New Drug
Lauren Howell, PharmD
In February 2024, FDA approved Exblifep (cefepime hydrochloride/enmetazobactam—Allecra Therapeutics), a new antibiotic that is indicated for complicated UTIs, including pyelonephritis, in individuals 18 years and older.
Exblifep is a combination of cefepime, a fourth-generation cephalosporin antibiotic, and enmetazobactam, a novel β-lactamase inhibitor.
With antibiotic resistance on the rise, Exblifep carries promise for patients with infections that are not susceptible to most of the antibiotics that are already on the market.
Recommended dosage and administration
In order to reduce the development of drug-resistant bacteria and ensure that Exblifep and other antibiotics maintain their effectiveness, Exblifep should only be used to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
It is supplied as a sterile powder for reconstitution in single-dose vials. In patients 18 years and older with an eGFR between 60 mL/min and 129 mL/min, the recommended dosage of Exblifep is 2.5 g (2 g cefepime and 0.5 g enmetazobactam) every 8 hours for 7 to 14 days. Administration should occur via I.V. infusion over 2 hours.
Dosage adjustments are required in patients with renal impairment who have an eGFR of less than 60 mL/min or greater than or equal to 130 mL/min. In patients on hemodialysis, doses should be administered after a hemodialysis session.
Adverse effects
Exblifep is contraindicated in patients with a history of serious hypersensitivity reaction to cefepime, enmetazobactam, or other β-lactam drugs. Hypersensitivity reactions have been reported in patients treated with Exblifep, and serious and occasionally fatal hypersensitivity reactions, including anaphylaxis, have been reported with use of β-lactams.
If an allergic reaction occurs, Exblifep should be discontinued and appropriate therapy should be initiated.
The most common adverse effects in patients treated with Exblifep during clinical trials were increased transaminases, increased bilirubin, headache, phlebitis, and infusion site reactions. As with almost all systemic antibiotics, there is also a risk for Clostridioides difficile–associated diarrhea.
Neurotoxicity has been reported with the use of cefepime. Most of these cases have been in patients with renal impairment who did not receive proper dosage adjustments. If neurotoxicity does occur, Exblifep should be discontinued and appropriate supportive measures should be started. Special attention should be given when selecting doses for older adult patients, and renal function should be monitored appropriately in these patients.
Clinical trials
In the clinical study used to show the efficacy of Exblifep, a total of 1,041 adults with a complicated UTI including pyelonephritis were randomized in a 1:1 ratio into a multinational, double blind, noninferiority trial. The trial compared 2.5 g of Exblifep to piperacillin/tazobactam (4 g piperacillin and 0.5 g tazobactam). For both drugs, the dose was administered over 2 hours every 8 hours for 7 days. For patients with concurrent bacteremia, the duration of therapy was extended to up to 14 days.
Exblifep demonstrated efficacy regarding composite response, which was defined as clinical cure and microbiological response 7 days after the end of treatment. Clinical cure was defined as the complete resolution of the baseline signs and symptoms that were present at screening. Microbiological response was defined as the baseline qualifying gram-negative pathogens being reduced to <103 colony-forming units/mL in urine culture and a negative blood culture if the patient initially had a positive blood culture.
For the Exblifep group, the composite response rate was 79.1%, compared to 58.9% in the piperacillin/tazobactam group. In patients with ESBL-producing bacteria at baseline, the composite response rate was 74% in the Exblifep group and 52% in the piperacillin/tazobactam group.
More studies are needed to determine the potential role of Exblifep in treating complicated UTIs and pyelonephritis. ■