Zerbaxa

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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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1. NAME OF THE MEDICINAL PRODUCT

Zerbaxa 1 g/0.5 g powder for concentrate for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each vial contains ceftolozane sulfate equivalent to 1 g ceftolozane and tazobactam sodium equivalent 
to 0.5 g tazobactam.

After reconstitution with 10 mL diluent, the total volume of the solution in the vial is 11.4 mL, which 
contains 88 mg/mL of ceftolozane and 44 mg/mL of tazobactam.

Excipient with known effect

Each vial contains 10 mmol (230 mg) of sodium.

When the powder is reconstituted with 10 mL of sodium chloride 9 mg/mL (0.9%) solution for 
injection, the vial contains 11.5 mmol (265 mg) of sodium.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for concentrate for solution for infusion (powder for concentrate).

White to yellowish powder.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Zerbaxa is indicated for the treatment of the following infections in adults (see section 5.1):

- Complicated intra-abdominal infections (see section 4.4);
- Acute pyelonephritis;
- Complicated urinary tract infections (see section 4.4);
- Hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).

Consideration should be given to official guidance on the appropriate use of antibacterial agents.

4.2 Posology and method of administration

Posology

The recommended intravenous dose regimen for patients with creatinine clearance > 50 mL/min is 
shown by infection type in Table 1.

 



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Table 1: Intravenous dose of Zerbaxa by type of infection in patients with creatinine clearance 
> 50 mL/min
Type of infection Dose Frequency Infusion 

time
Duration of 
treatment

Complicated intra-abdominal 
infection*

1 g ceftolozane / 
0.5 g tazobactam

Every 
8 hours

1 hour 4-14 days

Complicated urinary tract 
infection
Acute pyelonephritis

1 g ceftolozane / 
0.5 g tazobactam

Every 
8 hours

1 hour 7 days

Hospital-acquired pneumonia, 
including ventilator-associated 
pneumonia**

2 g ceftolozane / 
1 g tazobactam

Every 
8 hours

1 hour 8-14 days

*To be used in combination with metronidazole when anaerobic pathogens are suspected.
**To be used in combination with an antibacterial agent active against Gram-positive pathogens when 
these are known or suspected to be contributing to the infectious process.

Special populations

Elderly (≥ 65 years of age)
No dose adjustment is necessary for the elderly based on age alone (see section 5.2).

Renal impairment
In patients with mild renal impairment (estimated creatinine clearance [CrCL] > 50 mL/min), no dose 
adjustment is necessary (see section 5.2).

In patients with moderate or severe renal impairment, and in patients with end stage renal disease on 
haemodialysis, the dose should be adjusted as listed in Table 2 (see sections 5.1 and 6.6).

Table 2: Recommended intravenous dose regimens for Zerbaxa in patients with creatinine 
clearance ≤ 50 mL/min
Estimated 
CrCL 
(mL/min)*

Complicated intra-abdominal 
infections, complicated urinary tract 
infections, and acute pyelonephritis**

Hospital-acquired pneumonia, 
including ventilator-associated 
pneumonia**

30 to 50
500 mg ceftolozane / 250 mg tazobactam 
intravenously every 8 hours

1 g ceftolozane / 0.5 g tazobactam 
intravenously every 8 hours

15 to 29
250 mg ceftolozane / 125 mg tazobactam
intravenously every 8 hours

500 mg ceftolozane / 250 mg tazobactam
intravenously every 8 hours

End stage 
renal disease 
on 
haemodialysis

A single loading dose of 500 mg 
ceftolozane / 250 mg tazobactam
followed after 8 hours by a 100 mg 
ceftolozane / 50 mg tazobactam
maintenance dose administered every 
8 hours for the remainder of the 
treatment period (on haemodialysis days, 
the dose should be administered at the 
earliest possible time following 
completion of haemodialysis)

A single loading dose of 1.5 g 
ceftolozane / 0.75 g tazobactam followed
after 8 hours by a 300 mg ceftolozane / 
150 mg tazobactam maintenance dose 
administered every 8 hours for the 
remainder of the treatment period (on 
haemodialysis days, the dose should be 
administered at the earliest possible time 
following completion of haemodialysis)

*CrCL estimated using Cockcroft-Gault formula.
**All doses of Zerbaxa are administered intravenously over 1 hour and are recommended for all 
indications. The duration of treatment should follow the recommendations in Table 1.

Hepatic impairment
No dose adjustment is necessary in patients with hepatic impairment (see section 5.2).

 



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Paediatric population
The safety and efficacy of ceftolozane/tazobactam in children and adolescents below 18 years of age 
have not yet been established. No data are available.

Method of administration

Zerbaxa is to be administered by intravenous infusion over a 1 hour period for all doses.

Precautions to be taken before handling or administering the product
See section 6.2 for incompatibilities.

See section 6.6 for instructions on reconstitution and dilution of the medicinal product before 
administration.

4.3 Contraindications

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1;
- Hypersensitivity to any cephalosporin antibacterial agent;
- Severe hypersensitivity (e.g., anaphylactic reaction, severe skin reaction) to any other type of

beta-lactam antibacterial agent (e.g., penicillins or carbapenems).

4.4 Special warnings and precautions for use

Hypersensitivity reactions

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions are possible (see sections 4.3 
and 4.8). If a severe allergic reaction occurs during treatment with ceftolozane/tazobactam, the 
medicinal product should be discontinued and appropriate measures taken.

Patients who have a history of hypersensitivity to cephalosporins, penicillins or other beta-lactam
antibacterial agents may also be hypersensitive to ceftolozane/tazobactam.

Ceftolozane/tazobactam is contraindicated in patients with a history of hypersensitivity to ceftolozane, 
tazobactam, or cephalosporins (see section 4.3).

Ceftolozane/tazobactam is also contraindicated in patients with severe hypersensitivity (e.g.,
anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g.,
penicillins or carbapenems) (see section 4.3). 

Ceftolozane/tazobactam should be used with caution in patients with a history of any other type of 
hypersensitivity reaction to penicillins or other beta-lactam antibacterial agents. 

