• Hypersensitivity to the active substances, any of the excipients or to any cephalosporin antibacterial agent. 
• Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of β-lactam antibacterial agent (e.g. penicillins, monobactams or carbapenems).

• Very common:  Coombs direct test positive. 
• Common:  Candidiasis (including vulvovaginal candidiasis and oral candidiasis), eosinophilia, thrombocytosis, thrombocytopenia, headache, dizziness, diarrhoea, abdominal pain, nausea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, gamma-glutamyltransferase increased, blood lactate dehydrogenase increased, rash maculo-papular, urticaria, pruritus, infusion site thrombosis, infusion site phlebitis, pyrexia. 
• Uncommon: Clostridium difficile colitis, pseudomembranous colitis, neutropenia, leukopenia, lymphocytosis, paraesthesia, dysgeusia, blood creatinine and urea increased, acute kidney injury. 
• Very rare:  Tubulointerstitial nephritis. 
• Not known:  Agranulocytosis, haemolytic anaemia, anaphylactic reaction, Kounis syndrome (acute coronary syndrome associated with an allergic reaction), jaundice, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema, drug reaction with eosinophilia and systemic symptoms (DRESS). 

Please refer to Zavicefta Summary of Product Characteristics for further information on side effects.

• Hypersensitivity reactions: Treatment with Zavicefta must be discontinued immediately and adequate emergency measures must be initiated. There have been reports of hypersensitivity reactions which progressed to Kounis syndrome (acute allergic coronary arteriospasm that can result in myocardial infarction).  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.
• Clostridioides difficile-associated diarrhoea: Discontinuation of Zavicefta and the administration of specific treatment for Clostridioides difficile should be considered in patients who present with diarrhoea during or subsequent to the administration of Zavicefta.  Medicinal products that inhibit peristalsis should not be given. 
• Renal impairment: Dose should be reduced according to the degree of renal impairment.  Neurological sequelae, including tremor, myoclonus, non-convulsive status epilepticus, convulsion, encephalopathy and coma have occasionally been reported with ceftazidime when the dose has not been reduced in patients with renal impairment. Close monitoring of estimated creatinine clearance is advised. 
• Nephrotoxicity: 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. 
• Direct antiglobulin test (DAGT or Coombs test) seroconversion and potential risk of haemolytic anaemia: Ceftazidime/avibactam use may cause development of a positive direct antiglobulin test, which may interfere with the cross-matching of blood and/or may cause drug induced immune haemolytic anaemia. Patients experiencing anaemia during or after treatment with Zavicefta should be investigated for this possibility. 
• Spectrum of activity: Ceftazidime has little or no activity against the majority of Gram-positive organisms and anaerobes. Additional antibacterial agents should be used when these pathogens are known or suspected to be contributing to the infectious process.  The inhibitory spectrum of avibactam includes many of the enzymes that inactivate ceftazidime, including Ambler class A β lactamases and class C β-lactamases. Avibactam does not inhibit class B enzymes (metallo‑β-lactamases) and is not able to inhibit many of the class D enzymes. 
• Non-susceptible organisms: Prolonged use may result in the overgrowth of non-susceptible organisms (e.g. enterococci, fungi), which may require interruption of treatment or other appropriate measures. 
• Interference with laboratory tests: Ceftazidime may interfere with copper reduction methods (Benedict's, Fehling's, Clinitest) for detection of glycosuria leading to false positive results. Ceftazidime does not interfere with enzyme-based tests for glycosuria. 
• Controlled sodium diet: Consideration should be given to patients who are on a controlled sodium diet. Zavicefta is considered high in sodium. 
• Paediatric population: There is a potential risk of overdosing, particularly for paediatric patients aged from birth to less than 12 months of age. Care should be taken when calculating the volume of administration of the dose.

Zavicefta® (avibactam sodium, ceftazidime pentahydrate)

Zavicefta® (avibactam sodium, ceftazidime pentahydrate) 2g/0.5g powder for concentrate for
solution for infusion)