From the FDA Drug Label
2.3 Dosage in Adult Patients With Renal Impairment
The dosing recommendations for Zosyn (piperacillin/tazobactam) in patients with impaired renal function are as follows:
- Renal Impairment:
- CrCl ≥ 40 mL/min: No dosage adjustment is necessary.
- CrCl 20-40 mL/min: Dosage adjustments are recommended. However, the exact dosage adjustments for CrCl 20-40 mL/min and for CrCl < 20 mL/min are not provided in the given text. 1
From the Research
Zosyn (piperacillin/tazobactam) dosing should be adjusted based on creatinine clearance (CrCl) in patients with impaired renal function, with the most recent and highest quality study 2 guiding dosing recommendations to minimize the risk of adverse effects and optimize therapeutic outcomes.
Dosing Recommendations
- For patients with CrCl between 20-40 mL/min, the recommended dose is 2.25 g (2 g piperacillin/0.25 g tazobactam) every 6 hours.
- For patients with CrCl less than 20 mL/min, the dose should be reduced to 2.25 g every 8 hours.
- Patients on hemodialysis should receive 2.25 g every 12 hours plus an additional 0.75 g after each dialysis session.
- For continuous renal replacement therapy (CRRT), dosing typically ranges from 2.25 g every 6-8 hours depending on the specific CRRT modality and flow rates.
Rationale
These adjustments are necessary because piperacillin and tazobactam are primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation, increasing the risk of adverse effects such as neurotoxicity, seizures, and electrolyte disturbances, as highlighted in studies 3, 4.
Monitoring and Adjustment
Renal function should be monitored regularly during treatment, and doses adjusted accordingly if changes in renal function occur during therapy, to ensure optimal therapeutic outcomes and minimize the risk of adverse effects, as emphasized in 5 and 6.