Document
DailyMed Label: Cefazolin Sodium
Title
DailyMed Label: Cefazolin Sodium
Date
2021
Document type
DailyMed Prescription
Name
Cefazolin Sodium
Generic name
Cefazolin Sodium
Manufacturer
B. Braun Medical Inc.
Product information
NDC: 0264-3103
Product information
NDC: 0264-3103
Product information
NDC: 0264-3105
Product information
NDC: 0264-3105
Description
Cefazolin for Injection USP and Dextrose Injection USP is a sterile, nonpyrogenic, single-dose, packaged combination of Cefazolin Sodium USP (lyophilized) and sterile iso-osmotic diluent in the DUPLEX® sterile container. The DUPLEX® Container is a flexible dual chamber container.
After reconstitution the approximate osmolality for Cefazolin for Injection USP and Dextrose Injection USP is 290 mOsmol/kg.
The drug chamber is filled with sterile lyophilized Cefazolin Sodium USP, a semi-synthetic cephalosporin and has the following IUPAC nomenclature: Sodium ( 6R,7R )-3-[[(5-methyl-1,3,4-thiadiazol-2-yl)thio]methyl]-8-oxo-7-[2-(1 H -tetrazol-1-yl)acetamido]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate. Its empirical formula is C 14 H 13 N 8 NaO 4 S 3 and its molecular weight is 476.48.
Cefazolin Sodium USP has the following structural formula:
The sodium content is 48 mg/g of cefazolin sodium.
The diluent chamber contains Dextrose Injection USP, an iso-osmotic diluent using Hydrous Dextrose USP in Water for Injection USP. Dextrose Injection USP is sterile, nonpyrogenic, and contains no bacteriostatic or antimicrobial agents. Its empirical formula is C 6 H 12 O 6 •H 2 O and its molecular weight is 198.17.
Hydrous Dextrose USP has the following structural (molecular) formula:
Cefazolin Sodium USP is supplied as a lyophilized form equivalent to either 1 g or 2 g of cefazolin. Dextrose hydrous USP has been added to the diluent to adjust osmolality (approximately 2 g [4.0% w/v] and 1.5 g [3.0% w/v] for the 1 g and 2 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.
Reconstituted solutions of Cefazolin for Injection and Dextrose Injection range in color from pale yellow to amber.
Not made with natural rubber latex, PVC or 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.
Diagram of Cefazolin Molecular Structure
Diagram of Dextrose Molecular Structure
Indications
Cefazolin for Injection and Dextrose Injection is a cephalosporin antibacterial indicated for:
Treatment of the following infections caused by susceptible isolates of the designated microorganisms in adult and pediatric patients for whom appropriate dosing with this formulation can be achieved: ( 1 )
Respiratory tract infections ( 1.1 );
Urinary tract infections ( 1.2 );
Skin and skin structure infections ( 1.3 );
Biliary tract infections ( 1.4 );
Bone and joint infections ( 1.5 );
Genital infections ( 1.6 );
Septicemia ( 1.7 );
Endocarditis ( 1.8 )
Perioperative prophylaxis in adults and pediatric patients aged 10 to 17 years old for whom appropriate dosing with this formulation can be achieved ( 1.9 )
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefazolin for Injection and Dextrose Injection and other antibacterial drugs, Cefazolin for Injection and Dextrose Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. ( 1.10 ).
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of respiratory tract infections due to Streptococcus pneumoniae, Staphylococcus aureus and Streptococcus pyogenes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ] .
Limitations of Use
Injectable benzathine penicillin is considered the drug of choice in treatment and prevention of streptococcal infections, including the prophylaxis of rheumatic fever.
Cefazolin for Injection and Dextrose Injection is indicated for the eradication of streptococci from the nasopharynx; however, data establishing the efficacy of cefazolin in the subsequent prevention of rheumatic fever are not available.
