Zavicefta Special Precautions

Hypersensitivity reactions: As with all β-lactam antibacterial agents, serious and occasionally fatal hypersensitivity reactions have been reported. In case of severe 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 severe hypersensitivity reactions to ceftazidime, to other cephalosporins or to any other type of β-lactam agent. Caution should be used if ceftazidime-avibactam is given to patients with a history of non-severe hypersensitivity to other β-lactam agents.
Limitation of the clinical data: No clinical studies have been conducted in paediatric patients with nosocomial pneumonia. The efficacy of ceftazidime/avibactam for the treatment of paediatric patients ≥3 months of age with HAP/VAP is extrapolated from adults and is based on analyses of the pharmacokinetic-pharmacodynamic relationship for ceftazidime/avibactam and on paediatric experience with ceftazidime alone (see Pharmacology: Pharmacokinetics under Actions).
Clostridium difficile-associated diarrhoea: Antibacterial agent-associated colitis and pseudo-membranous colitis have been reported with nearly all anti-bacterial agents, including ceftazidime-avibactam, and 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 Zavicefta (see Adverse Reactions). 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.
Patients with renal impairment: Ceftazidime and avibactam are eliminated via the kidneys, therefore the dose should be reduced according to the degree of renal impairment. Patients with renal impairment should be closely monitored for both safety and efficacy. Neurological sequelae, including tremor, myoclonus, nonconvulsive status epilepticus, convulsion, encephalopathy and coma, have occasionally been reported with ceftazidime when the dose has not been reduced in patients with renal impairment (see Dosage & Administration).
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.
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.
Non-drug interference: Ceftazidime does not interfere with enzyme-based tests for glycosuria, but slight interference (false-positive) may occur with copper reduction methods (Benedict's, Fehling's, Clinitest). Ceftazidime does not interfere in the alkaline picrate assay for creatinine.
Direct antiglobulin test (DAGT or Coombs test) seroconversion and potential risk of haemolytic anaemia: Cephalosporin use may cause development of a positive direct antiglobulin test (DAGT, or Coombs test), which may interfere with the cross-matching of blood and/or may cause drug induced immune haemolytic anaemia. While DAGT seroconversion in patients receiving ceftazidime-avibactam (CAZ-AVI) was frequent in clinical studies, there was no evidence of haemolysis in patients who developed a positive DAGT on treatment (see Adverse Reactions). However, the possibility that haemolytic anaemia could occur in association with CAZ-AVI treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with CAZ-AVI should be investigated for this possibility.
Controlled sodium diet: For patients who are on a controlled sodium diet, the following important information about the ingredients of ceftazidime and avibactam should be considered: Each vial contains approximately 6.37 mmol of sodium per vial. This total is the combined sodium from avibactam sodium and the excipient sodium carbonate.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. dizziness), which may influence the ability to drive and use machines (see Adverse Reactions).