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
AVYCAZ was granted priority review and approval as a Qualified Infectious Disease Product (QDIP) in accordance with the Generating Antibiotics Incentives Now (GAIN) Act, which made it eligible for the
"The recent increase in the incidence of multi-drug resistant Gram-negative pathogens poses a significant threat to patients and places a tremendous strain on the U.S. healthcare system. The increasing prevalence of KPC-producing Enterobacteriaceae in particular, have 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," said
The approval of AVYCAZ was supported in part by the
AVYCAZ will be available in the second quarter of 2015.
AVYCAZ (ceftazidime-avibactam) consists of ceftazidime, a cephalosporin, and avibactam, a non-beta-lactam beta-lactamase inhibitor, and is approved for the treatment of cIAI (in combination with metronidazole) and cUTI infections including pyelonephritis caused by designated susceptible microorganisms in patients 18 years of age and older. AVYCAZ should be reserved for use in patients who have limited or no alternative treatment options as limited clinical safety and efficacy data for AVYCAZ are currently available.
The addition of avibactam to ceftazidime protects ceftazidime from breakdown by certain beta-lactamases. AVYCAZ addresses important needs in the treatment of cUTI and cIAI due to designated susceptible Gram-negative pathogens.
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.
IMPORTANT SAFETY INFORMATION
AVYCAZ is contraindicated in patients with known serious hypersensitivity to AVYCAZ, avibactam‑containing products, ceftazidime, or other members of the cephalosporin class.
WARNINGS AND PRECAUTIONS
- In a Phase 3 complicated intra-abdominal infections (cIAI) trial, clinical cure rates were lower in a subgroup of patients with baseline creatinine clearance (CrCL) of 30 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 30 to 50 mL/min. Monitor CrCL at least daily in 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.
- Clostridium 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, 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 creatinine clearance.
- Prescribing AVYCAZ in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.
- The most common adverse reactions (incidence of > 10% in either indication) were vomiting, nausea, constipation, and anxiety.
AVYCAZ is being jointly developed with
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
For more information, visit www.AVYCAZ.com.
About Gram-Negative Infections
Gram-negative bacteria are highly adaptive pathogens that can develop resistance through several mechanisms and can pass along genetic materials that allow other bacteria to become drug-resistant as well., Gram-negative bacteria are common causes of complicated intra-abdominal infections and urinary tract infections.,
Complicated intra-abdominal infections are a considerable problem, affecting approximately 1.1 million patients each year. The most common pathogens associated with intra-abdominal infections includeEscherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Providencia stuartii, Enterobacter cloacae, Klebsiella oxytoca and Pseudomonas aeruginosa.
Complicated urinary tract infections are also often caused by Gram-negative pathogens. Escherichia coli (E. coli) is one of the common organisms causing urinary tract infections (UTIs), affecting 2.9 million patients each year, and is becoming increasingly resistant to available antibiotics.,
According to the
For more information, visit
Statements contained in this press release that refer to future events or other non-historical facts are forward-looking statements that reflect
 Peleg A,
 Data on file
 Guidance for Control of Carbapenem-resistant Enterobacteriaceae (CRE).