Ceftazidime + Avibactam


Generic Medicine Info
Indications and Dosage
Intravenous
Complicated intra-abdominal infections
Adult: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

In combination with metronidazole, and with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours for 5-14 days.
Child: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

In combination with metronidazole, and with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration: 5-14 days. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).

Intravenous
Complicated urinary tract infections
Adult: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases including pyelonephritis: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours for 5-10 days, may be increased to 14 days in patients with bacteraemia. Total duration of treatment may include IV doses, followed by appropriate oral therapy.
Child: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases including pyelonephritis: In combination with antibacterial drug active against Gram-positive pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration: 5-14 days. Total duration of treatment may include IV doses, followed by appropriate oral therapy. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).

Intravenous
Hospital-acquired pneumonia
Adult: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases including ventilator-associated pneumonia: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours for 7-14 days.
Child: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases including ventilator-associated pneumonia: In combination with antibacterial drug(s) active against Gram-positive pathogens and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration: 7-14 days. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).

Intravenous
Bacteraemia
Adult: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases associated with or suspected to be associated with complicated intra-abdominal infections, complicated UTI, or hospital-acquired pneumonia (HAP): 2 g/0.5 g 8 hourly via infusion over 2 hours. Treatment duration may vary according to the site of infection.

Intravenous
Susceptible Gram-negative infections
Adult: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases due to aerobic organisms in patients with limited treatment options: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 2 g/0.5 g 8 hourly via infusion over 2 hours. Treatment duration may vary depending on the severity of the infection, pathogen(s), and clinical response of the patient.
Child: Available preparation:
Ceftazidime 2 g and avibactam 0.5 g powder for solution for infusion

For cases due to aerobic organisms in patients with limited treatment options: In combination with antibacterial drug(s) active against Gram-positive and/or anaerobic pathogens (when these are known or suspected to contribute to the infection): 3-<6 months 0.04 g/0.01 g/kg 8 hourly; 6 months to <18 years 0.05 g/0.0125 g/kg 8 hourly, up to Max of 2 g/0.5 g. All doses are given via infusion for over 2 hours. Treatment duration may vary depending on the severity of the infection, pathogen(s), and clinical and bacteriological progress of the patient. Treatment recommendations may vary among countries and individual products (refer to local detailed product guideline).
Renal Impairment
Complicated intra-abdominal infections; Complicated urinary tract infections; Hospital-acquired pneumonia; Bacteraemia; Susceptible Gram-negative infections:
Adult: CrCl is estimated using Cockcroft-Gault formula. ESRD including patients on haemodialysis: 0.75 g/0.1875 g 48 hourly via infusion over 2 hours after the haemodialysis session on haemodialysis days.
CrCl (mL/min) Dosage
6-15
0.75 g/0.1875 g 24 hourly via infusion over 2 hours.
16-30
0.75 g/0.1875 g 12 hourly via infusion over 2 hours.
31-50
1 g/0.25 g 8 hourly via infusion over 2 hours.

