From the FDA Drug Label
2.3 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, USP should be reduced based on the degree of renal impairment The recommended daily dosage of piperacillin and tazobactam for injection, USP 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 and tazobactam)
- Creatinine clearance, mL/minAll Indications (except nosocomial pneumonia)Nosocomial Pneumonia
- Administer piperacillin and tazobactam for injection by intravenous infusion over 30 minutes. † Creatinine clearance for patients not receiving hemodialysis ‡ 0.75 g (0.67 g piperacillin and 0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days Greater than 40 mL/min3.375 every 6 hours4.5 every 6 hours 20 to 40 mL/min†2.25 every 6 hours3.375 every 6 hours Less than 20 mL/min†2.25 every 8 hours2.25 every 6 hours Hemodialysis‡2.25 every 12 hours2.25 every 8 hours CAPD2.25 every 12 hours2.25 every 8 hours
The recommended renal dosing for 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 administered 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) requires dose adjustment in patients with renal impairment, with the most recent and highest quality study suggesting dose reductions for moderate to severe renal impairment. For patients with creatinine clearance (CrCl) greater than 40 mL/min, the standard dose of 3.375g every 6 hours or 4.5g every 6 hours can be used 2.
Key Considerations
- For moderate renal impairment (CrCl 20-40 mL/min), reduce the dose to 2.25g every 6 hours.
- For severe renal impairment (CrCl less than 20 mL/min), further reduce to 2.25g every 8 hours.
- Patients on hemodialysis should receive 2.25g every 8 hours with an additional 0.75g after each dialysis session.
- For continuous renal replacement therapy (CRRT), dosing typically ranges from 2.25g every 6 hours to 3.375g every 8 hours depending on the specific CRRT modality. Proper renal dosing is crucial because piperacillin and tazobactam are primarily eliminated by the kidneys, and accumulation in renal impairment can lead to neurotoxicity and seizures 3.
Monitoring and Adjustments
- Monitoring renal function during therapy is important, as dosing may need adjustment if kidney function changes.
- Despite dose reductions, Zosyn maintains its broad-spectrum activity against many gram-positive, gram-negative, and anaerobic bacteria. The most recent study from 2017 4 suggests that higher doses of TAZ/PIPC may worsen renal function, highlighting the importance of careful dose adjustment in patients with renal impairment. Overall, the evidence suggests that dose adjustments for Zosyn in patients with renal impairment are necessary to minimize the risk of adverse effects while maintaining its therapeutic efficacy 5, 6.