I®

Sterile Piperacillm/Tazobactam Sodium

PRESENTATION
TAZOCIN, piperadllinrtazobactam parenteral combination, is a white to off white sterile,
cryodesiccated powder consisting of piperacillin and tazobactam as their sodium salts
packaged in glass vials. The product does not contain excipients or preservatives.
Each TAZOCIN 4.5 g single dose vial contains an amount of drug sufficient lor withdrawal of
piperacillin sodium equivalent to 4 g of piperacillin and tazobactam sodium equivalent to 0.5 g
of tazobactam. The product also contains 1 mgedetatedisodium (dihydrate) (EDTA) per vial.

INDICATIONS AND USAGE

TAZOGIN is indicated for the treatment of patients with moderate to severe infections caused
by piperacillin resistant, piperacillin/tazobactam susceptible, [}-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, |i-laotamase producing strains of Escherichia coli or the following members of the
Bacteroides fiagilis group: B. tragilis, 8. ovatus,B. thetalotaomfcron orO. 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,
|i-lactamase producing strains of Staphylococcus aureus.

Postpartum endometritis Or pelvic inflammatory disease caused by piperacillin resistant,

|i- lactamase producing strains of Escherichia coli.
Community-acquired pneumonia (moderate severity only) caused by piperacillin resistant,
|!-lactamase producing strains of Haemophilus influenzae.
As a combination product, TAZOCIN 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 TAZOCIN 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, (5-lactamase producing organisms susceptible to TAZOCIN should not require the
addition of another antibiotic: • • ••

TAZOCIN 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
usuallybe performed before initiating antimicrobial treatment in order to isolateandidentify the
organisms causing infection and to determine their susceptibility to TAZOCIN. Antimicrobial
therapy should be adjusted, if appropriate, once the results of culture® and antimicrobial
susceptibility testing are known.

Adults and children:

Febrile neutropenic infections. Combination treatment with an amniogyteoside Is recommended.

DOSAGE AND ADMINISTRATION

TAZOCIN must be given by slow intravenous infusion (e.g., over 20-30 minutes} or. alow
intravenous injection (over at .east 3-S minutes).
• Duration of Therapy
The usual duration of TAZOCIN treatment Isfromseven to ten days.
The duration of therapy should be guided by the severity of the infection and the patient's
clinical and bacteriological progress.
• Adults and Children 12 Years and Older
In general, the recommended total daily dosage is 12 g piperacillin /1.5 g tazobactam given
in divided doses every 6 or 8 hours. Doses as high as 18 g piperacillin /2,25 g tazobactam
per day in divided doses can be used in severe infections.
In neutropenia the recommended dose is 4.5 g Tazocin (4 g piperacilltn/50u mg tazobactam)
given every 6 hours in combination with aminoglycoside.
Pediatric Neutropenia:
For children aged 2-12 years with normal renal function and weighing less than 50 kg, the
dose should be adjusted to 80 mg piperacillin/10 mg tazobactam per kg administered every
6 hours, in combination with the appropriate dose of an aminoglycoside,
For children weighing over 50 kg, follow the adutt dosing, In combination with the appropriate
dose of an aminogyiccside.
• Use In Patients with Renal Impairment
In patients with renai insufficiency or hemodialysis patients, intravenous dosages and
administration intervals should be adjusted to the degree of renal function impairment.
The recommended daily doses are as follows:
TAZOCIN DOSAGE RECOMMENDATIONS
Creatinine Clearance (ml/min) Recommended PiperacillirvTazobaclam Dosage
12g/1.5g/day
20-80 Divided doses
4 g/500 mg every 8 hours
8g/1 g/day
Divided doses
4 g/500 mg every 12 hours
for patients on hemodialysis, the maximum dose is 225 g TAZOCIN q eight hours. In
addition because hemodialysis removes 30% - 40% of a TAZOCIN dose in four hours, one
additional dose of 0.75 g TAZOCIN should be administered following each dialysis period.
For patients with renal failure, measurement of serum levels of piperacilin and tazobactam
will provide additional guidance for adjusting dosage.

