FORTUM FOR INJECTION 3G

Active substance: CEFTAZIDIME PENTAHYDRATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Fortum® for Injection 2g
Fortum® for Injection 3g

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Fortum for Injection: Vials contain 2g or 3g ceftazidime (as pentahydrate)
with sodium carbonate (118mg per gram of ceftazidime).
Fortum Monovial in a vial containing 2g ceftazidime pentahydrate.

3

PHARMACEUTICAL FORM
Powder for solution for injection or infusion

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Fortum is indicated for the treatment of the infections listed below in adults
and children including neonates (from birth).











Nosocomial pneumonia
Broncho-pulmonary infections in cystic fibrosis
Bacterial meningitis
Chronic suppurative otitis media
Malignant otitis externa
Complicated urinary tract infections
Complicated skin and soft tissue infections
Complicated intra-abdominal infections
Bone and joint infections
Peritonitis associated with dialysis in patients on CAPD.

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

Ceftazidime may be used in the management of neutropenic patients with
fever that is suspected to be due to a bacterial infection.
Ceftazidime may be used in the peri-operative prophylaxis of urinary tract
infections for patients undergoing trans-urethral resection of the prostate
(TURP).
The selection of ceftazidime should take into account its antibacterial
spectrum, which is mainly restricted to aerobic Gram negative bacteria (see
sections 4.4 and 5.1).
Ceftazidime should be co-administered with other antibacterial agents
whenever the possible range of causative bacteria would not fall within its
spectrum of activity.
Consideration should be given to official guidelines on the appropriate use of
antibacterial agents.
4.2

Posology and method of administration
Posology
Table 1: Adults and children ≥ 40 kg
Intermittent Administration
Infection

Dose to be administered

Broncho-pulmonary infections in
cystic fibrosis
Febrile neutropenia
Nosocomial pneumonia
Bacterial meningitis
Bacteraemia*
Bone and joint infections
Complicated skin and soft tissue
infections
Complicated intra-abdominal
infections
Peritonitis associated with dialysis in
patients on CAPD
Complicated urinary tract infections
Peri-operative prophylaxis for
transuretheral resection of prostate
(TURP)
Chronic suppurative otitis media
Malignant otitis externa
Continuous infusion
Infection

100 to 150 mg/kg/day every 8 h,
maximum 9 g per day1
2 g every 8 h

1-2 g every 8 h

1-2 g every 8 h or 12 h
1 g at induction of anaesthesia, and a
second dose at catheter removal

1 g to 2 g every 8 h
Dose to be administered

Febrile neutropenia
Nosocomial pneumonia
Broncho-pulmonary infections in
cystic fibrosis
Bacterial meningitis
Bacteraemia*
Bone and joint infections
Complicated skin and soft tissue
infections
Complicated intra-abdominal
infections
Peritonitis associated with dialysis in
patients on CAPD

Loading dose of 2 g followed by a
continuous infusion of 4 to 6 g every
24 h1

1

In adults with normal renal function 9 g/day has been used without adverse effects.
*When associated with or suspected to be associated with any of the infections listed in
section 4.1.

Table 2: Children < 40 kg
Infants and toddlers
Infection
>2 months and
children <40 kg
Intermittent Administration
Complicated urinary
tract infections
Chronic suppurative
otitis media
Malignant otitis
externa
Neutropenic children
Broncho-pulmonary
infections in cystic
fibrosis
Bacterial meningitis
Bacteraemia*
Bone and joint
infections
Complicated skin and
soft tissue infections
Complicated intraabdominal infections
Peritonitis associated
with dialysis in
patients on CAPD
Continuous Infusion

