Cefepime

Pharmacologic Category

Antibiotic, Cephalosporin (Fourth Generation)

Dosing: Adult

Usual dosage range:

Traditional intermittent infusion method (over 30 minutes): IV: 1 to 2 g every 8 to 12 hours. For coverage of serious Pseudomonas aeruginosa infections: 2 g every 8 hours (Crandon 2010; Koomanachai 2010; Su 2017). For infections caused by an organism with a minimum inhibitory concentration (MIC) <4 mg/L, 1 g every 6 hours achieves pharmacodynamic parameters comparable to 2 g every 8 hours; reserve for use in less serious infections (Lodise 2006; Roos 2006; Tam 2003).

Extended infusion method (off-label method): IV: 2 g every 8 hours infused over 3 or 4 hours (Arnold 2013; Bauer 2013; Koomanachai 2010; Nicasio 2009; Wrenn 2018); may give first dose over 30 minutes (Wrenn 2018).

Continuous infusion method (off-label method): IV: 4 to 6 g infused over 24 hours (Abdul-Aziz 2016; Georges 2005; Rhodes 2017a); may give first dose of 2 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations (eg, sepsis) is desired (Abdul-Aziz 2016; SCCM [Rhodes 2017b]).

Note: Extended and continuous infusion methods are based largely on pharmacokinetic and pharmacodynamic modeling data; clinical efficacy data are limited (Abdul-Aziz 2016; Bauer 2013; Burgess 2015; Georges 2005; MacVane 2014; Moehring 2019a; Rhodes 2017a).

Bloodstream infection (gram-negative bacteremia) (off-label use):

Community-acquired infection, without sepsis or septic shock (immunocompetent host and no infections with P. aeruginosa in prior 3 to 6 months): IV: 2 g every 12 hours (Moehring 2019b).

Health care–associated infection (including catheter-related infection, infection in immunocompromised hosts, patients with sepsis or septic shock, or for coverage of P. aeruginosa): IV: 2 g every 8 hours (IDSA [Mermel 2009]; Moehring 2019b; Su 2017). Note: For empiric therapy of gram-negative bloodstream infection in patients with sepsis or septic shock and for empiric therapy of P. aeruginosa bloodstream infection in patients with neutropenia or severe burns, some experts recommend giving cefepime with a second gram-negative active agent (Kanj 2019a; Moehring 2019b; SCCM [Rhodes 2017b]). Some experts also prefer the extended-infusion method in critical illness or if treating a susceptible organism with an elevated MIC (Moehring 2019a; SCCM [Rhodes 2017b]).

Duration of therapy: Usual duration is 7 to 14 days; individualize duration depending on source and extent of infection as well as clinical response. A 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Moehring 2019b; Yahav 2018). If neutropenic, extend treatment until afebrile for ≥48 hours and recovery of neutrophils (ANC ≥500 cells/mm³ and increasing) (IDSA [Freifeld 2011]). For P. aeruginosa bacteremia in neutropenic patients, some experts treat for a minimum of 14 days and until recovery of neutrophils (Kanj 2019b).

Cystic fibrosis, acute pulmonary exacerbation (off-label use): For empiric or targeted therapy of P. aeruginosa or other gram-negative bacilli:

IV: 2 g every 8 hours, usually given as part of an appropriate combination regimen (Flume 2009; Zobell 2013). Note: Some experts prefer the extended or continuous infusion method to optimize exposure (Simon 2019; Thompson 2016).

Duration of therapy: Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).

Diabetic foot infection, moderate to severe (off-label use): IV: 2 g every 8 to 12 hours in combination with other appropriate agents; for P. aeruginosa infection, use 2 g every 8 hours (Gentry 1991; So 2016; Weintrob 2019). Note: Empiric P. aeruginosa coverage with this dose is usually not indicated unless patient is at risk (eg, significant water exposure, warm climate) (IDSA [Lipsky 2012]; Weintrob 2019).

Duration of therapy: Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (IDSA [Lipsky 2012]; Weintrob 2019).

Intra-abdominal infection, health care–associated or high-risk community-acquired infection: Note: For community-acquired infection, reserve for severe infection or patients at high risk of adverse outcome and/or resistance (Barshak 2019; SIS/IDSA [Solomkin 2010]):

Cholecystitis, acute: IV: 2 g every 8 to 12 hours; if P. aeruginosa is suspected, use 2 g every 8 hours. Continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2019).

Other intra-abdominal infections (eg, cholangitis, perforated appendix, diverticulitis, intra-abdominal abscess): IV: 2 g every 8 to 12 hours in combination with metronidazole, and, when appropriate, other agents; if P. aeruginosa is suspected, use 2 g every 8 hours. Total duration of therapy (which may include oral step-down therapy) is 4 to 7 days following adequate source control (Barshak 2019; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration of therapy may be necessary (Barshak 2019; Pemberton 2019). Note: For patients who are critically ill or are at high risk for infection with drug-resistant pathogens, some experts favor the extended or continuous infusion method (Barshak 2019; WSES [Sartelli 2017]).

Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscess (off-label use): As a component of empiric therapy in patients at risk for P. aeruginosa or another resistant gram-negative bacteria (eg, neurosurgical or immunocompromised patients):

IV: 2 g every 8 hours as part of an appropriate combination regimen; duration generally ranges from 4 to 8 weeks for brain abscess and spinal epidural abscess and 6 to 8 weeks for intracranial epidural abscess (Bodilsen 2018; Sexton 2019a; Sexton 2019b; Southwick 2020).

Meningitis, bacterial (off-label use): Note: As a component of empiric therapy for health care–associated infections or infections in immunocompromised patients, or as pathogen-specific therapy (eg, gram-negative bacteria, including P. aeruginosa):

IV: 2 g every 8 hours; for empiric therapy, use in combination with other appropriate agents (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Treatment duration for gram-negative bacilli is a minimum of 10 to 14 days, although some experts recommend ≥21 days (Hasbun 2019; IDSA [Tunkel 2017]).

Neutropenic enterocolitis (typhlitis) (off-label use): IV: 2 g every 8 hours in combination with metronidazole (IDSA [Freifeld 2011]; Wong Kee Song 2019). In patients who have clinical resolution following neutropenia and who did not have signs of severe disease at the time of diagnosis, the duration of antibiotics is 14 days following recovery from neutropenia; many patients can be switched to an appropriate oral antibiotic regimen once neutropenia has resolved (Wong Kee Song 2019).

Neutropenic fever, high-risk cancer patients (empiric therapy): Note: High-risk patients are those expected to have an ANC ≤100 cells/mm³ for >7 days or an ANC ≤100 cells/mm³ for any expected duration if there are ongoing comorbidities (eg, sepsis, mucositis, significant hepatic or renal dysfunction) (IDSA [Freifeld 2011]; some experts use an ANC cutoff of <500 cells/mm³ to define high-risk patients (Wingard 2019).

IV: 2 g every 8 hours until afebrile for ≥48 hours and resolution of neutropenia (ANC ≥500 cells/mm³ and increasing) or standard duration for the specific infection identified, if longer than the duration of neutropenia. Additional agent(s) may be needed depending on clinical status (IDSA [Freifeld 2011]). Some experts prefer the extended infusion method, particularly in those who are critically ill (Moehring 2019a; SCCM [Rhodes 2017b]; Wingard 2019).

Osteomyelitis and/or discitis (off-label use): IV: 2 g every 8 to 12 hours for ≥6 weeks (IDSA [Berbari 2015]; Osmon 2019). For empiric therapy, use in combination with other appropriate agents (IDSA [Berbari 2015]).

Peritonitis, treatment (peritoneal dialysis patients) (off-label use): As a component of empiric therapy or as pathogen-directed therapy for gram-negative bacteria (eg, P. aeruginosa):

Note: Intraperitoneal is preferred to IV administration unless the patient shows signs of systemic infection, then IV is preferred (ISPD [Li 2016]).

Automated peritoneal dialysis (APD): Intraperitoneal: 1 g every 24 hours given in the longest dwell is preferred (ISPD [Li 2016]).

CAPD:

Intermittent: Intraperitoneal: 1 g added to one exchange of dialysis solution every 24 hours (to be given in the longest daily dwell) (ISPD [Li 2016]).

Continuous (with every exchange): Intraperitoneal: Loading dose: 250 to 500 mg/L of dialysate with first exchange of dialysate. Maintenance dose: 100 to 125 mg/L of dialysate with each subsequent exchange of dialysate (ISPD [Li 2016]).

Note: Consider 25% dose increase in patients on APD or CAPD with significant residual kidney function (urine output >100 mL/day) (Mancini 2018; Szeto 2018).

Pneumonia:

Community-acquired pneumonia: For empiric therapy of inpatients at risk of infection with a resistant gram-negative pathogen(s), including P. aeruginosa:

IV: 2 g every 8 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is a minimum of 5 days; a longer course may be required for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (IDSA/ATS [Metlay 2019]).

Hospital-acquired pneumonia or ventilator-associated pneumonia: For empiric therapy or pathogen-specific therapy of resistant gram-negative pathogen(s), including P. aeruginosa:

IV: 2 g every 8 hours, as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]), but longer courses may be warranted for severe or complicated infection or for P. aeruginosa infection (Kanj 2019b; Klompas 2019). Note: Some experts prefer the extended-infusion method, particularly in those who are critically ill or to optimize exposure if treating a susceptible organism with an elevated MIC (Klompas 2019; Moehring 2019a; SCCM [Rhodes 2017b]).

Prosthetic joint infection, pathogen-specific therapy for gram-negative bacilli (off-label use): IV: 2 g every 8 to 12 hours; duration varies but is generally 4 to 6 weeks for patients who undergo resection arthroplasty (Berbari 2019; IDSA [Osmon 2013]).

Sepsis and septic shock (broad-spectrum coverage, including P. aeruginosa) (off-label use): IV: 2 g every 8 hours (Alves 2014); use in combination with other appropriate agents. Initiate therapy as soon as possible and preferably within 1 hour of recognition of sepsis or septic shock. Usual duration of treatment is 7 to 10 days but may be longer or shorter depending on clinical response and/or source of infection (SCCM [Rhodes 2017b]). Some experts prefer the extended-infusion method (Moehring 2019a; SCCM [Rhodes 2017b]).

