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PIPERACILLIN/TAZOBACTAM 2G/0.25G POWDER FOR SOLUTION FOR INJECTION OR INFUSION

Active substance(s): PIPERACILLIN / TAZOBACTAM / PIPERACILLIN / TAZOBACTAM / PIPERACILLIN / TAZOBACTAM

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Piperacillin/Tazobactam 2 g/0.25 g powder for solution for infusion

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains piperacillin (as sodium salt) equivalent to 2 g and tazobactam (as
sodium salt) equivalent to 0.25 g.
Each vial of Piperacillin/Tazobactam 2 g/0.25 g powder for solution for infusion
contains 4.72 mmol (109 mg) of sodium.
Excipients:
For the full list of excipients, see section 6.1

3

PHARMACEUTICAL FORM
Powder for solution for infusion.
White to off-white powder.

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Piperacillin/tazobactam is indicated for the treatment of the following infections in
adults and children over 2 years of age (see sections 4.2 and 5.1):
Adults and adolescents
-

Severe pneumonia including hospital-acquired and ventilator-associated
pneumonia
Complicated urinary tract infections (including pyelonephritis)
Complicated intra-abdominal infections
Complicated skin and soft tissue infections (including diabetic foot infections)

Treatment of patients with bacteraemia that occurs in association with, or is suspected
to be associated with, any of the infections listed above.

Piperacillin/tazobactam may be used in the management of neutropenic patients with
fever suspected to be due to a bacterial infection.
Children 2-12 years of age
-

Complicated intra-abdominal infections

Piperacillin/tazobactam may be used in the management of neutropenic children with
fever suspected to be due to a bacterial infection.
Consideration should be given to official guidance on the appropriate use of
antibacterial agents.

4.2

Posology and method of administration
The dose and frequency of piperacillin/tazobactam depends on the severity and
localisation of the infection and expected pathogens.
Adult and adolescent patients
Infections
The usual dose is 4 g piperacillin / 0.5 g tazobactam given every 8 hours.

For nosocomial pneumonia and bacterial infections in neutropenic patients, the
recommended dose is 4 g piperacillin / 0.5 g tazobactam administered every 6
hours. This regimen may also be applicable to treat patients with other
indicated infections when particularly severe.
The following table summarises the treatment frequency and the
recommended dose for adult and adolescent patients by indication or
condition:
Treatment
frequency

Piperacillin/tazobactam 4 g / 0.5 g

Every 6 hours

Severe pneumonia
Neutropenic adults with fever suspected to be due to a bacterial
infection.

Every 8 hours

Complicated urinary tract infections (including pyelonephritis)
Complicated intra-abdominal infections
Skin and soft tissue infections (including diabetic foot
infections)

Renal impairment
The intravenous dose should be adjusted to the degree of actual renal impairment as
follows (each patient must be monitored closely for signs of substance toxicity;
medicinal product dose and interval should be adjusted accordingly):

Creatinine clearance
(ml/min)

Piperacillin/tazobactam (recommended dose)

> 40

No dose adjustment necessary

20-40

Maximum dose suggested: 4 g / 0.5 g every 8 hours

< 20

Maximum dose suggested: 4 g / 0.5 g every 12 hours

For patients on haemodialysis, one additional dose of piperacillin / tazobactam 2 g /
0.25 g should be administered following each dialysis period, because haemodialysis
removes 30%-50% of piperacillin in 4 hours.
Hepatic impairment
No dose adjustment is necessary (see section 5.2).
Elderly
No dose adjustment is required for the elderly with normal renal function or
creatinine clearance values above 40 ml/min.
Paediatric population (2-12 years of age)
Infections
The following table summarises the treatment frequency and the dose per body
weight for paediatric patients 2-12 years of age by indication or condition:

Dose per weight and
treatment frequency

Indication / condition

80 mg Piperacillin / 10 mg
Tazobactam per kg body weight
/ every 6 hours

Neutropenic children with fever suspected to be
due to bacterial infections*

100 mg Piperacillin / 12.5 mg
Tazobactam per kg body weight
/ every 8 hours

Complicated intra-abdominal infections*

* Not to exceed the maximum 4 g / 0.5 g per dose over 30 minutes.

