FOSFOMYCIN TROMETHAMINE
Clinical safety rating: safe
Human studies have proved safety
Fosfomycin inhibits bacterial cell wall synthesis by inactivating the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), which catalyzes the first step of peptidoglycan biosynthesis.
| Metabolism | Fosfomycin is primarily excreted unchanged in urine via glomerular filtration; metabolism is minimal, with no specific hepatic enzymes involved. Small amounts may be metabolized to inactive metabolites. |
| Excretion | Primarily excreted unchanged in urine via glomerular filtration (approximately 90% of absorbed dose within 24-48 hours); small amount (approximately 10%) excreted in feces via biliary elimination. |
| Half-life | Terminal elimination half-life is 5.7 hours (range 3-8 hours) in patients with normal renal function; approximately 50 hours in end-stage renal disease (CrCl <10 mL/min). |
| Protein binding | 0% bound to plasma proteins. |
| Volume of Distribution | Volume of distribution is 0.3 L/kg (range 0.2-0.4 L/kg), indicating distribution primarily into extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 30-40% (range 25-50%) from the tromethamine salt; food significantly reduces absorption by up to 30%. |
| Onset of Action | For urinary tract infections: clinical effects begin within 2-4 hours after oral administration as a single dose. |
| Duration of Action | Single-dose therapy provides bactericidal urine concentrations for 24-48 hours; clinical cure rates are comparable to multi-day regimens for uncomplicated UTI. |
3 g orally once as a single dose for uncomplicated urinary tract infection.
| Dosage form | FOR SOLUTION |
| Renal impairment | Contraindicated if creatinine clearance < 10 mL/min. No adjustment for GFR ≥ 10 mL/min. |
| Liver impairment | No dose adjustment required in hepatic impairment. |
| Pediatric use | Children ≥ 12 years: 3 g orally as a single dose. Children < 12 years: not recommended. |
| Geriatric use | No specific dose adjustment; use same single 3 g dose unless severe renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Metoclopramide may decrease serum levels Generally well-tolerated with diarrhea being the most common side effect.
| Breastfeeding | Fosfomycin is excreted into human breast milk in low amounts. M/P ratio is not established. The American Academy of Pediatrics considers it compatible with breastfeeding. Caution with repeated use due to potential for diarrhea and sensitization in the infant. |
| Teratogenic Risk | Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Use during first trimester only if clearly needed. Avoid in second and third trimester unless benefit outweighs potential risk of maternal diarrhea and electrolyte disturbances. |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
["Hypersensitivity to fosfomycin or any component of the formulation"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis and angioedema","Clostridioides difficile-associated diarrhea (CDAD)","Development of bacterial resistance with repeated use","Use with caution in renal impairment (creatinine clearance < 30 mL/min may reduce efficacy)","Oral formulation should not be used for pyelonephritis or perinephric abscess"] |
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| Fetal Monitoring | Monitor for maternal gastrointestinal adverse effects (nausea, diarrhea). Assess for signs of hypersensitivity. In prolonged use, monitor renal function and electrolyte balance. No specific fetal monitoring required. |
| Fertility Effects | No known adverse effects on human fertility. Animal studies show no impairment of fertility. |