Label: ZOSYN IN GALAXY CONTAINERS- tazobactam sodium and piperacillin sodium injection, solution

  • NDC Code(s): 0206-8860-01, 0206-8860-02, 0206-8861-01, 0206-8861-02, view more
    0206-8862-01, 0206-8862-02
  • Packager: Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc.
  • Category: HUMAN PRESCRIPTION DRUG LABEL
  • DEA Schedule: None
  • Marketing Status: New Drug Application

Drug Label Information

Updated June 10, 2020

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  • HIGHLIGHTS OF PRESCRIBING INFORMATION
    These highlights do not include all the information needed to use ZOSYN safely and effectively. See full prescribing information for ZOSYN.

    ZOSYN® (piperacillin and tazobactam) for injection, for intravenous use
    ZOSYN® (piperacillin and tazobactam) injection, for intravenous use
    Initial U.S. approval: 1993

    RECENT MAJOR CHANGES

    Indications and Usage (1)5/2020
    Dosage and Administration (2)5/2020
    Warnings and Precautions, Central Nervous System Adverse Reactions (5.4) 4/2020

    INDICATIONS AND USAGE

    ZOSYN is a combination of piperacillin, a penicillin-class antibacterial and tazobactam, a beta-lactamase inhibitor, indicated for the treatment of:

    • Intra-abdominal infections in adult and pediatric patients 2 months of age and older (1.1)
    • Nosocomial pneumonia in adult and pediatric patients 2 months of age and older (1.2)
    • Skin and skin structure infections in adults (1.3)
    • Female pelvic infections in adults (1.4)
    • Community-acquired pneumonia in adults (1.5)

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZOSYN and other antibacterial drugs, ZOSYN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. (1.6)

    DOSAGE AND ADMINISTRATION

    • Adult Patients With Indications Other Than Nosocomial Pneumonia; The usual daily dosage of ZOSYN for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam). (2.1)
    • Adult Patients with Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with ZOSYN at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam). (2.2)
    • Adult Patients with Renal Impairment: Dosage in patients with renal impairment (creatinine clearance ≤40 mL/min) and dialysis patients should be reduced, based on the degree of renal impairment. (2.3)
    • Pediatric Patients by Indication and Age: See Table below (2.4)
    Recommended Dosage of Zosyn for Pediatric Patients 2 months of Age and Older, Weighing up to 40 Kg and With Normal Renal Function
    AgeAppendicitis and /or PeritonitisNosocomial Pneumonia
    2 months to 9 months90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 (eight) hours90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 6 (six) hours
    Older than 9 months112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 (eight) hours112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 6 (six) hours
    • Administer ZOSYN by intravenous infusion over 30 minutes to both adult and pediatric patients (2.1, 2.2, 2.3, 2.4).
    • ZOSYN and aminoglycosides should be reconstituted, diluted, and administered separately. Co-administration via Y-site can be done under certain conditions. (2.7)
    • See the full prescribing information for the preparation and administration instructions for ZOSYN single-dose vials, pharmacy bulk vials and GALAXY containers.

    DOSAGE FORMS AND STRENGTHS

    • ZOSYN® for Injection: 2.25 g, 3.375 g, and 4.5 g lyophilized powder for reconstitution in single-dose vials and 40.5 g lyophilized powder for reconstitution in pharmacy bulk vials. (3)
    • ZOSYN® Injection: 2.25 g in 50 mL, 3.375 g in 50 mL, and 4.5 g in 100 mL frozen solution in single-dose GALAXY Containers. (3, 16)

    CONTRAINDICATIONS

    Patients with a history of allergic reactions to any of the penicillins, cephalosporins, or beta-lactamase inhibitors. (4)

    WARNINGS AND PRECAUTIONS

    • Serious hypersensitivity reactions (anaphylactic/anaphylactoid) reactions have been reported in patients receiving ZOSYN. Discontinue ZOSYN if a reaction occurs. (5.1)
    • ZOSYN may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis. Discontinue ZOSYN for progressive rashes. (5.2)
    • Hematological effects (including bleeding, leukopenia and neutropenia) have occurred. Monitor hematologic tests during prolonged therapy. (5.3)
    • As with other penicillins, ZOSYN may cause neuromuscular excitability or seizures. Patients receiving higher doses, especially in the presence of renal impairment may be at greater risk. Closely monitor patients with renal impairment or seizure disorders for signs and symptoms of neuromuscular excitability or seizures. (5.4)
    • Nephrotoxicity in critically ill patients has been observed; the use of ZOSYN was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs in a randomized, multicenter, controlled trial in critically ill patients. Based on this study, alternative treatment options should be considered in the critically ill population. If alternative treatment options are inadequate or unavailable, monitor renal function during treatment with ZOSYN. (5.5)
    • Clostridioides difficile-associated diarrhea: evaluate patients if diarrhea occurs. (5.7)

    ADVERSE REACTIONS

    The most common adverse reactions (incidence >5%) are diarrhea, constipation, nausea, headache, and insomnia. (6.1)


    To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

    DRUG INTERACTIONS

    • ZOSYN administration can significantly reduce tobramycin concentrations in hemodialysis patients. Monitor tobramycin concentrations in these patients. (7.1)
    • Probenecid prolongs the half-lives of piperacillin and tazobactam and should not be co-administered with ZOSYN unless the benefit outweighs the risk. (7.2)
    • Co-administration of ZOSYN with vancomycin may increase the incidence of acute kidney injury. Monitor kidney function in patients receiving ZOSYN and vancomycin. (7.3)
    • Monitor coagulation parameters in patients receiving ZOSYN and heparin or oral anticoagulants. (7.4)
    • ZOSYN may prolong the neuromuscular blockade of vecuronium and other non-depolarizing muscle relaxants. Monitor for adverse reactions related to neuromuscular blockade. (7.5)

    USE IN SPECIFIC POPULATIONS

    Dosage in patients with renal impairment (creatinine clearance ≤40 mL/min) should be reduced based on the degree of renal impairment. (2.3, 8.6)

    See 17 for PATIENT COUNSELING INFORMATION.

    Revised: 7/2020

  • Table of Contents

    FULL PRESCRIBING INFORMATION: CONTENTS*

    1 INDICATIONS AND USAGE

    1.1 Intra-abdominal Infections

    1.2 Nosocomial Pneumonia

    1.3 Skin and Skin Structure Infections

    1.4 Female Pelvic Infections

    1.5 Community-acquired Pneumonia

    1.6 Usage

    2 DOSAGE AND ADMINISTRATION

    2.1 Dosage in Adult Patients With Indications Other Than Nosocomial Pneumonia

    2.2 Dosage in Adult Patients With Nosocomial Pneumonia

    2.3 Dosage in Adult Patients With Renal Impairment

    2.4 Dosage in Pediatric Patients With Appendicitis/Peritonitis or Nosocomial Pneumonia

    2.5 Reconstitution and Dilution of Powder Formulations

    2.6 Directions for Use of ZOSYN in GALAXY Containers

    2.7 Compatibility with Aminoglycosides

    3 DOSAGE FORMS AND STRENGTHS

    4 CONTRAINDICATIONS

    5 WARNINGS AND PRECAUTIONS

    5.1 Hypersensitivity Adverse Reactions

    5.2 Severe Cutaneous Adverse Reactions

    5.3 Hematologic Adverse Reactions

    5.4 Central Nervous System Adverse Reactions

    5.5 Nephrotoxicity in Critically Ill Patients

    5.6 Electrolyte Effects

    5.7 Clostridioides difficile-Associated Diarrhea

    5.8 Development of Drug-Resistant Bacteria

    6 ADVERSE REACTIONS

    6.1 Clinical Trials Experience

    6.2 Postmarketing Experience

    6.3 Additional Experience with Piperacillin

    7 DRUG INTERACTIONS

    7.1 Aminoglycosides

    7.2 Probenecid

    7.3 Vancomycin

    7.4 Anticoagulants

    7.5 Vecuronium

    7.6 Methotrexate

    7.7 Effects on Laboratory Tests

    8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    8.2 Lactation

    8.4 Pediatric Use

    8.5 Geriatric Use

    8.6 Renal Impairment

    8.7 Hepatic Impairment

    8.8 Patients with Cystic Fibrosis

    10 OVERDOSAGE

    11 DESCRIPTION

    12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    12.2 Pharmacodynamics

    12.3 Pharmacokinetics

    12.4 Microbiology

    13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    15 REFERENCES

    16 HOW SUPPLIED/STORAGE AND HANDLING

    17 PATIENT COUNSELING INFORMATION

    *
    Sections or subsections omitted from the full prescribing information are not listed.
  • 1 INDICATIONS AND USAGE

    1.1 Intra-abdominal Infections

    ZOSYN is indicated in adults and pediatric patients (2 months of age and older) for the treatment of 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.

