CEFAZOLIN SODIUM-DEXTROSE

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
-Reconstituted solutions may range in color from pale yellow to yellow without a change in potency.
Intravenous Administration
Intermittent IV Infusion

Reconstitution/Preparation
Conventional Vials for Injection
-Reconstitute vials with Sterile Water for Injection according to the manufacturer's instructions.
-Shake well.
-Storage: Store reconstituted solutions at room temperature or under refrigeration according to the manufacturer's instructions.

Bulk Vials for Injection
-Reconstitute 10 g vial with 45 mL or 96 mL of diluent to yield 200 mg/mL and 100 mg/mL, respectively.
-Reconstitute 20 g vial with 87 mL of diluent to yield 200 mg/mL.
-Compatible diluents include Sterile Water for Injection, Bacteriostatic Water for Injection, or 0.9% Sodium Chloride Injection.
-Further dilution is required; pharmacy bulk vials are not intended for administration via direct IV injection.
-Storage: Use bulk vials within 4 hours of initial entry.

ADD-Vantage vials
-Reconstitute in 50 or 100 mL flexible containers with 0.9% Sodium Chloride Injection or 5% Dextrose Injection. ADD-Vantage vials are not to be used for direct IV injection or IM injection.
-Storage: The reconstituted solution is stable for 24 hours at room temperature.

Frozen Pre-mixed Bags
-Thaw frozen container at room temperature (20 to 25 degrees C or 68 to 77 degrees F) or under refrigeration (2 to 8 degrees C or 36 to 46 degrees F).
-Do not force thaw by immersion in water baths or by microwave irradiation.
-Storage: The thawed solution remains stable for 30 days under refrigeration (5 degrees C or 41 degrees F) or 48 hours at room temperature (25 degrees C or 77 degrees F). Do not refreeze.

DUPLEX Drug Delivery System
-Use only if container and seals are intact. To inspect the drug powder for foreign matter or discoloration, peel the foil strip from the drug chamber.
-Protect from light after removal of foil strip.
-Allow refrigerated product to reach room temperature before patient use.
-Unfold the container and point the set port downward. Starting at the hanger tab end, fold the 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.
-Agitate the liquid-powder mixture until the drug powder completely dissolves.
-Do not use plastic containers in series connections as this may 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.
-Do not introduce additives into the container.
-Storage: If the foil strip is removed, refold container and latch the side tab until ready to activate and use within 7 days. After reconstitution (activation), use within 24 hours if stored at room temperature or within 7 days if stored under refrigeration.

Dilution
-ADD-Vantage vials: After reconstitution, no further dilution is required.
-Conventional/Bulk Vials: Further dilute the reconstituted solution in a compatible IV solution according to the manufacturer's instructions to a concentration of 10 to 40 mg/mL.
-Storage: Store diluted solutions at room temperature or under refrigeration according to the manufacturer's instructions.

Intermittent IV Infusion Administration
-Infuse IV over approximately 15 to 30 minutes.

Intermittent IV Push
Reconstitution
-Reconstitute the 500 mg and 1 g vials with 2 mL and 2.5 mL of Sterile Water for Injection to yield concentrations of 225 mg/mL and 330 mg/mL, respectively.
-Storage: Reconstituted solutions are stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5 degrees C or 41 degrees F).

Dilution-Further dilute the reconstituted solution with 5 to 10 mL of Sterile Water for Injection to a maximum concentration of 100 mg/mL.
-Storage: Diluted solutions are stable for 24 hours at room temperature or for 10 days if stored under refrigeration (5 degrees C or 41 degrees F).

Intermittent IV Push Administration
-Administer slow IV push over at least 3 to 5 minutes.

Intramuscular Administration
Reconstitution
-Reconstitute the 500 mg and 1 g vials with 2 mL and 2.5 mL of Sterile Water for Injection to yield concentrations of 225 mg/mL and 330 mg/mL, respectively.
-Storage: Reconstituted solution is stable for 24 hours at room temperature or 10 days refrigerated.

Intramuscular Injection-Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid [children and adolescents only]).

Reports of increased BUN (azotemia) and serum creatinine concentrations, as well as renal failure (unspecified), have been received with cefazolin use. Acute tubulo-interstitial nephritis was reported in postmarketing experience with cefazolin. Renal impairment and toxic nephropathy have been reported for cephalosporin-class antibacterials.

