FORTUM 250 mg Powder and solvent for injection, IM IV, child infant, vial, powder/295mg

Powder for solution for injection (IM, IV)

The vial contains a sterile powder, white to cream-white in colour.

Each vial contains 250 mg of ceftazidime (as pentahydrate) and sodium carbonate (118 mg per gram of ceftazidime).

Excipient with known effect

Each vial contains 13 mg (0,57 mmol) of sodium per vial.

Excipients:

Fortum is indicated for the treatment of the following infections in adults, children and infants, including newborns (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 peritoneal dialysis in patients on CAPD.

Treatment of patients with bacteraemia associated with, or suspected to be associated with, any of the infections listed above.

Ceftazidime may be used in the management of neutropenic patients with fever suspected to be due to a bacterial infection.

Ceftazidime may be used as perioperative prophylaxis of urinary tract infections in patients undergoing transurethral resection of the prostate (TURP).

The choice of ceftazidime should take into account its antibacterial spectrum, which is mainly limited to aerobic Gram-negative bacteria (see sections Warnings and precautions and Pharmacodynamics).

Ceftazidime must be co-administered with other antibacterial agents whenever the possible range of causative bacteria is not covered by its spectrum of activity.

Official recommendations concerning the appropriate use of antibacterial agents should be taken into account.

Dosage

Table 1: Adults and children ≥ 40 kg

Discontinue administration
Infection	Dose to be administered
Broncho-pulmonary infections in cystic fibrosis	100 to 150 mg/kg/day every 8 h, with a maximum of 9 g per day1
Febrile neutropenia	2 g every 8 h
Nosocomial pneumonia
Bacterial meningitis
Bacteremia*
Bone and joint infections	1-2 g every 8 h
Complicated skin and soft tissue infections
Complicated intra-abdominal infections
Peritonitis associated with peritoneal dialysis in patients on CAPD
Complicated urinary tract infections	1-2 g every 8 h or 12 h
Peri-operative prophylaxis in transurethral resection of the prostate (TURP)	1 g at induction of anesthesia and a second dose at catheter removal
Chronic suppurative otitis media	1 g to 2 g every 8 h
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 The infusion duration of any dose of dissolved medicine must not exceed 9 h (see section Shelf life). After reconstitution, the unit dose in the infusion fluid must be administered within 9 h, for example for a daily dose of 8 g: 2 g loading dose followed by 2 g as a continuous infusion every 8 h.
Nosocomial pneumonia
Broncho-pulmonary infections in cystic fibrosis
Bacterial meningitis
Bacteremia*
Bone and joint infections
Complicated skin and soft tissue infections
Complicated intra-abdominal infections
Peritonitis associated with peritoneal dialysis in patients on CAPD
1 9 g/day has been used in adults with normal renal function without observing any adverse effects. * Concomitant, or suspected to be concomitant, with an infection listed in section Indications.

 

Table 2: Children < 40 kg

Very young children and infants > 2 months and children < 40 kg	Infection	Usual dose
Discontinue administration
	Complicated urinary tract infections	100-150 mg/kg/day divided into 3 doses, not exceeding a dose of 6 g/day
	Chronic suppurative otitis media
	Malignant otitis externa
	Neutropenic children	150 mg/kg/day divided into 3 doses, not exceeding a dose of 6 g/day
	Broncho-pulmonary infections in cystic fibrosis
	Bacterial meningitis
	Bacteremia*
	Bone and joint infections	100-150 mg/kg/day divided into 3 doses, not exceeding a dose of 6 g/day
	Complicated skin and soft tissue infections
	Complicated intra-abdominal infections
	Peritonitis associated with peritoneal dialysis in patients on CAPD
Continuous infusion
	Febrile neutropenia	Loading dose of 60-100 mg/kg followed by a continuous infusion of 100-200 mg/kg/day, with a maximum of 6 g/day
	Nosocomial pneumonia
	Broncho-pulmonary infections in cystic fibrosis
	Bacterial meningitis
	Bacteremia*
	Bone and joint infections
	Complicated skin and soft tissue infections
	Complicated intra-abdominal infections
	Peritonitis associated with peritoneal dialysis in patients on CAPD
Newborns and infants ≤ 2 months	Infection	Usual dose
Discontinue administration
	Majority of infections	25-60 mg/kg/day divided into 2 doses1
1 In neonates and infants ≤ 2 months, the serum half-life of ceftazidime may be 3 to 4 times longer than in adults. * Concomitant, or suspected to be concomitant, with an infection listed in section Indications.

Paediatric population

The safety and efficacy of Fortum administered as a continuous infusion in neonates and infants ≤ 2 months have not been established.

Elderly patients

Due to decreased clearance of ceftazidime in elderly subjects, the daily dose should normally not exceed 3 g in patients over 80 years of age.

Hepatic impairment

Available data do not indicate the need to adjust the dose in cases of mild to moderate hepatic impairment. There is no clinical trial data in patients with severe hepatic impairment (see also section Pharmacokinetics). Close clinical monitoring of tolerability and efficacy is advised.

Renal impairment

Ceftazidime is excreted unchanged by the kidneys. Therefore, the dosage should be reduced in patients with renal impairment (see also section Warnings and precautions).

An initial loading dose of 1 g must be administered. Maintenance doses should be based on creatinine clearance:

Table 3: Recommended Fortum maintenance doses in renal impairment - intermittent infusion

Adults and children ≥ 40 kg

Creatinine clearance (mL/min)	Approximate serum creatinine μmol/l (mg/dl)	Recommended unit dose of Fortum (g)	Frequency of administration (hours)
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

For patients with severe infections, the unit dose should be increased by 50%, or the frequency of administration should be increased.

In children, creatinine clearance should be adjusted according to body surface area or lean body mass.

Children < 40 kg

Creatinine clearance (ml/min)**	Approximate serum creatinine* μmol/l (mg/dl)	Recommended individual dose (in mg/kg body weight)	Frequency of administration (hours)
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
* Serum creatinine values are indicative values that may not indicate exactly the same degree of reduction for all patients with renal insufficiency. ** Estimated on the basis of body surface area, or measured.

Close clinical monitoring of tolerance and efficacy is advised.

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

Adults and children ≥ 40 kg

Creatinine clearance (mL/min)	Approximate serum creatinine μmol/l (mg/dl)	Frequency of administration (hours)
50-31	150-200 (1,7-2,3)	Loading dose of 2 g followed by 1 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

Particular attention must be paid to dose selection. Close clinical monitoring of tolerance and efficacy is advised.

Children < 40 kg

The safety and efficacy of Fortum administered by continuous infusion in children with renal impairment weighing less than 40 kg have not been established. Close clinical monitoring of tolerance and efficacy is advised.

In the case of continuous infusion in a child with renal impairment, creatinine clearance must be adjusted relative to body surface area or lean body mass.

Haemodialysis

The serum half-life during haemodialysis is 3 to 5 h.

After each haemodialysis session, the maintenance dose of ceftazidime recommended in tables 3 and 4 must be renewed.

Peritoneal dialysis

Ceftazidime may be used in peritoneal dialysis and continuous ambulatory peritoneal dialysis (CAPD).

In addition to intravenous use, ceftazidime may be incorporated into the dialysis fluid (usually 125-250 mg for 2 litres of dialysis solution).

In patients with renal impairment undergoing continuous arteriovenous haemodialysis or haemofiltration with high-permeability membranes: 1 g/day, either as a single dose or as divided doses. In patients undergoing haemofiltration with low-permeability membranes in an intensive care unit, follow the recommended dose for renal impairment.

In patients undergoing venovenous haemofiltration and venovenous haemodialysis, follow the dosage recommendations indicated in tables 5 and 6 below.

Table 5: Recommended doses for continuous venovenous haemofiltration

Residual renal function (creatinine clearance in mL/min)	Maintenance dose (mg) for an ultrafiltration rate (ml/min) of1 :
	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: Recommended doses for continuous venovenous haemodialysis

Residual renal function (creatinine clearance in mL/min)	Maintenance dose (mg) for a dialysate flow rate of1 :
	1,0 litre/h			2,0 litres/h
	Ultrafiltration rate (litres/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	1 000
15	500	750	750	750	750	1 000
20	750	750	1 000	750	750	1 000
1 Maintenance dose to be administered every 12 h.

Method of administration

The dose depends on the severity, susceptibility, site and type of infection as well as on the patient's age and renal function.

Fortum 500 mg and 250 mg must be administered by intravenous injection, or by deep intramuscular injection. The recommended intramuscular injection sites are the upper outer quadrant of the gluteus maximus or the lateral aspect of the thigh. Fortum solutions may be administered directly into the vein. The recommended standard route of administration is intravenous (intermittent administration). Intramuscular administration should only be considered when the intravenous route is not possible or is less appropriate for the patient.

Hypersensitivity to ceftazidime, to any other cephalosporin or to any of the excipients listed in section Composition.

History of severe hypersensitivity (for example, anaphylactic reaction) to any other type of beta-lactam antibacterial product (penicillins, monobactams and carbapenems).

Hypersensitivity

As with all beta-lactam antibacterial products, severe and sometimes fatal hypersensitivity reactions have been reported. In case of severe hypersensitivity reactions, treatment with ceftazidime must be stopped immediately and appropriate measures must be initiated.

Before starting treatment, it must be established whether the patient has a history of severe hypersensitivity to ceftazidime, to other cephalosporins or to any other type of beta-lactam. Caution is advised if ceftazidime is administered to patients with a history of non-severe hypersensitivity to other beta-lactam products.

Severe cutaneous adverse reactions (SCARs)

Severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalised exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported in association with ceftazidime treatment, with an unknown frequency.

Patients must be informed of the signs and symptoms of these reactions and closely monitored for skin reactions.

If signs and symptoms suggestive of these reactions appear, treatment with ceftazidime must be stopped immediately and an alternative treatment should be considered.

If the patient develops a serious reaction such as SJS, TEN, DRESS syndrome or AGEP associated with the use of ceftazidime, treatment with ceftazidime must not be resumed in this patient at any time.

Spectrum of activity

Ceftazidime has a limited antibacterial spectrum of activity. It is not appropriate to use it alone for the treatment of certain types of infections unless the causative agent is already documented and known to be susceptible, or there is a strong suspicion that the most likely causative agent can be treated by ceftazidime. This applies particularly to the treatment of patients with bacteraemia and to the treatment of bacterial meningitis, skin and soft tissue infections, and bone and joint infections. In addition, ceftazidime is susceptible to hydrolysis by several extended-spectrum beta-lactamases (ESBLs). Therefore, information on the prevalence of ESBL-producing organisms must be taken into account when choosing treatment with ceftazidime.

Pseudomembranous colitis

Cases of antibacterial-associated colitis and pseudomembranous colitis have been reported with almost all antibacterial products, including ceftazidime, with severity ranging from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who develop diarrhoea during or after administration of ceftazidime (see section Adverse effects). Discontinuation of ceftazidime treatment and administration of specific treatment against Clostridium difficile should be considered. Any administration of peristalsis inhibitors is contraindicated.

Renal function

Any concomitant treatment with high-dose cephalosporins and nephrotoxic medicinal products, for example aminoglycosides, or potent diuretics (for example, furosemide) may impair renal function.

Ceftazidime is eliminated by the renal route: therefore the dose should be reduced according to the degree of renal impairment. The safety and efficacy of the treatment must be closely monitored in patients with renal impairment. Neurological sequelae have occasionally been reported in cases where the dose was not reduced in patients with renal impairment (see sections Dosage and administration and Adverse effects).

Proliferation of non-susceptible micro-organisms

Prolonged use of this medicine may lead to proliferation of non-susceptible organisms (for example, enterococci and fungi), which may require discontinuation of treatment or other appropriate measures. Repeated assessment of the patient's health status is essential.

