What are the doripenem (generic name) dose modifications based on creatinine (Cr) clearance (CrCl) levels in patients with impaired renal function?

Doripenem Dose Modification Based on Creatinine Clearance

Standard Dosing for Normal Renal Function

For patients with creatinine clearance (CrCl) >50 mL/min, doripenem should be dosed at 500 mg intravenously every 8 hours as a 1-hour infusion. 1, 2

• This standard regimen achieves adequate pharmacodynamic targets (time above MIC >35% of dosing interval) for pathogens with MICs ≤1 mcg/mL 2
• Extended infusion over 4 hours improves target attainment, allowing coverage of pathogens with MICs up to 4 mcg/mL 2

Moderate Renal Impairment (CrCl 30-50 mL/min)

Reduce the dose to 250 mg intravenously every 8 hours as a 1-hour infusion. 2

• This reduced dose maintains efficacy against pathogens with doripenem MICs ≤2 mcg/mL 2
• Extended 4-hour infusions can be considered to optimize pharmacodynamic target attainment 2

Severe Renal Impairment (CrCl 10-29 mL/min)

Reduce the dose to 250 mg intravenously every 12 hours. 2

• Both 1-hour and 4-hour infusion durations are appropriate at this dosing interval 2
• This regimen provides adequate coverage for pathogens with MICs ≤2 mcg/mL 2

Continuous Renal Replacement Therapy (CRRT)

For patients on continuous venovenous hemodiafiltration (CVVHDF), maintain the standard dose of 500 mg intravenously every 8 hours. 3, 4

• CRRT accounts for approximately 30-37% of total doripenem clearance 3
• This dosing achieves favorable pharmacokinetic/pharmacodynamic targets for MICs up to 4 mg/L 3
• Doripenem concentrations remain above the minimum inhibitory concentration throughout CRRT sessions 4
• Critical caveat: Doripenem clearance during CRRT is significantly correlated with replacement fluid flow rate, so higher CRRT flow rates may require dose adjustments 3

Special Considerations for Critically Ill Patients

• Doripenem pharmacokinetics are similar between ICU and non-ICU patients when matched for renal function 1
• The primary determinant of dosing is underlying renal function (measured by CrCl) rather than ICU status 1
• Important pitfall: In critically ill patients, particularly those on CRRT, therapeutic drug monitoring should be strongly considered, as clearance can be significantly higher than predicted—up to 10.5 mL/min/kg compared to expected 2.4-4.8 mL/min/kg 5
• Continuous infusion strategies with therapeutic drug monitoring may optimize outcomes in complex patients receiving CRRT 5

Practical Algorithm

1. Calculate creatinine clearance using the Cockcroft-Gault equation 6
2. Select dose based on CrCl category:
   • CrCl >50 mL/min: 500 mg IV q8h 1, 2
   • CrCl 30-50 mL/min: 250 mg IV q8h 2
   • CrCl 10-29 mL/min: 250 mg IV q12h 2
   • On CRRT: 500 mg IV q8h 3, 4
3. Consider extended infusion (4 hours) for infections with higher MIC pathogens or to maximize pharmacodynamic target attainment 2
4. Monitor for clinical response and consider therapeutic drug monitoring in critically ill patients, especially those on CRRT 5