Cefepime Dosing in Renal Impairment
Cefepime requires dose adjustment in renal impairment by reducing dosing frequency while maintaining the milligram dose strength, as approximately 85% is renally excreted and accumulation leads to significant neurotoxicity risk. 1
Pharmacokinetic Rationale
- Cefepime elimination half-life increases from 2 hours in normal renal function to 13.5 hours in hemodialysis patients, necessitating interval extension rather than dose reduction 1, 2
- Total body clearance decreases proportionally with creatinine clearance, with significant linear correlation between the two parameters 2
- Peak concentrations (Cmax) remain unaffected by renal impairment (63.5-73.9 mcg/mL), but drug accumulation occurs with repeated dosing 2
- Volume of distribution remains stable at approximately 20 L regardless of renal function 2
Specific Dosing Recommendations by Renal Function
For patients with creatinine clearance <30 mL/min:
- Extend dosing interval to maintain concentration-dependent bactericidal activity 3
- The FDA label provides specific dose adjustments based on creatinine clearance, though exact recommendations require consultation of the full prescribing information 1
For hemodialysis patients:
- Administer cefepime after dialysis sessions to facilitate directly observed therapy and prevent premature drug removal 3
- Hemodialysis significantly shortens elimination half-life from 13.5 hours to 2.3 hours during dialysis 2
- Cefepime is effectively removed by hemodialysis, unlike rifampin which is not dialyzable 4
For continuous kidney replacement therapy (CKRT):
- Clearance averages 3.0 L/h/70 kg with effluent flows of 2603 mL/1.73 m²/h 5
- Standard dosing may fail to achieve stringent pharmacodynamic targets (100% fT > 4× MIC) 5
Critical Neurotoxicity Warning
Cefepime-induced encephalopathy is a serious, underrecognized complication that can occur even with appropriate dose adjustments:
- Neurotoxicity manifests as altered mental status, seizures, myoclonus, and encephalopathy 6, 7, 8
- Risk is highest in elderly patients and those with chronic uremia, who may require doses lower than standard renal-adjusted recommendations 7
- Toxicity has been reported even in patients receiving 50% of the recommended dose for renal impairment 7
- Immediate discontinuation and urgent hemodialysis can rapidly reverse neurotoxicity 7
Monitoring Requirements
- Monitor serum drug concentrations in severe renal impairment to avoid toxicity 3
- Assess neurological status closely in elderly hemodialysis patients, as they are particularly vulnerable 7
- Consider alternative cephalosporins with hepatic elimination (cefotaxime, ceftriaxone) or meropenem in high-risk patients 7
Common Pitfalls to Avoid
- Do not reduce the milligram dose amount while maintaining daily frequency, as this compromises concentration-dependent killing 3
- Do not administer before hemodialysis, as this removes drug and reduces efficacy 3
- Do not assume standard renal dosing is safe in very elderly patients with chronic uremia—consider further dose reduction or alternative agents 7
- Do not overlook subtle neurological changes as early signs of neurotoxicity, particularly confusion or myoclonus 6, 8