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           100 to 150 mg/kg/day every 8 h, cystic 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
Per-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
Nosocomial pneumonia



Broncho-pulmonary infections in                 Loading dose of 2 g followed by a cystic fibrosis                                 continuous infusion of 4 to 6 g every Bacterial meningitis                            24 h1
Bacteraemia*                                    The infusion of any unit of dissolved Bone and joint infections                       drug shall last no longer than 8h (see Complicated skin and soft tissue                section 6.3).
infections                                      Therefore, following reconstitution, Complicated intra-abdominal                     the unit dose in the infusion fluid infections                                      should be administered within 8h, for Peritonitis associated with dialysis in         example for 8 g per day: 2 g loading patients on CAPD                                dose followed by 2 g continuous infusion every 8 h.
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 4.1.
Table 2: Children < 40 kg

Infants and toddlers     Infection                        Usual dose
>2 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
Broncho-pulmonary            divided doses, maximum 6 infections in cystic         g/day 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
Nosocomial                   mg/kg followed by a pneumonia                    continuous infusion 100-200


Broncho-pulmonary         mg/kg/day, maximum 6 infections in cystic      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 with 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 than 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-Vit 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-Vit in renal impairment – intermittent infusion
Adults and children ≥ 40 kg
Approx. serum            Recommended                 Frequency of dosing Creatinine            creatinine              unit dose of                    (hourly) clearance           µmol/l(mg/dl)           Ceftazidime- Vit ml/min                                             (g)
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                    (hourly) (ml/min)**          µmol/l(mg/dl)         mg/kg 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 Ceftazidime-Vit in renal impairment – continuous infusion
Adults and children ≥ 40 kg
Creatinine clearance             Approx. Serum                    Frequency of dosing (ml/min)              creatinine µmol/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 (>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 Ceftazidime-Vit 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 liters 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             Maintenance dose (mg) for an ultrafiltration rate (ml/min) of1: renal 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 liter/h                      2.0 liter/h function       Ultrafiltration rate (liter/h)   Ultrafiltration rate (liter/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
1
Maintenance 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.

Ceftazidime-Vit 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-Vit 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.
Ceftazidime-Vit 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.