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    1st Generation Cephalosporin Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral first-generation cephalosporin
    Used for respiratory tract, urinary tract, skin and skin structure, biliary tract, bone and joint, and genital infections as well as sepsis, endocarditis, and perioperative prophylaxis
    Greater activity against gram-positive bacteria than most other cephalosporins, but limited activity against gram-negative bacteria

    COMMON BRAND NAMES

    Ancef, Kefzol

    HOW SUPPLIED

    Ancef/Cefazolin/Cefazolin Sodium Intravenous Inj Sol: 1mL, 20mg, 100mg
    Ancef/Cefazolin/Cefazolin Sodium/Kefzol Intramuscular Inj Pwd F/Sol: 1g, 2g, 10g, 20g, 500mg
    Ancef/Cefazolin/Cefazolin Sodium/Kefzol Intravenous Inj Pwd F/Sol: 1g, 2g, 10g, 20g, 300g, 500mg

    DOSAGE & INDICATIONS

    For the treatment of upper respiratory tract infections, skin and skin structure infections, and biliary tract infections.
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 6 to 8 hours. The usual maximum dose is 6 g/day.

    Infants, Children, and Adolescents

    25 to 75 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day). Up to 100 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day) for severe infections.

    Neonates 32 weeks gestation and older and 8 days and older

    50 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 younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of urinary tract infection (UTI).
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 12 hours for uncomplicated UTI; for moderate to severe infection, 1 g IV or IM every 6 to 8 hours. The usual maximum dose is 6 g/day.

    Infants, Children, and Adolescents

    25 to 75 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day). Up to 100 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day) for severe infections.

    Neonates 32 weeks gestation and older and 8 days and older

    50 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 younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of infective endocarditis.
    Intravenous or Intramuscular dosage
    Adults

    2 g IV every 8 hours is recommended by guidelines. The FDA-approved labeling recommends 1 to 1.5 g IV or IM every 6 hours. A maximum dose of 12 g/day has been used rarely in severe, life-threatening infections. Guidelines recommend cefazolin for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE) caused by S. pneumoniae. Cefazolin is recommended for 6 weeks for methicillin-susceptible staphylococcal NVE in penicillin-allergic (nonanaphylactoid-type) patients. Use for in combination with gentamicin (for first 2 weeks) and rifampin for at least 6 weeks for methicillin-susceptible staphylococcal PVE.

    Children and Adolescents

    100 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day). A maximum dose of 12 g/day has been used rarely in severe, life-threatening infections. Guidelines recommend cefazolin as an alternate therapy for highly penicillin-susceptible streptococcal infections; treat for 4 weeks for native valve endocarditis (NVE) and for 6 weeks or prosthetic valve endocarditis (PVE). Cefazolin is also recommended as alternate therapy for penicillin-susceptible and certain resistant staphylococcal infections; treat for 4 to 6 weeks with or without gentamicin for the first 3 to 5 days for NVE and for at least 6 weeks with gentamicin (for first 2 weeks) and rifampin for PVE.

    Infants

    100 mg/kg/day IV or IM divided every 8 hours.

    Neonates 32 weeks gestation and older and 8 days and older

    50 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 younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours.

    For surgical infection prophylaxis.
    For ophthalmic surgical infection prophylaxis†.
    Intraocular dosage
    Adults

    100 mg by subconjunctival injection or 1 to 2.5 mg by intracameral injection is optional at the end of the procedure. Perioperative antisepsis with povidone-iodine is recommended. The necessity of continuing topical antimicrobials postoperatively has not been established.

    Intramuscular or Intravenous dosage
    Adults weighing 120 kg or more

    1 g IM or IV or 2 or 3 g IV as a single dose within 30 to 60 minutes prior to the surgical incision. For lengthy operations (e.g., 2 hours or longer), additional doses of 0.5 to 3 g may be given during the procedure and postoperatively every 6 to 8 hours for 24 hours. Where the occurrence of infection may be particularly devastating (e.g. open-heart surgery, prosthetic arthroplasty), prophylaxis may be continued for up to 3 to 5 days.  Guidelines suggest 3 g IV for patients weighing 120 kg or more. For gynecologic procedures, the American College of Obstetricians and Gynecologists (ACOG) recommends 1 g IV, and for women with a body mass index (BMI) more than 35 or weight more than 100 kg, 2 g IV. Intraoperative redosing 4 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures is suggested by guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Cefazolin is FDA-approved for contaminated or potentially contaminated procedures, including vaginal hysterectomy and 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. open-heart surgery, prosthetic arthroplasty). Clinical practice guidelines recommend cefazolin monotherapy for cardiothoracic, 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 GI, colorectal, clean-contaminated head and neck, and urologic with prosthesis or clean-contaminated procedures.

    Adults weighing less than 120 kg

    1 g IM or IV or 2 g IV as a single dose within 30 to 60 minutes prior to the surgical incision. For lengthy operations (e.g., 2 hours or longer), additional doses of 0.5 to 2 g may be given during the procedure and postoperatively every 6 to 8 hours for 24 hours. Where the occurrence of infection may be particularly devastating (e.g. open-heart surgery, prosthetic arthroplasty), prophylaxis may be continued for up to 3 to 5 days.  For gynecologic procedures, the American College of Obstetricians and Gynecologists (ACOG) recommends 1 g IV, and for women with a body mass index (BMI) more than 35 or weight more than 100 kg, 2 g IV. Intraoperative redosing 4 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures is suggested by guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Cefazolin is FDA-approved for contaminated or potentially contaminated procedures, including vaginal hysterectomy and 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. open-heart surgery, prosthetic arthroplasty). Guidelines recommend cefazolin monotherapy for cardiothoracic, 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 GI, 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. For lengthy operations (e.g., 2 hours or longer), additional doses of 0.5 to 2 g may be given during the procedure and postoperatively every 6 to 8 hours for 24 hours. Where the occurrence of infection may be particularly devastating (e.g. open-heart surgery, prosthetic arthroplasty), prophylaxis may be continued for up to 3 to 5 days. Intraoperative redosing 4 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures is suggested by guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Cefazolin is FDA-approved for contaminated or potentially contaminated procedures, including vaginal hysterectomy and 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. open-heart surgery, prosthetic arthroplasty).

    Children and Adolescents 10 to 17 years weighing less than 50 kg

    1 g IM or IV as a single dose within 30 to 60 minutes prior to the surgical incision. For lengthy operations (e.g., 2 hours or longer), additional doses of 0.5 to 1 g may be given during the procedure and postoperatively every 6 to 8 hours for 24 hours. Where the occurrence of infection may be particularly devastating (e.g. open-heart surgery, prosthetic arthroplasty), prophylaxis may be continued for up to 3 to 5 days. Intraoperative redosing 4 hours from the first preoperative dose and duration of prophylaxis less than 24 hours for most procedures is suggested by guidelines. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Cefazolin is FDA-approved for contaminated or potentially contaminated procedures, including vaginal hysterectomy and 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. open-heart surgery, prosthetic arthroplasty).

    Infants and Children 1 month to 9 years†

    30 mg/kg (Max: 2 g/dose) IM or IV as a single dose within 60 minutes prior to the surgical incision. Repeat dose intraoperatively 4 hours after preoperative dose if operation still in progress. Depending on the procedure, 30 mg/kg/dose (Max: 2 g/dose) IV may be given postoperatively every 8 hours for 24 hours. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial.

    Neonates†

    30 mg/kg IM or IV as a single dose within 60 minutes prior to the surgical incision is reasonable based on the usual dose for neonates and surgical prophylaxis recommendations in other populations.

    For the treatment of prostatitis and epididymitis.
    Intravenous or Intramuscular dosage
    Adults

    500 mg to 1 g IV or IM every 6 to 8 hours. The usual maximum dose is 6 g/day. Not recommended for the treatment of sexually transmitted epididymitis.

    Infants, Children, and Adolescents

    25 to 100 mg/kg/day (Max: 6 g/day) IV or IM divided every 8 hours.

    Neonates 32 weeks gestation and older and 8 days and older†

    50 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 younger than 32 weeks gestation and 7 days and older†

    25 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 6 days†

    25 mg/kg/dose IV or IM every 12 hours.

    For the treatment of lower respiratory tract infections (LRTIs), including pneumococcal pneumonia and community-acquired pneumonia (CAP).
    For the treatment of nonspecific lower respiratory tract infections (LRTIs) and pneumococcal pneumonia.
    Intravenous or Intramuscular dosage
    Adults

    500 mg IV or IM every 12 hours for pneumococcal pneumonia; 500 mg to 1 g IV or IM every 6 to 8 hours for moderate to severe infections; 1 to 1.5 g IV or IM every 6 hours for life-threatening infections. In rare instance, doses up to 12 g/day have been used.

