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, fibrosis                                            maximum 9 g per day1 Febrile neutropenia
Nosocomial pneumonia                                2 g every 8 h
Bacterial meningitis
Bacteraemia*
Bone and joint infections
Complicated skin and soft tissue                    1-2 g every 8 h 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 transurethral resection of prostate                 second dose at catheter removal (TURP)
Chronic suppurative otitis media
Malignant otitis externa                            1 g to 2 g every 8 h Continuous infusion
Infection                                           Dose to be administered Febrile neutropenia                                 Loading dose of 2 g followed by a Nosocomial pneumonia                                continuous infusion of 4 to 6 g every 24 h1 Broncho-pulmonary infections in cystic              The infusion of any unit of dissolved drug fibrosis                                            shall last no longer than 9h (see section Bacterial meningitis                                6.3).
Bacteraemia*
Bone and joint infections                           Therefore, following reconstitution, the Complicated skin and soft tissue                    unit dose in the infusion fluid should be infections                                          administered within 9 h, for example for 8 Complicated intra-abdominal infections              g per day: 2 g loading dose followed by 2 Peritonitis associated with dialysis in             g continuous infusion every 8 h.
patients on CAPD
1Inadults 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    Infection                   Usual dose months and children
<40 kg
Intermittent Administration

Complicated urinary         100-150 mg/kg/day in three tract infections            divided doses, maximum 6
Chronic suppurative         g/day otitis media
Malignant otitis externa
Neutropenic children        150 mg/kg/day in three divided
Broncho-pulmonary           doses, maximum 6 g/day infections in cystic fibrosis
Bacterial meningitis
Bacteraemia*
Bone and joint              100 – 150 mg/kg/day in three infections                  divided doses, maximum 6
Complicated skin and        g/day 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
Nosocomial pneumonia        followed by a continuous
Broncho-pulmonary           infusion 100-200 mg/kg/day,
infections in cystic        maximum 6 g/day 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 ≤     Infection                   Usual dose
2 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 Fortum administered as continuous infusion to neonates and infants ≤ 2 months has not been established.

Elderly
In view of the age related reduced clearance of ceftazidime in elderly patients, the daily dose should not normally exceed 3 g in those over 80 years of age.

Hepatic impairment
Available data do not indicate the need for dose adjustment in mild or moderate liver function impairment. There are no study data in patients with severe hepatic impairment (see also section 5.2). Close clinical monitoring for safety and efficacy is advised.

Renal impairment
Ceftazidime is excreted unchanged by the kidneys. Therefore, in patients with impaired renal function, the dosage should be reduced (see also section 4.4).

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

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

Adults and children ≥ 40 kg

Creatinine         Approx. serum                Recommended                     Frequency of dosing clearance             creatinine             unit dose of Fortum (g)                  (hourly) ml/min              µmol/l(mg/dl)
50-31               150-200                            1                                 12 (1.7-2.3)
30-16               200-350                            1                                 24 (2.3-4.0)
15-6               350-500                           0.5                                24 (4.0-5.6)
<5                  >500                            0.5                                48 (>5.6)

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 dosing clearance             creatinine*             individual dose mg/kg                   (hourly) (ml/min)**           µmol/l (mg/dl)                body weight
50-31               150-200                          25                                  12 (1.7-2.3)
30-16              200-350                            25                                24 (2.3-4.0)
15-6               350-500                           12.5                               24 (4.0-5.6)
<5                  >500                            12.5                               48 (>5.6)
* The serum creatinine values are guideline values that may not indicate exactly the same degree of reduction for all patients with reduced renal function.
** Estimated based on body surface area, or measured.

Close clinical monitoring for safety and efficacy is advised.

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

Adults and children ≥ 40 kg

Creatinine clearance       Approx. Serum creatinine      Frequency of dosing (hourly) (ml/min)                 µmol/l (mg/dl)
50-31                       150-200               Loading dose of 2 g followed (1.7-2.3)                 by 1 g to 3 g /24 hours
30-16                      200-350               Loading dose of 2 g followed (2.3-4.0)                    by 1 g /24 hours
≤ 15                        > 350                       Not evaluated (>4.0)

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

Children < 40 kg

The safety and effectiveness of Fortum administered as continuous infusion in renally impaired children < 40 kg has not been established, Close clinical monitoring for safety and efficacy is advised.

If continuous infusion is used in children with renal impairment, the creatinine clearance should be adjusted for body surface area or lean body mass.

Haemodialysis
The serum half-life during haemodialysis ranges from 3 to 5 h.

Following each haemodialysis period, the maintenance dose of ceftazidime recommended in tables 3 & 4 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 tables 5 & 6 below.

Table 5: Continuous veno-venous haemofiltration dose guidelines

Residual renal         Maintenance dose (mg) for an ultrafiltration rate (ml/min) of1: function
(creatinine               5                16.7              33.3               50 clearance ml/min)
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                   Maintenance dose (mg) for a dialysate in flow rate of 1: renal                           1.0 litre/h                         2.0 litres/h function               Ultrafiltration rate (litre/h)      Ultrafiltration rate (litre/h) (creatinine           0.5           1.0            2.0    0.5           1.0            2.0 clearance in ml/min)
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
1Maintenance    dose to be administered every 12 h.


Method of administration

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

Fortum 1 g should be administered by intravenous injection or infusion, or by deep intramuscular injection. Recommended intramuscular injection sites are the upper outer quadrant of the gluteus maximus or lateral part of the thigh. Fortum solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids. The standard recommended route of administration is by intravenous intermittent injection or intravenous continuous infusion. Intramuscular administration should only be considered when the intravenous route is not possible or less appropriate for the patient.
Fortum 2 g should be administered by intravenous injection or infusion. Fortum solutions may be given directly into the vein or introduced into the tubing of a giving set if the patient is receiving parenteral fluids. The standard recommended route of administration is by intravenous intermittent injection or intravenous continuous infusion.