Renal impairment
The intravenous dose should be adjusted to the degree of actual renal impairment as
follows (each patient must be monitored closely for signs of substance toxicity;
medicinal product dose and interval should be adjusted accordingly):

Creatinine clearance
(ml/min)
> 50
50

Piperacillin/tazobactam (recommended dose)

No dose adjustment needed.
70 mg piperacillin / 8.75 mg tazobactam / kg every 8
hours.

For children on haemodialysis, one additional dose of 40 mg piperacillin / 5 mg
tazobactam / kg should be administered following each dialysis period.
Use in children aged below 2 years
The safety and efficacy of piperacillin/tazobactam in children 0- 2 years of age has
not been established.
No data from controlled clinical studies are available.

Treatment duration
The usual duration of treatment for most indications is in the range of 5-14 days.
However, the duration of treatment should be guided by the severity of the infection,
the pathogen(s) and the patient's clinical and bacteriological progress.
Method of administration
Piperacillin/tazobactam 2 g / 0.25 g is administered by intravenous infusion (over 30
minutes).
For instructions on reconstitution of the medicinal product before administration, see
section 6.6.

4.3

Contraindications

Hypersensitivity to the active substances, any other penicillin-antibacterial agent or to
any of the excipients listed in section 6.1.

History of acute severe allergic reaction to any other beta-lactam active substances
(e.g. cephalosporin, monobactam or carbapenem).
4.4

Special warnings and precautions for use
The selection of piperacillin/tazobactam to treat an individual patient should take into
account the appropriateness of using a broad-spectrum semi-synthetic penicillin based
on factors such as the severity of the infection and the prevalence of resistance to
other suitable antibacterial agents.
Before initiating therapy with piperacillin/tazobactam, careful inquiry should be made
concerning previous hypersensitivity reactions to penicillins, other beta-lactam agents
(e.g. cephalosporin, monobactam or carbapenem) and other allergens. Serious and
occasionally fatal hypersensitivity (anaphylactic/anaphylactoid [including shock])
reactions have been reported in patients receiving therapy with penicillins, including
piperacillin/tazobactam. These reactions are more likely to occur in persons with a
history of sensitivity to multiple allergens. Serious hypersensitivity reactions require
the discontinuation of the antibiotic, and may require administration of epinephrine
and other emergency measures.
Serious skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis
and drug reaction with eosinophilia and systemic symptoms have been reported in
patients receiving piperacillin/tazobactam (see section 4.8). If patients develop a skin
rash, they should be monitored closely and piperacillin/tazobactam discontinued if
lesions progress.
Antibiotic-induced pseudomembranous colitis may be manifested by severe,
persistent diarrhoea which may be life-threatening. The onset of pseudomembranous
colitis symptoms may occur during or after antibacterial treatment. In these cases
piperacillin/tazobactam, should be discontinued.
Therapy with piperacillin/tazobactam may result in the emergence of resistant
organisms, which might cause super-infections.
Bleeding manifestations have occurred in some patients receiving beta-lactam
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. If bleeding manifestations
occur, the antibiotic should be discontinued and appropriate therapy instituted.
Leukopenia and neutropenia may occur, especially during prolonged therapy;
therefore, periodic assessment of haematopoietic function should be performed.
As with treatment with other penicillins, neurological complications in the form of
convulsions may occur when high doses are administered, especially in patients with
impaired renal function.

Each vial of Piperacillin/Tazobactam 2 g/0.25 g powder for solution for infusion
contains 4.72 mmol (109 mg) of sodium. This should be taken into consideration for
patients who are on a controlled sodium diet.
Hypokalaemia may occur in patients with low potassium reserves or those receiving
concomitant medicinal products that may lower potassium levels; periodic electrolyte
determinations may be advisable in such patients.

Renal Impairment
Due to its potential nephrotoxicity (see section 4.8), piperacillin/tazobactam should be
used with care in patients with renal impairment or in hemodialysis patients.
Intravenous dosages and administration intervals should be adjusted to the degree of
renal function impairment (see section 4.2).
In a secondary analysis using data from a large multicenter, randomized-controlled
trial when glomerular filtration rate (GFR) was examined after administration of
frequently used antibiotics in critically ill patients, the use of piperacillin/tazobactam
was associated with a lower rate of reversible GFR improvement compared with the
other antibiotics. This secondary analysis concluded that piperacillin/tazobactam was
a cause of delayed renal recovery in these patients.