Serious and occasionally fatal hypersensitivity reactions have been reported in patients receiving beta-lactam antibiotics. Anaphylaxis (anaphylactoid reactions), urticaria, pruritus, drug fever, rash, and Stevens-Johnson syndrome have been reported with cefazolin. Serum sickness-like reaction and acute generalized exanthematous pustulosis (AGEP) have been reported in postmarketing experience with cefazolin. Erythema multiforme and toxic epidermal necrolysis have been reported for cephalosporin-class antibacterials. If an allergic reaction occurs, discontinue cefazolin use.

Gastrointestinal adverse reactions such as diarrhea, oral ulceration, vomiting, nausea, stomach cramps, epigastric pain, pyrosis (heartburn), flatulence, and anorexia have been reported with cefazolin therapy. In pediatric surgical prophylaxis trials, nausea was reported in 14.8% of patients.

Neutropenia, leukopenia, thrombocythemia/thrombocytosis, and thrombocytopenia have been reported during cefazolin therapy. Additionally, eosinophilia has been noted and may be associated with a hypersensitivity reaction. Cephalosporins may be associated with a fall in prothrombin activity (hypoprothrombinemia). Risk factors include renal or hepatic impairment, poor nutritional state, prolonged antibiotics, and patients previously stabilized on anticoagulant therapy. Monitor prothrombin time in patients at risk and administer vitamin K as necessary. Positive direct Coombs' tests have been reported in patients receiving cephalosporins. If hematological testing is done in patients receiving cephalosporins, a positive Coombs' test should be considered as being possibly due to the antibiotic. Aplastic anemia, hemolytic anemia, pancytopenia, and bleeding have been reported for cephalosporin-class antibacterials.

An injection site reaction of phlebitis or induration has been reported with cefazolin. Pain at the site of intramuscular administration has occurred infrequently. In pediatric surgical prophylaxis trials, infusion site pain was reported in 6.6% of patients.

Dizziness, fainting, lightheadedness, confusion, weakness, tiredness, hypotension, somnolence (drowsiness), and headache have been reported with cefazolin. In pediatric surgical prophylaxis studies, headache was reported in 4.9% of patients. Seizures may occur with cefazolin use, particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue cefazolin if seizures occur or make appropriate dosage adjustments in patients with renal impairment.

Transient elevated hepatic enzymes (SGOT, SGPT) and rise in alkaline phosphatase concentrations have been reported with cefazolin. Reports of hepatitis have been received. Hepatic impairment, including cholestasis, has been reported for cephalosporin-class antibacterials.

Microbial overgrowth and superinfection can occur with antibiotic use. C. difficile-associated diarrhea (CDAD) or pseudomembranous colitis has been reported with cefazolin. If pseudomembranous colitis is suspected or confirmed, ongoing antibacterial therapy not directed against C. difficile may need to be discontinued. Institute appropriate fluid and electrolyte management, protein supplementation, C. difficile-directed antibacterial therapy, and surgical evaluation as clinically appropriate. Oral candidiasis (thrush) as well as genital and anal pruritus (pruritus ani), including vulvar pruritus, genital and vaginal candidiasis, and vaginitis, have been reported with cefazolin.

Cefazolin is contraindicated in patients with cephalosporin hypersensitivity. Before starting therapy with cefazolin, inquire about previous hypersensitivity reactions to cefazolin, cephalosporins, penicillins, or other drugs. Use cefazolin with caution in patients with penicillin hypersensitivity because cross-hypersensitivity among beta-lactam antibiotics 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 occurs, discontinue treatment with the drug. Serious acute hypersensitivity reactions may require treatment with epinephrine and other emergency measures, including oxygen, intravenous fluids, intravenous antihistamines, corticosteroids, vasopressors, and airway management, as clinically indicated. Hypersensitivity reactions, including anaphylaxis, have been reported with the administration of dextrose-containing products. These reactions have been reported in patients receiving high concentrations of dextrose (i.e., 50% dextrose). They have also been reported when corn-derived dextrose solutions were administered to patients with or without a history of corn hypersensitivity.

After an initial loading dose, a lower daily cefazolin dose is required for patients with low urinary output due to renal impairment (CrCl less than 55 mL/minute in adults and 70 mL/minute in pediatric patients) or renal failure. Seizures may occur with cefazolin use, particularly in patients with renal impairment when the dosage is not reduced appropriately. Discontinue cefazolin if seizures occur or make appropriate dosage adjustments in patients with renal impairment. Continue anticonvulsant therapy in patients with known seizure disorder.

Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including cefazolin, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

All cephalosporins, including cefazolin, may rarely cause hypoprothrombinemia and have the potential to cause bleeding. Cephalosporins which contain the NMTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have been associated with an increased risk for bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency, significant hepatic disease) because these patients are at a higher risk for developing bleeding complications.

Administration of cefazolin may result in laboratory test interference. Specifically, a false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as cefazolin, and using glucose tests based on Benedict's copper reduction reaction that determine the amount of reducing substances like glucose in the urine. Diabetic patients who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on cefazolin treatment. Additionally, a positive direct Coombs test may develop in some patients. In hematologic studies or in transfusion cross-matching procedures when antiglobulin tests are performed on the minor side or in Coombs test of newborns whose mothers received cefazolin before delivery, clinicians should keep in mind that a positive Coombs test may be due to the drug. Cefazolin may also interfere with certain HPLC techniques and effect theophylline serum concentration measurements.

Use cefazolin for injection in dextrose with caution in patients with overt or known subclinical diabetes mellitus or carbohydrate intolerance for any reason. Also, patients with diabetes mellitus who test their urine for glucose should use glucose tests based on enzymatic glucose oxidase reactions while on cefazolin treatment. A false-positive reaction for glucose in the urine has been observed in patients receiving cephalosporins, such as cefazolin, and using glucose tests based on Benedict's copper reduction reaction that determine the amount of reducing substances like glucose in the urine.

Description: Cefazolin is a parenteral first-generation cephalosporin with greater activity against gram-positive bacteria than most other cephalosporins. Similar to other first-generation cephalosporins, cefazolin is active against gram-positive aerobic cocci, but has limited activity against gram-negative bacteria. Cefazolin is the primary agent used for surgical wound prophylaxis in cardiothoracic, vascular, and orthopedic procedures and for the prevention of infective endocarditis in high-risk cardiac patients undergoing dental, respiratory, or infected skin/skin structure or musculoskeletal procedures who are unable to take oral medications. Cefazolin is FDA-approved for use in pediatric patients older than 1 month of age.

Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: Escherichia coli, Proteus mirabilis, Staphylococcus aureus (MSSA), Staphylococcus epidermidis, Streptococcus agalactiae (group B streptococci), Streptococcus pneumoniae, Streptococcus pyogenes (group A beta-hemolytic streptococci), Streptococcus sp.
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.

This drug may also have activity against the following microorganisms: Haemophilus influenzae (beta-lactamase negative), Klebsiella pneumoniae, Shigella sp.
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.

For the treatment of upper respiratory tract infections:
-for the treatment of mild to moderate upper respiratory tract infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 25 to 50 mg/kg/day (Max: 1.5 g/day) IV or IM divided every 6 to 8 hours.
-for the treatment of severe upper respiratory tract infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 4 g/day) IV or IM divided every 6 to 8 hours.

For the treatment of lower respiratory tract infections (LRTIs), including community-acquired pneumonia (CAP):
-for the treatment of mild to moderate lower respiratory tract infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 25 to 50 mg/kg/day (Max: 4 g/day) IV or IM divided every 8 hours.
-for the treatment of severe lower respiratory tract infections:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 6 g/day) IV or IM divided every 6 to 8 hours. In rare instances, doses up to 12 g/day IV or IM have been used.
-for the treatment of community-acquired pneumonia (CAP) due methicillin-sensitive Staphylococcus aureus (MSSA):
Intravenous dosage:
Infants, Children, and Adolescents 4 months to 17 years: 150 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 10 days.

