Fetroja Dosing for CrCl 26 mL/min
For a patient with CrCl 26 mL/min, the recommended dose of Fetroja (cefiderocol) is 1 gram intravenously every 8 hours, infused over 3 hours. 1
Dosing Rationale
The FDA label explicitly specifies that patients with CrCl 15-29 mL/min require dose reduction to 1 gram every 8 hours over 3-hour infusion. 1 This patient with CrCl 26 mL/min falls directly within this renal function category and requires this specific dose adjustment.
Key Dosing Parameters by Renal Function
- CrCl 30-59 mL/min: 1.5 grams every 8 hours over 3 hours 1
- CrCl 15-29 mL/min: 1 gram every 8 hours over 3 hours 1
- CrCl <15 mL/min (with or without hemodialysis): 0.75 grams every 12 hours over 3 hours 1
Critical Clinical Considerations
Creatinine clearance must be calculated using the Cockcroft-Gault equation, as this is the method specified in the FDA labeling for dose adjustment decisions. 1
For patients with fluctuating renal function, the FDA label recommends monitoring CrCl and adjusting dosage accordingly. 1 This is particularly important in critically ill patients where renal function may change rapidly.
Pharmacokinetic Basis for Dose Adjustment
- Cefiderocol is primarily renally eliminated (61-71% excreted unchanged), making dose adjustment essential in renal impairment. 2
- Renal impairment significantly impacts AUC and half-life without affecting Cmax, supporting the need for dose reduction rather than interval extension alone. 3
- In patients with severe renal impairment (CrCl 15-29 mL/min), the AUC increases approximately 2.5-fold compared to normal renal function. 3
Treatment Duration and Monitoring
The recommended duration of treatment is 7-14 days, guided by the patient's clinical status. 1
Population pharmacokinetic analyses demonstrate that the percentage of time free drug concentrations exceed the MIC (%fT>MIC) was 100% in most patients at recommended doses, supporting adequate exposure even with renal dose adjustments. 4
Common Pitfalls to Avoid
- Do not use standard 2 gram every 8 hours dosing in patients with CrCl <60 mL/min, as this will result in drug accumulation and potential toxicity. 1
- Do not estimate renal function using methods other than Cockcroft-Gault, as the FDA dosing table is specifically based on this calculation method. 1
- Do not shorten the 3-hour infusion time, as this is the validated infusion duration for achieving optimal pharmacodynamic targets. 1
- If the patient requires hemodialysis in the future, remember that cefiderocol is removed by dialysis (approximately 60% removed during 3-4 hour session), and dosing should be administered immediately after HD completion. 1, 3