Drug Interactions between piperacillin / tazobactam and probenecid

MONITOR: Coadministration with probenecid may increase and prolong the serum concentrations of tazobactam. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of tazobactam via OAT1 and OAT3. A one gram oral dose of probenecid reduced the clearance of tazobactam (administered by injection in combination with piperacillin) by approximately 20% to 25% and prolonged its half-life by 71%. The peak plasma concentration was not affected.

MANAGEMENT: Although the clinical relevance of this interaction has not been established, caution may be advisable when probenecid must be used with tazobactam-containing preparations. The product labeling for piperacillin-tazobactam recommends avoiding concomitant use with probenecid unless the benefit outweighs the risk.

Probenecid may increase the plasma concentrations and half-lives of penicillins. The mechanism is competitive inhibition by probenecid of the renal tubular secretion of penicillins. While this interaction is often exploited to enhance the antibacterial effect of penicillins, toxicity may occur and should be considered if high penicillin dosages are administered intravenously.