Cefizox

CEFIZOX- ceftizoxime sodium injection, powder, lyophilized, for solution
Fujisawa Healthcare, Inc.

Fujisawa

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

FOR INTRAMUSCULAR

OR INTRAVENOUS USE

Description

Cefizox^® (ceftizoxime for injection, USP) is a sterile, semisynthetic, broad­spectrum, beta­lactamase resistant cephalosporin antibiotic for parenteral (IV, IM) administration. It is the sodium salt of [6R­[6a,7β(Z)]]­7­[[(2,3­dihydro­2­imino­4­ thiazolyl) (methoxyimino) acetyl] amino]­8­oxo­5­thia­1­azabicyclo [4.2.0] oct­2­ene­2­carboxylic acid. Its sodium content is approximately 60 mg (2.6 mEq) per gram of ceftizoxime activity.

It has the following structural formula:

C₁₂ H₁₂ N₅ NaO₅ S₂ 405.38

Ceftizoxime for injection, USP is a white to pale yellow crystalline powder.

Cefizox is supplied in vials equivalent to 500 mg, 1 gram or 2 grams of ceftizoxime, and in Piggyback Vials for IV admixture equivalent to 1 gram or 2 grams of ceftizoxime.

Clinical Pharmacology

The table below demonstrates the serum levels and duration of Cefizox (ceftizoxime for injection, USP) following IM administration of 500 mg and 1 gram doses, respectively, to normal volunteers.

Serum Concentrations After Intramuscular Administration Serum Concentration (μg/mL)

Dose	½ hr	1 hr	2 hr	4 hr	6 hr	8hr
500 mg	13.3	13.7	9.2	4.8	1.9	0.7
1 gm	36.0	39.0	31.0	15.0	6.0	3.0

Following IV administration of 1, 2, and 3 gram doses of Cefizox to normal volunteers, the following serum levels were obtained.

Serum Concentrations After Intravenous Administration Serum Concentration (μg/mL)

* ND=Not Done
Dose	5 min	10 min	30 min	1 hr	2 hr	4 hr	8 hr
1 gram	ND *	ND *	60.5	38.9	21.5	8.4	1.4
2 grams	131.8	110.9	77.5	53.6	33.1	12.1	2.0
3 grams	221.1	174.0	112.7	83.9	47.4	26.2	4.8

A serum half­life of approximately 1.7 hours was observed after IV or IM administration.

Cefizox is 30% protein bound.

Cefizox is not metabolized, and is excreted virtually unchanged by the kidneys in 24 hours. This provides a high urinary concentration. Concentrations greater than 6000 μg/mL have been achieved in the urine by 2 hours after a 1 gram dose of Cefizox intravenously. Probenecid slows tubular secretion and produces even higher serum levels, increasing the duration of measurable serum concentrations.

Cefizox achieves therapeutic levels in various body fluids, e.g., cerebrospinal fluid (in patients with inflamed meninges), bile, surgical wound fluid, pleural fluid, aqueous humor, ascitic fluid, peritoneal fluid, prostatic fluid and saliva, and in the following body tissues: heart, gallbladder, bone, biliary, peritoneal, prostatic, and uterine.

In clinical experience to date, no disulfiram­like reactions have been reported with Cefizox.

Microbiology

The bactericidal action of ceftizoxime results from inhibition of cell­wall synthesis. Ceftizoxime is highly resistant to a broad spectrum of beta­lactamases (penicillinase and cephalosporinase), including Richmond types I, II, III, TEM, and IV, produced by both aerobic and anaerobic gram­positive and gram­negative organisms. Ceftizoxime has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections described in the INDICATIONS AND USAGE section:

Aerobic Gram-Positive Microorganisms

Staphylococcus aureus (including penicillinase producing strains)

NOTE: Methicillin­resistant staphylococci are resistant to cephalosporins, including ceftizoxime.

Staphylococcus epidermidis (including penicillinase producing strains)

Streptococcus agalactiae

Streptococcus pneumoniae

Streptococcus pyogenes

NOTE: A streptococcal isolate that is susceptible to penicillin can be considered susceptible to ceftizoxime ⁴.

NOTE: Ceftizoxime is usually inactive against most strains of Enterococcus faecalis.

Aerobic Gram-Negative Microorganisms

Enterobacter spp.

Escherichia coli

Haemophilus influenzae (including ampicillin­resistant strains)

Klebsiella pneumoniae

Morganella morganii

Neisseria gonorrhoeae

Proteus mirabilis

Proteus vulgaris

Providencia rettgeri

Pseudomonas aeruginosa

Serratia marcescens

Anaerobic Microorganisms

Bacteroides spp.

Peptococcus spp.

Peptostreptococcus spp.

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ceftizoxime. However, the safety and effectiveness of ceftizoxime in treating clinical infections due to these microorganisms have not been established in adequate and well-controlled clinical trials.

Aerobic Gram-Negative Microorganisms

Aeromonas hydrophila

Citrobacter spp.

Moraxella catarrhalis

Neisseria meningitidis

Providencia stuartii

Susceptibility Testing Methods: