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  • Zavicefta®
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    Active Ingredient *
    Avibactam 0.5 g
    Ceftazidime (as Pentahydrate) 2 g

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    20 ml

    not in the basket chart 28700

    Dosage

    Recommended intravenous dose for patients with estimated CrCL ≥ 51 mL/min1:
    Complicated IAI2: 2 g/0.5 g, every 8 hours,  infusion for 2 hours for 5-14 days.
    Complicated UTI, including pyelonephritis3: 2 g/0.5 g, every 8 hours, infusion for 2 hours for 5-10 days4.
    Hospital-acquired pneumonia, including VAP3: 2 g/0.5 g, every 8 hours, infusion for 2 hours 7-14 days.
    Infections due to aerobic Gram-negative organisms in patients with limited treatment options 2,3: 2 g/0.5 g, every 8 hours, infusion for 2 hours,  guided by the severity of the infection, the pathogen(s) and the patient’s clinical and
    bacteriological progress5.
    1-CrCL estimated using the Cockcroft-Gault formula.
    2-To be used in combination with metronidazole when anaerobic pathogens are known or suspected to be contributing to the infectious process.
    3- To be used in combination with an antibacterial agent active against Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.
    4- The total duration shown may include intravenous Avibactam as sodium 0.5g, Ceftazidime as Pentahydrate 2g followed by appropriate oral therapy.
    5- There is very limited experience with the use of Avibactam as sodium 0.5g, Ceftazidime as Pentahydrate 2g for more than 14 days.
    Renal impairment: No dosage adjustment is required in patients with mild renal impairment (estimated CrCL ≥ 51 – ≤ 80 mL/min).
    For patients with estimated CrCL ≤ 50 mL/min: See prescribing information for full details.
    Hepatic impairment: No dosage adjustment is required in patients with hepatic impairment.
    Paediatric population: Safety and efficacy in children and adolescents below 18 years of age have not yet been established. No data are available.
    See prescribing information for full details.


    Indications

    Treatment of the following infections in adults:
    Complicated intra-abdominal infection (cIAI), used in combination with Metronidazole.
    Complicated urinary tract infection (cUTI), including pyelonephritis.
    Hospital-acquired pneumonia (HAP), including ventilator associated pneumonia (VAP).
    Treatment of infections due to aerobic Gram-negative organisms in adult patients with limited treatment options.
    Consideration should be given to official guidance on the appropriate use of antibacterial agents.


    Contra-Indications

    Hypersensitivity to the active substances or to any of the excipients.
    Hypersensitivity 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).


    Special Precautions

    Hypersensitivity reactions: Serious and occasionally fatal hypersensitivity reactions are possible.
    In case of hypersensitivity reactions, treatment with this agent 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: 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 the administration of this agent. Discontinuation of therapy with this agent and the administration of specific treatment for Clostridium difficile should be considered. Medicinal products that inhibit peristalsis should not be given.
    Renal impairment: Ceftazidime and avibactam are eliminated via the kidneys, therefore, the 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.
    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.
    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 (DAGT, or Coombs test), which may interfere with the cross-matching of blood and/or may cause drug- induced immune haemolytic anaemia (see section 4.8). While DAGT seroconversion in patients receiving this agent  was very common in clinical studies (the estimated range of seroconversion across Phase 3 studies was 3.2% to 20.8% in patients with a negative Coombs test at baseline and at least one follow-up test), 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 this agent treatment cannot be ruled out. Patients experiencing anaemia during or after treatment with this agent should be investigated for this possibility.
    Limitations of the clinical data: Clinical efficacy and safety studies of this agent have been conducted in cIAI, cUTI and HAP (including VAP).
    See prescribing information for full details.


    Side Effects

    Candidiasis (including vulvovaginal candidiasis and oral candidiasis), eosinophilia, thrombocytosis, thrombocytopenia, headache, dizziness, diarrhea, abdominal pain, nausea , vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased, gamma-glutamyltransferase increased, blood lactate dehydrogenase, rash maculo-papular, urticaria, pruritus, infusion site thrombosis, infusion site phlebitis, pyrexia.
    See prescribing information for full details.


    Drug interactions

    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 this uptake by 56% to 70% in vitro and, therefore, has the potential to alter the elimination of avibactam. Since a clinical interaction study of avibactam and probenecid has not been conducted, co-administration of avibactam with probenecid 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 to be low.
    Clinical data have demonstrated that there is no interaction between ceftazidime and avibactam, and between ceftazidime/avibactam and metronidazole.
    Other types of interaction: 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.


    Pregnancy and Lactation

    Pregnancy: Ceftazidime/avibactam should only be used during pregnancy if the potential benefit outweighs the possible risk.
    Lactation: Ceftazidime is excreted in human milk in small quantities.
    See prescribing information for full details.


    Overdose

    Overdose with ceftazidime/avibactam can lead to neurological sequelae including encephalopathy, convulsions and coma, due to the ceftazidime component.
    Serum levels of ceftazidime can be reduced by haemodialysis or peritoneal dialysis. During a 4-hour haemodialysis period, 55% of the avibactam dose was removed.


    Important notes

    Storage: Store below 30°C.
    After dilution: The chemical and physical in-use stability has been demonstrated for up to 24 hours at 2 – 8°C, followed by up to 12 hours at not more than 25°C.
    From a microbiological point of view, the medicinal product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 – 8ºC, unless reconstitution/dilution has taken place in controlled and validated aseptic conditions.


    Manufacturer
    GlaxoSmithKline Manufacturing S.p.A, Parma, Italy
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