What is the dose adjustment for Fosfomycin in severe renal impairment?

Fosfomycin Dosing in Severe Renal Impairment (eGFR 23)

Fosfomycin can be used at standard doses in severe renal impairment without dose reduction, as urinary concentrations remain therapeutic even with significantly impaired kidney function, though plasma half-life will be prolonged and close monitoring is warranted.

Pharmacokinetic Considerations in Severe Renal Impairment

• Fosfomycin is eliminated almost exclusively by glomerular filtration, making it highly dependent on renal function 1, 2
• In patients with severe renal impairment (eGFR 23 ml/min), plasma half-life increases substantially from the normal 1.9 hours to potentially 25 hours or more 3
• Despite reduced renal clearance, urinary concentrations remain consistently above 100 mcg/ml even in patients with very high plasma creatinine, maintaining therapeutic efficacy for urinary tract infections 4
• The volume of distribution (approximately 0.3 L/kg in healthy volunteers) may be altered in patients with renal impairment, though fosfomycin's hydrophilic nature and negligible protein binding limit this effect 1, 2

Dosing Recommendations

For urinary tract infections: Standard oral dosing of fosfomycin 3 grams as a single dose can be maintained without adjustment, as urinary concentrations remain therapeutic regardless of renal function 4

For systemic infections (intravenous): The evidence suggests that daily dosage can remain unchanged despite the degree of renal insufficiency, given fosfomycin's absence of renal and systemic toxicity 4. However, for severe infections requiring IV therapy:

• Standard dosing regimens of 4-8 grams every 6-12 hours have been studied primarily in patients with normal renal function 1
• With eGFR 23, expect plasma concentrations to be significantly elevated (potentially 2-3 fold higher) and half-life prolonged 3, 5
• Consider extending dosing intervals to every 12-24 hours rather than reducing the milligram dose to maintain concentration-dependent bactericidal activity, similar to principles used for aminoglycosides in renal impairment 6

Monitoring Strategy

• Baseline renal function assessment with serum creatinine and eGFR calculation 6
• Monitor renal function closely during treatment, checking creatinine at minimum every 3-7 days, as fosfomycin accumulation could theoretically worsen renal function 6
• If renal function deteriorates further during therapy, consider interrupting treatment and reassessing the risk-benefit ratio 6
• Clinical response monitoring is essential, as therapeutic drug monitoring for fosfomycin is not routinely available in most centers 2

Critical Pitfalls to Avoid

• Do not assume fosfomycin is contraindicated in renal impairment - unlike sofosbuvir and other renally-eliminated drugs that have strict eGFR cutoffs, fosfomycin maintains urinary efficacy even with severe renal dysfunction 4
• Avoid reducing the milligram dose excessively - this may compromise antimicrobial efficacy, as fosfomycin exhibits concentration-dependent killing 1
• Do not use fosfomycin monotherapy for serious systemic infections with organisms having MICs >64 mg/L, as even optimized dosing may not achieve adequate PK/PD targets 1
• Be cautious with concurrent nephrotoxic agents - while fosfomycin itself has minimal nephrotoxicity, combining it with other nephrotoxic drugs in a patient with eGFR 23 increases risk 4

Hemodialysis Considerations

If the patient progresses to requiring hemodialysis:

• Fosfomycin is dialyzable, with conventional hemodialysis removing approximately 37-38% of a dose 3
• Administer doses after hemodialysis sessions to prevent premature drug removal 6, 7
• Consider supplemental dosing post-dialysis if treating systemic infections 3