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Identification
NameCefepime
Accession NumberDB01413
TypeSmall Molecule
GroupsApproved
DescriptionCefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both Gram-negative and Gram-positive organisms than third-generation agents. Cefepime is usually reserved to treat severe nosocomial pneumonia, infections caused by multi-resistant microorganisms (e.g. Pseudomonas aeruginosa) and empirical treatment of febrile neutropenia.
Structure
Thumb
Synonyms
(6R,7R)-7-{[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetyl]amino}-3-[(1-methylpyrrolidinium-1-yl)methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
Cefepima
Cefepime
Cefepimum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CefepimeInjection, solution1 g/50mLIntravenousBaxter Healthcare Corporation2008-08-05Not applicableUs
Cefepime for InjectionPowder, for solution1 gIntramuscular; IntravenousApotex IncNot applicableNot applicableCanada
Cefepime for InjectionPowder, for solution2 gIntravenousApotex Inc2009-03-19Not applicableCanada
Cefepime Hydrochloride and DextroseInjection, solution1 g/50mLIntravenousB. Braun Medical Inc.2010-05-06Not applicableUs
Cefepime Hydrochloride and DextroseInjection, solution2 g/50mLIntravenousB. Braun Medical Inc.2010-05-06Not applicableUs
MaxipimeInjection, powder, for solution2 g/1IntravenousHospira, Inc.1996-01-18Not applicableUs
MaxipimeInjection, powder, for solution1 g/1IntravenousHospira, Inc.1996-01-18Not applicableUs
MaxipimeInjection, powder, for solution500 mg/1Intramuscular; IntravenousHospira, Inc.1996-01-18Not applicableUs
MaxipimeInjection, powder, for solution2 g/1IntravenousHospira, Inc.1996-01-18Not applicableUs
MaxipimeInjection, powder, for solution1 g/1Intramuscular; IntravenousCardinal Health1996-01-18Not applicableUs
MaxipimeInjection, powder, for solution1 g/1Intramuscular; IntravenousHospira, Inc.1996-01-18Not applicableUs
MaxipimeInjection, powder, for solution2 g/1IntravenousCardinal Health1996-01-18Not applicableUs
Maxipime for Injection -pws IV Im 1gPowder, for solution1 gIntramuscular; IntravenousBristol Myers Squibb Canada1995-12-312015-01-28Canada
Maxipime for Injection-pws IV 2gmPowder, for solution2 gIntravenousBristol Myers Squibb Canada1995-12-312015-01-28Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CefepimeInjection, powder, for solution2 g/1IntravenousQilu Pharmaceutical Co., Ltd.2016-02-01Not applicableUs
CefepimeInjection, powder, for solution1 g/1Intramuscular; IntravenousApotex Corporation2007-06-18Not applicableUs
CefepimeInjection, powder, for solution2 g/1IntravenousSagent Pharmaceuticals2008-05-01Not applicableUs
CefepimeInjection, powder, for solution2 g/1IntravenousFresenius Kabi USA, LLC2010-08-30Not applicableUs
CefepimeInjection2 g/1IntravenousSandoz Inc2010-12-21Not applicableUs
CefepimeInjection, powder, for solution1 g/1IntravenousHospira, Inc.2012-07-30Not applicableUs
CefepimeInjection, powder, for solution1 g/1Intramuscular; IntravenousApotex Corporation2007-06-18Not applicableUs
CefepimeInjection, powder, for solution1 g/20mLIntramuscular; IntravenousWG Critical Care, LLC2014-10-10Not applicableUs
CefepimeInjection, powder, for solution500 mg/1Intramuscular; IntravenousQilu Pharmaceutical Co., Ltd.2016-02-01Not applicableUs
CefepimeInjection, powder, for solution2 g/1IntravenousHospira, Inc.2012-07-30Not applicableUs
CefepimeInjection, powder, for solution2 g/1IntravenousApotex Corporation2007-06-18Not applicableUs
CefepimeInjection500 mg/1Intramuscular; IntravenousSandoz Inc2010-12-21Not applicableUs
CefepimeInjection, powder, for solution2 g/20mLIntravenousWG Critical Care, LLC2014-10-10Not applicableUs
CefepimeInjection, powder, for solution1 g/1Intramuscular; IntravenousQilu Pharmaceutical Co., Ltd.2016-02-01Not applicableUs
CefepimeInjection, powder, for solution1 g/1Intramuscular; IntravenousSagent Pharmaceuticals2008-05-01Not applicableUs
CefepimeInjection, powder, for solution1 g/1Intramuscular; IntravenousFresenius Kabi USA, LLC2010-08-30Not applicableUs
CefepimeInjection1 g/1Intramuscular; IntravenousSandoz Inc2010-12-21Not applicableUs