4.5

Interaction with other medicinal products and other forms of interaction
Non-depolarising muscle relaxants
Piperacillin when used concomitantly with vecuronium has been implicated in the
prolongation of the neuromuscular blockade of vecuronium. Due to their similar
mechanisms of action, it is expected that the neuromuscular blockade produced by
any of the non-depolarising muscle relaxants could be prolonged in the presence of
piperacillin.
Oral anticoagulants
During simultaneous administration of heparin, oral anticoagulants and other
substances that may affect the blood coagulation system including thrombocyte
function, appropriate coagulation tests should be performed more frequently and
monitored regularly.
Methotrexate
Piperacillin may reduce the excretion of methotrexate; therefore, serum levels of
methotrexate should be monitored in patients to avoid substance toxicity.
Probenecid

As with other penicillins, concurrent administration of probenecid and
piperacillin/tazobactam produces a longer half-life and lower renal clearance for both
piperacillin and tazobactam; however, peak plasma concentrations of either
substances are unaffected.
Aminoglycosides
Piperacillin, either alone or with tazobactam, did not significantly alter the
pharmacokinetics of tobramycin in subjects with normal renal function and with mild
or moderate renal impairment. The pharmacokinetics of piperacillin, tazobactam, and
the M1 metabolite were also not significantly altered by tobramycin administration.
The inactivation of tobramycin and gentamicin by piperacillin has been demonstrated
in patients with severe renal impairment.
For information related to the administration of piperacillin/tazobactam with
aminoglycosides please refer to sections 6.2.
Vancomycin
No pharmacokinetic interactions have been noted between piperacillin/tazobactam
and vancomycin.
Effects on laboratory tests
Non-enzymatic methods of measuring urinary glucose may lead to false-positive
results, as with other penicillins. Therefore, enzymatic urinary glucose measurement
is required under piperacillin/tazobactam therapy.
A number of chemical urine protein measurement methods may lead to false-positive
results. Protein measurement with dip sticks is not affected.
The direct Coombs test may be positive.
Bio-Rad Laboratories Platelia Aspergillus EIA tests may lead to false-positive results
for patients receiving piperacillin/tazobactam. Cross-reactions with non-Aspergillus
polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus
EIA test have been reported.
Positive test results for the assays listed above in patients receiving
piperacillin/tazobactam should be confirmed by other diagnostic methods.

4.6

Fertility, pregnancy and lactation
Pregnancy
There are no or a limited amount of data from the use of piperacillin/tazobactam in
pregnant women.
Studies in animals have shown developmental toxicity, but no evidence of
teratogenicity, at doses that are maternally toxic (see section 5.3).
Piperacillin and tazobactam cross the placenta. Piperacillin/tazobactam should only
be used during pregnancy if clearly indicated, i.e. only if the expected benefit
outweighs the possible risks to the pregnant woman and foetus.

Breast-feeding
Piperacillin is excreted in low concentrations in human milk; tazobactam
concentrations in human milk have not been studied. Women who are breast-feeding
should be treated only if the expected benefit outweighs the possible risks to the
woman and child.
Fertility
A fertility study in rats showed no effect on fertility and mating after intraperitoneal
administration of tazobactam or the combination piperacillin/tazobactam (see section
5.3).

4.7

Effects on ability to drive and use machines
No studies on the effect on the ability to drive and use machines have been
performed.

4.8

Undesirable effects
The most commonly reported adverse reaction is diarrhoea (occurring in 1 patient out
of 10).
Among the most serious adverse reactions pseudo-membranous colitis and toxic
epidermal necrolysis occur in 1 to 10 patients in 10,000. The frequencies for
pancytopenia, anaphylactic shock and Stevens-Johnson syndrome cannot be
estimated from the currently available data.
In the following table, adverse reactions are listed by system organ class and
MedDRA-preferred term. Within each frequency grouping, undesirable effects are
presented in order of decreasing seriousness.