Study and testing of interactions

Ceftazidime does not interfere with enzymatic tests for measuring glycosuria, but slight interference (false positives) may occur with copper-containing reagents (Benedict's or Fehling's solutions, Clinitest).

Ceftazidime does not interfere with the alkaline picrate colour reaction used to measure creatinine levels.

A positive Coombs test is observed in approximately 5 % of patients and may interfere with blood compatibility tests.

Sodium content

Important information about one of the components of Fortum:

Fortum 250 mg contains 13 mg (0,57 mmol) of sodium per vial, which is equivalent to 0,65 % of the maximum recommended daily dietary intake of sodium of 2 g per adult by the WHO.

These data should be taken into account in patients on a low-sodium diet.

Interaction studies have been conducted only with probenecid and furosemide.

Concomitant use of high doses in combination with nephrotoxic medicinal products may impair renal function (see section Warnings and precautions).

An antagonism between chloramphenicol and ceftazidime and other cephalosporins has been observed in vitro. The clinical relevance of this observation remains unknown, but if concomitant administration of ceftazidime and chloramphenicol is considered, this possibility of antagonism must be taken into account.

Pregnancy

There are limited data on the use of ceftazidime in pregnant women. Animal studies have not shown direct or indirect harmful effects on reproduction, on embryonic or foetal development, on parturition or on postnatal development (see section Preclinical safety).

Fortum should be prescribed to pregnant women only if the benefit outweighs the risk.

Breast-feeding

Ceftazidime is excreted in small amounts in breast milk, but at therapeutic doses of ceftazidime, no effect on breastfed newborns/infants is expected. Ceftazidime can therefore be used during breastfeeding.

Fertility

No data are available.

No studies on the effects of the product on the ability to drive vehicles and use machines have been performed. However, adverse reactions (for example, dizziness) may occur and affect the patient's ability to drive vehicles and use machines (see section Adverse effects).

The most frequently reported adverse reactions are: eosinophilia, thrombocytosis, phlebitis or thrombophlebitis with intravenous administration, diarrhoea, transient increase in liver enzymes, maculopapular or urticarial rash, pain and/or inflammation after intramuscular injection, and positive Coombs test.

Data from clinical studies, whether or not supported by a sponsor, were used to determine the frequency of common and uncommon adverse reactions. The frequencies assigned to all other adverse reactions were mainly determined using pharmacovigilance data (post-marketing) and refer to a reporting rate rather than an actual frequency. Within each frequency group, adverse reactions are presented in order of decreasing seriousness. The following convention was applied for the classification of frequencies:

• 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).
• Frequency not known (the frequency cannot be estimated from the available data).

System organ classes	Common	Uncommon	Very rare	Not known
Infections and infestations		Candidiasis (including vaginitis and oral thrush)
Blood and lymphatic system disorders	Hypereosinophilia Thrombocytosis	Neutropenia Leukopenia Thrombocytopenia		Agranulocytosis Haemolytic anaemia Lymphocytosis
Immune system disorders				Anaphylaxis (including bronchospasm and/or hypotension) (see section Warnings and precautions)
Nervous system disorders		Headache Vertigo		Neurological sequelae1 Paresthesias
Vascular disorders	Phlebitis or thrombophlebitis related to IV administration
Gastrointestinal disorders	Diarrhoea	Diarrhoea and colitis2 related to an antibacterial product (see section Warnings and precautions) Abdominal pain Nausea Vomiting		Dysgeusia
Hepatobiliary disorders	Transient increases in one or more liver enzymes3			Jaundice
Skin and subcutaneous tissue disorders	Maculopapular or urticarial rash	Pruritus		Lyell syndrome (toxic epidermal necrolysis) Stevens-Johnson syndrome Erythema multiforme Angioedema Drug hypersensitivity syndrome (DRESS)4 Acute generalised exanthematous pustulosis (AGEP)
Renal and urinary disorders		Transient increases in plasma urea, blood urea nitrogen, and/or serum creatinine	Interstitial nephritis Acute renal failure
General disorders and administration site conditions	Pain and/or inflammation after IM injection	Fever
Investigations	Positive Coombs test5

¹ Neurological sequelae have been reported, including tremors, myoclonus, convulsions, encephalopathy and coma, in renal-impaired patients for whom the dose of Fortum was not appropriately reduced.