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of urinary tract infections due to Escherichia coli , and Proteus mirabilis in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of skin and skin structure infections due to S. aureus , S. pyogenes , and Streptococcus agalactiae in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of biliary infections due to E. coli , various isolates of streptococci, P. mirabilis , and S. aureus in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of bone and joint infections due to S. aureus in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of genital infections due to E. coli , and P. mirabilis in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of septicemia due to S. pneumoniae , S. aureus , P. mirabilis , and E. coli in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of endocarditis due to S. aureus and S. pyogenes in adults and pediatric patients for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.2 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ].
Cefazolin for Injection and Dextrose Injection is indicated for perioperative prophylaxis in adults and pediatric patients aged 10 to 17 years old for whom appropriate dosing with this formulation can be achieved [see Dosage and Administration ( 2.1 , 2.3 , 2.4 , 2.5 ) and Use in Specific Populations (8.4) ] .
The perioperative use of Cefazolin for Injection and Dextrose Injection is indicated in adult and pediatric (aged 10 to 17 years old) surgical patients in whom infection at the operative site would present a serious risk (e.g., during open-heart surgery and prosthetic arthroplasty).
The prophylactic administration of Cefazolin for Injection and Dextrose Injection preoperatively, intraoperatively, and postoperatively may reduce the incidence of certain postoperative infections in patients undergoing surgical procedures which are classified as contaminated or potentially contaminated (e.g., vaginal hysterectomy, and cholecystectomy in high-risk patients such as those older than 70 years, with acute cholecystitis, obstructive jaundice, or common duct bile stones).
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Cefazolin for Injection and Dextrose Injection and other antibacterial drugs, Cefazolin for Injection and Dextrose Injection should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Dosage
If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered. ( 2.1 )
For intravenous use only administered over approximately 30 minutes. ( 2.1 )
Table 1: Recommended Dosing Schedule in Adult Patients with CLcr Greater Than or Equal To 55 mL/min. ( 2.1 , 2.2 and 2.3 )
Site and Type of Infection
Dose
Frequency
Moderate to severe infections
500 mg to 1 gram
every 6 to 8 hours
Mild infections caused by susceptible gram-positive cocci
250 mg to 500 mg
every 8 hours
Acute, uncomplicated urinary tract infections
1 gram
every 12 hours
Pneumococcal pneumonia
500 mg
every 12 hours
Severe, life-threatening infections (e.g., endocarditis, septicemia) In rare instances, doses of up to 12 grams of cefazolin per day have been used.
1 gram to 1.5 grams
every 6 hours
Perioperative prophylaxis
1 gram to 2 grams
½ to 1 hour prior to start of surgery
500 mg to 1 g
during surgery for lengthy procedures
500 mg to 1 g
every 6 to 8 hours for 24 hours postoperatively
Recommended Dosing Schedule in Pediatric Patients with CLcr Greater than or Equal to 70 mL/min. ( 2.1 , 2.2 , and 2.3 )
Site and Type of Infection
Dose
Frequency
Moderate to severe infections For the treatment indications (1.1 to 1.8)
25 to 50 mg per kg
divided into 3 or 4 equal doses
Severe infections
May increase to 100 mg per kg
divided into 3 or 4 equal doses
Perioperative prophylaxis (10 to 17 years old)
< 50 kg: 1 gram
½ to 1 hour prior to start of surgery
≥ 50 kg: 2 grams
500 mg to 1 g
during surgery for lengthy procedures
500 mg to 1 g
every 6 to 8 hours for 24 hours postoperatively
Dosage adjustment is required for adult patients with CLcr that is less than 55 mL/min and pediatric patients with CLcr that is less than 70 mL/min. ( 2.4 and 8.6 )
See full prescribing information for preparation and administration instructions. ( 2.5 )
If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.
Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.
D
osage for the Treatment of
Infections in
Adults with Creatinine Clearance (CLcr) Equal to 55 mL/min or Greater
The recommended adult dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8)] are outlined in Table 1 below. Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.
