Fetcroja

1 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX I 

 

SUMMARY OF PRODUCT CHARACTERISTICS 



 

2 

This medicinal product is subject to additional monitoring. This will allow quick identification of 

new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 

See section 4.8 for how to report adverse reactions. 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Fetcroja 1 g powder for concentrate for solution for infusion 

 

 

2. QUALITATIVE AND QUANTITATIVE COMPOSITION 

 

Each vial contains cefiderocol sulfate tosylate equivalent to 1 g of cefiderocol. 

 

Excipient with known effect 

 

Each vial contains 7.64 mmol of sodium (approximately 176 mg). 

 

For the full list of excipients, see section 6.1. 

 

 

3. PHARMACEUTICAL FORM 

 

Powder for concentrate for solution for infusion (powder for concentrate). 

 

White to off-white powder. 

 

 

4. CLINICAL PARTICULARS 

 

4.1 Therapeutic indications 

 

Fetcroja is indicated for the treatment of infections due to aerobic Gram-negative organisms in adults 

with limited treatment options (see sections 4.2, 4.4 and 5.1). 

 

Consideration should be given to official guidance on the appropriate use of antibacterial agents.  

 

4.2 Posology and method of administration 

 

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. 

 

Posology 

 

Table 1 Recommended dose of Fetcroja
1
 for patients with a creatinine clearance (CrCL) 

≥ 90 mL/min2 

Renal function Dose 
Frequency Duration of 

treatment 

Normal renal function 2 g Every 8 hours Duration in 

accordance with the 

site of infection
3
 

(CrCL ≥90 to < 120 mL/min) 

Augmented renal clearance 2 g Every 6 hours Duration in 

accordance with the 

site of infection
3
 

(CrCL ≥ 120 mL/min) 

1
To be used in combination with antibacterial agents active against anaerobic pathogens and/or Gram-positive 



 

3 

pathogens when these are known or suspected to be contributing to the infectious process. 

2
As calculated using the Cockcroft-Gault formula. 

3
e.g. for complicated urinary tract infections including pyelonephritis and complicated intra-abdominal infections 

the recommended treatment duration is 5 to 10 days. For hospital-acquired pneumonia including ventilator-

associated pneumonia the recommended treatment duration is 7 to 14 days. Treatment up to 21 days may be 

required. 

 

Special populations 

 

Renal impairment 

 

Table 2 Recommended dose of Fetcroja for patients with a CrCl < 90 ml/min
1
 

Renal function Dose Frequency 

Mild renal impairment 2 g Every 8 hours 

(CrCL ≥60 to < 90 mL/min) 
Moderate renal impairment 1.5 g Every 8 hours 

(CrCL ≥30 to < 60 mL/min) 

Severe renal impairment 1 g Every 8 hours 

(CrCL ≥15 to < 30 mL/min) 
End stage renal disease 0.75 g Every 12 hours 

 (CrCL < 15 mL/min)  

Patient with intermittent haemodialysis
2
 0.75 g Every 12 hours 

 

1
As calculated using the Cockcroft-Gault formula. 

2
As cefiderocol is removed by haemodialysis, administer cefiderocol at the earliest possible time after 

completion of haemodialysis on haemodialysis days. 

 

Hepatic impairment 

No dose adjustment is required in patients with hepatic impairment (see section 5.2). 

 

Elderly population 

No dosage adjustment is required (see section 5.2). 

 

Paediatric population 

The safety and efficacy of Fetcroja in children below 18 years of age has not yet been established. No 

data are available. 

 

Method of administration 

 

Intravenous use. 

Fetcroja is administered by intravenous infusion over 3 hours. 

 

For instructions on reconstitution and dilution of the medicinal product before administration, see 

section 6.6. 

 

4.3 Contraindications 

 

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 

 

Hypersensitivity to any cephalosporin antibacterial medicinal product. 

 



 

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Severe hypersensitivity (e.g. anaphylactic reaction, severe skin reaction) to any other type of beta-

lactam antibacterial agent (e.g. penicillins, monobactams or carbapenems). 

 

4.4 Special warnings and precautions for use 

 

Hypersensitivity reactions 

 

Hypersensitivity has been reported with cefiderocol (see sections 4.3 and 4.8). 

 

Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam 

antibacterial medicinal products may also be hypersensitive to cefiderocol. Before initiating therapy 

with Fetcroja, careful inquiry should be made concerning previous hypersensitivity reactions to beta-

lactam antibiotics (see section 4.3). 

 

If a severe allergic reaction occurs, treatment with Fetcroja must be discontinued immediately and 

adequate emergency measures must be initiated. 

 

Clostridioides difficile-associated diarrhoea 

 

Clostridioides difficile-associated diarrhoea (CDAD) has been reported with cefiderocol (see section 

4.8). The condition can range in severity from mild diarrhoea to fatal colitis and should be considered 

in patients who present with diarrhoea during or subsequent to the administration of cefiderocol. 

