Zosyn (Piperacillin / Tazobactam) - Indications and Dosage

INDICATIONS AND USAGE

ZOSYN is indicated for the treatment of patients with moderate to severe infections caused by piperacillin-resistant, piperacillin/tazobactam-susceptible, β-lactamase producing strains of the designated microorganisms in the specified conditions listed below:

Appendicitis (complicated by rupture or abscess) and peritonitis caused by piperacillin-resistant, β‑lactamase producing strains of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus. The individual members of this group were studied in less than 10 cases.

Uncomplicated and complicated skin and skin structure infections, including cellulitis, cutaneous abscesses, and ischemic/diabetic foot infections caused by piperacillin-resistant, β‑lactamase producing strains of Staphylococcus aureus.

Postpartum endometritis or pelvic inflammatory disease caused by piperacillin-resistant, β‑lactamase producing strains of Escherichia coli.

Community-acquired pneumonia (moderate severity only) caused by piperacillin-resistant, β‑lactamase producing strains of Haemophilus influenzae.

Nosocomial pneumonia (moderate to severe) caused by piperacillin-resistant, β-lactamase producing strains of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumanii, 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.)

ZOSYN is indicated only for the specified conditions listed above. Infections caused by piperacillin-susceptible organisms, for which piperacillin has been shown to be effective, are also amenable to ZOSYN treatment due to its piperacillin content. The tazobactam component of this combination product does not decrease the activity of the piperacillin component against piperacillin-susceptible organisms. Therefore, the treatment of mixed infections caused by piperacillin-susceptible organisms and piperacillin-resistant, β-lactamase producing organisms susceptible to ZOSYN should not require the addition of another antibiotic. (See DOSAGE AND ADMINISTRATION.)

ZOSYN is useful as presumptive therapy in the indicated conditions prior to the identification of causative organisms because of its broad spectrum of bactericidal activity against gram-positive and gram-negative aerobic and anaerobic organisms.

Appropriate cultures should usually be performed before initiating antimicrobial treatment in order to isolate and identify the organisms causing infection and to determine their susceptibility to ZOSYN. Antimicrobial therapy should be adjusted, if appropriate, once the results of culture(s) and antimicrobial susceptibility testing are known.

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

DOSAGE AND ADMINISTRATION

ZOSYN should be administered by intravenous infusion over 30 minutes.

The usual daily dose of ZOSYN for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam).

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). Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeruginosa is isolated. If Pseudomonas aeruginosa is not isolated, the aminoglycoside may be discontinued at the discretion of the treating physician.

Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, ZOSYN and the aminoglycoside are recommended for separate administration. ZOSYN and the aminoglycoside should be reconstituted, diluted, and administered separately when concomitant therapy with aminoglycosides is indicated. (See PRECAUTIONS, Drug Interactions.)

In circumstances where coadministration via Y-site is necessary, reformulated ZOSYN containing EDTA supplied in Galaxy containers is compatible for simultaneous coadministration via Y-site infusion only with the following aminoglycosides under the following conditions:

The following compatibility information does not apply to the ZOSYN (piperacillin/tazobactam) formulation not containing EDTA. This information does not apply to ZOSYN in vials or bulk pharmacy containers. Refer to the package insert for ZOSYN vials or bulk pharmacy containers for instructions.

TABLE 5

Aminoglycoside	ZOSYN Dose (grams)	Aminoglycoside Concentration Range* (mg/mL)	Acceptable Diluents
Amikacin	2.25, 3.375, 4.5	1.75 – 7.5	0.9% Sodium Chloride or 5% Dextrose
Gentamicin	2.25, 3.375, 4.5	0.7 – 3.32	0.9% Sodium Chloride or 5% Dextrose
*The concentration ranges in Table 5 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 is not compatible with tobramycin for simultaneous coadministration via Y-site infusion. Compatibility of ZOSYN with other aminoglycosides has not been established. Only the concentration and diluents for amikacin or gentamicin with the dosages of ZOSYN listed above have been established as compatible for coadministration via Y-site infusion. Simultaneous coadministration via Y-site infusion in any manner other than listed above may result in inactivation of the aminoglycoside by ZOSYN.