Table 1: Recommended Dosage in Adult Patients with CLcr Equal to 55 mL/min or Greater
If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.
.
Site and Type of Infection
Dose
Frequency
Moderate to severe infections
500 mg to 1 gram
every 6 to 8 hours
Mild infections caused by susceptible gram-positive cocci
250 mg to 500 mg
every 8 hours
Acute, uncomplicated urinary tract infections
1 gram
every 12 hours
Pneumococcal pneumonia
500 mg
every 12 hours
Severe, life-threatening infections (e.g., endocarditis, septicemia) In rare instances, doses of up to 12 grams of cefazolin per day have been used.
1 gram to 1.5 grams
every 6 hours
Dosage for the Treatment of
Infections in
Pediatric Patients with CLcr Equal to
70 mL/min or Greater
The recommended pediatric dosages for the treatment of infections [see Indications and Usage (1.1 to 1.8)] are outlined in Table 2 below. Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.
If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered [see Use in Specific Populations (8.4) ] .
Table 2: Recommended Dosage in Pediatric Patients with CLcr 70 mL/min or greater for Treatment of Infections [see Indications and Usage (1.1 to 1.8)]
Type of Severity
Recommended Total Daily Dosage
Mild to moderate infections
25 mg/kg to 50 mg/kg, divided into 3 or 4 equal doses
Severe infections
May increase to 100 mg/kg, divided into 3 or 4 equal doses
Dosage for Perioperative Prophylaxis in Adults with CLcr Equal to 55 mL/min or Greater
To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended dosages are described in Table 3 below.
Table 3: Recommended Dosage for Perioperative Prophylaxis in Adults with CLcr to
55 mL/min or Greater
Dose administered
½ hour to 1 hour prior to the start of surgery
Additional dose during lengthy operative procedures (e.g., 2 hours or more)
Dose for 24 hours postoperatively
1 g 2 g
500 mg to 1 g
500 mg to 1 g every 6 hours to 8 hours
If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended and an alternative formulation of cefazolin should be considered.
It is important that (i) the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibacterial concentrations are present in the serum and tissues at the time of initial surgical incision; and (ii) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient concentrations of the antibacterial drug at the anticipated moments of greatest exposure to infective organisms.
The perioperative prophylactic administration of cefazolin should usually be discontinued within a 24-hour period after the surgical procedure. In surgery where the occurrence of infection may be particularly devastating (e.g., open-heart surgery and prosthetic arthroplasty), the prophylactic administration of cefazolin may be continued for 3 days to 5 days following the completion of surgery.
Dosage
for
Perioperative
Prophyla
xis
in
Pediatric Patients
Aged 10 to 17 Years Old with CLcr 70 mL/min or Greater
To prevent postoperative infection in contaminated or potentially contaminated surgery, recommended doses are described in Table 4 below.
Table 4: Recommended Dosage for Perioperative Prophylaxis in Pediatric Patients with CLcr 70 mL/min or greater Aged 10 to 17 years Old
Body weight (kg)
Dose administered ½ to 1 hour prior to the start of surgery
Additional dose during lengthy operative procedures (e.g., 2 hours or more)
Dose for 24 hours postoperatively
Less than 50 kg
1 g
500 mg to 1 g
500 mg to 1 g every 6 hours to 8 hours
Greater than or equal to 50 kg
2 g
* If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.
It is important that (i) the preoperative dose be given just prior (1/2 hour to 1 hour) to the start of surgery so that adequate antibacterial concentrations are present in the serum and tissues at the time of initial surgical incision; and (ii) cefazolin be administered, if necessary, at appropriate intervals during surgery to provide sufficient concentrations of the antibacterial drug at the anticipated moments of greatest exposure to infective organisms.
The administration of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis should usually be discontinued within a 24-hour period after the surgical procedure. In surgery where the occurrence of infection may be particularly devastating the administration of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis may be continued for 3 days to 5 days following the completion of surgery.
