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Ceftazidim Sandoz

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Document: Ceftazidim Sandoz powder for solution for injection or infusion ENG SmPC change

SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE MEDICINAL PRODUCT

Ceftazidim Sandoz 500 mg powder for solution for injection

Ceftazidim Sandoz 1 g powder for solution for injection

Ceftazidim Sandoz 2 g powder for solution for injection

Ceftazidim Sandoz 1 g powder for solution for infusion

Ceftazidim Sandoz 2 g powder for solution for infusion

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

One vial contains ceftazidime pentahydrate corresponding to 500 mg, 1 g or 2 g of ceftazidime.


Excipient(s) with known effect:

Ceftazidim Sandoz 500 mg contains 26 mg of sodium per vial

Ceftazidim Sandoz 1 g contains 52 mg of sodium per vial

Ceftazidim Sandoz 2 g contains 104 mg of sodium per vial


For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Powder for solution for injection

Powder for solution for infusion


The powder is white to cream-coloured.

4. CLINICAL PARTICULARS


4.1 Therapeutic indications


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


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

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

Febrile neutropenia

2 g every 8 h

Nosocomial pneumonia

Bacterial meningitis

Bacteraemia*

Bone and joint infections

1-2 g every 8 h

Complicated skin and soft tissue infections

Complicated intra-abdominal infections

Peritonitis associated with dialysis in patients on CAPD

Complicated urinary tract infections

1-2 g every 8 h or 12 h

Peri-operative prophylaxis for transuretheral resection of prostate (TURP)

1 g at induction of anaesthesia,

and a second dose at catheter removal

Chronic suppurative otitis media

1 g to 2 g every 8h

Malignant otitis externa

Continuous Infusion

Infection

Dose to be administered

Febrile neutropenia

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

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

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 > 2 months and children < 40 kg

Infection

Usual dose

Intermittent Administration

Complicated urinary tract infections

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

Chronic suppurative otitis media

Malignant otitis externa

Neutropenic children

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

Broncho-pulmonary infections in cystic fibrosis

Bacterial meningitis

Bacteraemia*

Bone and joint infections

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

Complicated skin and soft tissue infections

Complicated intra-abdominal infections

Peritonitis associated with dialysis in patients on CAPD

Continuous Infusion

Febrile neutropenia

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

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

Neonates and infants

≤ 2 months

Infection

Usual dose

Intermittent Administration

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 ceftazidime 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.


Patients with 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.


Patients with 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 ceftazidime in renal impairment – intermittent infusion


Adults and children ≥ 40 kg


Creatinine clearance

(ml/min)

Approx. serum creatinine

μmol/l (mg/dl)

Recommended unit dose of ceftazidime (g)

Frequency of dosing(hourly)

50-31

150-200

(1.7-2.3)

1

12

30-16

200-350

(2.3-4.0)

1

24

15-6

350-500

(4.0-5.6)

0.5

24

<5

>500

(>5.6)

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)**

Approx. serum creatinine*

μmol/l (mg/dl)

Recommended individual dose mg/kg body weight

Frequency of dosing(hourly)

50-31

150-200

(1.7-2.3)

25

12

30-16

200-350

(2.3-4.0)

25

24

15-6

350-500

(4.0-5.6)

12.5

24

<5

>500

(>5.6)

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 ceftazidime in renal impairment – continuous infusion


Adults and children ≥ 40 kg


Creatinine clearance

(ml/min)

Approx. serum creatinine

μmol/l (mg/dl)

Frequency of dosing (hourly)

50-31

150-200

(1.7-2.3)

Loading dose of 2 g followed by 1 g to 3 g /24 hours

30-16

200-350

(2.3-4.0)

Loading dose of 2 g followed by 1 g/24 hours

≤15

>350

(>4.0)

Not evaluated

Caution is advised in dose selection. Close clinical monitoring for safety and efficacy is advised.


Children < 40 kg


The safety and effectiveness of ceftazidime 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 250 mg 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)

Maintenance dose (mg) for an ultrafiltration rate (ml/min) of 1:

5

16.7

33.3

50

0

250

250

500

500

5

250

250

500

500

10

250

500

500

750

15

250

500

500

750

20

500

500

500

750

1 Maintenance dose to be administered every 12 h.

Table 6: Continuous veno-venous haemodialysis dose guidelines


Residual renal function (creatinine clearance in ml/min)

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

0

500

500

500

500

500

750

5

500

500

750

500

500

750

10

500

500

750

500

750

1000

15

500

750

750

750

750

1000

20

750

750

1000

750

750

1000

1 Maintenance dose to be administered every 12 h.

Method of administration


Ceftazidime 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. Ceftazidime 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 listed in section 6.1.


History of severe hypersensitivity (e.g. anaphylactic reaction) to any other type of beta-lactam antibacterial agent (penicillins, monobactams and carbapenems).


4.4 Special warnings and precautions for use


Hypersensitivity

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.


Spectrum of activity

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.


Pseudomembranous colitis

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.


Renal function

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 sections 4.2 and 4.8).


Overgrowth of non-susceptible organisms

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.


Test and assay interactions

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.


Sodium content

Important information about one of the ingredients of Ceftazidim Sandoz:

500 mg powder for solution for injection:

Ceftazidim Sandoz 500 mg contains 26 mg of sodium per vial.

1 g powder for solution for injection/infusion:

Ceftazidim Sandoz 1 g contains 52 mg of sodium per vial.

2 g powder for solution for injection/infusion:

Ceftazidim Sandoz 2 g contains 104 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 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).


Ceftazidime 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


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).


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 un-sponsored 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 to < 1/10)

Uncommon (> 1/1,000 to < 1/100)

Rare (> 1/10,000 to < 1/1,000)

Very rare (< 1/10,000)

Not known (cannot be estimated from the available data)

Adverse drug reactions

System organ class

Common

Uncommon

Very rare

Not known

Infections and infestations

Candidiasis (including vaginitis and oral thrush)

Blood and lymphatic system disorders

Eosinophilia, thrombocytosis

Neutropenia, leucopenia, thrombocytopenia

Agranulocytosis, haemolytic anaemia, lymphocytosis

Immune system disorders


Anaphylaxis (including bronchospasm and/or hypotension) (see section 4.4)

Nervous system disorders

Headache, dizziness

Neurological sequelae1, paraesthesia

Vascular disorders

Phlebitis or thrombophlebitis with intravenous administration


Gastrointestinal disorders

Diarrhea

Antibacterial agent-associated diarrhoea and colitis2 (see section 4.4), abdominal pain, nausea, vomiting

Bad taste

Hepato-biliary disorders

Transient elevations in one or more hepatic enzymes3

Jaundice

Skin and subcutaneous tissue disorders

Maculopapular or urticarial rash

Pruritus

Erythema multiforme, fever, toxic epidermal necrolysis, Stevens Johnson syndrome, angioedema, DRESS4

Renal and urinary disorders

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

Interstitial nephritis, acute renal failure

General disorders and administration site conditions

Pain and/or inflammation after intramuscular injection

Fever

Investigations

Positive Coomb’s test5


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 ceftazidime 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 There have been rare reports where DRESS has been associated with ceftazidime

5A positive Coomb’s test develops in about 5% of patients and may interfere with blood cross matching.


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


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: Antibacterials 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:


Breakpoints

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


Organism

Breakpoints (mg/L)

S

I

R

Enterobacteriaceae

≤ 1

2-4

> 4

Pseudomonas aeruginosa

≤ 81

-

>8

Non-species related breakpoints2

≤4

8

>8

S=susceptible, I=intermediate, R=resistant.

1The breakpoints relate to high dose therapy (2 g x 3).

2Non-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-resistant S. aureus are resistant to ceftazidime.

££S. pneumoniae that demonstrate intermediate suseptibility 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 age-related decrease in renal clearance of ceftazidime. The mean elimination half-life 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.


6.2 Incompatibilities


Ceftazidime should not be mixed with solutions with a pH above 7.5 for example sodium bicarbonate solution for injection. Ceftazidime and aminoglycosides should not be mixed in the solution for infusion because of the risk for precipitation.


Cannulae and catheters for intravenous use should be flushed with physiological salt-solution between administrations of ceftazidime and vancomycin to avoid precipitation.


6.3 Shelf life


30 months

Reconstituted solution: The product should be used immediately.


6.4 Special precautions for storage


Keep the vial in the outer cartonin order toprotect from light.

