What is the dosing adjustment for Zavicefta (ceftazidime and avibactam) in patients with impaired renal function?

Zavicefta (Ceftazidime-Avibactam) Dosing in Renal Impairment

Zavicefta (ceftazidime-avibactam) requires specific dose adjustments based on the patient's renal function, with decreasing doses recommended as renal function declines.

Pharmacokinetic Considerations

Ceftazidime and avibactam are both primarily eliminated by the kidneys:

• Approximately 80-90% of ceftazidime is excreted unchanged by the kidneys within 24 hours 1
• About 97% of avibactam is recovered in urine, with 85% as unchanged drug 1
• Renal impairment significantly affects both drugs:
  • Ceftazidime's half-life is prolonged in renal impairment 1
  • Avibactam clearance decreases with declining renal function, leading to increased systemic exposure 1, 2

Recommended Dosing Adjustments

For Adults with Normal Renal Function (CrCl >50 mL/min):

• Standard dose: 2000 mg ceftazidime + 500 mg avibactam every 8 hours by 2-hour IV infusion 1, 3

For Adults with Renal Impairment:

Creatinine Clearance (CrCl)	Recommended Dose	Frequency
31-50 mL/min	1000 mg ceftazidime + 250 mg avibactam	Every 8 hours
16-30 mL/min	750 mg ceftazidime + 187.5 mg avibactam	Every 12 hours
6-15 mL/min	750 mg ceftazidime + 187.5 mg avibactam	Every 24 hours

For Patients on Hemodialysis:

• Administer Zavicefta after hemodialysis sessions 1, 2
• Approximately 55% of avibactam is removed during a 4-hour hemodialysis session 1
• Hemodialysis extraction coefficient for avibactam is 0.77 1

Special Considerations

1. Monitoring Requirements:

   • Monitor renal function (CrCl) at least daily in patients with changing renal function 1
   • Adjust dosage accordingly if renal function changes during treatment

2. Hepatic Impairment:

   • No dose adjustment is required for hepatic impairment 1
   • Avibactam does not undergo significant hepatic metabolism 1, 4

3. Acute Kidney Injury:

   • Be cautious about premature dose reduction in patients with acute kidney injury that may resolve quickly 5
   • Consider that 57.2% of AKI cases resolve within 48 hours 5

4. Elderly Patients:

   • Base dosage adjustments on renal function rather than age alone 1
   • Avibactam exposure is approximately 17% higher in elderly subjects, but this is not clinically significant 1

Clinical Pitfalls to Avoid

1. Underdosing: Insufficient dosing may lead to treatment failure, especially in serious infections.

2. Delayed Dose Adjustments: Failure to monitor renal function and adjust doses accordingly may result in toxicity or treatment failure.

3. Timing with Hemodialysis: Administering before rather than after hemodialysis will result in significant drug removal and potential underdosing.

4. Premature Dose Reduction: Consider that transient AKI may resolve quickly; reassess renal function frequently during the first 48 hours of treatment.

The dosing recommendations for Zavicefta maintain the 4:1 ratio of ceftazidime to avibactam across all dosage adjustments, which is essential for optimal antimicrobial activity 2.