Complicated intra-abdominal infections; Complicated urinary tract infections; Hospital-acquired pneumonia; Susceptible Gram-negative infections:
Child: CrCl is estimated using Schwartz bedside formula. 2-<18 years ESRD including patients on haemodialysis: 0.01875 g/0.00475 g/kg 48 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours after the haemodialysis session on haemodialysis days; CrCl 6-15 mL/min/1.73 m2: 0.01875 g/0.00475 g/kg 24 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 16-30 mL/min/1.73 m2: 0.01875 g/0.00475 g/kg 12 hourly (Max: 0.75 g/0.1875 g) via infusion over 2 hours; CrCl 31-50 mL/min/1.73 m2: 0.025 g/0.00625 g/kg 8 hourly (Max: 1 g/0.25 g) via infusion over 2 hours.
Reconstitution
Reconstitute vial labelled as 2 g ceftazidime/0.5 g avibactam with 10 mL sterile water for inj to prepare a concentration of 167.3 mg/mL ceftazidime and 41.8 mg/mL avibactam (volume of entire contents is approx 12 mL). Further dilute the reconstituted solution by transferring the appropriately calculated volume of reconstituted solution in an infusion bag containing 0.9% NaCl solution, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer’s solution to attain a final concentration of 8-40 mg/mL ceftazidime and 2-10 mg/mL avibactam. Total time interval when starting the reconstitution and completing the IV infusion preparation must not exceed 30 minutes.
Contraindications
Hypersensitivity to ceftazidime, avibactam, any other cephalosporins, or severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other β-lactam antibacterial (e.g. carbapenems, monobactams, penicillins).
Special Precautions
Patient with history of non-severe hypersensitivity reaction to penicillins, monobactams or carbapenems. Children. Renal impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Bacterial or fungal superinfection (prolonged use), severe neurological reactions (e.g. asterixis, encephalopathy, neuromuscular excitability, myoclonus, seizures, non-convulsive status epilepticus, coma).
Blood and lymphatic system disorders: Eosinophilia, thrombocytopenia, thrombocytosis.
Gastrointestinal disorders: Abdominal pain, vomiting, nausea, diarrhoea, dysgeusia.
General disorders and administration site conditions: Infusion site thrombosis or phlebitis, pyrexia.
Infections and infestations: Candidiasis including oral or vulvovaginal candidiasis.
Investigations: Increased ALT, AST, blood alkaline phosphatase, gamma-glutamyltransferase, and blood lactate dehydrogenase.
Metabolism and nutrition disorders: Hypokalaemia.
Nervous system disorders: Dizziness, headache.
Psychiatric disorders: Anxiety.
Renal and urinary disorders: Acute kidney injury, nephrolithiasis, renal impairment.
Skin and subcutaneous tissue disorders: Pruritus, urticaria, maculopapular rash.
Potentially Fatal: Serious hypersensitivity reactions, including anaphylactoid reactions and severe cutaneous adverse reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms); Clostridioides difficile-associated diarrhoea, pseudomembranous colitis.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery.
Monitoring Parameters
Perform culture and susceptibility tests; consult local institutional recommendations before treatment initiation due to antibiotic resistance risks. Assess patient's history of hypersensitivity reactions to ceftazidime, other cephalosporins, or any other type of β-lactam antibiotic prior to treatment initiation. Obtain renal function at baseline in all patients and at least daily in those with changing renal function. Monitor for signs and symptoms of anaphylaxis (during initial dose), serious skin reactions, and seizures or other neurologic activity, particularly in renally impaired patients.
Overdosage
Symptoms: Neurological sequelae including encephalopathy, convulsions, and coma. Management: May perform haemodialysis or peritoneal dialysis to reduce serum levels of ceftazidime.
Drug Interactions
Ceftazidime: Concomitant use of high dose cephalosporins and nephrotoxic agents (e.g. aminoglycosides, potent diuretics) may have adverse effects on renal function.
Avibactam: Elimination of avibactam may be altered by probenecid.
Lab Interference
Ceftazidime: May lead to positive direct antiglobulin test (DAGT) or Coombs' test which may interfere with blood cross-matching and/or cause drug-induced immune haemolytic anaemia. May cause false-positive urinary glucose test with copper reduction methods (e.g. Benedict's solution, Fehling's solution, Clinitest®).
Action
Description: Ceftazidime, a 3rd generation cephalosporin, binds to 1 or more penicillin-binding proteins (PBPs) which inhibits the final transpeptidation step of bacterial peptidoglycan cell wall synthesis, thus resulting in bacterial cell lysis and death.
Avibactam is a reversible non β-lactam β-lactamase inhibitor with minimal intrinsic antibacterial activity; however, it has the potential to enhance the activity of ceftazidime against β-lactamase-producing bacteria. It acts by forming a covalent adduct with the enzyme that is stable to hydrolysis.
Pharmacokinetics:
Distribution: Ceftazidime: Widely distributed throughout body tissues and fluids; therapeutic concentrations are achieved in the CSF when meninges are inflamed. Crosses the placenta; enters breast milk (small amounts). Volume of distribution: Mean: 18.1 L (single dose); 17 L (multiple dose). Plasma protein binding: Approx 10%.
Avibactam: Volume of distribution: Mean: 23.2 L (single dose); 22.2 L (multiple dose). Plasma protein binding: 5.7-8.2%.
Metabolism: Not metabolised.
Excretion: Terminal elimination half-life: Approx 2 hours.
Ceftazidime: Via urine (approx 80-90% as unchanged drug within 24 hours).
Avibactam: Via urine (approx 97%); bile (<1%); faeces (<0.25%).
Chemical Structure

Chemical Structure Image
Ceftazidime

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 5481173, Ceftazidime. https://pubchem.ncbi.nlm.nih.gov/compound/Ceftazidime. Accessed May 26, 2022.


Chemical Structure Image
Avibactam

Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 9835049, Avibactam. https://pubchem.ncbi.nlm.nih.gov/compound/Avibactam. Accessed Oct. 26, 2021.

Storage
Store intact vials between 15-30°C. Protect from light. Solutions after further dilution in 0.9% NaCl, 5% dextrose in water, combination of 0.45% NaCl and 2.5% dextrose, or Lactated Ringer's solution are stable for up to 12 hours at room temperature (≤25°C) and up to 24 hours when stored between 2-8°C.
MIMS Class
Cephalosporins
ATC Classification
J01DD52 - ceftazidime and beta-lactamase inhibitor ; Belongs to the class of third-generation cephalosporins. Used in the systemic treatment of infections.
References
Anon. Ceftazidime and Avibactam. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/10/2021.

Anon. Ceftazidime. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/10/2021.

Avycaz Powder for Solution (Allergan, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 30/09/2021.

Buckingham R (ed). Avibactam Sodium. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/10/2021.

Buckingham R (ed). Ceftazidime. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/10/2021.

Ceftazidime; Avibactam. Gold Standard Drug Database in ClinicalKey [online]. Elsevier Inc. https://www.clinicalkey.com. Accessed 15/10/2021.

Joint Formulary Committee. Ceftazidime with Avibactam. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 30/09/2021.

Pfizer New Zealand Limited. Zavicefta Powder for Injection data sheet 21 May 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 04/10/2021.

Zavicefta 2 g/0.5 g Powder for Concentrate for Solution for Infusion (Pfizer Limited). MHRA. https://products.mhra.gov.uk. Accessed 30/09/2021.

Zavicefta Powder for Concentrate for Solution for Infusion (Pfizer [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 01/10/2021.

Disclaimer: This information is independently developed by MIMS based on Ceftazidime + Avibactam from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2022 MIMS. All rights reserved. Powered by MIMS.com
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