For surgical infection prophylaxis:
-for general surgical infection prophylaxis:
Intravenous or Intramuscular dosage:
Infants and Children 1 month to 9 years*: 30 mg/kg (Max: 2 g/dose) IV or IM as a single dose within 60 minutes prior to the surgical incision; consider intraoperative redosing 4 hours from the first preoperative dose. May continue 30 mg/kg (Max: 2 g/dose) IV or IM every 6 to 8 hours for no more than 24 hours post-operatively if necessary. Guidelines recommend cefazolin monotherapy for gastrointestinal, biliary tract, hernia repair, clean head and neck with prosthesis, neurosurgical, urogynecology, orthopedic, vascular, certain transplantation, and plastic surgery procedures. Cefazolin is recommended as part of combination therapy for appendectomy, obstructed gastrointestinal, colorectal, clean-contaminated head and neck, and urologic with prosthesis or clean-contaminated procedures.
Children and Adolescents 10 to 17 years weighing less than 50 kg: 1 g IV or IM as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 4 hours from the first preoperative dose. May continue 500 mg to 1 g IV or IM every 6 to 8 hours for no more than 24 hours post-operatively if necessary. Cefazolin is FDA-approved for contaminated or potentially contaminated procedures, including cholecystectomy in high-risk patients, as well as in surgical patients in whom infection at the operative site would present a serious risk (e.g., prosthetic arthroplasty). Guidelines recommend cefazolin monotherapy for gastrointestinal, biliary tract, hernia repair, clean head and neck with prosthesis, neurosurgical, urogynecology, orthopedic, vascular, certain transplantation, and plastic surgery procedures. Cefazolin is recommended as part of combination therapy for appendectomy, obstructed gastrointestinal, colorectal, clean-contaminated head and neck, and urologic with prosthesis or clean-contaminated procedures.
Children and Adolescents 10 to 17 years weighing 50 kg or more: 2 g IV as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 4 hours from the first preoperative dose. May continue 500 mg to 1 g IV or IM every 6 to 8 hours for no more than 24 hours post-operatively if necessary. Cefazolin is FDA-approved for contaminated or potentially contaminated procedures, including cholecystectomy in high-risk patients, as well as in surgical patients in whom infection at the operative site would present a serious risk (e.g., prosthetic arthroplasty). Guidelines recommend cefazolin monotherapy for gastrointestinal, biliary tract, hernia repair, clean head and neck with prosthesis, neurosurgical, urogynecology, orthopedic, vascular, certain transplantation, and plastic surgery procedures. Cefazolin is recommended as part of combination therapy for appendectomy, obstructed gastrointestinal, colorectal, clean-contaminated head and neck, and urologic with prosthesis or clean-contaminated procedures.
-for surgical infection prophylaxis for cardiothoracic procedures:
Intravenous or Intramuscular dosage:
Infants and Children 1 month to 9 years*: 30 mg/kg (Max: 2 g/dose) IV or IM as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 4 hours from the first preoperative dose. May continue 30 mg/kg (Max: 2 g/dose) IV or IM every 6 to 8 hours for no more than 24 hours post-operatively if necessary. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Guidelines recommend cefazolin monotherapy for cardiothoracic surgery procedures.
Children and Adolescents 10 to 17 years weighing less than 50 kg: 1 g IV or IM as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 4 hours from the first preoperative dose. May continue 500 mg to 1 g IV or IM every 6 to 8 hours for no more than 24 hours post-operatively if necessary. Cefazolin is FDA-approved in surgical patients in whom infection at the operative site would present a serious risk (e.g., open-heart surgery). Where the occurrence of infection may be particularly devastating, prophylaxis may be continued for up to 3 to 5 days. However, a longer prophylaxis duration of 48 hours (or more) for certain cardiothoracic procedures is controversial. Guidelines recommend cefazolin monotherapy for cardiothoracic surgery procedures.
Children and Adolescents 10 to 17 years weighing 50 kg or more: 2 g IV as a single dose within 30 to 60 minutes prior to the surgical incision; consider intraoperative redosing 4 hours from the first preoperative dose. May continue 500 mg to 1 g IV or IM every 6 to 8 hours for no more than 24 hours post-operatively if necessary. Cefazolin is FDA-approved in surgical patients in whom infection at the operative site would present a serious risk (e.g., open-heart surgery). Where the occurrence of infection may be particularly devastating, prophylaxis may be continued for up to 3 to 5 days. However, a longer prophylaxis duration of 48 hours (or more) for certain cardiothoracic procedures is controversial. Guidelines recommend cefazolin monotherapy for cardiothoracic surgery procedures.

