Maxipime

4th Generation Cephalosporin Antibiotics

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

Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
Add 5 mL of compatible IV diluent to each 500 mg vial or 10 mL of diluent to each 1 g or 2 g vial. The resultant solution will be 100 mg/mL for the 500 mg and 1 g vials and 160 mg/mL for the 2 g vial. Further dilution is required.
Compatible diluents include Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 0.5% or 1% Lidocaine Hydrochloride Injection, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol.
Storage: Reconstituted solutions are stable for up to 24 hours at room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
 
Dilution
Dilute reconstituted solution with a compatible IV solution to provide a solution with a final concentration between 1 mg/mL and 40 mg/mL.
Compatible solutions include 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 10% Dextrose Injection, Lactated Ringer's Injection, 5% Dextrose and 0.9% Sodium Chloride Injection, Lactated Ringer's and 5% Dextrose Injection, or Normosol-R and Normosol-M in 5% Dextrose Injection.
Storage: Diluted solutions are stable for up to 24 hours at controlled room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
 
ADD-Vantage Vials
Constitute with 50 or 100 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
Storage: Solutions are stable for up to 24 hours at controlled room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
 
Frozen Pre-mixed Bags
Thaw frozen container at room temperature or under refrigeration. Do not force thaw by immersion in water baths or by microwave irradiation.
Storage: The thawed solution is stable for 7 days under refrigeration (5 degrees C, 41 degrees F) or for 24 hours at room temperature. 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. If the foil strip is removed and not used immediately, refold container and latch the side tab until ready to activate and use within 7 days.
Once ready for activation, do not use directly after refrigeration; allow the product to reach room temperature before patient use.
Unfold Duplex container and point the set port downward. Starting at the hanger tab end, fold the Duplex container just below the diluent meniscus trapping all air above the fold.
To activate, squeeze the folded diluent chamber until the seal between the diluent and powder opens, releasing diluent into the drug powder chamber.
Agitate the liquid-powder mixture until the drug powder completely dissolves.
Storage: After reconstitution (activation), use within 12 hours if stored at room temperature or within 5 days if stored under refrigeration.
 
Intermittent IV Infusion
Administer IV over a period of 30 minutes.
DUPLEX Drug Delivery System: Prior to attaching to IV set, fold the Duplex container, starting at the hanger tab end, just below the solution meniscus trapping all air above the fold. Squeeze the Duplex container until the seal between the reconstituted drug solution and the set port opens, releasing the liquid to the set port. Do not use in series connections.
 
Intravenous (IV) Push†
NOTE: Cefepime is not approved by the FDA for IV push administration.
Powder Vials for Injection
Reconstitution
A study included 368 adult hospitalized patients who received cefepime IV push (median 8 doses).
Doses of 1 g were reconstituted with 10 mL of 0.9% Sodium Chloride Injection and doses of 2 g were reconstituted with 20 mL of 0.9% Sodium Chloride Injection.
A study included 535 adult patients who received cefepime by IV push in the emergency department.
Doses of 1 and 2 g were reconstituted with 0.9% Sodium Chloride Injection to a total volume of 10 mL.
A study included 1,110 adult patients who received cephalosporins, including cefepime, by IV push in the emergency department.
Doses of 1 g were reconstituted with 10 mL of Sterile Water for Injection and doses of 2 g were reconstituted with 20 mL of Sterile Water for Injection.
Stability:
Solutions of 1 and 2 g reconstituted with 10 mL of a compatible solution are stable in the vial for up to 24 hours at room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
In a study, cefepime concentrations of 100 and 200 mg/mL in Sterile Water for Injection, 0.9% Sodium Chloride Injection, and 5% Dextrose Injection were stable in polypropylene syringes for 1 day at room temperature (22 to 24 degrees C), for 7 to 14 days at 4 degrees C, and up to 90 days at -20 degrees C. Concentrations were maintained at more than 90% of the initial concentration.
 
