Identification

Name
Cefixime
Accession Number
DB00671  (APRD00583)
Type
Small Molecule
Groups
Approved
Description

Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.

Structure
Thumb
Synonyms
  • (-)-Cefixim
  • Cefixim
  • Cefixima
  • Céfixime
  • Cefiximum
External IDs
FK 027 / FR 17027
Product Ingredients
IngredientUNIICASInChI Key
Cefixime trihydrate97I1C92E55125110-14-7IPYWNMVPZOAFOQ-NABDTECSSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Auro-cefiximePowder, for suspension100 mgOralAuro Pharma IncNot applicableNot applicableCanada
Auro-cefiximeTablet400 mgOralAuro Pharma Inc2014-10-24Not applicableCanada
SupraxPowder, for suspension500 mg/5mLOralLupin Pharmaceuticals2013-03-15Not applicableUs
SupraxCapsule400 mg/1OralPd Rx Pharmaceuticals, Inc.2013-03-15Not applicableUs
SupraxCapsule400 mg/1OralLupin Pharma2013-03-15Not applicableUs
SupraxTablet400 mgOralOdan Laboratories Ltd1990-12-31Not applicableCanada
SupraxTablet200 mgOralSanofi Aventis1990-12-312006-05-05Canada
SupraxTablet400 mgOralAventis Pharma Ltd.1990-12-312006-01-16Canada
SupraxCapsule400 mg/1OralLupin Pharmaceuticals2013-03-15Not applicableUs
SupraxCapsule400 mg/1OralRemedy Repack2015-07-08Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
CefiximePowder, for suspension200 mg/5mLOralBelcher Pharmaceuticals, LLC2017-03-15Not applicableUs
CefiximePowder, for suspension100 mg/5mLOralLupin Pharmaceuticals2015-04-20Not applicableUs
CefiximePowder, for suspension200 mg/5mLOralDr. Reddy’s Laboratories, Inc2017-08-03Not applicableUs
CefiximePowder, for suspension100 mg/5mLOralAurobindo Pharma2015-04-14Not applicableUs
CefiximePowder, for suspension500 mg/5mLOralBelcher Pharmaceuticals, LLC2017-03-15Not applicableUs
CefiximePowder, for suspension200 mg/5mLOralLupin Pharmaceuticals2015-04-20Not applicableUs
CefiximePowder, for suspension100 mg/5mLOralBelcher Pharmaceuticals, LLC2017-03-15Not applicableUs
CefiximePowder, for suspension200 mg/5mLOralAurobindo Pharma2015-04-14Not applicableUs
CefiximePowder, for suspension100 mg/5mLOralDr. Reddy’s Laboratories, Inc2017-08-03Not applicableUs
SupraxTablet400 mg/1OralA S Medication Solutions2008-04-012017-06-20Us27437 0201 08 nlmimage10 b51d5aaa
International/Other Brands
Cefixoral (Menarini) / Cefspan (GlaxoSmithKline) / Cephoral (Merck) / Fixam (Solas) / Fixspor (Invision) / Hifen (Hetero) / InfectoOpticef (Infectopharm) / Kuracef (Sanofi-Aventis) / Letix (Adley) / Ofex (Delta) / Omnatax-O (Abbott) / Oracef (Micro Labs) / Oroken (Sanofi Aventis) / Sancefix (Sandoz) / Secef (Novartis) / Supran (Teva) / Suprax 125 (Lupin) / Tricef (Merck) / Unixime (Firma) / Uro-Cephoral (Merck)
Categories
UNII
XZ7BG04GJX
CAS number
79350-37-1
Weight
Average: 453.45
Monoisotopic: 453.041289239
Chemical Formula
C16H15N5O7S2
InChI Key
OKBVVJOGVLARMR-QSWIMTSFSA-N
InChI
InChI=1S/C16H15N5O7S2/c1-2-6-4-29-14-10(13(25)21(14)11(6)15(26)27)19-12(24)9(20-28-3-8(22)23)7-5-30-16(17)18-7/h2,5,10,14H,1,3-4H2,(H2,17,18)(H,19,24)(H,22,23)(H,26,27)/b20-9-/t10-,14-/m1/s1
IUPAC Name
(6R,7R)-7-[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-[(carboxymethoxy)imino]acetamido]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
SMILES
[H][[email protected]]12SCC(C=C)=C(N1C(=O)[[email protected]]2NC(=O)C(=N/OCC(O)=O)\C1=CSC(N)=N1)C(O)=O

Pharmacology

Indication

For use in the treatment of the following infections when caused by susceptible strains of the designated microorganisms: (1) uncomplicated urinary tract infections caused by Escherichia coli and Proteus mirabilis, (2) otitis media caused by Haemophilus influenzae (beta-lactamase positive and negative strains), Moraxella catarrhalis (most of which are beta-lactamase positive), and S. pyogenes, (3) pharyngitis and tonsillitis caused by S. pyogenes, (4) acute bronchitis and acute exacerbations of chronic bronchitis caused by Streptococcus pneumoniae and Haemophilus influenzae (beta-lactamase positive and negative strains), and (5) uncomplicated gonorrhea (cervical/urethral) caused by Neisseria gonorrhoeae (penicillinase- and non-penicillinase-producing strains).

