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 ZOSYN should be reduced based on the degree of renal impairment The recommended daily dosage of ZOSYN for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1. Table 1: Recommended Dosage of ZOSYN in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin and tazobactam)*
- Administer ZOSYN 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 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 renal dosing for Zosyn 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 hemodialysis 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 toxicity and ensure effective treatment, with the most recent study 2 suggesting that using solely 4.5 or 3.375 g doses with prolonged infusions can provide similar or better probability of target attainment (PTA) compared to standard regimens. For patients with a CrCl greater than 40 mL/min, the standard dose of 3.375 g every 6 hours or 4.5 g every 6-8 hours can be used.
- For moderate renal impairment (CrCl 20-40 mL/min), the dose should be reduced to 2.25 g every 6 hours or 4.5 g every 8 hours as a prolonged infusion, as shown in the study 2.
- In severe renal impairment (CrCl less than 20 mL/min), the dose should be further reduced to 2.25 g every 8 hours or 4.5 g every 12 hours as a prolonged infusion.
- For patients on hemodialysis, 2.25 g every 8 hours is recommended with an additional 0.75 g after each dialysis session.
- Continuous renal replacement therapy (CRRT) patients typically receive 2.25 g every 6 hours or 4.5 g every 8 hours, depending on the specific CRRT modality, as suggested by the study 3. These adjustments are necessary because piperacillin and tazobactam are primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation, potentially causing toxicity if doses aren't appropriately reduced 4, 5, 6.