Zosyn 4.5g

— THERAPEUTIC CATEGORIES —
  • Bacterial infections
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Zosyn 4.5g Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Piperacillin 4g, tazobactam 0.5g; lyophilized pwd for IV inj after reconstitution; sodium content 2.84mEq/g of piperacillin.

    Pharmacological Class

    Broad-spectrum penicillin + β-lactamase inhibitor.

    See Also

    How Supplied

    Single-dose vials (2.25g, 3.375g)—24; (4.5g)—12

    How Supplied

    Zosyn® (piperacillin and tazobactam) Injection in Galaxy Containers are supplied as a frozen, iso-osmotic, sterile, nonpyrogenic solution in single-dose plastic containers as follows: 

    • 2.25 g (piperacillin sodium equivalent to 2 g piperacillin and tazobactam sodium equivalent to 0.25 g tazobactam) in 50 mL. Each container has 5.58 mEq (128 mg) of sodium. Supplied 24/box.

    • 3.375 g (piperacillin sodium equivalent to 3 g piperacillin and tazobactam sodium equivalent to 0.375 g tazobactam) in 50 mL. Each container has 8.38 mEq (192 mg) of sodium. Supplied 24/box.

    • 4.5 g (piperacillin sodium equivalent to 4 g piperacillin and tazobactam sodium equivalent to 0.5 g tazobactam) in 100 mL. Each container has 11.17 mEq (256 mg) of sodium. Supplied 12/box.

    Storage

    • Zosyn® Injection in Galaxy Containers should be stored at or below -20°C (-4°F).

    • For Galaxy Containers, the thawed solution is stable for 14 days under refrigeration (2°C to 8°C [36°F to 46°F]) or 24 hours at room temperature 20°C to 25°C [68°F to 77°F]. Do not refreeze thawed Zosyn Injection.

    Manufacturer

    Baxter

    Generic Availability

    YES

    Mechanism of Action

    Piperacillin sodium exerts bactericidal activity by inhibiting septum formation and cell wall synthesis of susceptible bacteria. In vitro, piperacillin is active against a variety of Gram-positive and Gram-negative aerobic and anaerobic bacteria. Tazobactam sodium has little clinically relevant in vitro activity against bacteria due to its reduced affinity to penicillin-binding proteins. It is, however, a beta-lactamase inhibitor of the Molecular class A enzymes, including Richmond-Sykes class III (Bush class 2b & 2b') penicillinases and cephalosporinases. It varies in its ability to inhibit class II and IV (2a & 4) penicillinases.

    Zosyn 4.5g Indications

    Indications

    Susceptible intra-abdominal infections (eg, appendicitis, peritonitis), moderate community-acquired pneumonia, moderate to severe nosocomial pneumonia, postpartum endometritis, pelvic inflammatory disease, skin and skin structure.

    Indications

    Intra-abdominal Infections

    • For the treatment to adults and pediatric patients (2 months of age and older) with appendicitis (complicated by rupture or abscess) and peritonitis caused by beta-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus.

    Nosocomial Pneumonia

    • For the treatment to adults and pediatric patients (2 months of age and older) with nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin and tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside).

    Skin and Skin Structure Infections

    • For the treatment of adults with uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses and ischemic/diabetic foot infections caused by beta-lactamase producing isolates of Staphylococcus aureus.

    Female Pelvic Infections

    • For the treatment of adults with postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of Escherichia coli.

    Community-acquired Pneumonia

    • For the treatment of adults with community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae.

     

    Zosyn 4.5g Dosage and Administration

    Adult

    Infuse over 30mins. Usually 3.375g every 6hrs for 7–10 days; renal impairment (CrCl 20–40mL/min): 2.25g every 6hrs; (CrCl <20mL/min): 2.25g every 8hrs; (hemodialysis or peritoneal dialysis): 2.25g every 12hrs, give additional 0.75g at end of hemodialysis. Nosocomial pneumonia (give with an aminoglycoside): 4.5g every 6hrs for 7–14 days (continue aminoglycoside for P. aeruginosa); renal impairment (CrCl 20–40mL/min): 3.375g every 6hrs; (CrCl <20mL/min): 2.25g every 6hrs; (hemodialysis or peritoneal dialysis): 2.25g every 8hrs, give additional 0.75g at end of hemodialysis.

