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EUROPEAN MEDICINES AGENCY

SCIENCE MEDICINES HEALTH

EMA/314117/2016

EMEA/H/C/004027

EPAR summary for the public

Zavicefta

ceftazidime / avibactam

This is a summary of the European public assessment report (EPAR) for Zavicefta. It explains how the Agency assessed the medicine to recommend its authorisation in the EU and its conditions of use. It is not intended to provide practical advice on how to use Zavicefta.

For practical information about using Zavicefta, patients should read the package leaflet or contact their doctor or pharmacist.

What is Zavicefta and what is it used for?

Zavicefta is an antibiotic used in adults to treat the following infections:

•    complicated (difficult to treat) infections of the tissues and organs within the belly (intra-abdominal infections);

•    complicated (difficult to treat) infections of the urinary tract (structures that carry urine), including pyelonephritis (kidney infection);

•    infections of the lungs that are caught in hospital (hospital-acquired pneumonia), including ventilator-associated pneumonia (pneumonia caught from a ventilator, which is a machine that helps a patient to breathe);

•    infections caused by Gram-negative bacteria (types of bacteria) when other treatments might not work.

Zavicefta contains the active substances ceftazidime and avibactam.

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How is Zavicefta used?

Zavicefta is available as a powder to be made up into a solution for infusion (drip) into a vein. The infusion is given over two hours, three times daily. Treatment usually lasts between 5 and 14 days, depending on the type of infection.

Doses may need to be reduced and/or given less often in patients with severely reduced kidney function.

Zavicefta can only be obtained with a prescription, and prescribers should take into account official guidance on the use of antibiotics.

For further information, see the package leaflet.

How does Zavicefta work?

The active substances in Zavicefta are ceftazidime and avibactam. Ceftazidime is an antibiotic called a cephalosporin, which belongs to the wider group 'beta-lactams'. It works by interfering with the production of certain molecules that bacteria need to build their protective cell walls. This causes weakness in the bacterial cell walls which then become prone to collapse, ultimately leading to the death of the bacteria.

Avibactam blocks the action of bacterial enzymes called beta-lactamases. These enzymes enable bacteria to break down beta-lactam antibiotics such as ceftazidime, making them resistant to the antibiotic's action. By blocking the action of these enzymes, avibactam allows ceftazidime to act against bacteria that would otherwise be resistant.

What benefits of Zavicefta have been shown in studies?

The benefits of Zavicefta have been shown in four main studies. In two studies, the effects of the combination of Zavicefta and metronidazole (another antibiotic) were compared with those of the antibiotic meropenem in 1490 patients with complicated intra-abdominal infection. Both studies showed that Zavicefta in combination with metronidazole was at least as effective as meropenem at curing the infection. In the first study, one of the patient groups studied showed 92% of patients (376 out of 410) treated with Zavicefta and metronidazole were cured, compared with 93% (385 out of 416) of patients treated with meropenem. In the second study, 94% of patients (166 out of 177) treated with Zavicefta and metronidazole were cured, compared with 94% (173 out of 184) of patients treated with meropenem.

A third study looked at 332 patients with complicated intra-abdominal or urinary tract infections caused by Gram-negative bacteria that were resistant to ceftazidime (could not be killed by ceftazidime). Zavicefta alone (for urinary tract infection) or in combination with metronidazole (for intra-abdominal infection) provided similar results to a number of alternative antibiotics in curing the infection: 91% of patients (140 out of 154) were cured after treatment with Zavicefta compared with 91% (135 out of 148) after treatment with the best alternative antibiotic. In addition, disease-causing bacteria were eliminated in 82% (126 out of 154) of patients after treatment with Zavicefta compared with 63% (94 out of 148) after treatment with the best alternative antibiotic. Due to the design of this study, this evidence of Zavicefta's benefits is not as strong as for the other studies; however these results support Zavicefta's activity when combined with the other studies.

In a fourth study, 1,020 patients with complicated urinary tract infections (including pyelonephritis) caused by Gram-negative bacteria were treated with Zavicefta or the antibiotic doripenem. One of the main measures of effectiveness was based on eliminating the disease-causing bacteria. Zavicefta was at least as effective as doripenem: 77% of patients (304 out of 393) treated with Zavicefta showed a response compared with 71% of patients (296 out of 417) treated with doripenem.

What are the risks associated with Zavicefta?

The most common side effects with Zavicefta (which affected more than 5 in 100 people) are nausea (feeling sick), diarrhoea and a positive result in a Coombs test (a sign of the development of antibodies that attack red blood cells). For the full list of all side effects with Zavicefta, see the package leaflet.

Zavicefta must not be used in patients who are hypersensitive (allergic) to the active substances in Zavicefta or any of the other ingredients, or in those who are hypersensitive to other cephalosporin antibiotics or have ever had a severe allergic reaction to another beta-lactam antibiotic.

Why is Zavicefta approved?

The Agency's Committee for Medicinal Products for Human Use (CHMP) decided that Zavicefta's benefits are greater than its risks and recommended that it be approved for use in the EU. The CHMP considered that the studies on Zavicefta show that is effective at treating complicated intra-abdominal and urinary tract infections. A study of Zavicefta in patients with hospital-acquired pneumonia has not yet been completed. However, the CHMP considered that the data already available supported Zavicefta's activity in hospital-acquired pneumonia and for the treatment of infections due to aerobic Gram-negative organisms in adult patients when other treatments might not work. Regarding Zavicefta's safety profile, side effects were those that can be expected for ceftazidime and a beta-lactamase inhibitor.

What measures are being taken to ensure the safe and effective use of Zavicefta?

The company that makes Zavicefta is carrying out a study to compare the effectiveness and safety of Zavicefta with meropenem (another antibiotic) for the treatment of hospital-acquired pneumonia.

Recommendations and precautions to be followed by healthcare professionals and patients for the safe and effective use of Zavicefta have also been included in the summary of product characteristics and the package leaflet.

Other information about Zavicefta

The European Commission granted a marketing authorisation valid throughout the European Union for Zavicefta on 24 June 2016.

The full EPAR for Zavicefta can be found on the Agency's website: ema.europa.eu/Find medicine/Human medicines/European public assessment reports. For more information about treatment with Zavicefta, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.

This summary was last updated in 06-2016.

Zavicefta

EMA/314117/2016

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