    Infants, Children, and Adolescents

    100 mg/kg/day IV or IM divided every 8 hours.

    Neonates 32 weeks gestation and older and 8 days and older†

    50 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 younger than 32 weeks gestation and 14 days and older†

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days†

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of community-acquired pneumonia (CAP).
    Intravenous dosage
    Infants 4 to 11 months, Children, and Adolescents

    150 mg/kg/day IV divided every 8 hours (Max: 6 g/day) for 10 days for infections due to methicillin-sensitive S. aureus.[46963]

    For the treatment of bacteremia.
    Intravenous or Intramuscular dosage
    Adults

    1 to 1.5 g IV or IM every 6 hours. A maximum dose of 12 g/day has been used rarely in severe, life threatening infections.

    Infants, Children, and Adolescents

    100 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day). A maximum dose of 12 g/day has been used rarely in severe, life-threatening infections.

    Neonates 32 weeks gestation and older and 8 days and older

    50 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 younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of bone and joint infections.
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 6 to 8 hours. Usual Maximum dose is 6 g/day.

    Infants, Children, and Adolescents

    25 to 75 mg/kg/day IV or IM divided every 8 hours is the usual dosage range; 100 mg/kg/day IV or IM divided every 8 hours (Max: 6 g/day) is recommended for severe infections in the FDA-approved labeling. Up to 150 mg/kg/day IV or IM divided every 6 to 8 hours (Max: 12 g/day) is recommended by the American Academy of Pediatrics (AAP) for bone/joint infections.

    Neonates 32 weeks gestation and older and 8 days and older

    50 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 younger than 32 weeks gestation and 14 days and older

    50 mg/kg/dose IV or IM every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days

    50 mg/kg/dose IV or IM every 12 hours.

    For the treatment of mastitis.
    Intravenous dosage
    Adults

    1 g IV every 8 hours for 10 to 14 days.

    For the treatment of neonatal mastitis.
    Intravenous dosage
    Infants 1 to 2 months

    25 to 75 mg/kg/day IV divided every 8 hours.[31700] [57437] [63245] [64275] Up to 100 mg/kg/day IV divided every 8 hours for severe infections.[31700]

    Neonates 32 weeks gestation and older and 8 days and older†

    50 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 younger than 32 weeks gestation and 14 days and older†

    50 mg/kg/dose IV every 8 hours.

    Neonates younger than 32 weeks gestation and 0 to 13 days†

    50 mg/kg/dose IV every 12 hours.

    For bacterial endocarditis prophylaxis†.
    Intravenous or Intramuscular dosage
    Adults

    1 g 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.

    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 perinatal Group B streptococcal infection prophylaxis† in patients allergic to penicillin.
    Intravenous dosage
    Pregnant females

    2 g IV load initiated at the time of labor or rupture of membranes, followed by 1 g IV every 8 hours until delivery. Cefazolin is recommended as an alternative for patients with a low-risk penicillin allergy. Antibiotics administered for at least 4 hours before delivery have been found to be highly effective at preventing the transmission of Group B Streptococcus.[64407]

    For the treatment of intraabdominal infections, including peritonitis†, appendicitis†, intraabdominal abscess†, biliary tract infections (cholecystitis), and peritoneal dialysis-related peritonitis†.
    For the treatment of complicated community-acquired intraabdominal infections with adequate source control.
    Intravenous or Intramuscular dosage
    Adults

    1 g IV or IM every 6 to 8 hours or 2 g IV 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.

    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.

    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.

    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 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 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.

    For the treatment of peritoneal dialysis-related peritonitis†.
    Intermittent Intraperitoneal dosage†
    Adults

    15 to 20 mg/kg/dose intraperitoneally every 24 hours for 14 to 21 days.

    Infants, Children, and Adolescents

    20 mg/kg/dose intraperitoneally every 24 hours for 14 to 21 days.

    Continuous Intraperitoneal dosage†
    Adults

    500 mg/L intraperitoneal loading dose, followed by 125 mg/L in each dialysate exchange. Treat for 14 to 21 days.

    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.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    12 g/day IV/IM.

    Geriatric

    12 g/day IV/IM.

    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.

    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.