System Organ
Class

Very
common >
1/10

Common
1/100 to < 1/10

Infections and
infestations

Candidiasis

Blood and
lymphatic
system disorders

thrombocytopenia,
anaemia, Coombs
direct test positive,
activated partial
thromboplastin
time prolonged

Immune system
disorders

Uncommon
1/1,000 to <
1/100

Rare

Frequency not known
(cannot be estimated from
1/10,000 to
the available data)
< 1/1,000

Agranulocyto
leukopenia,
prothrombin time sis, epistaxis,
prolonged

pancytopenia,neutropenia,
purpura, bleeding time
prolonged, haemolytic
anaemia, eosinophilia,
thrombocytosis

Anaphylactoid reactions,
anaphylactic reactions,

anaphylactoid shock,
anaphylactic shock,
hypersensitivity
Metabolism and
nutrition
disorders

Blood albumin
decreased, blood
protein total
decreased

Nervous system
disorders

Headache,
insomnia

Hypokalaemia
blood glucose
decrease

hypotension,
thrombophlebitis,
phlebitis,
flushing

Vascular
disorders

Gastrointestinal
disorders

Diarrhoea

abdominal pain,
vomiting, nausea,
constipation,
dyspepsia

pseudomembranous
colitis

Hepatobiliary
disorders

blood bilirubin
Alanine
increased
aminotransferase
increased, aspartate
aminotransferase
increased, blood
alkaline
phosphatase
increased

Skin and
subcutaneous
tissue disorders

rash, pruritus

Erythema
miltiforme,
urticaria, rash
maculopapular

Hepatitis, jaundice,
gamma-glutamyltransferase
increased

toxic
epidermal
necrolysis,
exanthema

Stevens-Johnson syndrome,
dermatitis bullus,
drug reaction with
eosinophilia and systemic
symptoms (DRESS)

Arthralgia,
myalgia

Musculoskeletal
and connective
tissue disorders
Renal and
urinary
disorders

Blood creatinine
increased, blood
urea increased

General
disorders and
administration
site conditions

Pyrexia, injectionsite reactions

renal failure,
tubulointestitial nephritis

chills

Piperacillin therapy has been associated with an increased incidence of fever and rash
in cystic fibrosis patients.

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal
product. Healthcare professionals are asked to report any suspected adverse reactions
via
UK
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard

4.9

Overdose
Symptoms
There have been post-marketing reports of overdose with piperacillin/tazobactam.
The majority of those events experienced including nausea, vomiting, and diarrhoea,
have also been reported with the usual recommended dose. Patients may experience
neuromuscular excitability or convulsions if higher than recommended doses are
given intravenously (particularly in the presence of renal failure).
Treatment
In the event of an overdose, piperacillin/tazobactam treatment should be
discontinued.
No specific antidote is known.
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 haemodialysis (see section 4.4).

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Antibacterials for systemic use, Combinations of
penicillins incl. beta-lactamase inhibitors; ATC code: J01C R05
Mechanism of action

Piperacillin, a broad spectrum, semisynthetic penicillin exerts bactericidal activity by
inhibition of both septum and cell-wall synthesis.
Tazobactam, a beta-lactam structurally related to penicillins, is an inhibitor of many
beta-lactamases which commonly cause resistance to penicillins and cephalosporins
but it does not inhibit AmpC enzymes or metallo beta-lactamases. Tazobactam
extends the antibiotic spectrum of piperacillin to include many beta-lactamaseproducing bacteria that have acquired resistance to piperacillin alone.
Phamacokinetic / Pharmacodynamic relationship
The time above the minimum inhibitory concentration (T>MIC) is considered to be
the major pharmacodynamic determinant of efficacy for piperacillin.
Mechanism of resistance
The two main mechanisms of resistance to piperacillin/tazobactam are:
• Inactivation of the piperacillin component by those beta-lactamases that are not
inhibited by tazobactam: beta-lactamases in the Molecular class B, C and D. In
addition, tazobactam does not provide protection against extended-spectrum betalactamases (ESBLs) in the Molecular class A and D enzyme groups.
• Alteration of penicillin-binding proteins (PBPs), which results in the reduction of
the affinity of piperacillin for the molecular target in bacteria.
Additionally, alterations in bacterial membrane permeability, as well as expression of
multi-drug efflux pumps, may cause or contribute to bacterial resistance to
piperacillin/tazobactam, especially in Gram-negative bacteria.
Breakpoints
EUCAST Clinical MIC Breakpoints for Piperacillin/Tazobactam (2009-12-02, v 1). For
Susceptibility Testing Purposes, the Concentration of Tazobactam is Fixed at 4 mg/l
Pathogen

Species-related breakpoints (S /R>)

Enterobacteriaceae

8/16

Pseudomonas

16/16

Gram-negative and
Gram-positive anaerobes

8/16

Non-species related
breakpoints

4/16

The susceptibility of streptococci is inferred from the penicillin susceptibility.
The susceptibility of staphylococci is inferred from the oxacillin susceptibility.
Susceptibility
The prevalence of acquired resistance may vary geographically and with time for
selected species and local information on resistance is desirable, particularly when
treating severe infections. As necessary, expert advice should be sought when the
local prevalence of resistance is such that the utility of the agent in at least some
types of infections is questionable.

