From the FDA Drug Label
2.4 Dosage in Adult Patients with Renal Impairment The FDA drug label does not answer the question.
From the Research
Zosyn (piperacillin-tazobactam) dosing should be adjusted based on the degree of renal impairment to minimize the risk of toxicity and ensure optimal therapeutic effects.
Key Considerations
- For patients with creatinine clearance (CrCl) between 20-40 mL/min, the recommended dose is 2.25 g every 6 hours 1.
- For patients with CrCl less than 20 mL/min, the dose should be reduced to 2.25 g every 8 hours 1.
- Patients on hemodialysis should receive 2.25 g every 12 hours plus an additional 0.75 g after each dialysis session 2.
- 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 1.
Rationale
These adjustments are necessary because piperacillin and tazobactam are primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation 2. Without appropriate dose adjustments, patients with renal impairment may experience toxicity, including neurotoxicity manifesting as seizures.
Additional Recommendations
Therapeutic drug monitoring may be beneficial in critically ill patients with fluctuating renal function to ensure optimal dosing 1. It is also important to be aware of the potential for rare but serious complications such as thrombocytopenia, as reported in a case study 3.
Evidence Base
The most recent and highest quality study supporting these recommendations is from 2017, which evaluated the pharmacodynamic exposure of piperacillin/tazobactam across the renal function range using 4.5 or 3.375 g dosing regimens 1. This study found that simplified dosing regimens using solely 4.5 or 3.375 g strengths can provide similar or better target attainment probabilities compared to standard regimens.