    Infants

    100 mg/kg/day IV/IM for most indications; however, doses up to 150 mg/kg/day IV have been used off-label.

    Neonates

    14 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.
    8 to 13 days: Safety and efficacy have not been established; however, doses up to 100 mg/kg/day IV/IM for neonates less than 32 weeks gestation and 150 mg/kg/day IV/IM for neonates 32 weeks gestation and older have been used off-label.
    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Adult patients (FDA-approved labeling) [31700]
    CrCl more than 54 mL/minute: No dosage adjustment needed.
    CrCl 35 to 54 mL/minute: Administer every 8 hours or longer.
    CrCl 11 to 34 mL/minute: After a normal loading dose, reduce maintenance dose by 50% and administer every 12 hours.
    CrCl 10 mL/minute or less: After a normal loading dose, reduce the recommended dose by 50% and administer every 18 to 24 hours.
     
    Adult patients (alternative)† [32569]
    CrCl more than 50 mL/minute: No dosage adjustment needed.
    CrCl 10 to 50 mL/minute: Administer the usual dose every 12 hours.
    CrCl less than 10 mL/minute: Reduce the recommended dose by 50% and administer every 24 to 48 hours.
     
    Pediatric patients (FDA-approved labeling) [31700]
    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.
     
    Pediatric patients (alternative)† [32569]
    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†
    Adult patients
    500 mg to 1 g IV every 24 hours; administer after hemodialysis on dialysis days. Alternatively, administer 1 to 2 IV every 48 to 72 hours after hemodialysis.[42303] Other recommendations suggest 15 to 20 mg/kg IV after hemodialysis.[32569]
     
    Pediatric patients
    25 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.[32569]
     
    Peritoneal dialysis†
    Adult patients
    500 mg IV every 12 hours.[32569]
     
    Pediatric patients
    25 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.[32569]
     
    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.[42303]
     
    Adult patients
    Administering the usual dose every 12 hours has generally been suggested for CRRT.[32569] More specifically, consider a 2 g IV loading dose, then 1 to 2 g IV every 12 hours for CVVH and a 2 g IV loading dose, then 1 g IV every 8 hours or 2 g IV every 12 hours for CVVHD or CVVHDF.[34038] [42303]
     
    Pediatric patients
    25 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.[32569]

    ADMINISTRATION

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intravenous (IV) Infusion
    Powder Vials for Injection
    Reconstitution
    Reconstitute powder with Sterile Water for Injection. Use 2 mL for 500 mg vial to yield 225 mg/mL and 2.5 mL for 1 g vial to yield 330 mg/mL.
    Shake well.
    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 in 50 to 100 mL of a compatible IV solution.
    ISMP recommended neonatal standard concentration: 100 mg/mL.
    Compatible IV solutions include 5% Dextrose Injection, 10% Dextrose Injection, 5% Dextrose in Lactated Ringer's Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.2% Sodium Chloride Injection, Lactated Ringer's Injection, Invert Sugar 5% in Sterile Water for Injection, Invert Sugar 10% in Sterile Water for Injection, or 5% Sodium Bicarbonate Injection.
    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).
     
    Bulk Vials for Injection
    Reconstitution
    Reconstitute 10 g vial with 45 mL or 96 mL 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 IV solutions 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.
     
    Dilution
    Further dilute the reconstituted solution in 50 to 100 mL of a compatible IV solution.
    ISMP recommended neonatal standard concentration: 100 mg/mL.
    Compatible IV solutions include 5% Dextrose Injection, 10% Dextrose Injection, 5% Dextrose in Lactated Ringer's Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, 5% Dextrose and 0.45% Sodium Chloride Injection, 5% Dextrose and 0.2% Sodium Chloride Injection, Lactated Ringer's Injection, Invert Sugar 5% in Sterile Water for Injection, Invert Sugar 10% in Sterile Water for Injection, or 5% Sodium Bicarbonate Injection.
    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).
     
    ADD-Vantage vials
    Reconstitution
    Reconstituted 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
    Preparation
    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.
     
    Intermittent IV Infusion
    Infuse IV over approximately 30 minutes.
     
    Intravenous (IV) Push
    Powder Vials for Injection
    FDA-labeled Reconstitution
    Reconstitute powder with Sterile Water for Injection. Use 2 mL for 500 mg vial to yield 225 mg/mL and 2.5 mL for 1 g vial to yield 330 mg/mL.
    Shake well.
    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).
     