Discontinuation of therapy with cefiderocol and the use of supportive measures together with the 

administration of specific treatment for Clostridioides difficile should be considered. Medicinal 

products that inhibit peristalsis should not be given. 

 

Seizure 

 

Cephalosporins have been implicated in triggering seizures. Patients with known seizure disorders 

should continue anticonvulsant therapy. Patients who develop focal tremors, myoclonus, or seizures 

should be evaluated neurologically and placed on anticonvulsant therapy if not already instituted. If 

necessary, the dose of cefiderocol should be adjusted based on renal function (see section 4.2). 

Alternatively, cefiderocol should be discontinued. 

 

Limitations of the clinical data 

 

In clinical trials, cefiderocol has only been used to treat patients with the following types of infection: 

complicated urinary tract infections (cUTI); hospital-acquired pneumonia (HAP), ventilator-associated 

pneumonia (VAP), healthcare-associated pneumonia (HCAP); sepsis and patients with bacteraemia 

(some with no identified primary focus of infection). 

 

The use of cefiderocol to treat patients with infections due to Gram-negative aerobic pathogens who 

have limited treatment options is based on pharmacokinetic-pharmacodynamic analyses for 

cefiderocol and on limited clinical data from a randomized clinical trial in which 80 patients were 

treated with Fetcroja and 38 patients were treated with best available therapy for infections caused by 

carbapenem-resistant organisms. 

 

All-cause mortality in patients with infections due to carbapenem-resistant Gram-negative bacteria 

 

A higher all-cause mortality rate was observed in patients treated with cefiderocol as compared to best 

available therapy (BAT) in a randomised, open-label trial in critically-ill patients with infections 

known or suspected to be due to carbapenem-resistant Gram-negative bacteria. The higher day 28 all-

cause mortality rate with cefiderocol occurred in patients treated for nosocomial pneumonia, 

bacteraemia and/or sepsis [25/101 (24.8%) vs. 9/49 (18.4%) with BAT; treatment difference 6.4%, 

95% CI (-8.6, 19.2)]. All-cause mortality remained higher in patients treated with cefiderocol through 

end-of-study [34/101 (33.7%) vs. 9/49 (18.4%) with BAT; treatment difference 15.3%, 95% CI (-0.2, 

28.6)]. The cause of the increase in mortality has not been established. In the cefiderocol group there 



 

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was an association between mortality and infection with Acinetobacter spp., which accounted for the 

majority of infections due to non-fermenters. In contrast, mortality was not higher in cefiderocol vs. 

BAT patients with infections due to other non-fermenters. 

 

Spectrum of activity of cefiderocol 

 

Cefiderocol has little or no activity against the majority of Gram-positive organisms and anaerobes 

(see section 5.1). Additional antibacterial medicinal products should be used when these pathogens are 

known or suspected to be contributing to the infectious process. 

 

Non-susceptible organisms 

 

The use of cefiderocol may result in the overgrowth of non-susceptible organisms, which may require 

interruption of treatment or other appropriate measures. 

 

Renal function monitoring 

 

Renal function should be monitored regularly as dose adjustment may be needed during the course of 

therapy. 

 

Drug/laboratory test interactions 

 

Cefiderocol may result in false-positive results in urine dipstick tests (urine protein, ketones, or occult 

blood). Alternative methods of testing should be used by the clinical laboratories to confirm positive 

tests. 

 

Antiglobulin test (Coombs test) seroconversion 

 

A positive direct or indirect Coombs test may develop during treatment with cefiderocol. 

 

Controlled sodium diet 

 

Each 1 g vial contains 7.64 mmol of sodium (approximately 176 mg).  

 

Each 2 g dose of cefiderocol, when reconstituted with 100 mL of 0.9% sodium chloride injection, 

provides 30.67 mmol (705 mg) of sodium and is approximately 35% of the WHO adult recommended 

maximum daily dietary intake. The total daily dose (2 g administered 3 times a day) of sodium from 

cefiderocol therapy is 2.1 g, just greater than the WHO recommend daily maximum of 2 g sodium for 

an adult. 

 

When reconstituted in 100 mL of 5% dextrose injection each 2 g dose of cefiderocol provides 

15.28 mmol (352 mg) of sodium. The total daily sodium dose (2 g administered 3 times a day) from 

cefiderocol reconstituted in 5% dextrose injection is 1,056 mg which is approximately 53% of the 

WHO adult recommended maximum daily dietary intake of 2 g sodium. 

 

4.5 Interaction with other medicinal products and other forms of interaction 

 

Cefiderocol induces CYP3A4 in vitro. Therefore, the metabolism of co-administered medicinal 

products that are substrates of CYP3A4 can increase and lead to decreased systemic exposure of these 

medicinal products. If cefiderocol is administered together with substrates of CYP3A4, the patients 

should be monitored for decreased efficacy of the concomitant drug. 

 

As the in vitro CYP3A4 induction by cefiderocol is PXR mediated, other PXR inducible proteins may 

also be induced, for example the CYP2C family and PgP. The clinical relevance of this induction is 

unknown. As a consequence, if cefiderocol is administered together with substrates of the CYP2C 

family or PgP, the patients should be monitored for decreased efficacy of the concomitant drug. 

 



 

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Based on in vitro studies and one phase 1 clinical evaluation no significant drug-drug interactions are 

anticipated between cefiderocol and substrates or inhibitors of cytochrome P450 enzymes (CYPs) or 

gut, renal or hepatic drug transporters (see section 5.2). 

 

4.6 Fertility, pregnancy and lactation 

 

Pregnancy 

 

There are no or limited amount of data (less than 300 pregnancy outcomes) from the use of cefiderocol 

sodium in pregnant women. Animal studies do not indicate direct or indirect harmful effects with 

respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid 

the use of Fetcroja during pregnancy. 

 

Breast-feeding 

 

It is unknown whether Fetcroja/metabolites are excreted in human milk. A decision must be made 

whether to discontinue breast-feeding or to discontinue/abstain from Fetcroja therapy taking into 

account the benefit of breast feeding for the child and the benefit of therapy for the woman. 

 

Fertility 

 

The effect of cefiderocol on fertility in humans has not been studied. Based on preclinical data, from a 

study with sub-clinical exposure, there is no evidence that Fetcroja has an effect on male or female 

fertility (see section 5.3). 

 

4.7 Effects on ability to drive and use machines 

 

Fetcroja has no or negligible influence on the ability to drive and use machines. 

 

4.8 Undesirable effects 

 

Summary of the safety profile 

 

The most common adverse reactions were diarrhoea (8.2%), vomiting (3.6%), nausea (3.3%) and 

cough (2%).  

 

Tabulated list of adverse reactions 

 

The following adverse reactions have been reported with cefiderocol during clinical studies (Table 3). 

Adverse reactions are classified according to frequency and System Organ Class (SOC). Frequency 

categories are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to 
<1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000); not known (cannot be estimated from the 
available data). Within each System Organ Class, undesirable effects are presented in order of 

decreasing seriousness. 

 

Table 3  Tabulated list of adverse reactions  

System organ 

class  

Common Uncommon 

(≥1/100 to <1/10) (≥1/1,000 to <1/100) 
Infections and 

infestations 

Candidiasis including oral candidiasis, 

vulvovaginal candidiasis, candiduria and 

candida infection, 

Clostridioides difficile colitis including 

pseudomembranous colitis and 

Clostridioides difficile infection 

 

Immune System 

Disorders 

 Hypersensitivity including skin 

reactions and Pruritus 



 

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Respiratory, 

thoracic and 

mediastinal 

disorders 

Cough   

Gastrointestinal 

disorders 

 

Diarrhoea, Nausea, Vomiting  

Skin and 

subcutaneous 

tissue disorders 

Rash including rash macular, rash maculo-

papular, rash erythematous and drug 

eruption 

 

General 

disorders and 

administration 

site conditions 

 

Infusion site reaction including infusion 

site pain, injection site pain, infusion site 

erythema and injection site phlebitis 

 

Investigations Alanine aminotransferase  increased, 

Gamma-glutamyltransferase  increased, 

Aspartate aminotransferase  increased, 

Hepatic function abnormal including liver 

function test increased, hepatic enzyme 

increased, transaminases increased and 

liver function test abnormal 

 

 

 

Reporting of suspected adverse reactions 

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 

allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 

professionals are asked to report any suspected adverse reactions via the national reporting system 

listed in Appendix V. 

 

4.9 Overdose 

 

There is no information on clinical signs and symptoms associated with an overdose of cefiderocol.  

 

In the event of overdose, patients should be monitored and treatment discontinuation and general 

supportive treatment should be considered.  

 

Approximately 60% of cefiderocol is removed by a 3- to 4-hour haemodialysis session. 

 

 

5. PHARMACOLOGICAL PROPERTIES 

 

5.1  Pharmacodynamic properties 

 

Pharmacotherapeutic group: Antibacterials for systemic use. ATC code: J01DI04 

 

Mechanism of action 

 

Cefiderocol is a siderophore cephalosporin. In addition to passive diffusion through outer membrane 

porin channels, cefiderocol is able to bind to extracellular free iron via its siderophore side chain, 

allowing active transport into the periplasmic space of Gram-negative bacteria through siderophore 

uptake systems. Cefiderocol subsequently binds to penicillin binding proteins (PBPs), inhibiting 

bacterial peptidoglycan cell wall synthesis which leads to cell lysis and death. 

