Usual Adult Dose for Intraabdominal Infection

2.5 g IV every 8 hours
Duration of therapy: 5 to 14 days

Comments:

• Metronidazole should be used concomitantly.

Use: In combination with metronidazole, for the treatment of complicated intraabdominal infections due to the following susceptible gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, K oxytoca, Citrobacter freundii complex, Pseudomonas aeruginosa

Usual Adult Dose for Pyelonephritis

2.5 g IV every 8 hours
Duration of therapy: 7 to 14 days

Uses:

• For the treatment of complicated urinary tract infections (including pyelonephritis) due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, E cloacae, C freundii complex, P mirabilis, P aeruginosa
• For the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to K pneumoniae, E cloacae, E coli, Serratia marcescens, P mirabilis, P aeruginosa, Haemophilus influenzae

Usual Adult Dose for Urinary Tract Infection

2.5 g IV every 8 hours
Duration of therapy: 7 to 14 days

Uses:

• For the treatment of complicated urinary tract infections (including pyelonephritis) due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, E cloacae, C freundii complex, P mirabilis, P aeruginosa
• For the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to K pneumoniae, E cloacae, E coli, Serratia marcescens, P mirabilis, P aeruginosa, Haemophilus influenzae

Usual Adult Dose for Nosocomial Pneumonia

2.5 g IV every 8 hours
Duration of therapy: 7 to 14 days

Uses:

• For the treatment of complicated urinary tract infections (including pyelonephritis) due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, E cloacae, C freundii complex, P mirabilis, P aeruginosa
• For the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to K pneumoniae, E cloacae, E coli, Serratia marcescens, P mirabilis, P aeruginosa, Haemophilus influenzae

Usual Pediatric Dose for Intraabdominal Infection

3 months to less than 6 months: 50 mg/kg IV every 8 hours
6 months to less than 18 years: 62.5 mg/kg IV every 8 hours

• Maximum dose: 2.5 g/dose

Duration of therapy: 5 to 14 days

Comments:

• Metronidazole should be used concomitantly.

Use: In combination with metronidazole, for the treatment of complicated intraabdominal infections due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, P mirabilis, E cloacae, K oxytoca, C freundii complex, P aeruginosa

Usual Pediatric Dose for Pyelonephritis

3 months to less than 6 months: 50 mg/kg IV every 8 hours
6 months to less than 18 years: 62.5 mg/kg IV every 8 hours

• Maximum dose: 2.5 g/dose

Duration of therapy: 7 to 14 days

Uses:

• For the treatment of complicated urinary tract infections (including pyelonephritis) due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, E cloacae, C freundii complex, P mirabilis, P aeruginosa
• For the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to K pneumoniae, E cloacae, E coli, S marcescens, P mirabilis, P aeruginosa, H influenzae

Usual Pediatric Dose for Urinary Tract Infection

3 months to less than 6 months: 50 mg/kg IV every 8 hours
6 months to less than 18 years: 62.5 mg/kg IV every 8 hours

• Maximum dose: 2.5 g/dose

Duration of therapy: 7 to 14 days

Uses:

• For the treatment of complicated urinary tract infections (including pyelonephritis) due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, E cloacae, C freundii complex, P mirabilis, P aeruginosa
• For the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to K pneumoniae, E cloacae, E coli, S marcescens, P mirabilis, P aeruginosa, H influenzae

Usual Pediatric Dose for Nosocomial Pneumonia

3 months to less than 6 months: 50 mg/kg IV every 8 hours
6 months to less than 18 years: 62.5 mg/kg IV every 8 hours

• Maximum dose: 2.5 g/dose

Duration of therapy: 7 to 14 days

Uses:

• For the treatment of complicated urinary tract infections (including pyelonephritis) due to the following susceptible gram-negative microorganisms: E coli, K pneumoniae, E cloacae, C freundii complex, P mirabilis, P aeruginosa
• For the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia due to K pneumoniae, E cloacae, E coli, S marcescens, P mirabilis, P aeruginosa, H influenzae

