Renal Dose Adjustment for Cefixime
Yes, cefixime requires dose adjustment in patients with creatinine clearance less than 60 mL/min. 1
Dosing Recommendations by Renal Function
The FDA-approved labeling explicitly states that dose adjustment is required when creatinine clearance falls below 60 mL/min 1. This threshold is more conservative than many other cephalosporins, which typically require adjustment only at lower clearance levels.
Specific Adjustments Based on Creatinine Clearance:
- CrCl ≥60 mL/min: Standard dosing (no adjustment needed) 1
- CrCl 21-60 mL/min: Reduce dose to 75% of standard dose 2
- CrCl <20 mL/min: Reduce dose to 50% of standard dose (200 mg daily instead of 400 mg) 3, 2
Pharmacokinetic Rationale
The need for dose adjustment stems from cefixime's dual elimination pathway. Approximately 40% of the drug is cleared renally unchanged, while 60% undergoes hepatic clearance 3. In patients with severe renal impairment (CrCl <20 mL/min), the elimination half-life increases from 3-4 hours to 12-14 hours 2. This prolonged half-life creates risk for drug accumulation with standard dosing 2.
Peak serum concentrations (Cmax) remain relatively unchanged across renal function levels, but the area under the curve (AUC) increases significantly as renal function declines 2, 4. This pattern supports extending dosing intervals or reducing total daily dose rather than maintaining standard regimens.
Dialysis Considerations
Hemodialysis:
- Hemodialysis removes only an insignificant fraction of cefixime from the body 4
- No supplemental dose is necessary after hemodialysis 4
- Patients should be monitored carefully while on dialysis 1
Peritoneal Dialysis:
- Continuous ambulatory peritoneal dialysis (CAPD) removes approximately 1.57% of the cefixime body burden over 72 hours 4
- No supplemental dosing required for CAPD patients 4
Important Clinical Considerations
The bioavailability of cefixime is approximately 40-50%, and this does not change with renal impairment 3. However, protein binding (normally 70%) may be altered in uremic patients 3.
Despite reduced renal clearance, urinary concentrations of cefixime remain above the MIC for most urinary tract pathogens for up to 24 hours post-dose, even in severe renal insufficiency 4. This makes cefixime a viable option for urinary tract infections in patients with compromised renal function, provided appropriate dose adjustments are made.
Key Pitfall to Avoid:
Do not wait until CrCl drops below 20 mL/min to adjust dosing. The FDA label specifies adjustment at CrCl <60 mL/min 1, which is earlier than many clinicians might expect based on experience with other beta-lactams. Research data confirms that pharmacokinetic alterations become statistically significant below 20 mL/min 4, but the conservative FDA threshold of 60 mL/min provides an appropriate safety margin.
Patients with cirrhosis require no dose adjustment despite a twofold increase in elimination half-life (approximately 6.5 hours), as hepatic clearance compensates adequately 3.