Cefuroxime and Dextrose

CEFUROXIME AND DEXTROSE- cefuroxime sodium injection, solution
B. Braun Medical Inc.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefuroxime for Injection USP and Dextrose Injection USP and other antibacterial drugs, Cefuroxime for Injection USP and Dextrose Injection USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

DESCRIPTION

Cefuroxime for Injection USP and Dextrose Injection USP is a sterile, nonpyrogenic, single use, packaged combination of Cefuroxime Sodium USP (crystalline) and Dextrose Injection USP (diluent) in the DUPLEX® sterile container. The DUPLEX® Container is a flexible dual chamber container.

The drug chamber is filled with sterile crystalline Cefuroxime for Injection USP, a semi-synthetic, broad-spectrum, cephalosporin antibacterial for parenteral administration. It is the sodium salt of (6R ,7R)-7-[2-(2-furyl)glyoxylamido]-3-(hydroxymethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, 7² -(Z)-(O -methyloxime), carbamate (ester).

Cefuroxime Sodium USP has the following structural formula:

The empirical formula is C₁₆ H₁₅ N₄ NaO₈ S, representing a molecular weight of 446.4.

Cefuroxime contains approximately 54.2 mg (2.4 mEq) of sodium per gram of cefuroxime activity.

The diluent chamber contains Dextrose Injection USP. The concentration of Hydrous Dextrose USP has been adjusted to render the reconstituted drug product iso-osmotic. Dextrose Injection USP is sterile, nonpyrogenic, and contains no bacteriostatic or antimicrobial agents.

Hydrous Dextrose USP has the following structural (molecular) formula:

The molecular weight of Hydrous Dextrose USP is 198.17.

Dextrose hydrous USP has been added to the diluent to adjust osmolality (approximately 2.05 g and 1.45 g to 750 mg and 1.5 g dosages, respectively).

After removing the peelable foil strip, activating the seals, and thoroughly mixing, the reconstituted drug product is intended for single intravenous use. When reconstituted, the approximate osmolality of the reconstituted solution for Cefuroxime for Injection USP and Dextrose Injection USP is 290 mOsmol/kg.

Not made with natural rubber latex, PVC or Di (2-ethylhexyl) phthalate (DEHP).

The DUPLEX® dual chamber container is made from a specially formulated material. The product (diluent and drug) contact layer is a mixture of thermoplastic rubber and a polypropylene ethylene copolymer that contains no plasticizers. The safety of the container system is supported by USP biological evaluation procedures.

CLINICAL PHARMACOLOGY

Following IV doses of 750 mg and 1.5 g, serum concentrations were approximately 50 and 100 mcg/mL, respectively, at 15 minutes. Therapeutic serum concentrations of approximately 2 mcg/mL or more were maintained for 5.3 hours and 8 hours or more, respectively. There was no evidence of accumulation of cefuroxime in the serum following IV administration of 1.5 g doses every 8 hours to normal volunteers. The serum half-life after IV injection is approximately 80 minutes.

Approximately 89% of a dose of cefuroxime is excreted by the kidneys over an 8-hour period, resulting in high urinary concentrations.

Intravenous doses of 750 mg and 1.5 g produced urinary levels averaging 1,150 and 2,500 mcg/mL, respectively, during the first 8-hour period.

The concomitant oral administration of probenecid with cefuroxime slows tubular secretion, decreases renal clearance by approximately 40%, increases the peak serum level by approximately 30%, and increases the serum half-life by approximately 30%. Cefuroxime is detectable in therapeutic concentrations in pleural fluid, joint fluid, bile, sputum, bone, and aqueous humor.

Cefuroxime is detectable in therapeutic concentrations in cerebrospinal fluid (CSF) of adults and pediatric patients with meningitis. The following table shows the concentrations of cefuroxime achieved in cerebrospinal fluid during multiple dosing of patients with meningitis.

Table 1. Concentrations of Cefuroxime Achieved in Cerebrospinal Fluid During Multiple Dosing of Patients with Meningitis

Patients	Dose	Number of Patients	Mean (Range) CSF Cefuroxime Concentrations (mcg/mL) Achieved Within 8 Hours Post Dose
Pediatric patients(4 weeks to 6.5 years)	200 mg/kg/day, dividedq 6 hours	5	6.6(0.9–17.3)
Pediatric patients(7 months to 9 years)	200 to 230 mg/kg/day,divided q 8 hours	6	8.3(<2–22.5)
Adults	1.5 grams q 8 hours	2	5.2(2.7–8.9)
Adults	1.5 grams q 6 hours	10	6.0(1.5–13.5)

Cefuroxime is approximately 50% bound to serum protein.

Microbiology

Mechanism of Action

Cefuroxime is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis. Cefuroxime has activity in the presence of some beta-Iactamases, both penicillinases and cephalosporinases, of Gram-negative and Gram-positive bacteria.

Resistance

Resistance to cefuroxime is primarily through hydrolysis by beta-Iactamase, alteration of penicillin-binding proteins (PBPs), and decreased permeability.

Interaction with Other Antimicrobials

In an in vitro study antagonistic effects have been observed with the combination of chloramphenicol and cefuroxime.

Antimicrobial Activity

Cefuroxime has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section:

Gram-negative bacteria

• Enterobacter spp.
• Escherichia coli
• Klebsiella spp.
• Haemophilus influenzae
• Neisseria meningitidis
• Neisseria gonorrhoeae

Gram-positive bacteria

• Staphylococcus aureus
• Streptococcus pneumoniae
• Streptococcus pyogenes

The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for cefuroxime against isolates of similar genus or organism group. However, the efficacy of cefuroxime in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

Gram-negative bacteria

Citrobacter spp.
Providencia rettgeri
Haemophilus parainfluenzae
Proteus mirabilis
Moraxella catarrhalis
Morganella morganii
Salmonella spp.
Shigella spp.

Gram-positive bacteria

Staphylococcus epidermidis