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Zosyn (Piperacillin / Tazobactam) - Drug Interactions, Contraindications, Overdosage, etc



Drug Interactions


The mixing of beta-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 ZOSYN containing EDTA supplied in vials or bulk pharmacy containers in certain diluents at specific concentrations for a simultaneous Y-site infusion. (See DOSAGE AND ADMINISTRATION.) Reformulated ZOSYN containing EDTA is not compatible with tobramycin for simultaneous coadministration 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 ZOSYN 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.


There have been post-marketing reports of overdose with piperacillin/tazobactam. The majority of those events experienced, including nausea, vomiting, and diarrhea, have also been reported with the usual recommended dosages. Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure).

Treatment should be supportive and symptomatic according to the patient's clinical presentation. Excessive serum concentrations of either piperacillin or tazobactam may be reduced by hemodialysis. Following a single 3.375 g dose of piperacillin/tazobactam, the percentage of piperacillin and tazobactam dose removed by hemodialysis was approximately 31% and 39%, respectively. (See CLINICAL PHARMACOLOGY.)


ZOSYN is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or β-lactamase inhibitors.


  1. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; 21st Informational Supplement. CLSI document M100-S21. CLSI, 940 West Valley Rd., Suite 1400, Wayne, PA 19087, 2011
  2. CLSI. Methods for Dilution Antimicrobial Susceptibility Test for Bacteria that Grow Aerobically; Approved Standard – 8th ed. CLSI document M07-A8, 2009.
  3. CLSI. Performance Standards for Antimicrobial Disk Susceptibility Test; Approved Standard – 10th ed. CLSI document M02-A10, 2009.
  4. CLSI. Methods for Antimicrobial Susceptibility Testing of Anaerobic Bacteria; Approved Standard – 7th ed. CLSI document M11-A7, 2007

DIASTIX is a registered trademark of Bayer Healthcare LLC.

CLINITEST is a registered trademark of Siemens Healthcare Diagnostics Inc.

Galaxy is a registered trademark of Baxter International Inc.

This product's label may have been updated. For current package insert and further product information, please visit www.pfizer.com or call our medical communications department toll-free at 1‑800‑438‑1985.

Distributed by Wyeth Pharmaceuticals Inc., a subsidiary of Pfizer Inc.

Manufactured by Baxter Healthcare Corporation, Deerfield, IL 60015

Novation and NOVAPLUS are registered trademarks of Novation LLC.


September 2012

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