Intermittent IV Push
Doses have been administered IVP at a rate of 2 to 5 minutes.

Powder Vials for Injection
Reconstitution:
Reconstitute with 1 of the following diluents: Sterile Water for Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection, 0.5% or 1% Lidocaine Hydrochloride Injection, or Sterile Bacteriostatic Water for Injection with Parabens or Benzyl Alcohol.
Add 1.3 mL of diluent to each 500 mg vial, or 2.4 mL of diluent to each 1 g vial.
The final concentration after constitution will be 280 mg/mL.
Storage: Reconstituted solutions are stable for up to 24 hours at controlled room temperature or 7 days refrigerated (2 to 8 degrees C, 36 to 46 degrees F).
 
Intramuscular Injection:
Inject deeply into a large muscle (i.e., upper outer quadrant of the gluteus maximus or lateral part of the thigh). To reduce injection site pain, mix cefepime with 1% lidocaine WITHOUT epinephrine.

seizures / Delayed / 0-1.0
azotemia / Delayed / 0-1.0
hyperkalemia / Delayed / 0-1.0
coma / Early / Incidence not known
anaphylactic shock / Rapid / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known

elevated hepatic enzymes / Delayed / 2.4-2.8
hypophosphatemia / Delayed / 2.8-2.8
eosinophilia / Delayed / 1.7-1.7
hypoprothrombinemia / Delayed / 1.4-1.6
phlebitis / Rapid / 1.3-1.3
erythema / Early / 0-1.0
vaginitis / Delayed / 0-1.0
pseudomembranous colitis / Delayed / 0-1.0
colitis / Delayed / 0-1.0
candidiasis / Delayed / 0-1.0
anemia / Delayed / 0-1.0
hypocalcemia / Delayed / 0-1.0
hypercalcemia / Delayed / 0-1.0
hyperphosphatemia / Delayed / 0-1.0
cholestasis / Delayed / Incidence not known
encephalopathy / Delayed / Incidence not known
aphasia / Delayed / Incidence not known
hallucinations / Early / Incidence not known
confusion / Early / Incidence not known
superinfection / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
bleeding / Early / Incidence not known
thrombocytopenia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known

rash / Early / 1.1-4.0
injection site reaction / Rapid / 0.6-3.0
diarrhea / Early / 0-3.0
nausea / Early / 0-2.0
headache / Early / 0-1.0
fever / Early / 0-1.0
urticaria / Rapid / 0-1.0
pruritus / Rapid / 0-1.0
vomiting / Early / 0-1.0

Maxipime

Rx

Parenteral fourth-generation cephalosporin. Pharmacokinetics and spectrum of activity similar to ceftazidime. Clinical uses are similar to those of the third-generation cephalosporins.

2 g IV every 8 hours for 7 days or until resolution of neutropenia. For patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be reevaluated.

50 mg/kg/dose IV every 8 hours (Max: 2 g/dose) for 7 days or until resolution of neutropenia. For patients whose fever resolves but who remain neutropenic for more than 7 days, the need for continued antimicrobial therapy should be reevaluated.

0.5 to 1 g IV or IM every 12 hours for 7 to 14 days with or without an aminoglycoside.

50 mg/kg/dose (Max: 1 g/dose) IV or IM every 12 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

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

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is less than 4 mg/L. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

30 mg/kg/dose IV 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.

2 g IV every 12 hours for 7 to 14 days with or without an aminoglycoside.

50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours. Treat for 24 to 48 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

50 mg/kg/dose IV every 12 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.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is less than 4 mg/L. Neonates are at risk for systemic infection and rapid change in their clinical condition. Treat UTIs as presumed pyelonephritis in these patients.

30 mg/kg/dose IV 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.

2 g IV every 12 hours for 10 days.

50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 days.

50 mg/kg/dose IV every 12 hours.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.

30 mg/kg/dose IV every 12 hours.

