Physical compatibility of ceftolozane-tazobactam with selected i.v. drugs during simulated Y-site administration

Abstract

Purpose. Results of a study to examine the physical compatibility of ceftolozane-tazobactam with common i.v. medications during simulated Y-site administration are presented. Methods. Ceftolozane-tazobactam was reconstituted according to manufacturer recommendations and diluted with 0.9% sodium chloride or 5% dextrose to solutions containing 15 mg (10 mg of ceftolozane and 5 mg of tazobactam)/mL. All other i.v. drugs were prepared according to manufacturer recommendations and diluted with 0.9% sodium chloride or 5% dextrose to standard concentrations used clinically. Y-site administration was simulated by mixing ceftolozane-tazobactam solution with each tested drug solution at a 1:1 ratio. Solutions were inspected for visual, turbidity, and pH changes immediately and 15, 60, and 120 minutes after mixing. Incompatibility was defined as precipitation, color change, a positive Tyndall test, a change in turbidity of ≥0.5 nephelometric turbidity unit, or a change in pH of ≥1 unit during the 120-minute observation period. Results. Of the 95 i.v. drugs tested, ceftolozane-tazobactam was compatible with 86 drugs in both diluents; notably, it was compatible with metronidazole in both solutions. No substantial pH changes were observed in any tested combination. Ceftolozane-tazobactam was incompatible with albumin, amphotericin B, caspofungin, cyclosporine, nicardipine, and phenytoin sodium due to turbidity changes and with propofol due to formation of an oily layer. Conclusion. Ceftolozane-tazobactam 15 mg (10 mg of ceftolozane and 5 mg of tazobactam)/mL was physically compatible with 86 of 95 study drugs tested in both 0.9% sodium chloride injection and 5% dextrose injection during simulated Y-site administration.