Can Zerbaxa Cause Elevated BUN?
Yes, Zerbaxa (ceftolozane-tazobactam) can cause elevated BUN, particularly in patients with pre-existing renal impairment, as the drug is primarily renally excreted and plasma exposure increases substantially as kidney function declines.
Mechanism and Risk Factors
- Ceftolozane-tazobactam is eliminated almost entirely through renal excretion, making it highly dependent on kidney function for clearance 1
- Plasma exposure increases progressively with declining renal function: in moderate renal impairment, drug exposure (AUC) increases 2.5-fold for ceftolozane and 2.2-fold for tazobactam; in severe impairment, dose-normalized exposure increases 4.4-fold and 3.8-fold respectively 1
- Patients with pre-existing renal dysfunction are at highest risk for further deterioration of renal function and accumulation of nitrogenous waste products like BUN 2
Clinical Monitoring Requirements
- Serial assessment of residual renal function is critical during treatment, as further deterioration can occur even with appropriate dose adjustments 3
- Monitor BUN and creatinine levels closely, particularly in patients starting with creatinine clearance <50 mL/min 1
- Watch for signs of drug accumulation including confusion, encephalopathy, or other neurological symptoms that may indicate excessive drug levels in the setting of worsening renal function 3
Dose Adjustment Algorithm
- No adjustment needed for mild renal impairment (CrCl 50-80 mL/min), as exposure increases only 1.4-fold for ceftolozane 1
- Moderate renal impairment (CrCl 30-50 mL/min) requires dose reduction to achieve exposures within established safety margins 1
- Severe renal impairment (CrCl 15-29 mL/min) requires both dose reduction and frequency adjustment 1
- End-stage renal disease on hemodialysis: administer after dialysis sessions, as approximately 66% of ceftolozane and 56% of tazobactam are removed during dialysis 1
Important Clinical Caveats
- The elevation in BUN may reflect worsening renal function rather than direct nephrotoxicity from the drug itself, as ceftolozane-tazobactam was well-tolerated across all renal impairment groups in pharmacokinetic studies 1
- Successful treatment without worsening renal function has been documented in case series of patients with chronic kidney disease treated for complicated infections 2
- Therapeutic drug monitoring should be considered in patients with unstable or severe renal impairment to optimize dosing and minimize toxicity risk 3
- Avoid assuming the drug is directly nephrotoxic: unlike aminoglycosides or capreomycin which cause direct nephrotoxicity 4, beta-lactams like ceftolozane primarily accumulate in renal dysfunction rather than causing primary kidney injury