2 g IV every 8 to 12 hours for 7 to 14 days for moderate or severe infections in patients with recent antibiotic exposure or infections with no complicating features or with ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

1 to 2 g IV every 8 to 12 hours for 10 days. For infections caused by P. aeruginosa, 2 g IV every 8 hours for 10 days.[31702] For hospital-acquired or postprocedural empyema, guidelines recommend cefepime in combination with metronidazole and vancomycin for at least 2 weeks after drainage and defervescence.[61949]

50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours for 10 days. For infections caused by P. aeruginosa, 50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours.

50 mg/kg/dose IV every 12 hours. For infections caused by P. aeruginosa, 50 mg/kg/dose IV every 8 hours.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.

30 mg/kg/dose IV every 12 hours.

2 g IV every 8 hours for at least 7 days.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours for at least 7 days.

2 g IV every 8 hours for 7 days.[61215]

1 g intraperitoneally every 24 hours for 21 to 28 days.

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

250 to 500 mg/L intraperitoneal loading dose, followed by 100 to 125 mg/L in each dialysate exchange. Treat for 21 to 28 days.

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

2 g IV every 8 to 12 hours as part of combination therapy for 7 to 10 days.

2 g IV every 8 to 12 hours as part of combination therapy for 7 to 10 days.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours. FDA-labeling for other populations suggests a duration of 7 to 10 days.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. FDA-labeling for other populations suggests a duration of 7 to 10 days.

30 mg/kg/dose IV every 12 hours. FDA-labeling for other populations suggests a duration of 7 to 10 days.

1 to 2 g IV every 8 to 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

1 to 2 g IV every 8 to 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

50 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.

30 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days.

1 to 2 g IV every 8 to 12 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

1 to 2 g IV every 8 to 12 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

2 g IV every 8 hours. Clinical practice guidelines recommend cefepime as standard therapy for P. aeruginosa infections and as an alternative for H. influenzae or S. pneumoniae infections. Cefepime is also recommended for empiric therapy in combination with vancomycin for purulent meningitis in patients with penetrating trauma, postneurosurgery, or with a CSF shunt.

50 mg/kg/dose IV every 8 hours (Max: 2 g/dose). Although cefepime is included as a treatment option in clinical guidelines for treatment of bacterial meningitis, the FDA-approved labeling specifically recommends against use in pediatric patients with meningitis or in those whom meningeal seeding from a distant site has occurred.

2 g IV every 8 hours.[38567] Guidelines recommend cefepime as an alternate therapy for 4 weeks for native valve endocarditis (NVE) and for 6 weeks for prosthetic valve endocarditis (PVE) caused by HACEK microorganisms. A cephalosporin in combination with an aminoglycoside for 6 weeks is also recommended for endocarditis due to non-HACEK gram-negative microorganisms. For patients with acute culture-negative NVE, cefepime plus vancomycin could be reasonable empiric therapy. For patients with early (less than 1 year after surgery) culture-negative PVE, cefepime plus vancomycin, rifampin, and gentamicin could be reasonable empiric therapy. Treat culture-negative endocarditis for 4 to 6 weeks.[60294]

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours. Guidelines recommend cefepime plus vancomycin, gentamicin, and rifampin (if prosthetic material is present) for culture-negative nosocomial endocarditis associated with vascular cannulae or early (less than 1 year after surgery) prosthetic valve endocarditis; treat for 4 to 6 weeks, with a longer course for PVE. Cefepime is also a preferred therapy in combination with an aminoglycoside for at least 6 weeks for non-HACEK gram-negative microorganisms.

50 mg/kg/dose IV every 8 to 12 hours.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less.

30 mg/kg/dose IV every 12 hours.

2 g IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

30 mg/kg/dose IV every 12 hours.

2 g IV every 8 to 12 hours for 6 weeks. May consider addition of ciprofloxacin or aminoglycoside for P. aeruginosa infections.