Dosage Recommendations in Adult Patients with CLcr less than 55 mL/min
The dosage recommendation for Cefazolin for Injection and Dextrose Injection in adult patients with renal impairment (CLcr less than 55 mL/min) is outlined in Table 5 below.
Table 5: Dosage Recommendation for Adult Patients with CLcr less than 55 mL/min
Creatinine Clearance
Dose
Frequency
35 to 54 mL/min
Recommended dose
every 8 hours or longer
11 to 34 mL/min
Half of recommended dose
If the recommended dose in adult patients with creatinine clearance equal to 35 mL/min or greater is 1 gram, then this product is not recommended for use in patients with creatinine clearance less than 35 mL/min and an alternative formulation of cefazolin should be considered.
every 12 hours
10 mL/min or less
Half of recommended dose
every 18 to 24 hours
Dosage
Recommendations
in
Pediatric
Patients with
CLcr less than 70 mL/min
The dosage recommendation for Cefazolin for Injection and Dextrose Injection in pediatric patients with renal impairment (CLcr less than 70 mL/min) is outlined in Table 6 below.
Table 6: Recommended Dosage in Pediatric Patients with CLcr less than 70 mL/min
Creatinine Clearance
Recommended Dosage
40 to 70 mL/min
60% of the normal daily dose given in equally divided doses every 12 hours
20 to 40 mL/min
25% of the normal daily dose given in equally divided doses every 12 hours
5 to 20 mL/min
10% of the normal daily dose every 24 hours
*If a dose of Cefazolin for Injection and Dextrose Injection is required that does not equal 1 gram or 2 grams, this product is not recommended for use and an alternative formulation of cefazolin should be considered.
This reconstituted solution of Cefazolin for Injection and Dextrose Injection is for intravenous use only.
Do not use plastic containers in series connections. Such use would result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. If administration is controlled by a pumping device, care must be taken to discontinue pumping action before the container runs dry or air embolism may result.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Use only if solution is clear and container and seals are intact.
DUPLEX® Container Storage
To avoid inadvertent activation, the DUPLEX® Container should remain in the folded position until activation is intended.
Patient Labeling and Drug Powder/Diluent Inspection
Apply patient-specific label on foil side of container. Use care to avoid activation. Do not cover any portion of foil strip with patient label.
Unlatch side tab and unfold DUPLEX® Container (see Diagram 1 ).
Visually inspect diluent chamber for particulate matter.
Use only if container and seals are intact.
To inspect the drug powder for foreign matter or discoloration, peel foil strip from drug chamber (see Diagram 2 ).
Protect from light after removal of foil strip.
Note: If foil strip is removed, the container should be re-folded and the side tab latched until ready to activate. The product must then be used within 7 days, but not beyond the labeled expiration date.
Reconstitution (Activation)
Do not use directly after storage by refrigeration, allow the product to equilibrate to room temperature before patient use.
Unfold the DUPLEX® Container and point the set port in a downward direction. Starting at the hanger tab end, fold the DUPLEX® Container just below the diluent meniscus trapping all air above the fold. To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber (see Diagram 3 ).
Agitate the liquid-powder mixture until the drug powder is completely dissolved.
Note: Following reconstitution (activation), product must be used within 24 hours if stored at room temperature or within 7 days if stored under refrigeration.
Administration
Visually inspect the reconstituted solution for particulate matter.
Point the set port in a downwards direction. Starting at the hanger tab end, fold the DUPLEX® Container just below the solution meniscus trapping all air above the fold. Squeeze the folded DUPLEX® Container until the seal between reconstituted drug solution and set port opens, releasing liquid to set port (see Diagram 4 ).
Prior to attaching the IV set, check for minute leaks by squeezing container firmly. If leaks are found, discard container and solution as sterility may be compromised.
Using aseptic technique, peel foil cover from the set port and attach sterile administration set (see Diagram 5 ).
Refer to directions for use accompanying the administration set.
