From the FDA Drug Label
In patients with varying degrees of renal impairment (creatinine clearances varying from 54 mL/min to 7 mL/min), the t1/2 of fosfomycin increased from 11 hours to 50 hours The percent of fosfomycin recovered in urine decreased from 32% to 11% indicating that renal impairment significantly decreases the excretion of fosfomycin.
The dosing of Fosfomycin 3g oral for UTI in 2 doses in patients with renal impairment is not directly addressed in the provided drug label. However, it is known that renal impairment significantly decreases the excretion of fosfomycin.
- The half-life of fosfomycin increases with decreasing renal function, which may lead to accumulation of the drug.
- No specific dosage adjustment is provided for patients with renal impairment, but it is essential to consider the reduced excretion and potential for accumulation when administering fosfomycin to these patients 1.
From the Research
For patients with renal impairment, fosfomycin dosing for UTI should be adjusted based on creatinine clearance, with the standard single 3g oral dose remaining appropriate for mild to moderate renal impairment (creatinine clearance >20 mL/min), and a reduced dose of 3g given as a single dose rather than multiple doses for severe renal impairment (creatinine clearance <20 mL/min). The question mentions two doses, but fosfomycin is typically administered as a single 3g sachet mixed with water for uncomplicated UTIs 2. For complicated UTIs, some clinicians use a regimen of 3g every 2-3 days for a total of 2-3 doses, but this is off-label 3. In renal impairment, drug clearance is reduced and the half-life is prolonged, which is why dose reduction or extended intervals between doses may be necessary 2. Fosfomycin achieves high urinary concentrations even in renal impairment, and its unique mechanism of action targeting bacterial cell wall synthesis makes it effective against many resistant pathogens in UTIs 4. Some studies suggest that fosfomycin is associated with fewer recurrences of UTI than other antibiotics, such as nitrofurantoin and co-trimoxazole, in patients with renal impairment 5. However, the evidence is limited, and more robust research is needed to confirm these findings 6. In clinical practice, the decision to adjust fosfomycin dosing in patients with renal impairment should be based on individual patient factors, including the severity of renal impairment and the presence of other comorbidities. Key considerations include:
- The patient's creatinine clearance and overall renal function
- The severity of the UTI and the presence of any complicating factors
- The potential for drug interactions and side effects
- The need for dose adjustment or alternative treatment options. Overall, fosfomycin remains a viable treatment option for UTIs in patients with renal impairment, but careful consideration of dosing and potential interactions is necessary to ensure optimal outcomes.