FETROJA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FETROJA (FETROJA).
Cefiderocol is a cephalosporin antibiotic that inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), particularly PBP3, and is stable against a broad range of beta-lactamases, including carbapenemases, due to its ability to penetrate the outer membrane via the bacterial iron transport system.
| Metabolism | Cefiderocol is primarily eliminated as unchanged drug via renal excretion; metabolism is minimal (<10%) with no major metabolites identified. Renal clearance is the main pathway, likely involving glomerular filtration and tubular secretion. |
| Excretion | Renal: approximately 65-70% of the dose excreted unchanged in urine; biliary/fecal: minimal (<1%) |
| Half-life | Terminal elimination half-life: 2.5-3.5 hours; prolonged in renal impairment (e.g., up to 5-6 hours in severe renal impairment), requiring dose adjustment |
| Protein binding | ~22% bound to plasma proteins (primarily albumin); low protein binding minimizes displacement interactions |
| Volume of Distribution | Steady-state Vd: 0.3-0.4 L/kg (absolute Vd ~20-30 L); indicates distribution primarily into extracellular fluid |
| Bioavailability | Bioavailability: not applicable (intravenous administration only); oral absorption negligible; intended for IV use |
| Onset of Action | Intravenous: rapid antibacterial effect within 1-2 hours; distribution to tissues occurs within first hour |
| Duration of Action | Duration: 8-12 hours based on dosing interval (every 8 hours); clinical effect sustained with repeated dosing; rapid bactericidal activity with post-antibiotic effect of 2-4 hours against Gram-negative pathogens |
| Molecular Weight | 752.2 Da |
1 gram intravenously over 3 hours every 8 hours in patients 18 years and older with creatinine clearance ≥ 60 mL/min.
| Dosage form | POWDER |
| Renal impairment | For CrCl 30-59 mL/min: 0.5 gram IV over 3 hours every 8 hours. For CrCl 15-29 mL/min: 0.25 gram IV over 3 hours every 8 hours. For end-stage renal disease (CrCl < 15 mL/min) not on hemodialysis: Not recommended. For patients on hemodialysis: 0.25 gram IV over 3 hours every 8 hours; administer after dialysis on dialysis days. |
| Liver impairment | No dose adjustment required for mild or moderate hepatic impairment (Child-Pugh class A or B). Not studied in severe hepatic impairment (Child-Pugh class C); use with caution. |
| Pediatric use | Safety and efficacy in pediatric patients (< 18 years) have not been established; no recommended dose. |
| Geriatric use | No dose adjustment based on age alone; dose adjustment based on renal function (CrCl) as in adults. Monitor renal function frequently due to age-related decline. |
| 1st trimester | Limited human data; based on animal studies, there is no evidence of teratogenicity, but risk cannot be excluded. Use only if clearly needed. |
| 2nd trimester | No adequate human studies; animal studies show no fetal harm. Consider maternal benefit vs. potential fetal risk. |
| 3rd trimester | No adequate human studies; avoid use during labor and delivery due to potential for neonatal adverse effects (e.g., diarrhea, candidiasis). |
Clinical note
Comprehensive clinical and safety monograph for FETROJA (FETROJA).
| Placental transfer | Cefiderocol crosses the placenta in animal studies; degree and rate in humans are unknown. |
| Breastfeeding | Cefiderocol is excreted into human breast milk in low concentrations. Because of the potential for serious adverse reactions in nursing infants, including alteration of gut flora, consider the developmental and health benefits of breastfeeding along with the mother's clinical need for FETROJA and any potential adverse effects on the breastfed infant. |
■ FDA Black Box Warning
None
| Serious Effects |
Known severe hypersensitivity to cefiderocol or other cephalosporinsHistory of severe hypersensitivity (e.g., anaphylaxis) to other beta-lactam antibiotics
| Precautions | Hypersensitivity reactions including anaphylaxis and severe cutaneous adverse reactions, Clostridioides difficile-associated diarrhea (CDAD), Seizures and other CNS adverse reactions, Reduced efficacy in patients with carbapenem-resistant infections who have creatinine clearance <30 mL/min, Development of resistance during therapy, Alteration of intestinal flora |
| Food/Dietary | No significant food interactions reported. Grapefruit may theoretically affect metabolism via CYP450, but clinical relevance is unknown; caution is advised. No restrictions on alcohol or other foods. |
Loading safety data…
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | Cefiderocol is classified as Pregnancy Category B. Animal reproduction studies have not demonstrated fetal risk, but there are no adequate and well-controlled studies in pregnant women. Use only if clearly needed and potential benefit justifies potential risk to the fetus. No known teratogenic effects in first trimester; second and third trimester risks are not defined but are expected to be low based on animal data. |
| Fetal Monitoring | Monitor for clinical response and adverse effects. No specific fetal monitoring required. Standard pregnancy monitoring is appropriate. |
| Fertility Effects | No known adverse effects on fertility. Animal studies have not shown impaired fertility. |
| Clinical Pearls | FETROJA (cefiderocol) is a siderophore cephalosporin with potent activity against carbapenem-resistant Gram-negative pathogens, including Pseudomonas aeruginosa, Acinetobacter baumannii, and Enterobacterales. It requires dose adjustment for renal impairment based on creatinine clearance. It is a first-line option for multidrug-resistant infections where other agents fail. Avoid concurrent use with probenecid as it reduces excretion. Monitor for Clostridioides difficile diarrhea. |
| Patient Advice | Complete the full course of the medication even if you feel better. · Inform your doctor if you have kidney disease; dose adjustment may be needed. · Report any signs of allergic reaction (rash, hives, difficulty breathing) or severe diarrhea. · This medication is given intravenously; keep all appointments for infusions. · Avoid grapefruit or grapefruit juice while taking this medication. |