• Use in Patients with Hepatic Impairment

No dosage adjustment of TAZOCIN is necessary in patients with hepatic impairment.
• Co-administration of piperacillin/tazobactam with Aminoglycosides
Due to the in vitro inactivation of the aminoglycoside by beta-lactam antibiotics, TAZOCIN
and the aminoglycoside are recommended for separate administration. TAZOCIN and the
aminoglycoside should be reconstituted and diluted separately whan concomitant therapy
with aminoglycosides is indicated (see Section COMPATIBILITIES. INCOMPATIBILITIES).
In clrcumstanceswterec^ containing
EDTA supplied in vials is compatible fcf simultaneous^ ^ via Y-site Infusion
only with the following aminoglycosides under the following conditions: - :
:

Aminoglycoside TAZOCIN TAZOCIN Aminoglycoside Acceptable Diluents

(grams) dose Diluent Concentration
Volume (mL) Range (mg/mL)'
Amikacin 2.25,3.375,4.5 50,100,150 1.75-7.5 0.9% Sodium chloride
or 5% dextrose
Gentamicin 2.25,3.375,4.5 100,150 0./-3.32 0.9% sodium chloride
or 5% dextrose
'Thsdoseof am rcglycosidesr-c J d tx: baijud c i oatient weight. stoics of infection (senous
or life threatening) and renal function (creatinine clearance).
Compatibility of TAZOCIN with other aminoglycosides has not been established. Only the
concentration and diluents fbramikacinand gentamicin with thedosages of TAZOCIN listed
in the above table have been established as compatible for co-administration via Y-site
infusion. Simultaneous co-administration via Y-site. in any manner other than listed above
may result in inactivation of the aminoglycoside by TAZOCIN.

CONTRAINDICATIONS
Hypersensitivity to any of the beta-iactems (lriG|udlng penicillins and cephalosporins) of to
beta-lactamase inhibitors.

SPECIAL WARNINGS
Before initiating therapywith TAZOCIN, carefu (inquiry should be made concerning previous
hypersensitivity reactions to penicillins, cephalosporins, arid Other allergens. Serious and
occasionally fatal hypersensitivity (ar>aphyiactic/anaphylactoid [including shock]) reactions
have been reported in patients receiving therapy with penicillins including TAZOCIN.

These reactions are more likely to occur in persons with a history of sensitivity to multiple
allergens. Serious hypersensitivityreactionsrequirethe discontinuation of the antibiotic, and
may require administration of epinephrine and other emergency measures.

Serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis,
have been reported in patients receiving TAZOCIN (see Section ADVERSE REACTIONS).
If patients develop a skin rash fhey should be monitored closely and PIPERACILLIN/
TAZOBACTAM discontinued if lesions progress.

Antibiotic-induced pseudomembranous colitis may be manifested by severe, persistent

diarrhea which may be life-threatening. The onset of pseudomembranous colitis symptoms
may occur during or after antibacterial treatment.
". ... ' " ' * 'iir^^it'(|ti'i |W|Wi<l*> I,
r

PRECAUTIONS 'j^iSPvs^- !•. * C - :

:

Bleeding manifestations have occurred in some patients receiving beta-lactarn antibiotics.

These reactions sometimes have 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 (seeSection INTERACTIONS). If bleeding manifestations occur,
the antibiotic should be discontinued and appropriate therapy instituted.

This product contains2.79 mEq(64mg)of sodium per gram of piperacillin which may increase
a patient's overall sodium intake. Hypokalemia may occur in patients with low potassium
reserves or who are receiving concomitant medications that may lower potassium levels;
periodic electrolyte determinations may be advisable in such patients;

LeulOTpenia^dTieotropenla-may occur, "especially during prolonged therapy. Therefore,

-

periodic assessment of hematopoietic function should be performed.

As with treatment with other penicillins, neurological com plications in the form of convulsions
may occur when high doses are administered, especially iri patients with impaired renal function.
• Use In Patients with Hepatic Impairment
No dosage adjustment of piperacillin/tazobactam is necessary in patients with hepatic
impairment. ~.'V.\
• Use in Patients with Renal Impairment
In patients with renal insufficiency or hemodialysis patients, the intravenous dose should be
PREGNANCY
Studies in mice and rats have not demonstrated any reproductive or embryo-fetal effects
of the piperacillin-tazobactam combination when administered intravenously. There are no
adequate and we!I-controlled studies with the piperacillin-tazobactam combination or with
piperacillin or tazobactam alone in pregnant women. Piperacillin and tazobactam cross the
placenta. Pregnant women should be treated only if the expected benefit outweighs the
possible nsks to the pregnant woman and le'us. ^••:%m%%£, • % ». .• • * • •

LACTATION
Piperacillin is excreted in low concentrations in human milk; tazobactam concentrations in
human milk have hot been studied. Women who are breast-feeding should be treated only
if the expected benefit outweighs the possible risks to the woman and child.

