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Ertapenem (INVANZ): A New Once a Day Carbapenem

Pham, Paul PharmD, BCPS

Infectious Diseases in Clinical Practice: January 2002 - Volume 11 - Issue 1 - p 30-31
SPECIAL ARTICLES: Profiles on New Drugs

This section represents a summary of information about newly approved drugs for infectious disease practitioners.

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.

FDA Indications:

  • 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)

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Pharmacology

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 [1]. Cross-resistance to ertepenem seen in Imipenem-1 metallo-beta-lactamase and SME-1 carbapenemmase producing organisms [2]. Acinetobacter spp and P. aeruginosa were much less susceptible compared to imipenem [3].

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.

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References

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.
© 2002 Lippincott Williams & Wilkins, Inc.