Invanz (Ertapenem Sodium) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Probenecid

Probenecid interferes with the active tubular secretion of ertapenem, resulting in increased plasma concentrations of ertapenem [see Clinical Pharmacology]. Co-administration of probenecid with ertapenem is not recommended.

Valproic Acid

Case reports in the literature have shown that co-administration of carbapenems, including ertapenem, to patients receiving valproic acid or divalproex sodium results in a reduction of valproic acid concentrations. The valproic acid concentrations may drop below the therapeutic range as a result of this interaction, therefore increasing the risk of breakthrough seizures. Although the mechanism of this interaction is unknown, data from in vitro and animal studies suggest that carbapenems may inhibit the hydrolysis of valproic acid's glucuronide metabolite (VPA-g) back to valproic acid, thus decreasing the serum concentrations of valproic acid [see Warnings and Precautions].

OVERDOSAGE

No specific information is available on the treatment of overdosage with INVANZ. Intentional overdosing of INVANZ is unlikely. Intravenous administration of INVANZ at a dose of 2 g over 30 min or 3 g over 1-2h in healthy adult volunteers resulted in an increased incidence of nausea. In clinical trials in adults, inadvertent administration of three 1 g doses of INVANZ in a 24 hour period resulted in diarrhea and transient dizziness in one patient. In pediatric clinical trials, a single intravenous dose of 40 mg/kg up to a maximum of 2 g did not result in toxicity.

In the event of an overdose, INVANZ should be discontinued and general supportive treatment given until renal elimination takes place.

INVANZ can be removed by hemodialysis; the plasma clearance of the total fraction of ertapenem was increased 30% in subjects with end-stage renal disease when hemodialysis (4 hour session) was performed immediately following administration. However, no information is available on the use of hemodialysis to treat overdosage.

CONTRAINDICATIONS

• INVANZ is contraindicated in patients with known hypersensitivity to any component of this product or to other drugs in the same class or in patients who have demonstrated anaphylactic reactions to beta-lactams.
• Due to the use of lidocaine HCl as a diluent, INVANZ administered intramuscularly is contraindicated in patients with a known hypersensitivity to local anesthetics of the amide type.

REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically. 9th Edition; CLSI Document M7-A9. CLSI, Wayne, PA, 2012.
2. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Disk Susceptibility Tests. 11^th Edition; CLSI Document M2-A11. CLSI, Wayne, PA, 2012.
3. Clinical and Laboratory Standards Institute (CLSI). Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria – 7^th Edition; CLSI Document M11-A7. CLSI, Wayne, PA, 2007.
4. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing – 22^nd Informational Supplement. CLSI Document M100-S22. CLSI, Wayne, PA, 2012.
5. Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS). Performance Standards for Antimicrobial Susceptibility of Anaerobic Bacteria; Informational Supplement. CLSI Document M11-S1. CLSI, Wayne, PA, 2010.