Fosfomycin Trometamol

1. Indications

Fosfomycin Trometamol is a broad-spectrum bactericidal antibiotic primarily used for urinary tract infections (UTIs).

Approved Indications:

• Acute Uncomplicated Cystitis:
• Treatment of bladder infections in adult women caused by Escherichia coli or Enterococcus faecalis.
• Prophylaxis:
• Prevention of recurrent UTIs in susceptible patients.

Off-label / Clinically Accepted Uses:

• UTIs in elderly men, often as part of a tailored therapy when resistance limits other options.
• Certain complicated urinary infections in combination with other antibiotics.
• Occasional use for neonatal or pediatric UTIs in selected cases under specialist supervision.

Adults:

• Standard dose: Single oral dose of 3 g, dissolved in water.
• Frequency: Usually single-dose therapy; repeat dosing only if clinically necessary.

Pediatrics:

• Not commonly used in children under 12 years; dosing must be weight-based and guided by a specialist.

Special Populations:

• Elderly: Single-dose regimen usually sufficient; monitor renal function.
• Renal impairment: Use with caution; dose adjustment may be required in severe renal impairment.
• Hepatic impairment: No dose adjustment required.

Administration Route:

• Oral solution: Dissolve the contents of the sachet in water before ingestion.
• Take on an empty stomach or 2–3 hours after meals for optimal absorption.

Fosfomycin Trometamol exerts bactericidal activity by inhibiting bacterial cell wall synthesis. It irreversibly inactivates the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), which catalyzes the initial step in peptidoglycan biosynthesis. This inhibition prevents formation of the bacterial cell wall, leading to cell lysis and death. Fosfomycin enters bacterial cells through glycerophosphate and hexose-6-phosphate transport systems, ensuring high intracellular concentrations, particularly in urinary tract pathogens.

• Absorption: Rapid absorption from the gastrointestinal tract; oral bioavailability ~30–40%.
• Distribution: Concentrates in urine at high bactericidal levels; low plasma protein binding (<5%).
• Metabolism: Minimal hepatic metabolism; primarily excreted unchanged.
• Half-life: 4–5 hours in adults with normal renal function; prolonged in renal impairment.
• Excretion: Mainly via urine (~90% within 24 hours); minor fecal excretion.
• Onset of Action: Rapid bactericidal effect within hours after administration.

• Pregnancy: Animal studies show no teratogenicity; limited human data suggest low risk. Use only if benefits outweigh potential risks (Category B).
• Lactation: Excreted in breast milk in small amounts; caution advised. Monitor infants for gastrointestinal disturbances.

• Primary Class: Antibiotic
• Subclass: Phosphonic acid derivative; cell wall synthesis inhibitor

• Known hypersensitivity to fosfomycin or any excipients.
• History of severe allergic reactions to antibiotics may require caution.
• Oral form contraindicated in patients with severe renal impairment without adjustment.

• Renal impairment: Monitor kidney function; adjust dosing in severe cases.
• Gastrointestinal effects: Diarrhea may indicate Clostridioides difficile infection; discontinue if severe.
• Hypersensitivity reactions: Rare anaphylaxis; discontinue immediately if it occurs.
• High-risk patients: Elderly, severely ill, or immunocompromised patients require careful monitoring.
• Recurrent UTIs: Investigate underlying causes to prevent repeated infections.

Common:

• Gastrointestinal: Diarrhea, nausea, abdominal pain, vomiting.
• Headache and dizziness (rare).

Serious / Rare:

• Hypersensitivity reactions including rash, urticaria, and anaphylaxis.
• Pseudomembranous colitis (rare).
• Electrolyte disturbances such as hypokalemia or hypernatremia with prolonged therapy.

Timing & Severity:

• GI effects typically appear within hours; generally mild and self-limiting.
• Severe hypersensitivity or colitis can occur after first dose.

• Nephrotoxic drugs: Monitor renal function; additive renal toxicity is possible.
• Antacids / Oral calcium or iron supplements: May reduce absorption; separate dosing by at least 2–3 hours.
• Live vaccines: May reduce efficacy of live bacterial vaccines if administered concomitantly.
• Other antibiotics: Generally compatible; combination therapy may be indicated for multi-drug-resistant infections.

• Fosfomycin Trometamol is recommended as first-line therapy for uncomplicated UTIs in adult women due to single-dose convenience and low resistance rates.
• Increasingly used in multidrug-resistant infections, particularly ESBL-producing E. coli.
• Updated guidelines emphasize monitoring renal function and proper patient selection to prevent recurrence and resistance development.

• Store at 20°C to 25°C (room temperature).
• Protect from moisture and light; do not freeze.
• Keep in original packaging until use; dissolve powder completely in water before ingestion.
• Avoid storing in bathroom or humid environments.