Piperacillin/Tazobactam (Tazact) Dosing in Renal Impairment
Piperacillin/tazobactam dosage must be adjusted when creatinine clearance is below 40 mL/min to prevent drug accumulation and toxicity while maintaining efficacy. 1
Dosage Adjustment Based on Renal Function
Normal Renal Function (CrCl > 40 mL/min)
- Standard dosing: 4.5g (4g piperacillin/0.5g tazobactam) IV every 6 hours
Moderate to Severe Renal Impairment
| Creatinine Clearance | Recommended Dosage |
|---|---|
| 20-40 mL/min | 3.375g IV every 6 hours |
| <20 mL/min | 2.25g IV every 6 hours |
End-Stage Renal Disease (ESRD) on Hemodialysis
- 2.25g IV every 8 hours
- Administer an additional dose after each dialysis session
- Hemodialysis removes approximately 30-40% of piperacillin and tazobactam 1
Continuous Renal Replacement Therapy (CRRT)
- Dosing depends on the specific CRRT modality:
- CVVH: 4.5g IV every 8 hours
- CVVHDF: 4.5g IV every 6 hours
- Consider therapeutic drug monitoring (TDM) due to significant variability in drug clearance 2
Pharmacokinetic Considerations
The need for dosage adjustment is based on the following pharmacokinetic changes in renal impairment:
Half-life increases with decreasing creatinine clearance:
- At CrCl <20 mL/min, piperacillin half-life increases twofold
- At CrCl <20 mL/min, tazobactam half-life increases fourfold 1
Both piperacillin and tazobactam are primarily eliminated via the kidney:
- 68% of piperacillin is excreted unchanged in urine
- 80% of tazobactam is excreted unchanged in urine 1
Special Considerations
Residual Renal Function in Dialysis Patients
- Residual renal function significantly impacts drug clearance
- Total clearance of piperacillin may increase fivefold in patients with residual CrCl >50 mL/min compared to those with residual CrCl <10 mL/min 2
Peritoneal Dialysis
- Peritoneal dialysis removes approximately 6% of piperacillin and 21% of tazobactam doses 1
- Standard dosing: 2.25g IV every 8 hours
Risk of Acute Kidney Injury (AKI)
- Higher doses (4.5g) may increase the risk of AKI in patients with pre-existing renal impairment
- A study showed AKI occurred in 25-38.5% of patients with chronic kidney disease receiving 4.5g doses compared to 0-5.6% with 2.25g doses 3
Continuous Infusion Option
- For critically ill patients with varying degrees of renal function, continuous infusion may provide more consistent therapeutic levels
- A dose of 12g/24h as continuous infusion is sufficient to reach target concentrations for most pathogens with MICs ≤8 mg/L 4
Monitoring Recommendations
Assess renal function at baseline and regularly during therapy
Consider therapeutic drug monitoring in:
- Critically ill patients with significant PK variability
- Patients undergoing renal replacement therapy
- Patients with signs of potential drug toxicity 2
Monitor for signs of toxicity:
- Seizures
- Neuromuscular excitability
- Electrolyte abnormalities
By adjusting the dosage based on renal function, clinicians can optimize the efficacy of piperacillin/tazobactam while minimizing the risk of adverse effects in patients with renal impairment.