Septic arthritis, without prosthetic material (off-label use): As a component of empiric therapy or pathogen-specific therapy for gram-negative pathogens (including P. aeruginosa): IV: 2 g every 8 to 12 hours; for empiric therapy, use in combination with other appropriate agents. Total treatment duration is 3 to 4 weeks (in the absence of osteomyelitis), including oral step-down therapy (Goldenberg 2019).

Skin and soft tissue infections, moderate to severe: As empiric or pathogen-directed therapy in patients with or at risk for gram-negative bacteria (eg, P. aeruginosa):

IV: 2 g every 8 to 12 hours. Usual duration is 10 to 14 days based on response to therapy (Hoepelman 1993; Kanj 2019c).

Urinary tract infection, complicated (including pyelonephritis): IV: 1 to 2 g every 12 hours; some experts prefer 2 g every 8 hours if P. aeruginosa is suspected. Switch to an appropriate oral regimen once patient has improvement in symptoms, if culture and susceptibility results allow. Duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days (Hooton 2019; IDSA [Gupta 2011]).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Altered kidney function: IV:

Cefepime Dose Adjustments for Kidney Function^a

CrCl

(mL/minute)^b

Dose

^aKuti 2010; Lodise 2006; Tam 2003; manufacturer's labeling.

^bCrCl can be calculated using the Cockcroft-Gault equation (Jonckheere 2016).

^cChoose usual recommended dose based on indication and disease severity (see adult dosing), then choose the adjusted dose from that column corresponding to the patient’s CrCl.

^dDose is decreased from 1 g every 6 hours to 1 g every 8 hours at CrCl <50 (Lodise 2006).

>60 (usual recommended dose)^c

1 g every 12 hours

2 g every 12 hours

1 g every 6 hours

2 g every 8 hours

30 to 60

1 g every 24 hours

1 g every 12 hours

1 g every 8 hours^d

2 g every 12 hours

11 to 29

500 mg every 24 hours

1 g every 24 hours

1 g every 12 hours

1 g every 12 hours

<11

250 mg every 24 hours

500 mg every 24 hours

1 g every 24 hours

1 g every 24 hours

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m²): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without significant organ dysfunction. Younger patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematological malignancies. A measured urinary clearance is necessary to identify these patients.

Note: Limited data available; dosing based on Monte Carlo simulation and expert opinion.

IV: Initial: 2 g every 6 hours infused over 3 hours when used empirically or in patients with known minimum inhibitory concentrations (MICs) >4 mg/L (Zasowski 2015). Closely monitor patient for response and adverse reactions (eg, neurotoxicity) due to drug accumulation. Consider obtaining drug concentrations when available.

Hemodialysis, intermittent (thrice weekly): Note: Achievement of cefepime pharmacodynamic targets is dependent on organism MIC, the absence or presence of residual kidney function, and interval between dialysis sessions (ie, 2- or 3-day interdialytic interval) (Descombes 2016; Perez 2012; Schmaldienst 2000). Factors such as severity of illness, location of infection, and patient weight should be considered when selecting between the higher and lower dosing regimens as well.

IV: Dialyzable (70% to 85% reduction in serum concentration from a 3.5- to 4-hour hemodialysis treatment with high flux filters [Descombes 2016; Schmaldienst 2000]).

Daily dosing (administer after hemodialysis on dialysis days): IV: Initial: 1 g (single dose) on day 1. Maintenance: 500 mg to 1 g every 24 hours (Heintz 2009; manufacturer’s labeling). Note: If the usual recommended dose for normal renal function is 2 g every 8 hours or 1 g every 6 hours, utilize 1 g every 24 hours; use 500 mg every 24 hours for all other doses (Lodise 2006; manufacturer’s labeling).

Thrice-Weekly (postdialysis) Dosing^a

Residual kidney function and organism susceptibility

Cefepime dose for a 2-day interdialytic interval (ie, next dialysis expected in 48 hours)

Cefepime dose for a 3-day interdialytic interval (ie, next dialysis expected in 72 hours)

^aExpert opinion derived from Descombes 2016; Perez 2012; Schmaldienst 2000.

Patient is anuric AND the organism MIC <4 mg/L

1.5 g after hemodialysis

2 g after hemodialysis

Any of the following:

Empiric therapy OR

Patient has residual kidney function OR

Organism MIC ≥4 mg/L

2 g after hemodialysis

2 g after hemodialysis

Peritoneal dialysis:

IV: 1 g every 24 hours (Lodise 2006; expert opinion).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or approximately 1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: IV: 2 g every 8 to 12 hours (Beumier 2014; Carlier 2015; Chaijamorn 2018; Philpott 2019; Shaw 2016).

Note: For severe infections or sepsis, the risks/benefits favor dosing on the higher side of the recommended frequency (Shaw 2016). For CRRT with other effluent rates: If effluent rate is <20 mL/kg/hour, 2 g every 12 hours is preferred (Allaouchiche 1997; Malone 2001). If effluent rate is ≥35 mL/kg/hour, 2 g every 8 hours is preferred (Chaijamorn 2018, Droege 2013).

PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection), organism MIC, residual kidney function, and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important.

Note: Regimens developed through Monte Carlo simulation only and based on daily treatments with 4 to 5 L/hour of dialysate/ultrafiltrate flow rate for each 8- to 10-hour session (Jang 2018).

Option 1: IV: 2 g loading dose, followed by 1 g every 6 hours regardless of when prolonged intermittent renal replacement therapy (PIRRT) treatments occur relative to cefepime infusions (Jang 2018).

Option 2 (if every 6 hours not desired [eg, patient self-administering]): IV: 2 g loading dose, followed by 2 g at beginning of PIRRT session, then 3 g after PIRRT session ends. Repeat regimen with every PIRRT session (Jang 2018).

Non-PIRRT days: IV: Select dose based on assessment of nondialysis kidney function (eg, CrCl <11, then 1 g every 24 hours).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

General dosing, susceptible infection (Red Book [AAP 2015]): Infants, Children, and Adolescents: IM, IV:

Mild to moderate infection: 50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose

Severe infection: 50 mg/kg/dose every 8 to 12 hours; maximum dose: 2,000 mg/dose

Cystic fibrosis, acute pulmonary exacerbation: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose; patients with more resistant pseudomonal isolates (MIC ≥16 mg/L) may require 50 mg/kg/dose every 6 hours (Zobell 2013)

Endocarditis, prosthetic valve, treatment within 1 year of replacement: Children and Adolescents: IV: 50 mg/kg/dose every 8 to 12 hours in combination with vancomycin and rifampin for 6 weeks plus gentamicin for the first 2 weeks; maximum dose: 2,000 mg/dose (AHA [Baltimore 2015])

Febrile neutropenia, empiric therapy: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Red Book [AAP 2015]); duration of therapy dependent upon febrile neutropenia risk-status; in high-risk patients, may discontinue empiric antibiotics if all of the following criteria met: Negative blood cultures at 48 hours; afebrile for at least 24 hours, and evidence of marrow recovery. In low-risk patients, may discontinue empiric antibiotics after 72 hours duration in patients with a negative blood culture and who have been afebrile for 24 hours regardless of marrow recovery status; follow-up closely (Lehrnbecher 2017).

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 12 hours in combination with metronidazole; maximum dose: 2,000 mg/dose. Note: IDSA guidelines recommend duration of 4 to 7 days (provided source controlled) (IDSA [Solomkin 2010]).

Meningitis: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose (Tunkel 2004)

Peritonitis (peritoneal dialysis) (ISPD [Warady 2012]): Infants, Children, and Adolescents: Intraperitoneal:

Intermittent: 15 mg/kg/dose every 24 hours into the long dwell

Continuous: Loading dose: 500 mg per liter of dialysate; maintenance dose: 125 mg per liter

Pneumonia, moderate to severe: Infants ≥2 months, Children, and Adolescents:

Due to P. aeruginosa: IV: 50 mg/kg/dose every 8 hours for 10 days; maximum dose: 2,000 mg/dose

Not due to P. aeruginosa: IV: 50 mg/kg/dose every 12 hours for 10 days; maximum dose: 2,000 mg/dose

Skin and skin structure infections, uncomplicated: Infants ≥2 months, Children, and Adolescents: IV: 50 mg/kg/dose every 12 hours for 10 days; maximum dose: 2,000 mg/dose

Urinary tract infection, complicated and uncomplicated: Infants ≥2 months, Children, and Adolescents:

Mild to moderate infection: IM, IV: 50 mg/kg/dose every 12 hours for 7 to 10 days; maximum dose: 1,000 mg/dose. Note: IM may only be considered for mild to moderate infections due to E. coli.

Severe infection: IV: 50 mg/kg/dose every 12 hours for 10 days; maximum dose: 2,000 mg/dose

Dosing: Renal Impairment: Pediatric

Altered kidney function: Infants ≥2 months, Children, and Adolescents: IV:

Cefepime Dosing Adjustments for Maintenance Dose in Renal Impairment

CrCl (mL/minute)

Recommended Dosing Schedule

Mild Infection

Moderate Infection

Severe Infection

Note: Dosing regimens reflect the similarity in cefepime pharmacokinetics between adult and pediatric patients and are proportional to the changes made in adult patients.

>60

(Normal recommended dosing schedule)

50 mg/kg/dose every 12 hours; maximum dose: 1,000 mg/dose

50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose

50 mg/kg/dose every 8 hours; maximum dose: 2,000 mg/dose

30-60

50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose

50 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose

50 mg/kg/dose every 12 hours; maximum dose: 2,000 mg/dose

11-29

25 mg/kg/dose every 24 hours; maximum dose: 500 mg/dose

25 to 50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose

50 mg/kg/dose every 24 hours; maximum dose: 2,000 mg/dose

<11

25 mg/kg/dose every 24 hours; maximum dose: 250 mg/dose

25 to 50 mg/kg/dose every 24 hours; maximum dose: 500 mg/dose

25 to 50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose

Augmented renal clearance (CrCl >130 mL/minute/1.73 m²): There are no pediatric-specific recommendations for dosing in patients with augmented renal clearance; based on adult pharmacokinetic studies, more frequent administration may be necessary.

