Fosfomycin Trometamol

J01X - Other antibacterials ATC J01XX01 Small molecule approved 1996 Oral

JFDA label: Unaira

Mechanism of Action

Inhibitor of UDP-N-acetylglucosamine 1-carboxyvinyltransferase — UDP-N-acetylglucosamine 1-carboxyvinyltransferase inhibitor

Target	Action	Gene / class
UDP-N-acetylglucosamine 1-carboxyvinyltransferase efficacy	INHIBITOR	murA

Indications

Approved

Uncomplicated urinary tract infections

Off-label

Urinary tract infections, complicated (in men)

Antimicrobial Spectrum

Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: curated.

Bacteria

Organism	Activity	MIC
Enterococcus faecalis	Susceptible	32.0 mg/L
Escherichia coli	Susceptible	32.0 mg/L
Klebsiella pneumoniae	Susceptible	32.0 mg/L
Escherichia coli	Resistant	32.0 mg/L

Class profile

gramStatus	Both
spectrumBreadth	Broad
atypicalCoverage	No
isBactericidal	1
moaCategory	Cell wall synthesis inhibitor (MurA inhibition, UDP-GlcNAc epoxidation)
pdIndex	Time-dependent
postAntibioticEffect	None
mrsaCoverage	0
resistanceMechanisms	MurA mutation,Fosfomycin transport mutations (glpT,uhpT)

Contraindications

Source: Lexicomp

Hypersensitivity to fosfomycin or any component of the formulation Absolute

Adverse Reactions

Very Common >10%Common 1–10%Uncommon 0.1–1% Rare 0.01–0.1%Very Rare <0.01%Not Known

Nervous system disorders (3)

Common dizziness · Headache · pain

Renal and urinary disorders (2)

Common dysmenorrhea · Vaginitis

Gastrointestinal disorders (4)

Common abdominal pain · Diarrhea · dyspepsia · nausea

Skin and subcutaneous tissue disorders (1)

Common Skin rash

Musculoskeletal and connective tissue disorders (2)

Common Back pain · weakness

Respiratory, thoracic and mediastinal disorders (2)

Common pharyngitis · Rhinitis

Dosing

Source: Lexicomp

Urinary tract infections, uncomplicated: Oral: Females: Single dose of 3 g in 3 to 4 oz (90 to 120 mL) of water Complicated UTI (off-label): Males: Oral: 3 g every 2 to 3 days for 3 doses (Neuner 2012; Pullukcu 2007) Prostatitis (off-label): Males: Oral: 3 g every 3 days for a total of 21 days (Shrestha, 2000)

Refer to adult dosing.

Warnings & Precautions

Source: Lexicomp

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. 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

Pregnancy & Lactation

Pregnancy

FDA category B

Adverse events have not been observed in animal reproduction studies. Fosfomycin crosses the placenta. Several studies have used a single dose therapy with fosfomycin for the treatment of asymptomatic bacteriuria in pregnant women (Reeves, 1992). However, when treatment is needed in pregnant women, an appropriate antibiotic with a 3 to 7 day regimen is currently recommended (Nicolle, 2005).

Lactation

Fosfomycin distributes into breast milk (Kirby, 1977). Due to the potential for serious adverse reactions in the nursing infant, the manufacturer recommends a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Monitoring

Efficacy	Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin)
Toxicity	Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea)
Clinical pearl	Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship).
Counseling	Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h.

Chemistry & Properties

Formula	C7H18NO7P
Molecular weight	259.19 g/mol
IUPAC name	2-amino-2-(hydroxymethyl)propane-1,3-diol;[(2R,3S)-3-methyloxiran-2-yl]phosphonic acid
CAS	78964-85-9
PubChem CID	10199068
InChIKey	`QZJIMDIBFFHQDW-LMLSDSMGSA-N`
logP	-0.09
Polar surface area	70.06 Å²
H-bond acceptors / donors	2 / 2
Drug-likeness (QED)	0.39
Lipinski violations	0

SMILES

C[C@@H]1O[C@@H]1P(=O)(O)O.NC(CO)(CO)CO

Biology & Pharmacokinetics

Pharmacokinetics predicted

Bioavailability	10.0%
Half-life	2.077 h
Volume of distribution	0.987 L/kg
Protein binding	5.6%
BBB penetrant	No

Enzyme interactions

Enzyme	Role	Detail
CYP2C9	Substrate	—
CYP2D6	Substrate	—
CYP3A4	Substrate	—

Transporters

BCRP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)

Registered Products (1)

Brand	Form / strength	Pack	Agent	Citizen (JOD)
Unaira	Sachet 5.631 g	1 SAC/1 BOX	Hikma Pharmaceuticals Co.Ltd/Jordan	3.630