    1.2 Nosocomial Pneumonia

    ZOSYN is indicated in adults and pediatric patients (2 months of age and older) for the treatment of nosocomial pneumonia (moderate to severe) caused by beta-lactamase producing isolates of Staphylococcus aureus and by piperacillin/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) [see Dosage and Administration (2)].

    1.3 Skin and Skin Structure Infections

    ZOSYN is indicated in adults for the treatment of 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.

    1.4 Female Pelvic Infections

    ZOSYN is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of Escherichia coli.

    1.5 Community-acquired Pneumonia

    ZOSYN is indicated in adults for the treatment of community-acquired pneumonia (moderate severity only) caused by beta-lactamase producing isolates of Haemophilus influenzae.

    1.6 Usage

    To reduce the development of drug-resistant bacteria and maintain the effectiveness of ZOSYN and other antibacterial drugs, ZOSYN should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

  • 2 DOSAGE AND ADMINISTRATION

    2.1 Dosage in Adult Patients With Indications Other Than Nosocomial Pneumonia

    The usual total daily dosage of ZOSYN for adult patients with indications other than nosocomial pneumonia is 3.375 g every six hours [totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam)], to be administered by intravenous infusion over 30 minutes. The usual duration of ZOSYN treatment is from 7 to 10 days.

    2.2 Dosage in Adult Patients With Nosocomial Pneumonia

    Initial presumptive treatment of adult patients with nosocomial pneumonia should start with ZOSYN at a dosage of 4.5 g every six hours plus an aminoglycoside, [totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam)], administered by intravenous infusion over 30 minutes. The recommended duration of ZOSYN treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom P. aeruginosa is isolated.

    2.3 Dosage in Adult Patients With Renal Impairment

    In adult patients with renal impairment (creatinine clearance ≤ 40 mL/min) and dialysis patients (hemodialysis and CAPD), the intravenous dose of ZOSYN should be reduced based on the degree of renal impairment. The recommended daily dosage of ZOSYN for patients with renal impairment administered by intravenous infusion over 30 minutes is described in Table 1.

    Table 1: Recommended Dosage of ZOSYN in Patients with Normal Renal Function and Renal Impairment (As total grams piperacillin/tazobactam)*
    Creatinine clearance, mL/minAll Indications (except nosocomial pneumonia)Nosocomial Pneumonia
    *
    Administer ZOSYN by intravenous infusion over 30 minutes.
    Creatinine clearance for patients not receiving hemodialysis
    0.75 g (0.67 g piperacillin/0.08 g tazobactam) should be administered following each hemodialysis session on hemodialysis days
    Greater than 40 mL/min3.375 every 6 hours4.5 every 6 hours
    20 to 40 mL/min2.25 every 6 hours3.375 every 6 hours
    Less than 20 mL/min2.25 every 8 hours2.25 every 6 hours
    Hemodialysis2.25 every 12 hours2.25 every 8 hours
    CAPD2.25 every 12 hours2.25 every 8 hours

    For patients on hemodialysis, the maximum dose is 2.25 g every twelve hours for all indications other than nosocomial pneumonia and 2.25 g every eight hours for nosocomial pneumonia. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g ZOSYN (0.67 g piperacillin/0.08 g tazobactam) should be administered following each dialysis period on hemodialysis days. No additional dosage of ZOSYN is necessary for CAPD patients.

    2.4 Dosage in Pediatric Patients With Appendicitis/Peritonitis or Nosocomial Pneumonia

    The recommended dosage for pediatric patients with appendicitis and/or peritonitis or nosocomial pneumonia aged 2 months of age and older, weighing up to 40 kg, and with normal renal function, is described in Table 2 [see Use in Specific Populations (8.4) and Clinical Pharmacology (12.3)].

    Table 2: Recommended Dosage of ZOSYN in Pediatric Patients 2 Months of Age and Older, Weighing Up to 40 kg, and With Normal Renal Function*
    AgeAppendicitis and/or PeritonitisNosocomial Pneumonia
    *
    Administer ZOSYN by intravenous infusion over 30 minutes
    2 months to 9 months90 mg/kg
    (80 mg piperacillin/10 mg tazobactam) every 8 (eight) hours
    90 mg/kg
    (80 mg piperacillin/10 mg tazobactam) every 6 (six) hours
    Older than 9 months of age112.5 mg/kg
    (100 mg piperacillin/12.5 mg tazobactam) every 8 (eight) hours
    112.5 mg/kg
    (100 mg piperacillin/12.5 mg tazobactam) every 6 (six) hours

    Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose [see Dosage and Administration (2.1, 2.2)].

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

    2.5 Reconstitution and Dilution of Powder Formulations

    Pharmacy bulk vials

    Reconstituted stock solution must be transferred and further diluted for intravenous infusion.

    The pharmacy bulk vial is for use in a hospital pharmacy admixture service only under a laminar flow hood. After reconstitution, entry into the vial must be made with a sterile transfer set or other sterile dispensing device, and contents should be dispensed as aliquots into intravenous solution using aseptic technique. Use entire contents of pharmacy bulk vial promptly. Discard unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

    Reconstitute the pharmacy bulk vial with exactly 152 mL of a compatible reconstitution diluent, listed below, to a concentration of 200 mg/mL of piperacillin and 25 mg/mL of tazobactam. Shake well until dissolved. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to and during administration whenever solution and container permit.

    Single dose vials

    Reconstitute ZOSYN vials with a compatible reconstitution diluent from the list provided below.

    2.25 g, 3.375 g, and 4.5 g ZOSYN should be reconstituted with 10 mL, 15 mL, and 20 mL, respectively. Swirl until dissolved.

    Compatible Reconstitution Diluents for Pharmacy and Single Dose Vials

    0.9% sodium chloride for injection
    Sterile water for injection
    Dextrose 5%
    Bacteriostatic saline/parabens
    Bacteriostatic water/parabens
    Bacteriostatic saline/benzyl alcohol
    Bacteriostatic water/benzyl alcohol

    Reconstituted ZOSYN solutions for both bulk and single dose vials should be further diluted (recommended volume per dose of 50 mL to 150 mL) in a compatible intravenous solution listed below. Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

    Compatible Intravenous Solutions for Pharmacy and Single Dose Vials

    0.9% sodium chloride for injection
    sterile water for injection1
    Dextran 6% in saline
    Dextrose 5%
    Lactated Ringer's Solution (compatible only with reformulated ZOSYN containing EDTA and is compatible for co-administration via a Y-site)

    ZOSYN should not be mixed with other drugs in a syringe or infusion bottle since compatibility has not been established.

    ZOSYN is not chemically stable in solutions that contain only sodium bicarbonate and solutions that significantly alter the pH.

    ZOSYN should not be added to blood products or albumin hydrolysates. Parenteral drug products should be inspected visually for particulate matter or discoloration prior to administration, whenever solution and container permit.


    1
    Maximum recommended volume per dose of sterile water for injection is 50 mL.

    Stability of ZOSYN Powder Formulations Following Reconstitution

    ZOSYN reconstituted from bulk and single vials is stable in glass and plastic containers (plastic syringes, I.V. bags and tubing) when used with compatible diluents. The pharmacy bulk vial should NOT be frozen after reconstitution. Discard unused portions after storage for 24 hours at room temperature or after storage for 48 hours at refrigerated temperature (2°C to 8°C [36°F to 46°F]).

    Single dose or pharmacy vials should be used immediately after reconstitution. Discard any unused portion after 24 hours if stored at room temperature (20°C to 25°C [68°F to 77°F]), or after 48 hours if stored at refrigerated temperature (2°C to 8°C [36°F to 46°F]). Vials should not be frozen after reconstitution.

    Stability studies in the I.V. bags have demonstrated chemical stability (potency, pH of reconstituted solution and clarity of solution) for up to 24 hours at room temperature and up to one week at refrigerated temperature. ZOSYN contains no preservatives. Appropriate consideration of aseptic technique should be used.