 

Resistance 

 

Mechanisms of bacterial resistance that may lead to resistance to cefiderocol include mutant or 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

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acquired PBPs; beta-lactamase enzymes with ability to hydrolyse cefiderocol; mutations affecting 

regulation of bacterial iron uptake; mutations in siderophore transport proteins; overexpression of 

native bacterial siderophores. 

 

The in vitro antibacterial activity effect of cefiderocol against normally susceptible species is not 

affected by the majority of beta-lactamases, including metallo-enzymes. Due to the siderophore-

mediated mode of cell entry, the in vitro activity of cefiderocol activity is generally less affected by 

porin loss or efflux-mediated resistance compared to many other beta-lactam agents. 

 

Cefiderocol has little or no activity against Gram-positive or anaerobic bacteria due to intrinsic 

resistance. 

 

Antibacterial activity in combination with other antibacterial agents 

 

In vitro studies demonstrated no antagonism between cefiderocol and amikacin, 

ceftazidime/avibactam, ceftolozane/tazobactam, ciprofloxacin, clindamycin, colistin, daptomycin, 

linezolid, meropenem, metronidazole, tigecycline, or vancomycin. 

 

Susceptibility testing breakpoints 

 

Minimum Inhibitory Concentration (MIC) breakpoints established by the European Committee on 

Antimicrobial Susceptibility Testing (EUCAST) for cefiderocol are as follows: 

 

 Minimum inhibitory concentrations (mg/L) 

Organisms Susceptible Resistant 

Enterobacterales ≤2 >2 
Pseudomonas aeruginosa ≤2 >2 

 

Pharmacokinetic/pharmacodynamic relationship 

 

The time that unbound plasma concentrations of cefiderocol exceeds the minimum inhibitory 

concentration (%fT>MIC) against the infecting organism has been shown to best correlate with efficacy. 

 

Antibacterial activity against specific pathogens 

 

In-vitro studies suggest that the following pathogens would be susceptible to cefiderocol in the 

absence of acquired mechanisms of resistance: 

 

Aerobic Gram-negative organisms 

Achromobacter spp. 

Acinetobacter baumannii complex 

Burkholderia cepacia complex 

Citrobacter freundii complex 

Citrobacter koseri 

Escherichia coli 

Enterobacter cloacae complex 

Klebsiella (Enterobacter) aerogenes 

Klebsiella pneumoniae 

Klebsiella oxytoca 

Morganella morganii 

Proteus mirabilis 

Proteus vulgaris 

Providencia rettgeri 

Serratia spp. 

Pseudomonas aeruginosa 

Serratia marcescens 



 

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Stenotrophomonas maltophilia 

 

In vitro studies indicate that the following species are not susceptible to cefiderocol: 

 

Aerobic Gram-positive organisms 

Anaerobic organisms 

 

Paediatric population 

 

The European Medicines Agency has deferred the obligation to submit the results of studies with 

Fetcroja in one or more subsets of the paediatric population in the treatment of infections due to 

aerobic Gram-negative bacteria (see section 4.2 for information on paediatric use). 

 

5.2 Pharmacokinetic properties 

 

After multiple dose administration of cefiderocol, there is no accumulation of cefiderocol administered 

every 8 hours in healthy adult subjects with normal renal function. 

 

Distribution 

 

The binding of cefiderocol to human plasma proteins, primarily albumin, is in the range of 40 to 60%, 

the geometric mean (CV%) volume of distribution during the terminal phase of cefiderocol in healthy 

adult subjects (n = 43) after intravenous administration of a single 2 g dose of cefiderocol was 18.0 L 

(18.1%), similar to extracellular fluid volume. 

 

Biotransformation 

 

After administration of a single 1 g dose of [
14

C]-labelled cefiderocol infused over 1 hour, cefiderocol 

accounted for 92.3% of the plasma AUC for total radioactivity. The most predominant metabolite, 

pyrrolidine chlorobenzamide (PCBA, which is a degradation product of cefiderocol), accounted for 

4.7% of the plasma AUC for total radioactivity, while other more minor metabolites each accounted 

for < 2% of the plasma AUC for total radioactivity. 

 

Interaction with other medicinal products. 

Co-administration with 2 g doses of cefiderocol given every 8 hours did not affect the 

pharmacokinetics of furosemide (a OAT1 and OAT3 substrate) or metformin (a OCT1, OCT2, and 

MATE2-K substrate). Co-administration with 2 g doses of cefiderocol given every 8 hours increased 

rosuvastatin (a OATP1B3 substrate) AUC by 21%, which was considered not to be clinically 

meaningful. 

 

Elimination 

 

The terminal elimination half-life in healthy adult subjects was 2 to 3 hours. The geometric mean 

(%CV) of clearance of cefiderocol in healthy subjects is estimated to be 5.18 (17.2%) L/hr. 