GERIATRIC USE
Patients over 65 years are not at an Increased risk of developing adverse effects solely
Reams* of age. &SkMr& ''i* '----
: i

•towever,dosage should be adjusted in the presence of renal insufficiency.

_ ^^^^^^^^^^iS&'iS -•• !•-< -4." .^tf** t*i**s :
? nws<*
INTERACTIONS • * '
• Nbn-depotarizingmusde'relaxanfe-
Piperacillin when used conccmilantty with vecuronium has been implicated in thB prolongation
of the neuromuscular blockade of vecuronium. Dueto their stmiiar mechanism of action, it is
expected that the neuromuscular blockade produced by any of then on-depolarizing muscle
relaxants could be prolonged In the presence of piperacillin.
• Orafanticoagularits'-'-.>/-K& •Ksvfe^'-;
During simultaneous administration of heparin^ oral anticoagulants and other drugs that
may affect the blood coagulation system including thrombocyte function, appropriate
coagulation tests should be performed more frequently and monitored regularly (see Section
PRECAUTIONS),
• Methotrexate
Piperacillin may reducethe excretion of methotrexate; therefore, serum levels of methotrexate
should be monitored In patients to avoid drug toxicity.
 8430112 RF - Laefus 262

• Probenecid : il&xV&A'*-*'
As with other penicillins, concurrent administration of probenecid and TAZOCIN produces
a longer half-iife and lower renal clearance for both piperacillin and tazobactam; however,
peak plasma concentrations of either drug are unaffected.
• Aminoglycosides . »
Piperacillin, either alone or with tazobactam, did not significantly alter fhe pharmacokinetics
of tobramycin in subjects with mild or moderate renal impairment. The pharmacokinetics
of piperacillin, tazobactam, and the M1 metabolite were also not significantly altered by
tobramycin administration, .t -,\

Tazocin is not compatible with tobramycin for simultaneous co-administration via Y-site infusion.
• Vancomycin
No pharmacokinetic Interactions have been noted between PIPERACIUJN/TAZOBACTAtvl
and vancomycin.

INTERFERENCE WITH LABORATORY AND OTHER DIAGNOSTIC TESTS - •

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

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

ADVERSE REACTIONS
Adverse reactions are listed in the Tahle in CIOMS frequency categories;
Very common: a 10%
Common: = 1%
Uncommon: a0.1%and<1%
Rare: 20.0t%and<0.1%
Very rare; <0.01%
Not known: frequency could not be accurately estimated from clinical studies
Body System Adverse Reaction
I nfactions and infestations
Uncommon: Candidal superinfection
Blood and lymphatic system ^ **- t

Uncommon: Leukopenia, neutropenia, thrombocytopenia

Rare: Anemia, bleeding manifestations {including purpura, epistaxis.
bleeding time prolonged), eosinophilia, haemdlytic anemia
Very rare: Agranulocytosis, Coombs direct test positive, Pancytopenia,
prolonged partial thromboplastin time, prothrombin time
prolonged, thrombocytosis

Immune system disorders

Uncommon: Hypersensitivity reaction
Rare: Anaphylactic/anaphylactoid reaction (including shock).
Metabolism and Nutrition Disorders
Very rare: Blood albumin decreased, Wood glucose decreased, blood
total protein decreased, hypokalemia
Nervous system disorders
Uncommon • Headacie, insomnia
Vascular disorders- u • • .-^»r
Uncommon: Hypotension, phlebitis, thrombophlebilis
Rare: Flushing
Gastrointestinal
Common: Diarrhea, nausea, vomiting
Uncommon: Constipation, dyspepsia, jaundice, stomatitis
Rare: Abdominal pain, pseudomembranous colrtis
Hepatobiliary
Uncommon: Alanine aminotransferase increased, aspartate
aminotransferase increased
Rare: Bilirubin Increased, blood alkaline phosphatase increased,
gamma-glutamyltransferase increased, hepatitis
Skin and subcutaneous tissue disorders
Common: Rash
Uncommon: Pruritis, urticaria . ,. _..,,„.., ,
Rare: Bullous dermatitis, erythema multiforme
Very Rare: Stevens-John son Syndrome, toxic epidermal necrolysis
Musculoskeletal, Connective tissue and bone disorders
Rare: ""..Arthralgia
Frequency unknown: Myalgia
Renal and urinary disorders
Uncommon: Blood creatinine Increased
Rare: Interstitial nephritis, renal failure
Very rare; Blood urea nitrogen increased
General disorders and administration site conditions
Uncommon: Fever, injection site reaction

