Ertapenem Once-Daily Dosing Interval
Ertapenem should be administered every 24 hours (once daily) in adults and adolescents ≥13 years, with doses given at the same time each day. 1, 2
Standard Dosing Schedule
Adults and Adolescents (≥13 years)
- 1 gram IV every 24 hours 1, 2
- The 24-hour interval is fixed and should not be shortened 2
- Doses can be administered as a 30-minute infusion (standard) or as a rapid 5-minute infusion with equivalent pharmacokinetics 3
Pediatric Patients (3 months to 12 years)
- 15 mg/kg IV every 12 hours (maximum 1 g/day) 1, 4
- Children require twice-daily dosing due to age-dependent differences in clearance and distribution volume 4
- Once-daily dosing is insufficient in this age group to maintain adequate free drug concentrations above the MIC for organisms near the susceptibility breakpoint 4
Pharmacokinetic Rationale
The once-daily dosing in adults is supported by:
- Elimination half-life of 4-4.5 hours in patients with normal renal function 5
- High protein binding (87.9-98.9%, concentration-dependent) that prolongs the effective duration 3
- Area under the curve (AUC) values that remain therapeutic over 24 hours at clinically relevant MICs 3
Probability of target attainment (40% fT>MIC) is 97% at MIC 0.25 mg/L but drops to only 1.7-2.8% at MIC 0.5 mg/L, indicating the importance of susceptibility testing 3
Critical Clinical Caveats
When NOT to Use Once-Daily Ertapenem
Patients in septic shock or critically ill should receive alternative carbapenems with more frequent dosing (meropenem 1g q6h, doripenem 500mg q8h, or imipenem/cilastatin 500mg q6h by extended infusion) 6, 5, 7
The rationale includes:
- Critically ill patients demonstrate enhanced volume of distribution (17L vs 8L in healthy volunteers) and increased clearance (43 mL/min vs 20 mL/min) 8
- Severe hypoalbuminemia (common in critical illness) dramatically reduces total drug concentrations while maintaining similar free drug levels 8
- Free plasma concentrations may only exceed MIC₉₀ of 2 mg/L for 6 hours (25% of dosing interval) in hypoalbuminemic patients with normal renal function 8
Special Populations Requiring Consideration
Patients with severe hypoalbuminemia and normal renal function may benefit from shortened dosing intervals or continuous infusion to ensure optimal free drug concentrations 8
Storage and Timing Constraints
- Reconstituted solution diluted in 0.9% sodium chloride may be stored at room temperature (25°C) for 6 hours OR refrigerated (5°C) for 24 hours then used within 4 hours after removal 2
- Solutions should not be frozen 2
- Carbapenems including ertapenem are particularly unstable after reconstitution and should not be stored for extended periods 6
Duration of Therapy
Treatment duration varies by indication:
- Intra-abdominal infections: 4 days if adequate source control in immunocompetent patients; up to 7 days if immunocompromised or critically ill 6
- Pneumonia: 5-7 days, continuing if afebrile for 48 hours with clinical stability 7
- Vertebral osteomyelitis: 6 weeks 7
- Hidradenitis suppurativa: Single 6-week course as third-line therapy 7