Effect on renal function

A decline in renal function has been seen in patients receiving ceftolozane/tazobactam.

Impaired renal function

The ceftolozane/tazobactam dose should be adjusted based on renal function (see section 4.2, Table 2).

In clinical trials of complicated intra-abdominal infections and complicated urinary tract infections, 
including pyelonephritis, the efficacy of ceftolozane/tazobactam was lower in patients with moderate 
renal impairment compared with those with normal or mildly impaired renal function at baseline. 
Patients with renal impairment at baseline should be monitored frequently for any changes in renal 
function during treatment and the dose of ceftolozane/tazobactam should be adjusted as necessary.

 



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Limitations of the clinical data

Patients who were immunocompromised, patients with severe neutropenia, and patients with end stage 
renal disease on haemodialysis were excluded from clinical trials.

Complicated intra-abdominal infections
In a trial in patients with complicated intra-abdominal infections, the most common diagnosis was 
appendiceal perforation or peri-appendiceal abscess (420/970 [43.3%] patients), of which 137/420 
(32.6%) had diffuse peritonitis at baseline. Approximately 82% of all patients in the trial had 
APACHE II (Acute Physiology and Chronic Health Evaluation II) scores of < 10 and 2.3% had 
bacteraemia at baseline. In the clinically evaluable (CE) patients, the clinical cure rates for 
ceftolozane/tazobactam were 95.9% in 293 patients aged less than 65 years and 87.8% in 82 patients 
aged 65 years or more.

Complicated urinary tract infections
Clinical efficacy data in patients with complicated lower urinary tract infection are limited. In a 
randomised active-controlled trial 18.2% (126/693) of microbiologically evaluable (ME) patients had 
complicated lower urinary tract infection, including 60/126 patients who were treated with 
ceftolozane/tazobactam. One of these 60 patients had bacteraemia at baseline.

Clostridioides difficile-associated diarrhoea

Antibacterial-associated colitis and pseudomembranous colitis have been reported with 
ceftolozane/tazobactam (see section 4.8). These types of infection may range in severity from mild to 
life-threatening. Therefore, it is important to consider this diagnosis in patients who present with 
diarrhoea during or subsequent to the administration of ceftolozane/tazobactam. In such 
circumstances, the discontinuation of therapy with ceftolozane/tazobactam and the use of supportive 
measures together with the administration of specific treatment for Clostridioides difficile should be 
considered.

Non-susceptible micro-organisms

The use of ceftolozane/tazobactam may promote the overgrowth of non-susceptible micro-organisms. 
If super infection occurs during or following treatment, appropriate measures should be taken.

Ceftolozane/tazobactam is not active against bacteria that produce beta-lactamase enzymes which are 
not inhibited by tazobactam (see section 5.1).

Direct antiglobulin test (Coombs test) seroconversion and potential risk of haemolytic anaemia

The development of a positive direct antiglobulin test (DAGT) may occur during treatment with
ceftolozane/tazobactam (see section 4.8). In clinical studies, there was no evidence of haemolysis in 
patients who developed a positive DAGT on treatment.

Sodium content

Ceftolozane/tazobactam contains 230 mg sodium per vial, equivalent to 11.5% of the WHO 
recommended maximum daily intake of 2 g sodium for an adult. The reconstituted vial with 10 mL of 
0.9% sodium chloride (normal saline) for injection contains 265 mg sodium per vial, equivalent to 
13.3% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

4.5 Interaction with other medicinal products and other forms of interaction

No significant medicinal product interactions are anticipated between ceftolozane/tazobactam and 
substrates, inhibitors, and inducers of cytochrome P450 enzymes (CYPs) based on in vitro and in vivo
studies.

 



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In vitro studies demonstrated that ceftolozane, tazobactam and the M1 metabolite of tazobactam did 
not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 and did not 
induce CYP1A2, CYP2B6, or CYP3A4 at therapeutic plasma concentrations.

Ceftolozane and tazobactam were not substrates for P-gp or BCRP, and tazobactam was not a 
substrate for OCT2, in vitro at therapeutic plasma concentrations. In vitro data indicate that 
ceftolozane did not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, MRP, BSEP, OAT1, 
OAT3, MATE1, or MATE2-K in vitro at therapeutic plasma concentrations. In vitro data indicate that 
neither tazobactam nor the tazobactam metabolite M1 inhibit P-gp, BCRP, OATP1B1, OATP1B3, 
OCT1, OCT2, or BSEP transporters at therapeutic plasma concentrations.

Tazobactam is a substrate for OAT1 and OAT3. In vitro, tazobactam inhibited human OAT1 and 
OAT3 transporters with IC50 values of 118 and 147 mcg/mL, respectively. Co-administration of 
ceftolozane/tazobactam with OAT1 and OAT3 substrate furosemide in a clinical study did not 
significantly increase furosemide plasma exposures (geometric mean ratios of 0.83 and 0.87 for Cmax
and AUC, respectively). However, active substances that inhibit OAT1 or OAT3 (e.g., probenecid) 
may increase tazobactam plasma concentrations.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no data on the use of ceftolozane/tazobactam in pregnant women. Tazobactam crosses the 
placenta. It is not known if ceftolozane crosses the placenta.

Animal studies with tazobactam have shown reproductive toxicity (see section 5.3) without evidence 
of teratogenic effects. Studies with ceftolozane in mice and rats have not shown evidence of 
reproductive toxicity or teratogenicity. Ceftolozane administered to rats during pregnancy and breast-
feeding was associated with a decrease in auditory startle response in postnatal day (PND) 60 male 
pups (see section 5.3).

Zerbaxa should only be used during pregnancy if the expected benefit outweighs the possible risks to 
the pregnant woman and foetus.

Breast-feeding

It is unknown whether ceftolozane and tazobactam are excreted in human milk. A risk to 
newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding 
or to discontinue/abstain from Zerbaxa therapy taking into account the benefit of breast-feeding for the 
child and the benefit of therapy for the woman.

Fertility

The effects of ceftolozane and tazobactam on fertility in humans have not been studied. Fertility 
studies in rats showed no effect on fertility and mating after intraperitoneal administration of 
tazobactam or intravenous administration of ceftolozane (see section 5.3).