    ZOSYN reconstituted from bulk and single vials can be used in ambulatory intravenous infusion pumps. Stability of ZOSYN in an ambulatory intravenous infusion pump has been demonstrated for a period of 12 hours at room temperature. Each dose was reconstituted and diluted to a volume of 37.5 mL or 25 mL. One-day supplies of dosing solution were aseptically transferred into the medication reservoir (I.V. bags or cartridge). The reservoir was fitted to a preprogrammed ambulatory intravenous infusion pump per the manufacturer's instructions. Stability of ZOSYN is not affected when administered using an ambulatory intravenous infusion pump.

    2.6 Directions for Use of ZOSYN in GALAXY Containers

    ZOSYN Injection is to be administered using sterile equipment, after thawing to room temperature.

    ZOSYN containing EDTA is compatible for co-administration via a Y-site intravenous tube with Lactated Ringer's injection, USP.

    Do NOT add supplementary medication.

    Unused portions of ZOSYN should be discarded.

    Do NOT use plastic containers in series connections. Such use could result in air embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.

    Thawing of Plastic Container

    Thaw frozen container at room temperature 20°C to 25°C [68°F to 77°F] or under refrigeration (2°C to 8°C [36°F to 46°F]). Do not force thaw by immersion in water baths or by microwave irradiation.

    Check for minute leaks by squeezing container firmly. If leaks are detected, discard solution as sterility may be impaired.

    The container should be visually inspected. Components of the solution may precipitate in the frozen state and will dissolve upon reaching room temperature with little or no agitation. Potency is not affected. Agitate after solution has reached room temperature. If after visual inspection, the solution remains cloudy or if an insoluble precipitate is noted or if any seals or outlet ports are not intact, the container should be discarded.

    Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.

    Storage

    Store in a freezer capable of maintaining a temperature of -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.

    2.7 Compatibility with Aminoglycosides

    Due to the in vitro inactivation of aminoglycosides by piperacillin, ZOSYN and aminoglycosides are recommended for separate administration. ZOSYN and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated [see Drug Interactions (7.1)].

    In circumstances where co-administration via Y-site is necessary, ZOSYN formulations containing EDTA are compatible for simultaneous co-administration via Y-site infusion only with the following aminoglycosides under the following conditions:

    Table 3: Compatibility with Aminoglycosides
    AminoglycosideZOSYN
    Dose
    (grams)
    ZOSYN
    Diluent Volume *
    (mL)
    Aminoglycoside Concentration Range
    (mg/mL)
    Acceptable Diluents
    *
    Diluent volumes apply only to single vials and bulk pharmacy containers
    The concentration ranges in Table 3 are based on administration of the aminoglycoside in divided doses (10–15 mg/kg/day in two daily doses for amikacin and 3–5 mg/kg/day in three daily doses for gentamicin). Administration of amikacin or gentamicin in a single daily dose or in doses exceeding those stated above via Y-site with ZOSYN containing EDTA has not been evaluated. See package insert for each aminoglycoside for complete Dosage and Administration instructions.
    ZOSYN 3.375 g per 50 mL GALAXY Containers are NOT compatible with gentamicin for co-administration via a Y-site due to the higher concentrations of piperacillin and tazobactam.
    Amikacin2.25
    3.375
    4.5
    50
    100
    150
    1.75 – 7.50.9% sodium chloride or 5% dextrose
    Gentamicin2.25
    3.375
    4.5
    50
    100
    150
    0.7 – 3.320.9% sodium chloride or 5% dextrose

    Only the concentration and diluents for amikacin or gentamicin with the dosages of ZOSYN listed above have been established as compatible for co-administration via Y-site infusion. Simultaneous co-administration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by ZOSYN.

    ZOSYN is not compatible with tobramycin for simultaneous co-administration via Y-site infusion. Compatibility of ZOSYN with other aminoglycosides has not been established.

    Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

  • 3 DOSAGE FORMS AND STRENGTHS

    ZOSYN® (piperacillin and tazobactam) Injection is supplied in GALAXY Containers as a frozen, iso-osmotic, sterile, non-pyrogenic solution in single-dose plastic containers:

    2.25 g (piperacillin sodium equivalent to 2 g piperacillin and tazobactam sodium equivalent to 0.25 g tazobactam) in 50 mL.

    3.375 g (piperacillin sodium equivalent to 3 g piperacillin and tazobactam sodium equivalent to 0.375 g tazobactam) in 50 mL.

    4.5 g (piperacillin sodium equivalent to 4 g piperacillin and tazobactam sodium equivalent to 0.5 g tazobactam) in 100 mL.

    ZOSYN® (piperacillin and tazobactam) for Injection is a white to off-white powder in vials2:

    • 2.25 g single-dose vial (piperacillin sodium equivalent to 2 grams of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam).
    • 3.375 g single-dose vial (piperacillin sodium equivalent to 3 grams of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam).
    • 4.5 g single-dose vial (piperacillin sodium equivalent to 4 grams of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam).
    • 40.5 g pharmacy bulk vial (piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams tazobactam).

    2
    Zosyn for Injection vials are not manufactured or distributed by Pfizer Inc.
  • 4 CONTRAINDICATIONS

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

  • 5 WARNINGS AND PRECAUTIONS

    5.1 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 or a history of sensitivity to multiple allergens. Before initiating therapy with ZOSYN, careful inquiry should be made concerning previous hypersensitivity reactions. If an allergic reaction occurs, ZOSYN should be discontinued and appropriate therapy instituted.

    5.2 Severe Cutaneous Adverse Reactions

    ZOSYN may cause severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis. If patients develop a skin rash they should be monitored closely and ZOSYN discontinued if lesions progress.

    5.3 Hematologic Adverse Reactions

    Bleeding manifestations have occurred in some patients receiving beta-lactam drugs, including piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure. If bleeding manifestations occur, ZOSYN should be discontinued and appropriate therapy instituted.

    The leukopenia/neutropenia associated with ZOSYN administration appears to be reversible and most frequently associated with prolonged administration.

    Periodic assessment of hematopoietic function should be performed, especially with prolonged therapy, i.e., ≥ 21 days [see Adverse Reactions (6.1)].

    5.4 Central Nervous System Adverse Reactions

    As with other penicillins, ZOSYN may cause neuromuscular excitability or seizures. Patients receiving higher doses, especially patients with renal impairment may be at greater risk for central nervous system adverse reactions. Closely monitor patients with renal impairment or seizure disorders for signs and symptoms of neuromuscular excitability or seizures [see Adverse Reactions (6.2)].

    5.5 Nephrotoxicity in Critically Ill Patients

    The use of ZOSYN was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs in a randomized, multicenter, controlled trial in critically ill patients [see Adverse Reactions (6.1)]. Based on this study, alternative treatment options should be considered in the critically ill population. If alternative treatment options are inadequate or unavailable, monitor renal function during treatment with ZOSYN [see Dosage and Administration (2.3)].

    Combined use of piperacillin/tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury [see Drug Interactions (7.3)].

    5.6 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. Periodic electrolyte determinations should be performed in patients with low potassium reserves, and the possibility of hypokalemia should be kept in mind with patients who have potentially low potassium reserves and who are receiving cytotoxic therapy or diuretics.

    5.7 Clostridioides difficile-Associated Diarrhea

    Clostridioides difficile-associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including ZOSYN, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.

    C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibacterial drug use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

    If CDAD is suspected or confirmed, ongoing antibacterial drug use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

    5.8 Development of Drug-Resistant Bacteria

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

  • 6 ADVERSE REACTIONS

    6.1 Clinical Trials Experience

    Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

    Clinical Trials in Adult Patients

    During the initial clinical investigations, 2621 patients worldwide were treated with ZOSYN in phase 3 trials. In the key North American monotherapy clinical trials (n=830 patients), 90% of the adverse events reported were mild to moderate in severity and transient in nature. However, in 3.2% of the patients treated worldwide, ZOSYN was discontinued because of adverse events primarily involving the skin (1.3%), including rash and pruritus; the gastrointestinal system (0.9%), including diarrhea, nausea, and vomiting; and allergic reactions (0.5%).

