Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Hypersensitivity reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions are possible (see sections 4.3 and 4.8).
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.

Ceftolozane/tazobactam is contraindicated in patients with a history of hypersensitivity to ceftolozane, tazobactam, or cephalosporins (see section 4.3).

Ceftolozane/tazobactam is also contraindicated in patients with severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-lactam antibacterial agent (e.g. penicillins or carbapenems) (see section 4.3).

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 patients receiving ceftolozane/tazobactam.
Impaired renal function

The ceftolozane/tazobactam dose should be adjusted based on renal function (see section 4.2, Table 2).

In clinical trials the efficacy of ceftolozane/tazobactam was lower in 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 and patients with severe neutropenia were excluded from clinical trials.

In a trial in patients with complicated intra-abdominal infections, the most common diagnosis was appendiceal perforation or peri-appendiceal abscess (420/970 [43.3%] patients), of which 137/420 (32.6%) had diffuse peritonitis at baseline. Approximately 82% of all patients in the trial had APACHE II (Acute Physiology and Chronic Health Evaluation II) scores of < 10 and 2.3% had bacteraemia at baseline. In the clinically evaluable (CE) patients, the clinical cure rates for ceftolozane/tazobactam were 95.9% in 293 patients aged less than 65 years and 87.8% in 82 patients aged 65 years or more.

Clinical efficacy data in patients with complicated lower urinary tract infection are limited. In a randomised active-controlled trial 18.2% (126/693) of microbiologically evaluable (ME) patients had complicated lower urinary tract infection (cLUTI), including 60/126 patients who were treated with ceftolozane/tazobactam. One of these 60 patients had bacteraemia at baseline.


Clostridium difficile-associated diarrhoea

Antibacterial-associated colitis and pseudomembranous colitis have been reported with ceftolozane/tazobactam (see section 4.8). 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. In such circumstances, the discontinuation of therapy with ceftolozane/tazobactam and the use of supportive measures together with the administration of specific treatment for Clostridium difficile should be considered.

Non-susceptible micro-organisms

The use of ceftolozane/tazobactam may promote the overgrowth of non-susceptible micro-organisms. If super infection occurs during or following treatment, appropriate measures should be taken.

Ceftolozane/tazobactam is not active against bacteria that produce beta-lactamase enzymes which are not inhibited by tazobactam. See section 5.1.

Direct antiglobulin test (Coombs test) seroconversion and potential risk of haemolytic anaemia 
The development of a positive direct antiglobulin test (DAGT) may occur during treatment with ceftolozane/tazobactam. The incidence of DAGT seroconversion in patients receiving ceftolozane/tazobactam was 0.2% in the clinical trials. In clinical studies, there was no evidence of haemolysis in patients who developed a positive DAGT on treatment.

Sodium content

Ceftolozane/tazobactam contains 10.0 mmol (230 mg) of sodium per vial. The reconstituted vial with 10 mL of 0.9% sodium chloride (normal saline) for injection contains 11.5 mmol (265 mg) of sodium. This should be taken into consideration while treating patients on controlled-sodium diet.

Effects on Driving

4.7    Effects on ability to drive and use machines

Zerbaxa may have a minor influence on the ability to drive and use machines. Dizziness may occur following administration of Zerbaxa (see section 4.8).