Cefiderocol is primarily eliminated by the kidneys. After administration of a single 1 g dose of [
14

C]-

labelled cefiderocol infused over 1 hour, the amount of total radioactivity excreted in urine was 98.6% 

of the administered dose, with 2.8% of the administered dose excreted in faeces. The amount of 

unchanged cefiderocol excreted in urine was 90.6% of the administered dose.  

 

Linearity/non-linearity 

 

Cefiderocol exhibits linear pharmacokinetics within the dose range of 100 mg to 4000 mg. 

 

Special populations 

 

In a population pharmacokinetic analysis, no clinically relevant effect on the pharmacokinetics of 

cefiderocol was observed with respect to age, gender or race. 



 

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Paediatric population 

Pharmacokinetic studies have not been performed with cefiderocol in infants and children under 18 

years of age (see section 4.2). 

 

Renal impairment 

The pharmacokinetics of cefiderocol after administration of a single 1 g dose was assessed in subjects 

with mild renal impairment (n=8, estimated glomerular filtration rate [eGFR] of 60 to < 90 

mL/min/1.73 m
2
), moderate renal impairment (n=7, eGFR 30 to < 60 mL/min/1.73 m

2
), severe renal 

impairment (n=6, eGFR less than 30 mL/min/1.73 m
2
), end-stage renal disease (ESRD) requiring 

haemodialysis (n=8), and healthy subjects with normal renal function (n=8, estimated creatinine 

clearance of at least 90 mL/min).  The geometric mean ratios (GMR; mild, moderate, severe or ESRD 

without haemodialysis/normal renal function) and 90% confidence intervals (CI) for the AUC of 

cefiderocol were 1.0 (0.8, 1.3), 1.5 (1.2, 1.9), 2.5 (2.0, 3.3) and 4.1 (3.3, 5.2), respectively.  

Approximately 60% of Fetcroja was removed by a 3- to 4-hour haemodialysis session.  

 

The recommended dose adjustments in subjects with varying degrees of renal impairment are expected 

to provide comparable exposures to subjects with normal renal function or mild renal impairment (see 

section 4.2).  

 

Patients with augmented renal clearance 

Simulations using the population PK model demonstrated that the recommended dose adjustment for 

ARC provide exposures, including %T>MIC, of Fetcroja comparable to those in patients with normal 

renal function.  

 

Hepatic impairment 

Hepatic impairment is not expected to alter the elimination of Fetcroja as hepatic 

metabolism/excretion represent a minor pathway of elimination of Fetcroja.  

 

5.3 Preclinical safety data 

 

Non-clinical data reveal no special hazard for humans based on conventional studies of safety 

pharmacology, or genotoxicity. Carcinogenicity studies with cefiderocol have not been conducted. 

 

Cefiderocol was negative for mutagenicity in an in vitro reverse mutation test with bacteria and in the 

in vitro HPRT gene mutation assay in human cells. Positive findings were seen in an in vitro 

chromosomal aberration test in cultured TK6 cells and an in vitro mouse lymphoma assay (MLA). 

There was no evidence of in vivo genotoxicity (rat micronucleus assay and comet assay in rats).  

 

Cefiderocol had no impairment of fertility and early embryonic development in rats treated with 

cefiderocol intravenously up to 1000 mg/kg/day corresponding to a margin to clinical exposure of 0.8. 

There was no evidence of teratogenicity or embryotoxicity in rats or mice that received 1000 

mg/kg/day or 2000 mg/kg/day respectively corresponding to margins to clinical exposure of 0.9 

and 1.3 

 

Cefiderocol had no adverse effects on growth and development, including neurobehavioural function 

in juvenile rats that received 1000 mg/kg/day subcutaneously during postnatal day (PND)7 to PND27, 

or 600 mg/kg/day intravenously from PND28 to PND48. 

 

 

6. PHARMACEUTICAL PARTICULARS 

 

6.1 List of excipients 

 

Sucrose  

Sodium chloride 

Sodium hydroxide (pH adjustment) 

 



 

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6.2 Incompatibilities 

 

This medicinal product must not be mixed with other medicinal products except those mentioned in 

section 6.6. 

 

6.3 Shelf life 

 

Powder 

 

3 years. 

 

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. 

 

Stability of the diluted solution in the infusion bag 

 

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. 

 

From a microbiological point of view, diluted products should be used immediately. 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. The 6-hour period 

at 25°C should be inclusive of the product administration period of 3 hours (see section 4.2). If storing 

the infusion solution in the refrigerator, the infusion bag should be removed and allowed to reach 

room temperature prior to use. 

 

For preparation of solution for administration, see Section 6.6. 

 

6.4 Special precautions for storage 

 

Store in a refrigerator (2°C – 8°C)  
 

Store in the original carton in order to protect from light. 