CefepimeInjection, powder, for solution2 g/1Intramuscular; IntravenousApotex Corporation2007-06-18Not applicableUs
Cefepime HydrochlorideInjection, powder, for solution1 g/1Intramuscular; IntravenousSandoz Inc2008-05-01Not applicableUs
Cefepime HydrochlorideInjection, powder, for solution2 g/1IntravenousSandoz Inc2008-05-01Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AxepimNot Available
CepimaxNot Available
CepimexNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Cefepime dihydrochloride monohydrate
ThumbNot applicableDBSALT000919
Cefepime hydrochloride
ThumbNot applicableDBSALT000920
Categories
UNII807PW4VQE3
CAS number88040-23-7
WeightAverage: 480.561
Monoisotopic: 480.124959288
Chemical FormulaC19H24N6O5S2
InChI KeyHVFLCNVBZFFHBT-ZKDACBOMSA-N
InChI
InChI=1S/C19H24N6O5S2/c1-25(5-3-4-6-25)7-10-8-31-17-13(16(27)24(17)14(10)18(28)29)22-15(26)12(23-30-2)11-9-32-19(20)21-11/h9,13,17H,3-8H2,1-2H3,(H3-,20,21,22,26,28,29)/b23-12-/t13-,17-/m1/s1
IUPAC Name
1-{[(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetamido]-2-carboxylato-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl}-1-methylpyrrolidin-1-ium
SMILES
CO\N=C(/C(=O)N[C@@H]1C(=O)N2[C@]1([H])SCC(C[N+]1(C)CCCC1)=C2C([O-])=O)C1=CSC(N)=N1
Pharmacology
IndicationFor the treatment of pneumonia (moderate to severe) caused by Streptococcus pneumoniae, including cases associated with concurrent bacteremia, Pseudomonas aeruginosa, Klebsiella pneumoniae, or Enterobacter species. Also for empiric treatment of febrile neutropenic patients and uncomplicated and complicated urinary tract infections (including pyelonephritis) caused by Escherichia coli or Klebsiella pneumoniae, when the infection is severe, or caused by Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis, when the infection is mild to moderate, including cases associated with concurrent bacteremia with these microorganisms. Also for the treatment of uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible strains only) or Streptococcus pyogenes and complicated intra-abdominal infections (used in combination with metronidazole) caused by Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, or Bacteroides fragilis.
Structured Indications
PharmacodynamicsCefepime is a fourth-generation cephalosporin antibiotic developed in 1994. Cefepime has an extended spectrum of activity against Gram-positive and Gram-negative bacteria, with greater activity against both Gram-negative and Gram-positive organisms than third-generation agents. Cefepime has good activity against important pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, and multiple drug resistant Streptococcus pneumoniae. A particular strength is its activity against Enterobacteriaceae. Whereas other cephalosporins are degraded by many plasmid- and chromosome-mediated beta-lactamases, cefepime is stable and is a front line agent when infection with Enterobacteriaceae is known or suspected
Mechanism of actionCephalosporins are bactericidal and have the same mode of action as other beta-lactam antibiotics (such as penicillins). Cephalosporins disrupt the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms. The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin binding proteins (PBPs).
TargetKindPharmacological actionActionsOrganismUniProt ID
Penicillin-binding protein 2Proteinyes
inhibitor
Escherichia coli (strain K12)P0AD65 details
Peptidoglycan synthase FtsIProteinyes
inhibitor
Escherichia coli (strain K12)P0AD68 details
Cell division proteinProteinyes
inhibitor
Pseudomonas aeruginosaQ51504 details
Penicillin-binding protein 2Proteinyes
inhibitor
Pseudomonas aeruginosaQ9X6V3 details
Related Articles
AbsorptionThe absolute bioavailability of cefepime after an IM dose of 50 mg/kg was 82.3 (±15)% in eight patients.
Volume of distribution
  • 18.0 ±2.0 L
  • 0.3 ±0.1 L/kg [Pediatric]
Protein bindingThe serum protein binding of cefepime is approximately 20% and is independent of its concentration in serum.
Metabolism

Hepatic. Cefepime is metabolized to N-methylpyrrolidine (NMP) which is rapidly converted to the N-oxide (NMP-N-oxide).

SubstrateEnzymesProduct
Cefepime
Not Available
N-MethylpyrrolidineDetails
Cefepime
Not Available
NMP-N-oxideDetails
Route of eliminationElimination of cefepime is principally via renal excretion with an average (±SD) half-life of 2 (±0.3) hours and total body clearance of 120 (±8) mL/min in healthy volunteers. Cefepime is excreted in human milk.
Half life2.0 (± 0.3) hours in normal patients. The average half-life in patients requiring hemodialysis was 13.5 (± 2.7) hours and in patients requiring continuous peritoneal dialysis was 19.0 (± 2.0) hours.
Clearance
  • 120 mL/min [Healthy adult male receiving a single 30-minute IV infusions of cefepime]
  • 3.3 +/-1.0 mL/min/kg [Petriatic patients (2 months – 11 years of age) receiving a single IV dose]
ToxicitySymptoms of overdose include seizures, encephalopathy, and neuromuscular excitability.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
BcgThe therapeutic efficacy of Bcg can be decreased when used in combination with Cefepime.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefepime.Approved
Food InteractionsNot Available
References
Synthesis Reference

Vijay Handa, Anand Kamat, Meenakshisunderam Sivakumaran, “Process for preparing cefepime.” U.S. Patent US20050043531, issued February 24, 2005.

US20050043531
General References
  1. Chapman TM, Perry CM: Cefepime: a review of its use in the management of hospitalized patients with pneumonia. Am J Respir Med. 2003;2(1):75-107. [PubMed:14720024 ]
External Links
ATC CodesJ01RA06J01DE01
AHFS Codes
  • 08:12.06.16
PDB EntriesNot Available
FDA labelDownload (244 KB)
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.9819
Blood Brain Barrier-0.9332
Caco-2 permeable-0.6669
P-glycoprotein substrateSubstrate0.9066
P-glycoprotein inhibitor INon-inhibitor0.7965
P-glycoprotein inhibitor IINon-inhibitor0.5353
Renal organic cation transporterNon-inhibitor0.7455
CYP450 2C9 substrateNon-substrate0.8806
CYP450 2D6 substrateNon-substrate0.8068
CYP450 3A4 substrateSubstrate0.6023
CYP450 1A2 substrateNon-inhibitor0.7233
CYP450 2C9 inhibitorNon-inhibitor0.736
CYP450 2D6 inhibitorNon-inhibitor0.8741
CYP450 2C19 inhibitorNon-inhibitor0.6986
CYP450 3A4 inhibitorNon-inhibitor0.8378
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8854
Ames testNon AMES toxic0.6625
CarcinogenicityNon-carcinogens0.9051
BiodegradationNot ready biodegradable0.6571
Rat acute toxicity2.3513 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9015
hERG inhibition (predictor II)Non-inhibitor0.734
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
InjectionIntramuscular; Intravenous1 g/1
InjectionIntramuscular; Intravenous500 mg/1
InjectionIntravenous2 g/1
Injection, powder, for solutionIntramuscular; Intravenous1 g/20mL
Injection, powder, for solutionIntramuscular; Intravenous2 g/1
Injection, powder, for solutionIntramuscular; Intravenous500 mg/1
Injection, powder, for solutionIntravenous2 g/20mL
Powder, for solutionIntravenous2 g
Injection, powder, for solutionIntramuscular; Intravenous1 g/1
Injection, powder, for solutionIntravenous2 g/1
Injection, solutionIntravenous1 g/50mL
Injection, solutionIntravenous2 g/50mL
Injection, powder, for solutionIntravenous1 g/1
Powder, for solutionIntramuscular; Intravenous1 g
Prices
Unit descriptionCostUnit
Maxipime 2 gram vial43.04USD vial
Cefepime hcl 2 gram vial40.36USD vial
Maxipime 1 gm piggyback vial23.24USD vial
Maxipime 1 gram vial21.7USD vial
Cefepime hcl 1 gm vial20.33USD vial
Cefepime 2 gm injection0.51USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.0173 mg/mLALOGPS
logP-0.37ALOGPS
logP-4.3ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)3.25ChemAxon
pKa (Strongest Basic)4.06ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area150.04 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity141.98 m3·mol-1ChemAxon
Polarizability47.53 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as cephalosporins. These are compounds containing a 1,2-thiazine fused to a 2-azetidinone to for a oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid moiety or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactams
Sub ClassBeta lactams
Direct ParentCephalosporins
Alternative Parents
Substituents
  • Cephalosporin
  • N-acyl-alpha amino acid or derivatives
  • Alpha-amino acid or derivatives
  • 2,4-disubstituted 1,3-thiazole
  • N-alkylpyrrolidine
  • Primary aromatic amine
  • Meta-thiazine
  • Heteroaromatic compound
  • Thiazole
  • Tertiary carboxylic acid amide
  • Quaternary ammonium salt
  • Pyrrolidine
  • Azole
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Oxime ether
  • Carboxylic acid salt
  • Carboxamide group
  • Azetidine
  • Azacycle
  • Dialkylthioether
  • Hemithioaminal
  • Thioether
  • Monocarboxylic acid or derivatives
  • Enamine
  • Carboxylic acid
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organic salt
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Organic zwitterion
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Serine-type d-ala-d-ala carboxypeptidase activity
Specific Function:
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. It synthesizes cross-linked peptidoglycan from lipid intermediates.
