Medication Guide App

Fosfomycin (Systemic)


VA CLASSIFICATION
Primary: AM900

Commonly used brand name(s): Monurol.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antibacterial (systemic)—

Indications

General considerations
Fosfomycin is active against most strains of Enterococcus faecalis and Escherichia coli {01}. Fosfomycin also exhibits in vitro minimum inhibitory concentrations of 64 micrograms per mL or less against most strains of Citrobacter diversus , Citrobacter freundii , Enterobacter aerogenes , Enterococcus faecium , Klebsiella oxytoca , Klebsiella pneumoniae , Proteus mirabilis , Proteus vulgaris , and Serratia marcescens {01}.

There is generally no cross-resistance between fosfomycin and other classes of antibacterial agents, such as beta-lactams and aminoglycosides {01}.

Accepted

Urinary tract infections, uncomplicated (treatment)—Fosfomycin is indicated in the treatment of uncomplicated urinary tract infections and acute cystitis, caused by E. coli or E. faecalis , in women {01}.

Unaccepted
Fosfomycin is not indicated for the treatment of perinephric abscess or pyelonephritis {01}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Phosphonic acid derivative {01}.
Molecular weight—
    Fosfomycin tromethamine: 259.2 {01}

Mechanism of action/Effect:

Fosfomycin inactivates enolpyruvyl transferase, which irreversibly blocks the condensation of uridine diphosphate- N-acetylglucosamine with phospho enolpyruvate, and inhibits bacterial cell wall synthesis {01}. Fosfomycin also decreases the adherence of bacteria to epithelial cells of the urinary tract {01}.

Absorption:

Fosfomycin tromethamine is rapidly absorbed following oral administration and converted to fosfomycin {01}. Oral bioavailability under fasting conditions is 37% {01}. When given with food, oral bioavailability is reduced to 30% {01}.

Distribution:

Fosfomycin is distributed to the bladder wall, kidneys, prostate, and seminal vesicles {01}.

Vol D—Mean steady-state following oral administration, 136.1 ± 44.1 L {01}.

Protein binding:

Fosfomycin is not bound to plasma proteins {01}.

Biotransformation:

Fosfomycin tromethamine is converted to the free acid fosfomycin {01}.

Half-life:

Elimination—Mean, 5.7 ± 2.8 hours {01}.

The elimination half-life is 40 hours in anuric patients undergoing hemodialysis {01}.

Onset of action:

2 to 3 days {01}.

Elimination:
    With normal renal function—

• Fecal: 18% of a 3-gram fosfomycin dose is eliminated {01}.


• Renal: 38% of a 3-gram fosfomycin dose is eliminated {01}.


• Fosfomycin tromethamine is excreted as fosfomycin {01}.

    With renal function impairment—

• Fosfomycin recovery in urine decreases from 32% to 11% {01}.



Precautions to Consider

Carcinogenicity

Long-term carcinogenicity studies in animals have not been done {01}.

Mutagenicity

Fosfomycin was not found to be mutagenic or genotoxic in vitro in the Ames test, in cultured human lymphocytes, or in Chinese hamster V79 cells, or in vivo in the mouse micronucleus assay {01}.

Pregnancy/Reproduction
Fertility—
Fertility and reproductive performance of male and female rats were not affected {01}.

Pregnancy—
Adequate and well-controlled studies in humans have not been done {01}. However, fosfomycin has been shown to cross the placenta {01}.

Studies in pregnant rabbits at dosages of 1000 mg per kg of body weight per day (approximately 9 and 2.7 times the human dose based on body weight and body surface area, respectively) showed fetotoxicity and maternal toxicity. {01}

FDA Pregnancy Category B {01}.

Breast-feeding

It is not known whether fosfomycin is distributed into breast milk {01}.

Pediatrics

Safety and efficacy have not been established in children up to 12 years of age {01}.


Geriatrics


The bacteriologic effectiveness and safety profiles for women older than 65 years of age did not show clinically significant differences, as compared with those for women 65 years of age and younger {01}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Cimetidine does not affect the pharmacokinetics of fosfomycin {01}.
Combinations containing the following medication, depending on the amount present, may also interact with this medication.

Metoclopramide    (concurrent use of metoclopramide increases gastrointestinal motility and lowers the serum concentration and urinary excretion of fosfomycin {01}; other medications that increase gastrointestinal motility may have the same effect {01})



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With physiology/laboratory test values
Alanine aminotransferase (ALT [SGPT]) {01} and
Alkaline phosphatase {01} and
Aspartate aminotransferase (AST [SGOT]) {01}    (serum values may be increased {01})


Bilirubin, serum {01}    (concentration may be increased {01})


Eosinophil count {01}    (may be increased {01})


Hematocrit {01} and
Hemoglobin {01}    (concentrations may be decreased {01})


Leukocyte count {01} and
Platelet count {01}    (may be increased or decreased {01})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Sensitivity to fosfomycin {01}
» Renal function impairment {01}    (clearance of fosfomycin may be decreased {01})



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

» Urine culture and susceptibility testing {01}    (recommended before and after completion of treatment {01})




Side/Adverse Effects

Note: Use of more than one dose to treat a single episode of acute cystitis may increase the incidence of adverse effects {01}.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence more frequent
    
Vaginitis (vaginal discharge and pain)—7.6%{01}



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Diarrhea —10.4%{01}
    
headache —10.3%{01}
    
nausea —5.2%{01}

Incidence less frequent
    
Abdominal pain —2.2%{01}
    
asthenia (weakness)—1.7%{01}
    
back pain —3%{01}
    
dizziness —2.3%{01}
    
dysmenorrhea (painful menstruation)—2.6%{01}
    
dyspepsia (heartburn; indigestion)—1.8%{01}
    
pain, nonlocalized —2.2%{01}
    
pharyngitis (sore throat)—2.5%{01}
    
rhinitis (runny or stuffy nose)—4.5%{01}
    
skin rash —1.4%{01}





Overdose
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
No cases of overdose in humans have been reported {01}.

Treatment of overdose
Supportive care—Patient should receive symptomatic and supportive therapy {01}. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Fosfomycin (Systemic) .

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to fosfomycin

Pregnancy—Fosfomycin crosses the placenta
Other medical problems, especially renal function impairment

Proper use of this medication
» Not taking medication in its dry form; taking immediately after dissolving in water

Taking with or without food

» Proper dosing

» Proper storage

Precautions while using this medication
» Checking with physician if there is no improvement in symptoms within 2 to 3 days


Side/adverse effects
Signs of potential side effects, especially vaginitis


Oral Dosage Forms

FOSFOMYCIN TROMETHAMINE FOR ORAL SOLUTION

Note: The dosing and strength of the dosage form available are expressed in terms of the fosfomycin free acid (not the tromethamine salt).


Usual adult dose
Urinary tract infections, uncomplicated
Oral, 3 grams (free acid) as a single dose {01}.


Usual adult prescribing limits
3 grams (free acid) per episode of acute cystitis {01}.

Usual pediatric dose
Children up to 12 years of age
Safety and efficacy have not been established {01}.


Usual geriatric dose
See Usual adult dose {01}.

Strength(s) usually available
U.S.—


3 grams (free acid) per packet (Rx) [Monurol (saccharin) (sucrose)]{01}

Note: The single-dose packet contains 5.63 grams of fosfomycin tromethamine, equivalent to 3 grams of fosfomycin free acid {01}.


Packaging and storage:
Store between 15 and 30 ºC (59 and 86 ºF) {01}.

Preparation of dosage form:
Empty entire contents of a single-dose packet into 3 or 4 ounces of water and stir until dissolved {01}. Do not use hot water {01}.

Stability:
After reconstitution, fosfomycin solution should be taken immediately {01}.

Auxiliary labeling:
   • Dissolve in water before taking {01}.



Developed: 10/20/1997
Revised: 07/28/1998



References
  1. Monurol package insert (Forest—US), Rev 1/97, Rec 4/97.
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