Posology : מינונים

4.2    Posology and method of administration

It is recommended that Zavicefta® should be used to treat infections due to aerobic Gram-negative organisms in adults and paediatric patients aged 3 months and older, with limited treatment options only 
after consultation with a physician with appropriate experience in the management of infectious diseases (see section 4.4).

Posology
Dosage in adults with creatinine clearance (CrCL) > 50 mL/min

Table 1 shows the recommended intravenous dose for adults with estimated creatinine clearance (CrCL) > 50 mL/min (see sections 4.4 and 5.1).
Table 1 Recommended dose for adults with estimated CrCL > 50 mL/min1
Type of infection              Dose of             Frequency  Infusion                   Duration of treatment ceftazidime/avibactam                    time cIAI 2, 3
2 g/0.5 g            Every 8    2 hours                          5-14 days hours cUTI, including                2 g/0.5 g            Every 8    2 hours                         5-10 days4 pyelonephritis3                                      hours

HAP/ VAP3                            2 g/0.5 g              Every 8        2 hours              7-14 days hours
Bacteraemia associated               2 g/0.5 g               Every         2 hours     Duration of treatment with, or suspected to be                                    8 hours                    should be in accordance associated with any of                                                                 with the site of infection.
the above infections
Infections due to aerobic            2 g/0.5 g              Every 8        2 hours      Guided by the severity Gram-negative                                                hours                      of the infection, the organisms in patients                                                                   pathogen(s) and the with limited treatment                                                                  patient’s clinical and options2,3                                                                              bacteriological progress5 1
CrCL estimated using the Cockcroft-Gault formula
2
To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process
3
To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process
4
The total duration shown may include intravenous Zavicefta® followed by appropriate oral therapy 5
There is very limited experience with the use of Zavicefta® for more than 14 days 
Dosage in paediatric patients with creatinine clearance (CrCL) >50 mL/min/1.73 m 2 
Table 2 shows the recommended intravenous doses for paediatric patients with estimated creatinine clearance (CrCL) > 50 mL/min/1.73 m2 (see sections 4.4 and 5.1).

Table 2: Recommended dose for paediatric patients with estimated CrCL1 > 50 mL/min/1.73 m2 Type of       Age group             Dose of            Frequency Infusion time     Duration of infection                    ceftazidime/avibactam7                                  treatment cIAI2,3

50 mg/kg/12.5 mg/kg
OR                                                          Every 8
6 months to                                              2 hours cUTI including                     to a maximum of           hours
<18 years pyelonephritis 3

2 g/0.5 g
OR                                                                                     cIAI: 5 – 14 Every 8
2 hours          days hours
HAP/VAP3
3 months to                                    Every 8                         cUTI4: 5 – 14 OR                                      40 mg/kg/10 mg/kg                            2 hours          days <6 months6                                      hours


Type of          Age group            Dose of             Frequency      Infusion time      Duration of infection                      ceftazidime/avibactam7                                         treatment Infections due
HAP/VAP: to aerobic
7 – 14 days
Gram-negative organisms in                                                                                    LTO: Guided patients with                                                                                   by the severity limited                                                                                         of the treatment                                                                                       infection, the options (LTO)2,3                                                                                pathogen(s) and the patient’s clinical and bacteriological progress5
1
CrCL estimated using the Schwartz bedside formula.
2
To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process.
3
To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.
4
The total treatment duration shown may include intravenous Zavicefta followed by appropriate oral therapy.
5
There is very limited experience with the use of Zavicefta for more than 14 days.
6
There is limited experience with the use of Zavicefta in paediatric patients 3 months to < 6 months (see section 5.2).
7
Ceftazidime/avibactam is a combination product in a fixed 4:1 ratio and dosage recommendations are based on the ceftazidime component only (see section 6.6).


Special populations
Elderly
No dosage adjustment is required in elderly patients (see section 5.2).

Renal impairment
No dosage adjustment is required in patients with mild renal impairment (estimated CrCL > 50 - ≤ 80 mL/min) (see section 5.2).

Table 3 shows the recommended dose adjustments for adults with estimated CrCL1 ≤ 50 mL/min (see sections 4.4 and 5.2).

