Drug Interaction Report

Coadministration with probenecid may increase the plasma concentrations of carbapenem antibiotics. The mechanism involves competitive inhibition of carbapenem renal excretion via active tubular secretion. Significant pharmacokinetic alterations have been reported for some carbapenems such as doripenem and meropenem, but not for others like ertapenem and imipenem. According to the product labeling for ertapenem, coadministration with probenecid (500 mg orally every 6 hours) resulted in a 25% increase in ertapenem systemic exposure (AUC) and a 20% and 35% reduction in plasma and renal clearance, respectively. The half-life increased from 4.0 to 4.8 hours. Similar changes have been reported for imipenem. Because of the small effect on half-life, the coadministration with probenecid to extend the half-life of ertapenem or imipenem is not recommended.