2 g IV every 12 hours for 4 to 6 weeks, which may be followed by long-term suppressive therapy. May consider addition of an aminoglycoside for P. aeruginosa infections; if aminoglycoside is in spacer and organism is aminoglycoside-susceptible, then double coverage is provided with IV or oral monotherapy.

2 g IV every 8 to 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 hours for 2 to 3 weeks. Generally, 2 weeks is appropriate for most patients; immunocompromised patients may require a longer duration.

2 g IV every 8 to 12 hours for 4 to 6 weeks.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 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.

50 mg/kg/dose IV every 8 to 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.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. 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.

30 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.

2 g IV every 8 to 12 hours. Treat for 1 to 2 weeks or until clinically improved, followed by oral step-down therapy for 2 to 4 weeks.

50 mg/kg/dose (Max: 2 g/dose) IV every 8 to 12 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.

50 mg/kg/dose IV every 8 to 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.

50 mg/kg/dose IV every 12 hours. May give 30 mg/kg/dose IV every 12 hours if target pathogen MIC is 4 mg/L or less. 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.

30 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.

†Indicates off-label use

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

Adult patients receiving a usual dose of 500 mg IV/IM every 12 hours (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 11 to 60 mL/minute: 500 mg IV/IM every 24 hours.
CrCl less than 11 mL/minute: 500 mg IV/IM once, then 250 mg IV/IM every 24 hours.
 
Adult patients receiving a usual dose of 1 g IV/IM every 12 hours (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 1 g IV/IM every 24 hours.
CrCl 11 to 29 mL/minute: 1 g IV/IM once, then 500 mg IV/IM every 24 hours.
CrCl less than 11 mL/minute: 1 g IV/IM once, then 250 mg IV/IM every 24 hours.
 
Adult patients receiving a usual dose of 2 g IV every 12 hours (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 2 g IV every 24 hours.
CrCl 11 to 29 mL/minute: 2 g IV once, then 1 g IV every 24 hours.
CrCl less than 11 mL/minute: 2 g IV once, then 500 mg IV every 24 hours.
 
Adult patients receiving a usual dose of 2 g IV every 8 hours (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 2 g IV every 12 hours.
CrCl 11 to 29 mL/minute: 2 g IV every 24 hours.
CrCl less than 11 mL/minute: 2 g IV once, then 1 g IV every 24 hours.
 
Adult patients (alternative)† [32569]
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 10 to 50 mL/minute: Administer 50% to 100% of the usual dose every 24 hours.
CrCl less than 10 mL/minute: Administer 25% to 50% of the usual dose every 24 hours.
 
Pediatric patients (non-neonatal)
Specific data in pediatric patients with impaired renal function are not available. Because cefepime pharmacokinetics are similar in adults and non-neonatal pediatric patients, changes in the dosage regimen proportional to those in adults are recommended for pediatric patients. The below recommendations for maintenance dose adjustments in pediatric patients are consistent with recommendations for adult patients with renal impairment.[31702]
 
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 12 hours with a Max of 1 g/dose (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 50 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
CrCl 11 to 29 mL/minute: 50 mg/kg/dose (Max: 1 g/dose) IV once, then 25 mg/kg/dose (Max: 500 mg/dose) IV every 24 hours.
CrCl less than 11 mL/minute: 50 mg/kg/dose (Max: 1 g/dose) IV once, then 12.5 mg/kg/dose (Max: 250 mg/dose) IV every 24 hours.
 
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 12 hours with a Max of 2 g/dose (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
CrCl 11 to 29 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV once, then 25 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
CrCl less than 11 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV once, then 12.5 mg/kg/dose (Max: 500 mg/dose) IV every 24 hours.
 
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 8 hours (FDA-labeling) [31702]
CrCl more than 60 mL/minute: No dosage adjustment needed.
CrCl 30 to 60 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours.
CrCl 11 to 29 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
CrCl less than 11 mL/minute: 50 mg/kg/dose (Max: 2 g/dose) IV once, then 25 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.
 