Usual dose

100-150 mg/kg/day in three
divided doses, maximum 6
g/day

150 mg/kg/day in three
divided doses, maximum 6
g/day

100 – 150 mg/kg/day in three
divided doses, maximum 6
g/day

Febrile neutropenia
Nosocomial
pneumonia
Broncho-pulmonary
infections in cystic
fibrosis
Bacterial meningitis
Bacteraemia*
Bone and joint
infections
Complicated skin and
soft tissue infections
Complicated intraabdominal infections
Peritonitis associated
with dialysis in
patients with CAPD
Infection

Neonates and infants
≤ 2 months
Intermittent Administration

Loading dose of 60-100
mg/kg followed by a
continuous infusion 100-200
mg/kg/day, maximum 6
g/day

Usual dose

Most infections

25-60 mg/kg/day in two
divided doses1
1
In neonates and infants ≤ 2 months, the serum half life of ceftazidime can be
three to four times that in adults.
*Where associated with, or suspected to be associated with, any of the
infections listed in section 4.1.
Paediatric population
The safety and efficacy of Fortum administered as continuous infusion to
neonates and infants ≤ 2 months has not been established.
Elderly
In view of the age related reduced clearance of ceftazidime in elderly patients,
the daily dose should not normally exceed 3 g in those over 80 years of age.
Hepatic impairment
Available data do not indicate the need for dose adjustment in mild or
moderate liver function impairment. There are no study data in patients with
severe hepatic impairment (see also section 5.2). Close clinical monitoring for
safety and efficacy is advised.
Renal impairment
Ceftazidime is excreted unchanged by the kidneys. Therefore, in patients with
impaired renal function, the dosage should be reduced (see also section 4.4).
An initial loading dose of 1 g should be given. Maintenance doses should be
based on creatinine clearance:

Table 3: Recommended maintenance doses of Fortum in renal impairment –
intermittent infusion
Adults and children ≥ 40 kg
Approx. serum
Creatinine
creatinine
clearance
μmol/l (mg/dl)
(ml/min)
50-31
150-200
(1.7-2.3)
30-16
200-350
(2.3-4.0)
15-6
350-500
(4.0-5.6)
<5
>500
(>5.6)

Recommended
unit dose of Fortum
(g)

Frequency of dosing
(hourly)

1

12

1

24

0.5

24

0.5

48

In patients with severe infections the unit dose should be increased by 50% or
the dosing frequency increased. In children the creatinine clearance should be
adjusted for body surface area or lean body mass.
Children < 40 kg
Creatinine
clearance
(ml/min)**
50-31
30-16
15-6
<5

Approx. serum
creatinine*
μmol/l(mg/dl)
150-200
(1.7-2.3)
200-350
(2.3-4.0)
350-500
(4.0-5.6)
>500
(>5.6)

Recommended
individual dose
mg/kg body weight

Frequency of dosing
(hourly)

25

12

25

24

12.5

24

12.5

48

*The serum creatinine values are guideline values that may not indicate exactly the same degree of
reduction for all patients with reduced renal function.
** Estimated based on body surface area, or measured.

Close clinical monitoring for safety and efficacy is advised.
Table 4: Recommended maintenance doses of Fortum in renal impairment –
continuous infusion
Adults and children ≥ 40 kg
Creatinine clearance
(ml/min)
50-31

Approx. Serum
creatinine µmol/l (mg/dl)
150-200
(1.7-2.3)

Frequency of dosing
(hourly)
Loading dose of 2 g
followed by 1 g to 3 g /24
hours