    FDA-labeled Dilution
    Further dilute the reconstituted solution with 5 mL of Sterile Water for Injection.
    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).
     
    Off-label Reconstitution / Dilution†
    A study included 1,110 adult patients who received cephalosporins, including cefazolin, by IV push in the emergency department.
    Doses of 1 and 2 g were reconstituted with 10 mL of Sterile Water for Injection.
    A health care system adult protocol used a dose of 1 g reconstituted with 10 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection.
    A maximum concentration of 100 mg/mL is recommended for pediatric patients.
     
    Intermittent IV Push
    Inject appropriate dose directly into a vein over 3 to 5 minutes or slowly into the tubing of a freely-flowing compatible IV solution.
    Doses have been administered over 2 to 5 minutes in adult studies.

    Intramuscular Administration

    Reconstitution
    Reconstitute powder with Sterile Water for Injection. Use 2 mL for 500 mg vial to yield 225 mg/mL and 2.5 mL for 1 g vial to yield 330 mg/mL. Reconstituted solutions may range in color from pale yellow to yellow without a change in potency.
    Storage: Reconstituted solution is stable for 24 hours at room temperature or 10 days refrigerated.[51610]
     
    Intramuscular Injection
    Inject deeply into a large muscle mass (e.g., anterolateral thigh or deltoid).[51610]

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Reconstituted product is stable for 24 hours at room temperature, or for 10 days if refrigerated (at 41 degrees F)
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use
    - Store reconstituted product in refrigerator (36 to 46 degrees F), discard after 10 days
    Ancef:
    - Protect from light
    - Reconstituted product is stable for 10 days when refrigerated (36 to 46 degrees F)
    - Reconstituted product is stable for 24 hours at room temperature
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Kefzol:
    - Protect from light
    - Reconstituted product is stable for 10 days when refrigerated (36 to 46 degrees F)
    - Reconstituted product is stable for 24 hours at room temperature
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Cephalosporin hypersensitivity, corn hypersensitivity, penicillin hypersensitivity

    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.[31700] 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.

    Renal failure, renal impairment, seizure disorder

    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.[31700]

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    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.

    Laboratory test interference

    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.[31700] Cefazolin may also interfere with certain HPLC techniques and effect theophylline serum concentration measurements.[44294]

    Coagulopathy, vitamin K deficiency

    Many cephalosporins have been rarely associated with a fall in prothrombin activity (hypoprothrombinemia). Those at risk include patients with renal or hepatic impairment, or poor nutritional state, as well as patients receiving a protracted course of antimicrobial therapy. Prothrombin time should be monitored in patients at risk and exogenous vitamin K administered as indicated. Cephalosporins that contain the NMTT side chain (e.g., cefoperazone, cefamandole, cefotetan) have been particularly associated with an increased risk for bleeding. Cephalosporins should be used cautiously in patients with a preexisting coagulopathy (e.g., vitamin K deficiency), since these patients may be at a higher risk for these complications. Also, positive direct Coombs' tests have been reported in patients receiving cephalosporins, including cefazolin. In patients receiving cephalosporins and undergoing hematologic testing, a positive Coombs' test should be considered as possibly being caused by the antibiotic. If anemia develops during or after treatment with cefazolin, drug-induced hemolytic anemia should be considered.[29920] [30066] [30067] [31700] [31702]

    Geriatric

    No overall differences in safety or effectiveness of cefazolin were observed between the older adult and younger adults in clinical trials. Cefazolin is excreted renally; because geriatric 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. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities. According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Diabetes mellitus

    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.

    Pregnancy

    While available studies cannot definitively establish the absence of risk, available data over several decades with cephalosporin use, including cefazolin, in human pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. These studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups. Cefazolin crosses the placenta. Animal reproduction studies with cefazolin during organogenesis at doses 1 to 3 times the maximum recommended human dose (MRHD) did not demonstrate adverse developmental outcomes.

