Cefoxitin sodium is available as a powder in vials containing the equivalent of 1 and 2 g of cefoxitin as the sodium salt3905 and a pharmacy bulk package containing 10 g of cefoxitin as the sodium salt.3906 The drug may be reconstituted with sterile water for injection, bacteriostatic water for injection, sodium chloride 0.9%, or dextrose 5%.3905; 3906 Each 1-g vial should be reconstituted with 10 mL to yield a solution containing cefoxitin 95 mg/mL.3905 Each 2-g vial should be reconstituted with 10 or 20 mL to yield a solution containing cefoxitin 180 or 95 mg/mL, respectively.3905 The 10-g pharmacy bulk package should be reconstituted with 43 or 93 mL to yield a solution containing cefoxitin 200 or 100 mg/mL, respectively.3906 After addition of the diluent, vials should be shaken and allowed to stand until the solution is clear.3905
For intravenous infusion, the reconstituted solution may be diluted further in 50 to 1000 mL of a compatible infusion solution.3905
Cefoxitin sodium also is available as a powder in single-dose dual-chamber flexible containers containing the equivalent of 1 or 2 g of cefoxitin as the sodium salt.3907 The diluent chamber for the 1- or 2-g dose contains approximately 50 mL of dextrose 4 or 2.2%, respectively, to yield an iso-osmotic solution upon reconstitution.3907
pH
Reconstituted solutions have a pH of 4.2 to 7.3905 The reconstituted drug in dual-chamber containers has a pH of about 6.5.3907
Osmolality
The osmolality of cefoxitin sodium 1 and 2 g was calculated for the following dilutions:1054
| Osmolality (mOsm/kg) | ||
|---|---|---|
| Cefoxitin in Diluent | 50 mL | 100 mL |
| 1 g in Dextrose 5% | 326 | 293 |
| 1 g in Sodium chloride 0.9% | 352 | 319 |
| 2 g in Dextrose 5% | 388 | 329 |
| 2 g in Sodium chloride 0.9% | 415 | 355 |
The osmolality of cefoxitin sodium (MSD) 50 mg/mL was determined to be 348 mOsm/kg in dextrose 5% and 361 mOsm/kg in sodium chloride 0.9%.1375
Cefoxitin sodium 1 and 2 g in dual-chamber flexible containers has an osmolality of 290 mOsm/kg when activated with the dextrose solution diluent.3907
The following maximum cefoxitin sodium concentrations were recommended to achieve osmolalities suitable for peripheral infusion in fluid-restricted patients:1180
| Diluent | Maximum Concentration (mg/mL) | Osmolality (mOsm/kg) |
|---|---|---|
| Dextrose 5% | 62 | 531 |
| Sodium chloride 0.9% | 56 | 508 |
| Sterile water for injection | 112 | 437 |
Sodium Content
Cefoxitin sodium contains approximately 53.8 mg (2.3 mEq) of sodium per gram of cefoxitin activity.3905
Cefoxitin sodium may be administered by direct intravenous injection or by intravenous infusion.3905 For direct intravenous injection, the reconstituted solution should be administered over 3 to 5 minutes directly into the vein or into the tubing of a running compatible infusion solution.3905 For intravenous infusion, the reconstituted solution may be diluted in 50 to 1000 mL of a compatible solution.3905
Solutions prepared from bulk pharmacy containers are intended only for intravenous infusion after dilution in a compatible solution.3906
Cefoxitin sodium in dual-chamber flexible containers and frozen premixed infusion solutions are intended for intravenous infusion over approximately 30 minutes.3907
The manufacturer states that cefoxitin sodium should not be admixed with aminoglycoside antibiotics such as amikacin sulfate, gentamicin sulfate, and tobramycin sulfate.3905 However, compatibility studies show that such admixtures may indeed be sufficiently stable to allow combined mixture in the same solution.
Intact vials should be stored between 2 and 25°C.3905 Exposure to temperatures above 50°C should be avoided.3905 Cefoxitin sodium powder is white to off-white in color.3905 Solutions may range from colorless to light amber.3905 Both the dry material and solutions may darken, depending on storage conditions; however, this discoloration is stated not to affect potency.3905 The concern over color is purely aesthetic.865
The manufacturer states that cefoxitin sodium solutions reconstituted with a recommended diluent to a concentration of 1 g/10 mL are stable for 6 hours at room temperature or 1 week under refrigeration.3905 Solutions diluted in 50 to 1000 mL of a manufacturer-recommended solution for infusion are stable for an additional 18 hours at room temperature or 48 hours under refrigeration.3905
Reconstituted solutions prepared from pharmacy bulk packages should be further diluted for infusion within 4 hours after initial entry into the vial.3906 Unused portions of pharmacy bulk packages should be discarded after 4 hours of initial entry.3906 Solutions diluted in 50 to 1000 mL of a manufacturer-recommended solution for infusion are stable for an additional 18 hours at room temperature or 48 under refrigeration.3906
Unactivated dual-chamber flexible plastic containers should be stored at controlled room temperature and not frozen.3907 Once the foil strip has been removed from the container, the product must be protected from light and used within 7 days, but not beyond the labeled expiration date.3907 Once reconstituted (activated), the drug should be used within 12 hours if stored at room temperature or 7 days if stored under refrigeration.3907 Do not freeze reconstituted solution.3907