Hemodialysis, intermittent: Note: Dosing regimens reflect the similarity in cefepime pharmacokinetics between adult and pediatric patients and are proportional to the changes made in adult patients. When possible, dose immediately after dialysis session.

Infants ≥2 months, Children, and Adolescents: IV:

Mild to moderate infections:

First dose: 50 mg/kg/dose; maximum dose: 1,000 mg/dose.

Maintenance dose: 25 to 50 mg/kg/dose every 24 hours; maximum dose: 500 mg/dose.

Severe infection: 25 to 50 mg/kg/dose every 24 hours; maximum dose: 1,000 mg/dose.

Peritoneal dialysis:

Peritoneal dialysis: Limited data available: Infants, Children, and Adolescents: IV: 50 mg/kg/dose every 24 hours (Aronoff 2007).

Continuous ambulatory peritoneal dialysis: Note: Dosing regimens reflect the similarity in cefepime pharmacokinetics between adult and pediatric patients and are proportional to the changes made in adult patients.

Infants ≥2 months, Children, and Adolescents: IV:

Mild infection: 50 mg/kg/dose every 48 hours; maximum dose: 1,000 mg/dose.

Moderate infection: 50 mg/kg/dose every 48 hours; maximum dose: 2,000 mg/dose.

Severe infection: 50 mg/kg/dose every 48 hours; maximum dose: 2,000 mg/dose.

Continuous renal replacement therapy (CRRT): Limited data available (Veltri 2004): Children and Adolescents:

<1,500 mL/m²/hour (<25 mL/m²/minute): 25 to 50 mg/kg/dose every 12 to 18 hours.

≥1,500 mL/m²/hour (≥25 mL/m²/minute): 25 to 50 mg/kg/dose every 12 hours.

Prolonged intermittent renal replacement therapy (PIRRT): There are no pediatric-specific recommendations for dosing in patients receiving PIRRT; based on adult experience, dose adjustment may be necessary.

Dosing: Hepatic Impairment: Pediatric

No dosage adjustments necessary.

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Intra-abdominal infection: Treatment, in combination with metronidazole, of complicated intra-abdominal infections caused by Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, or Bacteroides fragilis.

Neutropenic fever: Empiric treatment of febrile neutropenic patients.

Pneumonia (moderate to severe): Treatment of moderate to severe pneumonia caused by Streptococcus pneumoniae, including cases associated with concurrent bacteremia, P. aeruginosa, K. pneumoniae, or Enterobacter species.

Skin and soft tissue infection: Treatment of moderate to severe skin and soft tissue infections caused by Staphylococcus aureus (methicillin-susceptible isolates only) or Streptococcus pyogenes.

Urinary tract infection, including pyelonephritis: Treatment of urinary tract infections, including pyelonephritis, caused by E. coli, K. pneumoniae, or Proteus mirabilis, including cases associated with concurrent bacteremia with these microorganisms.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Bloodstream infection (gram-negative bacteremia)Level of Evidence [C, G]

Data from a prospective, randomized, open-comparison study support the use of cefepime in the treatment of gram-negative bacteremia ^Ref.

Based on the Infectious Diseases Society of America (IDSA) clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection, cefepime is effective and recommended for the treatment of intravascular catheter-related infection caused by Pseudomonas aeruginosa.

Cystic fibrosis, exacerbationLevel of Evidence [G]

Based on the Cystic Fibrosis Foundation's cystic fibrosis pulmonary guidelines, cefepime, as part of an appropriate combination regimen (which should include an additional antipseudomonal agent), is effective and recommended for the treatment of P. aeruginosa infection during an acute exacerbation of cystic fibrosis pulmonary disease.

Diabetic foot infection, moderate to severeLevel of Evidence [G]

Based on the IDSA guidelines for the diagnosis and treatment of diabetic foot infections, cefepime, in combination with other appropriate agents, is an effective and recommended treatment option for diabetic foot infections.

Intracranial abscess (brain abscess, intracranial epidural abscess) and spinal epidural abscessLevel of Evidence [C]

Clinical experience suggests the utility of cefepime in the management of brain abscess, intracranial epidural abscess, and spinal epidural abscess ^Ref.

Meningitis, bacterialLevel of Evidence [G]

Based on the IDSA guidelines for the management of bacterial meningitis and health care–associated ventriculitis and meningitis, cefepime is effective and recommended for the treatment of bacterial meningitis caused by P. aeruginosa; as an alternative agent for the treatment of meningitis caused by extended-spectrum beta-lactamase-producing gram-negative bacilli, H. influenzae, or S. pneumoniae (with a penicillin MIC ≥0.12 mcg/mL and cefotaxime or ceftriaxone MIC <1 mcg/mL); and as empiric therapy (in combination with vancomycin) for health care–associated ventriculitis or meningitis.

Neutropenic enterocolitis (typhlitis)Level of Evidence [G]

Based on the IDSA clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer, cefepime, in combination with metronidazole, is effective and recommended for the management of neutropenic enterocolitis (typhlitis).