30-16

200-350
Loading dose of 2 g
(2.3-4.0)
followed by 1 g /24 hours
≤ 15
> 350
Not evaluated
(>4.0)
Caution is advised in dose selection. Close clinical monitoring for safety and
efficacy is advised.
Children < 40 kg
The safety and effectiveness of Fortum administered as continuous infusion in
renally impaired children < 40 kg has not been established. Close clinical
monitoring for safety and efficacy is advised.
If continuous infusion is used in children with renal impairment, the creatinine
clearance should be adjusted for body surface area or lean body mass.
Haemodialysis
The serum half-life during haemodialysis ranges from 3 to 5 h.
Following each haemodialysis period, the maintenance dose of ceftazidime
recommended in the below table should be repeated.
Peritoneal dialysis
Ceftazidime may be used in peritoneal dialysis and continuous ambulatory
peritoneal dialysis (CAPD).
In addition to intravenous use, ceftazidime can be incorporated into the
dialysis fluid (usually 125 to 250mg for 2 litres of dialysis solution).
For patients in renal failure on continuous arterio-venous haemodialysis or
high-flux haemofiltration in intensive therapy units: 1 g daily either as a single
dose or in divided doses. For low-flux haemofiltration, follow the dose
recommended under renal impairment.
For patients on veno-venous haemofiltration and veno-venous haemodialysis,
follow the dosage recommendations in the tables below.
Table 5: Continuous veno-venous haemofiltration dose guidelines
Residual
renal function
(creatinine
clearance
ml/min)
0
5
10
15

Maintenance dose (mg) for an ultrafiltration rate (ml/min) of1:
5

16.7

33.3

50

250
250
250
250

250
250
500
500

500
500
500
500

500
500
750
750

20
1

500

500

500

750

Maintenance dose to be administered every 12 h.

Table 6: Continuous veno-venous haemodialysis dose guidelines
Residual
renal
function
(creatinine
clearance
in ml/min)
0
5
10
15
20
1

Maintenance dose (mg) for a dialysate in flow rate of 1:
1.0 litre/h
2.0 litre/h
Ultrafiltration rate (litre/h)
Ultrafiltration rate (litre/h)
0.5
1.0
2.0
0.5
1.0
2.0
500
500
500
500
750

500
500
500
750
750

500
750
750
750
1000

500
500
500
750
750

500
500
750
750
750

750
750
1000
1000
1000

Maintenance dose to be administered every 12 h.

Method of administration
Fortum should be administered by intravenous injection or infusion, or by
deep intramuscular injection. Recommended intramuscular injection sites are
the upper outer quadrant of the gluteus maximus or lateral part of the thigh.
Fortum solutions may be given directly into the vein or introduced into the
tubing of a giving set if the patient is receiving parenteral fluids.
The standard recommended route of administration is by intravenous
intermittent injection or intravenous continuous infusion. Intramuscular
administration should only be considered when the intravenous route is not
possible or less appropriate for the patient.
The dose depends on the severity, susceptibility, site and type of infection and
on the age and renal function of the patient.
4.3

Contraindications
Hypersensitivity to ceftazidime, to any other cephalosporin or to any of the
excipients.

4.4

History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type
of beta-lactam antibacterial agent (penicillins, monobactams and
carbapenems).
Special warnings and precautions for use
As with all beta-lactam antibacterial agents, serious and occasionally fatal
hypersensitivity reactions have been reported. In case of severe
hypersensitivity reactions, treatment with ceftazidime must be discontinued
immediately and adequate emergency measures must be initiated.

