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 Ceftazidime (as pentahydrate)/Avibactam (as sodium) (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: Use of ceftazidime-avibactam to treat patients with Gram negative aerobic infections (see Pharmacology: Pharmacodynamics under Actions for species against which evidence of clinical efficacy has been observed) where therapeutic options are limited should be only after consultation with a physician with appropriate experience in the management of infectious diseases. Use of ceftazidime-avibactam in these infections is based on PK/PD extrapolations: no clinical studies have been conducted.
No clinical studies have been conducted in pediatric patients with nosocomial pneumonia. The efficacy of Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) for the treatment of pediatric patients ≥3 months of age with HAP/VAP is extrapolated from adults and is based on analyses of the pharmacokinetic-pharmacodynamic relationship for Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) and on pediatric experience with ceftazidime alone (see Pharmacology: Pharmacokinetics under Actions).
Hospital-Acquired Pneumonia (HAP), including Ventilator-Associated Pneumonia (VAP): In a single study in patients with nosocomial pneumonia 280/808 (34.7%) had VAP and 40/808 (5.0%) were bacteremic at baseline.
Clostridium difficile-associated diarrhea: 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 diarrhea during or subsequent to the administration of Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) (see Adverse Reactions). Discontinuation of therapy with Ceftazidime (as pentahydrate)/Avibactam (as sodium) (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).
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.
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.
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 hemolytic anemia: 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 Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) was frequent in clinical studies, there was no evidence of hemolysis in patients who developed a positive DAGT on treatment (see Adverse Reactions). However, the possibility that hemolytic anemia could occur in association with Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) treatment cannot be ruled out. Patients experiencing anemia during or after treatment with Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) should be investigated for this possibility.
Controlled sodium diet: This medicinal product contains approximately 146 mg sodium per vial, equivalent to 7.3% of the WHO recommended maximum daily intake (RDI) of 2 g sodium for an adult.
The maximum daily dose of this product is equivalent to 22% of the WHO recommended maximum daily intake for sodium. Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) is considered high in sodium.
This should be considered when administering Ceftazidime (as pentahydrate)/Avibactam (as sodium) (Zavicefta) to patients who are on a controlled sodium diet.
Ceftazidime (as pentahydrate)/Avibactam (as sodium) Zavicefta may be diluted with sodium-containing solutions (see Special Precautions for Disposal and Other Handling under Cautions for Usage) and this should be considered in relation to the total sodium from all sources that will be administered to the patient.
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).
Use in Children: There is a potential risk of overdosing, particularly for pediatric patients aged from 3 to less than 12 months of age. Care should be taken when calculating the volume of administration of the dose (see Overdosage and Special Precautions for Disposal and Other Handling under Cautions for Usage).