For the treatment of infective endocarditis:
-for the treatment of native valve endocarditis due to highly susceptible streptococci, including viridans group streptococci* as well as groups A, B*, C*, G*, and nonenterococcal group D* streptococci:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours for 4 weeks as an alternative.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours for 4 weeks as an alternative.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours for 4 weeks as an alternative.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours for 4 weeks as an alternative.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 12 g/day) IV or IM divided every 8 hours for 4 weeks as an alternative.
-for the treatment of native valve endocarditis due to methicillin-susceptible S. aureus (MSSA):
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours for 4 to 6 weeks as an alternative; consider the addition of gentamicin for 3 to 5 days.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours for 4 to 6 weeks as an alternative; consider the addition of gentamicin for 3 to 5 days.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours for 4 to 6 weeks as an alternative; consider the addition of gentamicin for 3 to 5 days.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours for 4 to 6 weeks as an alternative; consider the addition of gentamicin for 3 to 5 days.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 12 g/day) IV or IM divided every 8 hours for 4 to 6 weeks as an alternative; consider the addition of gentamicin for 3 to 5 days.
-for the treatment of prosthetic valve endocarditis due to methicillin-susceptible S. aureus (MSSA):
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks as an alternative.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks as an alternative.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks as an alternative.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks as an alternative.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 12 g/day) IV or IM divided every 8 hours plus rifampin for at least 6 weeks and gentamicin for 2 weeks as an alternative.

For bacterial endocarditis prophylaxis*:
Intravenous or Intramuscular dosage:
Children and Adolescents: 50 mg/kg/dose (Max: 1 g/dose) IV or IM as a single dose given 30 to 60 minutes before procedure as an alternative for patients allergic to penicillin and/or unable to take oral medications. Prophylaxis is recommended for at-risk cardiac patients who are undergoing dental procedures that involve manipulation of gingival tissue, manipulation of the periapical region of teeth, or perforation of the oral mucosa.

For the treatment of prostatitis and epididymitis:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours.
Infants, Children, and Adolescents: 25 to 100 mg/kg/day (Max: 6 g/day) IV or IM divided every 8 hours.

For the treatment of bacteremia:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours. Guidelines recommend cefazolin for at least 14 days as a first-line treatment option for S. aureus bacteremia.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours. Guidelines recommend cefazolin for at least 14 days as a first-line treatment option for S. aureus bacteremia.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours. Guidelines recommend cefazolin for at least 14 days as a first-line treatment option for S. aureus bacteremia.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours. Guidelines recommend cefazolin for at least 14 days as a first-line treatment option for S. aureus bacteremia.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 6 g/day) IV or IM divided every 8 hours. Guidelines recommend cefazolin for 7 to 14 days as a first-line treatment option for S. aureus bacteremia.

For the treatment of bone and joint infections, including osteomyelitis, infectious arthritis, and infectious bursitis:
-for the treatment of osteomyelitis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 100 to 150 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 100 to 150 mg/kg/day (Max: 12 g/day) IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 3 to 4 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for severe or complicated infections.
-for the treatment of infectious arthritis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV every 12 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV every 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants 1 to 2 months: 100 to 150 mg/kg/day IV divided every 6 to 8 hours. Treat for 14 to 21 days or until clinically improved, followed by oral step-down therapy for a total duration of 4 to 6 weeks. A longer course (several months) may be needed for severe or complicated infections.
Infants, Children, and Adolescents 3 months to 17 years: 100 to 150 mg/kg/day (Max: 12 g/day) IV divided every 6 to 8 hours. Treat for 2 to 4 days or until clinically improved, followed by oral step-down therapy for a total duration of 2 to 3 weeks for uncomplicated cases. A longer course (i.e., 4 to 6 weeks or longer) may be needed for septic hip arthritis or severe or complicated infections.
-for the treatment of infectious bursitis:
Intravenous dosage:
Children and Adolescents: 100 to 150 mg/kg/day (Max: 12 g/day) IV divided every 6 to 8 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

For the treatment of neonatal mastitis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV every 12 hours.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV every 8 hours.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV every 12 hours.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV every 8 hours.
Infants 1 to 2 months: 25 to 75 mg/kg/day IV divided every 8 hours. Up to 100 mg/kg/day IV divided every 8 hours for severe infections.

For the treatment of urinary tract infection (UTI):
-for the treatment of acute, uncomplicated UTI:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents 2 months to 17 years: 25 to 50 mg/kg/day (Max: 2 g/day) IV or IM divided every 6 to 8 hours.
-for the treatment of moderate to severe UTI:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants younger than 2 months: 25 to 100 mg/kg/day (Max: 4 g/day) IV or IM divided every 6 to 8 hours. Infants younger than 2 to 3 months are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.
Infants, Children, and Adolescents 2 months to 17 years: 25 to 100 mg/kg/day (Max: 4 g/day) IV or IM divided every 6 to 8 hours.

