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INFECTIOUS DISEASES

Physical and Chemical Compatibility of Daptomycin with Nine Medications

Senior Director, Analytical Chemistry, Cubist Pharmaceuticals, Inc., Lexington, MA

Stephanie K Brodeur, MS

Senior Research Associate II, Analytical Chemistry, Cubist Pharmaceuticals, Inc.

Reprints: Jan-Ji Lai PhD, Cubist Pharmaceuticals, Inc., 65 Hayden Ave., Lexington, MA 02421-7994, fax 781/861-0620, jjlai{at}cubist.com

BACKGROUND: Hospitalized patients with serious gram-positive infections tend to require concomitant therapy. Unfortunately, a number of antimicrobial agents have demonstrated incompatibility with other agents commonly administered intravenously.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of the novel lipopeptide antibiotic daptomycin, at 20 mg/mL, with 9 commonly administered intravenous medications: aztreonam, ceftazidime, ceftriaxone, dopamine, gentamicin, fluconazole, heparin, levofloxacin, and lidocaine to support simultaneous Y-site administration.

METHODS: Daptomycin was admixed with each medication separately in NaCl 0.9%, incubated at room temperature, and assayed at 30, 60, and 120 minutes. Physical stability was assessed by visual inspection and by turbidity measurements. Chemical stability was assessed by HPLC analysis using standard methods.

RESULTS: All 9 daptomycin admixtures remained clear solutions, free of visible particulates. There were also few changes in turbidity (range 0 to –0.7 nephelometric turbidity units) during the study. In general, pH changes were within ± 0.06 of baseline readings for all admixtures. HPLC analysis indicated no significant reduction (<4%) in daptomycin potency after 120 minutes at room temperature compared with baseline values in all 9 admixtures tested. In addition, there was no significant reduction (<5%) in potency compared with baseline values of the 9 medications tested in the daptomycin admixtures.

CONCLUSIONS: The results of this study indicate that solutions of 9 commonly administered intravenous medications simultaneously Y-site administered with daptomycin are stable and compatible, based on both physical and chemical potency analyses.

Key Words: admixture, compatibility, daptomycin, stability

Published Online, August 24, 2004. www.theannals.com, DOI 10.1345/aph.1E124

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