4.7 Effects on ability to drive and use machines

Zerbaxa may have a minor influence on the ability to drive and use machines. Dizziness may occur 
following administration of Zerbaxa (see section 4.8).

 



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4.8 Undesirable effects

Summary of the safety profile

Zerbaxa was evaluated in Phase 3 comparator-controlled clinical trials of complicated intra-abdominal 
infections and complicated urinary tract infections (including pyelonephritis). 

The most common adverse reactions (≥ 3% in pooled Phase 3 trials of complicated intra-abdominal 
infections and complicated urinary tract infections, including pyelonephritis) occurring in patients 
receiving Zerbaxa were nausea, headache, constipation, diarrhoea, and pyrexia and were generally 
mild or moderate in severity.

Zerbaxa was evaluated in a Phase 3 comparator-controlled clinical trial of hospital-acquired
pneumonia, including ventilator-associated pneumonia.

The most common adverse reactions (≥ 5% in a Phase 3 trial of hospital-acquired pneumonia, 
including ventilator-associated pneumonia) occurring in patients receiving Zerbaxa were diarrhoea, 
alanine aminotransferase increased, and aspartate aminotransferase increased and were generally mild 
or moderate in severity.

Tabulated list of adverse reactions

The following adverse reactions have been identified during clinical trials with Zerbaxa. Adverse 
reactions are classified according to MedDRA system organ class and frequency. Frequency 
categories are derived according to the following conventions: common (≥ 1/100 to < 1/10), 
uncommon (≥ 1/1,000 to < 1/100) (see Table 3).

Table 3: Adverse reactions identified during clinical trials with ceftolozane/tazobactam

System organ class
Common 
(≥ 1/100 to < 1/10)

Uncommon 
(≥ 1/1,000 to < 1/100)

Infections and infestations Clostridioides difficile colitis2

Candidiasis including 
oropharyngeal and vulvovaginal1, 
Clostridioides difficile colitis1, 
fungal urinary tract infection1, 
Clostridioides difficile infection2

Blood and the lymphatic 
system disorders 

Thrombocytosis1 Anaemia1

Metabolism and nutrition 
disorders

Hypokalemia1
Hyperglycaemia1, 
hypomagnesaemia1, 
hypophosphataemia1

Psychiatric disorders Insomnia1, anxiety1

Nervous system disorders Headache1, dizziness1 Ischemic stroke1

Cardiac disorders
Atrial fibrillation1, tachycardia1, 
angina pectoris1

Vascular disorders Hypotension1 Phlebitis1, venous thrombosis1

Respiratory, thoracic, and 
mediastinal disorders

Dyspnoea1

Gastrointestinal disorders
Nausea1, diarrhoea3, constipation1, 
vomiting3, abdominal pain1

Gastritis1, abdominal distension1, 
dyspepsia1, flatulence1, ileus 
paralytic1

Skin and subcutaneous 
tissue disorders

Rash1 Urticaria1

Renal and urinary 
disorders

Renal impairment1, renal failure1

 



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System organ class
Common 
(≥ 1/100 to < 1/10)

Uncommon 
(≥ 1/1,000 to < 1/100)

General disorders and 
administration site 
conditions

Pyrexia1, infusion site reactions1

Investigations

Alanine aminotransferase increased3, 
aspartate aminotransferase increased3, 
transaminases increased2, liver function 
test abnormal2, blood alkaline 
phosphatase increased2, gamma-
glutamyltransferase increased2

Coombs test positive3, increased 
serum gamma-glutamyl 
transpeptidase (GGT)1, increased 
serum alkaline phosphatase1, 
Clostridioides test positive2

1 Specific for the complicated intra-abdominal infections, acute pyelonephritis, and complicated 
urinary tract infections indications treated with Zerbaxa (1 g / 0.5 g intravenously every 8 hours) for 
up to 14 days.
2 Specific for the hospital-acquired pneumonia, including ventilator-associated pneumonia indication 
treated with Zerbaxa (2 g / 1 g intravenously every 8 hours) for up to 14 days.
3 Applies across all indications: complicated intra-abdominal infections, acute pyelonephritis, 
complicated urinary tract infections, and hospital-acquired pneumonia, including ventilator-associated 
pneumonia.

Description of selected adverse reactions

Laboratory values
The development of a positive direct Coombs test may occur during treatment with Zerbaxa. The 
incidence of seroconversion to a positive direct Coombs test was 0.2% in patients receiving Zerbaxa 
and 0% in patients receiving the comparator in the complicated intra-abdominal infections and 
complicated urinary tract infections clinical trials. The incidence of seroconversion to a positive direct 
Coombs test was 31.2% in patients receiving Zerbaxa and 3.6% in patients receiving meropenem in 
the hospital-acquired pneumonia, including ventilator-associated pneumonia clinical trial. In clinical 
studies, there was no evidence of haemolysis in patients who developed a positive direct Coombs test 
in any treatment group.

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 the national reporting system 
listed in Appendix V.

4.9 Overdose

There is no experience with overdose of Zerbaxa. The highest single dose of Zerbaxa used in clinical 
trials was 3 g / 1.5 g of ceftolozane/tazobactam administered to healthy volunteers.

In the event of overdose, Zerbaxa should be discontinued and general supportive treatment given. 
Zerbaxa can be removed by haemodialysis. Approximately 66% of ceftolozane, 56% of tazobactam, 
and 51% of the M1 metabolite of tazobactam were removed by dialysis. 

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antibacterials for systemic use, other cephalosporins and penems, 
ATC code: J01DI54.

 

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Mechanism of action

Ceftolozane belongs to the cephalosporin class of antimicrobials. Ceftolozane exerts bactericidal 
activity through binding to important penicillin-binding proteins (PBPs), resulting in inhibition of 
bacterial cell-wall synthesis and subsequent cell death. 

Tazobactam is a beta-lactam structurally related to penicillins. It is an inhibitor of many molecular 
Class A beta-lactamases, including CTX-M, SHV, and TEM enzymes. See below.

