How to dose Zerbaxa (ceftolozane and tazobactam) in a patient with impaired renal function and elevated Blood Urea Nitrogen (BUN) levels?

Dosing Zerbaxa in Renal Impairment with Elevated BUN

Dose Zerbaxa based on creatinine clearance (CrCl), not BUN levels, using the FDA-approved renal dosing adjustments that reduce both dose and maintain frequency at every 8 hours. 1

Key Principle: CrCl Determines Dosing, Not BUN

• BUN alone is not used to guide Zerbaxa dosing—you must calculate CrCl using the Cockcroft-Gault formula to determine the appropriate dose adjustment. 1
• Elevated BUN may indicate renal impairment, but CrCl provides the quantitative measure needed for precise dose adjustment. 1

FDA-Approved Dosing Algorithm for Adults with Renal Impairment

For Complicated Intra-abdominal Infections (cIAI) and Complicated Urinary Tract Infections (cUTI):

• CrCl 30-50 mL/min: 750 mg (500 mg ceftolozane/250 mg tazobactam) IV every 8 hours 1
• CrCl 15-29 mL/min: 375 mg (250 mg ceftolozane/125 mg tazobactam) IV every 8 hours 1
• End-stage renal disease on hemodialysis: Loading dose of 750 mg, then 150 mg (100 mg/50 mg) IV every 8 hours; administer after dialysis on dialysis days 1

For Hospital-Acquired/Ventilator-Associated Bacterial Pneumonia (HABP/VABP):

• CrCl 30-50 mL/min: 1.5 g (1 g ceftolozane/0.5 g tazobactam) IV every 8 hours 1
• CrCl 15-29 mL/min: 750 mg (500 mg ceftolozane/250 mg tazobactam) IV every 8 hours 1
• End-stage renal disease on hemodialysis: Loading dose of 2.25 g, then 450 mg (300 mg/150 mg) IV every 8 hours; administer after dialysis on dialysis days 1

Pharmacokinetic Rationale

• Ceftolozane and tazobactam are renally cleared, with plasma exposure increasing proportionally as renal function declines. 2
• In moderate renal impairment (CrCl 30-50 mL/min), AUC increases 2.5-fold for ceftolozane and 2.2-fold for tazobactam compared to normal renal function. 2
• In severe renal impairment (CrCl 15-29 mL/min), dose-normalized AUC increases 4.4-fold for ceftolozane and 3.8-fold for tazobactam. 2

Critical Monitoring Requirements

• Monitor CrCl at least daily in patients with changing renal function and adjust Zerbaxa dosing accordingly. 1
• The 8-hour dosing interval is maintained across all renal function categories to preserve time-dependent beta-lactam pharmacodynamics. 1

Special Populations

Hemodialysis Patients:

• Both ceftolozane and tazobactam are significantly removed by hemodialysis (approximately 66% and 56% reduction in exposure, respectively). 2
• Always administer the dose at the earliest possible time following completion of dialysis. 1

Continuous Renal Replacement Therapy (CRRT):

• While not included in FDA labeling, research suggests doses of 750-1,500 mg every 8 hours may be appropriate depending on effluent flow rates. 3
• CRRT clearance approximates effluent flow rates, with no significant drug adsorption to hemofilters. 3

Common Pitfalls to Avoid

• Do not use BUN alone to guide dosing—always calculate CrCl using Cockcroft-Gault formula. 1
• Do not extend the dosing interval beyond 8 hours even in severe renal impairment; instead, reduce the dose while maintaining frequency. 1
• Do not skip the loading dose in ESRD patients—the loading dose ensures rapid achievement of therapeutic concentrations. 1
• Do not administer before hemodialysis—timing after dialysis prevents premature drug removal and facilitates directly observed therapy. 1