INVEXEM

Indications

• Abdominal infections
• Acute gynaecological infections
• Community-acquired pneumonia
• Diabetic foot infections of the skin and soft tissue
• Surgical prophylaxis, particularly colorectal surgery

Dosage

Children: For children aged 3 months to 17 years:

Adults: 1 g once daily by intravenous infusion.

Mechanism of action

Ertapenem exhibits a bactericidal mode of action by binding to and inhibiting bacterial penicillin-binding proteins (PBPs). It has a strong affinity for PBPs 1a, 1b, 2, 3, 4, and 5 in Escherichia coli, with preferential binding to PBPs 2 and 3. This binding interferes with the synthesis of the bacterial cell wall, inhibiting the lengthening and strengthening of the peptidoglycan structure, which is essential for bacterial integrity.

Pharmacodynamics

Ertapenem is characterized by time-dependent bactericidal activity, meaning its effectiveness is optimized when drug concentrations exceed the minimum inhibitory concentrations (MIC) for a significant duration of the dosing interval. It is stable against hydrolysis by various beta-lactamases, including penicillinases and cephalosporinases, but does not resist metallo-beta-lactamases. Its activity encompasses a wide range of both aerobic and anaerobic bacteria.

Pharmacokinetics

Ertapenem is administered via intravenous infusion and achieves peak serum concentrations within approximately 30 minutes to an hour. It does not require co-administration with cilastatin, as it is stable to renal enzyme inactivation. The drug is primarily excreted unchanged in the urine, with a half-life of about 4 hours, allowing for once-daily dosing.

Contra-indications

• Hypersensitivity to ertapenem or other carbapenems
• Severe allergic reactions to beta-lactam antibiotics

Adverse effects

• Nausea
• Diarrhea
• Headache
• Rash
• Seizures
• Elevated liver enzymes
• Thrombocytopenia
• Anemia

Interactions

• Probenecid may increase plasma concentrations of ertapenem
• Concurrent use with other neurotoxic drugs may increase the risk of seizures

Precautions

• Caution in patients with a history of seizures or CNS disorders
• Renal impairment may require dose adjustment
• Monitor renal function and signs of allergic reactions during treatment

Pregnancy

Ertapenem should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Limited data on use in pregnant women.

Breast-feeding

Ertapenem is excreted in breast milk. Caution should be exercised when administered to nursing mothers.

Storage

Store below 25°C. Protect from light. Do not freeze. Reconstituted solutions should be used promptly or stored in the refrigerator and used within 24 hours.

Formulations

• Solution for injection: 1 g/10 mL vials

Mechanism of action

Ertapenem exhibits a bactericidal mode of action. It works by binding to and inhibiting bacterial penicillin-binding proteins (PBPs). In _Escherichia coli_, it has a strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preferential binding to PBPs 2 and 3. Upon binding to PBPs, ertapenem inhibits bacterial cell wall synthesis by interfering with the lengthening and strengthening of the peptidoglycan portion of the cell wall, thereby inhibiting cell wall synthesis. Ertapenem is a synthetic carbapenem beta-lactam antibiotic that is structurally and pharmacologically related to imipenem and meropenem. Like meropenem but unlike imipenem, ertapenem has a methyl group at position 1 of the 5-membered ring, which confers stability against hydrolysis by dehydropeptidase 1 (DHP 1) present on the brush border of proximal renal tubular cells, and therefore does not require concomitant administration with a DHP-1 inhibitor such as cilastatin. Ertapenem has in vitro activity against Gram-positive and Gram-negative aerobic and anaerobic bacteria. The bactericidal activity of ertapenem results from the inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin binding proteins (PBPs). In Escherichia coli, it has strong affinity toward PBPs 1a, 1b, 2, 3, 4 and 5 with preference for PBPs 2 and 3. Antimicrobials are the most frequently implicated class of drugs in drug-induced seizure, with beta-lactams being the class of antimicrobials most often implicated. The seizure-inducing potential of the carbapenem subclass may be directly related to their beta-lactam ring structure. Data on individual carbapenems and seizure activity are scarce. To evaluate the available evidence on the association between carbapenem agents and seizure activity, /investigators/ conducted a literature search of the MEDLINE (1966-May 2010), EMBASE (1974-May 2010), and International Pharmaceutical Abstracts (1970-May 2010) databases. Reference citations from the retrieved articles were also reviewed. Mechanistically, seizure propensity of the beta-lactams is related to their binding to gamma-aminobutyric acid (GABA) receptors. There are numerous reports of seizure activity associated with imipenem-cilastatin, with seizure rates ranging from 3-33%. For meropenem, doripenem, and ertapenem, the seizure rate for each agent is reported as less than 1%. However, as their use increases and expands into new patient populations, the rate of seizures with these agents may increase. High-dose therapy, especially in patients with renal dysfunction, preexisting central nervous system abnormalities, or a seizure history increases the likelihood of seizure activity. ...

Pharmacodynamics

Ertapenem is a carbapenem antibiotic with time-dependent bactericidal activity. Its optimal bactericidal activity is achieved when drug concentrations exceed the minimal inhibitory concentrations (MIC) for a specified portion of the dosing interval. It works against Gram-positive and Gram-negative aerobic and anaerobic bacteria. It is stable against hydrolysis by various beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases, but not metallo-beta-lactamases.