Mechanisms of resistance

Mechanisms of bacterial resistance to ceftolozane/tazobactam include:
i. Production of beta-lactamases that can hydrolyse ceftolozane and which are not inhibited 

by tazobactam (see below)
ii. Modification of PBPs

Tazobactam does not inhibit all Class A enzymes.
In addition tazobactam does not inhibit the following types of beta-lactamase:

i. AmpC enzymes (produced by Enterobacterales)
ii. Serine-based carbapenemases (e.g., Klebsiella pneumoniae carbapenemases [KPCs])
iii. Metallo-beta-lactamases (e.g., New Delhi metallo-beta-lactamase [NDM])
iv. Ambler Class D beta-lactamases (OXA-carbapenemases)

Pharmacokinetic/pharmacodynamic relationships

For ceftolozane the time that the plasma concentration exceeds the minimum inhibitory concentration 
of ceftolozane for the infecting organism has been shown to be the best predictor of efficacy in animal 
models of infection. 

For tazobactam the PD index associated with efficacy was determined to be the percentage of the dose 
interval during which the plasma concentration of tazobactam exceeds a threshold value 
(%T > threshold). The time above a threshold concentration has been determined to be the parameter 
that best predicts the efficacy of tazobactam in in vitro and in vivo non-clinical models.

Susceptibility testing breakpoints

Minimum inhibitory concentration breakpoints established by the European Committee on 
Antimicrobial Susceptibility Testing (EUCAST) are as follows:

Minimum Inhibitory 
Concentrations (mg/L)

Pathogen Type of Infection Susceptible Resistant 
Enterobacterales Complicated intra-abdominal infections*

Complicated urinary tract infections*
Acute pyelonephritis*

≤ 1 > 1

Enterobacterales Hospital-acquired pneumonia, including 
ventilator-associated pneumonia**

≤ 2 > 2

P. aeruginosa Complicated intra-abdominal infections*
Complicated urinary tract infections*
Acute pyelonephritis*
Hospital-acquired pneumonia, including 
ventilator-associated pneumonia**

≤ 4 > 4

H. influenzae Hospital-acquired pneumonia, including 
ventilator-associated pneumonia**

≤ 0.5 > 0.5

*Based on 1 g ceftolozane / 0.5 g tazobactam intravenously every 8 hours.
**Based on 2 g ceftolozane / 1 g tazobactam intravenously every 8 hours.

 



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Clinical efficacy against specific pathogens

Efficacy has been demonstrated in clinical studies against the pathogens listed under each indication 
that were susceptible to Zerbaxa in vitro:

Complicated intra-abdominal infections

Gram-negative bacteria
Enterobacter cloacae
Escherichia coli 
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa

Gram-positive bacteria
Streptococcus anginosus
Streptococcus constellatus
Streptococcus salivarius

Complicated urinary tract infections, including pyelonephritis 

Gram-negative bacteria
Escherichia coli 
Klebsiella pneumoniae
Proteus mirabilis

Hospital-acquired pneumonia, including ventilator-associated pneumonia

Gram-negative bacteria
Enterobacter cloacae
Escherichia coli
Haemophilus influenzae
Klebsiella oxytoca
Klebsiella pneumoniae
Proteus mirabilis
Pseudomonas aeruginosa
Serratia marcescens

Clinical efficacy has not been established against the following pathogens although in vitro studies 
suggest that they would be susceptible to Zerbaxa in the absence of acquired mechanisms of 
resistance:
Citrobacter freundii
Citrobacter koseri
Klebsiella (Enterobacter) aerogenes
Morganella morganii
Proteus vulgaris
Serratia liquefaciens

In vitro data indicate that the following species are not susceptible to ceftolozane/tazobactam:
Staphylococcus aureus
Enterococcus faecalis
Enterococcus faecium

 



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Paediatric population

The European Medicines Agency has deferred the obligation to submit the results of studies with 
Zerbaxa in one or more subsets of the paediatric population in complicated intra-abdominal infection, 
complicated urinary tract infection, and hospital-acquired pneumonia, including ventilator-associated 
pneumonia (see section 4.2 for information on paediatric use).

5.2 Pharmacokinetic properties

The Cmax and AUC of ceftolozane/tazobactam increase approximately in proportion to dose within 
ceftolozane single-dose range of 250 mg to 3 g and tazobactam single-dose range of 500 mg to 1.5 g. 
No appreciable accumulation of ceftolozane/tazobactam is observed following multiple 1-hour IV 
infusions of 1 g / 0.5 g ceftolozane/tazobactam or 2 g / 1 g ceftolozane/tazobactam administered every 
8 hours for up to 10 days in healthy adults with normal renal function. The elimination half-life (t½) of 
ceftolozane or tazobactam is independent of dose.

Distribution

The binding of ceftolozane and tazobactam to human plasma proteins is low (approximately 16% to 
21% and 30%, respectively). The mean (coefficient of variation CV%) steady-state volume of 
distribution of ceftolozane/tazobactam in healthy adult males (n=51) following a single 1 g / 0.5 g IV 
dose was 13.5 L (21%) and 18.2 L (25%) for ceftolozane and tazobactam, respectively, similar to 
extracellular fluid volume.

Following 1 hour intravenous infusions of 2 g / 1 g ceftolozane/tazobactam or adjusted based on renal 
function every 8 hours in ventilated patients with confirmed or suspected pneumonia (N=22), 
ceftolozane and tazobactam concentrations in pulmonary epithelial lining fluid were greater than 
8 mcg/mL and 1 mcg/mL, respectively, over 100% of the dosing interval. Mean pulmonary 
epithelial-to-free plasma AUC ratios of ceftolozane and tazobactam were approximately 50% and 
62%, respectively and are similar to those in healthy subjects (approximately 61% and 63%, 
respectively) receiving 1 g / 0.5 g ceftolozane/tazobactam.

Biotransformation

Ceftolozane is eliminated in the urine as unchanged parent substance and thus does not appear to be 
metabolised to any appreciable extent. The beta-lactam ring of tazobactam is hydrolyzed to form the 
pharmacologically inactive, tazobactam metabolite M1.