    Table 4: Adverse Reactions from ZOSYN Monotherapy Clinical Trials
    System Organ Class
      Adverse Reaction
    Gastrointestinal disorders
      Diarrhea (11.3%)
      Constipation (7.7%)
      Nausea (6.9%)
      Vomiting (3.3%)
      Dyspepsia (3.3%)
      Abdominal pain (1.3%)
    General disorders and administration site conditions
      Fever (2.4%)
      Injection site reaction (≤1%)
      Rigors (≤1%)
    Immune system disorders
      Anaphylaxis (≤1%)
    Infections and infestations
      Candidiasis (1.6%)
      Pseudomembranous colitis (≤1%)
    Metabolism and nutrition disorders
      Hypoglycemia (≤1%)
    Musculoskeletal and connective tissue disorders
      Myalgia (≤1%)
      Arthralgia (≤1%)
    Nervous system disorders
      Headache (7.7%)
    Psychiatric disorders
      Insomnia (6.6%)
    Skin and subcutaneous tissue disorders
      Rash (4.2%, including maculopapular, bullous, and urticarial)
      Pruritus (3.1%)
      Purpura (≤1%)
    Vascular disorders
      Phlebitis (1.3%)
      Thrombophlebitis (≤1%)
      Hypotension (≤1%)
      Flushing (≤1%)
    Respiratory, thoracic and mediastinal disorders
      Epistaxis (≤1%)

    Nosocomial Pneumonia Trials

    Two trials of nosocomial lower respiratory tract infections were conducted. In one study, 222 patients were treated with ZOSYN in a dosing regimen of 4.5 g every 6 hours in combination with an aminoglycoside and 215 patients were treated with imipenem/cilastatin (500 mg/500 mg every 6 hours) in combination with an aminoglycoside. In this trial, treatment-emergent adverse events were reported by 402 patients, 204 (91.9%) in the piperacillin/tazobactam group and 198 (92.1%) in the imipenem/cilastatin group. Twenty-five (11.0%) patients in the piperacillin/tazobactam group and 14 (6.5%) in the imipenem/cilastatin group (p > 0.05) discontinued treatment due to an adverse event.

    The second trial used a dosing regimen of 3.375 g given every 4 hours with an aminoglycoside.

    Table 5: Adverse Reactions from ZOSYN Plus Aminoglycoside Clinical Trials*
    System Organ Class
      Adverse Reaction
    *
    For adverse drug reactions that appeared in both studies the higher frequency is presented.
    Blood and lymphatic system disorders
      Thrombocythemia (1.4%)
      Anemia (≤1%)
      Thrombocytopenia (≤1%)
      Eosinophilia (≤1%)
    Gastrointestinal disorders
      Diarrhea (20%)
      Constipation (8.4%)
      Nausea (5.8%)
      Vomiting (2.7%)
      Dyspepsia (1.9%)
      Abdominal pain (1.8%)
      Stomatitis (≤1%)
    General disorders and administration site conditions
      Fever (3.2%)
      Injection site reaction (≤1%)
    Infections and infestations
      Oral candidiasis (3.9%)
      Candidiasis (1.8%)
    Investigations
      BUN increased (1.8%)
      Blood creatinine increased (1.8%)
      Liver function test abnormal (1.4%)
      Alkaline phosphatase increased (≤1%)
      Aspartate aminotransferase increased (≤1%)
      Alanine aminotransferase increased (≤1%)
    Metabolism and nutrition disorders
      Hypoglycemia (≤1%)
      Hypokalemia (≤1%)
    Nervous system disorders
      Headache (4.5%)
    Psychiatric disorders
      Insomnia (4.5%)
    Renal and urinary disorders
      Renal failure (≤1%)
    Skin and subcutaneous tissue disorders
      Rash (3.9%)
      Pruritus (3.2%)
    Vascular disorders
      Thrombophlebitis (1.3%)
      Hypotension (1.3%)

    Other Trials: Nephrotoxicity

    In a randomized, multicenter, controlled trial in 1200 adult critically ill patients, piperacillin/tazobactam was found to be a risk factor for renal failure (odds ratio 1.7, 95% CI 1.18 to 2.43), and associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs1 [see Warnings and Precautions (5.5)].

    Adverse Laboratory Changes (Seen During Clinical Trials)

    Of the trials reported, including that of nosocomial lower respiratory tract infections in which a higher dose of ZOSYN was used in combination with an aminoglycoside, changes in laboratory parameters include:

    Hematologic—decreases in hemoglobin and hematocrit, thrombocytopenia, increases in platelet count, eosinophilia, leukopenia, neutropenia. These patients were withdrawn from therapy; some had accompanying systemic symptoms (e.g., fever, rigors, chills)

    Coagulation—positive direct Coombs' test, prolonged prothrombin time, prolonged partial thromboplastin time

    Hepatic—transient elevations of AST (SGOT), ALT (SGPT), alkaline phosphatase, bilirubin

    Renal—increases in serum creatinine, blood urea nitrogen

    Additional laboratory events include abnormalities in electrolytes (i.e., increases and decreases in sodium, potassium, and calcium), hyperglycemia, decreases in total protein or albumin, blood glucose decreased, gamma-glutamyltransferase increased, hypokalemia, and bleeding time prolonged.

    Clinical Trials in Pediatric Patients

    Clinical studies of ZOSYN in pediatric patients suggest a similar safety profile to that seen in adults.

    In a prospective, randomized, comparative, open-label clinical trial of pediatric patients, 2 to 12 years of age, with intra-abdominal infections (including appendicitis and/or peritonitis), 273 patients were treated with ZOSYN 112.5 mg/kg given IV every 8 hours and 269 patients were treated with cefotaxime (50 mg/kg) plus metronidazole (7.5 mg/kg) every 8 hours. In this trial, treatment-emergent adverse events were reported by 146 patients, 73 (26.7%) in the ZOSYN group and 73 (27.1%) in the cefotaxime/metronidazole group. Six patients (2.2%) in the ZOSYN group and 5 patients (1.9%) in the cefotaxime/metronidazole group discontinued due to an adverse event.

    In a retrospective, cohort study, 140 pediatric patients 2 months to less than 18 years of age with nosocomial pneumonia were treated with ZOSYN and 267 patients were treated with comparators (which included ticarcillin-clavulanate, carbapenems, ceftazidime, cefepime, or ciprofloxacin). The rates of serious adverse reactions were generally similar between the ZOSYN and comparator groups, including patients aged 2 months to 9 months treated with ZOSYN 90 mg/kg IV every 6 hours and patients older than 9 months and less than 18 years of age treated with ZOSYN 112.5 mg/kg IV every 6 hours.

    6.2 Postmarketing Experience

    In addition to the adverse drug reactions identified in clinical trials in Table 4 and Table 5, the following adverse reactions have been identified during post-approval use of ZOSYN. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

    Hepatobiliary—hepatitis, jaundice

    Hematologic—hemolytic anemia, agranulocytosis, pancytopenia

    Immune—hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock)

    Renal—interstitial nephritis

    Nervous system disorders—seizures

    Psychiatric disorders—delirium

    Respiratory—eosinophilic pneumonia

    Skin and Appendages—erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, (DRESS), acute generalized exanthematous pustulosis (AGEP), dermatitis exfoliative

    Postmarketing experience with ZOSYN in pediatric patients suggests a similar safety profile to that seen in adults.

    6.3 Additional Experience with Piperacillin

    The following adverse reaction has also been reported for piperacillin for injection:

    Skeletal—prolonged muscle relaxation [see Drug Interactions (7.5)].

  • 7 DRUG INTERACTIONS

    7.1 Aminoglycosides

    Piperacillin may inactivate aminoglycosides by converting them to microbiologically inert amides.

    In vivo inactivation:

    When aminoglycosides are administered in conjunction with piperacillin to patients with end-stage renal disease requiring hemodialysis, the concentrations of the aminoglycosides (especially tobramycin) may be significantly reduced and should be monitored.

    Sequential administration of ZOSYN and tobramycin to patients with either normal renal function or mild to moderate renal impairment has been shown to modestly decrease serum concentrations of tobramycin but no dosage adjustment is considered necessary.

    In vitro inactivation:

    Due to the in vitro inactivation of aminoglycosides by piperacillin, ZOSYN and aminoglycosides are recommended for separate administration. ZOSYN and aminoglycosides should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated. ZOSYN, which contains EDTA, is compatible with amikacin and gentamicin for simultaneous Y-site infusion in certain diluents and at specific concentrations. ZOSYN is not compatible with tobramycin for simultaneous Y-site infusion [see Dosage and Administration (2.7)].

    7.2 Probenecid

    Probenecid administered concomitantly with ZOSYN prolongs the half-life of piperacillin by 21% and that of tazobactam by 71% because probenecid inhibits tubular renal secretion of both piperacillin and tazobactam. Probenecid should not be co-administered with ZOSYN unless the benefit outweighs the risk.