Piperacillin therapy has been associated with an increased incidence, of fever and rash in
cystic fibrosis patients. . .]
OVERDOSAGE
There have been post-marketing reports of overdose with TAZOCIN. 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 cr
convulsions if higher than recommended doses are given intravenously (particularly in the
presence of renal failure).

I Treatment
Treatment should be supportive and symptomatic according to the patient's clinical
presentation.
Excessive serum concentrations of either piperacillin or tazobactam may be reduced by
hemodialysis.

PHARMACODYNAMIC PROPERTIES
• Pharmacotherapeutic group:
Antibactenals for systemic use, Combinations of penicillins including beta lactamase inhibitors:
ATCcode: J01CR05
• Mode of action:
TAZOCIN (Sterile piperacillin sodium/tazobactam sodium) is an injectablo antibacterial
combination consisting of the semisynthetic antibiotic piperacillin sodium and the ji-lactamase
Inhibitor tazobactam sodium for intravenous administration. Thus, pipeiaciltin/tazobactam
combines the properties of a broad-spectrum antibiotic and a ^-lactamase Inhibitor

Piperacillin sodium exerts bactericidal activity by inhibiting septum formation and cell wall
synthesis. Piperacillin and other ji-lactam antibiotics black the terminal transpeptidation
step of cell wall peptidcglycan biosynthesis in susceptible organisms by interacting with
the penicillin binding proteins pBPs), the bacterial enzymes that cany out this reaction. In
vitro, piperacillin is active against a variety of gram-positive and gram-negative aerobic and
anaerobic bacteria.

Piperacillin has reduced activity against bacteria harboring certain ji-iastamase enzymes,
which chemically inactivate piperacillin and other [!-lactam antibiotics. Tazobactam sodium,
which has very little intrinsic antimicrobial activity, due to its low affinity for PBPs, can restore
or enhance the activity of piperacillin against many of these resistant organisms. Tazobactam
is a potent inhibitor of many class A jl-lactamases (penicillinases, cephalosporin ases and
extended spectrum enzymes). It has variable activity against class Acarbapenemases and
class D {^-lactamases. It is not active against most class C cephalosporinases and inactive
against Class B metallo-f> lactamases.
Two features of piperacillin/tazobactam lead to increased activity against some organisms
harboring ji-lactamases that, when tested as enzyme preparations, are less inhibited by
tazobactam and other inhibitors: tazobactam does not induce chromosomally mediated
p-lactamases at tazobactam levels achieved with the recommended dosing regimen and
piperacillin Is relatively refractory to the action of some [i-lactamases.

Like other ((-lactam antibiotics, piperacillin, with or without tazobactam, demonstrates time-
dependent bactericidal activity against susceptible organisms.
• Mechanism of resistance: "r •
There are three major mechanisms of resistance to |i-laetam antibiotics: changes in the
target PBPs resulting In reduced affinity lor the antibiotics, destruction of the antibiotics
by bacterial [1-lactamases, and low intracellular antibiotic levels due to reduced uptake or
active efflux of the antibiotics.