² Diarrhoea and colitis may be related to Clostridium difficile and may present as pseudomembranous colitis.

³ ALAT (SGPT), ASAT (SGOT), LDH, GGT, alkaline phosphatases.

⁴ Rare cases of DRESS reactions have been reported with ceftazidime.

⁵ A positive Coombs test is observed in approximately 5 % of patients and may interfere with blood compatibility tests.

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: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Pharmacovigilance Centres - Website: https://signalement.social-sante.gouv.fr.

An overdose may lead to neurological sequelae, namely encephalopathy, convulsions and coma.

Symptoms of overdose may occur if the dose is not appropriately reduced in patients with renal insufficiency (see sections Dosage and administration and Warnings and precautions).

Serum concentrations of ceftazidime may be reduced by haemodialysis or peritoneal dialysis.

Pharmacotherapeutic class: Antibacterial for systemic use. Third-generation cephalosporins, ATC code: J01DD02.

Mechanism of action

Ceftazidime inhibits bacterial cell wall synthesis following its binding to penicillin-binding proteins (PBPs). This leads to interruption of the biosynthesis of the bacterial cell wall (peptidoglycans), which causes lysis and death of the bacterium.

Pharmacodynamic effects

In the case of cephalosporins, it has been demonstrated that the main pharmacokinetic/pharmacodynamic index correlating with efficacy in vivo is the percentage of the dosing interval during which the free concentration remains above the minimum inhibitory concentration (MIC) of ceftazidime for the targeted individual species (i.e., % T > MIC).

Clinical efficacy and safety
Resistance mechanism

Bacterial resistance to ceftazidime may be due to one or more of the following mechanisms:

• hydrolysis by beta-lactamases. Ceftazidime can be effectively hydrolysed by extended-spectrum beta-lactamases (ESBLs), which include ESBLs of the SHV family and AmpC enzymes that can be induced or stably derepressed in certain aerobic Gram-negative bacterial species
• reduced affinity of penicillin-binding proteins for ceftazidime
• impermeability of the outer membrane limiting access of ceftazidime to penicillin-binding proteins in Gram-negative organisms.
• bacterial efflux pumps.

Critical concentrations

Critical minimum inhibitory concentration (MIC) values established by theEuropean Committee on Antimicrobial Susceptibility Testing (EUCAST):

Organism	Critical values (mg/L)
	S	I	R
Enterobacterales	≤ 1	2-4	> 4
Pseudomonas aeruginosa	≤ 81	-	> 8
Breakpoints not linked to a species2	≤ 4	8	> 8

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

¹ The critical values refer to high-dose treatment (2 g x 3).

² Critical values not linked to a species have been determined mainly on the basis of PK/PD data and are independent of species-specific MIC distributions. They are to be considered only for species not mentioned in the table and annotations.

Microbiological susceptibility

The prevalence of acquired resistance may vary geographically and over time for certain species. Local information on resistance is therefore desirable, particularly when treating severe infections. If necessary, specialist advice should be sought, mainly when the usefulness of the medicinal product in certain infections may be questionable given the local prevalence of resistance.

Commonly susceptible species

Aerobic Gram-positive: Streptococcus pyogenes Streptococcus agalactiae

Aerobic Gram-negative: Citrobacter koseri Haemophilus influenzae Moraxella catarrhalis Neisseria meningitidis Pasteurella multocida Proteus mirabilis Proteus spp. (other) Providencia spp.

Species for which acquired resistance may be a problem

Aerobic Gram-negative: Acinetobacter baumannii+ Burkholderia cepacia Citrobacter freundii Enterobacter aerogenes Enterobacter cloacae Escherichia coli Klebsiella pneumoniae Klebsiella spp. (other) Pseudomonas aeruginosa Serratia spp. Morganella morganii

Aerobic Gram-positive: Staphylococcus aureus£ Streptococcus pneumoniae££ Viridans group streptococci

Anaerobic Gram-positive: Clostridium perfringens Peptostreptococcus spp.