    7.3 Vancomycin

    Studies have detected an increased incidence of acute kidney injury in patients concomitantly administered piperacillin/tazobactam and vancomycin as compared to vancomycin alone [see Warnings and Precautions (5.5)].

    Monitor kidney function in patients concomitantly administered with piperacillin/tazobactam and vancomycin.

    No pharmacokinetic interactions have been noted between piperacillin/tazobactam and vancomycin.

    7.4 Anticoagulants

    Coagulation parameters should be tested more frequently and monitored regularly during simultaneous administration of high doses of heparin, oral anticoagulants, or other drugs that may affect the blood coagulation system or the thrombocyte function [see Warnings and Precautions (5.3)].

    7.5 Vecuronium

    Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium. ZOSYN could produce the same phenomenon if given along with vecuronium. Due to their similar mechanism of action, it is expected that the neuromuscular blockade produced by any of the non-depolarizing muscle relaxants could be prolonged in the presence of piperacillin. Monitor for adverse reactions related to neuromuscular blockade (see package insert for vecuronium bromide).

    7.6 Methotrexate

    Limited data suggests that co-administration of methotrexate and piperacillin may reduce the clearance of methotrexate due to competition for renal secretion. The impact of tazobactam on the elimination of methotrexate has not been evaluated. If concurrent therapy is necessary, serum concentrations of methotrexate as well as the signs and symptoms of methotrexate toxicity should be frequently monitored.

    7.7 Effects on Laboratory Tests

    There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving piperacillin/tazobactam injection who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with the Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving piperacillin/tazobactam should be interpreted cautiously and confirmed by other diagnostic methods.

    As with other penicillins, the administration of ZOSYN may result in a false-positive reaction for glucose in the urine using a copper-reduction method (CLINITEST®). It is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    Piperacillin and tazobactam cross the placenta in humans. However, there are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. No fetal structural abnormalities were observed in rats or mice when piperacillin/tazobactam was administered intravenously during organogenesis at doses 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area (mg/m2). However, fetotoxicity in the presence of maternal toxicity was observed in developmental toxicity and peri/postnatal studies conducted in rats (intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21) at doses less than the maximum recommended human daily dose based on body-surface area (mg/m2) [see Data].

    The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively.

    Data

    Animal Data

    In embryo-fetal development studies in mice and rats, pregnant animals received intravenous doses of piperacillin/tazobactam up to 3000/750 mg/kg/day during the period of organogenesis. There was no evidence of teratogenicity up to the highest dose evaluated, which is 1 to 2 times and 2 to 3 times the human dose of piperacillin and tazobactam, in mice and rats respectively, based on body-surface area (mg/m2). Fetal body weights were reduced in rats at maternally toxic doses at or above 500/62.5 mg/kg/day, minimally representing 0.4 times the human dose of both piperacillin and tazobactam based on body-surface area (mg/m2).

    A fertility and general reproduction study in rats using intraperitoneal administration of tazobactam or the combination piperacillin/tazobactam prior to mating and through the end of gestation, reported a decrease in litter size in the presence of maternal toxicity at 640 mg/kg/day tazobactam (4 times the human dose of tazobactam based on body-surface area), and decreased litter size and an increase in fetuses with ossification delays and variations of ribs, concurrent with maternal toxicity at ≥640/160 mg/kg/day piperacillin/tazobactam (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area).

    Peri/postnatal development in rats was impaired with reduced pup weights, increased stillbirths, and increased pup mortality concurrent with maternal toxicity after intraperitoneal administration of tazobactam alone at doses ≥320 mg/kg/day (2 times the human dose based on body surface area) or of the combination piperacillin/tazobactam at doses ≥640/160 mg/kg/day (0.5 times and 1 times the human dose of piperacillin and tazobactam, respectively, based on body-surface area) from gestation day 17 through lactation day 21.

    8.2 Lactation

    Risk Summary

    Piperacillin is excreted in human milk; tazobactam concentrations in human milk have not been studied. No information is available on the effects of piperacillin and tazobactam on the breast-fed child or on milk production. The developmental and health benefits of breastfeeding should be considered 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.

    8.4 Pediatric Use

    The safety and effectiveness of ZOSYN for intra-abdominal infections, and nosocomial pneumonia have been established in pediatric patients 2 months of age and older.

    Use of ZOSYN in pediatric patients 2 months of age and older with intra-abdominal infections including appendicitis and/or peritonitis is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and in pediatric patients. This includes a prospective, randomized, comparative, open-label clinical trial with 542 pediatric patients 2 to 12 years of age with intra-abdominal infections (including appendicitis and/or peritonitis), in which 273 pediatric patients received piperacillin/tazobactam [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

    Use of ZOSYN in pediatric patients 2 months of age and older with nosocomial pneumonia is supported by evidence from well-controlled studies in adults with nosocomial pneumonia, a simulation study performed with a population pharmacokinetic model, and a retrospective, cohort study of pediatric patients with nosocomial pneumonia in which 140 pediatric patients were treated with ZOSYN and 267 patients treated with comparators (which included ticarcillin-clavulanate, carbapenems, ceftazidime, cefepime, or ciprofloxacin) [see Adverse Reactions (6.1) and Clinical Pharmacology (12.3)].

    The safety and effectiveness of ZOSYN have not been established in pediatric patients less than 2 months of age [see Clinical Pharmacology (12) and Dosage and Administration (2)].

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

    8.5 Geriatric Use

    Patients over 65 years are not at an increased risk of developing adverse effects solely because of age. However, dosage should be adjusted in the presence of renal impairment [see Dosage and Administration (2)].

    In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    ZOSYN contains 65 mg (2.84 mEq) of sodium per gram of piperacillin in the combination product. At the usual recommended doses, patients would receive between 780 and 1040 mg/day (34.1 and 45.5 mEq) of sodium. The geriatric population may respond with a blunted natriuresis to salt loading. This may be clinically important with regard to such diseases as congestive heart failure.

    This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

    8.6 Renal Impairment

    In patients with creatinine clearance ≤ 40 mL/min and dialysis patients (hemodialysis and CAPD), the intravenous dose of ZOSYN should be reduced to the degree of renal function impairment [see Dosage and Administration (2)].

    8.7 Hepatic Impairment

    Dosage adjustment of ZOSYN is not warranted in patients with hepatic cirrhosis [see Clinical Pharmacology (12.3)].

    8.8 Patients with Cystic Fibrosis

    As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients.

  • 10 OVERDOSAGE

    There have been postmarketing 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 seizures if higher than recommended doses are given intravenously (particularly in the presence of renal failure) [see Warnings and Precautions (5.4)].

    Treatment should be supportive and symptomatic according 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 the piperacillin and tazobactam dose removed by hemodialysis was approximately 31% and 39%, respectively [see Clinical Pharmacology (12)].

  • 11 DESCRIPTION

    ZOSYN (piperacillin and tazobactam) for Injection and ZOSYN (piperacillin and tazobactam) Injection are injectable antibacterial combination products consisting of the semisynthetic antibacterial piperacillin sodium and the beta-lactamase inhibitor tazobactam sodium for intravenous administration.

    Piperacillin sodium is derived from D(-)-α-aminobenzyl-penicillin. The chemical name of piperacillin sodium is sodium (2S,5R,6R)-6-[(R)-2-(4-ethyl-2,3-dioxo-1-piperazine-carboxamido)-2-phenylacetamido]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate. The chemical formula is C23H26N5NaO7S and the molecular weight is 539.5. The chemical structure of piperacillin sodium is:

    Chemical Structure

    Tazobactam sodium, a derivative of the penicillin nucleus, is a penicillanic acid sulfone. Its chemical name is sodium (2S,3S,5R)-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl)-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate-4,4-dioxide. The chemical formula is C10H11N4NaO5S and the molecular weight is 322.3. The chemical structure of tazobactam sodium is:

    Chemical Structure

    ZOSYN Injection in the GALAXY Container is a frozen iso-osmotic sterile non-pyrogenic premixed solution. The components and dosage formulations are given in the table below:

    Table 6: ZOSYN In GALAXY Containers Premixed Frozen Solution
    Component*FunctionDosage Formulations
    2.25 g/50 mL3.375 g/50 mL4.5 g/100 mL
    *
    Piperacillin and tazobactam are present in the formulation as sodium salts. Dextrose hydrous, sodium citrate dihydrate, and edetate disodium dihydrate amounts are approximate.
    Piperacillinactive ingredient2 g3 g4 g
    Tazobactambeta-lactamase inhibitor250 mg375 mg500 mg
    Dextrose Hydrousosmolality adjusting agent1 g350 mg2 g
    Sodium Citrate Dihydratebuffering agent100 mg150 mg200 mg
    Edetate Disodium Dihydratemetal chelator0.5 mg0.75 mg1 mg
    Water for Injectionsolventq.s. 50 mLq.s. 50 mLq.s. 100 mL

    ZOSYN contains a total of 2.84 mEq (65 mg) of sodium (Na+) per gram of piperacillin in the combination product.

