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Non-Depolarizing Muscle Relaxants: Piperacillin, when used concomitantly with vecuronium, has been implicated in prolonging the neuromuscular blockade of vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the non-depolarizing muscle relaxants could be prolonged in the presence of piperacillin.
Anticoagulants: During simultaneous administration of heparin, oral anticoagulants and other drugs that may affect the blood coagulation system, including thrombocyte function, appropriate coagulation tests should be performed more frequently and monitored regularly (see Precautions).
Methotrexate: Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of methotrexate should be monitored in patients to avoid drug toxicity.
Probenecid: As with other penicillins, concurrent administration of probenecid and piperacillin/tazobactam produces a longer half-life and lower renal clearance for both piperacillin and tazobactam; however, peak plasma concentrations of either drug are unaffected.
Aminoglycosides: Piperacillin, either alone or with tazobactam, did not significantly alter the pharmacokinetics of tobramycin in subjects with normal renal function and with mild or moderate renal impairment. The pharmacokinetics of piperacillin, tazobactam, and the M1 metabolite were also not significantly altered by tobramycin administration.
Vancomycin: Studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin/tazobactam and vancomycin as compared to vancomycin alone (see Precautions). Some of these studies have reported that the interaction is vancomycin dose-dependent. Expert guidelines recommend intensive vancomycin dosing and maintenance of trough levels between 15 mg/L and 20 mg/L which is an increase from previously published recommendations of target trough concentrations of 5-10 mg/L. Attaining these trough concentrations often requires practitioners to prescribe vancomycin doses which exceed manufacturers' recommendations. Therefore, it is possible that in addition to the increased risk of vancomycin-induced nephrotoxicity reported with adherence to these guidelines the risk of nephrotoxicity may also increase due to an interaction with piperacillin/tazobactam.
No pharmacokinetic interactions have been noted between piperacillin/tazobactam and vancomycin.
As with other penicillins, the administration of piperacillin/tazobactam may result in a false-positive reaction for glucose in urine using a copper-reduction method. It is thus recommended that glucose tests based on enzymatic glucose oxidase reactions be used.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus enzyme immunoassay (EIA) test in patients receiving piperacillin/tazobactam injection who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported.
Therefore, positive test results in patients receiving piperacillin/tazobactam should be interpreted cautiously and confirmed by other diagnostic methods.
