To determine the compatibility of norepinephrine bitartrate with levofloxacin, acyclovir, ampicillin/sulbactam, azithromycin, cefepime, and isavuconazonium sulfate for Y- site administration

Purpose:  Patients with sepsis commonly require both vasopressor support and effective intravenous antimicrobial therapy within the first hour of recognition of septic shock. However, data are inconclusive for some common antibiotics when infused concurrently with norepinephrine, the first-choice vasopressor. The purpose of this study was to determine the physical compatibility of norepinephrine bitrate when infused simultaneously with various antimicrobials such as levofloxacin, acyclovir, ampicillin/sulbactam, azithromycin, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam and isavuconazonium sulfate during simulated intravenous Y-site administration.

Methods:  Simulation of Y-compatibility of intravenous fluids can be experimentally demonstrated by mixing equal volumes of two drugs of interest. Hence, we prepared 1:1 mixture of norepinephrine bitartrate by mixing 32 micrograms/milliliter of norepinephrine bitartrate individually with clinically relevant concentrations of levofloxacin, acyclovir, ampicillin/sulbactam, azithromycin, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam and isavuconazonium sulfate. The physical stability of these mixtures was assessed via measurement of change in turbidity, visual inspection for color change, haziness, and precipitate formation within 0 to 4 hours after mixing.

Results:  The visual evaluation and turbidity measurements revealed that norepinephrine bitartrate is compatible with levofloxacin, acyclovir, ampicillin/sulbactam, azithromycin, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam and isavuconazonium sulfate. No color change, haziness, or precipitate formation was observed at 0 and 4 hours when the drugs were mixed at equal volume. The change in turbidity for the mixture as compared to the individual drugs was very minimal (0.001 to 0.004 nephelometric turbidity unit). No significant change in pH and temperature for the mixture was observed during the 4-hour period either.

Conclusion:  Therefore, our data indicates that norepinephrine bitartrate is compatible with levofloxacin, acyclovir, ampicillin/sulbactam, azithromycin, cefepime, ceftazidime/avibactam, ceftolozane/tazobactam and isavuconazonium sulfate for intravenous Y site infusion as evident by the physical stability of the mixture.