Clinical data in HABP/VABP, cUTI, and cIAI

Phase 3 adult trials1

HABP/VABP―REPROVE

Clinical efficacy demonstrated vs meropenem in critically ill patients

cUTI―RECAPTURE

Clinical efficacy demonstrated vs doripenem, including cases involving resistant Gram-negative pathogens

cUTI―REPRISE

Clinical efficacy demonstrated vs BAT in cases involving ceftazidime-NS Gram-negative pathogens

cIAI―RECLAIM

Clinical efficacy demonstrated vs meropenem, including cases involving resistant Gram-negative pathogens

Pediatric trials1

cIAI―ANDI

Clinical efficacy demonstrated vs meropenem in hospitalized pediatric patients aged 3 months to <18 years

cUTI―KURA

Clinical efficacy demonstrated vs cefepime in hospitalized pediatric patients aged 3 months to <18 years

INDICATIONS AND USAGE

Complicated Intra-Abdominal Infections (cIAI)

AVYCAZ® (ceftazidime and avibactam), in combination with metronidazole, is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and Pseudomonas aeruginosa.

Complicated Urinary Tract Infections (cUTI), including Pyelonephritis

AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii complex, Proteus mirabilis, and Pseudomonas aeruginosa.

Hospital-acquired Bacterial Pneumonia and Ventilator-associated Bacterial Pneumonia (HABP/VABP)

AVYCAZ (ceftazidime and avibactam) is indicated for the treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in adult and pediatric patients (at least 31 weeks gestational age) caused by the following susceptible Gram-negative microorganisms: Klebsiella pneumoniae, Enterobacter cloacae, Escherichia coli, Serratia marcescens, Proteus mirabilis, Pseudomonas aeruginosa, and Haemophilus influenzae.

Usage

To reduce the development of drug-resistant bacteria and maintain the effectiveness of AVYCAZ and other antibacterial drugs, AVYCAZ should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

AVYCAZ is contraindicated in patients with known serious hypersensitivity to the components of AVYCAZ (ceftazidime and avibactam), avibactam-containing products, or other members of the cephalosporin class.

WARNINGS AND PRECAUTIONS

  • In a Phase 3 cIAI trial in adult patients, clinical cure rates were lower in a subgroup of patients with baseline creatinine clearance (CrCl) of 30 to less than or equal to 50 mL/min compared to those with CrCl greater than 50 mL/min. The reduction in clinical cure rates was more marked in patients treated with AVYCAZ plus metronidazole compared to meropenem-treated patients. Within this subgroup, patients treated with AVYCAZ received a 33% lower daily dose than is currently recommended for patients with CrCl of 30 to less than or equal to 50 mL/min. Clinical cure rate in patients with normal renal function/mild renal impairment (CrCl greater than 50 mL/min) was 85% (322/379) with AVYCAZ plus metronidazole vs 86% (321/373) with meropenem, and clinical cure rate in patients with moderate renal impairment (CrCl 30 to less than or equal to 50 mL/min) was 45% (14/31) with AVYCAZ plus metronidazole vs 74% (26/35) with meropenem. The decreased clinical response was not observed for patients with moderate renal impairment at baseline (CrCl 30 to less than or equal to 50 mL/min) in the Phase 3 cUTI trials or the Phase 3 HABP/VABP trial. Monitor CrCl at least daily in adult and pediatric patients with changing renal function and adjust the dosage of AVYCAZ accordingly.
  • Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported in patients receiving beta-lactam antibacterial drugs. Before therapy with AVYCAZ is instituted, careful inquiry about previous hypersensitivity reactions to other cephalosporins, penicillins, or carbapenems should be made. Exercise caution if this product is to be given to a penicillin- or other beta-lactam-allergic patient because cross sensitivity among beta-lactam antibacterial drugs has been established. Discontinue the drug if an allergic reaction to AVYCAZ occurs.
  • Clostridioides difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including AVYCAZ, and may range in severity from mild diarrhea to fatal colitis. Careful medical history is necessary because CDAD has been reported to occur more than 2 months after the administration of antibacterial drugs. If CDAD is suspected or confirmed, antibacterials not directed against C. difficile should be discontinued, if possible.
  • Seizures, nonconvulsive status epilepticus (NCSE), encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported in patients treated with ceftazidime, particularly in the setting of renal impairment. Adjust dosing based on CrCl.
  • Prescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

ADVERSE REACTIONS

Adult cIAI, cUTI, and HABP/VABP Patients

The most common adverse reactions in adult patients with cIAI (≥5% when used with metronidazole) were diarrhea (8%), nausea (7%), and vomiting (5%). The most common adverse reactions in adult patients with cUTI (3%) were diarrhea and nausea. The most common adverse reactions in adult patients with HABP/VABP (≥5%) were diarrhea (15%) and vomiting (6%).

Pediatric Patients

The most common adverse reactions (>3%) in pediatric patients aged 3 months and older were vomiting, diarrhea, rash, and infusion site phlebitis.

The most common adverse reactions (>3%) in pediatric patients less than 3 months of age were vomiting and increased transaminases.