PREMIXED INTRAVENOUS SOLUTION

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MEFOXIN1 and other antibacterial drugs, MEFOXIN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

1

Mefoxin is a registered trademark of Bioniche Teoranta.

DESCRIPTION

Cefoxitin sodium is a semi-synthetic, broad-spectrum cepha antibiotic for intravenous administration. It is derived from cephamycin C, which is produced by Streptomyces lactamdurans. Its chemical name is sodium (6R,7S)-3-(hydroxymethyl)-7-methoxy-8-oxo-7-[2-(2-thienyl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate carbamate (ester). The empirical formula is C16H16N3NaO7S2, and the molecular weight is 449.44. The structural formula is:

Cefoxitin sodium contains approximately 53.8 mg (2.3 milliequivalents) of sodium per gram of cefoxitin activity.

Premixed Intravenous Solution MEFOXIN (Cefoxitin Injection) is supplied as a sterile, nonpyrogenic, frozen iso-osmotic solution of cefoxitin sodium. Each 50 mL contains Cefoxitin Sodium, USP equivalent to either 1 gram or 2 grams cefoxitin. Dextrose Hydrous, USP has been added to the above dosages to adjust osmolality (approximately 2 grams and 1.1 grams to 1 gram and 2 gram dosages, respectively). The pH is adjusted with sodium bicarbonate and may have been adjusted with hydrochloric acid. The pH is approximately 6.5. After thawing, the solution is intended for intravenous use only. Solutions of MEFOXIN range from colorless to light amber.

The plastic container is fabricated from a specially designed multilayer plastic (PL 2040). Solutions are in contact with the polyethylene layer of this container and can leach out certain chemical components of the plastic in very small amounts within the expiration period. The suitability and safety of the plastic has been confirmed in tests in animals according to the USP biological tests for plastic containers, as well as by tissue culture toxicity studies.

CLINICAL PHARMACOLOGY

Clinical Pharmacology

Following an intravenous dose of 1 gram of cefoxitin, serum concentrations were 110 mcg/mL at 5 minutes, declining to less than 1 mcg/mL at 4 hours. The half-life after an intravenous dose is 41 to 59 minutes. Approximately 85 percent of cefoxitin is excreted unchanged by the kidneys over a 6-hour period, resulting in high urinary concentrations. Probenecid slows tubular excretion and produces higher serum levels and increases the duration of measurable serum concentrations.

Cefoxitin passes into pleural and joint fluids and is detectable in antibacterial concentrations in bile.

In a published study of geriatric patients ranging in age from 64 to 88 years with normal renal function for their age (creatinine clearance ranging from 31.5 to 174.0 mL/min), the half-life for cefoxitin ranged from 51 to 90 minutes, resulting in higher plasma concentrations than in younger adults. These changes were attributed to decreased renal function associated with the aging process.

Microbiology

The bactericidal action of cefoxitin results from inhibition of cell wall synthesis. Cefoxitin has in vitro activity against a wide range of gram-positive and gram-negative organisms. The methoxy group in the 7α position provides cefoxitin with a high degree of stability in the presence of beta-lactamases, both penicillinases and cephalosporinases, of gram-negative bacteria.

Cefoxitin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section.

Aerobic gram-positive microorganisms

 

Staphylococcus aureus2 (including penicillinase-producing strains)

 

Staphylococcus epidermidis2

 

Streptococcus agalactiae

 

Streptococcus pneumoniae

 

Streptococcus pyogenes

Most strains of enterococci, e.g., Enterococcus faecalis, are resistant.

2

Staphylococci resistant to methicillin/oxacillin should be considered resistant to cefoxitin.

Aerobic gram-negative microorganisms

 

Escherichia coli

 

Haemophilus influenzae

 

Klebsiella spp. (including K. pneumoniae)

 

Morganella morganii

 

Neisseria gonorrhoeae (including penicillinase-producing strains)

 

Proteus mirabilis

 

Proteus vulgaris

 

Providencia spp. (including Providencia rettgeri)

Anaerobic gram-positive microorganisms

 

Clostridium spp.

 

Peptococcus niger

 

Peptostreptococcus spp.

Anaerobic gram-negative microorganisms

 

Bacteroides distasonis

 

Bacteroides fragilis

 

Bacteroides ovatus

 

Bacteroides thetaiotaomicron

 

Bacteroides spp.

The following in vitro data are available, but their clinical significance is unknown.

Cefoxitin exhibits in vitro minimum inhibitory concentrations (MIC's) of 8 µg/mL or less for aerobic microorganisms and 16 µg/mL or less for anaerobic microorganisms against most (≥ 90%) strains of the following microorganisms; however, the safety and effectiveness of cefoxitin in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic gram-negative microorganisms

 

Eikenella corrodens [non-β-lactamase producers]

 

Klebsiella oxytoca

Anaerobic gram-positive microorganisms

 

Clostridium perfringens

Anaerobic gram-negative microorganisms

 

Prevotella bivia (formerly Bacteroides bivius)

Cefoxitin is inactive in vitro against most strains of Pseudomonas aeruginosa and enterococci and many strains of Enterobacter cloacae.

Susceptibility Tests

Dilution Techniques

Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MIC's). These MIC's provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MIC's should be determined using a standardized procedure. Standardized procedures are based on a dilution method1 (broth or agar) or equivalent with standardized inoculum concentrations and standardized concentrations of cefoxitin powder. The MIC values should be interpreted according to the following criteria:

For testing aerobic microorganisms3,4,5 other than Neisseria gonorrhoeae:

3

Staphylococci exhibiting resistance to methicillin/oxacillin should be reported as also resistant to cefoxitin despite apparent in vitro susceptibility.

4

For testing Haemophilus influenzae these interpretative criteria applicable only to tests performed by broth microdilution method using Haemophilus Test Medium (HTM)1.

5

For testing streptococci these interpretative criteria applicable only to tests performed by broth microdilution method using cation-adjusted Mueller-Hinton broth with 2 to 5% lysed horse blood1.

For testing Neisseria gonorrhoeae6: