Document: spc-doc_PL 04569-0975 change

• spc-doc_PL 04416-0561
• spc-doc_PL 04569-0975
• spc-doc_PL 08828-0193
• spc-doc_PL 39655-0003

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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Ceftazidime 500mg, powder for solution for injection

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Ceftazidime pentahydrate equivalent to 500 mg of ceftazidime.

For one vial

For a full list of excipients, see section 6.1.

Ceftazidime 500 mg contains 25.3 mg (1.1 mmol) of sodium per vial

3    PHARMACEUTICAL FORM

Powder for solution for injection.

White or almost white, crystalline powder in vial.

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). ¹

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
Bacteraemia1
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
Bacteraemia1
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	100150 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	100150 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 100200 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.

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.

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 Ceftazidime in renal impairment -intermittent, infusion

Adults and children > 40 kg

Creatinine clearance (ml/min)	Approx. serum creatinine pmol/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	Approx.	serum	Recommended	Frequency of
(ml/min)**	creatinine*		individual dose	dosing

	frmol/l (mg/dl)	mg/kg body weight	(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 (>56)	12.5	48
* The serum creatinine values are guideline va same degree of reduction for all patients with re ** Estimated based on body surface area, or me		ues that may not indicate exactly the duced renal function. asured.

Table 4: Recommended maintenance doses of Ceftazidime in renal impairment -continuous infusion

Close clinical monitoring for safety and efficacy is advised.

Adults and children > 40 kg

Creatinine clearance	Approx. serum creatinine	Frequency of dosing
(ml/min)	frmol/l (mg/dl)	(hourly)
50-31	150-200	Loading dose of 2 g
	(1.7-2.3)	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
	(>40)

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 (litres/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.

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

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 sections 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 Ceftazidime:

The sodium content 50.6 mg per 1.0 g dose should be taken into account.

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)

Unknown (cannot be estimated from the available data)

System Organ Class	Common	Uncommon	Very rare	Unknown
Infections and infestations		Candidiasis (including vaginitis and oral thrush)
Blood and lymphatic system disorders	Eosinophilia Thrombocytosis	Neutropenia Leucopenia Thrombocyt openia		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	Diarrhoea	Antibacterial agent- associated diarrhoea and colitis2 (see section 4.4) Abdominal pain Nausea Vomiting		Bad taste
Hepatobiliary disorders	Transient elevations in one or more hepatic enzymes3			Jaundice
Skin and subcutaneous tissue disorders	Maculopapular or urticarial rash	Pruritus		Toxic epidermal necrolysis Stevens-johnson syndrome Erythema multiforme Angioedema

System Organ Class	Common	Uncommon	Very rare	Unknown
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 Coombs’ test4

¹There 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 (see section 4.4 and 4.5).

²    Diarrhoea and colitis may be associated with Clostridium difficile and may present as pseudomembranous colitis (see section 4.4).

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: 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:

•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	I	R
Enterobacteriaceae	< 1	2-4	> 4
Pseudomonas aeruginosa	< 81	-	> 8
Non-species related breakpoints2	<4	8	> 8

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

'The 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.

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 injection 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

2 years

Chemical and physical in-use stability after reconstitution /dilution in the following reconstitution /dilution solutions:

-    water for injections

-    0.9% sodium chloride solution

-    10% glucose solution

-    10% dextrans solution

-    sodium lactate solution

has been demonstrated for 4 hours at a temperature not exceeding 25°C or for 24 hours between 2°C and 8°C.

However, 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 been taken place in controlled and validated aseptic conditions.

6.4 Special precautions for storage

Before reconstitution : Keep the container in the outer packaging in order to protect from light.

This medicinal product does not require any special storage conditions.

For storage conditions of the reconstituted medicinal product, see section 6.3.

6.5 Nature and contents of container

Type III glass vial, closed with a chlorobutyl rubber stopper and a flip-off aluminium cap.

Pack sizes of 1, 5, 10, 25, 50 vials.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

All sizes of vials of Ceftazidime 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 reconstitution

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)	Approximate concentration (mg/ml)
500 mg powder for solution for injection
500 mg	Intramuscular Intravenous bolus	1.5 ml	260

		5 ml	90
1 g powder for solution for injection or infusion
1 g	Intramuscular	3 ml	260
	Intravenous bolus Intravenous infusion	10 ml	90
		50 ml*	20
2 g powder for solution for injection or infusion
2 g	Intravenous bolus	10 ml	170
	Intravenous infusion	50 ml*	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.

Preparation for direct administration for 500 mg IM-IV, 1 g IM-IV and 2 g IV The following reconstitution guidelines should be followed:

1.    Insert the syringe needle through the original vial closure and inject the recommended volume of diluent. The vacuum may assist entry of the diluent.

2.    Remove the syringe needle.

3.    Shake the original vial to dissolve the content. CO₂ is released and a clear solution will be obtained in about 1 to 2 minutes.

4.    Invert the original 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.

5.    The withdrawn solution may contain small bubbles of carbon dioxide; they may be disregarded.

For intravenous injection, the solution must be administered directly into the vein or introduced into the tubing of the giving set if the patient is receiving parenteral fluid.

Preparation for administration of 2 g vials by infusion

This vial may be constituted for short intravenous infusion (e.g. up to 30 minutes). Prepare using a total of 50ml of compatible diluent, added in TWO stages as below:

1.    Insert the syringe needle through the vial closure and add 10 ml of diluent. The vacuum may assist entry of the diluent.

2.    Remove the syringe needle.

3.    Shake the original vial to dissolve the content. CO₂ is released and a clear solution will be obtained in about 1 to 2 minutes.

4.    Do not insert a gas relief needle until the product has dissolved. Insert a gas relief needle through the vial closure to relive the internal pressure.

5.    Transfer the reconstituted solution to the final delivery vehicle, making up to a total volume of at least 50 ml, and administer by intravenous infusion over 15-30 minutes.

Reconstitution for 1 g and 2 g vials with a transfer cap

For use with transfer cap, the 1g presentation must be constituted in not less than 50mL infusion bag and the 2 g presentation must be constituted in not less than 100mL infusion bag to allow release of the gas.

1.    Position and fit the transfer cap on ceftazidime original vial in aseptic conditions on a plane surface.

2.    Adapt the set (transfer cap + original vial) on the injection site of the infusion bag in oblique position (vial at the top with regard to the bag).

3.    Push the injection site of the bag up to the end of the needle of the transfer cap.

4.    Invert the set group (vial down). Press the bag 2-3 times to fill the solution in about 3/4 of the vial volume for the 1 g presentation and in about 1/5 of the vial volume for the 2 g presentation.

5.    Shake the system (vial + transfer cap + bag), to dissolve the vial content. To avoid leaks, maintain the system (vial + transfer cap + bag) tighly together

6.    Invert again the system (vial on the top). Transfer the reconstituted solution into the infusion bag by squeezing and releasing the bag. If needed, repeat the previous steps in order to have well dissolved content of the vial into the bag.

7.    Remove slowly and carefully the transfer cap and the vial from the injection site of the bag, in oblique position (vial at the top).

Single use only.

Unused solution should be discarded.

Only clear solutions practically free from particles should be used.

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

7    MARKETING AUTHORISATION HOLDER

Generics [UK] Ltd t/a Mylan

Station Close

Potters Bar

Herts

EN6 1TL

8    MARKETING AUTHORISATION NUMBER(S)

PL 04569/0975

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

12/05/2013

10 DATE OF REVISION OF THE TEXT

12/05/2013

1

   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.