Ertapenem (INVANZ): A New Once a Day Carbapenem
Ertapenem has a very broad spectrum of activity similar to imipenem that includes all anaerobes and many gram-negative bacilli, with the exception of P. aeruginosa and Acinetobacter. As with imipenem, risk of seizure is low if the recommended dose is given. T ½ of 4–5hr suggests caution in using a 24hr dosing for severely ill patients (i.e. Bacteremia and/or JCV). Once-a-day dosing may allow for convenient outpatient intravenous treatment.
- Complicated intra-abdominal infections;
- Complicated skin and skin structure infections;
- Community acquired pneumonia;
- Complicated urinary tract infections (including pyelonephritis);
- Acute pelvic infections (postpartum endomyometritis, septic abortion, and post surgical gynecologic infections).
Manufacturer: Merck (West Point, PA)
Usual Adult Dose: 1 Gm IV or IM qd.
Cost: $38.00/day (AWP)
Absorption: 90% after IM administration.
Cmax: 155 mcg/ml; Cmin: 1mcg/ml at 24 hours (after 1 Gm IV).
Distribution: well distributed, Vd = 8.2L/kg.
Protein binding: 85–95%.
Metabolism/Excretion: Hydrolysing of beta-lactam ring. Metabolite and parent drug are renally excreted.
T1/2: 4 hours.
Spectrum: Like its big brother (Imipenem), ertapenem has a very broad spectrum of activity that includes all anaerobes and many aerobic gram-positive and gram-negative organisms. It has poor activity against P aeruginosa and Acinetobacter and lacks activity against Enterococcus faecium, S. epidermidis, B. Lepacia, S. maetophilia, and MRSA.
Spectrum comments: Ertapenem showed activity against a variety extended spectrum beta-lactamase producing K. pneumoniae and E. coli, but was less active against P. aeruginosa . Cross-resistance to ertepenem seen in Imipenem-1 metallo-beta-lactamase and SME-1 carbapenemmase producing organisms . Acinetobacter spp and P. aeruginosa were much less susceptible compared to imipenem .
Drug Interactions: Does not interact with cytochrome p450 isoform (1A2, 2C9, 2C19, 2D6, 2E1, and 3A4) or P-glycoprotein.
Probenecid-increases ertapenem AUC by 25%.
Not compatible with dextrose (do not co-infuse with dextrose or other medications).
Adverse Drug Reaction: Generally well tolerated. Occ: diarrhea, n/v, phlebitis, headache. Rare: seizures (reported in 0.5% of patients; patients with renal insufficiency and/or CNS disorder are at increased risk).
Pregnancy Risk: Category B: Not teratogenic in animal studies. No human data.
Breastfeeding compatibility: Excreted in breast milk. Use only when clearly indicated.
Dosing in renal insufficiency: <30 ml/min: 500 mg qd.
Dosing in Hemodialysis: 500 mg qd (150 mg supplement post-HD if daily dose given 6 hours within HD).
Dosing in Peritoneal Dialysis: No data.
Dosing in hepatic insufficiency: 1 gm qd (usual dose).
Clinical trials: Clinical studies submitted to the FDA showed that ertapenem was equivalent to piperacillin/ tazobactam for the treatment of complicated intra-abdominal infections, skin and skin structure infections, and acute pelvic infections. Ertapenem was also equivalent to ceftriaxone for the treatment of communityacquired pneumonia and complicated urinary tract infections.
1. Jones RN. In vitro evaluation of ertapenem (MK-0826), a long-acting carbapenems, tested against selected resistant strains. J Chemother 2001;(4):363–76.
2. Livermore DM, Oakton KJ, Carter MW, et al. Activity of Ertapenem (MK-0826) versus Enterobacteriaceae
with potent β-lactamases. AAC 2001; 45:2831–7.
3. Livermore DM, Carter MW, Bagel Simone, et al. In vitro activities of Ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia. AAC 2001; 45:1860–7.