Zavicefta (Ceftazidime-Avibactam) Dosing in Chronic Kidney Disease
Zavicefta requires dose reduction in patients with moderate to severe renal impairment (CrCl ≤50 mL/min) because both ceftazidime and avibactam are eliminated almost exclusively by the kidneys, and failure to adjust dosing results in significantly increased drug exposure and potential toxicity. 1, 2
Standard Dosing (Normal Renal Function)
- CrCl >50 mL/min: 2.5 grams (2 grams ceftazidime/0.5 grams avibactam) IV every 8 hours as a 2-hour infusion 1, 3
- No dose adjustment needed for patients with hepatic impairment 1, 2
Dose Adjustments by Renal Function
Moderate Renal Impairment
- CrCl 31-50 mL/min: 1.25 grams (1 gram ceftazidime/0.25 grams avibactam) IV every 8 hours 1
- This adjustment compensates for the 2.6-fold increase in avibactam exposure and prolonged ceftazidime half-life 1, 4
Severe Renal Impairment
- CrCl 16-30 mL/min: 0.94 grams (0.75 grams ceftazidime/0.19 grams avibactam) IV every 12 hours 1
- Avibactam exposure increases 3.8-fold in this population 1
Very Severe Renal Impairment
- CrCl 6-15 mL/min: 0.94 grams (0.75 grams ceftazidime/0.19 grams avibactam) IV every 24 hours 1
- Avibactam exposure increases 7-fold compared to normal renal function 1, 4
End-Stage Renal Disease (ESRD) on Hemodialysis
- Loading dose: 2.5 grams (2 grams ceftazidime/0.5 grams avibactam) IV as a single dose 1
- Maintenance: 0.94 grams (0.75 grams ceftazidime/0.19 grams avibactam) IV every 48 hours 1
- Critical timing: Administer after hemodialysis on dialysis days, as approximately 55% of avibactam is removed during a 4-hour hemodialysis session 1, 4
Monitoring Requirements
- Monitor creatinine clearance at least daily in patients with renal impairment and adjust dosing accordingly, as both drug exposures are highly dependent on renal function 1
- The 4:1 ratio of ceftazidime to avibactam is maintained across all dose adjustments because both drugs have similar linear relationships between clearance and creatinine clearance 4, 3
Pediatric Considerations (≥2 Years Old)
- Dose adjustments for pediatric patients aged 2 to <18 years with eGFR ≤50 mL/min/1.73 m² follow proportional reductions similar to adults 1, 5
- Insufficient data exists to recommend dosing for children <2 years old with renal impairment 1, 5
Critical Pitfalls to Avoid
- Do not use standard dosing in patients with CrCl ≤50 mL/min, as avibactam exposure can increase up to 19.5-fold in ESRD patients receiving post-dialysis doses without adjustment 1, 4
- Avoid dosing immediately before hemodialysis, as this results in premature drug removal and subtherapeutic levels 1
- Renal function can fluctuate rapidly in acute illness; some evidence suggests that premature dose reduction in acute kidney injury (which may resolve within 48 hours) could lead to treatment failure, though this remains controversial 6