Before beginning treatment, it should be established whether the patient has a
history of severe hypersensitivity reactions to ceftazidime, to other
cephalosporins or to any other type of beta-lactam agent. Caution should be
used if ceftazidime is given to patients with a history of non-severe
hypersensitivity to other beta-lactam agents.
Ceftazidime has a limited spectrum of antibacterial activity. It is not suitable
for use as a single agent for the treatment of some types of infections unless
the pathogen is already documented and known to be susceptible or there is a
very high suspicion that the most likely pathogen(s) would be suitable for
treatment with ceftazidime. This particularly applies when considering the
treatment of patients with bacteraemia and when treating bacterial meningitis,
skin and soft tissue infections and bone and joint infections. In addition,
ceftazidime is susceptible to hydrolysis by several of the extended spectrum
beta lactamases (ESBLs). Therefore information on the prevalence of ESBL
producing organisms should be taken into account when selecting ceftazidime
for treatment.
Antibacterial agent-associated colitis and pseudo-membranous colitis have
been reported with nearly all anti-bacterial agents, including ceftazidime, and
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 ceftazidime (see section 4.8).
Discontinuation of therapy with ceftazidime and the administration of specific
treatment for Clostridium difficile should be considered. Medicinal products
that inhibit peristalsis should not be given.
Concurrent treatment with high doses of cephalosporins and nephrotoxic
medicinal products such as aminoglycosides or potent diuretics (e.g.
furosemide) may adversely affect renal function.
Ceftazidime is eliminated via the kidneys, therefore the dose should be
reduced according to the degree of renal impairment. Patients with renal
impairment should be closely monitored for both safety and efficacy.
Neurological sequelae have occasionally been reported when the dose has not
been reduced in patients with renal impairment (see section 4.2 and 4.8).
Prolonged use may result in the overgrowth of non-susceptible organisms (e.g.
Enterococci, fungi) which may require interruption of treatment or other
appropriate measures. Repeated evaluation of the patient’s condition is
essential.
Ceftazidime does not interfere with enzyme-based tests for glycosuria, but
slight interference (false-positive) may occur with copper reduction methods
(Benedict’s, Fehling’s, Clinitest).
Ceftazidime does not interfere in the alkaline picrate assay for creatinine.

The development of a positive Coombs’ test associated with the use of
ceftazidime in about 5% of patients may interfere with the cross-matching of
blood.
Important information about one of the ingredients of Fortum:
2 g powder for solution for injection or infusion.
Fortum 2 g contains 104 mg of sodium per vial.
3 g powder for solution for injection or infusion.
Fortum 3 g contains 156 mg of sodium per vial.
This should be considered for patients who are on a controlled sodium diet.

4.5

Interaction with other medicinal products and other forms of interaction
Interaction studies have only been conducted with a probenecid and
furosemide.
Concurrent use of high doses with nephrotoxic medicinal products may
adversely affect renal function (see section 4.4).
Chloramphenicol is antagonistic in vitro with ceftazidime and other
cephalosporins. The clinical relevance of this finding is unknown, but if
concurrent administration of ceftazidime with chloramphenicol is proposed,
the possibility of antagonism should be considered.

4.6

Fertility, pregnancy and lactation
Pregnancy
There are limited amounts of data from the use of ceftazidime in pregnant
women. Animal studies do not indicate direct or indirect harmful effects with
respect to pregnancy, embryonal/foetal development, parturition or postnatal
development (see section 5.3).
Fortum should be prescribed to pregnant women only if the benefit outweighs
the risk.
Breast-feeding
Ceftazidime is excreted in human milk in small quantities but at therapeutic
doses of ceftazidime no effects on the breast-fed infant are anticipated.
Ceftazidime can be used during breast-feeding.
Fertility
No data are available.

4.7

Effects on ability to drive and use machines

4.8

No studies on the effects on the ability to drive and use machines have been
performed. However, undesirable effects may occur (e.g. dizziness), which
may influence the ability to drive and use machines (see section 4.8).
Undesirable effects
The most common adverse reactions are eosinophilia, thrombocytosis,
phlebitis or thrombophlebitis with intravenous administration, diarrhoea,
transient increases in hepatic enzymes, maculopapular or urticarcial rash, pain
and/or inflammation following intramuscular injection and positive Coomb’s
test.
Data from sponsored and unsponsored clinical trials have been used to
determine the frequency of common and uncommon undesirable effects. The
frequencies assigned to all other undesirable effects were mainly determined
using post-marketing data and refer to a reporting rate rather than a true
frequency. Within each frequency grouping, undesirable effects are presented
in order of decreasing seriousness. The following convention has been used
for the classification of frequency:
Very common (≥1/10)
Common (≥1/100 and <1/10)
Uncommon (≥1/1,000 and <1/100)
Rare (≥1/10,000 and <1/1000)
Very rare (<1/10,000)
Unknown (cannot be estimated from the available data)

