Fosfomycin

Identification

Name
Fosfomycin
Accession Number
DB00828
Description

An antibiotic produced by Streptomyces fradiae.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 138.059
Monoisotopic: 138.008195224
Chemical Formula
C3H7O4P
Synonyms
  • (-)-(1R,2S)-(1,2-Epoxypropyl)phosphonic acid
  • (1R,2S)-epoxypropylphosphonic acid
  • (2R-cis)-(3-Methyloxiranyl)phosphonic acid
  • 1R-cis-(1,2-epoxypropyl)phosphonic acid
  • cis-(1R,2S)-epoxypropylphosphonic acid
  • FCM
  • Fosfocina
  • Fosfomicina
  • Fosfomycin
  • Fosfomycine
  • Fosfomycinum
  • L-cis-1,2-epoxypropylphosphonic acid
  • Phosphomycin
  • Phosphonemycin
  • Phosphonomycin
External IDs
  • J01XX01

Pharmacology

Indication

For the treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of Escherichia coli and Enterococcus faecalis.

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

Fosfomycin is a broad spectrum antibiotic that concentrates in kidney and bladder and is used to treat uncomplicated urinary tract infections. Fosfomycin also reduces nephrotoxicity and ototoxicity of platinum-containing anti-tumor agents.

Mechanism of action

Fosfomycin is a phosphoenolpyruvate analogue produced by Streptomyces that irreversibly inhibits enolpyruvate transferase (MurA), which prevents the formation of N-acetylmuramic acid, an essential element of the peptidoglycan cell wall.

TargetActionsOrganism
AUDP-N-acetylglucosamine 1-carboxyvinyltransferase
inhibitor
Escherichia coli (strain K12)
Absorption

Fosfomycin tromethamine is rapidly absorbed following oral administration and converted to fosfomycin. Oral bioavailability under fasting conditions is 37%. When given with food, oral bioavailability is reduced to 30%

Volume of distribution
  • 136.1 ±44.1 L
Protein binding

0% (not bound to plasma proteins)

Metabolism

No transformation, excreted unchanged

Route of elimination

Fosfomycin is excreted unchanged in both urine and feces.

Half-life

5.7 (± 2.8) hours. The elimination half-life is 40 hours in anuric patients undergoing hemodialysis.

Clearance
  • 16.9 +/- 3.5 L/hr
Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

LD50>5 g/kg (rats). Side effects may include diarrhea

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

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbacavirFosfomycin may decrease the excretion rate of Abacavir which could result in a higher serum level.
AcarboseAcarbose may decrease the excretion rate of Fosfomycin which could result in a higher serum level.
AceclofenacAceclofenac may decrease the excretion rate of Fosfomycin which could result in a higher serum level.
AcemetacinAcemetacin may decrease the excretion rate of Fosfomycin which could result in a higher serum level.
AcenocoumarolThe risk or severity of bleeding can be increased when Fosfomycin is combined with Acenocoumarol.
AcetaminophenAcetaminophen may decrease the excretion rate of Fosfomycin which could result in a higher serum level.
AcetazolamideAcetazolamide may increase the excretion rate of Fosfomycin which could result in a lower serum level and potentially a reduction in efficacy.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Fosfomycin which could result in a higher serum level.
AclidiniumFosfomycin may decrease the excretion rate of Aclidinium which could result in a higher serum level.
AcrivastineFosfomycin may decrease the excretion rate of Acrivastine which could result in a higher serum level.
Additional Data Available
  • Extended Description
    Extended Description
    Available for Purchase

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity
    Available for Purchase

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level
    Available for Purchase

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action
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    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Fosfomycin calcium monohydrateT330QG2NYS26469-67-0MSHCINMVQZDXTG-JSTPYPERSA-N
Fosfomycin disodium97MMO19FNO26016-99-9QZIQJIKUVJMTDG-UHFFFAOYSA-L
Fosfomycin tromethamine7FXW6U30GY78964-85-9QZJIMDIBFFHQDW-LMLSDSMGSA-N
International/Other Brands
Veramina (Roux-Ocefa)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Fosfomycin Powder for Oral SolutionPowder, for solutionOralEndo Ventures LtdNot applicableNot applicableCanada flag
IvozfoPowder, for solutionIntravenousVerity Pharmaceuticals Inc.Not applicableNot applicableCanada flag
IvozfoPowder, for solutionIntravenousVerity Pharmaceuticals Inc.2020-02-12Not applicableCanada flag
IvozfoPowder, for solutionIntravenousVerity Pharmaceuticals Inc.Not applicableNot applicableCanada flag
MonurolPowder3 g/1OralAllergan, Inc.1996-12-19Not applicableUS flag
MonurolPowder, for solution3 gOralPaladin Labs Inc1999-09-15Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Fosfomycin TromethaminePowder3 g/1OralXiromed Llc2020-10-06Not applicableUS flag
Jamp-fosfomycinPowder, for solutionOralJamp Pharma Corporation2018-08-02Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number
    Available for Purchase

