Interactions : אינטראקציות

4.5 Interaction with other medicinal products and other forms of interaction

Non-depolarising muscle relaxants
Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. Due to their similar mechanisms of action, it is expected that the neuromuscular blockade produced by any of the non-depolarising muscle relaxants could be prolonged in the presence of piperacillin.

Anticoagulants
During simultaneous administration of heparin, oral anticoagulants and other substances that may affect the blood coagulation system including thrombocyte function, appropriate coagulation tests should be performed more frequently and monitored regularly.

Methotrexate
Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of methotrexate should be monitored in patients to avoid substance 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 substances 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.
The inactivation of tobramycin and gentamicin by piperacillin has been demonstrated in patients with severe renal impairment.
For information related to the administration of piperacillin / tazobactam with aminoglycosides please refer to sections 6.2 and 6.6

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 section 4.4)

Some of these studies have reported that the interaction is vancomycin dose dependent.

No pharmacokinetic interactions have been noted between piperacillin / tazobactam and vancomycin.


Effects on laboratory tests
Non-enzymatic methods of measuring urinary glucose may lead to false-positive results, as with other penicillins. Therefore, enzymatic urinary glucose measurement is required under Piperacillin/Tazobactam therapy.

A number of chemical urine protein measurement methods may lead to false-positive results.
Protein measurement with dip sticks is not affected.

The direct Coombs test may be positive.
Bio-Rad Laboratories Platelia Aspergillus EIA tests may lead to false-positive results for patients receiving Piperacillin/Tazobactam. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported.


Positive test results for the assays listed above in patients receiving Piperacillin/Tazobactam should be confirmed by other diagnostic methods.