Anaerobic Gram-negative: Fusobacterium spp.

Naturally resistant species

Aerobic Gram-positive: Enterococcus spp, including Enterococcus faecalis and Enterococcus faecium Listeria spp.

Anaerobic Gram-positive: Clostridium difficile

Anaerobic Gram-negative: Bacteroides spp. (many strains of Bacteroides fragilis are resistant).

Others: Chlamydia spp. Mycoplasma spp. Legionella spp.

£ Methicillin-susceptible Staphylococcus aureus are considered to show low sensitivity to ceftazidime. All methicillin-resistant Staphylococcus aureus are resistant to ceftazidime. ££ A reduced sensitivity to ceftazidime is at least expected when pneumococci present intermediate sensitivity or resistance to penicillin. + High levels of resistance have been observed in more than one location/country/region in Europe.

Absorption

After intramuscular administration of 500 mg and 1 g of ceftazidime, peak plasma concentrations of 18 and 37 mg/l, respectively, are rapidly reached. Five minutes after intravenous bolus injection of 500 mg, 1 g or 2 g, plasma levels of 46, 87 and 170 mg/l, respectively, were reached. The kinetics of ceftazidime are linear in the single-dose range of 0.5 to 2 g after intramuscular or intravenous administration.

Distribution

The serum protein binding rate of ceftazidime is low, at approximately 10 %. Concentrations above the MIC for common pathogenic organisms can be reached in tissues such as bone, myocardium, bile, bronchial secretions, aqueous humour, and synovial, pleural and peritoneal fluids. Ceftazidime crosses the placenta directly and easily and also passes into breast milk. Penetration of the intact blood-brain barrier is low, so low levels of ceftazidime are observed in the CSF in the absence of inflammation. However, concentrations of 4 to 20 mg/l or higher are reached in the CSF in cases of meningitis.

Biotransformation

Ceftazidime is not metabolised.

Elimination

Following parenteral administration, plasma levels decline with an elimination half-life of approximately 2 hours. Ceftazidime is entirely excreted in the urine by glomerular filtration, and approximately 80 to 90 % of the dose is recovered in the urine within 24 hours. Less than 1 % of ceftazidime is excreted via the bile.

Special populations

Renal impairment

Elimination of ceftazidime is reduced in patients with renal impairment, and the dose must therefore be reduced (see section Dosage and administration).

Hepatic impairment

The presence of mild to moderate hepatic impairment has no effect on the pharmacokinetics of ceftazidime in patients who received 2 g of this medicinal product intravenously every 8 hours for 5 days, provided that renal function has not been impaired (see section Dosage and administration).

Elderly patients

The reduced clearance observed in elderly patients was mainly due to the age-related decrease in renal clearance of ceftazidime. The mean elimination half-life ranged from 3,5 to 4 hours after administration of a single dose or repeated administration of 2 g/day as an IV bolus in patients aged 80 years or older.

Paediatric population

The half-life of ceftazidime is prolonged by 4,5 to 7,5 hours in premature and newborn infants after administration of doses between 25 and 30 mg/kg. However, at the age of 2 months, the half-life has the same values as that of an adult.

Non-clinical data from safety pharmacology, repeated-dose toxicity, genotoxicity and reproductive function studies revealed no particular risk for humans. No carcinogenicity study has been conducted with ceftazidime.

Fortum is less stable when injected with sodium bicarbonate than with other intravenous infusion fluids. Its use as a solvent is not recommended. Fortum and aminoglycosides must not be mixed in the same infusion bag or the same syringe. A precipitation phenomenon has been observed when vancomycin is mixed with a ceftazidime solution. Therefore, it is safer to flush infusion bags and tubing between administrations of these medicinal products.

3 years.

After reconstitution:

The physicochemical stability under the conditions of use is 6 days at 4 °C and 9 hours at 25 °C.