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code
    Available for Purchase

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
J01XX01 — Fosfomycin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as organic phosphonic acids. These are organic compounds containing phosphonic acid.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Organic phosphonic acids and derivatives
Sub Class
Organic phosphonic acids
Direct Parent
Organic phosphonic acids
Alternative Parents
Oxacyclic compounds / Epoxides / Organopnictogen compounds / Organophosphorus compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Aliphatic heteromonocyclic compound / Hydrocarbon derivative / Organic oxide / Organic oxygen compound / Organoheterocyclic compound / Organooxygen compound / Organophosphonic acid / Organophosphorus compound / Organopnictogen compound / Oxacycle
Molecular Framework
Aliphatic heteromonocyclic compounds
External Descriptors
epoxide, phosphonic acids (CHEBI:28915) / Aliphatic compounds (C06454)

Chemical Identifiers

UNII
2N81MY12TE
CAS number
23155-02-4
InChI Key
YMDXZJFXQJVXBF-STHAYSLISA-N
InChI
InChI=1S/C3H7O4P/c1-2-3(7-2)8(4,5)6/h2-3H,1H3,(H2,4,5,6)/t2-,3+/m0/s1
IUPAC Name
[(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
SMILES

References

Synthesis Reference

Graziano Castaldi, Claudio Giordano, "Process for the preparation of intermediates for the synthesis of fosfomycin." U.S. Patent US4937367, issued March, 1972.

US4937367
General References
Not Available
Human Metabolome Database
HMDB0014966
KEGG Drug
D04253
KEGG Compound
C06454
PubChem Compound
446987
PubChem Substance
46506665
ChemSpider
394204
BindingDB
50024894
RxNav
4550
ChEBI
28915
ChEMBL
CHEMBL1757
ZINC
ZINC000001530427
Therapeutic Targets Database
DAP000767
PharmGKB
PA164748039
PDBe Ligand
FCN
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Fosfomycin
AHFS Codes
  • 08:36.00 — Urinary Anti-infectives
PDB Entries
1lqp / 2bnn / 3d41 / 3quo / 4ir0 / 4jd1 / 4jh3 / 4jh4 / 4jh5 / 4jh6
show 2 more
FDA label
Download (267 KB)
MSDS
Download (61.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedPreventionAllograft Rejection / Asymptomatic Bacteriuria / Hospitalizations / Microbiologic Resistance / Urinary Tract Infection1
4CompletedPreventionAsymptomatic Bacteriuria / Urinary Tract Infection1
4CompletedPreventionUrinary Tract Infection1
4CompletedTreatmentInfective Endocarditis1
4CompletedTreatmentUrinary Tract Infection2
4RecruitingPreventionComplications / Infection / Prostate Cancer1
4RecruitingTreatmentProsthetic Joint Infection1
4TerminatedTreatmentUrinary Tract Infection1
4Unknown StatusTreatmentCystitis / Urinary Tract Infection1
3CompletedTreatmentGonorrhea1

