Cefuroxime Oral Dosing in CKD Stage 4
For patients with CKD stage 4 (creatinine clearance 15-29 mL/min), oral cefuroxime axetil should be dosed at 250-500 mg every 24 hours, representing a significant reduction from the standard twice-daily regimen. 1, 2
Renal Dose Adjustment Algorithm
The FDA-approved dosing for cefuroxime in renal impairment follows a clear stepwise approach based on creatinine clearance 1:
- CrCl >20 mL/min: Standard dosing (750 mg-1.5 g every 8 hours for IV; 250-500 mg every 12 hours for oral)
- CrCl 10-20 mL/min: 750 mg every 12 hours (IV formulation guidance)
- CrCl <10 mL/min: 750 mg every 24 hours (IV formulation guidance)
For oral cefuroxime axetil specifically in CKD stage 4 (CrCl 15-29 mL/min, which falls in the 10-49 mL/min range), pharmacokinetic studies demonstrate that the standard individual dose should be administered every 24 hours rather than the typical every 12 hours schedule 2.
Pharmacokinetic Rationale
The elimination half-life of cefuroxime increases dramatically with declining renal function 2:
- Normal renal function (CrCl >85 mL/min): T½ = 1.4 ± 0.33 hours
- Mild impairment (CrCl 50-84 mL/min): T½ = 2.4 ± 0.65 hours
- Moderate-severe impairment (CrCl 15-49 mL/min): T½ = 4.6 ± 2.32 hours
- Severe impairment (CrCl <15 mL/min): T½ = 16.8 ± 10.2 hours
The elimination rate constant correlates directly with creatinine clearance: kel (h⁻¹) = 0.0046 × CrCl + 0.0108 2. This linear relationship confirms that both systemic and renal clearance decrease proportionally with declining kidney function, necessitating interval extension rather than dose reduction alone 2.
Practical Dosing Recommendations
For CKD stage 4 patients (CrCl 15-29 mL/min):
- Mild-moderate infections: 250 mg orally every 24 hours 2
- More severe infections: 500 mg orally every 24 hours 2
- Uncomplicated UTIs: 125 mg every 24 hours may be sufficient (extrapolated from normal dosing) 3
The volume of distribution remains unchanged across all levels of renal function (0.82 ± 0.27 L/kg), so loading doses do not require adjustment—only the maintenance interval 2.
Critical Monitoring Considerations
Renal function must be monitored during therapy, as cefuroxime and other cephalosporins can occasionally cause acute renal failure, particularly in patients with pre-existing kidney disease 4. If renal function deteriorates further during treatment, the dosing interval should be extended to every 48 hours if CrCl falls below 10 mL/min 2.
Important Caveats
- These recommendations apply to oral cefuroxime axetil specifically; IV cefuroxime dosing follows similar principles but uses different absolute doses 1, 2
- The bioavailability of oral cefuroxime axetil is approximately 68% when taken with food, and absorption is enhanced by food intake 3
- For patients on hemodialysis, an additional dose should be administered after each dialysis session, as cefuroxime is dialyzable 1
- Protein binding (33%) is relatively low and unchanged in renal impairment, minimizing concerns about drug accumulation 3
Alternative Considerations
If more aggressive dosing is required for severe infections in CKD stage 4, consider switching to IV cefuroxime with appropriate renal dosing (750 mg every 12 hours for CrCl 10-20 mL/min) rather than increasing oral doses, as this provides more predictable pharmacokinetics 1.