System Organ
Class
Infections and
infestations

Common

Blood and
lymphatic system
disorders

Eosinophilia
Thrombocytosis

Uncommon
Candidiasis
(including vaginitis
and oral thrush)
Neutropenia
Leucopenia
Thrombocytopenia

Immune system
disorders

Nervous system
disorders
Vascular disorders

Headache
Dizziness
Phlebitis or
thrombophlebitis
with intravenous

Very rare

Unknown

Agranulocytosis
Haemolytic
anaemia
Lymphocytosis
Anaphylaxis
(including
bronchospasm
and/or
hypotension)
(see section 4.4)
Neurological
sequelae1
Paraesthesia

Gastrointestinal
disorders

administration
Diarrhoea

Transient
elevations in one
or more hepatic
enzymes3
Maculopapular or
Skin and
subcutaneous tissue urticarial rash
disorders

Antibacterial
agent-associated
diarrhoea and
colitis2 (see section
4.4)
Abdominal pain
Nausea
Vomiting

Bad taste

Hepatobiliary
disorders

Renal and urinary
disorders

General disorders
and administration
site conditions

Investigations

Pain and/or
inflammation
after
intramuscular
injection
Positive Coombs’
test4

Jaundice

Pruritus

Transient
elevations of blood
urea, blood urea
nitrogen and/or
serum creatinine
Fever

Toxic epidermal
necrolysis
Stevens-johnson
syndrome
Erythema
multiforme
Angioedema
Interstitial
nephritis
Acute
renal
failure

1

There have been reports of neurological sequelae including tremor, myoclonia, convulsions,
encephalopathy and coma in patients with renal impairment in whom the dose of Fortum has
not been appropriately reduced.
2
Diarrhoea and colitis may be associated with Clostridium difficile and may present as
pseudomembranous colitis.
3
ALT (SGPT), AST (SOGT), LHD, GGT, alkaline phosphatase.
4
A positive Coombs test develops in about 5% of patients and may interfere with blood cross
matching.

4.9

Overdose
Overdose can lead to neurological sequelae including encephalopathy,
convulsions and coma.
Symptoms of overdose can occur if the dose is not reduced appropriately in
patients with renal impairment (see sections 4.2 and 4.4).

Serum levels of ceftazidime can be reduced by haemodialysis or peritoneal
dialysis.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic group: Anti-bacterials for systemic use.
Third-generation cephalosporins ATC code: J01DD02
Mechanism of action
Ceftazidime inhibits bacterial cell wall synthesis following attachment to penicillin
binding proteins (PBPs). This results in the interruption of cell wall (peptidoglycan)
biosynthesis, which leads to bacterial cell lysis and death.
PK/PD relationship
For cephalosporins, the most important pharmacokinetic-pharmacodynamic index
correlating with in vivo efficacy has been shown to be the percentage of the dosing
interval that the unbound concentration remains above the minimum inhibitory
concentration (MIC) of ceftazidime for individual target species (i.e. %T>MIC).
Mechanism of Resistance
Bacterial resistance to ceftazidime may be due to one or more of the following
mechanisms:


hydrolysis by beta-lactamases. Ceftazidime may be efficiently hydrolysed by
extended-spectrum beta-lactamases (ESBLs), including the SHV family of
ESBLs, and AmpC enzymes that may be induced or stably derepressed in certain
aerobic Gram-negative bacterial species



reduced affinity of penicillin-binding proteins for ceftazidime



outer membrane impermeability, which restricts access of ceftazidime to
penicillin binding proteins in Gram-negative organisms



bacterial efflux pumps.

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

Breakpoints (mg/L)
S
1

8



Pseudomonas

1



Enterobacteriaceae

I

R

2-4

>4

-

>8

aeruginosa
4



Non-species related
breakpoints2

8

>8

S=Susceptible, I=Intermediate, R=Resistant
1

The breakpoints relate to high dose therapy (2 g x 3).

