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Compatibility of filgrastim with selected antimicrobial drugs during simulated Y-site administration
1College of Pharmacy, Medical University of South Carolina (MUSC), Charleston 29425-2303, USA. hallpd@musc.edu
Abstract:
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.
Insights
Filgrastim generally maintains its activity when mixed with common antimicrobial drugs, though some combinations require caution. This study assessed filgrastim compatibility with various antibiotics and antifungals during simulated Y-site administration.
Area of Science:
- Pharmacology
- Drug Compatibility Studies
- Clinical Pharmacy
Background:
- Filgrastim is a granulocyte colony-stimulating factor used to stimulate white blood cell production.
- Co-administration of medications via Y-site is common in clinical practice, necessitating compatibility assessments.
- Understanding drug interactions is crucial for safe and effective patient care, especially in immunocompromised individuals.
Purpose of the Study:
- To evaluate the in vitro compatibility of filgrastim with several commonly used antimicrobial agents.
- To assess the impact of Y-site co-administration on filgrastim activity and antimicrobial drug stability.
- To identify potential drug interactions that may affect therapeutic efficacy or patient safety.
Main Methods:
- Filgrastim solutions at two concentrations were combined with imipenem-cilastatin, ceftazidime, fluconazole, gentamicin, tobramycin, and amikacin.
- Mixtures were prepared in triplicate, simulating Y-site administration, and stored at approximately 25°C for up to four hours.
- Assays included measurement of filgrastim activity (in vitro bioassay), antimicrobial drug concentrations (HPLC/FPIA), pH, and visual inspection for physical changes.
Main Results:
- Filgrastim retained its activity in most combinations, except for lower concentration filgrastim with gentamicin and higher concentration filgrastim with imipenem-cilastatin.
- Antimicrobial drug concentrations remained stable throughout the study period.
- No significant physical changes (precipitation, color change, haze) were observed; pH changes were negligible, except for an increase with ceftazidime.
Conclusions:
- Filgrastim demonstrates good compatibility with most tested antimicrobial drugs during short-term Y-site co-administration.
- Specific combinations, namely filgrastim with gentamicin or imipenem-cilastatin, require careful consideration due to potential loss of filgrastim activity.
- Antimicrobial agents generally remained stable, supporting their co-administration with filgrastim under appropriate monitoring.