For the treatment of intraabdominal infections, including peritonitis*, appendicitis*, intraabdominal abscess*, biliary tract infections, and peritoneal dialysis-related peritonitis*:
-for the treatment of complicated community-acquired intraabdominal infections with adequate source control:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours as part of combination therapy for 7 to 10 days.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours as part of combination therapy for 7 to 10 days.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours as part of combination therapy for 7 to 10 days.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours as part of combination therapy for 7 to 10 days.
Infants, Children, and Adolescents: 25 to 100 mg/kg/day (Max: 6 g/day) IV or IM divided every 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.
-for the treatment of peritoneal dialysis-related peritonitis*:
Intermittent Intraperitoneal dosage*:
Infants, Children, and Adolescents: 20 mg/kg/dose intraperitoneally every 24 hours for 14 to 21 days.
Continuous Intraperitoneal dosage*:
Infants, Children, and Adolescents: 500 mg/L intraperitoneal loading dose, followed by 125 mg/L in each dialysate exchange. Treat for 14 to 21 days.

For the treatment of uncomplicated and complicated skin and skin structure infections, including cellulitis, erysipelas, skin abscesses, necrotizing infections, and pyomyositis:
-for the treatment of mild skin and skin structure infections:
Intravenous or Intramuscular dosage:
Infants, Children, and Adolescents: 25 to 50 mg/kg/day (Max: 1.5 g/day) IV or IM divided every 6 to 8 hours.
-for the treatment of cellulitis and erysipelas due to methicillin-sensitive Staphylococcus aureus (MSSA):
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours for 5 to 14 days.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 8 days and older: 50 mg/kg/dose IV or IM every 8 hours for 5 to 14 days.
Infants, Children, and Adolescents: 50 mg/kg/day (Max: 3 g/day) IV or IM divided every 8 hours for 5 to 14 days.
-for the treatment of cellulitis and erysipelas due to Streptococcus sp.:
Intravenous or Intramuscular dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV or IM every 12 hours for 5 to 14 days.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV or IM every 8 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV or IM every 12 hours for 5 to 14 days.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV or IM every 8 hours for 5 to 14 days.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 3 g/day) IV or IM divided every 8 hours for 5 to 14 days.
-for the treatment of purulent skin and soft tissue infections, including skin abscesses:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV every 12 hours for 5 to 10 days plus incision and drainage.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV every 8 hours for 5 to 10 days plus incision and drainage.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV every 12 hours for 5 to 10 days plus incision and drainage.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV every 8 hours for 5 to 10 days plus incision and drainage.
Infants, Children, and Adolescents: 50 mg/kg/day (Max: 3 g/day) IV divided every 8 hours for 5 to 10 days plus incision and drainage.
-for the treatment of necrotizing infections of the skin, fascia, and muscle:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for MSSA infections.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for MSSA infections.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for MSSA infections.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for MSSA infections.
Infants, Children, and Adolescents: 100 mg/kg/day (Max: 3 g/day) IV divided every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours for MSSA infections.
-for the treatment of pyomyositis:
Intravenous dosage:
Neonates younger than 32 weeks gestation and 0 to 6 days*: 25 mg/kg/dose IV every 12 hours for 14 to 21 days.
Neonates younger than 32 weeks gestation and 7 days and older*: 25 mg/kg/dose IV every 8 hours for 14 to 21 days.
Neonates 32 weeks gestation and older and 0 to 7 days*: 50 mg/kg/dose IV every 12 hours for 14 to 21 days.
Neonates 32 weeks gestation and older and 8 days and older*: 50 mg/kg/dose IV every 8 hours for 14 to 21 days.
Infants, Children, and Adolescents: 50 mg/kg/day (Max: 3 g/day) IV divided every 8 hours for 14 to 21 days.