Renal Insufficiency

In patients with renal insufficiency (Creatinine Clearance ≤ 40 mL/min), the intravenous dose of ZOSYN should be adjusted to the degree of actual renal function impairment. In patients with nosocomial pneumonia receiving concomitant aminoglycoside therapy, the aminoglycoside dosage should be adjusted according to the recommendations of the manufacturer. The recommended daily doses of ZOSYN for patients with renal insufficiency are as follows:

Recommended Dosing of ZOSYN in Patients with Normal Renal Function and Renal Insufficiency (As total grams piperacillin/tazobactam)

Renal Function (Creatinine Clearance, mL/min)	All Indications (except nosocomial pneumonia)	Nosocomial Pneumonia
>40 mL/min	3.375 q 6 h	4.5 q 6 h
20-40 mL/min*	2.25 q 6 h	3.375 q 6 h
<20 mL/min*	2.25 q 8 h	2.25 q 6 h
Hemodialysis**	2.25 q 12 h	2.25 q 8 h
CAPD	2.25 q 12 h	2.25 q 8 h
* Creatinine clearance for patients not receiving hemodialysis ** 0.75 g should be administered following each hemodialysis session on hemodialysis days

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 should be administered following each dialysis period on hemodialysis days. No additional dosage of ZOSYN is necessary for CAPD patients.

Duration of Therapy

The usual duration of ZOSYN treatment is from seven to ten days. However, the recommended duration of ZOSYN treatment of nosocomial pneumonia is 7 to 14 days. In all conditions, the duration of therapy should be guided by the severity of the infection and the patient's clinical and bacteriological progress.

Pediatric Patients

For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended ZOSYN dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended ZOSYN dosage based on pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours (see PRECAUTIONS, General, Pediatric Use and CLINICAL PHARMACOLOGY). Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. There are no dosage recommendations for ZOSYN in pediatric patients with impaired renal function.

ZOSYN in Galaxy containers should not be used in pediatric patients who require less than the full adult dose of ZOSYN in order to prevent unintentional overdose. The other available formulations of ZOSYN can be used in this population.

DIRECTIONS FOR USE OF ZOSYN (PIPERACILLIN AND TAZOBACTAM INJECTION) IN GALAXY CONTAINERS (PL 2040 PLASTIC)

ZOSYN Injection (PL 2040 Plastic) is to be administered using sterile equipment after thawing to room temperature.

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

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

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.

STORAGE

Store in a freezer capable of maintaining a temperature of -20°C (-4°F).

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.

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 ANTIBIOTICS.

DO NOT ADD SUPPLEMENTARY MEDICATION.

UNUSED PORTIONS OF ZOSYN SHOULD BE DISCARDED.

CAUTION: 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.

Preparation for administration:

1. Suspend container from eyelet support.
2. Remove protector from outlet port at bottom of container.
3. Attach administration set. Refer to complete directions accompanying set.

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

HOW SUPPLIED

ZOSYN (piperacillin and tazobactam injection) in Galaxy Container (PL 2040 Plastic) is 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 0206-2409-02

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 0206-2411-02

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 0206-2413-02

Store at or below -20°C (-4°F). [See DOSAGE AND ADMINISTRATION, DIRECTIONS FOR USE OF ZOSYN (PIPERACILLIN AND TAZOBACTAM INJECTION) IN GALAXY CONTAINERS (PL 2040 PLASTIC).]

Also Available

ZOSYN (piperacillin and tazobactam for injection, USP) is also supplied as follows:

2.25 g single-dose vial containing piperacillin sodium equivalent to 2 g of piperacillin and tazobactam sodium equivalent to 0.25 g of tazobactam. Each vial contains 5.58 mEq (128 mg) of sodium. Supplied 10/box—NDC 0206-2404-02

3.375 g single-dose vial containing piperacillin sodium equivalent to 3 g of piperacillin and tazobactam sodium equivalent to 0.375 g of tazobactam. Each vial contains 8.38 mEq (192 mg) of sodium. Supplied 10/box—NDC 0206-2405-02

4.5 g single-dose vial containing piperacillin sodium equivalent to 4 g of piperacillin and tazobactam sodium equivalent to 0.5 g of tazobactam. Each vial contains 11.17 mEq (256 mg) of sodium. Supplied 10/box—NDC 0206-2408-02

Also Available

ZOSYN (piperacillin and tazobactam for injection, USP) is also supplied as a powder in the pharmacy bulk vial as follows:

40.5 g pharmacy-bulk vial containing piperacillin sodium equivalent to 36 grams of piperacillin and tazobactam sodium equivalent to 4.5 grams of tazobactam. Each pharmacy-bulk vial contains 100.4 mEq (2,304 mg) of sodium. NDC 0206-2416-01

ZOSYN (piperacillin and tazobactam for injection, USP) vials should be stored at controlled room temperature 20°C to 25°C (68°F to 77°F) prior to reconstitution.