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Aminoglycosides: The mixing of β-lactam antibiotics with aminoglycosides in vitro can result in substantial inactivation of the aminoglycoside. However, amikacin and gentamicin have been shown to be compatible in vitro with reformulated piperacillin/tazobactam containing EDTA supplied in vials or bulk pharmacy containers in certain diluents at specific concentrations for a simultaneous Y-site infusion. Reformulated piperacillin/tazobactam containing EDTA is not compatible with tobramycin for simultaneous co-administration via Y-site infusion.
The inactivation of aminoglycosides in the presence of penicillin-class drugs has been recognized. It has been postulated that penicillin-aminoglycoside complexes form; these complexes are microbiologically inactive and of unknown toxicity. Sequential administration of this drug with tobramycin to patients with normal renal function and mild to moderate renal impairment has been shown to modestly decrease serum concentrations of tobramycin but does not significantly affect tobramycin pharmacokinetics. When aminoglycosides are administered in combination with piperacillin to patients with end-stage renal disease requiring hemodialysis, the concentrations of the aminoglycosides (especially tobramycin) may be significantly altered and should be monitored. Since aminoglycosides are not equally susceptible to inactivation by piperacillin, consideration should be given to the choice of the aminoglycoside when administered in combination with piperacillin to these patients.
Probenecid: Similar with other penicillins, concurrent administration of probenecid and piperacillin/tazobactam produced a longer half-life (piperacillin by 21%, tazobactam by 71%) and lower renal clearance for both piperacillin and tazobactam. However, peak plasma concentrations of either drug are unaffected.
Vancomycin: No pharmacokinetic interactions have been noted between this drug and vancomycin.
Heparin: Coagulation parameters should be tested more frequently and monitored regularly during simultaneous administration of high doses of heparin, oral anticoagulants, or other drugs that may affect the blood coagulation system or the thrombocyte function.
Vecuronium: Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. This product (piperacillin/tazobactam) could produce the same phenomenon if given along with 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. (See package insert for vecuronium bromide.)
Methotrexate: Limited data suggests that co-administration of methotrexate and piperacillin may reduce the clearance of methotrexate due to competition for renal secretion. The impact of tazobactam on the elimination of methotrexate has not been evaluated. If concurrent therapy is necessary, serum concentrations of methotrexate as well as the signs and symptoms of methotrexate toxicity should be frequently monitored.
Drug/Laboratory Test Interactions: As with other penicillins, the administration of this product (piperacillin and tazobactam for injection) may result in a false-positive reaction for glucose in the urine using a copper-reduction method (CLINITEST). It is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as DIASTIX or TES-TAPE) be used.
There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus 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 the 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.