Important Administration Instructions
Do not use in series connections.
Do not introduce additives into the DUPLEX® Container.
Administer Cefazolin for Injection and Dextrose Injection intravenously over approximately 30 minutes.
Diagram 1
Diagram 2
Diagram 3
Diagram 4
Diagram 5
Dosage forms
Dual-chamber, single-dose packaged combination of Cefazolin Sodium USP (lyophilized) and sterile iso-osmotic diluent in the DUPLEX® sterile container consisting of :
• 1 g Cefazolin for Injection USP and 50 mL 4% Dextrose Injection USP
• 2 g Cefazolin for Injection USP and 50 mL 3% Dextrose Injection USP
Dual-Chamber in single-dose Duplex ® Container:
1 g Cefazolin for Injection USP and 50 mL 4% Dextrose Injection USP ( 3 )
2 g Cefazolin for Injection USP and 50 mL 3% Dextrose Injection USP ( 3 )
Contraindications
Hypersensitivity to cefazolin or other cephalosporin class antibacterial drugs, penicillins, or other beta-lactams ( 4.1 )
Cefazolin for Injection and Dextrose Injection is contraindicated in patients who have a history of immediate hypersensitivity reactions (e.g., anaphylaxis, serious skin reactions) to cefazolin or the cephalosporin class of antibacterial drugs, penicillins, or other beta-lactams [see
Warnings and Precautions (5.1) ] .
Warnings
Hypersensitivity reactions : Cross-hypersensitivity may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue the drug. ( 5.1 )
Clostridioides difficile
-associated diarrhea (CDAD): May range from mild diarrhea to fatal colitis. Evaluate if diarrhea occurs. ( 5.3 )
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with Cefazolin for Injection and Dextrose Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or carbapenems. Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibacterial drugs has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy. If an allergic reaction to Cefazolin for Injection and Dextrose Injection occurs, discontinue the drug.
Seizures may occur with the administration of Cefazolin for Injection and Dextrose Injection, particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue Cefazolin for Injection and Dextrose Injection if seizures occur or make appropriate dosage adjustments in patients with renal impairment [see Dosage and Administration (2.4) ] . Anticonvulsant therapy should be continued in patients with known seizure disorders.
Clostridioides difficile -associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including cefazolin, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile .
C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing isolates of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial drug treatment of C. difficile , and surgical evaluation should be instituted as clinically indicated.
Hypersensitivity reactions, including anaphylaxis, have been reported with administration of dextrose-containing products. These reactions have been reported in patients receiving high concentrations of dextrose (i.e. 50% dextrose) 1 . The reactions have also been reported when corn-derived dextrose solutions were administered to patients with or without a history of hypersensitivity to corn products. 2
Prescribing cefazolin for injection and dextrose injection in the absence of proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
As with other antimicrobials, prolonged use of Cefazolin for Injection and Dextrose Injection may result in overgrowth of nonsusceptible microorganisms. Repeated evaluation of the patient's condition is essential. Should superinfection occur during therapy, appropriate measures should be taken.
The administration of cefazolin may result in a false-positive reaction with glucose in the urine when using glucose tests based on Benedict’s copper reduction reaction that determine the amount of reducing substances like glucose in the urine. It is recommended that glucose tests based on enzymatic glucose oxidase be used.
Positive direct Coombs' tests have been reported during treatment with cefazolin. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs' testing of newborns whose mothers have received cephalosporin antibacterial drugs before parturition, it should be recognized that a positive Coombs' test may be due to the drug.
As with other dextrose-containing solutions, Cefazolin for Injection and Dextrose Injection should be prescribed with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason.
Adverse reactions
The following serious adverse reactions to Cefazolin for Injection and Dextrose Injection are described below and elsewhere in the labeling:
Drug interactions
The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with Cefazolin for Injection and Dextrose Injection is not recommended.