Elimination

Ceftolozane, tazobactam and the tazobactam metabolite M1 are eliminated by the kidneys. Following 
administration of a single 1 g / 0.5 g IV dose of ceftolozane/tazobactam to healthy male adults greater 
than 95% of ceftolozane was excreted in the urine as unchanged parent substance. More than 80% of 
tazobactam was excreted as the parent compound with the remaining amount excreted as the 
tazobactam M1 metabolite. After a single dose of ceftolozane/tazobactam, renal clearance of 
ceftolozane (3.41 - 6.69 L/h) was similar to plasma clearance (4.10 - 6.73 L/h) and similar to the 
glomerular filtration rate for the unbound fraction, suggesting that ceftolozane is eliminated by the 
kidney via glomerular filtration.

The mean terminal elimination half-life of ceftolozane and tazobactam in healthy adults with normal 
renal function is approximately 3 hours and 1 hour, respectively. 

Linearity/non-linearity

The Cmax and AUC of ceftolozane/tazobactam increase in proportion to dose. Plasma levels of 
ceftolozane/tazobactam do not increase appreciably following multiple IV infusions of up to 

 



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2.0 g / 1.0 g administered every 8 hours for up to 10 days in healthy adults with normal renal function. 
The elimination half-life (t½) of ceftolozane is independent of dose.

Special populations

Renal impairment
Ceftolozane/tazobactam and the tazobactam metabolite M1 are eliminated by the kidneys. 

The ceftolozane dose normalized geometric mean AUC increased up to 1.26-fold, 2.5-fold, and 5-fold 
in subjects with mild, moderate, and severe renal impairment, respectively, compared to healthy 
subjects with normal renal function. The respective tazobactam dose normalized geometric mean AUC 
increased approximately up to 1.3-fold, 2-fold, and 4-fold. To maintain similar systemic exposures to 
those with normal renal function, dosage adjustment is required (see section 4.2).

In subjects with end stage renal disease on haemodialysis, approximately two-thirds of the 
administered ceftolozane/tazobactam dose is removed by haemodialysis. The recommended dose in
complicated intra-abdominal infections, complicated urinary tract infections, and acute pyelonephritis
subjects with end stage renal disease on haemodialysis is a single loading dose of 500 mg / 250 mg 
ceftolozane/tazobactam followed by a 100 mg / 50 mg maintenance dose of ceftolozane/tazobactam 
administered every 8 hours for the remainder of the treatment period. The recommended dose in 
hospital-acquired pneumonia, including ventilator-associated pneumonia subjects with end stage renal 
disease on haemodialysis is a single loading dose of 1.5 g / 0.75 g ceftolozane/tazobactam followed by 
a 300 mg / 150 mg maintenance dose of ceftolozane/tazobactam administered every 8 hours for the 
remainder of the treatment period. With haemodialysis, the dose should be administered immediately 
following completion of dialysis (see section 4.2).

Augmented renal clearance
Following a single 1-hour intravenous infusion of 2 g / 1 g ceftolozane/tazobactam to critically ill 
patients with CrCL greater than or equal to 180 mL/min (N=10), mean terminal half-life values of 

ceftolozane and tazobactam were 2.6 hours and 1.5 hours, respectively. Free plasma ceftolozane 
concentrations were greater than 8 mcg/mL over 70% of an 8-hour period; free tazobactam 
concentrations were greater than 1 mcg/mL over 60% of an 8-hour period. No dose adjustment of 
ceftolozane/tazobactam is recommended for hospital-acquired pneumonia, including ventilator-
associated pneumonia patients with augmented renal clearance.

Hepatic impairment
As ceftolozane/tazobactam does not undergo hepatic metabolism, the systemic clearance of 
ceftolozane/tazobactam is not expected to be affected by hepatic impairment. No dose adjustment is 
recommended for ceftolozane/tazobactam in subjects with hepatic impairment (see section 4.2).

Elderly
In a population pharmacokinetic analysis of ceftolozane/tazobactam, no clinically relevant differences
in exposure were observed with regard to age. No dose adjustment of ceftolozane/tazobactam based on 
age alone is recommended.

Paediatric patients
Safety and efficacy in paediatric patients have not been established.

Gender
In a population pharmacokinetic analysis of ceftolozane/tazobactam, no clinically relevant differences 
in AUC were observed for ceftolozane and tazobactam. No dose adjustment is recommended based on 
gender.

Ethnicity
In a population pharmacokinetic analysis of ceftolozane/tazobactam, no clinically relevant differences 
in ceftolozane/tazobactam AUC were observed in Caucasians compared to other ethnicities. No dose 
adjustment is recommended based on race.

 



13

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity or genotoxicity. Carcinogenicity studies with 
ceftolozane/tazobactam have not been conducted.

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the 
maximum human exposure indicating little relevance to clinical use.

Adverse reactions not observed in clinical studies, but seen in animals at exposure levels similar to 
clinical exposure levels and with possible relevance to clinical use were as follows: ceftolozane 
administered to rats during pregnancy and breast-feeding was associated with a decrease in auditory 
startle response in postnatal day (PND) 60 male pups at maternal doses of 300 and 1,000 mg/kg/day. 
A dose of 300 mg/kg/day to rats was associated with a ceftolozane plasma exposure (AUC) value 
lower than the ceftolozane plasma AUC value at the highest recommended human dose of 2 grams 
every 8 hours.

Peri/postnatal development was impaired (reduced pup weights, increase in stillbirths, increase in pup 
mortality) concurrent with maternal toxicity after intraperitoneal administration of tazobactam in the 
rat.

Environmental risk assessment (ERA)

Environmental risk assessment studies have shown that one of the active ingredients, ceftolozane, may 
pose a risk to surface water organisms (see section 6.6).

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride
Arginine
Citric acid, anhydrous

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products except those mentioned in 
section 6.6.

6.3 Shelf life

3 years.

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 
24 hours at room temperature or 4 days at 2 to 8°C. The medicinal product is photosensitive and 
should be protected from light when not stored in the original carton.

From a microbiological point of view, the medicinal product should be used immediately upon 
reconstitution. 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 2 to 8°C, unless 
reconstitution/dilution has taken place in controlled and validated aseptic conditions.