For bacterial infection prophylaxis after penetrating trauma*:
-for bacterial infection prophylaxis after penetrating central nervous system trauma*:
Intravenous dosage:
Infants, Children, and Adolescents: 25 to 75 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 5 days or until CSF leak is closed, whichever is longer. Add metronidazole for penetrating spinal cord injury if abdominal cavity is involved and consider adding metronidazole for penetrating brain injury if gross contamination with organic debris.
-for bacterial infection prophylaxis after penetrating maxillofacial and neck trauma or chest trauma*:
Intravenous dosage:
Infants, Children, and Adolescents: 25 to 75 mg/kg/day (Max: 6 g/day) IV divided every 8 hours. Add metronidazole for penetrating chest trauma with esophageal disruption and continue for 1 day after definitive washout.
-for bacterial infection prophylaxis after penetrating abdominal trauma*:
Intravenous dosage:
Infants, Children, and Adolescents: 25 to 75 mg/kg/day (Max: 6 g/day) IV divided every 8 hours plus metronidazole for 1 day after definitive washout.
-for bacterial infection prophylaxis after penetrating extremity trauma (including skin, soft tissue, and bone with or without open fractures)*:
Intravenous dosage:
Infants, Children, and Adolescents: 25 to 75 mg/kg/day (Max: 6 g/day) IV divided every 8 hours for 1 to 3 days.

Maximum Dosage Limits:
-Neonates
younger than 32 weeks gestation and 0 to 6 days: Safety and efficacy have not been established; however, doses up to 50 mg/kg/day IV/IM have been used off-label.
younger than 32 weeks gestation and 7 days and older: Safety and efficacy have not been established; however, doses up to 75 mg/kg/day IV/IM have been used off-label.
32 weeks gestation and older and 0 to 7 days: Safety and efficacy have not been established; however, doses up to 100 mg/kg/day IV/IM have been used off-label.
32 weeks gestation and older and 8 days and older: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day IV/IM have been used off-label.
-Infants
100 mg/kg/day IV/IM for most indications; however, doses up to 150 mg/kg/day IV have been used off-label.
-Children
100 mg/kg/day (Max: 6 g/day) IV/IM for most indications; however, doses up to 150 mg/kg/day (Max: 12 g/day) IV have been used off-label.
-Adolescents
100 mg/kg/day (Max: 6 g/day) IV/IM for most indications; however, doses up to 150 mg/kg/day (Max: 12 g/day) IV have been used off-label.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
FDA-approved labeling
CrCl more than 70 mL/minute: No dosage adjustment needed.
CrCl 40 to 70 mL/minute: After a normal loading dose, administer 60% of the normal daily dose divided every 12 hours.
CrCl 20 to 39 mL/minute: After a normal loading dose, administer 25% of the normal daily dose divided every 12 hours.
CrCl 5 to 19 mL/minute: After a normal loading dose, administer 10% of the normal daily dose divided every 24 hours.

Alternative*
The following dose adjustments are based on a usual pediatric dose of 50 to 100 mg/kg/day IV divided every 8 hours:
GFR 30 mL/minute/1.73m2 or more: No dosage adjustment needed.
GFR 10 to 29 mL/minute/1.73m2: 25 mg/kg/dose (Max: 2 g/dose) IV every 12 hours.
GFR less than 10 mL/minute/1.73m2: 25 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.

Intermittent hemodialysis*
25 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.

Peritoneal dialysis*
25 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.

Continuous renal replacement therapy (CRRT)*
NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.

25 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Cefazolin, a beta-lactam antibiotic similar to penicillins, inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. Penicillin-binding proteins are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. Penicillin-binding proteins vary among different bacterial species. Thus, the intrinsic activity of cefazolin as well as other cephalosporins and penicillins against a particular organism depends on their ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefazolin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.

Beta-lactams, including cefazolin, exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above the MIC). This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase. Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Cephalosporins require free drug concentrations to be above the MIC for 35% to 40% of the dosing interval for bacteriostatic activity and 60% to 70% of the dosing interval for bactericidal activity.

The susceptibility interpretive criteria for cefazolin are delineated by pathogen. The MICs are defined for Enterobacterales as susceptible at 2 or less mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more for infections other than uncomplicated urinary tract infections (UTIs) due to E. coli, K. pneumoniae, and P. mirabilis (based on a dosage regimen of 2 g IV every 8 hours) and susceptible at 16 mcg/mL or less and resistant at 32 mcg/mL or more for uncomplicated UTIs due to E. coli, K. pneumoniae, and P. mirabilis (based on a dosage regimen of 1 g IV every 12 hours); however, the FDA does not recognize separate susceptibility test interpretive criteria for uncomplicated UTIs. The MICs are defined for Vibrio sp. (excluding V. cholerae) as susceptible at 2 or less mcg/mL or less, intermediate at 4 mcg/mL, and resistant at 8 mcg/mL or more (based on a dosage regimen of 2 g IV every 8 hours). Penicillin-susceptible beta-hemolytic streptococci and methicillin-susceptible staphylococci can be considered susceptible to cefazolin.

