Is Fosfomycin (Monurol) safe to use in a patient with Acute Kidney Injury (AKI)?

Fosfomycin Use in Acute Kidney Injury

Fosfomycin can be used in patients with AKI, but requires dose adjustment based on renal function and dialysis status, as it is eliminated almost entirely by glomerular filtration and accumulates significantly in renal impairment. 1

Safety Profile in AKI

• Fosfomycin is recommended as a first-line agent for UTI treatment but requires dose adjustment in AKI. 2
• The FDA label confirms that in patients with renal impairment (creatinine clearance 7-54 mL/min), the half-life of fosfomycin increases dramatically from 11 hours to 50 hours, and urinary recovery decreases from 32% to 11%, indicating that renal impairment significantly decreases fosfomycin excretion. 1
• In anuric patients undergoing hemodialysis, the elimination half-life extends to 40 hours, demonstrating substantial drug accumulation. 1

Dosing Recommendations

For Non-Dialysis AKI Patients

• The standard oral dose of 3 grams as a single sachet may need to be avoided or used with extreme caution in severe AKI (CrCl <30 mL/min), as the drug will accumulate significantly with prolonged half-life up to 50 hours. 1
• Monitor renal function closely during antibiotic therapy, as recommended for all patients with AKI receiving antibiotics. 2

For Patients on Dialysis

• For patients undergoing prolonged intermittent renal replacement therapy (PIRRT), fosfomycin is eliminated rapidly with a dialyzer clearance of 183 mL/min, removing approximately 74% of the initial dose. 3
• A loading dose of 8 grams followed by maintenance doses of 5 grams after each dialysis session is recommended for anuric patients on slow-extended daily dialysis (SLEDD). 4
• For patients on PIRRT with dialysis intensity of 1.5 L/h, dosing of 5 g every 8 hours is required to maintain adequate plasma levels, though drug accumulation may occur depending on dialysis frequency. 3
• Therapeutic drug monitoring is strongly recommended in critically ill patients with AKI undergoing dialysis therapy, as fosfomycin serum concentrations exhibit wide variability. 4

Critical Considerations

• Avoid combining fosfomycin with other nephrotoxic medications, particularly the "triple whammy" of NSAIDs + diuretics + ACE inhibitors/ARBs, which more than doubles AKI risk. 5, 6
• Obtain urine culture before starting antibiotics to guide definitive therapy, and only use antibiotics when infection is strongly suspected. 2
• Fosfomycin is not inherently nephrotoxic and does not cause direct tubular toxicity, making it safer than aminoglycosides or vancomycin in patients with compromised renal function. 5
• The oral bioavailability of fosfomycin is reduced to 30% under fed conditions, though it can be taken without regard to food as urinary concentrations remain therapeutic. 1

Monitoring Requirements

• Establish intensive monitoring during acute AKI phase, including daily eGFR and serum creatinine measurements. 6
• Monitor for drug accumulation signs, particularly in patients not receiving dialysis or with infrequent dialysis sessions. 3
• Ensure adequate hydration when administering fosfomycin, particularly in patients at risk for crystal nephropathy. 5

When to Avoid

• Do not treat asymptomatic bacteriuria in patients with AKI, as this increases unnecessary antibiotic exposure. 2
• Exercise extreme caution in severe AKI (CrCl <15 mL/min) without dialysis support, as drug accumulation will be substantial. 1