ZOSYN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOSYN (ZOSYN).
Piperacillin, a semisynthetic penicillin, inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs). Tazobactam, a beta-lactamase inhibitor, inactivates beta-lactamases, preventing piperacillin degradation.
| Metabolism | Piperacillin undergoes minimal hepatic metabolism; tazobactam is metabolized to an inactive metabolite. Both are primarily excreted unchanged in urine via glomerular filtration and tubular secretion. |
| Excretion | Primarily renal; piperacillin 68% unchanged, tazobactam 80% unchanged; biliary/fecal excretion <10% |
| Half-life | Piperacillin ~0.7-1.2 h; tazobactam ~0.7-1.0 h; extended in renal impairment (piperacillin up to 3.3 h, tazobactam up to 4.7 h in CrCl <20 mL/min) |
| Protein binding | Piperacillin ~30% (primarily albumin); tazobactam ~30% (albumin) |
| Volume of Distribution | Piperacillin ~0.18-0.3 L/kg; tazobactam ~0.2-0.3 L/kg; distributes into tissues including lung, bile, CSF (non-inflamed minimal) |
| Bioavailability | Only IV administration; oral bioavailability not applicable |
| Onset of Action | IV: within 30 minutes (peak concentrations achieved at end of infusion) |
| Duration of Action | Approximately 6-8 hours; dosing interval q6h (q8h for moderate renal impairment) based on susceptibility and infection severity |
| Brand Substitutes | Blucillin Tazo 4000mg/500mg Injection, Cadigard 4000 mg/500 mg Injection, Pisa 4000 mg/500 mg Injection, Tazomac 4.5gm Injection, Maxotaz 4000 mg/500 mg Injection |
3.375 g (piperacillin 3 g / tazobactam 0.375 g) intravenously every 6 hours over 30 minutes; for nosocomial pneumonia, 4.5 g intravenously every 6 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl 20-40 mL/min: 3.375 g IV every 8 hours; CrCl <20 mL/min: 2.25 g IV every 8 hours; for hemodialysis: 2.25 g IV every 12 hours, with an additional 0.75 g after dialysis. |
| Liver impairment | No dose adjustment required for hepatic impairment; pharmacokinetics not significantly altered. |
| Pediatric use | For children ≥2 months and ≤40 kg: 100 mg piperacillin/kg (as ZOSYN) IV every 8 hours (max 4.5 g/dose) for appendicitis/peritonitis; for infants 2-9 months: 80 mg piperacillin/kg IV every 8 hours; for infants >9 months and ≤40 kg: 100 mg piperacillin/kg IV every 8 hours. |
| Geriatric use | Dose based on renal function; no additional age-related adjustments except monitoring for renal clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOSYN (ZOSYN).
| Breastfeeding | Piperacillin and tazobactam are excreted in human milk in low concentrations. M/P ratio not established. Consider risk-benefit; use with caution in breastfeeding mothers. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies. Adequate human studies are lacking; use only if clearly needed. First trimester: no known fetal risk; second and third trimesters: no documented adverse effects. |
| Fetal Monitoring |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to piperacillin, tazobactam, or any penicillin-class antibiotic","History of allergic reaction to beta-lactamase inhibitors"]
| Precautions | ["Hypersensitivity reactions including anaphylaxis (cross-sensitivity with cephalosporins)","Hematologic effects (neutropenia, leukopenia, thrombocytopenia with prolonged therapy)","Renal impairment: dose adjustment required; risk of neurotoxicity with high doses","Clostridioides difficile-associated diarrhea (CDAD)","Electrolyte disturbances (hypokalemia)","Hemorrhagic manifestations reported with high doses"] |
Loading safety data…
| Monitor for signs of hypersensitivity, diarrhea (including C. difficile), renal function, and hepatic function. In neonates born to mothers treated near term, monitor for potential alterations in gut flora. |
| Fertility Effects | No evidence of impaired fertility from animal studies. No human data on fertility effects. |