FETROJA ®- cefiderocol SO4 tosylate
Drug UPDATES: [Drug information (pdf)]
PACKAGE INSERT -Dosing: Click (+) next to Dosage and Administration section (drug info link)
0.9% sodium chloride injection, USP or
5% dextrose injection, USP
[0.75 to 2 grams*] [100 ml ] [3 hours]
*See dose based on CLcr below.
Reconstitute the powder for injection in the FETROJA vial with 10 mL of either 0.9% sodium chloride injection, USP or 5% dextrose injection, USP and gently shake to dissolve. Allow the vial(s) to stand until the foaming generated on the surface has disappeared (typically within 2 minutes). The final volume of the reconstituted solution will be approximately 11.2 mL.
- CLcr ≥ 120 mL/min: 2 grams IV q6h
- CLcr 60 to 119 mL/min: 2 grams IV q8h
- CLcr 30 to 59 mL/min: 1.5 grams IV q8h
- CLcr 15 to 29 mL/min: 1 gram IV q8h.
- ESRD Patients (CLcr less than 15 mL/min) with or without intermittent HD: 0.75 grams IV q12h.
Storage of Reconstituted Solutions
Reconstituted FETROJA
Upon reconstitution with the appropriate diluent, the reconstituted FETROJA solution in the vial should be immediately transferred and diluted into the infusion bag. Reconstituted FETROJA can be stored for up to 1 hour at room temperature. Discard any unused reconstituted solution.
Diluted FETROJA Infusion Solution
The diluted FETROJA infusion solution in the infusion bag is stable for up to 6 hours at room temperature.
The diluted FETROJA infusion solution in the infusion bag may also be refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours, protected from light; and then the infusion should be completed within 6 hours at room temperature.
FETROJA is a cephalosporin antibacterial drug product consisting of cefiderocol sulfate tosylate for intravenous infusion. Cefiderocol functions as a siderophore
FETROJA 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).
Cefiderocol has no clinically relevant in vitro activity against most Gram-positive bacteria and anaerobic bacteria. Cefiderocol has shown in vitro activity against some isolates of S. maltophilia, and meropenem-resistant Enterobacteriaceae, P. aeruginosa, and A. baumannii. Cefiderocol is active against some P. aeruginosa and A. baumannii isolates resistant to meropenem, ciprofloxacin, and amikacin. Cefiderocol is active against some E. coli isolates containing mcr-1.
Cefiderocol demonstrated in vitro activity against certain Enterobacteriaceae genetically confirmed to contain the following: ESBLs (TEM, SHV, CTX-M, oxacillinase [OXA]), AmpC, AmpC-type ESBL (CMY), serine-carbapenemases (such as KPC, OXA-48), and metallo-carbapenemases (such as NDM and VIM). Cefiderocol demonstrated in vitro activity against certain P. aeruginosa genetically confirmed to contain VIM, GES, AmpC and certain A. baumannii containing OXA-23, OXA-24/40, OXA-51, OXA-58. Cefiderocol has demonstrated in vitro activity against some K. pneumoniae isolates with OmpK35/36 porin deletion and some isolates of P. aeruginosa with OprD porin deletion.
INDICATIONS AND USAGE 
1.1 Complicated Urinary Tract Infections (cUTI), Including Pyelonephritis
FETROJA® is indicated in 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.
Approval of this indication is based on limited clinical safety and efficacy data for FETROJA.
1.2 Usage
To reduce the development of drug-resistant bacteria and maintain the effectiveness of FETROJA and other antibacterial drugs, FETROJA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
FETROJA is contraindicated in patients with a known history of severe hypersensitivity to cefiderocol or other beta-lactam antibacterial drugs, or any other component of FETROJA.
- Increase in All-Cause Mortality in Patients With Carbapenem-Resistant Gram-Negative Bacterial Infections: An increase in all-cause mortality was observed in FETROJA-treated patients compared to those treated with best available therapy (BAT). Reserve FETROJA for use in patients who have limited or no alternative treatment options for the treatment of cUTI. Closely monitor the clinical response to therapy in patients with cUTI. (5.1)
- Hypersensitivity Reactions: Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterial drugs. Hypersensitivity was observed with FETROJA. Cross-hypersensitivity may occur in patients with a history of penicillin allergy. If an allergic reaction occurs, discontinue FETROJA. (5.2)
- Clostridioides difficile-Associated Diarrhea (CDAD): CDAD has been reported with nearly all systemic antibacterial agents, including FETROJA. Evaluate if diarrhea occurs. (5.3)
- Seizures and Other Central Nervous System (CNS) Adverse Reactions: CNS adverse reactions such as seizures have been reported with FETROJA. If focal tremors, myoclonus, or seizures occur, evaluate patients to determine whether FETROJA should be discontinued. (5.4)
The most frequently occurring adverse reactions in greater than or equal to 2% of patients treated with FETROJA were diarrhea, infusion site reactions, constipation, rash, candidiasis, cough, elevations in liver tests, headache, hypokalemia, nausea, and vomiting.
