Incompatibility of fluorouracil with leucovorin calcium or levoleucovorin calcium

The physical compatibility of fluorouracil mixed with leucovorin calcium or levoleucovorin calcium, undiluted and modestly diluted with 5% dextrose injection, was evaluated. Fluorouracil 50 mg/mL was combined in duplicate with leucovorin or levoleucovorin 20 mg/mL (as the calcium salt) in 250-mL polyvinyl chloride (PVC) portable-pump reservoirs in six volume ratios, either undiluted or diluted with 5% dextrose injection (to a final volume 25% greater than the drug volume). Duplicate reservoirs of each combination were stored for seven days at 4, 23, or 32 °C. Samples were evaluated visually with a high-intensity monodirectional light beam to observe development of particulates. Turbidimetry and light-obscuration particle counting and sizing also were used to evaluate compatibility. Small amounts of tiny crystalline particles developed in most of the combinations, usually by four days. In some cases, the particles could be seen in normal diffuse room light. Particle content was greater with higher leucovorin concentrations and over longer storage periods. Storage temperature did not play a consistent role in particle development. Fluorouracil and leucovorin calcium or levoleucovorin calcium were not compatible when stored in PVC reservoirs at 4, 23, or 32 °C.