FDA Approves Label Update for Ceftazidime/ Avibactam (Avycaz)

New phase 3 data added

The FDA has approved a supplemental new drug application to update the label for ceftazidime/avibactam (Avycaz, Allergan/AstraZeneca) with clinical data from a phase 3 trial that evaluated the treatment’s safety and efficacy in combination with metronidazole in patients with complicated intra-abdominal infections (cIAIs) caused by designated susceptible microorganisms. The revised label also contains data from a subset of patients in this trial with infections due to ceftazidime-nonsusceptible pathogens, as well as a subset of patients that had pathogens producing certain extended-spectrum beta-lactamases (ESBLs).

The phase 3 study showed that clinical cure rates at the test-of-cure time point met the primary endpoint of statistical noninferiority to meropenem. In a subset of patients with infections due to ceftazidime-resistant pathogens, as well as a subset that had pathogens that produced certain ESBLs, clinical cure rates for patients treated with ceftazidime/avibactam were similar to the overall results.

Ceftazidime/avibactam has demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and ESBLs of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemases (KPCs), AmpC beta-lactamases, and certain oxacillinases. Ceftazidime/avibactam also demonstrated in vitro activity against Pseudomonas aeruginosa in the presence of some AmpC beta-lactamases and certain strains lacking outer-membrane porin. Ceftazidime/avibactam is not active against bacteria that produce metallo-beta lactamases and may not have activity against gram-negative bacteria that overexpress efflux pumps or have porin mutations.

Ceftazidime is a third-generation cephalosporin and an established treatment for serious gram-negative bacterial infections, and avibactam is a non-beta lactam beta-lactamase inhibitor. Ceftazidime/avibactam was developed to treat certain serious gram-negative bacterial infections.

The addition of avibactam to ceftazidime protects ceftazidime from breakdown by certain beta-lactamases. Ceftazidime/avibactam offers a differentiated profile in the treatment of cIAIs (in combination with metronidazole) and complicated urinary tract infections (cUTIs) caused by designated microorganisms through its in vitro activity against Enterobacteriaceae, including those that produce certain ESBLs and KPCs, and difficult-to-treat P. aeruginosa.

Avycaz (ceftazidime and avibactam), in combination with metronidazole, is indicated for the treatment of cIAIs caused by the following susceptible gram-negative microorganisms: Escherichia coli, K. pneumoniae, Proteus mirabilis, Enterobacter cloacae, Klebsiella oxytoca, Citrobacter freundii complex, and P. aeruginosa in patients 18 years of age or older.

Avycaz is also indicated for the treatment of cUTIs, including pyelonephritis caused by the following susceptible microorganisms: E. coli, K. pneumoniae, Citrobacter koseri, Enterobacter aerogenes, E. cloacae, C. freundii, Proteus spp., and P. aeruginosa in patients 18 years of age or older. In the treatment of cUTIs, ceftazidime/avibactam should be reserved for use in patients who have limited or no alternative treatment options.

Source: Allergan; June 23, 2016.