What is the recommended dose of Doripenem (doripenem) for patients with impaired renal function?

Doripenem Dosing in Renal Impairment

For patients with impaired renal function, doripenem 250 mg every 8 hours (infused over 1 hour) is recommended for creatinine clearance 30-50 mL/min, and 250 mg every 12 hours for creatinine clearance 10-29 mL/min. 1

Standard Dosing in Normal Renal Function

For critically ill patients with normal renal function (CrCl >90 mL/min), the standard dose is doripenem 500 mg every 8 hours for intra-abdominal infections and serious gram-negative infections. 1

Renal Impairment Dosing Adjustments

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

• Dose: 250 mg every 8 hours infused over 1 hour 2
• This regimen maintains adequate pharmacokinetic/pharmacodynamic targets for pathogens with MICs ≤2 mg/L 2

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

• Dose: 250 mg every 12 hours infused over 1 hour 2
• Extended infusion over 4 hours can be considered to improve target attainment for organisms with higher MICs (up to 4 mg/L) 2

Continuous Renal Replacement Therapy (CRRT)

For critically ill patients receiving continuous venovenous hemodiafiltration or hemodialysis:

• Recommended dose: 1 gram every 8 hours 3
• A loading dose of 1.5-2 grams may be considered for critically ill septic patients 3
• The original 500 mg every 8 hours recommendation was based on non-septic patients and may be inadequate for critically ill septic patients 3
• CVVHDF clearance accounts for approximately 30-37% of total doripenem clearance 4
• Mean hemofilter clearance is approximately 36.53 mL/min with steady-state trough levels around 8.5 mg/L 3

Important CRRT Considerations

• Doripenem clearance during CVVHDF correlates significantly with replacement fluid flow rate 4
• The 500 mg every 8 hours dose achieves favorable pharmacokinetics for MICs up to 4 mg/L in standard CVVHDF settings (blood flow 200 mL/h, dialysate 1000 mL/h, replacement fluid 1000 mL/h) 4
• However, for septic patients with higher severity of illness, the 1 gram every 8 hours regimen is preferred 3

Optimizing Doripenem Efficacy

Extended Infusion Strategy

• 4-hour infusions improve target attainment compared to 1-hour infusions 2
• Extended infusions allow adequate coverage for pathogens with MICs up to 4 mg/L, even in patients with normal renal function 2
• This strategy is particularly valuable when treating infections with less susceptible organisms 2

Pharmacodynamic Targets

• Doripenem efficacy correlates with time above MIC (T>MIC) of 35% of the dosing interval 2, 5
• For patients with CrCl >50 mL/min receiving 500 mg every 8 hours as 1-hour infusion: adequate for MICs ≤1 mg/L 2
• Same dose as 4-hour infusion: adequate for MICs ≤4 mg/L 2

Critical Clinical Pearls

Avoid underdosing in CRRT patients: The updated recommendation of 1 gram every 8 hours for CRRT patients reflects recognition that critically ill septic patients require higher doses than the original 500 mg recommendation, which was based on non-septic populations. 3

Monitor for accumulation: While doripenem does not show considerable accumulation at steady state in CRRT patients, individual pharmacokinetic variability exists, particularly related to replacement fluid flow rates. 4, 3

Consider pathogen MIC: Dosing decisions should account for the suspected or documented MIC of the infecting organism, with extended infusions preferred when MICs approach 2-4 mg/L. 2, 5