Reconstituted solution: should be used immediately.


From a microbiological point of view, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless reconstitution has taken place in controlled and validated aseptic conditions.


6.5 Nature and contents of container


500 mg powder for solution for injection:

15 ml vial of clear glass hydr. class III Ph. Eur. with rubber stopper and flip-off crimp seal


1.0 g powder for solution for injection:

20 ml vial of clear glass hydr. class III Ph. Eur. with rubber stopper and flip-off crimp seal


2.0 g powder for solution for injection:

50 ml vial of clear glass hydr. class III Ph. Eur. with rubber stopper and flip-off crimp seal


1.0 g powder for solution for infusion:

50 ml vial of clear glass hydr. class II Ph. Eur. with rubber stopper and flip-off crimp seal


2.0 g powder for solution for infusion:

50 ml vial of clear glass hydr. class II Ph. Eur. with rubber stopper and flip-off crimp seal

100 ml vial of clear glass hydr. class II Ph. Eur. with rubber stopper and flip-off crimp seal


Pack sizes: 1, 5, 5X1, 10, 10X1, 25, 50 vials


Not all pack sizes may be marketed.


6.6 Special precautions for disposal and other handling


Instructions for constitution of the solution for injection/infusion:

Amounts of solvent to be added for the preparation of a solution for injection/infusion and the concentrations of the solutions are given in the table below:

i.m. injection

conc. (mg/ml)

i.v. injection

conc. (mg/ml)

i.v. infusion

conc. (mg/ml)

Ceftazidime 500 mg

Ceftazidime 1.0 g

Ceftazidime 2.0 g

1.5 ml

3.0 ml

-----

333

333

-----

5.0 ml

10.0 ml

10.0 ml

100

100

200

--------

50 ml*

50 ml*

-------

20

40

*Note: Addition of solvent should be performed in two stages (see further instructions below).


As the product dissolves, carbon dioxide is released and a positive pressure develops. Hence, it is recommended that the following techniques of reconstitution are adopted.


For 500 mg, 1g and 2 g i.m./i.v solution for injection:

1. Inject the diluent and shake well to dissolve.

2. Carbon dioxide is released as the antibiotic dissolves, generating pressure within the vial. The solution will become clear within 1 to 2 minutes.

3. Invert the vial and completely depress the syringe plunger prior to insertion.

4. Insert the needle through the vial stopper. Be sure the needle remains within the solution and withdraw contents of the vial in the usual manner. Pressure in the vial may aid withdrawal.

5. The withdrawn solution may contain carbon dioxide bubbles, which should be expelled from the syringe before injection.


For 1 g and 2 g solution for infusion:

1. Inject 10 ml of the diluent and shake to dissolve.

2. Carbon dioxide is released as the antibiotic dissolves, generating pressure within the vial.

The solution will become clear within 1 to 2 minutes.

3. Insert a vent needle to release pressure before adding additional diluent to the vial. Add diluent and then remove the vent needle.

4. Additional pressure that may develop in the vial especially after storage, should be relieved prior to administration to the patient.


NOTE: To preserve product sterility, it is important that a vent needle isnot inserted through the vial closure before the product has dissolved.


Other information

The colour of the ceftazidime solutions range from light yellow to amber depending on concentration, diluent and storage conditions used. Within the stated recommendations, the product potency is not adversely affected by such colour variations.


At ceftazidime concentrations between 20 mg/ml and 333 mg/ml the Ceftazidime Sandoz powders for injection/infusion may be mixed in commonly used solutions for infusion:

0.9% sodium chloride solution (physiological saline solution),

5% glucose solution,

0.9% sodium chloride + 5% glucose solution,

Ringer Lactate Solution


When reconstituted for intramuscular use, the Ceftazidime Sandoz powder for injection/infusion can also be diluted with 1% lidocaine solutions.


7. MARKETING AUTHORISATION HOLDER


[to be completed nationally]


8. MARKETING AUTHORISATION NUMBER(S)


[to be completed nationally]


9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION


Date of first authorisation: {DD month YYYY}

Date of latest renewal: {DD month YYYY}


[to be completed nationally]


10. DATE OF REVISION OF THE TEXT


24 September 2015

[to be completed nationally]