Stability and compatibility study of cefepime in comparison with ceftazidime for potential administration by continuous infusion under conditions pertinent to ambulatory treatment of cystic fibrosis patients and to administration in intensive care units

• Published in: Journal of antimicrobial chemotherapy Vol. 51; no. 3; pp. 651 - 658
• Main Authors: Baririan, Nariné, Chanteux, Hugues, Viaene, Eric, Servais, Hélène, Tulkens, Paul M.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2003; Oxford Publishing Limited (England)
• Subjects: Ambulatory Care - methods; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cefepime; Ceftazidime - administration & dosage; Ceftazidime - analysis; Ceftazidime - pharmacokinetics; Cephalosporins - administration & dosage; Cephalosporins - analysis; Cephalosporins - pharmacokinetics; Chemical Precipitation; compatibility; continuous infusion; Cystic Fibrosis - drug therapy; Cystic Fibrosis - metabolism; degradation; Drug Incompatibility; Drug Stability; Drug Storage; Drug Therapy, Combination - administration & dosage; Drug Therapy, Combination - pharmacokinetics; Infusions, Intravenous; Intensive Care Units; Medical sciences; Pharmacology. Drug treatments; stability; Human; Intensive care; Stability; Intravenous administration; Cefepime; β-Lactams; Cystic fibrosis; Degradation; Antibiotic; Chemotherapy; Cephalosporin derivatives; Treatment; Drug interaction; Application method; Ambulatory; Antibacterial agent; Compatibility; Ceftazidime
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkg134

Cefepime has been examined for stability, potential liberation of degradation products and compatibility with other drugs under conditions mimicking its potential use by continuous infusion in cystic fibrosis and intensive care patients (5–12% w/v solutions; temperatures from 20 to 37°C; 1 h contact at 25°C with other drugs frequently co-administered by intravenous route to these types of patients). Ceftazidime was used as a comparator based on a previous normative study with this antibiotic for the same indications. Based on a limit of max. 10% degradation, cefepime can be considered stable for a maximum of 24 h at 25°C, but for only ∼14 h at 30°C, and for <10 h at 37°C. Cefepime released so far unidentified degradation products if maintained at >30°C for >12 h as shown from a marked increase in pH and from the development of a strong red–purple colour. Incompatibilities were observed with erythromycin, propofol, midazolam, phenytoin, piritramide, theophylline, nicardipine, N-acetylcysteine and a concentrated solution of dobutamine. We conclude that: (i) cefepime cannot be used safely by continuous infusion if containers are kept for more than a few hours at 37°C (as will be the case for cystic fibrosis patients if using portable pumps carried under clothes); (ii) caution must be exercised in intensive care patients if the temperature and co-administration of other drugs is not kept under tight control. The nature and safety of the cefepime degradation products need to be studied further.