Physical Compatibility of Cefiderocol with Selected Intravenous Drugs During Simulated Y-site Administration

The physical compatibility of cefiderocol for injection (prepared as a diluted 2% cefiderocol solution) with potential co-administration drug products is presented. The compatibility of cefiderocol with a selection of 91 intravenous drugs was tested at clinically relevant concentrations using the admixed volume ratio 1:1. Compatibility of the mixtures was determined by visual observations, turbidity, and particulate-matter measurements. The mixtures were examined immediately after mixing, and then at 1 hour and 4 hours thereafter at room temperature. When using 0.9% sodium chloride or 5% dextrose injection for diluents, solutions of dobutamine hydrochloride, esomeprazole sodium, methylprednisolone acetate, propofol, rocuronium bromide, amiodarone hydrochloride, famotidine, labetalol hydrochloride, mycophenolate mofetil, acyclovir sodium, amphotericin B, caspofungin acetate, doxycycline, posaconazole, diphenhydramine hydrochloride, and phenytoin sodium were found to cause visible cloudiness upon mixing with 2% cefiderocol in both diluents. Solutions of lorazepam, tobramycin sulfate, and vancomycin hydrochloride were determined incompatible by examining the mixtures with the aid of a Tyndall light. These 19 drugs were clearly incompatible with cefiderocol for injection by visual examination. In addition, solutions of iron sucrose and albumin were incompatible with 2% cefiderocol based on sub-visual tests for turbidity and/or particulate matter. Based on sub-visual data, the 0.9% sodium chloride admixture of aminophylline and 2% cefiderocol was incompatible, while inconclusive results were obtained for the 0.9% sodium chloride admixtures of 2% cefiderocol with amikacin sulfate. Similarly, the 5% dextrose admixtures of either ciprofloxacin or polymyxin B sulfate with 2% cefiderocol were incompatible, whereas data for phenylephrine hydrochloride morphine sulfate, or undiluted sodium bicarbonate were inconclusive. Overall, the 2% cefiderocol solution was physically compatible with 63 of 91 drugs challenged at 1:1 volume ratio in both 0.9% sodium chloride and 5% dextrose diluents for at least 4 hours at the concentrations tested in this study.