ZOSYN IN PLASTIC CONTAINER
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZOSYN IN PLASTIC CONTAINER (ZOSYN IN PLASTIC CONTAINER).
Piperacillin, a ureidopenicillin, inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), inhibiting transpeptidation and autolysin inhibitors. Tazobactam, a beta-lactamase inhibitor, irreversibly inactivates beta-lactamases, preventing hydrolysis of piperacillin.
| Metabolism | Piperacillin and tazobactam are eliminated primarily by renal excretion. A small fraction of piperacillin is metabolized to desethylpiperacillin (minor metabolite). Tazobactam is metabolized to a single inactive metabolite (M1). Both are minimally metabolized by the liver. |
| Excretion | Piperacillin: ~68% renal (glomerular filtration and tubular secretion), 9-17% biliary. Tazobactam: ~80% renal (unchanged and inactive metabolite). Mean cumulative urinary recovery: piperacillin 68%, tazobactam 80%; fecal recovery: piperacillin ~11%, tazobactam <1%. |
| Half-life | Piperacillin: 0.7-1.2 hours (normal renal function). Tazobactam: 0.7-0.9 hours. Clinically, half-life extends to 2-6 hours in renal impairment (CrCl <20 mL/min); requires dose adjustment. |
| Protein binding | Piperacillin: 26-33% (primarily albumin). Tazobactam: 20-23% (primarily albumin). |
| Volume of Distribution | Piperacillin: 0.18-0.25 L/kg (total body water); Tazobactam: 0.21-0.28 L/kg. Distributes into tissues like lung, skin, muscle, bile; low CNS penetration unless inflamed meninges. |
| Bioavailability | IV only: 100% bioavailable. |
| Onset of Action | IV: Rapid, within 30 minutes (bactericidal levels achieved) following infusion start. |
| Duration of Action | IV: 4-6 hours (serum concentrations above MIC for susceptible organisms). Dosed every 6-8 hours; extended infusions (4 hours) used for resistant pathogens. |
3.375 g (piperacillin 3 g + tazobactam 0.375 g) intravenously every 6 hours over 30 minutes. For nosocomial pneumonia, 4.5 g every 6 hours.
| Dosage form | INJECTABLE |
| Renal impairment | CrCl >40 mL/min: no adjustment; CrCl 20-40 mL/min: 2.25 g every 6 hours; CrCl <20 mL/min: 2.25 g every 8 hours; hemodialysis: 2.25 g every 12 hours plus 0.75 g after each dialysis. |
| Liver impairment | No dose adjustment required for hepatic impairment; piperacillin undergoes minimal hepatic metabolism. |
| Pediatric use | Infants >2 months and children <40 kg: 100 mg piperacillin/kg every 6 hours; maximum 4 g piperacillin per dose. For intra-abdominal infections: 80-100 mg piperacillin/kg every 6 hours. |
| Geriatric use | Adjust dose based on renal function (CrCl); consider age-related decline in creatinine clearance. No specific dose adjustment solely for age. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZOSYN IN PLASTIC CONTAINER (ZOSYN IN PLASTIC CONTAINER).
| Breastfeeding | Piperacillin and tazobactam are excreted in human milk in low concentrations. M/P ratio not established. Caution should be exercised. Consider developmental and health benefits of breastfeeding along with mother's clinical need. |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; however, no adequate well-controlled studies in pregnant women. Potential fetal risk cannot be ruled out. Use only if clearly needed. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: RENAL IMPAIRMENT. In patients with renal impairment (creatinine clearance ≤ 40 mL/min), the dosing interval must be adjusted to reduce the risk of accumulation and neurotoxicity (including seizures).
| Serious Effects |
["Known hypersensitivity to piperacillin, tazobactam, or any penicillin-class antibiotics","Hypersensitivity to beta-lactamase inhibitors (e.g., clavulanic acid, sulbactam, tazobactam)","Severe hypersensitivity reaction to cephalosporins or carbapenems (cross-reactivity may occur)"]
| Precautions | ["Hypersensitivity reactions (including anaphylaxis) in patients with beta-lactam allergy (penicillins, cephalosporins, carbapenems)","Renal impairment: dose adjustment required; risk of neurotoxicity (seizures) with high doses or renal failure","Hematologic effects: prolonged bleeding time, thrombocytopenia, neutropenia, agranulocytosis (especially with prolonged therapy >10 days)","Clostridioides difficile-associated diarrhea: may occur; treat with appropriate antibiotics","Electrolyte disturbances: hypernatremia due to sodium content (2.8 mEq/g piperacillin)","Neuromuscular excitability: may occur with high doses, especially in renal impairment","Hepatic dysfunction: transient elevations in liver enzymes; hepatitis rarely","Overgrowth of nonsusceptible organisms (including fungi) with prolonged use"] |
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| Monitor maternal renal function, CBC with differential, and signs of bleeding or hypersensitivity. Fetal monitoring as clinically indicated. |
| Fertility Effects | No human data on fertility effects. Animal studies show no impairment of fertility. |