Rx only

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

DESCRIPTION

Cefazolin for Injection, USP is a semi-synthetic cephalosporin for parenteral administration.  It is 5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 3-{[(5-methyl-1,3,4-thiadiazol-2-yl)thio]-methyl}-8-oxo-7-[[(1H-tetrazol-1-yl)acetyl] amino]-, monosodium salt (6R-trans).  The sodium content is 48 mg/g of cefazolin sodium.

 The structural formula is as follows:

       C14H13N8NaO4S3                                M.W. 476.5

            The pH of the constituted solution is between 4.5 and 6.

            Cefazolin for Injection, USP is supplied in 500 mg or 1 gram vials.  Each vial contains cefazolin sodium equivalent to 500 mg or 1 gram of cefazolin.  It is to be administered by intramuscular or intravenous routes.

CLINICAL PHARMACOLOGY

After intramuscular administration of cefazolin to normal volunteers, the mean serum concentrations were 37 mcg/mL at 1 hour and 3 mcg/mL at 8 hours following a 500 mg dose, and 64 mcg/mL at 1 hour and 7 mcg/mL at 8 hours following a 1 gram dose.

            Studies have shown that following intravenous administration of cefazolin to normal volunteers, mean serum concentrations peaked at approximately 185 mcg/mL and were approximately 4 mcg/mL at 8 hours for a 1 gram dose.

            The serum half-life for cefazolin is approximately 1.8 hours following IV administration and approximately 2 hours following IM administration.

            In a study (using normal volunteers) of constant intravenous infusion with dosages of 3.5 mg/kg for 1 hour (approximately 250 mg) and 1.5 mg/kg the next 2 hours (approximately 100 mg), cefazolin produced a steady serum level at the third hour of approximately 28 mcg/mL.

            Studies in patients hospitalized with infections indicate that cefazolin produces mean peak serum concentrations approximately equivalent to those seen in normal volunteers.

            Bile concentrations in patients without obstructive biliary disease can reach or exceed serum concentrations by up to five times; however, in patients with obstructive biliary disease, bile concentrations of cefazolin are considerably lower than serum concentrations (<1 mcg/mL).

            In synovial fluid, the cefazolin concentration becomes comparable to that reached in serum at about 4 hours after drug administration.

                                    Studies of cord blood show prompt transfer of cefazolin across the placenta.  Cefazolin is present in very low concentrations in the milk of nursing mothers.

            Cefazolin is excreted unchanged in the urine.  In the first 6 hours approximately 60% of the drug is excreted in the urine and this increases to 70 to 80% within 24 hours. Cefazolin achieves peak urine concentrations of approximately 2400 mcg/mL and 4000 mcg/mL respectively following 500 mg and 1 gram intramuscular doses.

            In patients undergoing peritoneal dialysis (2 L/hr.), cefazolin produced mean serum levels of approximately 10 and 30 mcg/mL after 24 hours’ instillation of a dialyzing solution containing 50 mg/L and 150 mg/L, respectively.  Mean peak levels were 29 mcg/mL (range 13 to 44 mcg/mL) with 50 mg/L (three patients), and 72 mcg/mL (range 26 to 142 mcg/mL) with 150 mg/L (six patients).  Intraperitoneal administration of cefazolin is usually well tolerated.

            Controlled studies on adult normal volunteers, receiving 1 gram 4 times a day for 10 days, monitoring CBC, AST (SGOT), ALT (SGPT), bilirubin, alkaline phosphatase, BUN, creatinine and urinalysis, indicated no clinically significant changes attributed to cefazolin.

Microbiology

In vitro tests demonstrate that the bactericidal action of cephalosporins results from inhibition of cell wall synthesis.  Cefazolin has been shown to be active against the following organisms both in vitro and in clinical infections as described in the INDICATIONS AND USAGE.

 Gram-Positive Aerobes

            Staphylococcus aureus (including  beta-lactamase-producing strains)

            Staphylococcus epidermidis

           Streptococcus pyogenes, Streptococcus agalactiae, and other strains of streptococci

            Streptococcus pneumoniae

           Methicillin-resistant staphylococci are uniformly resistant to cefazolin, and many strains of enterococci are resistant.

 Gram-Negative Aerobes

            Escherichia coli

           Proteus mirabilis

Most strains of indole positive Proteus (Proteus vulgaris), Enterobacter spp., Morganella morganii, Providencia rettgeri, Seratia spp., and Pseudomonas spp. are resistant to cefazolin.

Susceptibility Tests:

Diffusion Techniques:

 Quantitative methods that require measurement of zone diameters provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure1 that has been recommended for use with disks to test the susceptibility of microorganisms to cefazolin uses the 30 mcg cefazolin disk. Results of the standardized single-disk susceptibility test1 with a 30 mcg cefazolin disk should be interpreted according to the following criteria:

Standardized single-disk susceptibility test should be performed ONLY with a 30 mcg cefazolin disk.

A report of “Susceptible” indicates that the pathogen is likely to be inhibited by usually achievable concentrations of the antimicrobial compound in the blood. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that usually achievable concentrations of the antimicrobial compound in the blood are unlikely to be inhibitory and that other therapy should be selected.

Standardized susceptibility test procedures require the use of laboratory control microorganisms. The 30 mcg cefazolin disk should provide the following zone diameters in these laboratory test quality control strains:

The cefazolin disk should not be used for testing susceptibility to other cephalosporins.

Dilution Techniques:

Quantitative methods that are used to determine minimum inhibitory concentrations provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. One such standardized procedure uses a standardized dilution method2 (broth, agar, or microdilution) or equivalent with cefazolin powder. The MIC values obtained should be interpreted according to the following criteria.

Interpretation should be as stated above for results using dilution techniques.

As with standard diffusion techniques, dilution methods require the use of laboratory control microorganisms. Standard cefazolin powder should provide the following MIC values:

INDICATIONS AND USAGE

Cefazolin for Injection is indicated in the treatment of the following serious infections due to susceptible organisms:

            Respiratory Tract Infections: Due to S. pneumoniae, S. aureus (including beta-lactamase-producing strains) and S. pyogenes.  

            Injectable benzathine penicillin is considered to be the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.

            Cefazolin is effective in the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available.

            Urinary Tract Infections: Due to E. coli, P. mirabilis.

            Skin and Skin Structure Infections: Due to S. aureus (including beta-lactamase-producing strains), S. pyogenes, and other strains of streptococci.

            Biliary Tract Infections: Due to E. coli, various strains of streptococci, P. mirabilis, and S. aureus.

            Bone and Joint Infections: Due to S. aureus.

            Genital Infections: (i.e., prostatitis, epididymitis) due to E. coli, P. mirabilis.

            Septicemia: Due to S. pneumoniae, S. aureus (including beta-lactamase-producing strains), P. mirabilis, E. coli.

            Endocarditis: Due to S. aureus (including beta-lactamase-producing strains) and S.