Zerbaxa

Posology The recommended intravenous dose regimen for adult patients with creatinine clearance > 50 mL/min is shown by infection type in Table 1. 5 g tazobactam Every 8 hours 1 hour 7 days Hospital-acquired pneumonia, including ventilator-associated pneumonia*** 2 g ceftolozane / 1 g tazobactam Every 8 hours 1 hour 8-14 days *Creatinine clearance estimated using Cockcroft-Gault formula.

**To be used in combination with metronidazole when anaerobic pathogens are suspected. ***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.

73 m2 is shown by infection type in Table 2. 5 g tazobactam**** Every 8 hours 1 hour 7-14 days***** *Defined as > 32 weeks gestational age and ≥ 7 days postnatal. **eGFR estimated using Bedside Schwartz equation. ***To be used in combination with metronidazole when anaerobic pathogens are suspected.

5 g tazobactam. *****The total treatment duration shown may include intravenous Zerbaxa followed by appropriate oral therapy. 2). 2). 6). 75 g tazobactam followed after 8 hours by a 300 mg ceftolozane / 150 mg tazobactam maintenance dose administered every 8 hours for the remainder of the treatment period (on haemodialysis days, the dose should be administered at the earliest possible time following completion of haemodialysis) *Creatinine clearance estimated using Cockcroft-Gault formula.

**All doses of Zerbaxa are administered intravenously over 1 hour and are recommended for all indications. The duration of treatment should follow the recommendations in Table 1. 2). 2). Paediatric population The safety and efficacy of ceftolozane/tazobactam in children and adolescents below 18 years of age have not yet been established for the treatment of hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP).

Method of administration Zerbaxa is to be administered by intravenous infusion over a 1 hour period for all doses. 2 for incompatibilities. 6 for instructions on reconstitution and dilution of the medicinal product before administration.

Summary of the safety profile Zerbaxa was evaluated in Phase 3 comparator-controlled clinical trials of complicated intra-abdominal infections and complicated urinary tract infections (including pyelonephritis) in adult patients. The most common adverse reactions (≥ 3% in pooled Phase 3 trials of complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis) occurring in patients receiving Zerbaxa were nausea, headache, constipation, diarrhoea, and pyrexia and were generally mild or moderate in severity.

Zerbaxa was evaluated in a Phase 3 comparator-controlled clinical trial of adult patients with hospital- acquired pneumonia, including ventilator-associated pneumonia. The most common adverse reactions (≥ 5% in a Phase 3 trial of hospital-acquired pneumonia, including ventilator-associated pneumonia) occurring in patients receiving Zerbaxa were diarrhoea, alanine aminotransferase increased, and aspartate aminotransferase increased and were generally mild or moderate in severity.

8 Tabulated list of adverse reactions The following adverse reactions have been identified during adult clinical trials with Zerbaxa. Adverse reactions are classified according to MedDRA system organ class and frequency. Frequency categories are derived according to the following conventions: common (≥ 1/100 to < 1/10), uncommon (≥ 1/1 000 to < 1/100) (see Table 4).

5 g intravenously every 8 hours) for up to 14 days. 2 Specific for the hospital-acquired pneumonia, including ventilator-associated pneumonia indication treated with Zerbaxa (2 g / 1 g intravenously every 8 hours) for up to 14 days.

3 Applies across all indications: complicated intra-abdominal infections, acute pyelonephritis, complicated urinary tract infections, and hospital-acquired pneumonia, including ventilator-associated pneumonia. 9 Paediatric population The safety assessment in paediatric patients, aged from birth to less than 18 years, is based on the safety data from two trials in which 70 patients with complicated intra-abdominal infections and 100 patients with complicated urinary tract infections (including acute pyelonephritis) received Zerbaxa.

8). If a severe allergic reaction occurs during treatment with ceftolozane/tazobactam, the medicinal product should be discontinued and appropriate measures taken. Patients who have a history of hypersensitivity to cephalosporins, penicillins or other beta-lactam antibacterial agents may also be hypersensitive to ceftolozane/tazobactam.

3). 3). Ceftolozane/tazobactam should be used with caution in patients with a history of any other type of hypersensitivity reaction to penicillins or other beta-lactam antibacterial agents. Effect on renal function A decline in renal function has been seen in adult patients receiving ceftolozane/tazobactam.

2, Table 3). In clinical trials of complicated intra-abdominal infections and complicated urinary tract infections, including pyelonephritis, the efficacy of ceftolozane/tazobactam was lower in adult patients with moderate renal impairment compared with those with normal or mildly impaired renal function at baseline.

Patients with renal impairment at baseline should be monitored frequently for any changes in renal function during treatment and the dose of ceftolozane/tazobactam should be adjusted as necessary. Limitations of the clinical data Patients who were immunocompromised, patients with severe neutropenia, and patients with end stage renal disease on haemodialysis were excluded from clinical trials.

6%) had diffuse peritonitis at baseline. 3% had bacteraemia at baseline. 8% in 82 patients aged 65 years or more. Complicated urinary tract infections Clinical efficacy data in adult patients with complicated lower urinary tract infection are limited.

2% (126/693) of microbiologically evaluable (ME) patients had complicated lower urinary tract infection, including 60/126 patients who were treated with ceftolozane/tazobactam. One of these 60 patients had bacteraemia at baseline. 8).

These types of infection may range in severity from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of ceftolozane/tazobactam.

, penicillins or carbapenems). 5