Zavicefta (Ceftazidime-Avibactam) Infusion Stability and Preparation
Preparation and Dilution
Zavicefta should be reconstituted and diluted to achieve concentrations between 8 mg/mL and 40 mg/mL for ceftazidime (with corresponding avibactam concentrations of 2 mg/mL to 10 mg/mL), and the constituted solution must be transferred to an infusion bag within 30 minutes of reconstitution. 1
Reconstitution Steps:
- After constitution with appropriate diluent, hold the constituted solution for no longer than 30 minutes prior to transfer and dilution in a suitable infusion bag 1
- Compatible diluents include: 0.9% sodium chloride, 5% dextrose, combinations of dextrose and sodium chloride (up to 2.5% dextrose and 0.45% sodium chloride), and lactated Ringer's injection 1
Infusion Duration
The standard infusion duration is 2-3 hours for the 2.5 g dose administered every 8 hours. 2
- For patients with normal renal function (CrCl >50 mL/min), the standard dose of 2.5 g IV every 8 hours over 2-3 hours is recommended 2
- Extended infusion of 3 hours has been associated with improved 30-day survival in patients with KPC-producing infections 3
- For severe infections requiring higher PK/PD targets, infusion duration may need to be extended to 3-4 hours to achieve 100% time above MIC 4
Stability Limits
Room Temperature Storage:
Diluted Zavicefta solutions are stable for 12 hours when stored at room temperature (21-23°C). 1
Refrigerated Storage:
Diluted solutions may be refrigerated at 2-8°C for up to 24 hours, followed by an additional 12 hours at room temperature (total 36 hours maximum from dilution). 1
Key Stability Points:
- The 30-minute time limit after constitution is critical before transfer to infusion bag 1
- Once diluted in the infusion bag, the solution maintains stability for 12 hours at room temperature 1
- If refrigerated immediately after dilution, the solution can be stored for 24 hours, then must be used within 12 hours after returning to room temperature 1
Dosing Adjustments
Standard Dosing:
- CrCl >50 mL/min: 2.5 g IV every 8 hours 2
- Dose reduction required for moderate to severe renal impairment per FDA labeling to prevent neurotoxicity 2
Special Populations:
- For patients on hemodialysis, administer after dialysis as approximately 55% of avibactam is removed during a 4-hour session 2
- In critically ill patients receiving continuous venovenous hemodiafiltration, 2.5 g infused over 2 hours every 8 hours achieves appropriate PK/PD targets 5
Important Caveats
- Monitor for neurotoxicity (seizures, encephalopathy, confusion), particularly in patients with renal impairment, due to risk of beta-lactam accumulation 2
- The highest concentration (40 mg/mL ceftazidime/10 mg/mL avibactam) should not be used during Y-site co-administration with other drugs 1
- For severe infections or augmented renal clearance, consider extended infusion times (3-4 hours) or continuous infusion to optimize PK/PD targets 4, 6