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Cefiderocol

Medically reviewed by Drugs.com. Last updated on July 26, 2020.

Pronunciation

(SEF i DER oh kol)

Index Terms

  • Cefiderocol Sulfate Tosylate
  • Fetroja
  • S-649266

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous [preservative free]:

Fetroja: 1 g (1 ea)

Brand Names: U.S.

  • Fetroja

Pharmacologic Category

  • Antibiotic, Cephalosporin

Pharmacology

Cefiderocol is a siderophore cephalosporin. A catechol side chain promotes formation of chelated complexes with ferric iron, allowing use of iron transport systems to deliver cefiderocol across the outer membrane of gram-negative bacilli. The cephalosporin moiety binds to penicillin-binding proteins which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis.

Distribution

Vd: 18 (±3.36) L.

Metabolism

Minimal.

Excretion

Urine: 98.6% (90.6% as unchanged drug); feces: 2.8%.

Half-Life Elimination

2 to 3 hours.

Protein Binding

40% to 60% (primarily to albumin).

Special Populations: Renal Function Impairment

AUC increased 1.37-, 2.35-, 3.21-, and 4.69-fold in patients with CrCl 60 to 89 mL/minute, 30 to 59 mL/minute, 15 to 29 mL/minute, and <15 mL/minute, respectively, compared to patients with CrCl 90 to 119 mL/minute. Patients with CrCl ≥120 mL/minute experience increased cefiderocol clearance. Approximately 60% of cefiderocol is removed by a 3- to 4-hour hemodialysis session.

Use: Labeled Indications

Pneumonia, hospital-acquired and ventilator-associated: Treatment of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia, caused by the following susceptible gram-negative microorganisms: Acinetobacter baumannii complex, Escherichia coli, Enterobacter cloacae complex, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Serratia marcescens, in patients ≥18 years of age.

Urinary tract infection, complicated (including pyelonephritis): Treatment of complicated urinary tract infections, including pyelonephritis, caused by the following susceptible gram-negative microorganisms: E. coli, K. pneumoniae, Proteus mirabilis, P. aeruginosa, and E. cloacae complex, in patients ≥18 years of age.

Contraindications

Severe hypersensitivity to cefiderocol, other beta-lactam antibacterial drugs, or any other component of the formulation.

Dosing: Adult

Pneumonia, hospital-acquired and ventilator-associated: IV: 2 g every 8 hours for 7 to 14 days. Note: For patients with CrCl ≥120 mL/minute, increase dose to 2 g every 6 hours.

Urinary tract infection, complicated (including pyelonephritis): IV: 2 g every 8 hours for 7 to 14 days. Note: For patients with CrCl ≥120 mL/minute, increase dose to 2 g every 6 hours.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

IV: Reconstitute 1 g vial with 10 mL of NS or D5W; gently shake to dissolve. Allow the vial to stand until the foaming generated on the surface has disappeared (typically within 2 minutes). The final volume of the reconstituted solution is ~11.2 mL; withdraw appropriate volume from reconstituted vial and add to 100 mL infusion bag of NS or D5W.

Administration

IV: Administer by intermittent IV infusion over 3 hours.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Protect from light. Reconstituted vials may be stored at room temperature for ≤1 hour. As of July 2020, the manufacturer's labeling states diluted solutions for infusion may be stored at room temperature for ≤6 hours or at 2°C to 8°C (36°F to 46°F) for ≤24 hours (and protected from light); prior to July 2020, the manufacturer's labeling only stated storage at room temperature for ≤4 hours was acceptable. Infusion should be completed within 6 hours after removal from refrigeration.

Drug Interactions

Aminoglycosides: Cephalosporins may enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. Monitor therapy

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Probenecid: May increase the serum concentration of Cephalosporins. Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Consider therapy modification

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Consider therapy modification

Vitamin K Antagonists (eg, warfarin): Cephalosporins may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Test Interactions

May result in false-positive urine dipstick tests (eg, urine protein, ketones, occult blood).

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

1% to 10%:

Cardiovascular: Atrial fibrillation (<2%), bradycardia (<2%), cardiac failure (<2%), peripheral edema (<2%)

Central nervous system: Headache (2%), insomnia (<2%), restlessness (<2%), seizure (<2%)

Dermatologic: Skin rash (3%), pruritus (<2%)

Endocrine & metabolic: Hypokalemia (2%), hypervolemia (<2%), hypocalcemia (<2%)

Gastrointestinal: Diarrhea (4%), constipation (3%), nausea (2%), vomiting (2%), abdominal pain (<2%), biliary colic (<2%), cholecystitis (<2%), cholelithiasis (<2%), Clostridioides difficile associated diarrhea (<2%), decreased appetite (<2%), dysgeusia (<2%), stomatitis (<2%), xerostomia (<2%)

Genitourinary: Finding of blood in urine (<2%)

Hematologic & oncologic: Increased INR (<2%), prolonged prothrombin time (<2%), thrombocythemia (<2%)

Hepatic: Increased liver enzymes (2%)

Hypersensitivity: Drug-induced hypersensitivity reaction (<2%)

Infection: Candidiasis (2%)

Local: Infusion site reaction (4%)

Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (<2%)

Respiratory: Cough (2%), dyspnea (<2%), pleural effusion (<2%)

Miscellaneous: Fever (<2%)

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Serious, sometimes fatal, hypersensitivity reactions may occur. Use caution in patients with a history of penicillin, cephalosporin, or other beta-lactam sensitivity; cross-hypersensitivity may occur. If a hypersensitivity reaction occurs, discontinue therapy and institute supportive measures.

• Neurotoxicity: Neurological reactions have been reported with cephalosporins, including encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia, and nonconvulsive status epilepticus. Risk may be increased in patients with a history of seizure disorders and/or in the presence of renal impairment; ensure dose adjusted for renal function. If neurotoxicity occurs, obtain a neurological evaluation to determine if cefiderocol should be discontinued.

• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including Clostridioides (formerly Clostridium) difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.

Disease-related concerns:

• Renal impairment: Use with caution in patients with renal impairment (CrCl ≤60 mL/minute); dosage adjustments recommended. May increase risk of neurotoxicity.

• Seizure disorders: Use with caution in patients with a history of seizure disorder.

Other warnings/precautions:

• Appropriate use: Increased mortality was seen among critically ill patients receiving cefiderocol compared to recipients of best available therapy (most often containing colistin) for the treatment of carbapenem-resistant gram-negative bacterial infections, including pneumonia, bloodstream infection, and sepsis. The cause of the increase in mortality has not been established; closely monitor response to therapy in patients treated with cefiderocol.

Monitoring Parameters

Monitor renal function. Observe for signs and symptoms of anaphylaxis during first dose.

Pregnancy Considerations

In general, an increase in most types of birth defects or adverse maternal or fetal outcomes was not found following exposure to cephalosporins.

Patient Education

What is this drug used for?

• It is used to treat a urinary infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Diarrhea

• Injection site irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat

• Confusion

• Seizures

• Abnormal movements

• Extra muscle action

• Tremors

• Thrush

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine’s uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.