    Children

    <2 months: not established. Infuse over 30mins. Appendicitis/peritonitis: 2 months–9 months: 90mg/kg every 8hrs. ≥9 months (≤40kg): 112.5mg/kg every 8hrs; (>40kg): use Adult dose. Nosocomial pneumonia: 2 months–9 months: 90mg/kg every 6hrs. ≥9 months (≤40kg): 112.5mg/kg every 6hrs; (>40kg): use Adult dose. Both: renal impairment: not determined.

    Zosyn 4.5g Contraindications

    Contraindications

    Penicillin, cephalosporin, or β-lactamase inhibitor allergy.

    Zosyn 4.5g Boxed Warnings

    Not Applicable

    Zosyn 4.5g Warnings/Precautions

    Warnings/Precautions

    Discontinue if hypersensitivity occurs or severe skin reactions (eg, Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS) progress; monitor closely. Neuromuscular excitability or convulsions: monitor closely (esp. in renal impairment or seizure disorders). Nephrotoxicity in critically ill patients: consider alternative treatments; if inadequate or unavailable, monitor renal function. Cystic fibrosis (increased fever/rash risk). Renal impairment. Monitor electrolytes, hematopoiesis (esp. with prolonged therapy); discontinue if bleeding disorders occur. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Hypersensitivity Adverse Reactions

    • Serious and occasionally fatal hypersensitivity (anaphylactic/anaphylactoid) reactions (including shock) have been reported in patients receiving therapy with Zosyn. These reactions are more likely to occur in individuals with a history of penicillin, cephalosporin, or carbapenem hypersensitivity.

    • Discontinue Zosyn and institute appropriate therapy if allergic reaction occurs.

    Severe Cutaneous Adverse Reactions

    • Severe cutaneous adverse reactions may occur including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis.

    • Monitor patients closely if they develop a skin rash, and discontinue Zosyn if lesions progress.

    Hemophagocytic Lymphohistiocytosis (HLH)

    • Signs and symptoms of HLH may include fever, rash, lymphadenopathy, hepatosplenomegaly and cytopenia.

    • Discontinue Zosyn immediately if HLH is suspected and institute appropriate treatment.

    Hematologic Adverse Reactions 

    • Bleeding manifestations have occurred and are sometimes associated with abnormalities of coagulation tests (eg, clotting time, platelet aggregation and prothrombin time). These reactions are more likely to occur in patients with renal failure.

    • Discontinue Zosyn and institute appropriate therapy if bleeding manifestations occur.

    • Perform periodic assessment of hematopoietic function especially with prolonged therapy of 21 days or longer.

    Central Nervous System Adverse Reactions

    • May cause neuromuscular excitability or seizures. Increased risk for CNS adverse reactions in patients receiving higher doses, especially patients with renal impairment.

    • Monitor closely for neuromuscular excitability or seizures in patients with renal impairment or seizure disorders. 

    Nephrotoxicity in Critically Ill Patients

    • In a clinical trial, Zosyn was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function in critically ill patients compared with other beta-lactam antibacterial drugs.

    • Consider alternative treatment options in critically ill individuals. If alternative options are unavailable or inadequate, monitor renal function during treatment with Zosyn.

    Electrolyte Effects

    • Zosyn contains a total of 2.84 mEq (65 mg) of Na+ (sodium) per gram of piperacillin in the combination product. This should be considered when treating patients requiring restricted salt intake. 

    • Perform periodic electrolyte determinations in patients with low potassium reserves, and the potential risk for hypokalemia.

    Clostridioides difficile-Associated Diarrhea

    • Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Zosyn.

    • Consider CDAD in all patients who present with diarrhea after treatment.

    • If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued.

    • Institute appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation.

    Development of Drug-Resistant Bacteria

    • Prescribing Zosyn in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of development of drug-resistant bacteria.

    Pregnancy Considerations

    Risk Summary

    • Piperacillin and tazobactam cross the placenta in humans. There are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage.

    Nursing Mother Considerations

    Risk Summary

    • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for Zosyn and any potential adverse effects on the breastfed child from Zosyn or from the underlying maternal condition.

    Pediatric Considerations

    • Safety and effectiveness of Zosyn have not been established in pediatric patients less than 2 months of age.

    • Dosage of Zosyn in pediatric patients with renal impairment has not been determined.

    Geriatric Considerations

    • Use caution in elderly patients. Start at the low end of the dosing range.

    • Elderly patients may respond with a blunted natriuresis to salt loading, which may be clinically important with regard to such diseases as congestive heart failure.

    • Greater risk for toxic reactions in patients with impaired renal function. Monitor renal function.

    Renal Impairment Considerations

    • Reduce dose of Zosyn to the degree of renal function impairment in patients with creatinine clearance ≤40mL/min and dialysis patients.

    Other Considerations for Specific Populations

    Patients with Cystic Fibrosis

    • Piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

    Zosyn 4.5g Pharmacokinetics

    Absorption

    • Maximum observed concentration for piperacillin: 134 mcg/mL (for 2.25 g); 242 mcg/mL (for 3.375 g); 298 mcg/mL (for 4.5 g).

    • Maximum observed concentration for tazobactam: 15 mcg/mL (for 2.25 g); 24 mcg/mL (for 3.375 g); 34 mcg/mL (for 4.5 g).

    Distribution

    • Approximately 30% plasma protein bound.

    • Piperacillin and tazobactam are widely distributed into tissues and body fluids including intestinal mucosa, gallbladder, lung, female reproductive tissues, interstitial fluid, and bile.

    • Volume of distribution for piperacillin: 17.4 L (for 2.25 g); 15.1 L (for 3.375 g); 15.4 L (for 4.5 g).

    • Volume of distribution for tazobactam: 17.0 L (for 2.25 g); 14.8 L (for 3.375 g); 14.7 L (for 4.5 g).

    Metabolism

    • Piperacillin is metabolized to a minor microbiologically active desethyl metabolite. Tazobactam is metabolized to a single metabolite that lacks pharmacological and antibacterial activities.

    Elimination

    Renal. Half-life: 0.7–1.2 hours.

    Zosyn 4.5g Interactions

    Interactions

    Potentiated by probenecid; do not coadminister unless benefit outweighs the risk. May antagonize aminoglycosides (eg, tobramycin); monitor. May potentiate non-depolarizing neuromuscular blockers (eg, vecuronium); monitor. Monitor methotrexate, heparin, anticoagulants. Monitor renal function with concomitant vancomycin. May cause false (+) Clinitest, Coomb's or Bio-Rad Aspergillus EIA test.

    Zosyn 4.5g Adverse Reactions

    Adverse Reactions

    Diarrhea, constipation, nausea, headache, insomnia; rash (may be severe), pruritus, local reactions, C. difficile-associated diarrhea, hemophagocytic lymphohistiocytosis (discontinue if suspected); rare: bleeding.

    Zosyn 4.5g Clinical Trials

    See Literature

    Zosyn 4.5g Note

    Not Applicable

    Zosyn 4.5g Patient Counseling

    Patient Counseling

    Serious Hypersensitivity Reactions

    • Advise patients, their families, or caregivers that serious hypersensitivity reactions, including serious allergic cutaneous reactions, could occur and would require immediate treatment.

    • Discontinue Zosyn and institute appropriate therapy if allergic reaction occurs.

    Hemophagocytic Lymphohistiocytosis

    • Advise patients that excessive immune activation may occur prior to initiation and patients should report any signs or symptoms (eg, fever, rash, or lymphadenopathy) to a healthcare provider immediately. 

    Diarrhea

    • Advise patients that diarrhea is a common problem caused by antibacterial drugs.

    • Contact a healthcare provider if diarrhea occurs. 

    Antibacterial Resistance

    • Advise patients that Zosyn does not treat viral infections (eg, common cold).

    Pregnancy and Lactation

    • Counsel patients that Zosyn crosses the placenta in humans and is excreted in human milk.

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