1292 PiPeracillin Sodium–TazobacTam Sodium aSHP inJecTable druG inFormaTion
Piperacillin Sodium–Tazobactam Sodium
AHFS 8:12.16.16
Products
The fixed combination of piperacillin sodium–tazobactam
sodium is available as a lyophilized powd er in preservative-free
single-dose and ADD-Vantage vials containing 2.25 g (pipera-
cillin 2 g plus tazobactam 250 mg), 3.375 g (piperacillin 3 g plus
tazobactam 375 mg), or 4.5 g (piperacillin 4 g plus tazobactam
500 mg) as the sodium salts.2918 2919 2921 The drug is also available
in a pharmacy bulk package containing 40.5 g (piperacillin 36 g
plus tazobactam 4.5 g) as the sodium salts.2918 2920
Generic piperacillin sodium–tazobactam sodium and Zosyn
(Wyeth) products are not identical.2922 2932 In 2006, all Zosyn
products were reformulated to contain edetate disodium dihy-
drate (EDTA) as a metal chelator and sodium citrate as a buffering
agent; these excipients were added to address issues with sporadic
batch failures associated with excessive particulate matter
related to commercially available diluents and solutions with
acidic pH and the presence of trace amounts of zinc ions.2922 2932
Other piperacillin sodium–tazobactam sodium products do n ot
contain EDTA, sodium citrate, or any other excipients.2919 2920 2921
These formulation differences between Zosyn products and other
piperacillin sodium–tazobactam sodium products have been
demonstrated to result in some differing compatibilities with
certain solutions (e.g., Ringer’s injection, lactated).2922 2932 2985
Therefore, results of compatibility tests for one formula-
tion cannot be extrapolated to another.2922 2932 (See Solution
Compatibility.)
Each 2.25, 3.375, or 4.5 g (combined components) single-
dose vial should be reconstituted with 10, 15, or 20 mL, respec-
tively, of s terile water for injection, sodium chloride 0.9%,
bacteriostatic water for injection or bacteriostatic sodium
chloride 0.9% (preserved with benzyl alcohol or parabens), or
dextrose 5% and should be swirled until dissolved.2918 2921 The
contents of each single-dose vial should then be diluted in 50
to 150 mL of a compatible infusion solution; however, if sterile
water for injection is used as the diluent, the maximum recom-
mended volume per dose is 50 mL.2918 2921
ADD-Vantage vials of piperacillin sodium–tazobactam
sodium should be prepared with 50 or 100 mL of dextrose 5% or
sodium chloride 0.9% in ADD-Vantage diluent bags.2919
The 40.5-g pharmacy bulk package should be recons tituted
with 152 mL of sterile water for injection, sodium chloride 0.9%,
bacteriostatic water for injection or bacteriostatic sodium chlo-
ride 0.9% (preserved with benzyl alcohol or parabens), or
dextrose 5% and should be shaken until dissolved; the resulting
solution contains piperacillin 200 mg/mL plus tazobactam 25
mg/mL.2918 2920 The reconstituted pharmacy bulk package solu-
tion mus t be diluted further in a compatible infusion solution;
the recommended volume per dose is 50 to 100 mL;2918 2920 2922
however, if sterile water for injection is used as the diluent, the
maximum recommended volume per dose is 50 mL.2918 2920 2922
Piperacillin sodium–tazobactam sodium (Zosyn, Wyeth) also
is available as a frozen iso-osmotic premixed injection in single-
dose Galaxy containers containing piperacillin 40 mg/mL plus
tazobactam 5 mg/mL or piperacillin 60 mg/mL plus tazobactam
7.5 mg/mL, as well as EDTA and sodium citrate dihydrate, in
water for injection.2918 2922 Dextrose hydrous is added to adjust
the osmolality, and sodium bicarbonate and hydrochloric acid
are used to adjust the pH.2918 2922
pH
Zosyn (Wyeth) products: From 5.5 to 6.8.2918 2922
Sodium Content
Zosyn (Wyeth) products contain 2.79 mEq (64 mg) of sodium
per gram of piperacillin in the combination product.2918
Generic piperacillin sodium–tazobactam sodium products
contain 2.35 mEq (54 mg) of sodium per gram of piperacillin in
the combination product.2919 2920 2921
Trade Name(s)
Zosyn
Administration
Piperacillin–tazobactam solution for infusion prepared from
single-dose vials or the pharmacy bulk package should be
administered by intravenous infusion over at leas t 30 minutes
after dilution in a compatible diluent to provide a recommended
volume per dose of 50 to 150 mL.2918 2920 2921 Such solutions
for infusion prepared using single-dose vials or the pharmacy
bulk package also can be infused using ambulatory infusion
pumps.2918 2920 2921
Piperacillin sodium–tazobactam sodium (Zosyn, Wyeth)
frozen iso-osmotic premixed injection in single-dose Galaxy
containers should be thawed (see Stability: Freezing Solutions),
and the solution should be administered by intravenous infusion
over at least 30 minutes.2918
Use of extended infusion s trategies (e.g., infusion over 4
hours) for piperacillin–tazobactam has been described in the
literature.2934 In such circums tances, however, careful attention
must be paid to the possibility of incomplete dose adminis tra-
tion resulting from drug loss through tubing residuals.2934 Such
loss is a function of both the concentration of the solution being
infused and the residual volume of the specific t ubing used for
administration.2934
Stability
The white to off-white2918 2920 2921 or yellowish2919 piperacillin
sodium–tazobactam sodium lyophilized powder in intact vials
should be stored at controlled room temperature.2918 2919 2920 2921
Single-dose vials of the solution should be used immedi-
ately after reconstitution.2918 2921 Any remaining unused portion
DOI: 10.37573/9781585286850.317