Osteomyelitis and/or discitisLevel of Evidence [C, G]

Data from a limited number of patients suggest that cefepime may be beneficial for the treatment of osteomyelitis ^Ref.

Based on the IDSA guidelines for the diagnosis and treatment of native vertebral osteomyelitis in adults, cefepime is an effective and recommended agent for the treatment of native vertebral osteomyelitis due to P. aeruginosa or Enterobacteriaceae.

Prosthetic joint infectionLevel of Evidence [G]

Based on the IDSA guidelines for the diagnosis and management of prosthetic joint infection, cefepime is an effective and recommended agent for the treatment of prosthetic joint infection due to P. aeruginosa or Enterobacter spp.

Sepsis and septic shockLevel of Evidence [G]

Based on the Society of Critical Care Medicine international guidelines for management of sepsis and septic shock, cefepime, in combination with other appropriate agents, is effective and recommended for broad-spectrum antibacterial coverage (including P. aeruginosa) in the management of sepsis and septic shock.

Septic arthritisLevel of Evidence [C]

Clinical experience suggests the utility of cefepime for the treatment of septic arthritis ^Ref.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Cephalosporins

Clinical Practice Guidelines

Cystic Fibrosis:

Cystic Fibrosis Foundation, "Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations," 2009

Diabetic Foot Infection:

IDSA, “The Diagnosis and Treatment of Diabetic Foot Infections,” 2012

Endocarditis:

AHA, "Infective Endocarditis in Childhood," October 2015

Intraabdominal Infection:

IDSA, “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children,” January 2010

Meningitis, Bacterial

IDSA, “Practice Guidelines for the Management of Bacterial Meningitis,” November 2004

Meningitis and Ventriculitis, Healthcare-associated:

IDSA, "Clinical Practice Guidelines for Healthcare-Associated Ventriculitis and Meningitis," February 2017

Neutropenic Fever:

ASCO/IDSA, "Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy," February 2018

Osteomyelitis, Native Vertebral:

IDSA, "Clinical Practice Guidelines for the Diagnosis and Treatment of Native Vertebral Osteomyelitis in Adults," 2015

Opportunistic Infections:

DHHS, "Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents," October 2014 [Note: Information contained within this monograph is pending revision based on these more recent guidelines]

Pneumonia, Community-Acquired:

ATS/IDSA, "Diagnosis and Treatment of Adults With Community-Acquired Pneumonia," October 2019

Pneumonia, Hospital-Acquired and Ventilator-Associated:

IDSA/ATS, "Management of Adults with Hospital-Acquired and Ventilator-Associated Pneumonia," July 2016

Prosthetic Joint Infection:

IDSA, “Diagnosis and Management of Prosthetic Joint Infection: Clinical Practice Guideline,” January 2013

Skin and Soft-tissue Infection:

IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014

Administration: IM

Inject deep IM into large muscle mass.

Administration: IV

Administer as an intermittent infusion over 30 minutes.

Off-label:

Direct IV: Inject direct IV over 5 minutes (Garrelts 1999).

Extended infusion: In certain patients where extended infusions may be appropriate, doses are usually infused over 3 to 4 hours (Bauer 2013; Nicasio 2010).

Administration: Injectable Detail

pH: 4-6

Administration: Pediatric

Parenteral:

IV: Administer as an intermittent IV infusion over 30 minutes; in adult clinical trials, cefepime has been administered by direct IV injection over 3 to 5 minutes at final concentrations of 40 mg/mL (Garrelts 1999) and 100 mg/mL (Jaruratanasirikul 2002; Lipman 1999) for severe infections

IM: Administer by deep IM injection into large muscle mass

Storage/Stability

Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Protect from light. After reconstitution, stable in NS and D5W for 24 hours at 20°C to 25°C (68°F to 77°F) and 7 days at 2°C to 8°C (36°F to 46°F). Refer to the manufacturer's product labeling for other acceptable reconstitution solutions.

Dual chamber containers: Store unactivated containers at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 85°F). Do not freeze. Following reconstitution, use within 12 hours if stored at room temperature or within 5 days if stored under refrigeration.

Premixed solution: Store frozen at -20°C (-4°F). Thawed solution is stable for 24 hours at room temperature or 7 days under refrigeration; do not refreeze.

Preparation for Administration: Adult

IV: Reconstitute 500 mg vial with 5 mL and 1 or 2 g vial with 10 mL of a compatible diluent (resulting concentration of 100 mg/mL for 500 mg and 1 g vial and 160 mg/mL for 2 g vial) and further dilute in a compatible IV infusion fluid.

IM: Reconstitute 500 mg or 1 g vial with 1.3 mL or 2.4 mL, respectively, of SWFI, NS, D5W, lidocaine 0.5% or 1%, or bacteriostatic water for injection; resulting concentration is 280 mg/mL.

Preparation for Administration: Pediatric

Parenteral:

IV: Reconstitute 500 mg vial with 5 mL and 1 or 2 g vial with 10 mL of a compatible diluent (resulting concentration of 100 mg/mL for 500 mg and 1 g vial and 160 mg/mL for 2 g vial); further dilute in D5W, NS, D10W, D5NS, or D5LR; final concentration should not exceed 40 mg/mL.