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. Drug information
2.1 Recommended Dosage
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 [see DOSAGE AND ADMINISTRATION (2.2)].
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.
2.2 Dosage Adjustments In Patients With Renal Impairment (CLcr Less Than 60 mL/min and CLcr 120 mL/min or Greater)
Dosage Adjustments in Patients with CLcr Less Than 60 mL/min
Dosage adjustment of FETROJA is recommended in patients with CLcr less than 60 mL/min (Table 1). For patients with fluctuating renal function, monitor CLcr and adjust dosage accordingly.
| Estimated Creatinine Clearance (CLcr)* | Dose | Frequency | Infusion Time |
|---|---|---|---|
| Patients with CLcr 30 to 59 mL/min | 1.5 grams | Every 8 hours | 3 hours |
| Patients with CLcr 15 to 29 mL/min | 1 gram | Every 8 hours | 3 hours |
| ESRD Patients (CLcr less than 15 mL/min) with or without intermittent HD† | 0.75 gram | Every 12 hours | 3 hours |
- *CLcr = creatinine clearance estimated by Cockcroft-Gault equation.
- †Cefiderocol is removed by hemodialysis (HD); thus, complete hemodialysis (HD) at the latest possible time before the start of cefiderocol dosing.
ESRD = end-stage renal disease; HD = hemodialysis.
Dosage Adjustments in Patients with CLcr 120 mL/min or Greater
For patients with CLcr greater than or equal to 120 mL/min, FETROJA 2 grams administered every 6 hours by IV infusion over 3 hours is recommended.
2.3 Preparation of FETROJA Solution for Administration
FETROJA is supplied as a sterile, lyophilized powder that must be reconstituted and subsequently diluted using aseptic technique prior to intravenous infusion.
Preparation of Doses
Reconstitute the powder for injection in the FETROJA vial with 10 mL of either 0.9% sodium chloride injection, USP or 5% dextrose injection, USP and gently shake to dissolve. Allow the vial(s) to stand until the foaming generated on the surface has disappeared (typically within 2 minutes). The final volume of the reconstituted solution will be approximately 11.2 mL. The reconstituted solution is for intravenous infusion only after dilution in an appropriate infusion solution.
To prepare the required doses, withdraw the appropriate volume of reconstituted solution from the vial according to Table 2 below. Add the withdrawn volume to an infusion bag containing 100 mL of 0.9% sodium chloride injection, USP or 5% dextrose injection, USP [see DOSAGE AND ADMINISTRATION (2.4)].
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. FETROJA infusions are clear, colorless solutions. Discard any unused FETROJA solution in the vial (see TABLE 2).
| FETROJA Dose | Number of 1-gram FETROJA Vials to be Reconstituted | Volume to Withdraw from Reconstituted Vial(s) | Total Volume of FETROJA Reconstituted Solution for Further Dilution into at Least 100 mL |
|---|---|---|---|
| 2 grams | 2 vials | 11.2 mL (entire contents) of each vial | 22.4 mL |
| 1.5 grams | 2 vials | 11.2 mL (entire contents) of first vial AND 5.6 mL from second vial | 16.8 mL |
| 1 gram | 1 vial | 11.2 mL (entire contents) | 11.2 mL |
| 0.75 gram | 1 vial | 8.4 mL | 8.4 mL |
2.4 Drug Compatibility
FETROJA solution for administration is compatible with:
- 0.9% sodium chloride injection, USP
- 5% dextrose injection, USP
The compatibility of FETROJA solution for administration with solutions containing other drugs or other diluents has not been established.
2.5 Storage of Reconstituted Solutions
Reconstituted FETROJA
Upon reconstitution with the appropriate diluent, the reconstituted FETROJA solution in the vial should be immediately transferred and diluted into the infusion bag. Reconstituted FETROJA can be stored for up to 1 hour at room temperature. Discard any unused reconstituted solution.
Diluted FETROJA Infusion Solution
The diluted FETROJA infusion solution in the infusion bag is stable for up to 6 hours at room temperature.
The diluted FETROJA infusion solution in the infusion bag may also be refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours, protected from light; and then the infusion should be completed within 6 hours at room temperature.
FETROJA 1 gram is supplied as a white to off-white, sterile, lyophilized powder for reconstitution in single-dose, clear glass vials; each vial contains 1 gram of cefiderocol.
FETROJA 1 gram (cefiderocol) for injection is supplied as a white to off-white sterile lyophilized powder for reconstitution in single-dose, clear glass vials (NDC 59630-266-01) sealed with a rubber stopper (not made with natural rubber latex) and an aluminum seal with flip-off cap. Each vial is supplied in cartons containing 10 single-dose vials.
NDC 59630-266-10 FETROJA (cefiderocol) 1 gram/vial, 10 vials/carton
16.2 Storage and Handling
FETROJA vials should be stored refrigerated at 2°C to 8°C (36°F to 46°F). Protect from light. Store in the carton until time of use. Reconstituted and diluted solutions of FETROJA can be stored at room temperature
