FDA: Exblifep Approved for Complicated Urinary Tract Infections

Drug Topics JournalDrug Topics June 2024
Volume 168
Issue 05

Cefepime/enmetazobactam was granted a 5-year exclusivity extension under GAIN Act legislation.

The FDA approved cefepime/enmetazobactam (Exblifep) in February 2024 for the treatment of complicated urinary tract infections (cUTI) including pyelonephritis caused by designated susceptible microorganisms in patients 18 years and older.1

Cefepime/enmetazobactam is a combination of a cephalosporin antibacterial agent and a β-lactamase inhibitor. The cefepime component is a fourth-generation cephalosporin antibacterial agent that binds penicillin-binding proteins on certain bacteria, resulting in inhibition of cell wall synthesis and bacterial cell death. The enmetazobactam component is a β-lactamase inhibitor that protects cefepime from enzymatic degradation by some bacterial species.

The FDA also granted a 5-year exclusivity extension to the manufacturer under the Generating Antibiotic Incentives Now (GAIN) Act legislation, aimed at incentivizing the development of new antimicrobials.1


Approval was based on a multicenter, randomized, double-blind, noninferiority phase 3 trial evaluating the efficacy and safety of cefepime/enmetazobactam (NCT03687255).2 Eligible participants (adults with cUTI or acute pyelonephritis) were randomly assigned to receive either cefepime 2 g/enmetazobactam 0.5 g (n = 345) or piperacillin 4 g/tazobactam 0.5 g (n = 333). Treatments were administered intravenously every 8 hours for 7 days, or up to 14 days for patients experiencing concurrent bacteremia. Comparisons between the 2 antibiotics were made based on the number of colony-forming units remaining after treatment.

The primary study end point was the proportion of participants infected with a nonresistant strain of bacteria who received the study drug and achieved a clinical cure with eradication of the bacterial infection.

Clinical cure was defined as the complete resolution of the baseline symptoms of cUTI or pyelonephritis that were present at screening. Microbiological response was defined as a reduction in causative pathogens in urine culture and a negative blood culture. Composite response included both microbiological and clinical cure results.

Among patients with concomitant bacteremia, those administered cefepime/enmetazobactam demonstrated greater rates of composite responses compared to those administered piperacillin/tazobactam (71.1% vs 50.0%, respectively). Overall, 79.1% of participants who received cefepime/enmetazobactam achieved a composite response vs 58.9% who received piperacillin/tazobactam, with a between group difference of 21.2% (95% CI, 14.3%-27.9%).


The most common adverse reactions included increased transaminase levels (20%), increased bilirubin levels (7%), headache (5%), infusion site reactions (5%), diarrhea (4%), and anemia (3%). Cefepime/enmetazobactam use is contraindicated in patients with a history of hypersensitivity reactions to β-lactam antibiotics and carries a warning regarding hypersensitivity reactions.

Neurotoxicity is a known risk associated with cefepime administration, particularly in patients with impaired renal function. The development of Clostridioides difficile–associated diarrhea is a risk associated with use of many systemic antibiotic agents. There are no data available evaluating whether cefepime/enmetazobactam causes birth defects.

Dosing and Administration

The recommended dosage of cefepime/enmetazobactam for the treatment of cUTI is 2.5 g (cefepime 2 g and enmetazobactam 0.5 g) every 8 hours by intravenous infusion administered over 2 hours for a duration of 7 to 14 days. Cefepime/enmetazobactam is excreted by the kidneys; renal function should be monitored, as dosing adjustments are necessary for those with renal impairment.

Cefepime/enmetazobactam is supplied as a 2.5-g single-dose vial, which must be reconstituted and further diluted into a 250-mL bag of appropriate fluid for infusion. Drug administration must be completed within 6 hours of dilution.


Are you ready to elevate your pharmacy practice? Sign up today for our free Drug Topics newsletter and get the latest drug information, industry trends, and patient care tips, straight to your inbox.

1. Allecra Therapeutics announces US FDA approval for Exblifep for the treatment of complicated urinary tract infections. News release. Allecra Therapeutics. February 27, 2024. Accessed May 16, 2024. https://www.businesswire.com/news/home/20240227132611/en/Allecra-Therapeutics-Announces-U.S.-FDA-Approval-for-EXBLIFEP%C2%AE-for-the-Treatment-of-Complicated-Urinary-Tract-Infections 
2. Kaye KS, Belley A, Barth P, et al. Effect of cefepime/enmetazobactam vs piperacillin/tazobactam on clinical cure and microbiological eradication in patients with complicated urinary tract infection or acute pyelonephritis. JAMA. 2022;328(13):1304-1314. doi:10.1001/jama.2022.17034
Recent Videos
© 2024 MJH Life Sciences

All rights reserved.