Probenecid: The renal excretion of cefazolin is inhibited by probenecid. Co-administration of probenecid with cefazolin for injection is not recommended. ( 7 )
Use in_specific_populations
Available data from published prospective cohort studies, case series and case reports over several decades with cephalosporin use, including cefazolin, in pregnant women have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Cefazolin crosses the placenta.
Animal reproduction studies with rats, mice and rabbits administered cefazolin during organogenesis at doses 1 to 3 times the maximum recommended human dose (MRHD) did not demonstrate adverse developmental outcomes. In rats subcutaneously administered cefazolin prior to delivery and throughout lactation, there were no adverse effects on offspring at a dose approximately 2 times the MRHD (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Human Data
While available studies cannot definitively establish the absence of risk, published data from case-control studies and case reports over several decades have not identified an association with cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.
Animal Data
Reproduction studies have been performed in rats, mice and rabbits administered cefazolin during organogenesis at doses of 2000, 4000 and 240 mg/kg/day (approximately 1 to 3 times the maximum recommended human dose on a body surface area comparison). There was no evidence of any adverse effects on embryofetal development due to cefazolin. In a peri-postnatal study in rats, cefazolin administered subcutaneously up to 1200 mg/kg/day (approximately 2 times the MRHD based on body surface area comparison) to pregnant dams prior to delivery and through lactation caused no adverse effects on offspring.
Data from published literature report that cefazolin is present in human milk, but is not expected to accumulate in a breastfed infant. There are no data on the effects of cefazolin on the breastfed child or on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Cefazolin for Injection and Dextrose Injection and any potential adverse effects on the breastfed child from Cefazolin for Injection and Dextrose Injection or from the mother’s underlying condition.
Cefazolin for Injection and Dextrose Injection is indicated for the treatment of respiratory tract infections, urinary tract infections, skin and skin structure infections, biliary tract infections, bone and joint infections, genital infections, septicemia, and endocarditis in pediatric patients for whom appropriate dosing with this formulation can be achieved, and for perioperative prophylaxis in pediatric patients aged 10 to 17 years old [see
Indications and Usage (1.1 to 1.9)] .
Safety and effectiveness of Cefazolin for Injection and Dextrose Injection in premature infants and neonates have not been established and is not recommended for use in this age group of pediatric patients. Dosing for cefazolin in pediatric patients younger than one month old has not been established.
Because of the limitations of the available strengths and administration requirements (i.e., administration of fractional doses is not recommended) of Cefazolin for Injection and Dextrose Injection, and to avoid unintentional overdose, this product is not recommended for use if a dose of Cefazolin for Injection and Dextrose Injection that does not equal 1 gram or 2 grams is required and an alternative formulation of cefazolin should be considered [see Dosage and Administration ( 2.2 , 2.3 , 2.4 and 2.5 )] .
The safety and effectiveness of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis have been established in pediatric patients aged 10 to 17 years old. Use of Cefazolin for Injection and Dextrose Injection in these age groups is supported by evidence from adults with additional safety and pharmacokinetic data in pediatric patients aged 10 to 17 years old. Safety and pharmacokinetics were evaluated in two multicenter, non-comparative studies (Study 1 and Study 2). These studies were conducted to assess the safety and pharmacokinetics of a single 30-minute infusion of either 1 gram or 2 grams (based on weight) of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis in pediatric patients. Study 1 evaluated the safety and pharmacokinetics of 1 g of Cefazolin for Injection and Dextrose Injection in pediatric patients aged 10 to 17 years old scheduled for surgery with a weight of at least 25 kg but less than 60 kg and, 2 g in pediatric patients with a weight of at least 60 kg. Study 2 evaluated 1 g of Cefazolin for Injection and Dextrose Injection in pediatric patients aged 10 to 12 years old scheduled for surgery with a weight of at least 25 kg but less than 50 kg and, 2 g in pediatric patients with a weight of at least 50 kg to less than 85 kg [see Dosage and Administration (2.3) , Adverse Reactions (6.1) and Clinical Pharmacology (12.3) ] .