In gram-positive bacteria, changes in PBPs are the primary mechanism of resistant to

|S-lactam antibiotics, including piperacillin/tazobactam. This mechanism is responsible for
methicillin resistance in staphylococci and penicillin resistance in Streptococcus pneumoniae
and vlridans group streptococci. Resistance caused by changes in PBPs also occurs in
fastidious gram-negative species such as Haemophilus influenzas and Neisseria gonorrhoeae
Piperacillin/tazobactani is not active against strains in which resistance to |)-lactam antibiotics
tedetemined by altered PBPs. As indicated above, there are some (S-lactamases that are
not inhibited by tazobactam.
• Methodology for determining the in uitro susceptibility of bacteria to piperacillin/
tazobactam:
Susceptibility testing should be conducted using standardized laboratory methods, such
as those described by the Clinical and Laboratory Standards Institute (CLSI). These include
dilution methods (minimal inhibitory concentration, MIC, determination) and disk susceptibility
methods. Both CLSI and the European Committee on Antimicrobial Susceptibility Testing
(EUCAST) provide susceptibility Interpretive criteria for some bacterial species based on
these methods. It should be noted that for the disk diffusion method. CLSI and EUCAST
use disks with different drug contents.

The CLSI interpretive criteria for susceptibility testing of piperacillin/tazobactam are listed
in the following lable:

CLSI SUSCEPTIBILITY INTERPRETIVE CRITERIA FOR PIPERACILLIN/

TAZOBACTAM
Minimal Inhibitory Disk" Diffusion
Concentration (MIC) Inhibition Zone
Pathogen in mg/L of Piperacillin' (mm Diameter)
S I R S I R
Enterobacteriaceae and
Acinetobact&r baumanii S16 32-64 2 128 • 2 2 1 ,16 •20 s17
Psaudomonas aeruginosa £16 32-64 5 128 2 21 15 •20 514

.
Certain other non-fastidious
gram-negative bacilli' . •— 2 21 18 •20 £17
Haemophilus influenzae *1 - i2 £21 -
Staphylococcus aureus s"8 216 218 S17
Bactaroides frag/fa group " £32 64 2128
Source: Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial
Susceptibility Testing; 22 Informational Suoplement. CLSI document M100-S22. CLSI,
na

Wayne, PA, 2012.

S = Susceptible. I = Intermediate. R - Resistant.
3
MICs are determined using a fixed concentration of 4 mg/L tazobactam and varying the
concentration of piperacillin.
0
CLSI interpretive criteria are based on disks containing 100 ug of piperacillin and 10 pg
of tazobactam.
c
Refer to CLSI Document M100-S22 Table 2B-5 for list of organisms included.
0
With the exception of Bacteroides fragilis itself, MICs are determined by agar dilution onfy.
Standardized susceptibility test procedures require the use of quality control microorganisms
to control the technical aspects of the test procedures. Quality control microorganisms are
specific strains with intrinsic biological properties relating to resistance mechanisms and their
genetic expression within the microorganism; the specific strains used for susceptibility test
quality control are not clinically significant.

Organisms and quality control ranges for piperacillin/tazobactam to be utilized with CLSI
methodology and susceptibility test interpretive criteria are listed in the following table:
 QUALITY CONTROL RANGES FOR PIPERACILLIN/TAZOBACTAM TO B E USED IN
CONJUNCTION WITH CLSI SUSCEPTIBILITY TEST INTERPRETIVE CRITERIA
Minimal inhibitor)' Disk Diffusion inhibition
Concentration 2one Diameter
Quality Control Strain ;: Range in mg/L of Range in mm
piperacillin
Escherichia apti ATCC 25922 1-4 24-30
Escherichia coli ATCC 35218 6.5-2 24-30
Pseudomonas aeruginosa ATCC 27853 1-8- i 25-aa •.
Haemophilus influenzae ATCC 49247' 0.06-0.5 i 33-38
Staphylococcus aureus ATCC 29213 C-25-,2
Staphylococcus aureus KiCC 2592$ • 27-36
Bacteroides fragilis ATCC 25285 0,12 - .0.5*
Bacteroides thetaiotaomicron ATCC 29741 4-16" .;, u," , -
Source: Clinical and Laboratory Standards Institute; Performance Standards for Antimicrobial
Susceptibility Testing; 22™ informational Supplement. CLSI document M100-S22. CLSI,
Wayne. PA, 2012.
a
Agar dilution only.
EUCAST has also established clinical breakpoints for piperacillin/tazobactam against some
organisms. Uke CLSI, theEUCASTMIC susceptibility criteria are based on a fixed concentration
of 4 mg/L of tazobactam. However, for inhibition zone determination, the disks contain 30 ug
of piperacillin and 6 pg of tazobactam. The EUCAST rationale document for piperacillin/
tazobactam states that breakpoints for Pseudomonas aeruginosa apply to dosages of 4 g,
4 times daily, whereas the breakpoints for other organisms are based on 4 g, 3 times daily.