IM: Reconstitute 500 mg or 1 g vial with 1.3 mL or 2.4 mL, respectively, of SWFI, NS, D5W, lidocaine 0.5% or 1%, or bacteriostatic water for injection to a final concentration of 280 mg/mL

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe dizziness

• Passing out

• Severe fatigue

• Bruising

• Bleeding

• Severe loss of strength and energy

• Chills

• Sore throat

• Unable to pass urine

• Change in amount of urine passed

• Dark urine

• Yellow skin

• Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Confusion

• Seizures

• Difficulty speaking

• Sensing things that seem real but are not

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to cefepime, other cephalosporins, penicillins, other beta-lactam antibiotics, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Elevated INR: May be associated with increased INR, especially in nutritionally-deficient patients, prolonged treatment, hepatic or renal disease.

• Hypersensitivity: May occur; use caution in patients with a history of penicillin sensitivity; cross-hypersensitivity may occur. If a hypersensitivity reaction occurs, discontinue therapy and institute supportive measures.

• Neurotoxicity: Severe neurological reactions (some fatal) have been reported, including encephalopathy, aphasia, myoclonus, seizures, and nonconvulsive status epilepticus. Risk may be increased in the presence of renal impairment; ensure dose adjusted for renal function and discontinue therapy if patient develops neurotoxicity; effects are often reversible upon discontinuation of cefepime.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment (CrCl ≤60 mL/minute); dosage adjustments recommended. May increase risk of encephalopathy, myoclonus, and seizures.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Serious adverse reactions have occurred in elderly patients with renal insufficiency given unadjusted doses of cefepime, including life-threatening or fatal occurrences of encephalopathy, myoclonus, and seizures.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Adjust dose for renal function.

Warnings: Additional Pediatric Considerations

The manufacturer does not recommend the use of cefepime in pediatric patients for the treatment of serious infections due to Haemophilus influenzae type b, for suspected meningitis, or for meningeal seeding from a distant infection site. However, limited data suggest that cefepime may be a valuable alternative for treating bacterial meningitis in children in conjunction with other agents like vancomycin in areas with a high incidence of cephalosporin nonsusceptible pneumococci (Haase 2004).

Pregnancy Risk Factor

B

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Cefepime crosses the placenta.

Breast-Feeding Considerations

Small amounts of cefepime are excreted in breast milk. The manufacturer recommends that caution be exercised when administering cefepime to nursing women. Non-dose-related effects could include modification of bowel flora.

Lexicomp Pregnancy & Lactation, In-Depth

• Cefepime

Briggs' Drugs in Pregnancy & Lactation

• Cefepime

Adverse Reactions

>10%: Hematologic & oncologic: Positive direct Coombs test (without hemolysis; 16%)

1% to 10%:

Cardiovascular: Localized phlebitis (1%)

Central nervous system: Headache (≤1%)

Dermatologic: Skin rash (1% to 4%), pruritus (≤1%)

Endocrine & metabolic: Hypophosphatemia (3%)

Gastrointestinal: Diarrhea (≤3%), nausea (≤2%), vomiting (≤1%)

Hematologic & oncologic: Eosinophilia (2%)

Hepatic: Increased serum ALT (3%), abnormal partial thromboplastin time (2%), increased serum AST (2%), abnormal prothrombin time (1%)

Hypersensitivity: Hypersensitivity (in patients with a history of penicillin allergy: ≤10%)

Miscellaneous: Fever (≤1%)

<1%, postmarketing, and/or case reports: Agranulocytosis, anaphylactic shock, anaphylaxis, anemia, aphasia, brain disease, Clostridioides (formerly Clostridium) difficile-associated diarrhea, colitis, coma, confusion, decreased hematocrit, erythema, hallucination, hypercalcemia, hyperkalemia, hyperphosphatemia, hypocalcemia, increased blood urea nitrogen, increased serum alkaline phosphatase, increased serum bilirubin, increased serum creatinine, leukopenia, local inflammation, local pain, myoclonus, neurotoxicity, neutropenia, oral candidiasis, pseudomembranous colitis, seizure, status epilepticus (nonconvulsive), stupor, thrombocytopenia, urticaria, vaginitis

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Cephalosporin Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Aminoglycosides: Cephalosporins (4th Generation) may enhance the nephrotoxic effect of Aminoglycosides. Risk C: Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy

Probenecid: May increase the serum concentration of Cephalosporins. Risk C: Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. Risk D: Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy

Test Interactions

Positive direct Coombs', false-positive urinary glucose test using cupric sulfate (Benedict's solution, Clinitest®, Fehling's solution), false-positive serum or urine creatinine with Jaffé reaction, false-positive urinary proteins and steroids

Monitoring Parameters

Monitor renal function. Observe for signs and symptoms of anaphylaxis during first dose.