The safety and effectiveness of Cefazolin for Injection and Dextrose Injection for perioperative prophylaxis have not been established in pediatric patients younger than 10 years old.
Of the 920 subjects who received cefazolin in clinical studies, 313 (34%) were 65 years and over, while 138 (15%) were 75 years and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function [see
Dosage and Administration (2.
4)
and Warnings and Precautions (5.2) ].
When Cefazolin for Injection and Dextrose Injection is administered to adult and pediatric patients with low urinary output because of impaired renal function (creatinine clearance less than 55 mL/min and 70 mL/min for adults and pediatric patients, respectively), lower daily dosage is required [see Dosage and Administration (2.4) and Warnings and Precautions (5.2) ].
How supplied
Cefazolin for Injection USP and Dextrose Injection USP in the single-dose DUPLEX® Container is a flexible dual chamber container supplied in two concentrations. After reconstitution, the concentrations are equivalent to 1 g and 2 g cefazolin. The diluent chamber contains approximately 50 mL of Dextrose Injection USP. Dextrose Injection USP has been adjusted to 4.0% and 3.0% for the 1 g and 2 g doses, respectively, such that the reconstituted solution is iso-osmotic.
Cefazolin for Injection USP and Dextrose Injection USP is supplied sterile and nonpyrogenic in the DUPLEX® Container packaged 24 units per case.
NDC
REF
Dose
Volume
0264-3103-11
3103-11
1 g
50 mL
0264-3105-11
3105-11
2 g
50 mL
Store the unactivated unit at 20-25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.] Do not freeze.
As with other cephalosporins, reconstituted Cefazolin for Injection USP and Dextrose Injection USP tends to darken depending on storage conditions, within the stated recommendations. However, product potency is not adversely affected.
Use only if prepared solution is clear and free from particulate matter.
Clinical pharmacology
Cefazolin is an antibacterial drug [see
Microbiology (12.4)
].
The pharmacokinetic/pharmacodynamic relationship for cefazolin has not been evaluated in patients.
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.
In a study 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) in healthy volunteers, cefazolin serum concentrations at the third hour were approximately 28 mcg/mL.
Plasma pharmacokinetic parameters of cefazolin in healthy volunteers (N=12) following a single 15-minute IV infusion of 2 grams of Cefazolin for Injection and Dextrose Injection are summarized in Table 7.
Table
7: Mean (Standard Deviation) Plasma Pharmacokinetic Parameters of Cefazolin in Healthy Volunteers
N
C max
(mcg/mL)
T max
T max reported as median (range)
(h)
AUC 0-inf
(mcg*h/mL)
t 1/2
(h)
CL
(L/h)
V z
(L)
Single 2 grams Dose as a 15-Minute IV Infusion
12
280.9 (45.9)
0.25 (0.25-0.33)
509.9 (89.3)
2.01 (0.28)
4.03 (0.68)
11.50 (1.53)
N= number of subjects observed; C max = maximum plasma concentration; T max = time to maximum plasma concentration; AUC 0-inf = area under the plasma concentration-time curve extrapolated to infinity; t 1/2 = apparent plasma terminal elimination half-life; CL = total clearance; V z = volume of distribution
Studies in patients hospitalized with infections indicate that cefazolin mean peak serum concentrations were approximately equivalent to those seen in healthy 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 (less than 1.0 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.
Specific Populations
Pediatric Patients for Perioperative Prophylaxis
A simulation based on pharmacokinetic data from healthy adults (n=24), pediatric patients aged 10 to 17 years (n=26: Study 1 [see Adverse Reactions (6.1) ] ), and pediatric patients aged 10 to 12 years (n=12: Study 2 [see Adverse Reactions (6.1) ] indicate that the administration of a 1 gram cefazolin dose for pediatric patients weighing less than 50 kg and a 2 grams cefazolin dose for those weighing 50 kg or greater will provide comparable exposures between pediatric patients aged 10 to 17 years and healthy adults receiving 2 grams Cefazolin for Injection and Dextrose Injection [see Dosage and Administration ( 2.2 and 2.3 ) and Use in Specific Populations (8.4) ].
