When ertapenem is administered with probenecid, probenecid competes for active tubular secretion and thus inhibits the renal excretion of ertapenem. This leads to small but statistically significant increases in the elimination half-life (19%) and in the extent of systemic exposure (25%). No dosage adjustment is necessary when ertapenem is given with probenecid. Because of the small effect on half-life, the coadministration with probenecid to extend the half-life of ertapenem is not recommended.
In vitro studies indicate that ertapenem does not inhibit P-glycoprotein-mediated transport of digoxin or vinblastine and that ertapenem is not a substrate for P-glycoprotein-mediated transport. In vitro studies in human liver microsomes indicate ertapenem does not inhibit metabolism mediated by any of the six major cytochrome p450 (CYP) isoforms: 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4. Drug interactions caused by inhibition of P-glycoprotein-mediated drug clearance or CYP-mediated drug clearance are unlikely.
Other than with probenecid, no specific clinical drug interaction studies have been conducted.
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 Precautions.)