 

For storage conditions after reconstitution and dilution of the medicinal product, see section 6.3. 

 

6.5 Nature and contents of container 

 

14 mL vial (Type I clear glass vial), chlorobutyl elastomeric stopper, and aluminum seal with a plastic 

flip-off cap. The vials are packed in a cardboard carton. 

 

Pack size of 10 vials. 

 

6.6 Special precautions for disposal and other handling 

 

Each vial is for single use only. 

 

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. The vial(s) should be allowed to stand until 



 

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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). 

 

To prepare the required doses, the appropriate volume of reconstituted solution should be withdrawn 

from the vial according to Table 4. Add the withdrawn volume 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, inspect the resulting diluted drug product solution in the infusion bag visually for particulate 

matter and discoloration prior to use.  Do not use discoloured solutions or solutions with visible 

particles. 

 

Table 4 Preparation of cefiderocol doses 

Cefideroco

l dose 

Number of 1 g 

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 

 

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

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 

 

7. MARKETING AUTHORISATION HOLDER 

 

Shionogi B.V. 

Kingsfordweg 151, 

1043GR Amsterdam 

Netherlands 

 

 

8. MARKETING AUTHORISATION NUMBER(S) 

 

EU/1/20/1434/001 

 

 

 

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 

 

Date of first authorisation: 23 april 2020 

 

 

 



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10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European 

Medicines Agency http://www.ema.europa.eu. 



 

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ANNEX II 

 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 

AND USE 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 

THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 

PRODUCT 

 

 



 

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A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 

 

Name and address of the manufacturer responsible for batch release 

 

ACS Dobfar S.P.A. 

Nucleo Industriale S. Atto 

Localita S. Nicolo a Tordino 

64100 

Teramo 

ITALY 

 

Shionogi B.V. 

Kingsfordweg 151, 

1043GR Amsterdam 

Netherlands 

 

The printed package leaflet of the medicinal product must state the name and address of the 

manufacturer responsible for the release of the concerned batch. 

 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 

 

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 

Characteristics, section 4.2). 

 

 

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  

 

 Periodic safety update reports (PSURs) 
 

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 

reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 

subsequent updates published on the European medicines web-portal. 

 

 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 

 

 Risk Management Plan (RMP) 
 

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 

and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 

and any agreed subsequent updates of the RMP. 

 

An updated RMP should be submitted: 

 At the request of the European Medicines Agency; 
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 

an important (pharmacovigilance or risk minimisation) milestone being reached.  

 

 

 



 

16 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

ANNEX III 

 

LABELLING AND PACKAGE LEAFLET 



 

17 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A. LABELLING 



 

18 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 

 

CARTON 

 

 

1. NAME OF THE MEDICINAL PRODUCT 

 

Fetcroja 1 g powder for concentrate for solution for infusion 

cefiderocol 

 

 

2. STATEMENT OF ACTIVE SUBSTANCE(S) 

 

Each vial contains cefiderocol sulfate tosylate equivalent to 1 g of cefiderocol. 

 

 

3. LIST OF EXCIPIENTS 

 

Contains sodium – see leaflet for further information 
 

 

4. PHARMACEUTICAL FORM AND CONTENTS 

 

Powder for concentrate for solution for infusion 

10 vials 

 

 

5. METHOD AND ROUTE(S) OF ADMINISTRATION 

 

Read the package leaflet before use. 

Intravenous use 

Dilute before use 

 

 

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 

 

Keep out of the sight and reach of children. 

 

 

7. OTHER SPECIAL WARNING(S), IF NECESSARY 

 

 

8. EXPIRY DATE 

 

EXP 

 

 

9. SPECIAL STORAGE CONDITIONS 

 

Store in a refrigerator 

 

Store in the original carton in order to protect from light. 

 

 



 

19 

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 

APPROPRIATE 

 

 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 

 

Shionogi B.V.  

Kingsfordweg 151 

1043GR Amsterdam 

Netherlands 

 

 

12. MARKETING AUTHORISATION NUMBER(S)  

 

EU/1/20/1434/001 

 

 

13. BATCH NUMBER 

 

Lot 

 

 

14. GENERAL CLASSIFICATION FOR SUPPLY 

 

 

15. INSTRUCTIONS ON USE 

 

 

16. INFORMATION IN BRAILLE 

 

Justification for not including Braille accepted. 

 

 

17. UNIQUE IDENTIFIER – 2D BARCODE 
 

2D barcode carrying the unique identifier included. 