2

Non-species related breakpoints have been determined mainly on the basis of PK/PD data and
are independent of MIC distributions of specific species. They are for use only for species not
mentioned in the table or footnotes.

Microbiological 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 ceftazidime in at least some
types of infections is questionable.

Commonly Susceptible Species
Gram-positive aerobes:
Streptococcus pyogenes
Streptococcus agalactiae
Gram-negative aerobes:
Citrobacter koseri
Escherichia coli
Haemophilus influenzae
Moraxella catarrhalis
Neisseria meningitidis
Proteus mirabilis
Proteus spp. (other)
Providencia spp.
Species for which acquired resistance may be a problem
Gram-negative aerobes:
Acinetobacter baumannii£+
Burkholderia cepacia
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Klebsiella pneumoniae
Klebsiella spp. (other)
Pseudomonas aeruginosa
Serratia spp.
Morganella morganii
Gram-positive aerobes:
Staphylococcus aureus£
Streptococcus pneumoniae££
Gram-positive anaerobes:
Clostridium perfringens
Peptococcus spp.
Peptostreptococcus spp.
Gram-negative anaerobes
Fusobacterium spp.

Inherently resistant organisms
Gram-positive aerobes:
Enterococci including Enterococcus faecalis and Enterococcus faecium
Listeria spp.
Gram-positive anaerobes:
Clostridium difficile
Gram-negative anaerobes
Bacteroides spp. (many strains of Bacteroides fragilis are resistant).
Others:
Chlamydia spp.
Mycoplasma spp.
Legionella spp.
£

S.aureus that is methicillin-susceptible are considered to have inherent low susceptibility to
ceftazidime. All methicillin-resistance S. aureus are resistant to ceftazidime.

££

S.pneumoniae that demonstrate intermediate susceptibility or are resistant to penicillin can be
expected to demonstrate at least reduced susceptibility to ceftazidime.

+High rates of resistance have been observed in one or more areas/countries/regions within the
EU.

5.2

Pharmacokinetic properties
Absorption
After intramuscular administration of 500 mg and 1 g of ceftazidime, peak
plasma levels of 18 and 37 mg/l, respectively are achieved rapidly. Five
minutes after intravenous bolus injection of 500 mg, 1 g or 2 g, plasma levels
are 46, 87 and 170 mg/l, respectively. The kinetics of ceftazidime are linear
within the single dose range of 0.5 to 2 g following intravenous or
intramuscular dosing.
Distribution
The serum protein binding of ceftazidime is low at about 10%. Concentrations
in excess of the MIC for common pathogens can be achieved in tissues such as
bone, heart, bile, sputum, aqueous humour, synovial, pleural and peritoneal
fluids. Ceftazidime crosses the placenta readily, and is excreted in the breast
milk. Penetration of the intact blood-brain barrier is poor, resulting in low
levels of ceftazidime in the CSF in the absence of inflammation. However,
concentrations of 4 to 20 mg/l or more are achieved in the CSF when the
meninges are inflamed.
Biotransformation
Ceftazidime is not metabolised.
Elimination

After parenteral administration plasma levels decrease with a half-life of about
2 h. Ceftazidime is excreted unchanged into the urine by glomerular filtration;
approximately 80 to 90 % of the dose is recovered in the urine within 24 h.
Less than 1 % is excreted via the bile.
Special patient populations
Renal impairment
Elimination of ceftazidime is decreased in patients with impaired renal
function and the dose should be reduced (see section 4.2).
Hepatic impairment
The presence of mild to moderate hepatic dysfunction had no effect on the
pharmacokinetics of ceftazidime in individuals administered 2 g intravenously
every 8 hours for 5 days, provided renal function was not impaired (see section
4.2).
Elderly
The reduced clearance observed in elderly patients was primarily due to agerelated decrease in renal clearance of ceftazidime. The mean elimination halflife ranged from 3.5 to 4 hours following single or 7 days repeat BID dosing of
2 g IV bolus injections in elderly patients 80 years or older.
Paediatric population
The half-life of ceftazidime is prolonged in preterm and term neonates by 4.5
to 7.5 hours after doses of 25 to 30 mg/kg. However, by the age of 2 months
the half-life is within the range for adults.
5.3

Preclinical safety data
Non-clinical data reveal no special hazard for humans based on studies of
safety pharmacology, repeat dose toxicity, genotoxicity, toxicity to
reproduction. Carcinogenicity studies have not been performed with
ceftazidime.

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Sodium carbonate (anhydrous sterile)

6.2

Incompatibilities
Ceftazidime is less stable in Sodium Bicarbonate Injection than other
intravenous fluids. It is not recommended as a diluent.
Ceftazidime and aminoglycosides should not be mixed in the same giving set
or syringe.
Precipitation has been reported when vancomycin has been added to
ceftazidime in solution. It is recommended that giving sets and intravenous
lines are flushed been administration of these two agents.

6.3

Shelf life
Fortum Monovial - Two years for the unconstituted product and 24 hours for
the constituted product when stored below 30ºC and protected from light.
Three years when stored below 25ºC and protected from light.

6.4

Special precautions for storage
The unconstituted product should be stored below 25ºC and protected from
light.
Constituted solutions may be stored in the refrigerator (2 – 8ºC) for up to 24
hours.

6.5

Nature and contents of container
Individually cartoned vials containing 2g ceftazidime (as pentahydrate) for
intravenous use in packs of 1 or 5.
Individually cartoned Monovials containing 2g ceftazidime (as pentahydrate)
for intravenous infusion.
Individually cartoned vials containing 2g ceftazidime (as pentahydrate) for
intravenous infusion in packs of 1 or 5.
Individually cartoned vials containing 3g ceftazidime (as pentahydrate) for
intravenous and intravenous infusion use.
Not all pack sizes may be marketed.

6.6

Special precautions for disposal and other handling
All sizes of vials of Fortum are supplied under reduced pressure. As the
product dissolves, carbon dioxide is released and a positive pressure develops.
Small bubbles of carbon dioxide in the constituted solution may be ignored.
Instructions for constitution
See table for addition volumes and solution concentrations, which may be
useful when fractional doses are required.
Vial size

Amount of diluent
to be added (ml)
250 mg powder for solution for injection
250 mg
Intramuscular
1.0 ml
Intravenous bolus
2.5 ml
500 mg powder for solution for injection
500 mg
Intramuscular
1.5 ml
Intravenous bolus
5 ml
1 g powder for solution for injection or infusion
1g
Intramuscular
3 ml
Intravenous bolus
10 ml
Intravenous infusion 50 ml*
2 g powder for solution for injection or infusion

Approximate
concentration (mg/ml)
210
90
260
90
260
90
20

2g

Intravenous bolus
10 ml
Intravenous infusion 50 ml*
3 g powder for solution for injection or infusion
3g
Intravenous bolus
15 ml
Intravenous infusion 75 ml*

170
40
170
40

*Note: Addition should be in two stages.
Solutions range in colour from light yellow to amber depending on
concentration, diluent and storage conditions used. Within the stated
recommendations, product potency is not adversely affected by such colour
variations.
Ceftazidime at concentrations between 1 mg/ml and 40 mg/ml is compatible
with:














sodium chloride 9 mg/ml (0.9%) solution for injection
M/6 sodium lactate injection
compound sodium lactate injection (Hartmann's solution)
5% dextrose injection
0.225% sodium chloride and 5% dextrose injection
0.45% sodium chloride and 5% dextrose injection
0.9% sodium chloride and 5% dextrose injection
0.18% sodium chloride and 4% dextrose injection
10% dextrose injection
Dextran 40 injection 10% in 0.9% sodium chloride injection
Dextran 40 injection 10% in 5% dextrose injection
Dextran 70 injection 6% in 0.9% sodium chloride injection
Dextran 70 injection 6% in 5% dextrose injection

Ceftazidime at concentrations between 0.05 mg/ml and 0.25 mg/ml is
compatible with Intra-peritoneal Dialysis Fluid (Lactate).
Ceftazidime may be constituted for intramuscular use with 0.5% or 1%
Lidocaine Hydrochloride Injection.
Preparation of solution for bolus injection
1. Insert the syringe needle through the vial closure and inject the
recommended volume of diluent. The vacuum may assist entry of the
diluent. Remove the syringe needle.
2. Shake to dissolve: carbon dioxide is released and a clear solution will be
obtained in about 1 to 2 minutes.
3. Invert the vial. With the syringe plunger fully depressed, insert the needle
through the vial closure and withdraw the total volume of solution into the
syringe (the pressure in the vial may aid withdrawal). Ensure that the
needle remains within the solution and does not enter the head space. The
withdrawn solution may contain small bubbles of carbon dioxide; they
may be disregarded.

These solutions may be given directly into the vein or introduced into the
tubing of a giving set if the patient is receiving parenteral fluids. Ceftazidime
is compatible with the most commonly used intravenous fluids.
Preparation of solutions for iv infusion from ceftazidime injection in standard
vial presentation (mini-bag or burette-type set):
Prepare using a total of 50 ml (for 1 g and 2 g vials) and 75 ml (for 3 g vials)
of compatible diluents, added in TWO stages as below.

1. Introduce the syringe needle through the vial closure and inject 10 ml of
diluent for the 2 g vial and 15 ml for the 3 g vial.
2. Withdraw the needle and shake the vial to give a clear solution.
3. Do not insert a gas relief needle until the product has dissolved. Insert a
gas relief needle through the vial closure to relieve the internal pressure.
4. Transfer the reconstituted solution to final delivery vehicle (e.g. mini-bag
or burette-type set) making up a total volume of a least 50 ml (75 ml for
the 3 g vial), and administer by intravenous infusion over 15 to 30 min.
Note: To preserve product sterility, it is important that the gas relief needle is
not inserted through the vial closure before the product has dissolved,
Preparation of solution for for intravenous infusion (Monovial presentation)
The contents of the Monovial are added to small volume infusion bags
containing 0.9% Sodium Chloride solution for Injection, or 5% Dextrose
Injection, or another compatible fluid.
The 2 g Monovial presentation must be constituted using 100 ml infusion bag.
1. Peel off the removable top part of the label and remove the cap.
2. Insert the needle of the Monovial into the additive port of the infusion bag.
3. To activate, push the plastic needle holder of the Monovial down onto the
vial shoulder until a “click” is heard.
4. Holding it upright, fill the vial to approximately two-thirds capacity by
squeezing the bag several times.
5. Shake the vial to reconstitute the ceftazidime.
6. On reconstitution, the ceftazidime will effervesce slightly.
7. With the vial uppermost, transfer the reconstituted ceftazidime into the
infusion bag by squeezing and releasing the bag.
8. Repeat steps 4 to 7 to rinse the inside of the vial. Dispose of the empty
Monovial safely. Check that the powder has dissolved, and that the bag
has no leaks.

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

7

MARKETING AUTHORISATION HOLDER
Glaxo Operations UK Ltd
980 Great West Road
Brentford
Middlesex
TW8 9GS
United Kingdom
Trading as
GlaxoSmithKline UK
Stockley Park West
Uxbridge
Middlesex UB11 1BT

8

MARKETING AUTHORISATION NUMBER(S)
PL 00004/0294

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
17/01/2011

10

DATE OF REVISION OF THE TEXT
12/07/2013

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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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