Advanced Practitioners Physical Assessment/Monitoring

Assess results of culture/sensitivity tests and patient's allergy history prior to therapy. Obtain renal function tests. Monitor for signs of anaphylaxis during fist dose. Assess for effectiveness of treatment. Test for C. difficile if patient develops diarrhea.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor closely for signs of hypersensitivity (shortness of breath, dyspnea, chest pain, complaints of difficulty swallowing or throat tightness, or change in vital signs). Monitor for severe or bloody diarrhea and send a specimen to the lab for C. difficile. Monitor for improvement of infection.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous, as hydrochloride:

Generic: 2 g/100 mL (100 mL)

Solution, Intravenous, as hydrochloride [preservative free]:

Generic: 1 g/50 mL (50 mL)

Solution Reconstituted, Injection, as hydrochloride:

Generic: 1 g (1 ea [DSC])

Solution Reconstituted, Injection, as hydrochloride [preservative free]:

Maxipime: 1 g (1 ea [DSC]); 2 g (1 ea [DSC])

Generic: 1 g (1 ea); 2 g (1 ea)

Solution Reconstituted, Intravenous, as hydrochloride [preservative free]:

Maxipime: 1 g (1 ea [DSC]); 2 g (1 ea [DSC])

Generic: 1-5 GM-%(50ML) (1 ea); 2-5 GM-%(50ML) (1 ea)

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Injection, as hydrochloride:

Generic: 1 g (1 ea); 2 g (1 ea)

Anatomic Therapeutic Chemical (ATC) Classification

• J01DE01

Generic Available (US)

Yes

Pricing: US

Solution (Cefepime HCl Intravenous)

1 gm/50 mL (per mL): $0.64

2 g/100 mL (per mL): $0.51

Solution (reconstituted) (Cefepime HCl Injection)

1 g (per each): $6.36 - $20.33

2 g (per each): $11.64 - $40.36

Solution (reconstituted) (Cefepime-Dextrose Intravenous)

1GM 5%(50ML) (per each): $19.12

2GM 5%(50ML) (per each): $29.15

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysis and murein hydrolases) while cell wall assembly is arrested.

Pharmacodynamics/Kinetics

Absorption: IM: Rapid and complete

Distribution: V_d:

Neonates (Capparelli 2005):

PMA <30 weeks: 0.51 L/kg

PMA >30 weeks: 0.39 L/kg

Infants and Children 2 months to 11 years: 0.3 L/kg

Adults: 18 L, 0.26 L/kg; penetrates into inflammatory fluid at concentrations ~80% of serum concentrations and into bronchial mucosa at concentrations ~60% of plasma concentrations; crosses the blood-brain barrier

Protein binding, plasma: ~20%

Metabolism: Minimally hepatic

Half-life elimination:

Neonates: 4 to 5 hours (Lima-Rogel 2008)

Children 2 months to 6 years: 1.77 to 1.96 hours

Adults: 2 hours

Hemodialysis: 13.5 hours

Continuous peritoneal dialysis: 19 hours

Time to peak: IM: 1 to 2 hours; IV: 0.5 hours

Excretion: Urine (85% as unchanged drug)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Total body clearance is decreased proportionally with creatinine clearance.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Rare occurrence of oral candidiasis.

Effects on Bleeding

No information available to require special precautions

Index Terms

Cefepime HCl; Cefepime HCl/D5W; Cefepime Hydrochloride

FDA Approval Date

January 18, 1996

References

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Brand Names: International

Abypim (UA); Acedrin (PY); Alcemax (PH); Amfapime (VN); Axepim (FR); Axera (PH); Biocepime (ID); Caprifim (ID); Cebopim (UA); Cefamax (TH); Cefemax (TW); Cefemet (ID); Cefepima (CO); Ceficad (IN); Cefipex (LB); Cefpas (LK); Cepimax (EG); Cepiram (PH); Curafep (EG); Deltacef (TR); Dimipra (PH); Epime (LK); Exepime (ID, UA); Falocef (ID); Forgen (BD); Forzyn Beta (PY); Funjapin (TW); Imation (CR, DO, EC, GT, HN, NI, PA, SV); Interprim (ID); Macef (ID); Macepim (TW); Maxapin (PH); Maxcef (BR, CR, DO, GT, HN, LK, NI, PA, SV, UY); Maxef (MX); Maxicef (LK); Maxilan (ID); Maxipime (AE, AT, BB, BE, BG, BH, CH, CL, CN, CZ, DE, DK, EC, EE, EG, ES, FI, GR, HK, HR, HU, IT, JO, JP, KR, LB, LT, LU, MX, MY, NL, PE, PK, PL, PT, RU, SA, SE, SG, SI, SK, TR, TW, VE, VN, ZA); Megapime (MY, TH); Pimcef (PE); Pime (TH); Pozine G (BH); Pozineg (ET, QA); Procepim (ID); Protec (AE, BH, KW, QA, SA); Qpime (AE, LB); Quadrocef (UA); Rapime (ID); Rovatim (PH); Salapime (LB); Sanpime (PH); Sefepim (MY); Sefpime (PH, TH); Sepime (PH); Silex (PH); Supecef (TW); Superpime (BD); Tetracef (BD); Tsepim (UA); Uniceme (VN); Unipim (BD); Vidapime (PH); Vifepime (VN); Wincef (EG); Zepim (PH); Zepime (PH); Zepym (PH)

Last Updated 3/5/20