 



14

6.4 Special precautions for storage

Store in a refrigerator (2°C – 8°C).

Store in the original package in order to protect from light.

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3.

6.5 Nature and contents of container

20 mL vial (Type I clear glass) with stopper (bromobutyl rubber) and flip-off seal.

Pack size of 10 vials.

6.6 Special precautions for disposal and other handling

Each vial is for single use only.

Aseptic technique must be followed in preparing the infusion solution.

Preparation of doses

The powder for concentrate for solution for infusion for each vial is reconstituted with 10 mL of water 
for injections or sodium chloride 9 mg/mL (0.9%) solution for injection per vial; following 
reconstitution the vial should be shaken gently to dissolve the powder. The final volume is 
approximately 11.4 mL per vial. The resultant concentration is approximately 132 mg/mL (88 mg/mL 
of ceftolozane and 44 mg/mL of tazobactam) per vial. 

CAUTION: THE RECONSTITUTED SOLUTION IS NOT FOR DIRECT INJECTION.

See section 4.2 for recommended dose regimens for Zerbaxa based on indication and renal function.
The preparation for each dose is shown below.

For preparation of the 2 g ceftolozane / 1 g tazobactam dose: Withdraw the entire contents from 
two reconstituted vials (approximately 11.4 mL per vial) using a syringe and add it to an infusion bag 
containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 1.5 g ceftolozane / 0.75 g tazobactam dose: Withdraw the entire contents from 
one reconstituted vial (approximately 11.4 mL per vial) and 5.7 mL from a second reconstituted vial 
using a syringe and add it to an infusion bag containing 100 mL of 0.9% sodium chloride for injection 
(normal saline) or 5% glucose injection.

For preparation of the 1 g ceftolozane / 0.5 g tazobactam dose: Withdraw the entire contents 
(approximately 11.4 mL) of the reconstituted vial using a syringe and add it to an infusion bag 
containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 500 mg ceftolozane / 250 mg tazobactam dose: Withdraw 5.7 mL of the 
contents of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium 
chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 300 mg ceftolozane / 150 mg tazobactam dose: Withdraw 3.5 mL of the 
contents of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium 
chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 250 mg ceftolozane / 125 mg tazobactam dose: Withdraw 2.9 mL of the 
contents of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium 
chloride for injection (normal saline) or 5% glucose injection.

 



15

For preparation of the 100 mg ceftolozane / 50 mg tazobactam dose: Withdraw 1.2 mL of the contents 
of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium chloride for 
injection (normal saline) or 5% glucose injection.

Zerbaxa solution for infusion is clear and colourless to slightly yellow.

Variations in colour within this range do not affect the potency of the product.

One of the active ingredients, ceftolozane, may have harmful effects if it reaches the aquatic 
environment (see section 5.3). Do not throw away any unused medicinal product or waste material via 
wastewater. Any unused medicinal product or waste material should be disposed of in accordance with 
local requirements. These measures will help protect the environment.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/15/1032/001

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 18 September 2015
Date of latest renewal:

10. DATE OF REVISION OF THE TEXT

MM/YYYY

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu.

 



16

ANNEX II

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT

 



17

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release

Laboratoires Merck Sharp & Dohme Chibret 
Route de Marsat
Riom 
63963, Clermont Ferrand Cedex 9
France

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to medical prescription.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation
marketing authorisation and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.

 



18

ANNEX III

LABELLING AND PACKAGE LEAFLET

 



19

A. LABELLING

 



20

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

CARTON

1. NAME OF THE MEDICINAL PRODUCT

Zerbaxa 1 g / 0.5 g powder for concentrate for solution for infusion
ceftolozane / tazobactam

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each vial contains ceftolozane sulfate equivalent to 1 g ceftolozane and tazobactam sodium equivalent 
to 0.5 g tazobactam.

3. LIST OF EXCIPIENTS

Sodium chloride, arginine, citric acid, anhydrous

4. PHARMACEUTICAL FORM AND CONTENTS

Powder for concentrate for solution for infusion
10 vials

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
For intravenous use after reconstitution and dilution.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Store in a refrigerator.
Store in the original package in order to protect from light.

 



21

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S) 

EU/1/15/1032/001

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Justification for not including Braille accepted.

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC
SN
NN

 



22

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL LABEL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE OF ADMINISTRATION

Zerbaxa 1 g / 0.5 g powder for concentrate 
ceftolozane / tazobactam

2. METHOD OF ADMINISTRATION

For IV use after reconstitution and dilution

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

6. OTHER

 



23

B. PACKAGE LEAFLET

 



24

Package leaflet: Information for the patient

Zerbaxa 1 g / 0.5 g powder for concentrate for solution for infusion
ceftolozane / tazobactam

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you.
- Keep this leaflet. You may need to read it again.
- If you have any further questions, ask your doctor or pharmacist.
- If you get any side effects, talk to your doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Zerbaxa is and what it is used for 
2. What you need to know before you take Zerbaxa
3. How to take Zerbaxa
4. Possible side effects 
5. How to store Zerbaxa
6. Contents of the pack and other information

1. What Zerbaxa is and what it is used for

Zerbaxa is a medicine used to treat a range of bacterial infections. It contains two active substances:
- ceftolozane, an antibiotic that belongs to the group of “cephalosporins” and which can kill 

certain bacteria that can cause infection;
- tazobactam, which blocks the action of certain enzymes called beta-lactamases. These enzymes 

make bacteria resistant to ceftolozane by breaking down the antibiotic before it can act. By 
blocking their action, tazobactam makes ceftolozane more effective at killing bacteria. 

Zerbaxa is used in adults to treat complicated infections within the abdomen, kidney and urinary 
system infections, and an infection of the lungs called “pneumonia”.

2. What you need to know before you take Zerbaxa

Do not take Zerbaxa
- if you are allergic to ceftolozane, tazobactam or any of the other ingredients of this medicine 

(listed in section 6). 
- if you are allergic to medicines known as “cephalosporins”. 
- if you have had a severe allergic reaction (e.g., severe skin peeling; swelling of the face, hands, 

feet, lips, tongue or throat; or difficulty swallowing or breathing) to certain other antibiotics 
(e.g., penicillins or carbapenems).

