Doripenem Dosing in Renal Impairment
For patients with impaired renal function, dose doripenem 250 mg every 8 hours (infused over 1 hour) when creatinine clearance is 30-50 mL/min, and 250 mg every 12 hours when creatinine clearance is 10-29 mL/min. 1
Standard Dosing Framework
Normal Renal Function (CrCl >90 mL/min)
- Administer doripenem 500 mg every 8 hours for critically ill patients with intra-abdominal infections and serious gram-negative infections 1
- This standard dosing achieves adequate pharmacokinetic/pharmacodynamic targets for pathogens with MICs ≤1 mg/L when using 1-hour infusions 2
Moderate Renal Impairment (CrCl 30-50 mL/min)
- Reduce dose to 250 mg every 8 hours, infused over 1 hour 1
- This regimen maintains efficacy against pathogens with doripenem MICs ≤2 mg/L based on pharmacokinetic modeling 2
Severe Renal Impairment (CrCl 10-29 mL/min)
- Reduce dose to 250 mg every 12 hours, infused over 1 hour 1
- This dosing interval prevents drug accumulation while maintaining therapeutic concentrations for susceptible organisms 2
Special Populations Requiring Renal Replacement Therapy
Continuous Venovenous Hemodiafiltration (CVVHDF)
- For critically ill patients on CVVHDF, use 500 mg every 8 hours as a 60-minute infusion 3
- CVVHDF clearance accounts for approximately 30-37% of total doripenem clearance, with the remainder from residual renal and non-renal mechanisms 3
- This dosing achieves favorable pharmacokinetic/pharmacodynamic targets for pathogens with MICs up to 4 mg/L 3
Continuous Hemodiafiltration (CHDF)
- Administer 250 mg every 12 hours during CHDF (dialysis rate 500 mL/h, hemofiltration rate 300 mL/h) 4
- CHDF has minimal effect on doripenem clearance (approximately 13.5 mL/min), allowing dose adjustment primarily based on residual renal function 4
Slow Low-Efficiency Dialysis (SLED)
- The standard manufacturer dosing based on creatinine clearance can be used without modification during SLED 5
- Doripenem concentrations remain above minimum inhibitory concentrations throughout SLED treatment 5
Critical Considerations for Optimizing Therapy
Extended Infusion Strategy
- Consider extending infusion time to 4 hours when treating infections caused by organisms with higher MICs (2-4 mg/L) 2
- Extended infusions improve target attainment by maximizing the time drug concentrations remain above the MIC 2
Loading Doses in Critically Ill Patients on CRRT
- For septic patients on continuous renal replacement therapy, consider a loading dose of 1.5-2 g followed by 1 g every 8 hours 6
- Mean volume of distribution in critically ill patients is approximately 59 liters, supporting the need for higher initial dosing 6
Common Pitfalls to Avoid
- Do not use normalized GFR (mL/min/1.73 m²) for dosing decisions—use absolute creatinine clearance calculated by the Cockcroft-Gault formula to prevent dosing errors 7
- Avoid underdosing in patients on CRRT—the original 500 mg every 8 hours recommendation was based on nonseptic patients and may be insufficient for critically ill septic patients 6
- Monitor for drug accumulation in severe renal impairment—doripenem half-life increases substantially (mean 7.9 hours) in patients with creatinine clearance <30 mL/min 4