From the FDA Drug Label
2.4 Dosage in Adult Patients with Renal Impairment In adult patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of piperacillin and tazobactam for injection should be reduced based on the degree of renal impairment The recommended daily dosage of piperacillin and tazobactam for injection for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1 Table 1: Recommended Dosage of Piperacillin and Tazobactam for Injection in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam) Creatinine clearance, mL/min | All Indications (except nosocomial pneumonia) | Nosocomial Pneumonia Greater than 40 mL/min | 3.375 every 6 hours | 4.5 every 6 hours 20 to 40 mL/min | 2.25 every 6 hours | 3.375 every 6 hours Less than 20 mL/min | 2.25 every 8 hours | 2.25 every 6 hours Hemodialysis** | 2.25 every 12 hours | 2.25 every 8 hours CAPD | 2.25 every 12 hours | 2.25 every 8 hours
The recommended renal dosing for Zosyn (piperacillin and tazobactam) is as follows:
- For patients with creatinine clearance greater than 40 mL/min, the dose is 3.375 g every 6 hours for all indications except nosocomial pneumonia, and 4.5 g every 6 hours for nosocomial pneumonia.
- For patients with creatinine clearance 20 to 40 mL/min, the dose is 2.25 g every 6 hours for all indications except nosocomial pneumonia, and 3.375 g every 6 hours for nosocomial pneumonia.
- For patients with creatinine clearance less than 20 mL/min, the dose is 2.25 g every 8 hours for all indications except nosocomial pneumonia, and 2.25 g every 6 hours for nosocomial pneumonia.
- For patients on hemodialysis, the dose is 2.25 g every 12 hours for all indications except nosocomial pneumonia, and 2.25 g every 8 hours for nosocomial pneumonia, with an additional dose of 0.75 g after each dialysis session.
- For patients on CAPD, the dose is 2.25 g every 12 hours for all indications except nosocomial pneumonia, and 2.25 g every 8 hours for nosocomial pneumonia 1.
From the Research
Zosyn (piperacillin-tazobactam) dosing in patients with renal impairment should be adjusted based on creatinine clearance (CrCl) to prevent underexposure or toxicity, with the most recent study suggesting higher than standard dosing regimens may be needed in critically ill patients with augmented renal clearance 2.
Key Considerations
- For patients with CrCl of 20-40 mL/min, the recommended dose is 3.375 g every 6 hours.
- For patients with CrCl less than 20 mL/min, the dose should be reduced to 2.25 g every 6 hours.
- For patients on hemodialysis, administer 2.25 g every 8 hours with an additional 0.75 g after each dialysis session.
- For continuous renal replacement therapy (CRRT), dosing typically ranges from 2.25-3.375 g every 6-8 hours depending on the specific CRRT modality and flow rates.
Rationale
The pharmacokinetics of piperacillin and tazobactam are affected by renal impairment, with reduced clearance leading to increased drug concentrations and potential toxicity 3. Conversely, augmented renal clearance can result in underexposure to the antibiotic, increasing the risk of treatment failure 2.
Supporting Evidence
A study published in 2018 found that critically ill patients with augmented renal clearance required higher than standard dosing regimens to achieve optimal antibiotic exposure when receiving piperacillin-tazobactam by continuous infusion 2. Another study from 2010 identified optimal renal dosage adjustments for traditional and extended-infusion piperacillin-tazobactam dosing regimens, highlighting the importance of considering renal function when selecting a dosing strategy 4.
Clinical Implications
Monitoring renal function throughout therapy is essential, as dosing may need to be readjusted if kidney function changes during treatment. By adjusting the dose of Zosyn based on CrCl and considering the potential for augmented renal clearance, clinicians can help ensure optimal antibiotic exposure and minimize the risk of toxicity or treatment failure.