Warnings and precautions
Talk to your doctor or pharmacist before taking Zerbaxa if you know you are, or have previously been 
allergic to cephalosporins, penicillins or other antibiotics.

Talk to your doctor or pharmacist if you develop diarrhoea while taking Zerbaxa.

Infections caused by bacteria that are not sensitive to Zerbaxa or caused by a fungus can occur during 
or following treatment with Zerbaxa. Tell your doctor if you think you may have another infection.

Treatment with Zerbaxa sometimes causes production of antibodies that react with your red blood 
cells. If you are told that you have an abnormal blood test (called Coombs test) tell your doctor that 
you are having or have recently had Zerbaxa.

 



25

Children and adolescents
This medicine should not be given to children under 18 years old because there is not enough 
information on use in this age group.

Other medicines and Zerbaxa
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

Some medicines may interact with ceftolozane and tazobactam. These include:
- Probenecid (a medicine for gout). This can increase the time it takes for tazobactam to leave 

your body.

Pregnancy and breast-feeding
If you are pregnant or breast-feeding, or think you may be pregnant, ask your doctor or pharmacist for 
advice before taking this medicine. Your doctor will advise if you should receive Zerbaxa during 
pregnancy. 

If you are breast-feeding, your doctor will advise you on whether you should stop breast-feeding or 
stop or avoid Zerbaxa therapy, taking into account the benefit of breast-feeding for the child and the 
benefit of therapy for you.

Driving and using machines
Zerbaxa may cause dizziness, which can affect your ability to drive and use machines. 

Zerbaxa contains sodium
This medicine contains 230 mg sodium (main component of cooking/table salt) in each vial. This is 
equivalent to 11.5% of the recommended maximum daily dietary intake of sodium for an adult. The 
reconstituted vial with 10 mL of 0.9% sodium chloride (normal saline) for injection contains 265 mg 
sodium in each vial. This is equivalent to 13.3% of the recommended maximum daily dietary intake of 
sodium for an adult.

3. How to take Zerbaxa

Your doctor or other healthcare professional will give you this medicine into one of your veins
through an infusion (a drip) lasting one hour. The dose of medicine given to you depends on whether 
or not you have kidney problems.

Adults
The dose depends on the type of infection that you have, where the infection is in your body and how 
serious the infection is. Your doctor will decide on the dose that you need.

The recommended dose of Zerbaxa is 1 g of ceftolozane and 0.5 g of tazobactam or 2 g of ceftolozane 
and 1 g of tazobactam every 8 hours, which is given into one of your veins (directly into the 
bloodstream).

Treatment with Zerbaxa normally lasts between 4 and 14 days, depending on the severity and location 
of the infection and on how your body responds to the treatment.

Patients with kidney problems
Your doctor may need to reduce the dose of Zerbaxa or decide how often Zerbaxa is given to you. 
Your doctor may also want to test your blood to make sure you receive an appropriate dose, especially 
if you have to take this medicine for a long time.

 



26

If you take more Zerbaxa than you should
As this product is given by a doctor or other healthcare professional, it is very unlikely that you will be 
given too much Zerbaxa. However, if you have any concerns you should let your doctor, nurse or 
pharmacist know immediately.

If you stop taking Zerbaxa
If you think you have not been given a dose of Zerbaxa, tell your doctor or other healthcare 
professional immediately.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor straight away if you get these symptoms as you may need urgent medical 
treatment:
- Sudden swelling of your lips, face, throat or tongue; a severe rash; and, swallowing or breathing 

problems. These may be signs of a severe allergic reaction (anaphylaxis) and may be life-
threatening

- Diarrhoea that becomes severe or does not go away or stool that contains blood or mucus during 
or after treatment with Zerbaxa. In this situation, you should not take medicines that stop or 
slow bowel movement

Patients treated for complicated infections within the abdomen, and kidney and urinary system
Common side effects (may affect up to 1 in 10 people):

Headache, stomach ache, constipation, diarrhoea, nausea, vomiting, increase in liver enzymes 
(from blood tests), rash, fever (high temperature), decrease in blood pressure, decrease in 
potassium (from blood tests), increase in the number of certain types of blood cells known as 
platelets, dizziness, anxiety, difficulty sleeping, infusion site reactions

Uncommon side effects (may affect up to 1 in 100 people):
Inflammation of the large intestine due to C. difficile bacteria, inflammation of the stomach, 
abdominal distension, indigestion, excessive gas in stomach or bowel, obstruction of the 
intestine, yeast infection in the mouth (thrush), yeast infection of female genitalia, fungal 
urinary tract infection, increase in sugar (glucose) levels (from blood tests), decrease in 
magnesium levels (from blood tests), decrease in phosphate levels (from blood tests), ischemic 
stroke (stroke caused by reduced blood flow in brain), irritation or inflammation of a vein at 
injection site, venous thrombosis (blood clot in a vein), low red blood cell counts, atrial 
fibrillation (rapid or irregular heartbeat), fast heart beat, angina pectoris (chest pain or feeling of 
tightness, pressure or heaviness in chest), itchy rash or swellings on the skin, hives, Coombs test 
positive (a blood test that looks for antibodies that may fight against your red blood cells),
kidney problems, kidney disease, shortness of breath

Patients treated for an infection of the lungs called “pneumonia”
Common side effects (may affect up to 1 in 10 people):

Inflammation of the large intestine due to C. difficile bacteria, diarrhoea, vomiting, increase in 
liver enzymes (from blood tests)

Uncommon side effects (may affect up to 1 in 100 people):
Infection due to C. difficile bacteria, C. difficile test positive (from stool test), Coombs test 
positive (a blood test that looks for antibodies that may fight against your red blood cells)

 



27

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine.

5. How to store Zerbaxa

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and vial after “EXP.” The 
expiry date refers to the last day of that month.

Unopened vials: Store in a refrigerator (2°C – 8°C).

