Stability and compatibility of vancomycin for administration by continuous infusion

Vancomycin is increasingly used by continuous infusion, but few specific data are available about stability under practical conditions of preparation and use, and compatibility with other intravenous drugs commonly used in the routine hospital setting. Vancomycin stability [defined as recovery ≥ 93% of the original content (validated HPLC assay)] was examined throughout the whole process of centralized preparation, storage and use in the ward by infusion for up to 48 h, with allowances for deviations from recommended practice [exposure to high temperature; use of concentrated solutions (up to 83 g/L)]. Compatibility was assessed by mimicking co-administration in a single line via Y-shaped connectors with contact of 1 h at 25°C, followed by visual inspection (professional viewer), detection of particulate matter (particle analyser) and HPLC assay of vancomycin. Vancomycin was stable during the whole process and also during 72 h exposure of concentrated solutions at temperatures up to 37°C. Major incompatibilities were seen with β-lactams (temocillin, piperacillin/tazobactam, ceftazidime, imipenem, cefepime and flucloxacillin) and moxifloxacin, but not with ciprofloxacin, aminoglycosides and macrolides. Propofol, valproic acid, phenytoin, theophylline, methylprednisolone and furosemide were also incompatible, whereas ketamine, sufentanil, midazolam, morphine, piritramide, nicardipine, urapidil, dopamine, dobutamine and adrenaline were compatible. No effect or incompatibility with N-acetyl-cysteine or amino acid solutions was detected. Centralized preparation of vancomycin and its use by continuous infusion in wards is safe concerning stability, but careful attention must be paid to incompatibilities. Several drugs (including all β-lactams) require distinct intravenous lines or appropriate procedures to avoid undue contact.