Pharmacoeconomics

Manufacturers
  • Zambon spa italy
Packagers
  • Forest Pharmaceuticals
  • Zambon Ltd.
Dosage Forms
FormRouteStrength
PowderOral2 g
Injection, powder, for solutionIntravenous1 g
Injection, powder, for solutionIntravenous4 g
Injection, powder, for solutionParenteral40 mg/ml
Tablet, effervescent3 g
Injection, powder, for solution2 g
Injection, powder, for solutionIntravenous8 g
Injection, powder, for solutionParenteral4 g
Injection, powder, for solutionParenteral8 g
Injection, powder, lyophilized, for solutionIntravenous1 g
Injection, powder, lyophilized, for solutionIntravenous4 g
Injection, powder, for solution1 g
Injection, powder, for solution4 g
Tablet500 mg
Powder, for suspensionOral3 g
Powder, for solutionParenteral40 MG/ML
Powder, for solutionIntravenous
Powder, for solutionOral
Granule, for solutionOral2 G
Granule, for solutionOral3 G
PowderOral3 g/1
Injection, powder, for solution
Capsule, coatedOral500 mg
Powder, for solutionOral3 g
PowderOral3 g
GranuleOral3 g
Prices
Unit descriptionCostUnit
Monurol 3 gm Packets50.87USD packet
Monurol 3 gm sachet47.07USD each
Viramune 200 mg tablet9.48USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)94 °CPhysProp
water solubility50 mg/mL (Sodium salt)Not Available
logP-1.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility46.9 mg/mLALOGPS
logP-0.86ALOGPS
logP-0.74ChemAxon
logS-0.47ALOGPS
pKa (Strongest Acidic)1.25ChemAxon
pKa (Strongest Basic)-4.3ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area70.06 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity25.87 m3·mol-1ChemAxon
Polarizability10.8 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption-0.5
Blood Brain Barrier+0.9382
Caco-2 permeable-0.6652
P-glycoprotein substrateNon-substrate0.7234
P-glycoprotein inhibitor INon-inhibitor0.8938
P-glycoprotein inhibitor IINon-inhibitor0.9878
Renal organic cation transporterNon-inhibitor0.9505
CYP450 2C9 substrateNon-substrate0.7514
CYP450 2D6 substrateNon-substrate0.8332
CYP450 3A4 substrateNon-substrate0.6513
CYP450 1A2 substrateNon-inhibitor0.8492
CYP450 2C9 inhibitorNon-inhibitor0.8551
CYP450 2D6 inhibitorNon-inhibitor0.9202
CYP450 2C19 inhibitorNon-inhibitor0.8016
CYP450 3A4 inhibitorNon-inhibitor0.9624
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.944
Ames testNon AMES toxic0.6575
CarcinogenicityNon-carcinogens0.6059
BiodegradationNot ready biodegradable0.894
Rat acute toxicity2.5802 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9456
hERG inhibition (predictor II)Non-inhibitor0.9491
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
GC-MS Spectrum - GC-MS (2 TMS)GC-MSsplash10-03di-2980000000-005d5b96a1e9219362d0
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-MSGC-MSsplash10-03di-2980000000-005d5b96a1e9219362d0
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

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Udp-n-acetylglucosamine 1-carboxyvinyltransferase activity
Specific Function
Cell wall formation. Adds enolpyruvyl to UDP-N-acetylglucosamine. Target for the antibiotic fosfomycin.
Gene Name
murA
Uniprot ID
P0A749
Uniprot Name
UDP-N-acetylglucosamine 1-carboxyvinyltransferase
Molecular Weight
44817.24 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Kim DH, Lees WJ, Kempsell KE, Lane WS, Duncan K, Walsh CT: Characterization of a Cys115 to Asp substitution in the Escherichia coli cell wall biosynthetic enzyme UDP-GlcNAc enolpyruvyl transferase (MurA) that confers resistance to inactivation by the antibiotic fosfomycin. Biochemistry. 1996 Apr 16;35(15):4923-8. [PubMed:8664284]
  4. Eschenburg S, Priestman M, Schonbrunn E: Evidence that the fosfomycin target Cys115 in UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is essential for product release. J Biol Chem. 2005 Feb 4;280(5):3757-63. Epub 2004 Nov 5. [PubMed:15531591]
  5. McCoy AJ, Sandlin RC, Maurelli AT: In vitro and in vivo functional activity of Chlamydia MurA, a UDP-N-acetylglucosamine enolpyruvyl transferase involved in peptidoglycan synthesis and fosfomycin resistance. J Bacteriol. 2003 Feb;185(4):1218-28. [PubMed:12562791]
  6. Brown ED, Vivas EI, Walsh CT, Kolter R: MurA (MurZ), the enzyme that catalyzes the first committed step in peptidoglycan biosynthesis, is essential in Escherichia coli. J Bacteriol. 1995 Jul;177(14):4194-7. [PubMed:7608103]
  7. Samland AK, Amrhein N, Macheroux P: Lysine 22 in UDP-N-acetylglucosamine enolpyruvyl transferase from Enterobacter cloacae is crucial for enzymatic activity and the formation of covalent adducts with the substrate phosphoenolpyruvate and the antibiotic fosfomycin. Biochemistry. 1999 Oct 5;38(40):13162-9. [PubMed:10529188]

Drug created on June 13, 2005 07:24 / Updated on November 25, 2020 08:52

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