2 DOSAGE AND ADMINISTRATION
2.1 Important Administration Instructions
If a dose of ZOSYN is required that does not equal 2.25 g, 3.375 g, or 4.5 g, ZOSYN injection in GALAXY Containers is not recommended for use and an alternative formulation of ZOSYN should be considered.
2.2 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.
2.3 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.
2.4 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.
|Creatinine clearance, mL/min||All Indications (except nosocomial pneumonia)||Nosocomial Pneumonia|
|Greater than 40 mL/min||3.375 every 6 hours||4.5 every 6 hours|
|20 to 40 mL/min†||2.25 every 6 hours||3.375 every 6 hours|
|Less than 20 mL/min†||2.25 every 8 hours||2.25 every 6 hours|
|Hemodialysis‡||2.25 every 12 hours||2.25 every 8 hours|
|CAPD||2.25 every 12 hours||2.25 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.
2.5 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)].
|Age||Appendicitis and/or Peritonitis||Nosocomial Pneumonia|
|2 months to 9 months||90 mg/kg|
(80 mg piperacillin/10 mg tazobactam) every 8 (eight) hours
(80 mg piperacillin/10 mg tazobactam) every 6 (six) hours
|Older than 9 months of age||112.5 mg/kg|
(100 mg piperacillin/12.5 mg tazobactam) every 8 (eight) hours
(100 mg piperacillin/12.5 mg tazobactam) every 6 (six) hours
Dosage of ZOSYN in pediatric patients with renal impairment has not been determined.
2.6 Reconstitution and Dilution of ZOSYN for Injection
Reconstitution of ZOSYN For Injection for Adult Patients and Pediatric Patients Weighing Over 40 kg
Pharmacy Bulk Vials
Reconstituted pharmacy bulk vial 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.
Reconstitute ZOSYN single-dose 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. After reconstitution, the single-dose vials will have a concentration of 202.5 mg/mL (180 mg/mL of piperacillin and 22.5 mg/mL of tazobactam).
Compatible Reconstitution Diluents for Pharmacy Bulk Vials and Single-Dose Vials
0.9% sodium chloride for injection
Sterile water for injection
Bacteriostatic saline/benzyl alcohol
Bacteriostatic water/benzyl alcohol
Dilution of the Reconstituted ZOSYN Solution for Adult Patients and Pediatric Patients Weighing Over 40 kg
Reconstituted ZOSYN solutions for both pharmacy bulk vials 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 Bulk Vials and Single-Dose Vials
0.9% sodium chloride for injection
Sterile water for injection (Maximum recommended volume per dose of sterile water for injection is 50 mL)
Dextran 6% in saline
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.
2.7 Directions for Use of ZOSYN Injection
Important Administration Instructions for ZOSYN Injection in GALAXY Containers
Administer ZOSYN Injection in GALAXY Containers 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 Injection 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.
Administration Instructions for ZOSYN Injection in GALAXY Containers to Adult Patients
Administer by infusion over a period of at least 30 minutes. During the infusion it is desirable to discontinue the primary infusion solution.
Storage of ZOSYN Injection
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 Injection.
2.8 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:
Diluent Volume *
|Aminoglycoside Concentration Range †|
|1.75 – 7.5||0.9% sodium chloride or 5% dextrose|
|0.7 – 3.32||0.9% 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.