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. |
| Molecular Weight | Piperacillin sodium: 539.5 Da; Tazobactam sodium: 322.3 Da; Piperacillin/tazobactam combination: MW ~861.8 Da (combined as sodium salts). |
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 | Animal studies have shown no risk; no adequate human studies. Use only if clearly needed. |
| 2nd trimester | Caution in pregnant women; piperacillin/tazobactam crosses placenta and achieves fetal serum levels. Use only if benefit outweighs risk. |
| 3rd trimester | Near term, use only if clearly indicated; potential risk of kernicterus due to bilirubin displacement from albumin. |
Clinical note
Comprehensive clinical and safety monograph for ZOSYN IN PLASTIC CONTAINER (ZOSYN IN PLASTIC CONTAINER).
| Placental transfer | Piperacillin and tazobactam cross the placenta; fetal serum concentrations reach approximately 33-100% of maternal levels within 1-2 hours of dosing. |
| Breastfeeding | Piperacillin and tazobactam are excreted into breast milk in low concentrations (piperacillin milk/plasma ratio ~0.1-0.2). Considered compatible with breastfeeding; monitor infant for rash, diarrhea, or candidiasis. |
■ 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 |
Hypersensitivity to piperacillin, tazobactam, or any penicillinHypersensitivity to beta-lactam antibiotics (e.g., cephalosporins)History of severe allergic reaction (anaphylaxis) to any beta-lactam
| 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 |
Loading safety data…
| Lactation Rating | L2 (Safe) |
| 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 | 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. |
| Food/Dietary |
| No known food interactions. Take with or without food. Maintain adequate hydration unless fluid restricted per clinical condition. |
| Clinical Pearls | ZOSYN IN PLASTIC CONTAINER is a combination of piperacillin (an extended-spectrum penicillin) and tazobactam (a beta-lactamase inhibitor). It is primarily used for moderate-to-severe infections including intra-abdominal, skin and soft tissue, gynecologic, and community-acquired pneumonia. Dosage adjustment is required in renal impairment (CrCl <40 mL/min). Prolonged infusion may improve outcomes in critically ill patients. Monitor for hypersensitivity reactions, especially in penicillin-allergic patients. Use with caution in patients with cystic fibrosis due to risk of drug fever. Reconstitute and administer within specified time frames per manufacturer guidelines to maintain potency. |
| Patient Advice | Take this medication exactly as prescribed, even if you feel better. · Tell your healthcare provider immediately if you experience any signs of allergic reaction, including rash, itching, swelling, or difficulty breathing. · This medication may cause diarrhea; contact your doctor if diarrhea becomes severe or contains blood or mucus. · Inform your doctor if you have kidney disease, as dose adjustments may be needed. · Do not take any other medications (including over-the-counter) without consulting your healthcare provider. · If you miss a dose, take it as soon as you remember, but skip it if it is almost time for the next dose. Do not double doses. · Monitor for signs of superinfection (e.g., oral thrush, vaginal yeast infection) and report them to your doctor. |