Zavicefta (Ceftazidime-Avibactam) Dosage Adjustment in Renal Impairment
Zavicefta (ceftazidime-avibactam) dosage must be reduced in patients with renal impairment, with specific adjustments based on creatinine clearance, as both active components are primarily excreted by the kidneys. 1
Pharmacokinetic Considerations
- Both ceftazidime and avibactam are primarily eliminated by the kidneys, with approximately 80-90% of ceftazidime and 97% of avibactam excreted unchanged in the urine 1
- Avibactam clearance decreases significantly in renal impairment, resulting in 2.6-fold, 3.8-fold, and 7-fold increases in systemic exposure in mild, moderate, and severe renal impairment, respectively 1
- Ceftazidime's serum half-life is significantly prolonged in patients with impaired renal function 1
Recommended Dosage Adjustments
For Adult Patients:
| Creatinine Clearance | Recommended Dosage Regimen |
|---|---|
| >50 mL/min | Standard dose (2.5g q8h) |
| 31-50 mL/min | 1.25g q8h |
| 16-30 mL/min | 0.94g q12h |
| 6-15 mL/min | 0.94g q24h |
| ESRD on hemodialysis | 0.94g q48h (give after hemodialysis) |
- Renal function should be monitored at least daily in these patients, as exposure of both ceftazidime and avibactam is highly dependent on renal function 1
- Dose adjustments should be made promptly if changes in renal function occur 1
Special Considerations
- For patients on hemodialysis, approximately 55% of the avibactam dose is removed during a 4-hour hemodialysis session 1
- Administration of Zavicefta should occur after hemodialysis to avoid premature removal of the drug 1, 2
- Unlike some antibiotics where only the dosing interval is extended, Zavicefta requires both dose reduction and interval extension in severe renal impairment 1
Monitoring Recommendations
- Regular monitoring of renal function is essential for patients receiving Zavicefta, particularly those with fluctuating renal function 1
- Therapeutic drug monitoring may be considered in critically ill patients with unstable renal function 3
- Clinical response and potential adverse effects should be closely monitored in patients with renal impairment 1
Practical Approach
- Calculate creatinine clearance using the Cockcroft-Gault formula or other validated methods before initiating therapy 4
- Reassess renal function daily in hospitalized patients with unstable renal function 1
- Adjust dosage promptly when significant changes in renal function are observed 1
Unlike some other antibiotics where the dosing principles focus on maintaining the same dose but extending intervals, Zavicefta requires both dose reduction and interval adjustment due to the significant impact of renal function on both active components 1.