Cefepime hydrochloride is available as 1 and 2 g of cefepime in vials.3295 The drug also may be available in a 500-mg vial.3295; 3324 The products contain L-arginine in an approximate concentration of 707 mg/g of cefepime to control the pH of the reconstituted solution.3295
For intramuscular administration, reconstitute the 500-mg and 1-g vials with 1.3 and 2.4 mL, respectively, of sterile water for injection, sodium chloride 0.9%, dextrose 5%, lidocaine hydrochloride 0.5 or 1%, or bacteriostatic water for injection preserved with parabens or benzyl alcohol to yield a solution with a cefepime concentration of 280 mg/mL.3295
For intravenous injection, reconstitute the 500-mg and 1-g vials with 5 and 10 mL, respectively, of a compatible diluent to yield a solution with a cefepime concentration of 100 mg/mL; reconstitute the 2-g vial with 10 mL of a compatible diluent to yield a solution with a cefepime concentration of 160 mg/mL.3295 The reconstituted solutions should be added to compatible intravenous solutions for intermittent intravenous infusion.3295
Cefepime hydrochloride also is available as 1 and 2 g of cefepime in ADD-Vantage vials.3295 Each ADD-Vantage vial also contains L-arginine in an approximate concentration of 707 mg/g of cefepime.3295 ADD-Vantage vials of cefepime hydrochloride should be prepared with 50 or 100 mL of dextrose 5% or sodium chloride 0.9% in ADD-Vantage diluent bags.3295
Cefepime hydrochloride is available as 1 and 2 g of cefepime in a dual-chamber flexible container.3297 The drug chamber also contains L-arginine in an approximate concentration of 725 mg/g of cefepime.3297 The diluent chamber contains approximately 50 mL of dextrose 5% for use as a diluent.3297
Cefepime is available in 1- and 2-g sizes as a frozen premixed solution in 50- and 100-mL bags, respectively.3296 Approximately 1.03 or 2.06 g of dextrose hydrous has been added to the 50- or 100-mL bags, respectively, to adjust the osmolality.3296 The frozen premixed solution also contains L-arginine in an approximate concentration of 725 mg/g of cefepime with or without hydrochloric acid in water for injection for intravenous infusion.3296
pH
The pH of the reconstituted solution and the frozen premixed solution ranges from 4 to 6.3295; 3296; 3297
Osmolality
Cefepime 1 and 2 g in dual-chamber flexible containers has an approximate osmolality of 431 and 577 mOsm/kg, respectively, when activated with the dextrose solution diluent.3297
Frozen premixed solutions of cefepime are iso-osmotic.3296
Cefepime hydrochloride is administered by intermittent intravenous infusion over approximately 30 minutes;3295; 3296; 3297 the manufacturer states that the drug also can be given by intramuscular injection for certain indications.3295
Intact vials of cefepime hydrochloride should be stored at controlled room temperature and protected from light.3295 Reconstituted solutions may vary from pale yellow to amber.3295 Both the powder and reconstituted solutions may darken during storage like other cephalosporins.3295; 3297 In one study, solutions of cefepime in sterile water for injection at concentrations greater than 50 g/L underwent marked color changes (i.e., from light yellow to dark red) in 2 hours at 37°C.3105 When stored as recommended, the drug is not adversely affected.3295; 3279
Reconstituted solutions of cefepime hydrochloride in compatible diluents are stable for 24 hours at room temperatures of 20 to 25°C and for 7 days under refrigeration at 2 to 8°C.3295 Cefepime 1 and 2 g in dual-chamber flexible plastic containers with dextrose solution diluent should be used within 12 hours after activation if stored at room temperature and in 5 days if stored under refrigeration.3297
pH Effects
Cefepime hydrochloride is most stable at pH values in the range of 4 to 5. At higher pH values, cefepime hydrochloride is less stable. Cefepime hydrochloride decomposition results in alkaline degradation products, which may increase the rate of loss.2513; 2514; 2515
Freezing Solutions
The commercially available frozen injection should be thawed at room temperature of 25°C or under refrigeration at 5°C; solutions should not be subject to force thawing by immersion in water baths or microwaving.3296 The manufacturer indicates that the thawed solution is stable for 24 hours at room temperature of 25°C or 7 days under refrigeration at 5°C.3296 Thawed solutions should not be refrozen.3296
Syringes
Cefepime (Bristol-Myers Squibb) 100 and 200 mg/mL in dextrose 5%, sodium chloride 0.9%, and sterile water for injection was packaged as 10 mL of solution in 10-mL polypropylene syringes and capped (Becton Dickinson). The samples were stored frozen at ?20°C for 90 days and were also tested without having been frozen. The solutions remained stable for up to 14 days refrigerated at 4°C, losing 10% or less of the cefepime. In samples stored at room temperature of about 23°C, less than 10% loss occurred in 1 day in most cases, but losses as high as 13% occurred in 2 days in some (but not all) samples that were evaluated.2220; 2221 Samples refrigerated up to 5 days followed by room temperature storage exhibited similar stability, exhibiting less than 10% loss in 1 day but higher losses after 2 days.2220
Cefepime (Bristol-Myers Squibb) 20 mg/mL in sodium chloride 0.9% was packaged in 10-mL polypropylene syringes (Becton Dickinson) and stored at 25 and 5°C. The drug solutions remained clear, but the color deepened to a darker yellow during storage at room temperature. About 5% loss occurred in 2 days and 11% loss in 4 days at 25°C. About 3% loss was found after 21 days at 5°C. The losses were comparable to the drug solution stored in a glass flask, indicating sorption to syringe components did not occur.2341
Central Venous Catheter
Cefepime (Bristol-Myers Squibb) 5 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Delivery of the cefepime hydrochloride ranged from 92 to 95% of the initial concentration among the 3 lumens. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Peritoneal Dialysis Solutions
Cefepime (Bristol-Myers Squibb) 0.125 and 0.25 mg/mL in Inpersol peritoneal dialysis solution with dextrose 4.25% is stable, exhibiting 3% loss in 7 days at 5°C, 2% loss in 24 hours at room temperature, and 8% loss in 24 hours at 37°C.1682
Cefepime (Bristol-Myers Squibb) 0.1 mg/mL in Delflex solution with dextrose 1.5% stored at various temperatures was evaluated for physical and chemical stability. No visible particulates or changes in color or clarity were observed in any sample. Cefepime exhibited no loss in 14 days at 4°C, 7% loss in 7 days at 25°C, and 4% loss in 24 hours and 9% loss in 48 hours at body temperature.2283
Cefepime (Bristol-Myers Squibb) 0.48 mg/mL was found to exhibit less than 10% loss in icodextrin 7.5% peritoneal dialysis solution (Extraneal) after 7 days at refrigerator temperature, 2 days at room temperature, and 4 hours at 37°C.2616
Cefepime hydrochloride was evaluated for stability in pH-neutral Balance with dextrose 1.5% (Fresenius).3270 Bags of 2-compartment pH-neutral Balance with 1.5% dextrose contained cefepime 250 mg/L in the non-dextrose (i.e., buffer solution) compartment for storage at 4 and 25°C; for bags intended for storage at 37°C, the initial concentration of cefepime in the non-dextrose compartment also was 250 mg/L; however, the 2 compartments were combined immediately prior to storage at 37°C for a final cefepime concentration of 125 mg/L.3270 No color change or precipitation was noted on visual assessment and no meaningful pH changes occurred.3270 Less than 10% loss of cefepime occurred in 7 days at 4°C, 3 days at 25°C, and 12 hours at 37°C.3270
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