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. |
| Molecular Weight | 182.09 |
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 | Limited human data; animal studies show no teratogenicity at clinically relevant doses. Use only if clearly needed. |
| 2nd trimester | No evidence of fetal harm; use if benefits outweigh risks. |
| 3rd trimester | Consider risk of neonatal diarrhea due to alteration of gut flora; use with caution near term. |
Clinical note
Metoclopramide may decrease serum levels Generally well-tolerated with diarrhea being the most common side effect.
| Placental transfer | Fosfomycin crosses the placenta; animal studies show transfer, and human data indicate detectable levels in cord blood. |
| Breastfeeding | Fosfomycin is excreted into breast milk in low amounts; limited data suggest no adverse effects in infants. However, potential for diarrhea and alteration of infant gut flora. |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to fosfomycin or any component of the formulationSevere renal impairment (creatinine clearance <10 mL/min) for oral formulation (tromethamine salt)
| 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 |
| Food/Dietary | Avoid food intake within 1 hour before and 2 hours after administration; avoid calcium-rich foods (e.g., dairy products) and calcium-containing supplements as they can reduce absorption. |
Loading safety data…
| Lactation Rating |
| L2 - Safer |
| 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. |
| 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. |
| Clinical Pearls | Administer on an empty stomach (1 hour before or 2 hours after meals) to maximize absorption; dissolution in 90-120 mL of water is recommended; avoid concurrent calcium salts as they may reduce absorption; single-dose therapy is effective for uncomplicated UTIs; may be used in pregnancy (category B). |
| Patient Advice | Take exactly as prescribed, usually as a single dose. · Dissolve the powder in about 3-4 ounces of cold water; stir until dissolved and drink immediately. · Do not take with food; take on an empty stomach. · Avoid taking calcium supplements, antacids, or dairy products within 2-3 hours of dosing. · May cause diarrhea, which is usually mild and resolves; contact your doctor if severe or persistent. · Inform your doctor if you are pregnant or breastfeeding. |