Renal Dose Adjustments

Adult Patients:

• Estimated CrCl 31 to 50 mL/min: 1.25 g IV every 8 hours
• Estimated CrCl 16 to 30 mL/min: 0.94 g IV every 12 hours
• Estimated CrCl 6 to 15 mL/min: 0.94 g IV every 24 hours
• Estimated CrCl up to 5 mL/min: 0.94 g IV every 48 hours

Pediatric Patients:
Less than 2 years:

• Renal dysfunction: Data not available

2 years or older:

• Estimated GFR 31 to 50 mL/min/1.73 m2: 31.25 mg/kg IV every 8 hours
• Maximum dose: 1.25 g/dose
• Estimated GFR 16 to 30 mL/min/1.73 m2: 23.75 mg/kg IV every 12 hours
• Maximum dose: 0.94 g/dose
• Estimated GFR 6 to 15 mL/min/1.73 m2: 23.75 mg/kg IV every 24 hours
• Maximum dose: 0.94 g/dose
• Estimated GFR up to 5 mL/min/1.73 m2: 23.75 mg/kg IV every 48 hours
• Maximum dose: 0.94 g/dose

Comments:

• Estimated CrCl calculated using the Cockcroft-Gault formula in adult patients; estimated GFR calculated using the Schwartz bedside formula in pediatric patients 2 years or older.
• Pediatric dosing derived based on population pharmacokinetic modeling, which assumed renal dysfunction had similar proportional effects in adults and pediatric patients 2 years or older.
• CrCl in adult patients and estimated GFR in pediatric patients should be monitored at least daily in those with changing renal function; dose should be adjusted accordingly.

Liver Dose Adjustments

Liver dysfunction: No adjustment recommended

Precautions

CONTRAINDICATIONS:

• Known serious hypersensitivity to either active component, avibactam-containing products, or other cephalosporins

Safety and efficacy have not been established in patients younger than 3 months.

Consult WARNINGS section for additional precautions.

Dialysis

Hemodialysis:
Adult Patients:

• Estimated CrCl 6 to 15 mL/min: 0.94 g IV every 24 hours
• Estimated CrCl up to 5 mL/min: 0.94 g IV every 48 hours

Pediatric Patients:
Less than 2 years: Data not available

2 years or older:

• Estimated GFR up to 5 mL/min/1.73 m2: 23.75 mg/kg IV every 48 hours
• Maximum dose: 0.94 g/dose

Comments:

• Estimated CrCl calculated using the Cockcroft-Gault formula in adult patients; estimated GFR calculated using the Schwartz bedside formula in pediatric patients 2 years or older.
• Pediatric dosing derived based on population pharmacokinetic modeling, which assumed renal dysfunction had similar proportional effects in adults and pediatric patients 2 years or older.
• Both components are hemodialyzable; this drug should be administered after hemodialysis on hemodialysis days.
• CrCl in adult patients and estimated GFR in pediatric patients should be monitored at least daily in those with changing renal function; dose should be adjusted accordingly.

Other Comments

2.5 g avibactam-ceftazidime contains 2 g ceftazidime and 0.5 g avibactam
1.25 g avibactam-ceftazidime contains 1 g ceftazidime and 0.25 g avibactam
0.94 g avibactam-ceftazidime contains 0.75 g ceftazidime and 0.19 g avibactam

62.5 mg/kg avibactam-ceftazidime contains 50 mg/kg ceftazidime and 12.5 mg/kg avibactam
50 mg/kg avibactam-ceftazidime contains 40 mg/kg ceftazidime and 10 mg/kg avibactam
31.25 mg/kg avibactam-ceftazidime contains 25 mg/kg ceftazidime and 6.25 mg/kg avibactam
23.75 mg/kg avibactam-ceftazidime contains 19 mg/kg ceftazidime and 4.75 mg/kg avibactam

Administration advice:

• Administer all doses by IV infusion over 2 hours.
• Do not use the highest recommended concentration (ceftazidime 40 mg/mL and avibactam 10 mg/mL) during coadministration of this drug with other drugs through the same IV line.