 

 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 

 

PC 

SN 

NN 

 



 

20 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 

 

VIAL LABEL 

 

 

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 

 

Fetcroja 1 g powder for concentrate 

cefiderocol 

IV 

 

 

2. METHOD OF ADMINISTRATION 

 

 

3. EXPIRY DATE 

 

EXP 

 

 

4. BATCH NUMBER 

 

Lot 

 

 

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 

 

1 g 

 

 

6. OTHER 

 

 



 

21 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

B. PACKAGE LEAFLET 



 

22 

Package leaflet: Information for the user 

 

Fetcroja 1 g powder for concentrate for solution for infusion 

cefiderocol 

 

This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects, you may get. See the end of section 4 

for how to report side effects.  

 

Read all of this leaflet carefully before you start using this medicine because it contains 

important information for you. 

- Keep this leaflet. You may need to read it again. 

- If you have any further questions, ask your doctor or nurse. 

- If you get any side effects, talk to your doctor or nurse. This includes any possible side effects 

not listed in this leaflet. See section 4. 

 

 

What is in this leaflet 

 

1. What Fetcroja is and what it is used for 

2. What you need to know before you are given Fetcroja 

3. How Fetcroja is used 

4. Possible side effects  

5. How to store Fetcroja  

6. Contents of the pack and other information 

 

 

1. What Fetcroja is and what it is used for 

 

Fetcroja contains the active substance cefiderocol. It is an antibiotic medicine that belongs to a group 

of antibiotics called cephalosporins. Antibiotics help to fight bacteria that cause infections.  

 

Fetcroja is used in adults to treat infections caused by certain types of bacteria when other antibiotics 

cannot be used.  

 

 

2. What you need to know before you are given Fetcroja  

 

Do not use Fetcroja 

 if you are allergic to cefiderocol or any of the other ingredients of this medicine (listed in section 
6); 

 if you are allergic to other antibiotics known as cephalosporins; 
 if you have had a severe allergic reaction to certain antibiotics, such as penicillins or 

carbapenems. This can include severe skin peeling, swelling of the hands, face, feet, lips, tongue 

or throat; or difficulty swallowing or breathing.  

➔ Tell your doctor if any of these apply to you.  

 

Warnings and precautions 

Talk to your doctor or nurse before you are given Fetcroja: 

 if you have ever had any allergic reaction to other antibiotics. See also section above, “Do not 
use Fetcroja”; 

 if you have kidney problems. Your doctor will adjust your dose to ensure you don’t get too much 
or too little medicine; 

 if you suffer from diarrhoea during your treatment; 
 if you are on a low sodium diet; 
 if you have ever had seizures. 



 

23 

➔ Talk to your doctor or nurse before you are given Fetcroja. 

 

New Infection 

Although Fetcroja can fight certain bacteria, there is a possibility that you may get a different infection 

caused by another organism during or after your treatment. Your doctor will monitor you closely for 

any new infections and give you another treatment if necessary. 

 

Blood/laboratory Tests 

Tell your doctor that you are taking Fetcroja if you are going to have any blood/laboratory tests. This 

is because you may get an abnormal result. With something called a “Coombs test” this looks for the 
presence of antibodies that can destroy red blood cells or may be affected by the response of your 

immune system to Fetcroja. Fetcroja may also result in false-positive results in urine dipstick tests 

(urine protein or diabetes markers). 

 

Children and adolescents 

Fetcroja should not be given to children and adolescents under the age of 18. This is because it is not 

known if the medicine is safe to use in these age groups. 

 

Other medicines and Fetcroja 

Tell your doctor or nurse if you are taking, have recently taken or might take any other medicines. 

 

Pregnancy and breast-feeding 

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 

your doctor for advice before taking this medicine. 

 

Driving and using machines 

Fetcroja does not affect your ability to drive or operate machinery. 

 

Fetcroja contains sodium 

This medicine contains 7.64 mmol (176 mg) of sodium per vial. The total daily dose is 2.1 g, just 

greater than the WHO recommend daily maximum of 2 g sodium for an adult. Talk to your doctor 

before you are given Fetcroja if you are on a low sodium diet. 

 

 

3. How Fetcroja is used 

 

Your doctor or nurse will give you this medicine as an infusion (a drip) into your vein over 3 hours, 

three times a day. The usual recommended dose is 2 g. 

 

The number of days you will be given Fetcroja treatment depends on the type of infection you have 

and how well your infection is clearing. 

 

If you get any pain where the Fetcroja infusion goes into your vein, tell your doctor or nurse. 

 

People with kidney problems 

If you have kidney problems, talk to your doctor before you are given Fetcroja. The doctor will adjust 

your dose of Fetcroja. 

 

If you are given more Fetcroja than you should 

Fetcroja will be given to you by a doctor or nurse, so it is unlikely you will be given the wrong dose. 

Tell your doctor or nurse straight away if you think you have been given more Fetcroja than you 

should have. 

 

If you miss a dose of Fetcroja  

If you think you have not been given a dose of Fetcroja, tell your doctor or nurse straight away. 

 

If you have any further questions on the use of this medicine, ask your doctor or nurse. 



