Doripenem Dosage Recommendations
For patients with normal renal function, doripenem should be administered at 500 mg every 8 hours as a 1-hour infusion, while patients with impaired renal function require dose adjustments based on creatinine clearance. 1
Dosing Based on Renal Function
Normal Renal Function (CrCl >50 mL/min)
- 500 mg IV every 8 hours as a 1-hour infusion 1
- For difficult-to-treat infections or higher MICs (2-4 μg/mL), consider extended 4-hour infusions to improve target attainment 2
Moderate Renal Impairment (CrCl 30-50 mL/min)
- 250 mg IV every 8 hours as a 1-hour infusion 2
Severe Renal Impairment (CrCl 10-29 mL/min)
- 250 mg IV every 12 hours as a 1-hour or 4-hour infusion 2
End-Stage Renal Disease on Continuous Renal Replacement Therapy
- For CVVHDF: 500 mg IV every 8 hours 3
- Doripenem clearance by CVVHDF accounts for approximately 30-37% of total clearance and is significantly correlated with replacement fluid flow rate 3
Special Considerations
Loading Doses
- A full loading dose should be administered regardless of renal function to rapidly achieve therapeutic concentrations in critically ill patients 4
- This is particularly important in sepsis where pathophysiological changes affect drug disposition 4
Extended Infusions
- Extended infusions (4 hours) improve pharmacodynamic target attainment, especially for pathogens with higher MICs 2, 5
- Consider extended infusions for critically ill patients with serious infections, particularly when targeting organisms with MICs ≥2 μg/mL 2, 6
Therapeutic Drug Monitoring
- Consider therapeutic drug monitoring in critically ill patients, especially those with fluctuating renal function 1, 4
- Target plasma trough concentration for intermittent administration and steady-state concentration for continuous administration 1
- Perform monitoring 24-48 hours after treatment initiation, after dosage changes, or with significant changes in clinical condition 1
Clinical Applications
Intra-Abdominal Infections
- Doripenem 500 mg every 8 hours is recommended for critically ill patients with intra-abdominal infections, particularly those at risk for infection with ESBL-producing Enterobacteriaceae 1
Augmented Renal Clearance
- Patients with enhanced renal function (augmented renal clearance) may require increased doses or extended infusions to maintain adequate drug concentrations 5
- When MIC is >1 μg/mL, increasing the dose or prolonging infusion time is essential in patients with normal or enhanced renal function 5
Pitfalls and Caveats
- Avoid underdosing in critically ill patients with sepsis, as pathophysiological changes can significantly affect antibiotic pharmacokinetics 4
- Residual renal function in patients on renal replacement therapy can significantly impact clearance and should be considered when determining dosage 1
- Monitor for adverse effects, particularly in patients with renal impairment, as accumulation can occur with inappropriate dosing 4
- Reassess antibiotic regimen daily based on clinical response, culture results, and changes in renal function 4
By following these evidence-based dosing recommendations for doripenem, clinicians can optimize antimicrobial efficacy while minimizing the risk of adverse effects, ultimately improving patient outcomes in terms of morbidity and mortality.