Physical compatibility of colistin with analgesics during simulated Y-site administration

Special consideration is needed when intravenous drugs are administered simultaneously using a Y-site connector. This study aimed to investigate the physical compatibility of colistin with 6 analgesics at concentrations commonly used in clinical practice.

A pharmaceutical preparation of colistin was dissolved according to the manufacturer's instructions and diluted to a concentration of 1.5 mg/mL or 0.67 mg/mL (of colistin base). Simulated administration via Y-site infusion set was performed by mixing 5 mL of colistin solution with an equal volume of a solution of one of 6 intravenous analgesics. Infusion solutions of ibuprofen, ketoprofen, metamizole sodium, morphine sulfate, paracetamol, and tramadol hydrochloride were studied. For each analgesic tested, concentrates for injection were diluted with 2 solvents, resulting in 11 different combinations with each concentration of the colistin solution. The mixtures were visually inspected, and their turbidity was measured directly after mixing and at 3 consecutive time points (30, 60, and 120 minutes). Additionally, the pH of the mixtures was measured after 120 minutes and compared with the pH of the analgesic and the colistin solutions.

During visual inspection with the unaided eye, no precipitate formation or gas evolution was observed in any of the tested analgesics except for sodium metamizole, where the yellow color of the solutions was observed. For samples containing the mixture of ibuprofen and colistin, the turbidity measurements revealed the presence of turbidity in the studied mixtures. The greatest change in pH relative to the value immediately after preparation was noted for combinations of ketoprofen and morphine sulfate with the tested antibiotic.

Colistin was found to be incompatible with ibuprofen and metamizole sodium formulations. It should also not be combined with morphine sulfate due to the significant differences in the pH value of the preparations. The colistin 0.67 mg/mL and 1.5 mg/mL infusion solutions were physically compatible with ketoprofen, tramadol hydrochloride, and paracetamol.