General

Pronunciation:
sef-i-der-oh-kol

Trade Name(s)

• Fetroja

Ther. Class.

anti-infectives

Pharm. Class.

cephalosporin derivatives

Indications

• Complicated urinary tract infections, including pyelonephritis, in patients who have limited or no alternative treatment options.
• Hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia.

Action

Functions as a siderophore and binds to extracellular free ferric iron. Iron transport systems then deliver cefiderocol across the outer membrane of gram-negative bacilli, where it binds to the bacterial cell wall membrane, causing cell death.

Therapeutic Effect(s):

Bactericidal action against susceptible bacteria.

Spectrum:

Active against the following gram-negative bacilli: Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Serratia marcescens.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Some distribution to tissues.

Metabolism and Excretion: Undergoes minimal metabolism by liver; primarily excreted in urine (99%; 91% as unchanged drug).

Half-life: 2–3 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• Known serious hypersensitivity to cefiderocol or other beta-lactams.

Use Cautiously in:

• Carbapenem-resistant gram-negative bacterial infections, including nosocomial pneumonia, bloodstream infections, and sepsis (↑ risk of mortality);
• Seizure disorders;
• Renal impairment (dosage ↓ required for CCr <60 mL/min);
• OB:  Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:   Safety and effectiveness not established in children;
• Geri:   Dose adjustment may be necessary in older adults for age-related ↓ in renal function.

Adverse Reactions/Side Effects

Derm: rash

EENT: thrush

F and E: hypokalemia

GI: ↑ liver enzymes, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, diarrhea, nausea, vomiting

GU: candiduria, vaginal candidiasis

Local: infusion site reactions

Neuro: headache, SEIZURES

Resp: cough

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

IV (Adults): CCr ≥120 mL/min:  2 g every 6 hr for 7–14 days;  CCr 60–119 mL/min:  2 g every 8 hr for 7–14 days.

Renal Impairment 
IV (Adults): CCr 30–59 mL/min:  1.5 g every 8 hr for 7–14 days;  CCr 15–29 mL/min:  1 g every 8 hr for 7–14 days;  CCr <15 mL/min (with or without hemodialysis):  0.75 g every 12 hr for 7–14 days (in patients receiving hemodialysis, administer dose immediately following hemodialysis session);  Continuous renal replacement therapy:  Effluent flow rate ≥4.1 L/hr: 2 g every 8 hr for 7–14 days; effluent flow rate 3.1–4 L/hr: 1.5 g every 8 hr for 7–14 days; Effluent flow rate 2.1–3 L/hr: 2 g every 12 hr for 7–14 days; Effluent flow rate ≤2 L/hr: 1.5 g every 12 hr for 7–14 days.

Availability

Lyophilized powder for injection: 1 g/vial

Assessment

• Assess for infection (vital signs, appearance of urine, WBC) at beginning of and during therapy. Monitor clinical response to therapy closely.
• Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
• Observe for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Notify health care professional immediately if these occur.
• Obtain specimens for culture and sensitivity prior to therapy. First dose may be given before receiving results.
• Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
• Monitor for seizure activity and other CNS adverse reactions (nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, myoclonia), especially in patients with a history of epilepsy and/or renal impairment. Dose adjustment may be necessary, and patient should receive a neurological evaluation. Institute seizure precautions as indicated.

Lab Test Considerations:

• Monitor renal function during therapy, especially in older adults.
• May cause false-positive results in dipstick tests (urine protein, ketones, occult blood). Use alternate clinical laboratory methods of testing to confirm positive tests.
• May ↑ liver enzymes.
• May cause hypokalemia.

Implementation

Patient/Family Teaching

• Explain purpose and side effects to patient.
• Advise patient to report the signs of superinfection (furry overgrowth on the tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
• Instruct patient to notify health care professional immediately if diarrhea, abdominal cramping, fever, or bloody stools or signs and symptoms of anaphylaxis occur and not to treat with antidiarrheals without consulting health care professional.
• Inform patient of risk of seizures, especially in patient with a seizure disorder. Advise patient to notify health care professional immediately if seizure occurs.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Rep:  Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

Resolution of the signs and symptoms of infection.