Store in the original package in order to protect from light.

Do not throw away any medicines via wastewater. Any unused medicinal product or waste material 
should be disposed of in accordance with local requirements. These measures will help protect the 
environment.

6. Contents of the pack and other information

What Zerbaxa contains
- The active substances are ceftolozane and tazobactam.
- Each vial contains ceftolozane sulfate equivalent to 1 g ceftolozane and tazobactam sodium 

equivalent to 0.5 g tazobactam. For doses above 1 g ceftolozane and 0.5 g tazobactam, two vials 
are used.

- The other excipients are sodium chloride, arginine, and citric acid, anhydrous.

What Zerbaxa looks like and contents of the pack
Zerbaxa is a white to slightly yellow powder for concentrate for solution for infusion (powder for 
concentrate) supplied in a vial.

Zerbaxa is available in packs containing 20 mL Type I clear glass vial with stopper (bromobutyl 
rubber) and flip-off seal.

Pack size of 10 vials.

Marketing Authorisation Holder
Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

Manufacturer
Laboratoires Merck Sharp & Dohme Chibret
Route de Marsat
Riom 
63963, Clermont Ferrand Cedex 9
France

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


28

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България 
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak@merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 4482 4000
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
MSD SHARP & DOHME GMBH
Tel: 0800 673 673 673 (+49 (0) 89 4561 2612)
e-mail@msd.de

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@ msd.no

Ελλάδα
MSD Α.Φ.Β.Ε.Ε.
Τηλ: +30 210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Merck Sharp & Dohme de España, S.A.
Tel: +34 91 321 06 00
msd_info@merck.com

Polska
MSD Polska Sp.z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

France
MSD France
Tél: + 33 (0) 1 80 46 40 40

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o. 
Tel: + 385 1 6611 333
croatia_info@merck.com

România
Merck Sharp & Dohme Romania S.R.L.
Tel: +40 21 529 29 00
msdromania@merck.com

 



29

Ireland
Merck Sharp & Dohme Ireland (Human Health) 
Limited
Tel: +353 (0)1 299 8700
medinfo_ireland@merck.com

Slovenija
Merck Sharp & Dohme, inovativna zdravila d.o.o.
Tel: + 386 1 5204 201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak@merck.com

Ιtalia
MSD Italia S.r.l.
Tel: +39 06 361911
medicalinformation.it@merck.com

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 800 00 673 (+357 22866700)
cyprus_info@merck.com 

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364224
msd_lv@merck.com.

United Kingdom
Merck Sharp & Dohme Limited
Tel: +44 (0) 1992 467272
medicalinformationuk@merck.com

This leaflet was last revised in {month YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

---------------------------------------------------------------------------------------------------------------------------

The following information is intended for healthcare professionals only:

Preparation of solutions

Each vial is for single use only.

Aseptic technique must be followed in preparing the infusion solution. 

Preparation of doses

The powder for concentrate for solution for infusion for each vial is reconstituted with 10 mL of water 
for injections or sodium chloride 9 mg/mL (0.9%) solution for injection per vial; following 
reconstitution the vial should be shaken gently to dissolve the powder. The final volume is 
approximately 11.4 mL per vial. The resultant concentration is approximately 132 mg/mL (88 mg/mL 
of ceftolozane and 44 mg/mL of tazobactam) per vial. 

CAUTION: THE RECONSTITUTED SOLUTION IS NOT FOR DIRECT INJECTION.

See section 4.2 of the Summary of Product Characteristics for recommended dose regimens for 
Zerbaxa based on indication and renal function. The preparation for each dose is shown below.

 



30

For preparation of the 2 g ceftolozane / 1 g tazobactam dose: Withdraw the entire contents from 
two reconstituted vials (approximately 11.4 mL per vial) using a syringe and add it to an infusion bag 
containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 1.5 g ceftolozane / 0.75 g tazobactam dose: Withdraw the entire contents from 
one reconstituted vial (approximately 11.4 mL per vial) and 5.7 mL from a second reconstituted vial 
using a syringe and add it to an infusion bag containing 100 mL of 0.9% sodium chloride for injection 
(normal saline) or 5% glucose injection.

For preparation of the 1 g ceftolozane / 0.5 g tazobactam dose: Withdraw the entire contents 
(approximately 11.4 mL) of the reconstituted vial using a syringe and add it to an infusion bag 
containing 100 mL of 0.9% sodium chloride for injection (normal saline) or 5% glucose injection. 

For preparation of the 500 mg ceftolozane / 250 mg tazobactam dose: Withdraw 5.7 mL of the 
contents of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium 
chloride for injection (normal saline) or 5% glucose injection. 

For preparation of the 300 mg ceftolozane / 150 mg tazobactam dose: Withdraw 3.5 mL of the 
contents of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium 
chloride for injection (normal saline) or 5% glucose injection.

For preparation of the 250 mg ceftolozane / 125 mg tazobactam dose: Withdraw 2.9 mL of the 
contents of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium 
chloride for injection (normal saline) or 5% glucose injection. 

For preparation of the 100 mg ceftolozane / 50 mg tazobactam dose: Withdraw 1.2 mL of the contents 
of the reconstituted vial and add it to an infusion bag containing 100 mL of 0.9% sodium chloride for 
injection (normal saline) or 5% glucose injection. 

Zerbaxa solution for infusion is clear and colourless to slightly yellow.

Variations in colour within this range do not affect the potency of the product.

After reconstitution and dilution, chemical and physical in-use stability has been demonstrated for 
24 hours at room temperature or 4 days at 2 to 8°C. The medicinal product is photosensitive and 
should be protected from light when not stored in the original carton.

From a microbiological point of view, the medicinal product should be used immediately upon 
reconstitution. 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 2 to 8°C, unless 
reconstitution/dilution has taken place in controlled and validated aseptic conditions.

One of the active ingredients, ceftolozane, may have harmful effects if it reaches the 
aquatic environment. Do not throw away any unused medicinal product or waste 
material via wastewater. Any unused medicinal product or waste material should be 
disposed of in accordance with local requirements. These measures will help protect the 
environment.

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET