Monurol

Urinary Antibiotics and/or Sulfonamides

Fosfomycin is administered orally without regard to meals.

Do not administer dry powder. Pour the entire contents of a sachet containing the equivalent of 3 g of fosfomycin into 3—4 oz (1/2 cup) of water; do not use hot water. Stir to dissolve. Take immediately after dissolving.

toxic megacolon / Delayed / 0-1.0
hepatic necrosis / Delayed / 0-1.0
optic neuritis / Delayed / 0-1.0
angioedema / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
hearing loss / Delayed / 0-1.0
aplastic anemia / Delayed / 0-1.0
C. difficile-associated diarrhea / Delayed / Incidence not known

vaginitis / Delayed / 5.5-7.6
constipation / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
jaundice / Delayed / 0-1.0
migraine / Early / 0-1.0
dysuria / Early / 0-1.0
hematuria / Delayed / 0-1.0
lymphadenopathy / Delayed / 0-1.0
superinfection / Delayed / Incidence not known
pseudomembranous colitis / Delayed / Incidence not known

diarrhea / Early / 9.0-10.4
headache / Early / 3.9-10.3
nausea / Early / 4.1-5.2
rhinitis / Early / 4.5-4.5
back pain / Delayed / 3.0-3.0
dysmenorrhea / Delayed / 2.6-2.6
pharyngitis / Delayed / 2.5-2.5
dizziness / Early / 1.3-2.3
abdominal pain / Early / 2.2-2.2
dyspepsia / Early / 1.1-1.8
asthenia / Delayed / 1.1-1.7
rash / Early / 1.4-1.4
anorexia / Delayed / 0-1.0
xerostomia / Early / 0-1.0
vomiting / Early / 0-1.0
flatulence / Early / 0-1.0
influenza / Delayed / 0-1.0
infection / Delayed / 0-1.0
paresthesias / Delayed / 0-1.0
drowsiness / Early / 0-1.0
insomnia / Early / 0-1.0
myalgia / Early / 0-1.0
fever / Early / 0-1.0
pruritus / Rapid / 0-1.0

Monurol

Rx

Antibiotic; used for uncomplicated UTIs; may be synergistic with beta-lactam antibiotics; sustains effective urinary concentrations for over 3 days; efficacy as a single dose appears to be less than that for fluoroquinolones or co-trimoxazole.

3 g PO as a single dose.

3 g PO as a single dose.

3 g PO as a single dose.

3 g PO as a single dose, or alternatively, 3 g PO every 48 hours for 3 doses.

3 g PO once daily for 1 week, then 3 g PO every 48 hours for 6 to 12 weeks as an alternative for ESBL-producing E. coli.

3 g PO every 10 days. The duration of prophylaxis is variable and should be assessed routinely. Generally 3 to 12 months is suggested; however, longer durations have been used.  

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available. The half-life of fosfomycin increases and urinary excretion decreases as renal impairment progresses.

Bethanechol: (Moderate) Bethanechol increases gastrointestinal motility and may decrease the systemic absorption of fosfomycin when the drugs are coadministered. This may result in lower fosfomycin serum concentrations and urinary excretion. Since fosfomycin is given as a single dose, separating times of administration may limit the interaction.
Cisapride: (Moderate) Cisapride may decrease the systemic absorption of fosfomycin due to the prokinetic action of cisapride. This may result in lower fosfomycin serum concentrations and urinary excretion. Monitor for evidence of clinical effectiveness of fosfomycin. Since fosfomycin is given as a single dose, separating times of administration may limit the interaction.
Metoclopramide: (Moderate) When coadministered with fosfomycin, metoclopramide, a drug which increases gastrointestinal motility, lowers the serum concentration and urinary excretion of fosfomycin. Other drugs that increase gastrointestinal motility may produce similar effects. Monitor for evidence of clinical effectiveness of fosfomycin. Since fosfomycin is given as a single dose, separating times of administration may limit the interaction.
Prucalopride: (Moderate) Prucalopride may decrease the systemic absorption of fosfomycin due to the prokinetic action of prucalopride. This may result in lower fosfomycin serum concentrations and urinary excretion. Monitor for evidence of clinical effectiveness of fosfomycin. Since fosfomycin is given as a single dose, separating times of administration may limit the interaction.

Fosfomycin/Fosfomycin Tromethamine/Monurol Oral Gran: 3g

Women: 3 g PO as a single dose.
Men: Safety and efficacy have not been established.

Women: 3 g PO as a single dose.
Men: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Fosfomycin inhibits one of the first steps in the synthesis of peptidoglycan. After transport into bacterial cells via glycerol-3-phosphate or glucose-6-phosphate transport systems, fosfomycin, through its epoxide group, irreversibly inactivates the enzyme enolpyruvyl transferase by taking the place of phosphoenolpyruvate. Inactivation of this enzyme blocks the condensation of uridine diphosphate-N-acetylglucosamine with p-enolpyruvate, a key first step in bacterial cell wall synthesis. Fosfomycin also binds other p-enolpyruvate dependent enzymes, but irreversible inactivation does not occur. Inhibition of peptidoglycan synthesis results in accumulation of the nucleotide precursors and subsequent death and bacterial cell lysis. Fosfomycin is bactericidal in the urine at therapeutic doses. Clinicians are advised to consult susceptibility data at the institution in which they practice to determine fosfomycin activity.

Fosfomycin is administered orally as fosfomycin tromethamine. In the systemic circulation, fosfomycin is not bound to plasma proteins. The drug is distributed to the kidneys, bladder wall, prostate, and seminal vesicles. Fosfomycin has been shown to cross the placenta. Fosfomycin is not metabolized and excretion occurs via both urine and feces. Approximately 38% of a dose is recovered from urine and 18% from feces. A mean urinary concentration of 706 +/- 466 mcg/mL was attained within 2—4 hours after a single 3-gram oral dose under fasting conditions. After a high-fat meal, a mean urinary concentration of 537 +/- 252 mcg/mL was achieved within 6—8 hours. The cumulative amount of fosfomycin excreted in the urine was the same under fed and fasting conditions. Urinary concentrations >= 100 mcg/mL were maintained for 26 hours. The mean elimination half-life is 5.7 +/- 2.8 hours.

Following administration, fosfomycin tromethamine is rapidly absorbed and converted to the free acid, fosfomycin. The absolute oral bioavailability under fasting conditions is 37% and is reduced to 30% under fed conditions. Following a single 3-gram oral dose, mean maximum serum concentrations were achieved within 2 hours or 4 hours on an empty stomach or with a high-fat meal, respectively.

Fosfomycin crosses the placental barrier. The FDA labeling suggests that fosfomycin should be used during pregnancy only if clearly needed. While there are no adequate and well-controlled studies with fosfomycin in pregnant women, observational data suggest that the single-dose use during pregnancy may be well tolerated during pregnancy.

Limited data indicate that fosfomycin produces low levels in milk. The manufacturer recommends that the use of fosfomycin in breast-feeding mothers should be undertaken with caution. In 2 women, after 1—2 grams of fosfomycin given by injection, colostrum concentrations were 4.8 mg/L and milk concentrations were 3.6 mg/L. Cephalexin, nitrofurantoin, or sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. However, site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Trimethoprim (in combination with sulfamethoxazole) and nitrofurantoin are considered to be usually compatible with breast-feeding by the AAP. Cephalosporins, such as cephalexin, are generally considered to be compatible with breast-feeding. If fosfomycin is used, alterations to the infants' gut flora may be altered; monitor appropriately. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.