FAERS Analysis Provides New Insights on Cefiderocol Adverse Effects

In 2017, World Health Organization (WHO) staff warned the public about antibiotic-resistant Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.¹ Two years later, the FDA approved cefiderocol (Fetroja; Shionogi) to defeat these bacteria.² However, in 2023, WHO issued a press release warning about antimicrobial resistance.³ The burning question remains: what adverse effects occur after taking cefiderocol?

Bacterial culture | Image credit: analysis121980 | stock.adobe.com

A team of researchers from China addressed this issue in a study published in the March 2025 issue of BMC Pharmacology and Toxicology. They analyzed data from the FDA’s Adverse Event Reporting System on cefiderocol. Of those case reports, the most common adverse effects include bacterial resistance, candida, and treatment failure or death.¹

Patients included in the dataset received either 1 or 2 weeks of cefiderocol therapy. After analyzing the data, the researchers found an average adverse effect start date on the seventh day. While receiving cefiderocol, a patient should avoid fecal occult blood tests or dipstick tests because they will test positive for protein, ketones, or blood. Patients may use those testing methods again 15 hours after the last dose.¹

In contrast to the study findings, the prescribing information for cefiderocol lists different common adverse effects. Individuals with a urinary tract infection reported diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, liver enzyme elevations, headache, low potassium levels, nausea, and vomiting.⁴ Patients with hospital-acquired bacterial pneumonia or ventilator-acquired bacterial pneumonia showed elevations in liver enzyme levels, hypokalemia, diarrhea, hypomagnesemia, and atrial fibrillation.⁴

Hospital staff should only administer cefiderocol through an intravenous line to patients who are at least 18 years of age.⁴ It is administered over 3 hours regardless of creatinine clearance (CrCL), but the frequency of administration changes depending on whether a patient has CrCL above or below 15 mL/min.⁴ The Table describes dose adjustments based on the patient’s CrCL.⁴ One way to monitor for adverse effects is checking blood creatinine. If it is too high, the kidneys will be unable to remove waste products. This is advisable because cefiderocol is structurally similar to cefepime, so kidney damage may occur.¹ If blood magnesium is too low, there is a chance that seizures may occur.⁵

Table. Dose adjustments based on CrCL

Besides the adverse effects, researchers have concluded there were no clinically significant drug interactions. In one study, although rosuvastatin blood levels were slightly raised, no adverse effects occurred. Therefore, the blood elevation raise was considered clinically insignificant. Metformin and furosemide did not raise cefiderocol blood levels.⁶ Another study demonstrated the same results and also reported no drug interaction with digoxin.⁷

Cefiderocol is a novel cephalosporin active against gram-negative bacteria such as Proteus mirabilis, Pseudomonas aeruginosa, Escherichia coli, Enterobacter cloacae, and Klebsiella pneumoniae. Pharmacists are crucial team members when monitoring patients for adverse effects or drug interactions when using this treatment.

REFERENCES

1. Lin H, Zhu C, Liu S, Bi Y, Hu J, Ju M. Post-market safety profile of cefiderocol: a real-world pharmacovigilance exploratory analysis based on US FDA adverse event reporting system (FAERS). BMC Pharmacol Toxicol. 2025;26(1):58. doi:10.1186/s40360-025-00894-3

2. FDA approves new antibacterial drug to treat complicated urinary tract infections as part of ongoing efforts to address antimicrobial resistance. News release. FDA. November 14, 2019. Accessed April 21, 2025. https://www.fda.gov/news-events/press-announcements/fda-approves-new-antibacterial-drug-treat-complicated-urinary-tract-infections-part-ongoing-efforts

3. Antimicrobial Resistance. World Health Organization. November 21, 2023. Accessed April 21, 2025. https://www.who.int/news-room/fact-sheets/detail/antimicrobial-resistance

4. Fetroja [prescribing information]. Shionogi Inc; updated September 2020. Accessed April 21, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/209445s002lbl.pdf

5. Chen BB, Prasad C, Kobrzynski M, Campbell C, Filler G. Seizures related to hypomagnesemia: a case series and review of the literature. Child Neurol Open. 2016:3:2329048X16674834. doi:10.1177/2329048X16674834

6. Katsube T, Miyazaki S, Narukawa Y, Hernandez-Illas M, Wajima T. Drug-drug interaction of cefiderocol, a siderophore cephalosporin,via human drug transporters. Eur J Clin Pharmacol. 2018;74(7):931-938. doi:10.1007/s00228-018-2458-9

7. Stopfer P, Giessmann T, Hohl K, et al. Optimization of a drug transporter probe cocktail: potential screening tool for transporter-mediated drug-drug interactions. Br J Clin Pharmacol. 2018;84(9):1941-1949. doi:10.1111/bcp.13609