*In four Phase III clinical trials, the adverse event profile of ZAVICEFTA was similar to that seen with either best available therapy, doripenem or meropenem^1–4

• Overall rates of any AE were low in the ZAVICEFTA and comparator arms^1–4​​​​​​​​​​​​​​​​​​​​​
• Rates of all other AE categories were low and balanced across treatment arms^1–4
• Most common (>5%) AEs for ZAVICEFTA were positive direct Coombs test, nausea and diarrhoea^5*
• Nausea and diarrhoea were usually mild or moderate in intensity^1-5
• Low potential for drug-drug interactions⁵

*Based on data from seven Phase II and Phase III clinical trials in 2024 adult patients treated with ZAVICEFTA.⁵

Serious and occasionally fatal hypersensitivity reactions are possible. In case of hypersensitivity reactions, treatment with ZAVICEFTA must be discontinued immediately and adequate emergency measures must be initiated. 

Before beginning treatment, it should be established whether the patient has a history of hypersensitivity reactions to ceftazidime, to other cephalosporins or to any other type of β-lactam antibacterial agent. Caution should be used if ceftazidime/ avibactam is given to patients with a history of non-severe hypersensitivity to penicillins, monobactams or carbapenems. 

Clostridium difficile-associated diarrhoea has been reported with ceftazidime/ avibactam and can range in severity from mild to life-threatening.

This diagnosis should be considered in patients who present with diarrhoea during or subsequent to administration of ZAVICEFTA. 

Discontinuation of therapy with ZAVICEFTA and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given. 

In vitro drug combination studies with ZAVICEFTA have demonstrated neither synergy nor antagonism with the following drugs: metronidazole, tobramycin, levofloxacin, vancomycin, linezolid, colistin and tigecycline. 

Concurrent treatment with high doses of cephalosporins and nephrotoxic medicinal products such as aminoglycosides or potent diuretics (e.g. furosemide) may adversely affect renal function. Chloramphenicol is antagonistic in vitro with ceftazidime and other cephalosporins. The clinical relevance of this finding is unknown, but due to the possibility of antagonism in vivo this drug combination should be avoided.

In vitro, avibactam is a substrate of OAT1 and OAT3 transporters which might contribute to the active uptake of avibactam from the blood compartment and therefore affect its excretion. Probenecid, a potent OAT inhibitor, inhibits avibactam uptake by 56–70%, potentially altering the elimination of avibactam. Since a clinical interaction trial of avibactam and probenecid has not been conducted, co-administration is not recommended.

Avibactam showed no significant inhibition of cytochrome P450 enzymes in vitro. Avibactam and ceftazidime showed no in vitro cytochrome P450 induction at clinically relevant concentrations. Avibactam and ceftazidime do not inhibit the major renal or hepatic transporters in the clinically relevant exposure range, therefore the interaction potential via these mechanisms is considered low.

Clinical data have demonstrated that there is no interaction between ceftazidime and avibactam, and between ZAVICEFTA and metronidazole.