The predominant mechanisms of resistance include the presence of extended-spectrum beta-lactamases and enzymatic hydrolysis.

Pharmacokinetics: Cefazolin is administered intravenously and intramuscularly. Approximately 80% of circulating drug is protein-bound. It is widely distributed into most body tissues and fluids; however, cefazolin does not reach therapeutic concentrations within the CSF. The drug concentrates in the urine at concentrations much higher than peak serum concentrations. Bile concentrations in patients without obstructive biliary disease can reach or exceed serum concentrations by up to 5 times; however, in patients with obstructive biliary disease, bile concentrations of cefazolin are considerably lower than serum concentrations (less than 1 mcg/mL). In synovial fluid, the cefazolin concentration becomes comparable to that reached in the serum at about 4 hours after drug administration. Cefazolin is not hepatically metabolized. Cefazolin is largely excreted unchanged into the urine with approximately 60% excreted within the first 6 hours, reaching 70% to 80% within the first 24 hours. In non-neonatal patients, including adults, with normal renal function, the elimination half-life is approximately 1.8 hours after IV administration and 2 hours after IM administration.

Affected cytochrome P450 isoenzymes: none


-Route-Specific Pharmacokinetics
Intravenous Route
Studies have shown that after IV administration of cefazolin to normal adult volunteers, mean serum concentrations peaked at 185 mcg/mL and were approximately 4 mcg/mL at 8 hours after a 1 g dose. After a single 2 g dose, the mean Tmax was 0.25 hours and mean Cmax was 280.9 mcg/mL. In a study of constant IV infusion of 3.5 mg/kg for 1 hour and 1.5 mg/kg for the next 2 hours in healthy volunteers, serum concentrations at the third hour were approximately 28 mcg/mL. Studies in hospitalized patients with infections indicate that cefazolin mean peak serum concentrations were approximately equivalent to those seen in healthy volunteers. When given as a slow IV push over 2 to 3 minutes, peak concentrations are achieved approximately 15 minutes after administration.

Intramuscular Route
Peak serum concentrations of cefazolin occur within 1 hour after an intramuscular (IM) dose. After IM administration of cefazolin to normal adult volunteers, the mean serum concentrations were 37 mcg/mL at 1 hour after a 500 mg dose, and 64 mcg/mL at 1 hour after a 1 g dose.


-Special Populations
Pediatrics
Neonates
Protein binding in neonatal patients is highly variable; a study in neonates 2 to 28 days found the unbound fraction to be 0.22 to 0.83. The half-life of cefazolin in neonates is approximately 3 to 5 hours.

Infants and Children
A simulation based on pharmacokinetic data from healthy adults (n = 24) and pediatric patients aged 10 to 17 years (n = 26) and 10 to 12 years (n = 12) indicates that the administration of cefazolin 1 g for pediatric patients weighing less than 50 kg and 2 g for those weighing 50 kg or more will provide comparable exposures between pediatric patients aged 10 to 17 years and healthy adults receiving cefazolin 2 g. In a pharmacokinetic study of infants and children (n = 9; 0.8 to 10 years) undergoing gastrointestinal surgery, mean clearance and elimination half-life values after a single IV cefazolin dose (15 to 26 mg/kg) were 1.4 mL/kg/minute and 1.7 hours, respectively.

Renal Impairment
Cefazolin is moderately dialyzable with 20% to 50% of the dose removed by dialysis. Data are unavailable in pediatric patients with renal impairment; however, in a pharmacokinetic study (n = 17) in adults with different degrees of renal function, elimination half-life of cefazolin was prolonged to approximately 10 hours in patients with a CrCl of 20 mL/minute and ranged from 15 to 45 hours in patients with a CrCl less than 5 mL/minute.

In patients undergoing peritoneal dialysis (2 L/hour), cefazolin produced mean serum concentrations of approximately 10 and 30 mcg/mL after 24 hours intraperitoneal instillation of a dialyzing solution containing 50 mg/L and 150 mg/L, respectively. Mean peak concentrations were 29 mcg/mL (range 13 to 44 mcg/mL) with 50 mg/L (n = 3), and 72 mcg/mL (range 26 to 142 mcg/mL) with 150 mg/L (n = 6). Intraperitoneal administration is usually well tolerated.