Compatibility of filgrastim with selected antimicrobial drugs during simulated Y-site administration

The compatibility of filgrastim with imipenem-cilastatin, ceftazidime, fluconazole, gentamicin, tobramycin, and amikacin was studied. Filgrastim 40 micrograms/mL or filgrastim 10 micrograms/mL (with human albumin) was combined with (1) imipenem-cilastatin 5 mg/mL (in terms of imipenem content), (2) ceftazidime 10 mg/mL (as the sodium salt), (3) fluconazole 2 mg/ mL, (4) gentamicin 1.6 mg/ mL (as the sulfate), (5) tobramycin 1.6 mg/mL (as the sulfate), or (6) amikacin 5 mg/ mL (as the sulfate). Equal volumes (5 mL) of the test-agent solutions were added in pairs to glass containers (simulating Y-site administration) in triplicate. Samples were analyzed for filgrastim activity, drug concentration, pH, and visible physical changes during storage at approximately 25 degrees C for up to four hours. Filgrastim activity was measured by the in vitro bioassay, and antimicrobial drug concentrations were measured by stability-indicating high-performance liquid chromatography or fluorescence polarization immunoassay. Filgrastim retained its activity, except for the combination of filgrastim at the lower concentration with gentamicin or at the higher concentration with imipenem-cilastatin. Antimicrobial drug concentrations did not change significantly during the study. No precipitation, color change, or haze was noted in any mixture. Changes in pH were negligible except for an increase in the mixture of filgrastim at either concentration with ceftazidime. In most cases, filgrastim retained its activity in the presence of a variety of antimicrobial drugs for up to four hours; in all cases, the antimicrobial drugs remained stable.