ceFAZolin 2 GM Injection
Generic Name: CEFAZOLIN SODIUM
Brand Name: Cefazolin Sodium
- Substance Name(s):
- CEFAZOLIN SODIUM
DRUG INTERACTIONS
7 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 )
OVERDOSAGE
10 Accidental overdosage resulting in seizures may occur in patients with renal impairment who receive doses greater than the recommended dosage of Cefazolin for Injection and Dextrose Injection [see Warnings and Precautions (5.2) ].
If seizures associated with accidental overdosage occur, discontinue Cefazolin for Injection and Dextrose Injection and give supportive treatment.
DESCRIPTION
11 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
HOW SUPPLIED
16 /STORAGE AND HANDLING 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.
RECENT MAJOR CHANGES
Indications and Usage, Perioperative Prophylaxis ( 1.9 ) 12/2019 Dosage and Administration, Dosage for Treatment of Indicated Infections in Pediatric Patients ( 2.3 ) 12/2019 Dosage and Administration, Dosage for Perioperative Prophylactic Use in Pediatric Patients Aged 10 to 17 ( 2.4 ) 12/2019 Dosage and Administration, Dosage in Pediatric Patients with Renal Impairment ( 2.6 ) 12/2019 Indications and Usage, Perioperative Prophylaxis ( 1.9 ) 11/2020 Dosage and Administration, Dosage for the Treatment of Infections ( 2.2 ) 11/2020 Dosage and Administration, Dosage for Perioperative Prophylaxis ( 2.3 ) 11/2020 Dosage and Administration, Dosage Recommendations in Adult and Pediatric Patients with Renal Impairment ( 2.4 ) 11/2020
GERIATRIC USE
8.5 Geriatric Use 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) ].
DOSAGE FORMS AND STRENGTHS
3 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 )
MECHANISM OF ACTION
12.1 Mechanism of Action Cefazolin is an antibacterial drug [see Microbiology (12.4) ].
INDICATIONS AND USAGE
1 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 ).
1.1 Respiratory Tract Infections 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.
1.2 Urinary Tract Infections 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) ].
1.3 Skin and Skin Structure Infections 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) ].
1.4 Biliary Tract Infections 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) ].
1.5 Bone and Joint Infections 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) ].
1.6 Genital Infections 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) ].
1.7 Septicemia 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) ].
1.8 Endocarditis 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) ].
1.9 Perioperative Prophylaxis 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).
1.10 Usage 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.
PEDIATRIC USE
8.4 Pediatric Use 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.
PREGNANCY
8.1 Pregnancy Risk Summary 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.
Data 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.
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS 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 ) 5.1 Hypersensitivity Reactions to Cefazolin, Cephalosporins, Penicillins, or Other Beta-lactams 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.
5.2 Seizures in Patients with Renal Impairment 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.
5.3 Clostridioides difficile -associated Diarrhea 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.
5.4 Hypersensitivity to Dextrose-containing Products 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 5.5 Risk of Development of Drug-resistant Bacteria 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.
5.6 Drug/Laboratory Test Interactions Urinary Glucose 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.
Coombs’ Test 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.
5.7 Patients with Overt or Known Subclinical Diabetes Mellitus or Carbohydrate Intolerance 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.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION Serious Allergic Reactions Advise patients that allergic reactions, including serious allergic reactions could occur and that serious reactions require immediate treatment and discontinuation of Cefazolin for Injection and Dextrose Injection.
Patients should report to their health care provider any previous allergic reactions to cefazolin, cephalosporins, penicillins, or other similar antibacterials.
Seizures Advise patients that seizures could occur with Cefazolin for Injection and Dextrose Injection.
Instruct patients to inform a healthcare provider at once of any signs and symptoms of seizures, for immediate treatment, dosage adjustment, or discontinuation of Cefazolin for Injection and Dextrose Injection.
Diarrhea Advise patients that diarrhea is a common problem caused by antibacterials, which usually ends when the antibacterial is discontinued.
Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the antibacterials.
If this occurs, patients should contact a physician as soon as possible.
Antibacterial Resistance Patients should be counseled that antibacterial drugs, including Cefazolin for Injection and Dextrose Injection should only be used to treat bacterial infections.
They do not treat viral infections (e.g., the common cold).
When Cefazolin for Injection and Dextrose Injection is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed.
Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Cefazolin for Injection and Dextrose Injection or other antibacterial drugs in the future.
DOSAGE AND ADMINISTRATION
2 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 ) 2.1 Important Administration Instructions 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.
2.2 Dosage for the Treatment of Infections 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 2.3 Dosage for Perioperative Prophylaxis 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.
2.4 Dosage Recommendations in Adult and Pediatric Patients with Renal Impairment 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.
2.5 Preparation for Use of Cefazolin for Injection and Dextrose Injection in DUPLEX® Container 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