ZAVICEFTA POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION 2G/0.5G

4.1 Therapeutic indications

Zavicefta is indicated in adults, infants (aged 3 months and older), children, and adolescents for the treatment of the following infections (see sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information):

• Complicated Intra-Abdominal Infection (cIAI)
• Complicated Urinary Tract Infection (cUTI), including pyelonephritis
• Hospital-acquired Pneumonia (HAP), including ventilator associated pneumonia (VAP)

Treatment of adult patients with bacteraemia that occurs in association with, or is suspected to be associated with cIAI, cUTI, or HAP/VAP.

Consideration should be given to official guidance on the appropriate use of antibacterial agents. For treatment of cIAI use in combination with metronidazole.

4.3 Contraindications

Hypersensitivity to the active substances or to any of the excipients listed in section 6.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Hypersensitivity to the cephalosporin class of antibacterials.

Immediate and severe hypersensitivity (e.g. anaphylactic reaction) to any other type of β-lactam antibacterial agent (e.g. penicillins, monobactams or carbapenems).

4.2 Posology and method of administration

Dosage in Adults with Creatinine Clearance (CrCl >50 mL/min)

The recommended dosage of Zavicefta in adults is 1 vial where each vial contains 2 g ceftazidime and 0.5 g avibactam administered by intravenous (IV) infusion over 2 hours. Treatment is repeated every 8 hours. The duration of treatment is provided in Table 1.

Treatment Duration for Adult Patients

The duration of treatment should be guided by the severity of the infection, the pathogen(s) and the patient’s clinical and bacteriological progress.

Dosage in paediatric patients with creatinine clearance (CrCl) >50 mL/min/1.73 m2

The recommended dosage of Zavicefta in paediatric patients (3 months to <18 years) is based on the age and weight of the patient. Zavicefta is administered every 8 hours by intravenous infusion over 2 hours, see Table 2 (see also sections 4.4 and 5.1 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). The duration of therapy should be guided by the severity, site of infection and the patient’s clinical and bacteriological progress.

Special populations

Elderly patients

No dosage adjustment is considered necessary in elderly patients (≥65 years). The dose regimen should be adjusted if renal impairment is present (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Patients with renal impairment

The following dose adjustment is recommended in patients with renal impairment (see sections 4.4 and 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Dose adjustments for Zavicefta for patients with an estimated creatinine clearance (CrCl) ≤50 mL/min are outlined in Table 3 below.

Dosage in adults and paediatric patients with creatinine clearance (CrCl) ≤50 mL/min

Dosage in paediatric patients <2 years of age with creatinine clearance (CrCl) ≤50 mL/min/1.73 m2

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.

In patients with impaired renal function, regular monitoring of estimated creatinine clearance is advised as in some patients, especially early in the course of their infection, the creatinine clearance estimated from serum creatinine can change quickly.

Haemodialysis

Both ceftazidime and avibactam are haemodialysable; thus, Zavicefta should be administered after haemodialysis on haemodialysis day.

Haemofiltration

There is insufficient data to make specific dosage adjustment recommendations for patients undergoing continuous veno-venous haemofiltration.

Peritoneal dialysis

There is insufficient data to make specific dosage adjustment recommendations for patients undergoing peritoneal dialysis.

Patients with hepatic impairment

No dosage adjustment is considered necessary in patients with hepatic impairment (see section 5.2 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Close clinical monitoring for safety and efficacy is advised.

Paediatric patients

Safety and efficacy in paediatric patients <18 years of age have not been established for HAP/VAP and is based on extrapolation (see section 4.4 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Safety and efficacy in paediatric patients <3 months old have not been established.

Method of administration

Zavicefta is administered to adults by intravenous infusion over 2 hours in an appropriate infusion volume (see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). For paediatric patients, the infusion volume may be adjusted (see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Constitution and compatibility

For instructions on reconstitution and dilution of the medicinal product before administration see section 6.6 – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.