    ZOSYN (piperacillin and tazobactam) for Injection, is a white to off-white sterile, cryodesiccated powder consisting of piperacillin and tazobactam as their sodium salts packaged in glass vials.3 The formulation also contains edetate disodium dihydrate (EDTA) and sodium citrate.

    • Each ZOSYN 2.25 g single dose vial contains an amount of drug sufficient for withdrawal of piperacillin sodium equivalent to 2 grams of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam. The product also contains 0.5 mg of EDTA per vial.
    • Each ZOSYN 3.375 g single dose vial contains an amount of drug sufficient for withdrawal of piperacillin sodium equivalent to 3 grams of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam. The product also contains 0.75 mg of EDTA per vial.
    • Each ZOSYN 4.5 g single dose vial contains an amount of drug sufficient for withdrawal of piperacillin sodium equivalent to 4 grams of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam. The product also contains 1 mg of EDTA per vial.
    • Each Zosyn 40.5 g pharmacy bulk vial contains piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 g of tazobactam sufficient for delivery of multiple doses.

    3
    Zosyn for Injection vials are not manufactured or distributed by Pfizer Inc.
  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    ZOSYN is an antibacterial drug [see Microbiology (12.4)].

    12.2 Pharmacodynamics

    The pharmacodynamic parameter for piperacillin/tazobactam that is most predictive of clinical and microbiological efficacy is time above MIC.

    12.3 Pharmacokinetics

    The mean and coefficients of variation (CV%) for the pharmacokinetic parameters of piperacillin and tazobactam after multiple intravenous doses are summarized in Table 7.

    Table 7: Mean (CV%) Piperacillin and Tazobactam PK Parameters
    Cmax : maximum observed concentration, AUC: Area under the curve, CL=clearance, CLR= Renal clearance
    V=volume of distribution, T1/2 = elimination half-life
    *
    Piperacillin and tazobactam were given in combination, infused over 30 minutes.
    Numbers in []parentheses are coefficients of variation [CV%].
    Piperacillin
    Piperacillin/Tazobactam Dose*Cmax (mcg/mL)AUC (mcg∙h/mL)CL (mL/min)V
    (L)
    T1/2
    (h)
    CLR (mL/min)
    2.25 g134131 [14]25717.40.79--
    3.375 g242242 [10]20715.10.84140
    4.5 g298322 [16]21015.40.84--
    Tazobactam
    Piperacillin/Tazobactam Dose*Cmax (mcg/mL)AUC (mcg∙h/mL)CL (mL/min)V
    (L)
    T1/2 (h)CLR (mL/min)
    2.25 g1516.0 [21]25817.00.77--
    3.375 g2425.0 [8]25114.80.68166
    4.5 g3439.8 [15]20614.70.82--

    Peak plasma concentrations of piperacillin and tazobactam are attained immediately after completion of an intravenous infusion of ZOSYN. Piperacillin plasma concentrations, following a 30-minute infusion of ZOSYN, were similar to those attained when equivalent doses of piperacillin were administered alone. Steady-state plasma concentrations of piperacillin and tazobactam were similar to those attained after the first dose due to the short half-lives of piperacillin and tazobactam.

    Distribution

    Both piperacillin and tazobactam are approximately 30% bound to plasma proteins. The protein binding of either piperacillin or tazobactam is unaffected by the presence of the other compound. Protein binding of the tazobactam metabolite is negligible.

    Piperacillin and tazobactam are widely distributed into tissues and body fluids including intestinal mucosa, gallbladder, lung, female reproductive tissues (uterus, ovary, and fallopian tube), interstitial fluid, and bile. Mean tissue concentrations are generally 50% to 100% of those in plasma. Distribution of piperacillin and tazobactam into cerebrospinal fluid is low in subjects with non-inflamed meninges, as with other penicillins (see Table 8).

    Table 8: Piperacillin/Tazobactam Concentrations in Selected Tissues and Fluids after Single 4 g/0.5 g 30-min IV Infusion of ZOSYN
    Tissue or FluidN*Sampling period
    (h)
    Mean PIP Concentration Range
    (mg/L)
    Tissue:Plasma RangeTazo Concentration Range
    (mg/L)
    Tazo Tissue:Plasma Range
    *
    Each subject provided a single sample.
    Time from the start of the infusion
    Skin350.5 – 4.534.8 – 94.20.60 – 1.14.0 – 7.70.49 – 0.93
    Fatty Tissue370.5 – 4.54.0 – 10.10.097 – 0.1150.7 – 1.50.10 – 0.13
    Muscle360.5 – 4.59.4 – 23.30.29 – 0.181.4 – 2.70.18 – 0.30
    Proximal Intestinal Mucosa71.5 – 2.531.40.5510.31.15
    Distal Intestinal Mucosa71.5 – 2.531.20.5914.52.1
    Appendix220.5 – 2.526.5 – 64.10.43 – 0.539.1 – 18.60.80 – 1.35

    Metabolism

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

    Excretion

    Following single or multiple ZOSYN doses to healthy subjects, the plasma half-life of piperacillin and of tazobactam ranged from 0.7 to 1.2 hours and was unaffected by dose or duration of infusion.

    Both piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and tubular secretion. Piperacillin is excreted rapidly as unchanged drug with 68% of the administered dose excreted in the urine. Tazobactam and its metabolite are eliminated primarily by renal excretion with 80% of the administered dose excreted as unchanged drug and the remainder as the single metabolite. Piperacillin, tazobactam and desethyl piperacillin are also secreted into the bile.

    Specific Populations

    Renal Impairment

    After the administration of single doses of piperacillin/tazobactam to subjects with renal impairment, the half-life of piperacillin and of tazobactam increases with decreasing creatinine clearance. At creatinine clearance below 20 mL/min, the increase in half-life is twofold for piperacillin and fourfold for tazobactam compared to subjects with normal renal function. Dosage adjustments for ZOSYN are recommended when creatinine clearance is below 40 mL/min in patients receiving the usual recommended daily dose of ZOSYN. See Dosage and Administration (2) for specific recommendations for the treatment of patients with renal -impairment.

    Hemodialysis removes 30% to 40% of a piperacillin/tazobactam dose with an additional 5% of the tazobactam dose removed as the tazobactam metabolite. Peritoneal dialysis removes approximately 6% and 21% of the piperacillin and tazobactam doses, respectively, with up to 16% of the tazobactam dose removed as the tazobactam metabolite. For dosage recommendations for patients undergoing hemodialysis [see Dosage and Administration (2)].

    Hepatic Impairment

    The half-life of piperacillin and of tazobactam increases by approximately 25% and 18%, respectively, in patients with hepatic cirrhosis compared to healthy subjects. However, this difference does not warrant dosage adjustment of ZOSYN due to hepatic cirrhosis.

    Pediatrics

    Piperacillin and tazobactam pharmacokinetics were studied in pediatric patients 2 months of age and older. The clearance of both compounds is slower in the younger patients compared to older children and adults.

    In a population PK analysis, estimated clearance for 9 month-old to 12 year-old patients was comparable to adults, with a population mean (SE) value of 5.64 (0.34) mL/min/kg. The piperacillin clearance estimate is 80% of this value for pediatric patients 2 – 9 months old. In patients younger than 2 months of age, clearance of piperacillin is slower compared to older children; however, it is not adequately characterized for dosing recommendations. The population mean (SE) for piperacillin volume of distribution is 0.243 (0.011) L/kg and is independent of age.

    Geriatrics

    The impact of age on the pharmacokinetics of piperacillin and tazobactam was evaluated in healthy male subjects, aged 18 – 35 years (n=6) and aged 65 to 80 years (n=12). Mean half-life for piperacilln and tazobactam was 32% and 55% higher, respectively, in the elderly compared to the younger subjects. This difference may be due to age-related changes in creatinine clearance.

