Adult Dosing

Complicated intra-abdominal infections (used in combination with metronidazole)

• 2.5 g (2 g ceftazidime/0.5 g avibactam) IV infusion over 2 hours q8 hrs x 5-14 days

Complicated urinary tract Infections including pyelonephritis

• 2.5 g (2 g ceftazidime/0.5 g avibactam) IV infusion over 2 hours q8 hrs x 7-14 days

Note:

• The above dosage is recommended for patients with creatinine clearance (CrCl) >50 mL/min
• Refer package insert for preparation of the ceftazidime/avibactam solution for administration and drug compatibility

Pediatric Dosing

• Safety and effectiveness in pediatric patients have not been established

[Outline]

• Adult Dosing
• Pediatric Dosing

• Used in combination with metronidazole for the treatment of complicated intra-abdominal infections (cIAI) caused by susceptible bacteria: <i>Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca, </i>and <i>Pseudomonas aeruginosa</i> in patients 18 years or older
• Treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by susceptible bacteria: <i>Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Proteus </i> spp., and <i>Pseudomonas aeruginosa </i> in patients 18 years or older

Note:

• Ceftazidime/avibactam should only be used to treat infections that are proven or strongly suspected to be caused by susceptible bacteria to reduce the development of drug-resistant bacteria and to maintain the efficacy of the medication

• Hypersensitivity to any of the ingredients of the product
• Hypersensitivity to other members of cephalosporin class

• N/A

Renal Dose Adjustment (Based on CrCl)

Moderately or severely impaired renal function (CrCl 50 mL/min)

• CrCl 31-50 mL/min: 1.25 g (ceftazidime 1 g and avibactam 0.25 g) IV infusion over 2 hrs q8 hrs
• CrCl 16-30 mL/min: 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) IV infusion over 2 hrs q12 hrs
• CrCl 6-15 mL/min: 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) IV infusion over 2 hrs q24 hr
• CrCl 5 mL/min: 0.94 g (ceftazidime 0.75 g and avibactam 0.19 g) IV infusion over 2 hrs q48 hr

Note:

• For patients with changing renal function, CrCl should be monitored at least daily and dosage of ceftazidime/avibactam adjusted accordingly
• Both ceftazidime and avibactam are hemodialyzable; hence, the medication should be administered after hemodialysis on hemodialysis days

Hepatic impairment

• Hepatic impairment: No dose adjustments

• In a cIAI clinical trial, clinical cure rates were lower in patients with baseline CrCl of 30 to 50 mL/min compared to those with CrCl >50 mL/min. The reduction in cure rates was more in patients treated with ceftazidime/ avibactam plus metronidazole (45% cure rate) compared with meropenem-treated patients (74% cure rate). The dose of ceftazidime/avibactam was 33% lower than the dose recommended for patients with moderate renal impairment. Monitor CrCl at least daily in patients with changing renal function and adjust the dose accordingly
• Serious and occasionally fatal anaphylactic and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Inquire about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems before initiating the therapy. Use cautiously in penicillin or other beta-lactam-allergic patients because cross sensitivity among beta-lactam antibacterial drugs has been established. Discontinue the drug if an allergic reaction occurs
• <i>Clostridium difficile</i>-associated diarrhea (CDAD) ranging in severity from mild diarrhea to fatal colitis has been reported with therapy. If CDAD is suspected or confirmed, discontinue the antibacterial drugs not directed against <i>C. difficile</i>. Manage fluid and electrolyte levels, supplement protein intake, and monitor antibacterial treatment for CDAD
• Central nervous system reactions such as seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dose based on CrCl
• Prescribe ceftazidime/avibactam only to those patients with proven or strongly suspected bacterial infection to avoid risk of developing drug-resistant bacteria

Cautions: Use cautiously in:

• Renal impairment
• Hypersensitivity to penicillin
• History of antibiotic associated colitis
• Seizure disorder

Pregnancy Category:B

Breastfeeding: Safety unknown. Ceftazidime: Limited information indicates that maternal doses of ceftazidime up to 2 grams produce low levels in milk that are not expected to cause adverse effects in breastfed infants. This information is based upon LactMed database (available at http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT). This drug is compatible and considered safe with breastfeeding based upon data from AAP Policy Guidelines (available at http://aappolicy.aappublications.org/cgi/content/full/pediatrics;108/3/776 last accessed 06 February 2016). Manufacturer advises caution.

• GI: Vomiting, nausea, abdominal pain, constipation, upper abdominal pain
• PSYCH: Anxiety
• CNS: Dizziness
• LABTEST: Increased alkaline phosphatase, increased alanine aminotransferase, positive direct Coombs test

ceftazidime

• Third-generation cephalosporins; exerts bactericidal action by binding to essential penicillin-binding proteins (PBPs) thereby inhibiting final transpeptidation step of peptidoglycan synthesis in the bacterial cell-wall synthesis causing inhibition of cell-wall biosynthesis
• Metabolism: Minimally metabolized, 80-90% of the dose eliminated as unchanged drug
• Excretion: Excreted in urine (80-90%)
• Half-life: 2.76 hours

avibactam

• Non-beta-lactam, beta-lactamase inhibitor; protects ceftazidime from degradation by inactivating some -lactamase enzymes and effectively extends the antibiotic spectrum of ceftazidime to include many gram-negative bacteria normally not susceptible to ceftazidime
• Metabolism: Not metabolized in the liver; major drug-related component eliminated as unchanged avibactam
• Excretion: Excreted in urine (97%)
• Half-life: 2.71 hours

US Trade Name(s)

• Avycaz

US Availability

Avycaz (ceftazidime/avibactam)

• PWDR for INJ: 2.5 g (2 g/0.5 g) vials

Canadian Trade Name(s)

• N/A

Canadian Availability

• N/A

UK Trade Name(s)

• N/A

UK Availability

• N/A

Australian Trade Name(s)

• N/A

Australian Availability

• N/A

[Outline]

Antimicrobials

Antibiotic Combinations

Infectious Disease

Antibiotic Combinations