Exposure of cefoxitin sodium (MSD) 40 mg/mL in sterile water for injection to 37°C for 24 hours, to simulate the use of a portable infusion pump, resulted in about a 3 to 4% cefoxitin loss.1391
Cefoxitin sodium solutions reconstituted as indicated in Table 1 are stable for 48 hours at 25°C and at least 7 days and, in some cases, up to 1 month at 5°C.308
Table 1. Stability of Reconstituted Cefoxitin Sodium 1 g308
| Diluent | Volume | Remarks |
|---|---|---|
| Bacteriostatic water for injection (benzyl alcohol) | 2 mL | 9% decomposition in 48 hr at 25°C. 4% in 7 days and 10% in 1 month at 5°C |
| Bacteriostatic water for injection (parabens) | 2 mL | 9% decomposition in 48 hr at 25°C. 5% in 7 days and 12% in 1 month at 5°C |
| Dextrose 5% | 10 mL | 9% decomposition in 48 hr at 25°C, 2% in 7 days at 5°C |
| Lidocaine HCl 0.5% (with parabens) | 2 mL | 8% decomposition in 48 hr at 25°C. 5% in 7 days and 10% in 1 month at 5°C |
| Lidocaine HCl 1% (with parabens) | 2 mL | 7% decomposition in 48 hr at 25°C. 2% in 7 days and 10% in 1 month at 5°C |
| Sodium chloride 0.9% | 10 mL | 8% decomposition in 48 hr at 25°C |
| Water for injection | 10 mL | 10% decomposition in 48 hr at 25°C, 1% in 7 days at 5°C |
| Water for injection | 4 mL | 7% decomposition in 48 hr at 25°C, 2% in 7 days at 5°C |
| Water for injection | 2 mL | 8% decomposition in 48 hr at 25°C. 2% in 7 days and 10% in 1 month at 5°C |
| (In plastic syringe) | 10 mL | 6% decomposition in 24 hr and 11% in 48 hr at 25°C |
Cefoxitin sodium (MSD) 1 and 2 g/10 mL in sterile water for injection, packaged in plastic syringes (Monoject), exhibited a 10% cefoxitin sodium loss in 2 days at 24°C and 23 days at 4°C. Less than 10% loss occurred in 3 months frozen at -15°C.1178
pH Effects
Cefoxitin sodium at 1 and 10 mg/mL in aqueous solution is stable over pH 4 to 8. The time to 10% decomposition when stored at 25°C was essentially independent of pH, ranging from 40 to 44 hours at pH 4 to 5 to 33 hours at pH 8. Under refrigeration, a pH 7 (unbuffered) aqueous solution showed 10% decomposition in 26 days. At pH less than 4, precipitation of the free acid may occur. Above pH 8, hydrolysis of the ß-lactam group may result.308
In another study, cefoxitin sodium in aqueous solution at 25°C exhibited minimum rates of decomposition at pH 5 to 7. The solutions in this pH range showed 10% decomposition in about 2 days. At pH 3, about 40 hours elapsed before 10% decomposition occurred. However, at pH 9, only 14 hours was required to incur a 10% loss.630
Freezing Solutions
The stability of cefoxitin sodium reconstituted with the diluents as shown in Table 2 was evaluated in the frozen state at -20°C. The solutions retained adequate potency for at least 30 weeks.308
An approximate twofold increase in particles of 2 to 60 µm produced by freezing and thawing cefoxitin sodium (MSD) 2 g/100 mL of dextrose 5% (Travenol) was reported. The reconstituted drug was filtered through a 0.45-µm filter into polyvinyl chloride (PVC) bags of solution and frozen for 7 days at -20°C. Thawing was performed at room temperature (29°C) for 12 hours. Although the total number of particles increased significantly, no particles greater than 60 µm were observed; the solutions complied with USP standards for particle sizes and numbers in large volume parenteral solutions.822
Table 2. Stability of Reconstituted Cefoxitin Sodium 1 g Frozen at -20°C308
| Diluent | Volume | Remarks |
|---|---|---|
| Bacteriostatic water for injection (benzyl alcohol) | 10 mL | 2% decomposition in 30 weeks. Thawed solutions showed 6% decomposition in 24 hr at 25°C and 1% in 7 days at 5°C |
| Bacteriostatic water for injection (parabens) | 10 mL | 2% decomposition in 30 weeks. Thawed solutions showed no decomposition in 24 hr at 25°C and 1% in 7 days at 5°C |
| Dextrose 5% | 10 mL | 3% decomposition in 30 weeks. Thawed solutions showed 8% decomposition in 24 hr at 25°C and 6% in 7 days at 5°C |
| Lidocaine HCl 0.5% | 2 mL | 2% cefoxitin decomposition in 26 weeks. Thawed solutions showed 6% decomposition in 24 hr at 25°C. Lidocaine stable |
| Sodium chloride 0.9% | 10 mL | 5% decomposition in 30 weeks. Thawed solutions showed 3% decomposition in 24 hr at 25°C and 6% in 7 days at 5°C |
| Water for injection | 10 mL | 1% decomposition in 30 weeks. Thawed solutions showed 3% decomposition in 24 hr at 25°C and 5% in 7 days at 5°C |
| Water for injection | 4 mL | No decomposition in 13 weeks |
A 3% or less cefoxitin sodium (MSD) loss was reported from a solution containing 40 mg/mL in sterile water for injection in PVC and glass containers after 30 days at -20°C. Subsequent thawing and storage for 4 days at 5°C, followed by 24 hours at 37°C to simulate the use of a portable infusion pump, resulted in an additional 3 to 4% cefoxitin sodium loss.1391
Sorption
Cefoxitin sodium was shown not to exhibit sorption to PVC bags and tubing, polyethylene tubing, Silastic tubing, and polypropylene syringes.536; 606
Central Venous Catheter
Cefoxitin sodium (Merck) 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. Essentially complete delivery of the drug was found with little or no drug loss occurring. 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
For a list of references cited in the text of this monograph, search the monograph titled References.