    Race

    The effect of race on piperacillin and tazobactam was evaluated in healthy male volunteers. No difference in piperacillin or tazobactam pharmacokinetics was observed between Asian (n=9) and Caucasian (n=9) healthy volunteers who received single 4/0.5 g doses.

    Drug Interactions

    The potential for pharmacokinetic drug interactions between ZOSYN and aminoglycosides, probenecid, vancomycin, heparin, vecuronium, and methotrexate has been evaluated [see Drug Interactions (7)].

    12.4 Microbiology

    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. Tazobactam does not induce chromosomally-mediated beta-lactamases at tazobactam concentrations achieved with the recommended dosage regimen.

    Antimicrobial Activity

    ZOSYN has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections [see Indications and Usage (1)]:

    Aerobic bacteria

    Gram-positive bacteria

    Staphylococcus aureus (methicillin susceptible isolates only)

    Gram-negative bacteria

    Acinetobacter baumannii
    Escherichia coli
    Haemophilus influenzae
    (excluding beta-lactamase negative, ampicillin-resistant isolates)
    Klebsiella pneumoniae
    Pseudomonas aeruginosa
    (given in combination with an aminoglycoside to which the isolate is susceptible)

    Anaerobic bacteria

    Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron, and B. vulgatus)

    The following in vitro data are available, but their clinical significance is unknown.

    At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin/tazobactam against isolates of similar genus or organism group.

    However, the efficacy of ZOSYN in treating clinical infections caused by these bacteria has not been established in adequate and well-controlled clinical trials.

    Aerobic bacteria

    Gram-positive bacteria

    Enterococcus faecalis (ampicillin or penicillin-susceptible isolates only)
    Staphylococcus epidermidis (methicillin susceptible isolates only)

    Streptococcus agalactiae4
    Streptococcus pneumoniae4 (penicillin-susceptible isolates only)
    Streptococcus pyogenes4
    Viridans group streptococci4

    Gram-negative bacteria

    Citrobacter koseri
    Moraxella catarrhalis
    Morganella morganii
    Neisseria gonorrhoeae
    Proteus mirabilis
    Proteus vulgaris
    Serratia marcescens
    Providencia stuartii
    Providencia rettgeri
    Salmonella enterica

    Anaerobic bacteria

    Clostridium perfringens
    Bacteroides distasonis
    Prevotella melaninogenica


    4
    These are not beta-lactamase producing bacteria and, therefore, are susceptible to piperacillin alone.

    Susceptibility Testing

    For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Carcinogenesis

    Long-term carcinogenicity studies in animals have not been conducted with piperacillin/tazobactam, piperacillin, or tazobactam.

    Mutagenesis

    Piperacillin/tazobactam was negative in microbial mutagenicity assays, the unscheduled DNA synthesis (UDS) test, a mammalian point mutation (Chinese hamster ovary cell HPRT) assay, and a mammalian cell (BALB/c-3T3) transformation assay. In vivo, piperacillin/tazobactam did not induce chromosomal aberrations in rats.

    Fertility

    Reproduction studies have been performed in rats and have revealed no evidence of impaired fertility when piperacillin/tazobactam is administered intravenously up to a dose of 1280/320 mg/kg piperacillin/tazobactam, which is similar to the maximum recommended human daily dose based on body-surface area (mg/m2).

  • 15 REFERENCES

    1. Jensen J-US, Hein L, Lundgren B, et al. BMJ Open 2012; 2:e000635. doi:10.1136.
  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    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/tazobactam sodium equivalent to 0.25 g tazobactam) in 50 mL. Each container has 5.58 mEq (128 mg) of sodium. Supplied 24/box—NDC 0206-8860-02
    • 3.375 g (piperacillin sodium equivalent to 3 g piperacillin/tazobactam sodium equivalent to 0.375 g tazobactam) in 50 mL. Each container has 8.38 mEq (192 mg) of sodium. Supplied 24/box—NDC 0206-8861-02
    • 4.5 g (piperacillin sodium equivalent to 4 g piperacillin/tazobactam sodium equivalent to 0.5 g tazobactam) in 100 mL. Each container has 11.17 mEq (256 mg) of sodium. Supplied 12/box—NDC 0206-8862-02

    ZOSYN Injection in GALAXY Containers should be stored at or below -20°C (-4°F).

  • 17 PATIENT COUNSELING INFORMATION

    Serious Hypersensitivity Reactions

    Advise patients, their families, or caregivers that serious hypersensitivity reactions, including serious allergic cutaneous reactions, could occur that require immediate treatment. Ask them about any previous hypersensitivity reactions to ZOSYN, other beta-lactams (including cephalosporins), or other allergens [see Warnings and Precautions (5.2)].

    Diarrhea

    Advise patients, their families, or caregivers that diarrhea is a common problem caused by antibacterial drugs which usually ends when the drug is discontinued. Sometimes after starting treatment with antibacterial drugs, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as two or more months after having taken the last dose of the drug. If this occurs, patients should contact their physician as soon as possible.

    Antibacterial Resistance

    Counsel patients that antibacterial drugs including ZOSYN should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When ZOSYN is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by ZOSYN or other antibacterial drugs in the future.

    Counsel patients that ZOSYN can cross the placenta in humans and is excreted in human milk.

  • SPL UNCLASSIFIED SECTION

    FigureThis product's labeling may have been updated. For the most recent prescribing information, please visit http://www.pfizer.com.Figure

    Logo

    CLINITEST® is a registered trademark of Siemens Healthcare Diagnostics Inc.

    GALAXY is a registered trademark of Baxter International Inc.

    LAB-0690-13.0

  • PRINCIPAL DISPLAY PANEL – 2.25 g Container

    ZOSYN®
    (Piperacillin and Tazobactam
    Injection)

    2.25 g

    Rx only

    GALAXY

    Single Dose
    Container

    50 mL
    Iso-osmotic

    NDC 0206-8860-01
    Code 2G3575
    Sterile Nonpyrogenic

    Store at or below -20°C/-4°F. Thaw at room temperature 20° to 25°C (68° to 77°F)
    or under refrigeration 2° to 8°C (36° to 46°F). DO NOT FORCE THAW BY IMMERSION
    IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution remains
    stable for 14 days under refrigeration or 24 hours at room temperature.

    Do not refreeze.

    Dosage and Use: For intravenous use only. As directed by a physician. See Package Insert.
    Cautions: Do not add supplementary medication or additives. Must not be used
    in series connections. Check for minute leaks and solution clarity.

    Each 50 mL contains: Piperacillin Sodium equivalent to 2 g Piperacillin and
    Tazobactam Sodium equivalent to 0.25 g Tazobactam in Water for Injection.

    Approximately 1 g Dextrose Hydrous added to adjust osmolality. Approximately
    100 mg Sodium Citrate Dihydrate added as a buffer. pH adjusted with sodium
    bicarbonate and hydrochloric acid. pH 5.5 - 6.8

    Each 50 mL also contains approximately 0.5 mg Edetate Disodium Dihydrate added
    as a metal chelator.

    GALAXY is a registered trademark of Baxter International Inc.

    Distributed by
    Wyeth Pharmaceuticals LLC
    A subsidiary of Pfizer Inc
    Philadelphia, PA 19101

    PL 2040 Plastic

    14605200
    07-34-00-0150

    Pfizer Injectables

    PRINCIPAL DISPLAY PANEL – 2.25 g Container
  • PRINCIPAL DISPLAY PANEL – 2.25 g Container Box Label

    ZOSYN®
    (Piperacillin and Tazobactam
    Injection)

    Rx only

    2.25 g

    2 x 12 x 50 mL Single Dose Containers
    Contains 2 boxes of 12 of NDC 0206-8860-01
    Iso-osmotic
    Store at or
    below -20°C/-4°F.
    Do not refreeze.

    NDC 0206-8860-02
    Contains 24 of NDC 0206-8860-01
    Code 2G3575

    Pfizer Injectables

    PRINCIPAL DISPLAY PANEL – 2.25 g Container Box Label
  • PRINCIPAL DISPLAY PANEL – 3.375 g Container

    ZOSYN®
    (Piperacillin and Tazobactam
    Injection)

    3.375 g

    Rx only

    GALAXY

    Single Dose
    Container

    50 mL
    Iso-osmotic

    NDC 0206-8861-01
    Code 2G3576
    Sterile Nonpyrogenic

    Store at or below -20°C/-4°F. Thaw at room temperature 20° to 25°C (68° to 77°F)
    or under refrigeration 2° to 8°C (36° to 46°F). DO NOT FORCE THAW BY IMMERSION
    IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution remains
    stable for 14 days under refrigeration or 24 hours at room temperature.