The EUCAST breakpoints for piperacillin/tazobactam are listed in the following table:

EUCAST SUSCEPTIBILITY INTERPRETIVE CRITERIA FOR PIPERACILLIN/

TAZOBACTAM : •
Minimal Inhibitory Disk Diffusion
0

D . Concentration (MIC) Inhibition Zone

fatnogen mg/Lof Piperacillin"
i n (mm Diameter)
S R S R
Enterpbacfe/faceae £8 >16 . 2 20 <17
Pseudomonas aeruginosa S16. >16- • • S 19 <19
Gram-positive anaerobes <8 >16 -• -
Gram-negative anaerobes SB its
Non-species related <A >16 i- LT w v •
Sources:
EUCAST Clinical Break point Table v. 2.0,1 January, 2012.
Piperacillin-tazobactam: Rationale for the EUCAST clinical breakpoints, version 1.0,
22 November 2010
S = Susceptible. R = Resistant.
" MICs are determined using a fixed concentration of 4 mg/L tazobactam and varying the
concentration of piperacillin.
0
EUCAST interpretive c-teria are based on disks containing 30 ug of piperacillin and 6 pg
of tazobactam.
Per EUCAST, for species without piperacillin/tazobactam breakpoints: Susceptibility in
staphylococci is inferred from cefoxitin/oxacillin susceptibility. For groups A, B, C and G
streptococci and Sfrr^ofococcus pneumoniae, susceptibility Is inferredfrombenzylpenlcillin
susceptibility. For other streptococci, enterococci, and [i-lactamase negative Haemophilus
influenzae, susceptibility is inferred from amoxicillins;lavulanate susceptibility. There are no
EUCAST breakpoints forvic/netobacter. The EUCAST rationale document for piperacillin/
tazobactam states that in endocarditis caused by streptococci otherihan groupsA,-B, Cacd
G and S. pneumoniae: national or international guidelines should be" referred to.
Quality control ranges for EUCAST susceptibility breakpoints are listed in the following table.
QUALITY CONTROL RANGES FOR PIPERACILUN/TAZOB ACTAM TO B E USED IN
CONJUNCTION WITH EUCAST SUSCEPTIBILITY TEST INTERPRETIVE CRITERIA
Minimal Inhibitory Disk Diffusion
Concentration Inhibition
Quality Control Strain 2one Diameter
Range in mg/L of
piperacillin Range in mm
Escherichia coli ATCC 25922 1 -4 21 -27
Pseudomonas aeruginosa ATCC 27853 1-8 23-29
Source: EUCAST recommended strains for internal quality control. Version 2.0,1 January,
2012.
• Antibacterial spectrum:
Piperacillin/tazobactam has been shown to be active against most strains of the following
microorganisms, both In vitro and in the indicated clinical infections.
Aerobic and facultative gram-positive microorganisms:
Staphylococcus aureus (methlcillin-susceptible strains only)
Aerobic and facultative gram-negative microorganisms:
-4dnefobac!er baumanil
Escherichia coli
Haemophilus influenzae (excluding |l-lactamase negative, ampiclllin-resislant isolates)
Klebsiella pneumoniae
Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate
is susceptible)
^IWljTTW j $ c" V • • A P f T ^ . , •
Gram-negative anaerobes:
Bacteroides fragilis group (S. fragilis, B ovafus, S thetaiotaomicron, and B vulgalus)
The following in vitro data are available, but their clinical significance is unknown.
At least 90% of thefollowingmicroorganisms exhibit an in vitro minimal inhibitory concentration
(MIC) less than orequal to the susceptible breakpoint for piperacillin/tazobactam. However,
the safety and effectiveness of piperacillin/tazobactam in treating clinical infections due
to these bacteria have not been established in adequate and welf-controlled clinical trials.

Aerobic and facultative gram-positive microorganisms:

Enterococcus faecalis (ampicillin- or penicillin-susceptible isolates only)
Staphylococcus epidermidis (methicill in-susceptible isolates only)
Streptococcus agaiactiae 1

Streptococcus pneumoniae' (penicillin-susceptible isolates only)

Streptococcus pyogenes' , .... - .,
Viridansgroup streplococcit _ •'Vj*^,^-. , .

