How is fosfomycin dosing affected in patients with impaired renal (kidney) function?

Fosfomycin Dosing in Kidney Disease

No dose adjustment is necessary for fosfomycin in patients with renal impairment, including those with severe kidney disease or on dialysis, though drug accumulation occurs and monitoring for toxicity is prudent. 1

Pharmacokinetics in Renal Impairment

The FDA label provides clear guidance on fosfomycin behavior in kidney disease:

• Half-life increases dramatically with declining renal function: from 11 hours (CrCl 54 mL/min) to 50 hours (CrCl 7 mL/min), and up to 40 hours in anuric patients on hemodialysis 1
• Urinary recovery decreases from 32% to 11% as renal function declines, indicating significantly reduced renal excretion 1
• Despite reduced excretion, urinary concentrations remain therapeutic (>100 mcg/mL) for extended periods even in severe renal insufficiency 2

Dosing Recommendations by Renal Function

Mild to Moderate Renal Impairment (CrCl >30 mL/min)

• Standard 3-gram single dose requires no adjustment 1
• Urinary concentrations remain well above MIC for typical uropathogens 3

Severe Renal Impairment (CrCl <30 mL/min)

• No dose reduction recommended by FDA labeling 1
• Urinary concentrations remain therapeutic (>100 mcg/mL) regardless of creatinine level 2
• In elderly patients with mean CrCl 40 mL/min, urinary levels exceeded 1,383 mg/L in first 12 hours and remained >165 mg/L at 36-48 hours 3
• 37% of dose recovered unchanged in urine over 84 hours despite impaired function 3

Hemodialysis Patients

• Standard 3-gram dose for uncomplicated UTI 1
• For serious systemic infections requiring IV therapy: 5 grams every 8 hours is needed due to significant dialytic removal 4
• Dialysis removes approximately 74% of administered dose with median clearance of 183 mL/min 4
• Drug accumulation occurs between dialysis sessions, with Cmax increasing from 267 to 926 mg/L after multiple doses 4

Critical Clinical Considerations

Common pitfall: The lack of dose adjustment recommendation contradicts typical antibiotic dosing principles. This is because:

• Fosfomycin concentrates in urine even with minimal renal function 2
• The target site (urinary tract) maintains therapeutic levels despite reduced systemic clearance 3
• Systemic accumulation occurs but fosfomycin lacks significant renal or systemic toxicity 2

For oral therapy (uncomplicated UTI):

• Single 3-gram dose regardless of renal function 1
• Therapeutic urinary levels maintained for 48+ hours in renal impairment 3
• No adjustment needed even in dialysis patients 1

For IV therapy (serious infections):

• Patients on PIRRT require higher doses (5g q8h) due to dialytic clearance 4
• Monitor for accumulation with repeated dosing 4
• T>MIC remains 100% in dialysis patients despite removal 4

Monitoring Strategy

While dose adjustment isn't required, vigilance for drug accumulation is warranted:

• Elimination half-life extends 4-5 fold in severe renal impairment 1
• Wide variability in urinary recovery (15-60%) observed in elderly patients with renal dysfunction 3
• For IV therapy in dialysis patients, plasma levels increase substantially with repeated dosing 4