Structured Indications
Pharmacodynamics

Cefixime, an antibiotic, is a third-generation cephalosporin like ceftriaxone and cefotaxime. Cefixime is highly stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and some cephalosporins due to the presence of beta-lactamases, may be susceptible to cefixime. The antibacterial effect of cefixime results from inhibition of mucopeptide synthesis in the bacterial cell wall.

Mechanism of action

Like all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.

TargetActionsOrganism
APenicillin-binding protein 2
inhibitor
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Absorption

About 40%-50% absorbed orally whether administered with or without food, however, time to maximal absorption is increased approximately 0.8 hours when administered with food.

Volume of distribution
Not Available
Protein binding

65% (concentration independent)

Metabolism

Hepatic. Approximately 50% of the absorbed dose is excreted unchanged in the urine in 24 hours.

Route of elimination
Not Available
Half life

3-4 hours (may range up to 9 hours). In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours.

Clearance
Not Available
Toxicity

Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.

Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AcenocoumarolCefixime may increase the anticoagulant activities of Acenocoumarol.Approved
BCG vaccineThe therapeutic efficacy of BCG vaccine can be decreased when used in combination with Cefixime.Investigational
ClorindioneCefixime may increase the anticoagulant activities of Clorindione.Experimental
DicoumarolCefixime may increase the anticoagulant activities of Dicoumarol.Approved
DiphenadioneCefixime may increase the anticoagulant activities of Diphenadione.Experimental
Ethyl biscoumacetateCefixime may increase the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
FluindioneCefixime may increase the anticoagulant activities of Fluindione.Investigational
PhenindioneCefixime may increase the anticoagulant activities of Phenindione.Approved, Investigational
PhenprocoumonCefixime may increase the anticoagulant activities of Phenprocoumon.Approved, Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Cefixime.Approved
ProbenecidThe serum concentration of Cefixime can be increased when it is combined with Probenecid.Approved
TioclomarolCefixime may increase the anticoagulant activities of Tioclomarol.Experimental
WarfarinCefixime may increase the anticoagulant activities of Warfarin.Approved
Food Interactions
  • Preferably on an empty stomach, rate of absorption is decreased but extenet of absorption remains the same: not really problematic.

References

Synthesis Reference

Pandurang Deshpande, "Process for the preparation of cefixime." U.S. Patent US20040082560, issued April 29, 2004.

US20040082560
General References
  1. McMillan A, Young H: The treatment of pharyngeal gonorrhoea with a single oral dose of cefixime. Int J STD AIDS. 2007 Apr;18(4):253-4. [PubMed:17509176]
  2. Adam D, Hostalek U, Troster K: 5-day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10-day penicillin V therapy. Cefixime Study Group. Infection. 1995;23 Suppl 2:S83-6. [PubMed:8537138]
External Links
Human Metabolome Database
HMDB14809
KEGG Drug
D00258
KEGG Compound
C06881
PubChem Compound
5362065
PubChem Substance
46508684
ChemSpider
4514923
BindingDB
84007
ChEBI
472657
ChEMBL
CHEMBL1541
Therapeutic Targets Database
DAP000439
PharmGKB
PA164768821
HET
C04
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Cefixime
ATC Codes
J01DD08 — Cefixime
AHFS Codes
  • 08:12.06.12 — Third Generation Cephalosporins
PDB Entries
4kou
FDA label
Download (3.07 MB)
MSDS
Download (43.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1CompletedTreatmentDiarrhea / Drug/Agent Toxicity by Tissue/Organ / Neuroblastomas1
1CompletedTreatmentGonorrhoea2
1CompletedTreatmentNeuroblastomas1
1CompletedTreatmentTumors, Solid1
1CompletedTreatmentUnspecified Adult Solid Tumor, Protocol Specific1
2RecruitingTreatmentUrinary Tract Infections (UTIs)1
3RecruitingPreventionChronic Kidney Disease (CKD) / Renal Hypodysplasia, Nonsyndromic, 1 / Vesicoureteral Reflux1
3TerminatedTreatmentCervicitis / Vaginitis Bacterial1
4Unknown StatusTreatmentSalmonella Typhi Infection1

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
  • Lupin pharmaceuticals inc
  • Lupin ltd
Packagers
Dosage forms
FormRouteStrength
TabletOral400 mg
Powder, for suspensionOral100 mg/5mL
CapsuleOral400 mg/1
Powder, for solutionOral100 mg
Powder, for suspensionOral100 mg
Powder, for suspensionOral200 mg/5mL
Powder, for suspensionOral500 mg/5mL
TabletOral200 mg
TabletOral400 mg/1
Tablet, chewableOral100 mg/1
Tablet, chewableOral200 mg/1
Prices
Unit descriptionCostUnit
Suprax 400 mg Tablet3.86USD tablet
Suprax 100 mg/5ml Suspension2.8USD ml
Suprax 20 mg/ml Suspension0.45USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9233112No2008-12-142028-12-14Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)218-225 °CNot Available
water solubility55.11 mg/LNot Available
logP-0.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.104 mg/mLALOGPS
logP0.25ALOGPS
logP-1.2ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)3.45ChemAxon
pKa (Strongest Basic)2.92ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area184.51 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity104.91 m3·mol-1ChemAxon
Polarizability41.62 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7776
Blood Brain Barrier-0.9704
Caco-2 permeable-0.7432
P-glycoprotein substrateSubstrate0.6934
P-glycoprotein inhibitor INon-inhibitor0.8863
P-glycoprotein inhibitor IINon-inhibitor0.8724
Renal organic cation transporterNon-inhibitor0.8301
CYP450 2C9 substrateNon-substrate0.9002
CYP450 2D6 substrateNon-substrate0.8161
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9029
Ames testNon AMES toxic0.7495
CarcinogenicityNon-carcinogens0.8549
BiodegradationNot ready biodegradable0.9911
Rat acute toxicity1.6878 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9897
hERG inhibition (predictor II)Non-inhibitor0.895
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-004i-3920000000-3269e737530417831893

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Lactams
Sub Class
Beta lactams
Direct Parent
Cephalosporins
Alternative Parents
N-acyl-alpha amino acids and derivatives / 2,4-disubstituted thiazoles / 1,3-thiazines / 2-amino-1,3-thiazoles / Dicarboxylic acids and derivatives / Tertiary carboxylic acid amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Amino acids / Azetidines
show 9 more
Substituents
Cephalosporin / N-acyl-alpha amino acid or derivatives / Alpha-amino acid or derivatives / 2,4-disubstituted 1,3-thiazole / Meta-thiazine / Dicarboxylic acid or derivatives / 1,3-thiazol-2-amine / Heteroaromatic compound / Azole / Tertiary carboxylic acid amide
show 23 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
cephalosporin (CHEBI:472657)

Targets

Kind
Protein
Organism
Haemophilus influenzae (strain ATCC 51907 / DSM 11121 / KW20 / Rd)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Penicillin binding
Specific Function
Cell wall formation; PBP-2 is responsible for the determination of the rod shape of the cell. Its synthesize cross-linked peptidoglycan from the lipid intermediates (By similarity).
Gene Name
mrdA
Uniprot ID
P44469
Uniprot Name
Penicillin-binding protein 2
Molecular Weight
73812.47 Da
References
  1. Takahata S, Senju N, Osaki Y, Yoshida T, Ida T: Amino acid substitutions in mosaic penicillin-binding protein 2 associated with reduced susceptibility to cefixime in clinical isolates of Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2006 Nov;50(11):3638-45. Epub 2006 Aug 28. [PubMed:16940068]
  2. Zhao S, Duncan M, Tomberg J, Davies C, Unemo M, Nicholas RA: Genetics of chromosomally mediated intermediate resistance to ceftriaxone and cefixime in Neisseria gonorrhoeae. Antimicrob Agents Chemother. 2009 Sep;53(9):3744-51. doi: 10.1128/AAC.00304-09. Epub 2009 Jun 15. [PubMed:19528266]

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 cat...
Gene Name
SLC22A5
Uniprot ID
O76082
Uniprot Name
Solute carrier family 22 member 5
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
Substrate
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
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Wenzel U, Gebert I, Weintraut H, Weber WM, Clauss W, Daniel H: Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells. J Pharmacol Exp Ther. 1996 May;277(2):831-9. [PubMed:8627565]
  2. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH: Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308. [PubMed:9092716]
  3. 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]
  4. Terada T, Saito H, Mukai M, Inui K: Characterization of stably transfected kidney epithelial cell line expressing rat H+/peptide cotransporter PEPT1: localization of PEPT1 and transport of beta-lactam antibiotics. J Pharmacol Exp Ther. 1997 Jun;281(3):1415-21. [PubMed:9190878]
  5. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833]
  6. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [PubMed:15618677]
  7. Tamai I, Nakanishi T, Hayashi K, Terao T, Sai Y, Shiraga T, Miyamoto K, Takeda E, Higashida H, Tsuji A: The predominant contribution of oligopeptide transporter PepT1 to intestinal absorption of beta-lactam antibiotics in the rat small intestine. J Pharm Pharmacol. 1997 Aug;49(8):796-801. [PubMed:9379359]
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
Uniprot Name
Solute carrier family 15 member 2
Molecular Weight
81782.77 Da
References
  1. Ganapathy ME, Prasad PD, Mackenzie B, Ganapathy V, Leibach FH: Interaction of anionic cephalosporins with the intestinal and renal peptide transporters PEPT 1 and PEPT 2. Biochim Biophys Acta. 1997 Mar 13;1324(2):296-308. [PubMed:9092716]
  2. Terada T, Saito H, Mukai M, Inui K: Recognition of beta-lactam antibiotics by rat peptide transporters, PEPT1 and PEPT2, in LLC-PK1 cells. Am J Physiol. 1997 Nov;273(5 Pt 2):F706-11. [PubMed:9374833]
  3. 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]

Drug created on June 13, 2005 07:24 / Updated on November 19, 2017 20:33