 

24 

4. Possible side effects 

 

Like all medicines, this medicine can cause side effects, although not everybody gets them. 

 

Serious side effects 

Tell your doctor straight away if you notice any of the following serious side effects – you may need 
urgent medical treatment: 

 Severe allergic reaction – signs include sudden swelling of your lips, face, throat or tongue; a 
severe rash or other severe skin reactions; difficulty swallowing or breathing. This reaction may be 

life-threatening. 

 Diarrhoea that gets worse or does not go away, or stools that contain blood or mucus. This may 
happen during treatment, or after it has been stopped. If this happens, do not take medicines that 

stop or slow bowel movement. 

➔ Tell your doctor straight away if you notice any of the serious side effects above.  

 

Other side effects 

Tell your doctor or nurse if you notice any of the following side effects. 

 

Common 

(may affect up to 1 in 10 people) 

 Feeling sick (nausea) or being sick (vomiting) 
 Swelling, redness and/or pain around the needle where the medicine is given into a vein 
 Yeast infections e.g. thrush 
 Increase in levels of liver enzymes, shown in blood tests 
 Cough 
 Rash, with small raised bumps 
 Severe gut infection known as Clostridioides difficile colitis. Symptoms include watery diarrhoea, 

abdominal pain, fever, etc. 

 

Uncommon 

(may affect up to 1 in 100 people) 

 Allergy to Fetcroja 
 

Reporting of side effects 

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not 

listed in this leaflet. You can also report side effects directly via the national reporting system listed in 

Appendix V. By reporting side effects, you can help provide more information on the safety of this 

medicine. 

 

 

5. How to store Fetcroja 

 

Keep this medicine out of the sight and reach of children. 

 

Do not use this medicine after the expiry date which is stated on the label. The expiry date refers to the 

last day of that month. 

 

Store unopened vials in a refrigerator (2°C - 8°C). 

 

Store in the original package in order to protect from light. 

 

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 

throw away medicnes you no longer use. These measures will help protect the environment. 

 

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


 

25 

6. Contents of the pack and other information 

 

What Fetcroja contains 

- The active substance is cefiderocol sulfate tosylate, equivalent to 1 g cefiderocol.  

- The other excipients are sucrose, sodium chloride and sodium hydroxide.  

 

What Fetcroja looks like and contents of the pack 

Fetcroja is a white to off-white powder for concentrate for solution for infusion in a vial. It is available 

in packs containing 10 vials. 

 

Marketing Authorisation Holder  

Shionogi B.V.  

Kingsfordweg 151 

1043GR Amsterdam 

Netherlands 

 

Manufacturer 

ACS DOBFAR S.P.A 

Nucleo Industriale S. Atto 

(loc. S. Nicolo’ a Tordino) 
64100 Teramo (TE) 

 

Shionogi B.V.  

Kingsfordweg 151 

1043GR Amsterdam 

Netherlands 

 

For any information about this medicine, please contact the local representative of the Marketing 

Authorisation Holder: 

 

AT, BE, BG, CY, CZ, DK, EE, EL, FI, FR, 

HR, HU, IE, IS,  

LT, LU, LV, MT, NL, NO, PL, PT, RO, SE, 

SI, SK 

Shionogi B.V. Tel/Tel./ Teл./ Tlf/ Tél/ Puh/ 
Sími/ Τηλ: 
+31 (0) 20 703 8327 

contact@shionogi.eu 

 

Deutschland 

Shionogi GmbH 

Tel: + 49 (0)30 2062980 66 

kontakt@shionogi.eu 

 

España 

Shionogi SLU 

Tel: + 34 911 239 258 

contacta@shionogi.eu 

 

Italia 

Shionogi Srl 

Tel: + 39 06 94 805 118 

contattaci@shionogi.eu 

UK 

Shionogi B.V. 

Tel: + 44 (0)20 3053 4190 

contact@shionogi.eu 

 

 

  

This leaflet was last revised in. 

 

 

Other sources of information 

 

Detailed information on this medicine is available on the European Medicines Agency web site: 

http://www.ema.europa.eu  



 

26 

 

--------------------------------------------------------------------------------------------------------------------------- 

 

 

 

The following information is intended for healthcare professionals only: 

 

Each vial is for single use only. 

 

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. 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). 

 

To prepare the required doses, the appropriate volume of reconstituted solution should be withdrawn 

from the vial according to the table below. Add the withdrawn volume 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, inspect the resulting diluted drug product solution in the infusion bag visually for particulate 

matter and discoloration prior to use. Do not use discoloured solutions or solutions with visible 

particles. 

 

Preparation of cefiderocol doses 

Cefiderocol 

dose 

Number of 1 g 

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 

 

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

 

Any unused medicinal product or waste material should be disposed of in accordance with local 

requirements. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET