin with 5-FU necessitates sequential infusion due to incompatibility, leading to calcium carbonate precipitation and potential IV catheter occlusion. In contrast, sodium-based levoleucovorin (disodium levoleucovorin-Khapzory) exhibits higher solubility in the low pH environment of 5-FU, enabling combination within a single IV bag for simultaneous infusion. This study aims to assess the safety of combining different concentrations of disodium levoleucovorin with 5-FU to create a single IV admixture bag or single pump Y-site, without risk of precipitate formation and catheter occlusion. Compatibility of admixture 5-FU and disodium levoleucovorin in a 0.9% sodium chloride IV bag was evaluated, focussing on clarity (suspension, precipitation, and haziness). Particulate matter analysis was conducted at 25°C/60% relative humidity, for 29 samples at five timepoints. Defined pass criteria included a minimum of 6000 particles ≥10 µm per container and 600 particles ≥25 µm. All prepared concentrations remained clear for up to 72 h with no observed suspension, precipitation or haziness at any concentration or time point. Combining 5-FU and disodium levoleucovorin in admixture IV bags eliminates the risk of catheter occlusion associated with calcium-based levoleucovorin formulations. This approach offers a more favorable operational and safety profile, enhancing convenience for patients and cost-efficiency for institutions.