Gene Name:
mrdA
Uniprot ID:
P0AD65
Molecular Weight:
70856.1 Da
References
  1. Grassi GG, Grassi C: Cefepime: overview of activity in vitro and in vivo. J Antimicrob Chemother. 1993 Nov;32 Suppl B:87-94. [PubMed:8150771 ]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
yes
Actions
inhibitor
General Function:
Peptidoglycan glycosyltransferase activity
Specific Function:
Essential cell division protein that is required for the synthesis of peptidoglycan at the division septum (PubMed:1103132, PubMed:9614966). Catalyzes the synthesis of cross-linked peptidoglycan from the lipid-linked precursors (PubMed:7030331). Required for localization of FtsN (PubMed:9282742).
Gene Name:
ftsI
Uniprot ID:
P0AD68
Molecular Weight:
63876.925 Da
References
  1. Grassi GG, Grassi C: Cefepime: overview of activity in vitro and in vivo. J Antimicrob Chemother. 1993 Nov;32 Suppl B:87-94. [PubMed:8150771 ]
Kind
Protein
Organism
Pseudomonas aeruginosa
Pharmacological action
yes
Actions
inhibitor
General Function:
Peptidoglycan glycosyltransferase activity
Specific Function:
Not Available
Gene Name:
pbpB
Uniprot ID:
Q51504
Molecular Weight:
62855.78 Da
References
  1. Grassi GG, Grassi C: Cefepime: overview of activity in vitro and in vivo. J Antimicrob Chemother. 1993 Nov;32 Suppl B:87-94. [PubMed:8150771 ]
Kind
Protein
Organism
Pseudomonas aeruginosa
Pharmacological action
yes
Actions
inhibitor
General Function:
Penicillin binding
Specific Function:
Not Available
Gene Name:
pbpA
Uniprot ID:
Q9X6V3
Molecular Weight:
72212.855 Da
References
  1. Grassi GG, Grassi C: Cefepime: overview of activity in vitro and in vivo. J Antimicrob Chemother. 1993 Nov;32 Suppl B:87-94. [PubMed:8150771 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Symporter activity
Specific Function:
Sodium-ion dependent, high affinity carnitine transporter. Involved in the active cellular uptake of carnitine. Transports one sodium ion with one molecule of carnitine. Also transports organic cations such as tetraethylammonium (TEA) without the involvement of sodium. Also relative uptake activity ratio of carnitine to TEA is 11.3.
Gene Name:
SLC22A5
Uniprot ID:
O76082
Molecular Weight:
62751.08 Da
References
  1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. [PubMed:10636865 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name:
SLC15A1
Uniprot ID:
P46059
Molecular Weight:
78805.265 Da
References
  1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. [PubMed:10636865 ]
  2. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Peptide:proton symporter activity
Specific Function:
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides.
Gene Name:
SLC15A2
Uniprot ID:
Q16348
Molecular Weight:
81782.77 Da
References
  1. Ganapathy ME, Huang W, Rajan DP, Carter AL, Sugawara M, Iseki K, Leibach FH, Ganapathy V: beta-lactam antibiotics as substrates for OCTN2, an organic cation/carnitine transporter. J Biol Chem. 2000 Jan 21;275(3):1699-707. [PubMed:10636865 ]
  2. Luckner P, Brandsch M: Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1. Eur J Pharm Biopharm. 2005 Jan;59(1):17-24. [PubMed:15567297 ]
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Drug created on July 19, 2007 09:47 / Updated on August 17, 2016 12:23