    Breast-feeding

    Data from published literature report that cefazolin is present in human milk, but is not expected to accumulate in the breast-feeding infant. There are no data on the effects of cefazolin on the breast-fed child or on milk production. Previous American Academy of Pediatrics (AAP) recommendations considered cefazolin as generally compatible with breast-feeding.[27500]

    ADVERSE REACTIONS

    Severe

    interstitial nephritis / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    aplastic anemia / Delayed / Incidence not known
    hemolytic anemia / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known

    Moderate

    oral ulceration / Delayed / Incidence not known
    neutropenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    bleeding / Early / Incidence not known
    hypoprothrombinemia / Delayed / Incidence not known
    thrombocytosis / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    confusion / Early / Incidence not known
    hepatitis / Delayed / Incidence not known
    cholestasis / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    candidiasis / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    vaginitis / Delayed / Incidence not known

    Mild

    nausea / Early / 14.8-14.8
    injection site reaction / Rapid / 6.6-6.6
    headache / Early / 4.9-4.9
    urticaria / Rapid / Incidence not known
    rash / Early / Incidence not known
    fever / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    diarrhea / Early / Incidence not known
    anorexia / Delayed / Incidence not known
    vomiting / Early / Incidence not known
    flatulence / Early / Incidence not known
    pyrosis (heartburn) / Early / Incidence not known
    dizziness / Early / Incidence not known
    weakness / Early / Incidence not known
    drowsiness / Early / Incidence not known
    pruritus ani / Early / Incidence not known

    DRUG INTERACTIONS

    Clofarabine: (Moderate) Concomitant use of clofarabine, a substrate of OAT1 and OAT3, and cefazolin, an inhibitor of OAT1 and OAT3, may result in increased clofarabine levels. Therefore, monitor for signs of clofarabine toxicity such as gastrointestinal toxicity (e.g., nausea, vomiting, diarrhea, mucosal inflammation), hematologic toxicity, and skin toxicity (e.g. hand and foot syndrome, rash, pruritus) in patients also receiving OAT1 and OAT3 inhibitors.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Avoid coadministration of rifampin and cefazolin in patients at increased risk of bleeding. If no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated. Postmarketing reports suggest that concomitant administration of high doses of rifampin and cefazolin may prolong the prothrombin time, leading to severe vitamin K-dependent coagulation disorders that may be life-threatening or fatal.
    Isoniazid, INH; Rifampin: (Moderate) Avoid coadministration of rifampin and cefazolin in patients at increased risk of bleeding. If no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated. Postmarketing reports suggest that concomitant administration of high doses of rifampin and cefazolin may prolong the prothrombin time, leading to severe vitamin K-dependent coagulation disorders that may be life-threatening or fatal.
    Loop diuretics: (Minor) Nephrotoxicity associated with cephalosporins may be potentiated by concomitant therapy with loop diuretics. Clinicians should be aware that this may occur even in patients with minor or transient renal impairment.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Rifampin: (Moderate) Avoid coadministration of rifampin and cefazolin in patients at increased risk of bleeding. If no alternative treatment options are available, closely monitor prothrombin time and other coagulation tests, and administer vitamin K as indicated. Postmarketing reports suggest that concomitant administration of high doses of rifampin and cefazolin may prolong the prothrombin time, leading to severe vitamin K-dependent coagulation disorders that may be life-threatening or fatal.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including cephalosporins, may increase the INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Additionally, certain cephalosporins (cefotetan, cefoperazone, cefamandole) are associated with prolongation of the prothrombin time due to the methylthiotetrazole (MTT) side chain at the R2 position, which disturbs the synthesis of vitamin K-dependent clotting factors in the liver. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.

    PREGNANCY AND LACTATION

    Pregnancy

    While available studies cannot definitively establish the absence of risk, available data over several decades with cephalosporin use, including cefazolin, in human pregnancy have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. These studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups. Cefazolin crosses the placenta. Animal reproduction studies with cefazolin during organogenesis at doses 1 to 3 times the maximum recommended human dose (MRHD) did not demonstrate adverse developmental outcomes.

    Data from published literature report that cefazolin is present in human milk, but is not expected to accumulate in the breast-feeding infant. There are no data on the effects of cefazolin on the breast-fed child or on milk production. Previous American Academy of Pediatrics (AAP) recommendations considered cefazolin as generally compatible with breast-feeding.[27500]

    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 due to E. coli, K. pneumoniae, and P. mirabilis (based on a dose of 2 g every 8 hours) and susceptible at 16 mcg/mL or less and resistant at 32 mcg/mL or more for uncomplicated urinary tract infections due to E. coli, K. pneumoniae, and P. mirabilis (based on a dose of 1 g every 12 hours).
     
    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 and drug transporters: none

    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.