General Information

Fetroja (cefiderocol) is a cephalosporin antibacterial.

Fetroja is specifically indicated for patients 18 years of age or older who have limited or no alternative treatment options for the treatment of complicated urinary tract infections (cUTIs), including pyelonephritis caused by the following susceptible Gram-negative microorganisms: Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Enterobacter cloacae complex.

Fetroja is supplied as an injection for intravenous administration. The recommended dosage of Fetroja is 2 grams administered every 8 hours by intravenous (IV) infusion over 3 hours in adults with a creatinine clearance (CLcr) of 60 to 119 mL/min.  Dosage adjustment is recommended for patients with CLcr less than 60 mL/min or for patients with CLcr 120 mL/min or greater. Please see drug label for specific dosing recommendations. The recommended duration of treatment with Fetroja is 7 to 14 days. The duration of therapy should be guided by the severity of infection and the patient’s clinical status for up to 14 days.

Clinical Results

FDA Approval

The approval of Fetroja was based on data from the pivotal APEKS-cUTI study, a multinational, multicenter, double-blind clinical trial that evaluated the efficacy and safety of Fetroja versus imipenem/cilastatin (IPM/CS) in patients with cUTI. Study results showed the response rates for the composite endpoint of microbiological eradication and clinical response at the test of cure (TOC) were significantly higher in the Fetroja arm compared to the IPM/CS arm. In the study, 72.6% (183/252) of patients in the Fetroja arm met the primary endpoint versus 54.6% (65/119) in the IPM/CS arm at TOC. The adjusted difference between the groups was 18.58%. Clinical response rates at the TOC visit were similar between Fetroja and IPM/CS.

Side Effects

Adverse effects associated with the use of Fetroja may include, but are not limited to, the following:

 diarrhea

infusion site reactions

constipation

rash

candidiasis

cough

elevations in liver tests

headache

hypokalemia

nausea

vomiting

Mechanism of Action

Fetroja (cefiderocol) is a cephalosporin antibacterial with activity against Gram-negative aerobic bacteria. Cefiderocol functions as a siderophore and binds to extracellular free ferric iron.  In addition to passive diffusion via porin channels, cefiderocol is actively transported across the outer cell membrane of bacteria into the periplasmic space using a siderophore iron uptake mechanism. Cefiderocol exerts bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins (PBPs).

Additional Information

For additional information regarding Fetroja or complicated urinary tract infections, please visit the Shionogi web page.