Pediatric patients (alternative)† [32569]
GFR more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
GFR 10 to 50 mL/minute/1.73 m2: 50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.
GFR less than 10 mL/minute/1.73 m2: 50 mg/kg/dose (Max: 2 g/dose) IV every 48 hours.
 
Intermittent hemodialysis
NOTE: Approximately 68% of the total amount of cefepime present in the body at the start of dialysis will be removed during a 3-hour dialysis period. Administer doses at the same time each day and after the completion of hemodialysis on hemodialysis days.[31702]
 
Adult patients receiving a usual dose of 500 mg IV/IM every 12 hours, 1 g IV/IM every 12 hours, or 2 g IV every 12 hours (FDA-labeling)
1g IV/IM once, then 500 mg IV/IM every 24 hours.[31702]
 
Adult patients receiving a usual dose of 2 g IV every 8 hours (FDA-labeling)
1 g IV every 24 hours.[31702]
 
Adult patients (alternative)†
Administer 25% to 50% of the usual dose every 24 hours.[32569] A dose 2 g IV after each dialysis session has also been suggested.
 
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 12 hours (FDA-labeling)
25 mg/kg/dose (Max: 1 g/dose) IV on day 1, then 12.5 mg/kg/dose (Max: 500 mg/dose) IV every 24 hours thereafter.[31702]
 
Pediatric patients receiving a usual dose of 50 mg/kg/dose IV every 8 hours (FDA-labeling)
25 mg/kg/dose (Max: 1 g/dose) IV every 24 hours.[31702]
 
Pediatric patients (alternative)†
50 mg/kg/dose (Max: 2 g/dose) IV every 24 hours.[32569]
 
Peritoneal dialysis
Adult and Pediatric patients (FDA-approved labeling)
For continuous ambulatory peritoneal dialysis (CAPD), FDA-labeling suggests administering recommended doses of cefepime as indicated for the infection and extend the dosing interval to every 48 hours.[31702]
 
Adult patients (alternative)†
Administer 25% to 50% of the usual dose every 24 hours.[32569]
 
Pediatric patients (alternative)†
50 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
Doses of 1 to 2 g IV every 12 hours or a 2 g IV loading dose then 1 g IV every 8 to 12 hours have generally been suggested for CRRT.[32569] General recommendations for patients receiving CVVH suggest 1 to 2 g IV every 12 hours. A 2 g loading dose may be used.[34038] [42303] General recommendations for patients receiving CVVHD and CVVHDF suggest 2 g IV every 12 hours or 1 g IV every 8 hours. A 2 g loading dose may be used. In patients with pathogens with a MIC of 4 mcg/mL or higher, a dose of 2 g IV every 8 hours might be needed.[34038] [42303] More specific recommendations based on ultrafiltrate rates (UFRs) suggest 1 g IV every 8 hours in patients receiving CVVH, CVVHD, or CVVHDF with a UFR of 1 L/hour and 1 g IV every 6 hours or 2 g IV every 8 hours with a UFR of 2 L/hour or higher. Alternatively, a 2 g IV loading dose then 4 g given as a continuous IV infusion can be considered for patients receiving CVVH or CVVHD with a UFR of 3 L/hour or higher.[65398] Pharmacokinetic modeling suggests these doses are sufficient to reach target attainment; however, in patients with more resistant pathogens, there is a higher chance for suboptimal concentrations.[65400] [65401]
 
Pediatric patients
25 to 50 mg/kg/dose (Max: 2 g/dose) IV every 12 hours. Pediatric recommendations are based on limited study data, mainly derived from adult patients, and extrapolation of CRRT clearance based on cefepime pharmacokinetic parameters.
 
Hybrid hemodialysis†
NOTE: Hybrid hemodialysis modalities include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g., intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.[65397]
 
Adult patients
In a Monte Carlo simulation study using population pharmacokinetic data, dosing was studied using 4 different PIRRT setting simulations over 8 to 10 hours/day. A dose of 2 g IV as a loading dose then 1 g IV every 6 hours achieved at least a 90% probability of target attainment for an 8-hour PIRRT session. An alternative regimen that meets the goal is 2 g IV pre-PIRRT, then 3 g IV post-PIRRT.[65394]
 
Pediatric patients
Cefepime dosing data are not available in pediatric patients receiving hybrid hemodialysis. Based on adult data, dosage adjustments may be necessary.[65394]

Amikacin: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Aminoglycosides: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Gentamicin: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
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.
Paromomycin: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Plazomicin: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
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.
Streptomycin: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
Tobramycin: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
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.

Cefepime/Cefepime Hydrochloride Intravenous Inj Sol: 1g, 2g, 50mL, 100mL
Cefepime/Cefepime Hydrochloride/Maxipime Intramuscular Inj Pwd F/Sol: 1g, 2g
Cefepime/Cefepime Hydrochloride/Maxipime Intravenous Inj Pwd F/Sol: 1g, 2g

6 g/day IV or 2 g/day IM.

6 g/day IV or 2 g/day IM.

150 mg/kg/day IV (Max: 6 g/day) or 100 mg/kg/day IM (Max: 2 g/day).

150 mg/kg/day IV (Max: 6 g/day) or 100 mg/kg/day IM (Max: 2 g/day).

2 to 11 months: 150 mg/kg/day IV or 100 mg/kg/day IM.
1 month: Safety and efficacy have not been established; however, doses up to 150 mg/kg/day IV or 100 mg/kg/day IM have been used off-label.

Neonates 36 weeks gestation and older: Safety and efficacy have not been established; however, doses up to 100 mg/kg/day IV have been used off-label.
Neonates less than 36 weeks gestation: Safety and efficacy have not been established; however, doses up to 60 mg/kg/day IV have been used off-label.

Cefepime, a beta-lactam antibiotic, is mainly bactericidal. Like other cephalosporins and penicillins, cefepime 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. PBPs 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. PBPs vary among different bacterial species. Thus, the intrinsic activity of cefepime, as well as other cephalosporins and penicillins, against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, cefepime'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.[51464] [51465] Prevention of the autolysin response to beta-lactam antibiotic exposure through the loss of autolytic activity (mutation) or inactivation of autolysin (low-medium pH) by the microorganism can lead to tolerance to the beta-lactam antibiotic resulting in bacteriostatic activity.[51465]
 
Beta-lactams, including cefepime, 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).[34143] [34145] [35436] [35437] [35438] [35439] 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.[35436] [35437] [35438]
 
The susceptibility interpretive criteria for cefepime are delineated by pathogen. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacterales. The MICs for Enterobacterales are defined by the FDA as susceptible at 2 mcg/mL or less, intermediate at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more; for isolates with an intermediate susceptibility, the recommended dose is 2 g IV every 8 hours in patients with normal renal function. The MICs for Enterobacterales are defined by CLSI as susceptible at 2 mcg/mL or less, susceptible-dose dependent (SDD) at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more; the breakpoint for susceptible is based on a dose of 1 g IV every 12 hours, and the breakpoint for SDD is based on dosage regimens that result in higher cefepime exposure (up to the approved maximum dosage regimen). The CLSI and the FDA differ on MIC interpretation for P. aeruginosa. The MICs for P. aeruginosa are defined by the FDA as susceptible at 8 mcg/mL or less and resistant at 16 mcg/mL or more; the recommended dose is 2 g IV every 8 hours in patients with normal renal function. The MICs for P. aeruginosa are defined by CLSI as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more; the breakpoints are based on a dose of 1 g IV every 8 hours or 2 g IV every 12 hours. The MICs are defined for Acinetobacter sp. and non-Enterobacterales as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more. The MICs are defined for S. pneumoniae for meningitis isolates as susceptible at 0.5 mcg/mL or less, intermediate at 1 mcg/mL, and resistant at 2 mcg/mL or more. The MICs are defined for S. pneumoniae for non-meningitis isolates as susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for Streptococcus sp. Viridans group susceptible at 1 mcg/mL or less, intermediate at 2 mcg/mL, and resistant at 4 mcg/mL or more. The MICs are defined for beta-hemolytic streptococci and N. gonorrhoeae as susceptible at 0.5 mcg/mL or less. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 2 mcg/mL or less. Methicillin-susceptible staphylococci may be considered susceptible to cefepime.[63320] [63321]
 