From a microbiological point of view, the reconstituted solution should be used immediately. If this is not the case, the storage duration and conditions before use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2 °C and 8 °C, unless reconstitution has taken place under controlled and validated aseptic conditions.

After dilution:

The physicochemical stability under the conditions of use is 6 days at 4 °C and 9 hours at 25 °C.

From a microbiological point of view, the reconstituted and diluted solution should be used immediately. If this is not the case, the storage duration and conditions before use are the responsibility of the user and should normally not exceed 24 hours at a temperature between 2 °C and 8 °C, unless reconstitution has taken place under controlled and validated aseptic conditions.

Store at a temperature not exceeding 25 °C.

Store the vials in the outer carton in order to protect from light.

For storage conditions of the medicinal product after reconstitution, see section Shelf life.

All sizes of Fortum vials are supplied under partial vacuum. When the product dissolves, carbon dioxide is released and positive pressure develops. Small carbon dioxide bubbles in the reconstituted solution may be disregarded.

Instructions for reconstitution

See table 7 for the volumes to add and the solution concentrations (which may be useful when fractional doses are required).

Table 7: Powder for solution for injection

Presentation		Quantity of solvent to add (ml)	Approximate concentration (mg/mL)
250 mg	Intramuscular	1,0 ml	210
	Intravenous bolus	2,5 ml	90

Note: The volume of the ceftazidime solution after reconstitution is increased due to the drug displacement factor; the concentrations obtained, expressed in mg/ml, are detailed in the table above. 

The solutions present a light yellow to amber color depending on their concentration, the solvent used, and their storage conditions. These color changes do not decrease the efficacy of the product within the framework of the recommendations set out.

At concentrations between 1 mg/ml and 40 mg/ml, ceftazidime is compatible with the following solutions for IV administration:

• sodium chloride at 9 mg/ml (0,9 %) solution for injection
• sodium lactate M/6
• Ringer's lactate solution (or Hartmann's solution)
• dextrose solution at 5 %
• sodium chloride solution at 0,225 % + glucose solution at 5 %
• sodium chloride solution at 0,45 % + glucose solution at 5 %
• sodium chloride solution at 0,9 % + glucose solution at 5 %
• sodium chloride solution at 0,18 % + glucose solution at 4 %
• dextrose solution at 10 %
• dextran 40, at 10 % in sodium chloride at 0,9 %
• dextran 40, at 10 % in a glucose solution at 5 %
• dextran 70, at 6 % in sodium chloride at 0,9 %
• dextran 70, at 6 % in a glucose solution at 5 %.

At concentrations between 0,05 mg/ml and 0,25 mg/ml, ceftazidime is compatible with intraperitoneal dialysis fluid (lactate).

When the product is intended for intramuscular administration, ceftazidime at concentrations detailed in table 7 may be reconstituted with 0,5 % or 1 % lidocaine hydrochloride solution for injection.

Preparation of solutions for bolus injection

1. Insert the needle of the syringe into the vial stopper and inject the recommended volume of solvent. The vacuum may facilitate entry of the solvent. Remove the needle from the stopper.
2. Shake well to dissolve the product: carbon dioxide is released and a clear solution is obtained after approximately 1 to 2 minutes.
3. Invert the vial. Ensure the syringe plunger is fully withdrawn, then insert the needle into the vial stopper and aspirate the total volume of the solution into the syringe (the pressure in the vial should facilitate aspiration). Ensure the needle is well immersed in the solution and not in the empty space. The aspirated solution may contain small carbon dioxide bubbles: do not be concerned by them.

These solutions may be administered directly into the vein or introduced into the tubing of an infusion set if the patient receives parenteral fluids. Ceftazidime is compatible with the IV solutions listed above.

 

Any unused antibiotic solution must be discarded.

For single use only.

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

List I
Medicine subject to hospital prescription.

Marketing authorisation (AMM)

CIP 3400937232654 (Fl pdre/295mg).

Price:

3,11 euros (Fl pdre/295mg).

Reimbursed by Social Security at 65 %.
Collection.