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 |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for FETROJA (FETROJA).
| Breastfeeding | It is not known whether cefiderocol is excreted in human milk. No specific M/P ratio available. Caution should be exercised when administered to a breastfeeding woman due to potential for disruption of infant gut flora and allergic sensitization. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to cefiderocol or other cephalosporins","Severe hypersensitivity to other beta-lactam antibiotics (e.g., penicillins, carbapenems)"]
| 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"] |
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| 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. |