Posology : מינונים

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              100 to 150 mg/kg/day every 8 h, maximum 9 g per day1 fibrosis
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                      1 g at induction of anaesthesia, and a second transuretheral resection of prostate                dose at catheter removal (TURP)
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             Infection                              Usual dose and children < 40 kg
Intermittent Administration

Complicated urinary tract              100-150 mg/kg/day in three divided infections                             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
Nosocomial pneumonia                    100-200 mg/kg/day, maximum 6 g/day 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               Infection                               Usual dose months

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 3g 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            Approx. serum                  Recommended             Frequency of clearance              creatinine µmol/l              unit dose of          dosing (hourly) (ml/min)              (mg/dl)                        Ceftazidime
(g)
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          Approx. serum                   Recommended             Frequency of clearance            creatinine* µmol/l             individual dose        dosing (hourly) (ml/min)**            (mg/dl)                          mg/kg body weight
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             Approx. serum
(ml/min)                   creatinine µmol/l                    Frequency of dosing (mg/dl)                                     (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                                       Maintenance dose (mg) (Creatinine                                       for an ultrafiltration rate (ml/min) of1: Clearance ml/min)                 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 Maintenance dose should be administered every 12 hours.
1


Table 6: Continuous veno-venous haemodialysis dose guidelines

Residual renal function               Maintenance dose (mg) for a dialysate in flow rate of1: (Creatinine Clearance ml/min)                      1.0 litre/h                          2.0 litre/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           1000 15                      500         750               750           750         750           1000 20                      750         750               1000          750         750           1000
1
Maintenance dose should be administered every 12 hours.

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.

For instructions on reconstitution of the medicinal product before administration, see section 6.6.