Actavis plc, global pharmaceutical company, has launched Avycaz (ceftazidime-avibactam) in the United States to treat adult patients with complicated intra-abdominal infections (cIAI) (in combination with metronidazole) and complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible bacteria, including certain Enterobacteriaceae and Pseudomonas aeruginosa.

Avycaz is now available for ordering by hospitals across the United States. As only limited clinical safety and efficacy data for Avycaz are currently available, Avycaz should be reserved for use in patients who have limited or no alternative treatment options.

"In light of the urgent medical need in the US for new antimicrobial treatments that address some of the most difficult to treat pathogens, Actavis increased the company's manufacturing focus to ensure Avycaz would be available as soon as possible following FDA approval," said William Meury, president, Actavis Branded Pharma.

"We are proud to provide healthcare providers with this new therapeutic option that addresses serious Gram-negative infections for which there are few treatment options today."

Avycaz combines ceftazidime, a cephalosporin with in vitro activity against certain gram-negative and gram-positive bacteria, and avibactam, a non-beta-lactam beta-lactamase inhibitor that inactivates certain key beta-lactamases and protects ceftazidime from degradation by these beta-lactamases. The addition of avibactam to ceftazidime protects ceftazidime from breakdown by Extended Spectrum Beta-Lactamases (ESBL), Klebsiella pneumoniae carbapenemase (KPC) and AmpC producing pathogens. Avycaz is part of Actavis' leading portfolio of infectious disease products that address some of the most dangerous pathogens.

Avycaz received a priority review and FDA approval was supported in part by the FDA's previous findings of efficacy and safety of ceftazidime for the treatment of cIAI and cUTI. In addition, the contribution of avibactam to Avycaz was primarily established via in vitro data and animal models of infection. Avycaz was studied in two phase II, randomized, blinded, active controlled, multicenter trials, one each in cIAI and cUTI, including pyelonephritis. These studies were not designed with any formal hypotheses for inferential testing against the active comparators.

Avycaz for injection is supplied in single-use, clear glass vials for reconstitution. It is available to hospitals for purchase in cartons of ten (10) 2.5 g vials.

Avycaz, in combination with metronidazole, is indicated for the treatment of cIAI caused by the following susceptible microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca and Pseudomonas aeruginosa.

Avycaz is indicated for the treatment of cUTI including pyelonephritis caused by the following susceptible microorganisms:  Escherichia coli, Klebsiella pneumoniae, Citrobacter koseri, Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii, Proteus spp. and Pseudomonas aeruginosa.

Avycaz demonstrated in vitro activity against Enterobacteriaceae in the presence of some beta-lactamases and extended-spectrum beta-lactamases (ESBLs) of the following groups: TEM, SHV, CTX-M, Klebsiella pneumoniae carbapenemase (KPCs), AmpC, and certain oxacillinases (OXA). Avycaz also demonstrated in vitro activity against P. aeruginosa in the presence of some AmpC beta-lactamases, and certain strains lacking outer membrane porin (OprD). Avycaz 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.



The recommended dosage of Avycaz for patients with normal renal function [creatinine clearance (CrCL) >50 mL/min] is 2.5 grams (2 grams ceftazidime and 0.5 grams avibactam) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older. For patients with changing or impaired renal function (CrCL <50mL/min), CrCL should be monitored at least daily and the dosage of Avycaz should be adjusted accordingly. For treatment of cIAI, metronidazole should be given concurrently.

Avycaz is contraindicated in patients with known serious hypersensitivity to Avycaz, avibactam-containing products, ceftazidime, or other members of the cephalosporin class. The most common adverse reactions (incidence of > 10% in either indication) were vomiting, nausea, constipation, and anxiety.

Avycaz is being jointly developed with AstraZeneca. Actavis holds the rights to commercialize Avycaz in North America, while AstraZeneca holds the rights to commercialize ceftazidime-avibactam in the rest of the world.

Phase III studies including studies evaluating Avycaz for the treatment of cIAI and cUTI  are underway and targeted for completion in late 2015. The company intends to submit the phase III results to the FDA as a supplemental NDA.