Zerbaxa Dosing in Renal Impairment
For adult patients with renal impairment, Zerbaxa requires dose reduction based on creatinine clearance, with specific adjustments for CrCl ≤50 mL/min, while pediatric patients with eGFR ≤50 mL/min/1.73m² should not receive Zerbaxa due to lack of established dosing. 1
Adult Dosing Adjustments by Renal Function
Moderate Renal Impairment (CrCl 30-50 mL/min)
- For cIAI and cUTI: 750 mg (ceftolozane 500 mg/tazobactam 250 mg) IV every 8 hours 1
- For HABP/VABP: 1.5 g (ceftolozane 1 g/tazobactam 0.5 g) IV every 8 hours 1
- All doses administered over 1 hour infusion 1
Severe Renal Impairment (CrCl 15-29 mL/min)
- For cIAI and cUTI: 375 mg (ceftolozane 250 mg/tazobactam 125 mg) IV every 8 hours 1
- For HABP/VABP: 750 mg (ceftolozane 500 mg/tazobactam 250 mg) IV every 8 hours 1
End-Stage Renal Disease on Hemodialysis
- For cIAI and cUTI: Single loading dose of 750 mg, followed by 150 mg (ceftolozane 100 mg/tazobactam 50 mg) maintenance dose every 8 hours 1
- For HABP/VABP: Single loading dose of 2.25 g (ceftolozane 1.5 g/tazobactam 0.75 g), followed by 450 mg (ceftolozane 300 mg/tazobactam 150 mg) maintenance dose every 8 hours 1
- Critical timing: Administer doses at the earliest possible time following completion of hemodialysis 1
Monitoring Requirements
Monitor creatinine clearance at least daily in patients with changing renal function and adjust Zerbaxa dosage accordingly. 1 This is particularly important because:
- Zerbaxa is substantially excreted by the kidney, increasing the risk of adverse reactions in renal impairment 1
- Approximately 66% of ceftolozane and 56% of tazobactam are removed by hemodialysis 1
- The drug's pharmacokinetics are significantly influenced by renal function 2
Pediatric Considerations
Zerbaxa is not recommended in pediatric patients (birth to <18 years) with eGFR ≤50 mL/min/1.73m² because dosage adjustment has not been established in this population. 1 This represents a critical gap in pediatric dosing guidance that clinicians must recognize.
Important Clinical Pitfalls
Acute Kidney Injury Considerations
A substantial proportion of patients with infections present with acute kidney injury (AKI) on admission that may resolve within 48 hours 3. Premature dose reduction based on initial creatinine clearance in the setting of resolving AKI may lead to subtherapeutic dosing and reduced clinical response. 3 This is particularly relevant as ceftolozane/tazobactam carries precautionary statements for reduced clinical response in patients with baseline CrCl 30-50 mL/min 3.
Elderly Patients
Elderly patients are more likely to have decreased renal function, requiring careful dose selection based on renal function monitoring 1. The risk of adverse reactions is greater in this population due to reduced renal clearance 1.
Alternative Dosing Strategies
Research suggests that alternative regimens using full doses with extended intervals (every 12 or 24 hours) or prolonged infusions may achieve similar pharmacokinetic/pharmacodynamic targets in renal impairment 2, though these are not FDA-approved and would require clinical validation before implementation.
Creatinine Clearance Calculation
Use the Cockcroft-Gault formula to estimate creatinine clearance for dosing decisions, as specified in the FDA labeling 1. This is the standard referenced in the prescribing information despite other formulas potentially offering better accuracy in certain populations 4.