What is the recommended dosing for Cefepime (Cefepime) in patients with varying degrees of renal function, including those with normal renal function and impaired renal function?

Cefepime Dosing in Patients with Varying Renal Function

Cefepime dosing should be adjusted based on renal function, with standard dosing of 1-2g every 8-12 hours for patients with normal renal function, while patients with impaired renal function require dose reduction to prevent neurotoxicity. 1

Dosing for Normal Renal Function

• For adults with normal renal function (CrCl >60 mL/min), the recommended dosing is 1-2g every 8-12 hours depending on the severity of infection 1
• In critically ill patients with normal renal function, higher doses may be required initially due to increased clearance and volume of distribution, with 2g every 8 hours often recommended 2
• For pediatric patients with normal renal function, the recommended dose is 50 mg/kg every 8-12 hours (not to exceed 2g per dose) 2

Dosing for Impaired Renal Function

Moderate Renal Impairment

• For patients with CrCl 30-60 mL/min: 1-2g every 12-24 hours 1
• Dose adjustment is necessary as cefepime is primarily excreted unchanged by the kidneys (approximately 85% of the administered dose) 1

Severe Renal Impairment

• For patients with CrCl 11-29 mL/min: 1g every 24 hours 1
• For patients with CrCl ≤10 mL/min: 0.5g every 24 hours 1
• Patients on hemodialysis require 1g on day 1, followed by 0.5g every 24 hours, with supplemental doses after dialysis 1

Considerations for Neurotoxicity Risk

• Cefepime has a higher risk of neurotoxicity compared to many other beta-lactams, with a relative pro-convulsive activity of 160 (compared to penicillin G at 100) 2

• Risk factors for cefepime-induced neurotoxicity include:

  • Advanced age (>65 years) 3
  • Renal impairment or acute kidney injury during treatment 3
  • ICU admission 3
  • Excessive plasma concentrations (trough levels >22 mg/L) 2

• To minimize neurotoxicity risk, free plasma concentrations should not exceed eight times the MIC of the targeted pathogen 2

Special Populations

Critically Ill Patients

• Consider higher initial doses due to increased clearance and volume of distribution 2
• For severe infections like hospital-acquired pneumonia, 1-2g every 8 hours is recommended 2
• For intra-abdominal infections in critically ill patients, 2g every 8 hours is recommended 2

Pediatric Patients

• For children, the recommended dose is 50 mg/kg every 8-12 hours (maximum 2g per dose) 2
• Pediatric pharmacokinetics are similar to adults when adjusted for weight 1
• A 50 mg/kg dose in a pediatric patient provides comparable exposure to a 2g dose in adults 1

Elderly Patients

• Dosage adjustment is necessary in elderly patients with decreased creatinine clearance 1
• Elderly patients have a higher risk of cefepime-induced neurotoxicity, requiring careful monitoring 3

Administration Methods

• For severe infections, especially with pathogens having high MICs, prolonged or continuous infusions may improve efficacy 2
• Extended infusion over 3-4 hours may optimize pharmacokinetic/pharmacodynamic parameters 2
• Continuous infusion appears to provide higher efficacy with lower risk of neurotoxicity in critically ill patients 4

Monitoring Recommendations

• Therapeutic drug monitoring should be considered in critically ill patients, especially those with fluctuating renal function 2
• Monitor for signs of neurotoxicity, including confusion, encephalopathy, myoclonus, and seizures 2
• Regular assessment of renal function is essential, as acute kidney injury significantly increases the risk of neurotoxicity 3

By following these dosing recommendations and monitoring parameters, clinicians can optimize cefepime therapy while minimizing the risk of adverse effects, particularly neurotoxicity in patients with impaired renal function.