Compared with third-generation cephalosporins, cefepime possesses an increased ability to penetrate the bacterial cell's outer membrane and a lower rate of hydrolysis by bacterial beta-lactamases. Cefepime exists as a zwitterion and it is thought that this property enhances its ability to penetrate porin channels in the cell walls of gram-negative bacteria.[23705] [51569] Cefepime has a low affinity for chromosomally-encoded beta-lactamases and is highly resistant to hydrolysis by most beta-lactamases.[51569]

Cefepime is administered intravenously and intramuscularly. The average steady-state Vd in adults is 18 L. In general, pediatric patients have slightly faster clearance and larger Vd than adults. The Vd of cefepime in pediatric patients is approximately 0.37 L/kg. Approximately 20% of the circulating drug is protein-bound. It is distributed into most body tissues and fluids. In a pediatric pharmacokinetic trial, CSF concentrations peaked 30 minutes after the dose and were lowest immediately before the next dose; however, there was relatively little variation in CSF concentrations over the 8-hour dosing interval.
 
Cefepime is metabolized to N-methylpyrrolidine (NMP), which is rapidly converted to the N-oxide (NMP-N-oxide). Urinary recovery of unchanged cefepime accounts for approximately 85% of the administered dose in adults. Less than 1% of the administered dose is recovered from urine as NMP, 6.8% as NMP-N-oxide, and 2.5% as an epimer of cefepime. The elimination half-life in children with normal renal function is approximately 1.7 hours compared to 2 hours in adults.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

Cefepime pharmacokinetics are linear over the dose range of 250 mg to 2 g IV. The mean peak serum concentrations (Cmax) are 39.1 mcg/mL with a 500 mg IV dose, 81.7 mcg/L with a 1 g IV dose, and 163.9 mcg/mL with a 2 g IV dose in healthy adult males. There is no evidence of accumulation in healthy adult male volunteers receiving clinically relevant doses for a period of 9 days.

Cefepime pharmacokinetics are linear over the dose range of 500 mg to 2 g IM. The mean peak serum concentrations (Cmax) are 13.9 mcg/mL with a 500 mg IV dose, 29.6 mcg/L with a 1 g IV dose, and 57.5 mcg/mL with a 2 g IV dose in healthy adult males. Cmax occurs approximately 1.5 hours after IM administration in adults. In pediatric patients who received a 50 mg/kg/dose IV and IM, the absolute bioavailability of the IM dose was 82.3%.

Available data from observational studies and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no cases of cefepime exposure during pregnancy reported from postmarketing experience or clinical trials; however, cefepime crosses the placenta. Cefepime was not embryocidal and did not cause fetal malformations when administered to animals during organogenesis at doses up to 1.6-times the maximum recommended clinical dose based on body surface area. [51569]

Cefepime is excreted in human milk at low concentrations. A nursing infant consuming approximately 1,000 mL/day of human milk would receive approximately 0.5 mg/day of cefepime. In a pharmacokinetic study in 9 healthy lactating women, the mean breast milk concentrations of cefepime were approximately 0.5 mcg/mL during the first 8 hours after a single 1,000 mg IV dose. Concentrations declined and became undetectable at 12 to 24 hours after the dose. The mean cumulative breast milk excretion of cefepime over 24 hours was 0.01% of the administered dose. There is no information regarding the effects of cefepime on milk production or on the breast-fed infant. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for cefepime and any potential adverse effects on the breast-fed child from cefepime or the underlying maternal condition. [51569]