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.
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. 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.
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: 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 hemolytic anemia. While DAGT seroconversion in patients receiving Zavicefta was frequent in clinical studies, there was no evidence of haemolysis in patients who developed a positive DAGT on treatment. However, the possibility that haemolytic anaemia could occur in association with Zavicefta treatment cannot be ruled out. 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. 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).
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: 2 g powder for solution for infusion (Ceftazidime 2 g contains 4.52 mmol of sodium per vial); and 500 mg powder for solution for infusion (Avibactam 500 mg contains 1.92 mmol of sodium per vial).
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.
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. In patients with renal impairment, close monitoring of estimated creatinine clearance is advised. In some patients, the creatinine clearance estimated from serum creatinine can change quickly, especially early in the course of treatment for the infection.