Aerobic and facultative gram-negative microorganisms:

Citroba cter koseri
Moraxeila catarrhalis
Morganella morganii
Neisseria gonorrhoeae
Proteus mirabilis
Proteus vulgaris
Serratla marcescens
Providencia stuartii
Providencia rettgeri
Salmonella enterics

Gram-positive anaerobes: • .
Clostridium perfringens
G ram - n egative an aerobes:
Bacteroides distasonis
Prevotella melaninogenica
'These are not ^-lactamase producing bacteria and, therefore, are susceptible to piperacillin
alone.

COMPATIBILITIES, INCOMPATIBILITIES
Solutions known to be compatible with TAZOCIN containing EDTA for reconstitu'ion are:
• 0.9% Sodium Chloride for Injection
• SterileWaterforlnjection
• Dextrose 5%
• Bacteriostatic Saline/Parabens
• Bacteriostatic Water/Parabens
• Bacteriostatic Saline/Benzyl alcohol
• Bacteriostatic Water/Benzyl alcohol
The reconstituted solution of TAZOCIN containing EDTA may be further diluted to the
desired volume (e.g. 50 mL to 150 mL) with one of the compatible solvents for intravenous
use listed below:
• 0,9% Sodium Chloride for Injection
• SterileWaterforlnjection'
• Dextrose 5%
• Dextran6%inSaline
• Lactated Ringers Injection
• Hart mann's Solution
• Ringers Acetate
• Ringer's Acetate/Mai ate
'Maximum recommended volume of Sterile Water for Injection per dose is 50 mL
Whenever TAZOCIN is used concurrently with another antibiotic (e.g. aminoglycosides), the
drugs must be administered separately. The mixing of TAZOCIN with an aminoglycoside in
vitro canresultin substantial inactivation of the aminoglycoside.

The mixing of beta-lactam antibiotics with aminoglycoside in vitro can result in substantial
inactivation of the aminoglycoside. However, amikacin and gentamicin were determined
to be compatible with 1AZCCIN in vitro in certain diluents at specific concentrations (see
Section DOSAGE AND ADMINISTRATION).
TAZOCIN should not be mixed wilh other drugs in a syringe or infusion bottle since compatibility
has not been established.
Because of chemical instability, TAZOCIN should not be used with solutions containing only
sodium bicarbonate.
TAZOCIN should not be added to blood products or albumin hydrolysatcs.
HANDLING
Directions For Fieconstitution and Dilution For Use.

Intravenous use only: Reconstitute each vial with the volume of solvent shown in the table
below, using one of the compatible solvents for reconstitution. Swiri until dissolved.
When swirled constantly, reconstitution generally occurs within 5 to 10 minutes.

Volume ot Compatible Solvent to be

Vial Size (piperacillin/tazobactam)
Added to Vial
4.50 g 20 mL

HOW SUPPLIED

TAZOCIN (sterile piperacillin sodium and tazobactam sodium) is supplied in the following sizes:
Each TAZOCIN 4.5 g vial provides 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. ^ j w i ^ ^ ' i g B S i ^ i - ^ ' s ^ .-¬
Before reconstitution, store TAZOCIN vials below 25°C. TAZOCIN vials should be used
immediately after reconstitution. For vials not used immediately after reconstitution, please
follow these guidelines:
• Discard any unused portion after 24 hours if stored below 25"C, but outside of the
refrigerator.
• Discard any unused portion after 7 days, if refrigerated (between 2°C to 8°C).
• Vials should not be frozen after reconstitution.

PRODUCT LICENCE NUMBERS

TAZOCIN ; Box, 12 vials @4.5 g, Reg. No. DKI11344Q0144A1
HARUS DENGAN RESEP DOKTER
Manufactured and packaged by
Wyeth Lederle S.r.l
Via Franco Gorgone
Zona Indus!riale
1-95100 Catania CT, Italy

Imported by:
PT. Plizer Indonesia
Jakarta, Indonesia
. ... . • • • g
CDS date: March 08,2013
Supersedes: March 09,2012
Approved by BPOM: May 13,2016