The US Food and Drug Administration (FDA) has approved a supplemental New Drug Application to update the label for ceftazidime-avibactam (Avycaz, Allergan, AstraZeneca) to include clinical data from a phase 3 trial evaluating the safety and efficacy of ceftazidime-avibactam, in combination with metronidazole, for the indication of complicated intra-abdominal infections (cIAI) caused by designated susceptible microorganisms, according to a company news release.
The label will also be updated to include data from a subset of patients in the same trial with infections caused by ceftazidime-nonsusceptible (CAZ-NS) pathogens and a subset who had pathogens producing certain extended-spectrum beta-lactamases (ESBLs).
"Complicated intra-abdominal infections represent a major therapeutic challenge for physicians," David Nicholson, PhD, chief research and development officer, Allergan, said in the release. "Avycaz has been used in thousands of patients with these difficult-to-treat infections since it was first approved by the FDA in February 2015. The addition of these data to the label provides physicians with consistent evidence of the activity of Avycaz against some of the most challenging pathogens, including those for which we currently have limited treatment options."
The approval follows a review of data from the trial, which showed that the drug met the primary end point of statistical noninferiority to meropenem at the test-of-cure time point. Clinical cure rates in the two subsets of patients were similar to the overall results.
The FDA approved ceftazidime-avibactam in February 2015 for treatment of adults with cIAI, "in combination with metronidazole, and complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa," the company explains in the news release.
Ceftazidime-avibactam is an antibiotic consisting of ceftazidime, which is a third-generation cephalosporin established as a respected treatment for serious gram-negative bacterial infections. Avibactam is a non-β-lactam β-lactamase inhibitor; adding it to ceftazidime prevents ceftazidime from being broken down by certain β-lactamases.
Ceftazidime-avibactam "offers a differentiated profile in the treatment of cIAI (in combination with metronidazole) and cUTI caused by designated microorganisms through its in vitro activity against Enterobacteriaceae, including those that produce certain ESBLs and [Klebsiella pneumoniae carbapenemases], and difficult-to-treat Pseudomonas aeruginosa," the company explains in the news release.
Prescribers should reserve ceftazidime-avibactam for use in those with cUTI who have limited or no alternative treatment options, because only limited safety and efficacy data are currently available. Phase 3 studies of the drug in this group have been completed, and the company will submit the analysis of the study data later this year.
Ceftazidime-avibactam should be used only in patients with indicated infections that have been proven or are strongly suspected to be caused by susceptible bacteria. It should not be used in patients who have a known serious hypersensitivity to either component, avibactam-containing products, or other cephalosporins.
Caution should be exercised if using this drug in patients allergic to penicillin or other β-lactams because cross-sensitivity has occured among β-lactam antibacterial drugs. Ceftazidime-avibactam should be discontinued if the patient develops an allergic reaction.
Close observation should be made for Clostridium difficile-associated diarrhea. If the patient develops suspected or confirmed C difficile-associated diarrhea, antibacterials not directed against C difficile should be discontinued, if possible.
There have been reports of seizures, nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia in patients treated with ceftazidime, particularly in the those with renal impairment. The patient's dosing should be adjusted based on creatinine clearance.
The most commonly reported adverse reactions in patients with cIAI (incidence of ≥ 5% when used with metronidazole) were diarrhea (8%), nausea (7%), and vomiting (5%). The most common adverse reactions in patients with cUTI (incidence of ≥ 10%) were constipation (10%) and anxiety (10%).
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Cite this: FDA Approves Updated Label for Avycaz - Medscape - Jun 27, 2016.
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