Cefazolin is a bactericidal agent that acts by inhibition of bacterial cell wall synthesis.
Predominant mechanisms of bacterial resistance to cephalosporins include the presence of extended-spectrum beta-lactamases and enzymatic hydrolysis.
Cefazolin has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see
Indications and Usage (1) ] .
Gram-positive bacteria
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Methicillin-resistant staphylococci are uniformly resistant to cefazolin.
Gram-negative bacteria
Escherichia coli
Proteus mirabilis
Most isolates of indole positive Proteus (Proteus vulgaris) , Enterobacter spp ., Morganella morganii, Providencia rettgeri, Serratia spp ., and Pseudomonas spp. are resistant to cefazolin.
For specific information regarding susceptibility test interpretive criteria, and associated test methods and quality control standards recognized by FDA for this drug, please see: http://www.fda.gov/STIC .
Nonclinical toxicology
Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of Cefazolin for Injection and Dextrose Injection have not been performed.
Fertility studies conducted in rats subcutaneously administered cefazolin at doses of 2000 mg/kg/day (approximately 3 times the maximum recommended human dose based on body surface area comparison) showed no impairment of mating and fertility.
Package label
PRINCIPAL DISPLAY PANEL - 1g Cefazolin
Cefazolin for Injection USP and Dextrose Injection USP
1g*
REF 3103-11 NDC 0264-3103-11
DUPLEX®
CONTAINER
50 mL
Use only after mixing contents of both chambers. For IV Use Only Iso-osmotic Single Dose Sterile/Nonpyrogenic
* Contains Cefazolin Sodium USP equivalent to 1 g cefazolin.
Reconstitution: Hold container with set port in a downward direction and fold the diluent chamber just below the solution meniscus. To activate seal, squeeze folded diluent chamber until seal between diluent and drug chamber opens, releasing diluent into drug chamber. Agitate the reconstituted solution until the drug powder is completely dissolved. Fold the container a second time and squeeze until seal between drug chamber and set port opens.
After reconstitution each 50 mL single dose unit contains: Cefazolin for Injection USP (equivalent to 1 g cefazolin) with approx. 2.0 g (4.0% w/v) Hydrous Dextrose USP in Water for Injection USP. Sodium content is 48 mg/g of cefazolin sodium. Approximate osmolality: 290 mOsmol/kg
Prior to Reconstitution: Store at 20-25°C (68-77°F). Excursions permitted to 15-30°C (59-86°F). [See USP Controlled Room Temperature.] Use only if container and seals are intact. Do not peel foil strip until ready for use. After foil strip removal, product must be used within 7 days, but not beyond the labeled expiration date. Protect from light after removal of foil strip.
After Reconstitution: Use only if prepared solution is clear and free from particulate matter. Use within 24 hours if stored at room temperature or within 7 days if stored under refrigeration. Do not use in a series connection. Do not introduce additives into this container. Prior to administration check for minute leaks by squeezing container firmly. If leaks are found, discard container and solution as sterility may be impaired. Do not freeze.
Not made with natural rubber latex, PVC or DEHP.
B. Braun Medical Inc.
Bethlehem, PA 18018-3524
Rx only
Prepared in USA. API from USA and Italy.
LD-201-7 Y37-002-541
EXP LOT
PEEL HERE
Drug Chamber
Discard unit if foil strip is damaged. Peel foil strip only when ready for use. Visually inspect drug prior to reconstitution. See package insert for complete directions for reconstitution and administration. LD-336-1 X27-001-485
3103-11 Container Label
Drug Chamber Label
1 organization
1 product
Product
Cefazolin SodiumOrganization
B. Braun Medical Inc.