Government and Regulations

FDA approves antibacterial combo drug Avycaz



The Food and Drug Administration has approved the antibacterial drug ceftazidime-avibactam (Avycaz) on Feb. 25 for complicated intra-abdominal infections in combination with metronidazole, and for complicated urinary tract infections including pyelonephritis in adults.

“It is important that the use of Avycaz be reserved for situations where there are limited or no alternative antibacterial drugs for treating a patient’s infection,” Dr. Edward Cox, director of the FDA’s Office of Antimicrobial Products in the Center for Drug Evaluation and Research, said in a statement.

Avycaz is a fixed-combination drug containing ceftazidime, a previously approved cephalosporin with in vitro activity against certain gram-negative and gram-positive bacteria, and avibactam, a beta-lactamase inhibitor.

The addition of avibactam to ceftazidime protects ceftazidime from breakdown by extended spectrum beta-lactamases, Klebsiella pneumoniae carbapenemase (KPC), and AmpC-producing pathogens, according to David Nicholson, Ph.D., executive vice president of branded research and development at Actavis, which is jointly developing the drug with AstraZeneca.

“The FDA approval of Avycaz is an important step forward in enhancing our ability to respond to serious pathogens caused by difficult-to-treat gram-negative pathogens,” he said in a statement.

The recent rise in the incidence of multidrug-resistant gram-negative pathogens poses a significant threat to patients and places a tremendous strain on the U.S. health care system, Dr. Jose Vazquez, chief of infectious disease at Georgia Regents University in Augusta, Ga., commented in the same statement.

“The increasing prevalence of KPC-producing Enterobacteriaceae in particular, has become a major therapeutic challenge for physicians managing these infections. Unfortunately, there are currently a limited number of safe and effective antimicrobials to treat these serious infections,” he said.

Avycaz was granted priority review and named a Qualified Infectious Disease Product (QIDP), a designation given to antibacterial products to treat serious or life-threatening infections.

Its efficacy was supported in part by findings of the efficacy and safety of ceftazidime for the treatment of complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI). The contribution of avibactam to Avycaz was based on data from in vitro studies and animal models of infection. Avycaz was also studied in two phase II trials, one each in cIAI and cUTI.

The most common side effects are vomiting, nausea, constipation, and anxiety. The FDA advises health care professionals to inform patients of these risks and that decreased efficacy, seizures, and other neurologic events were seen in patients with renal impairment. Serious skin reactions and anaphylaxis may occur in patients with penicillin allergies.

The recommended dosage for patients with normal renal function is 2.5 g administered every 8 hours by intravenous infusion over 2 hours in adults aged 18 years and older. For patients with changing or impaired renal function (creatinine clearance < 50 mL/min), CrCL should be monitored at least daily and the dosage adjusted accordingly.

In a phase III trial of intra-abdominal infections, clinical cure rates were lower in the subgroup of patients with CrCL of 30-50 mL/min, compared with those with CrCL greater than 50 mL/min, according to the company. The reduction in cure rates was more marked in patients treated with Avycaz plus metronidazole vs. meropenem-treated patients.

Avycaz will be available in the second quarter of 2015, according to the company. Phase III studies evaluating Avycaz for the treatment of cIAI and cUTI are ongoing and targeted for completion in late 2015.

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