Dosage in adults with CrCL ≤ 50 mL/min

Table 3 Recommended dose for adults with estimated CrCL 1 ≤ 50 mL/min Age Group          Estimated CrCL                    Dose of          Frequency                  Infusion (mL/min)              ceftazidime/avibactam2, 4                              time Adults                                                                Every 31-50                       1 g/0.25 g
8 hours
Every
16-30
12 hours
Every
6-15                                                                    2 hours 0.75 g/0.1875 g       24 hours
End Stage Renal Disease including on haemodialysis3                                Every
48 hours


1
CrCL estimated using the Cockcroft-Gault formula
2
Dose recommendations are based on pharmacokinetic modelling (see section 5.2).
3
Ceftazidime and avibactam are removed by haemodialysis (see sections 4.9 and 5.2). Dosing of Zavicefta® on haemodialysis days should occur after completion of haemodialysis.
4 Ceftazidime/avibactam is a combination product in a fixed 4:1 ratio and dosage recommendations are based on the ceftazidime component only (see section 6.6).

Table 4 and Table 5 show the recommended dose adjustments for paediatric patients with estimated CrCL ≤ 50 mL/min/1.73 m2 according to different age groups (see sections 4.4 and 5.2).

Dosage in paediatric patients ≥ 2 years of age with CrCl ≤ 50 mL/min/1.73 m2 
Table 4: Recommended dose for paediatric patients with estimated CrCL1 ≤ 50 mL/min/1.73 m2 Age Group          Estimated CrCL                      Dose of            Frequency    Infusion (mL/min/1.73 m2)            ceftazidime/avibactam2, 4                  time 25 mg/kg/6.25 mg/kg to a maximum of             Every
31-50
8 hours
1 g/0.25 g


Every
16-30
Paediatric                                                                       12 hours 2 hours patients aged                                     18.75 mg/kg/4.7 mg/kg 2 years to
<18 years                                              to a maximum of 0.75 g/0.1875 g            Every
6-15
24 hours


End Stage Renal Disease                                          Every including on haemodialysis3                                       48 hours 
1
CrCL estimated using the Schwartz bedside formula.
2
Dose recommendations are based on pharmacokinetic modelling (see section 5.2).
3
Ceftazidime and avibactam are removed by haemodialysis (see sections 4.9 and 5.2). Dosing of Zavicefta on haemodialysis days should occur after completion of haemodialysis.
4
Ceftazidime/avibactam is a combination product in a fixed 4:1 ratio and dosage recommendations are based on the ceftazidime component only (see section 6.6).


Dosage in paediatric patients <2 years of age with CrCl ≤ 50 mL/min/1.73 m 2 
Table 5: Recommended dose for paediatric patients with estimated CrCL1 ≤ 50 mL/min/1.73 m2 Age          Estimated CrCL                       Dose of              Frequency     Infusion Group        (mL/min/1.73 m2)             ceftazidime/avibactam2,3                      time 3 to < 6                                                                         Every 20 mg/kg/5 mg/kg months                                                                          8 hours 31 to 50
6 months
Every to < 2                                          25 mg/kg/6.25 mg/kg
8 hours years
2 hours
3 to < 6                                                                        Every 15 mg/kg/3.75 mg/kg months                                                                         12 hours 16 to 30
6 months
Every to < 2                                         18.75 mg/kg/4.7 mg/kg
12 hours years
1
Calculated using the Schwartz bedside formula
2
Dose recommendations are based on pharmacokinetic modelling).
3
Ceftazidime/avibactam is a combination product in a fixed 4:1 ratio and dosage recommendations are based on the ceftazidime component only.

There is insufficient information to recommend a dosage regimen for paediatric patients < 2 years of age that have a CrCL < 16 mL/min/1.73 m2.

Hepatic impairment
No dosage adjustment is required in patients with hepatic impairment (see section 5.2).

Paediatric population
The safety and efficacy of Zavicefta in paediatric patients < 3 months old have not been established. No data are available.

Method of administration

Intravenous use.
Zavicefta® is administered by intravenous infusion over 120 minutes in an appropriate infusion volume (see section 6.6)..

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