Storage requirements:

• Unconstituted vials: Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F); protect from light. Store in carton until time of use.
• After constitution with appropriate diluent: May hold the constituted solution no more than 30 minutes before transfer and dilution in appropriate infusion bag
• After dilution of constituted solutions with appropriate diluents: Solutions in the infusion bags are stable for 12 hours when stored at room temperature; solutions in the infusion bags may also be refrigerated at 2C to 8C (36F to 46F) for up to 24 hours, then should be used within 12 hours of subsequent storage at room temperature

Reconstitution/preparation techniques:

• The dry powder must be constituted and then diluted prior to IV infusion.
• The manufacturer product information should be consulted.

IV compatibility:

• Compatible diluent for constitution only: Sterile water for injection, USP
• Compatible diluents for constitution and dilution: 0.9% sodium chloride injection, USP; 5% dextrose injection, USP; all combinations of dextrose injection and sodium chloride injection, USP, containing up to 2.5% dextrose, USP, and 0.45% sodium chloride, USP; lactated ringer's injection, USP
• At the range of diluted concentrations of ceftazidime 8 mg/mL and avibactam 2 mg/mL to ceftazidime 40 mg/mL and avibactam 10 mg/mL, this drug is compatible with more commonly used IV infusion fluids in infusions bags (including Baxter Mini-Bag Plus) such as the above compatible diluents for constitution and dilution and Baxter Mini-Bag Plus containing 0.9% sodium chloride injection or 5% dextrose injection
• Any drug not listed below should not be coadministered with this drug through the same IV line (or cannula):
• Compatible drugs for use with 0.9% sodium chloride, 5% dextrose, or lactated ringer's injection as diluents: Daptomycin; dexmedetomidine injection; dopamine hydrochloride (HCl) injection; furosemide injection; gentamicin injection; imipenem and cilastatin for injection; magnesium sulfate injection; norepinephrine bitartrate injection; phenylephrine HCl injection; vasopressin injection; vecuronium bromide; metronidazole injection; aztreonam injection or aztreonam for injection; colistimethate for injection; amikacin sulfate injection; azithromycin for injection; ceftaroline fosamil for injection; levofloxacin
• Compatible drugs for use with 0.9% sodium chloride or 5% dextrose injection as diluents: Ertapenem sodium; potassium phosphates injection
• Compatible drugs for use with 5% dextrose or lactated ringer's injection as diluents: Heparin sodium injection; linezolid injection; tobramycin injection or tobramycin for injection
• Compatible drugs for use with 1 compatible diluent only: Meropenem for injection (0.9% sodium chloride injection diluent only); sodium bicarbonate injection (5% dextrose injection diluent only); tedizolid phosphate for injection (5% dextrose injection diluent only); potassium chloride in water for injection (40 mEq/100 mL) (lactated ringer's injection diluent only)

General:

• The dose is expressed as the total of ceftazidime content plus avibactam content.
• To reduce the development of drug-resistant organisms and maintain effective therapy, this drug should be used only to treat or prevent infections proven or strongly suspected to be caused by susceptible bacteria.
• Culture and susceptibility information should be considered when selecting/modifying antibacterial therapy or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy.

Monitoring:

• Renal: CrCl in adult and pediatric patients with changing renal function (at least daily, especially early in therapy); renal function in older adult patients

Patient advice:

• Avoid missing doses and complete the entire course of therapy.
• Consult health care provider at once if any neurological signs/symptoms (including encephalopathy [disturbance of consciousness including confusion, hallucinations, stupor, coma], myoclonus, seizures) occur.
• Consult health care provider if severe watery or bloody diarrhea develops.