Using Fetcroja^®

Dosage
SPECIAL POPULATIONS
RECONSTITUTION AND ADMINISTRATION
STORAGE

ANTIMICROBIAL COVERAGE

In vitro testing of cefiderocol against over 30,000 clinical isolates of aerobic Gram-negative bacteria in multi-national surveillance studies have shown high rates of susceptibility, even against isolates with extreme drug resistance, resistance to carbapenems and other last-line antibiotics.^2–4

It is recommended that Fetcroja^® should be used to treat patients that have limited treatment options only after consultation with a physician with appropriate experience in the management of infectious diseases.¹

Fetcroja^® should be used in combination with antibacterial agents active against anaerobic pathogens and/or Gram-positive pathogens when these are known or suspected to be contributing to the infectious process.¹

Dosage

The recommended dosage and frequency of Fetcroja^® is as follows:¹

Recommended dose of Fetcroja^® for patients with a creatinine clearance (CrCL) ≥90 mL/min*

RENAL FUNCTION	DOSE	FREQUENCY
Normal renal function (CrCL ≥90 to <120 mL/min)	2 g	Every 8 hours
Augmented renal clearance (CrCL ≥120 mL/min)	2 g	Every 6 hours

*As calculated using the Cockcroft-Gault formula.

Duration of treatment should be determined by the site of infection. So, for complicated urinary tract infections – including pyelonephritis and complicated intra-abdominal infections – the recommended treatment duration is 5 to 10 days.¹

For hospital-acquired pneumonia – including ventilator-associated pneumonia – the recommended treatment duration is 7 to 14 days.¹

Treatment up to 21 days may be required.¹

SPECIAL POPULATIONS

Renal impairment¹

Recommended dose of Fetcroja^® for patients with a CrCl <90 mL/min*

RENAL FUNCTION	DOSE	FREQUENCY
Mild renal impairment (CrCL ≥60 to <90 mL/min)	2 g	Every 8 hours
Moderate renal impairment (CrCL ≥30 to <60 mL/min)	1.5 g	Every 8 hours
Severe renal impairment (CrCL ≥15 to <30 mL/min)	1 g	Every 8 hours
End stage renal disease (CrCL <15 mL/min)	0.75 g	Every 12 hours
Patient with intermittent haemodialysis^†	0.75 g	Every 12 hours

^*As calculated using the Cockcroft-Gault formula.

^†As cefiderocol is removed by haemodialysis, administer cefiderocol at the earliest possible time after completion of haemodialysis on haemodialysis days.

Hepatic impairment¹

No dose adjustment is required in patients with hepatic impairment.

Elderly population¹

No dosage adjustment is required.

Paediatic population¹

The safety and efficacy of Fetcroja^® in children below 18 years of age has not yet been established. No data are available.

RECONSTITUTION AND ADMINISTRATION

Fetcroja^® is administered by intravenous infusion over 3 hours.¹

The powder should be reconstituted with 10 mL of either sodium chloride 9 mg/mL (0.9%) solution for injection or 5% dextrose injection taken from the 100 mL bags that will be used to prepare the final infusion solution and should be gently shaken to dissolve.¹

The vial(s) should be allowed to stand until the foaming generated on the surface has disappeared (typically within 2 minutes). The final volume of the reconstituted solution in the vial will be approximately 11.2 mL (caution: the reconstituted solution is not for direct injection).¹

To prepare the required doses, the appropriate volume of reconstituted solution should be withdrawn from the vial according to the following table:

Preparation of cefiderocol doses¹

Cefiderocol dose	Number of 1g cefiderocol vials to be reconstituted	Volume to withdraw from reconstituted vial(s)	Total volume of cefiderocol solution required for further dilution in at least 100 mL of 0.9% sodium chloride injection or 5% dextrose injection
2 g	2 vials	11.2 mL (entire contents) from both vials	22.4 mL
1.5 g	2 vials	11.2 mL (entire contents) from first vial AND 5.6 mL from second vial	16.8 mL
1 g	1 vial	11.2 mL (entire contents)	11.2 mL
0.75 g	1 vial	8.4 mL	8.4 mL

The withdrawn volume should be added to the infusion bag containing the remainder of the 100 mL of sodium chloride 9 mg/mL (0.9%) solution for injection, or 5% dextrose injection.

The resulting diluted drug product solution in the infusion bag should be inspected visually for particulate matter and discoloration prior to use. Discoloured solutions or solutions with visible particles should not be used.¹

Standard aseptic techniques should be used for solution preparation and administration.¹

STORAGE

Vials of Fetcroja^® powder have a shelf life of 3 years. They should be stored in a refrigerator (2 to 8°C) in their original carton in order to protect them from light.¹

Stability of the Diluted Solution in the Infusion Bag

Each vial is intended for single use only – any unused medicinal product or waste material should be disposed of in accordance with local requirements.¹

Chemical, microbiological and physical in-use stability after dilution has been demonstrated for 6 hours at 25°C and for 24 hours at 2 to 8°C protected from light, followed by 6 hours at 25°C.¹

From a microbiological point of view, diluted products should be used immediately.¹

If not used immediately, in-use storage times and conditions are the responsibility of the user and would normally not be longer than 6 hours at 25°C or 24 hours at 2 to 8°C protected from light, followed by 6 hours at 25°C, unless dilution has taken place in controlled and validated aseptic conditions.¹

The 6-hour period at 25°C should be inclusive of the product administration period of 3 hours. If storing the infusion solution in the refrigerator, the infusion bag should be removed and allowed to reach room temperature prior to use.¹

Stability of reconstituted solution in the vial

Chemical and physical in-use stability after reconstitution has been demonstrated for 1 hour at 25°C.

From a microbiological point of view, unless the method of opening/reconstitution precludes the risk of microbial contamination, the reconstituted product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user and should not be more than 1 hour at 25°C

References:

Fetcroja^® (cefiderocol) Summary of Product Characteristics.
Fetcroja^® (cefiderocol) CHMP opinion https://www.ema.europa.eu/en/medicines/human/EPAR/fetcroja#assessment-history-section. Accessed January 2023.
Hackel MA, et al. In vitro activity of the siderophore cephalosporin, cefiderocol, against a recent collection of clinically relevant Gram-negative bacilli from North America and Europe, including carbapenem-nonsusceptible isolates (SIDERO-WT-2014 Study). Antimicrob Agents Chemother. 2017;61:e00093-17.
Thalhammer F. Behandlung multiresistenter Enterobakterien. JATROS Infektiologie & Gastroenterologie-Hepatologie 01/2018,10-12.