Groupings of relevant species according to piperacillin/tazobactam susceptibility
COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive micro-organisms
Enterococcus faecalis
Listeria monocytogenes
Staphylococcus aureus, methicillin-susceptible£
Staphylococcus species, coagulase negative, methicillin-susceptible
Streptococcus pyogenes
Group B streptococci
Aerobic Gram-negative micro-organisms
Citrobacter koseri
Haemophilus influenza
Moraxella catarrhalis
Proteus mirabilis
Anaerobic Gram-positive micro-organisms
Clostridium species
Eubacterium species
Peptostreptococcus species
Anaerobic Gram-negative micro-organisms
Bacteroides fragilis group
Fusobacterium species
Porphyromonas species
Prevotella species
SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM
Aerobic Gram-positive micro-organisms
Enterococcus faecium$,+
Streptococcus pneumonia
Streptococcus viridans group
Aerobic Gram-negative micro-organisms
Acinetobacter baumannii$
Burkholderia cepacia
Citrobacter freundii
Enterobacter species
Escherichia coli

Klebsiella pneumonia
Morganella morganii
Proteus vulgaris
Providencia ssp.
Pseudomonas aeruginosa
Serratia species
INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-positive micro-organisms
Corynebacterium jeikeium
Aerobic Gram-negative micro-organisms
Legionella species
Stenotrophomonas maltophilia+,$
Other microorganisms
Chlamydophilia pneumonia
Mycoplasma pneumonia
$

Species showing natural intermediate susceptibility.
Species for which high-resistance rates (more than 50%) have been observed in one or more
areas/countries/regions within the EU.
£
All methicillin-resistant staphylococci are resistant to piperacillin/tazobactam.
+

5.2

Pharmacokinetic properties
Absorption
The peak piperacillin and tazobactam concentrations after 4 g / 0.5 g administered
over 30 minutes by intravenous infusion are 298 µg/ml and 34 µg/ml respectively.
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/tazobactam is widely distributed in tissue and body fluids including
intestinal mucosa, gall bladder, lung, bile and bone. Mean tissue concentrations are
generally 50 to 100% of those in plasma. Distribution into cerebrospinal fluid is low
in subjects with non-inflamed meninges, as with other penicillins.
Biotransformation
Piperacillin is metabolised to a minor microbiologically active desethyl metabolite.
Tazobactam is metabolised to a single metabolite, which has been found to be
microbiologically inactive.

Elimination
Piperacillin and tazobactam are eliminated via the kidney by glomerular filtration and
tubular secretion.
Piperacillin is excreted rapidly as unchanged substance with 68% of the administered
dose appearing in the urine. Tazobactam and its metabolite are eliminated primarily
by renal excretion, with 80% of the administered dose appearing as unchanged
substance and the remainder as the single metabolite. Piperacillin, tazobactam, and
desethyl piperacillin are also secreted into the bile.
Following single or multiple doses of piperacillin/tazobactam to healthy subjects, the
plasma half-life of piperacillin and tazobactam ranged from 0.7 to 1.2 hours and was
unaffected by dose or duration of infusion. The elimination half-lives of both
piperacillin and tazobactam are increased with decreasing renal clearance.
There are no significant changes in piperacillin pharmacokinetics due to tazobactam.
Piperacillin appears to slightly reduce the clearance of tazobactam.
Special populations
The half-life of piperacillin and of tazobactam increases by approximately 25% and
18%, respectively, in patients with hepatic cirrhosis compared to healthy subjects.
The half-life of piperacillin and tazobactam increases with decreasing creatinine
clearance. The increase in half-life is two-fold and four-fold for piperacillin and
tazobactam, respectively, at creatinine clearance below 20 ml/min compared to
patients with normal renal function.
Haemodialysis removes 30% to 50% of piperacillin/tazobactam, 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 18% of the tazobactam dose removed as the tazobactam
metabolite.
Paediatric population
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 paediatric
patients 2-9 months of age. The population mean (SE) for piperacillin volume of
distribution is 0.243 (0.011) l/kg and is independent of age.
Elderly patients
The mean half-life for piperacillin and tazobactam were 32% and 55% longer,
respectively, in the elderly compared with younger subjects. This difference may be
due to age-related changes in creatinine clearance.
Race
No difference in piperacillin or tazobactam pharmacokinetics was observed between
Asian (n=9) and Caucasian (n=9) healthy volunteers who received single 4 g / 0.5 g
doses.

5.3

Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of
repeated dose toxicity and genotoxicity. Carcinogenicity studies have not been
conducted with piperacillin/tazobactam.
A fertility and general reproduction study in rats using intraperitoneal administration
of tazobactam or the combination piperacillin/tazobactam reported a decrease in litter
size and an increase in fetuses with ossification delays and variations of ribs,
concurrent with maternal toxicity. Fertility of the F1 generation and embryonic
development of the F2 generation were not impaired.
Teratogenicity studies using intravenous administration of tazobactam or the
combination piperacillin/tazobactam in mice and rats resulted in slight reductions in
rat fetal weights at maternally toxic doses but did not show teratogenic effects.
Peri/postnatal development was impaired (reduced pup weights, increase in stillbirths,
increase in pup mortality) concurrent with maternal toxicity after intraperitoneal
administration of tazobactam or the combination piperacillin/tazobactam in the rat.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
None.

6.2

Incompatibilities
This medicinal product must not be mixed with other medicinal products except those
mentioned in section 6.6.
Whenever piperacillin/tazobactam is used concurrently with another antibiotic (e.g.
aminoglycosides), the substances must be administered separately. The mixing of
beta-lactam antibiotics with an aminoglycoside in vitro can result in substantial
inactivation of the aminoglycoside.
Piperacillin/tazobactam should not be mixed with other substances in a syringe or
infusion bottle since compatibility has not been established.
Piperacillin/tazobactam should be administered through an infusion set separately
from any other drugs unless compatibility is proven.
Due to chemical instability, piperacillin/tazobactam should not be used in solutions
containing only sodium bicarbonate.
Lactated Ringer's solution is not compatible with piperacillin/tazobactam.

Piperacillin/tazobactam should not be added to blood products or albumin
hydrolysates.

6.3

Shelf life
Unopened vial: 2 years
Diluted infusion solution
After reconstitution, chemical and in-use stability has been demonstrated for 24 hours
when stored in a refrigerator at 2-8°C.
From a microbiological point of view, once opened, the product should be used
immediately. If not used immediately, in-use storage times and conditions prior to use
are the responsibility of the user and would normally not be longer than 24 hours at 28°C, unless reconstitution has taken place in controlled and validated aseptic
conditions.

6.4

Special precautions for storage

This medicinal product does not require any special temperature storage conditions.
Keep vial(s) in the outer carton.
For storage conditions after reconstitution of the medicinal product, see section 6.3.
6.5

Nature and contents of container
Type I glass vials with a bromo butyl rubber stopper and flip off seal.
Pack sizes: 1 or 12 vials per carton.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
The reconstitution and dilution is to be made under aseptic conditions. The solution is
to be inspected visually for particulate matter and discoloration prior to
administration. The solution should only be used if the solution is clear and free from
particles.

Intravenous use

Reconstituted each vial with the volume of solvent shown in the table below, using
one of the compatible solvents for reconstitution.
Swirl until dissolved (for details on handling, please see below).

Content of vial

Volume of solvent* to be added to vial

2 g / 0.25 g (2 g piperacillin and
0.25 g tazobactam)

10 ml

* compatible solvent for reconstitution
-

0.9% (9 mg/ml) sodium chloride solution for injection
Sterile water for injections(1)
Glucose 5%

(1)

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

The reconstituted solutions should be withdrawn from the vial by syringe. When
reconstituted as directed the vial contents withdrawn by stringe will provide the
labelled amount of piperacillin and tazobactam.
The reconstituted solutions may be further diluted to the desired volume (e.g. 50 ml to
150 ml) with one of the following compatible solvents:
-

0.9% (9 mg/ml) sodium chloride solution for injection
Glucose 5%

See section 6.2 for incompatibilities.
Any unused medicinal product or waste material should be disposed of in accordance
with local requirements.
For single use only. Discard any unused solution.

7

MARKETING AUTHORISATION HOLDER

Hospira UK Limited
Horizon, Honey Lane, Hurley
Maidenhead
SL6 6RJ
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 04515/0373

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
27/06/2008

10

DATE OF REVISION OF THE TEXT
20/09/2016

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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