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) ... For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia.
The dose of Zosyn (piperacillin and tazobactam) for patients with End-Stage Renal Disease (ESRD) is as follows:
- For patients on hemodialysis, the maximum dose is 2.25 g every 12 hours for all indications other than nosocomial pneumonia and 2.25 g every 8 hours for nosocomial pneumonia.
- An additional dose of 0.75 g should be administered following each dialysis period on hemodialysis days. 1
From the Research
For patients with end-stage renal disease (ESRD) requiring Zosyn (piperacillin-tazobactam), the recommended dose is 2.25 grams (2 grams piperacillin/0.25 grams tazobactam) intravenously every 8 hours, with an additional dose after each dialysis session for those on hemodialysis, as supported by the most recent evidence 2.
Key Considerations
- The dosage adjustment is necessary because piperacillin and tazobactam are primarily eliminated by the kidneys, and patients with ESRD have significantly reduced drug clearance 3.
- Without proper adjustment, the drug can accumulate to toxic levels, potentially causing neurotoxicity including seizures, as reported in a case study 4.
- Each dose should be administered over 30 minutes to minimize vein irritation.
- Monitor patients for signs of adverse effects including hypersensitivity reactions, electrolyte abnormalities, and bleeding risk, especially with prolonged use.
Patient-Specific Factors
- For severe infections such as nosocomial pneumonia or in critically ill patients, a higher dose of 3.375 grams (3 grams piperacillin/0.375 grams tazobactam) every 8 hours may be used.
- Patients on continuous renal replacement therapy (CRRT) may require individualized dosing due to significant patient-to-patient variability in pharmacokinetic parameters 2.
Clinical Evidence
- A systematic review of the literature found that the effects of different doses and membrane fluxes for hemodialysis, as well as interventions aimed at preventing secondary complications, are important considerations in the management of ESRD 5.
- However, the most recent and highest-quality study on this topic is a 2012 study on the pharmacokinetics and pharmacodynamics of piperacillin-tazobactam in patients treated with CRRT 2, which provides the best evidence for dosing recommendations in this population.