    Do not refreeze.

    Dosage and Use: For intravenous use only. As directed by a physician. See Package Insert.
    Cautions: Do not add supplementary medication or additives. Must not be used
    in series connections. Check for minute leaks and solution clarity.

    Each 50 mL contains: Piperacillin Sodium equivalent to 3 g Piperacillin and
    Tazobactam Sodium equivalent to 0.375 g Tazobactam in Water for Injection.

    Approximately 350 mg Dextrose Hydrous added to adjust osmolality. Approximately
    150 mg Sodium Citrate Dihydrate added as a buffer. pH adjusted with sodium
    bicarbonate and hydrochloric acid. pH 5.5 - 6.8

    Each 50 mL also contains approximately 0.75 mg Edetate Disodium Dihydrate added
    as a metal chelator.

    GALAXY is a registered trademark of Baxter International Inc.

    Distributed by
    Wyeth Pharmaceuticals LLC
    A subsidiary of Pfizer Inc
    Philadelphia, PA 19101

    PL 2040 Plastic

    14604900
    07-34-00-0151

    Pfizer Injectables

    PRINCIPAL DISPLAY PANEL – 3.375 g Container
  • PRINCIPAL DISPLAY PANEL – 3.375 g Container Box Label

    ZOSYN®
    (Piperacillin and Tazobactam
    Injection)

    Rx only

    3.375g

    2 x 12 x 50 mL Single Dose Containers
    Contains 2 boxes of 12 of NDC 0206-8861-01
    Iso-osmotic
    Store at or
    below -20°C/-4°F.
    Do not refreeze.

    NDC 0206-8861-02
    Contains 24 of NDC 0206-8861-01
    Code 2G3576

    Pfizer Injectables

    PRINCIPAL DISPLAY PANEL – 3.375 g Container Box Label
  • PRINCIPAL DISPLAY PANEL – 4.5 g Container

    ZOSYN®
    (Piperacillin and Tazobactam
    Injection)

    4.5 g

    Rx only

    GALAXY

    Single Dose
    Container

    100 mL
    Iso-osmotic

    NDC 0206-8862-01
    Code 2G3577
    Sterile Nonpyrogenic

    Store at or below -20°C/-4°F. Thaw at room temperature 20° to 25°C (68° to 77°F)
    or under refrigeration 2° to 8°C (36° to 46°F). DO NOT FORCE THAW BY IMMERSION
    IN WATER BATHS OR BY MICROWAVE IRRADIATION. Thawed solution remains
    stable for 14 days under refrigeration or 24 hours at room temperature.

    Do not refreeze.

    Dosage and Use: For intravenous use only. As directed by a physician. See Package Insert.
    Cautions: Do not add supplementary medication or additives. Must not be used
    in series connections. Check for minute leaks and solution clarity.

    Each 100 mL contains: Piperacillin Sodium equivalent to 4 g Piperacillin and
    Tazobactam Sodium equivalent to 0.5 g Tazobactam in Water for Injection.

    Approximately 2 g Dextrose Hydrous added to adjust osmolality. Approximately
    200 mg Sodium Citrate Dihydrate added as a buffer. pH adjusted with sodium
    bicarbonate and hydrochloric acid. pH 5.5 - 6.8

    Each 100 mL also contains approximately 1 mg Edetate Disodium Dihydrate added
    as a metal chelator.

    GALAXY is a registered trademark of Baxter International Inc.

    Distributed by
    Wyeth Pharmaceuticals LLC
    A subsidiary of Pfizer Inc
    Philadelphia, PA 19101

    PL 2040 Plastic

    14605100
    07-34-00-0152

    Pfizer Injectables

    PRINCIPAL DISPLAY PANEL – 4.5 g Container
  • PRINCIPAL DISPLAY PANEL – 4.5 g Container Box Label

    ZOSYN®
    (Piperacillin and Tazobactam
    Injection)

    Rx only

    4.5 g

    2 x 6 x 100 mL Single Dose Containers
    Contains 2 boxes of 6 of NDC 0206-8862-01
    Iso-osmotic
    Store at or
    below -20°C/-4°F.
    Do not refreeze.

    NDC 0206-8862-02
    Contains 12 of NDC 0206-8862-01
    Code 2G3577

    Pfizer Injectables

    PRINCIPAL DISPLAY PANEL – 4.5 g Container Box Label
  • INGREDIENTS AND APPEARANCE
    ZOSYN   IN GALAXY CONTAINERS
    tazobactam sodium and piperacillin sodium injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0206-8860
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TAZOBACTAM SODIUM (UNII: UXA545ABTT) (TAZOBACTAM - UNII:SE10G96M8W) TAZOBACTAM250 mg  in 50 mL
    PIPERACILLIN SODIUM (UNII: M98T69Q7HP) (PIPERACILLIN ANHYDROUS - UNII:9I628532GX) PIPERACILLIN ANHYDROUS2 g  in 50 mL
    Inactive Ingredients
    Ingredient NameStrength
    DEXTROSE MONOHYDRATE (UNII: LX22YL083G) 1 g  in 50 mL
    SODIUM CITRATE, UNSPECIFIED FORM (UNII: 1Q73Q2JULR) 100 mg  in 50 mL
    EDETATE DISODIUM (UNII: 7FLD91C86K) 0.5 mg  in 50 mL
    SODIUM BICARBONATE (UNII: 8MDF5V39QO)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0206-8860-0224 in 1 BOX03/01/1998
    1NDC:0206-8860-0150 mL in 1 BAG; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA05075003/01/1998
    ZOSYN   IN GALAXY CONTAINERS
    tazobactam sodium and piperacillin sodium injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0206-8861
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TAZOBACTAM SODIUM (UNII: UXA545ABTT) (TAZOBACTAM - UNII:SE10G96M8W) TAZOBACTAM375 mg  in 50 mL
    PIPERACILLIN SODIUM (UNII: M98T69Q7HP) (PIPERACILLIN ANHYDROUS - UNII:9I628532GX) PIPERACILLIN ANHYDROUS3 g  in 50 mL
    Inactive Ingredients
    Ingredient NameStrength
    DEXTROSE MONOHYDRATE (UNII: LX22YL083G) 1.5 g  in 50 mL
    SODIUM CITRATE, UNSPECIFIED FORM (UNII: 1Q73Q2JULR) 150 mg  in 50 mL
    EDETATE DISODIUM (UNII: 7FLD91C86K) 0.75 mg  in 50 mL
    SODIUM BICARBONATE (UNII: 8MDF5V39QO)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0206-8861-0224 in 1 BOX03/01/1998
    1NDC:0206-8861-0150 mL in 1 BAG; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA05075003/01/1998
    ZOSYN   IN GALAXY CONTAINERS
    tazobactam sodium and piperacillin sodium injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC:0206-8862
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    TAZOBACTAM SODIUM (UNII: UXA545ABTT) (TAZOBACTAM - UNII:SE10G96M8W) TAZOBACTAM500 mg  in 100 mL
    PIPERACILLIN SODIUM (UNII: M98T69Q7HP) (PIPERACILLIN ANHYDROUS - UNII:9I628532GX) PIPERACILLIN ANHYDROUS4 g  in 100 mL
    Inactive Ingredients
    Ingredient NameStrength
    DEXTROSE MONOHYDRATE (UNII: LX22YL083G) 2 g  in 100 mL
    SODIUM CITRATE, UNSPECIFIED FORM (UNII: 1Q73Q2JULR) 200 mg  in 100 mL
    EDETATE DISODIUM (UNII: 7FLD91C86K) 1 mg  in 100 mL
    SODIUM BICARBONATE (UNII: 8MDF5V39QO)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    WATER (UNII: 059QF0KO0R)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC:0206-8862-0212 in 1 BOX03/01/1998
    1NDC:0206-8862-01100 mL in 1 BAG; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    NDANDA05075003/01/1998
    Labeler - Wyeth Pharmaceuticals LLC, a subsidiary of Pfizer Inc. (113008515)
    Establishment
    NameAddressID/FEIBusiness Operations
    Baxter Healthcare Corporation194684502ANALYSIS(0206-8860, 0206-8861, 0206-8862) , LABEL(0206-8860, 0206-8861, 0206-8862) , MANUFACTURE(0206-8860, 0206-8861, 0206-8862) , PACK(0206-8860, 0206-8861, 0206-8862)