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General Information
Exblifep is a combination of cefepime, a cephalosporin antibacterial, and enmetazobactam, a beta-lactamase inhibitor.
Exblifep is specifically indicated for the treatment of patients 18 years and older with complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible microorganisms.
Exblifep is suppled as a solution for intravenous administration. The recommended dosage of Exblife is 2.5 grams (2 grams cefepime and 0.5 grams enmetazobactam) administered every 8 hours by intravenous (IV) infusion over 2 hours in patients 18 years of age and older with an estimated glomerular filtration rate (eGFR) between 60 and 129 mL/min. The duration of treatment is 7 days and up to 14 days for patients with concurrent bacteremia.
Please see drug prescribing label for recommended dosing/administration in patients with renal dysfunction.
Mechanism of Action
Exblifep is a combination of cefepime and enmetazobactam.
The cefepime component of Exblifep is a cephalosporin antibacterial drug. The bactericidal action of cefepime results from the inhibition of cell wall synthesis. Cefepime penetrates the cell wall of most grampositive and gram-negative bacteria to bind penicillin-binding protein (PBP) targets. Cefepime is stable to hydrolysis by some beta-lactamases, including penicillinases and cephalosporinases produced by gram-negative and gram-positive bacteria, with the exception of extended spectrum beta-lactamases (ESBL), some oxacillinases, and carbapenem hydrolyzing beta-lactamases.
The enmetazobactam component of Exblifep is a beta-lactamase inhibitor that protects cefepime from degradation by certain serine beta-lactamases such as ESBL.
Side Effects
Adverse effects associated with the use of Exblifep may include, but are not limited to, the following:
- transaminases increased
- increased bilirubin
- headache
- phlebitis/infusion site reactions
Clinical Trial Results
The FDA approval of Exblifep was based on a totality of clinical data that demonstrated Exblifep effectiveness against antimicrobial resistance in gram-negative bacteria, especially resistance mediated by both ESBL (Extended Spectrum Beta Lactamases) and AmpC. This included data from data from the phase 3 ALLIUM trial.
The Phase 3, randomized, double-blind, active-controlled, multi-center, noninferiority clinical trial was conducted at 90 sites in Europe, North and Central America, South America, and South Africa and enrolled 1,041 adult patients ≥18 years of age with a clinical diagnosis of complicated UTI or acute pyelonephritis caused by gram-negative urinary pathogens. Eligible patients were randomized to receive either 2 g cefepime/0.5 g enmetazobactam or 4 g piperacillin/0.5 g tazobactam by 2-hour infusion every 8 hours for 7 days.
Among patients with cUTI or acute pyelonephritis caused by gram-negative pathogens, cefepime/enmetazobactam, compared with piperacillin/tazobactam, met criteria for noninferiority as well as superiority with respect to the primary outcome of clinical cure and microbiological eradication. The primary outcome occurred in 79.1% (273/345) of patients receiving cefepime/enmetazobactam compared to 58.9% (196/333) receiving piperacillin/tazobactam in the primary analysis data set (between group difference: 21.2%). In the 20.9% (142/678) of patients with an ESBL-producing baseline pathogen, 73.7% (56/76) of patients in the cefepime/enmetazobactam group and 51.5% (34/66) of those in the piperacillin/tazobactam group achieved the composite outcome (difference 30.2%).