Fetroja (cefiderocol sulfate tosylate)

Dosage of cefiderocol sulfate tosylate is expressed in terms of cefiderocol.

Cefiderocol sulfate tosylate is administered by IV infusion.

Cefiderocol sulfate tosylate is commercially available as a white to off-white, sterile, lyophilized powder that must be reconstituted and diluted prior to IV infusion.

Although the drug is compatible with 0.9% sodium chloride injection and 5% dextrose injection, compatibility with other diluents or other drugs has not been established to date.

No dosing information is available for this tab.

In vitro, cefiderocol does not inhibit cytochrome P-450 (CYP) isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, or 3A4. The drug is not an inducer of CYP1A2, 2B6, or 3A4 in vitro.

In vitro, cefiderocol is not an inhibitor of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump transporters, organic anion transporting polypeptide (OATP) 1B1, or multidrug and toxin extrusion (MATE) 1, and is not a substrate of P-gp, BCRP, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 2, MATE1, or MATE2-K.

Concomitant use of cefiderocol did not result in clinically important effects on the pharmacokinetics of furosemide (OAT1 and OAT3 substrate), metformin (OCT1, OCT2, and MATE2-K substrate), or rosuvastatin (OATP1B3 substrate).

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Antibiotics/Fecal Microbiota

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota is a suspension of live bacteria, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota. Antibacterial treatment should be completed for 24 to 72 hours before initiating treatment with fecal microbiota. Do not use antibiotics for up to 8 weeks after fecal microbiota.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota.

Antibiotics/Fecal Microbiota Spores

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Fecal microbiota spores is a suspension of live bacterial spores, which may be compromised by concurrent use of antibiotics.(1)

CLINICAL EFFECTS: Antibiotics may decrease the effectiveness of fecal microbiota spores.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Antibiotics should not be used concurrently with fecal microbiota spores. Antibacterial treatment should be completed for 2 to 4 days before initiating treatment with fecal microbiota spores.(1)

DISCUSSION: Antibiotics may compromise the effectiveness of fecal microbiota spores.

Antimicrobials/Live Typhoid Vaccine

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: The antimicrobial may be active against the organism in the live-vaccine. Antimicrobial therapy may prevent the vaccine organism from replicating enough to trigger an immune response.(1)

CLINICAL EFFECTS: Vaccination may be ineffective.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: Do not give oral typhoid vaccine until 72 hours after the last dose of antimicrobial. If possible, to optimize vaccine effectiveness, do not start antibacterial drugs for 72 hours after the last dose of oral typhoid vaccine. A longer interval should be considered for long-acting antimicrobials, such as azithromycin.(3)

DISCUSSION: Because antimicrobial therapy may prevent sufficient vaccine-organism replication to generate an immune response, the manufacturer of live-attenuated typhoid vaccine and the Centers for Disease Control (CDC) state that the vaccine should not be administered to patients receiving antimicrobial therapy.(1-3)

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known history of severe hypersensitivity to cefiderocol or other beta-lactam antibacterials or other components of the preparation.

There are no contraindication contraindications for this drug.

• Chronic kidney disease stage 3A (moderate) GFR 45-59 ml/min
• Chronic kidney disease stage 3B (moderate) GFR 30-44 ml/min
• Chronic kidney disease stage 4 (severe) GFR 15-29 ml/min
• Clostridioides difficile infection

• Seizure disorder

Patients with HABP/VABP: The most frequent adverse effects reported in 4% or more of patients treated with cefiderocol were elevated liver enzymes, hypokalemia, diarrhea, hypomagnesemia, and atrial fibrillation.

Patients with cUTIs: The most frequently reported adverse effects reported in 2% or more of patients treated with cefiderocol include diarrhea, infusion site reactions, constipation, rash, candidiasis (oral or vulvovaginal candidiasis, candiduria), cough, elevated liver enzymes, headache, hypokalemia, nausea, and vomiting.

More Frequent

• Abnormal hepatic function tests
• Hypokalemia

Rare or Very Rare

• Atrial fibrillation
• Biliary calculus
• Bradycardia
• Cholecystitis
• Chronic heart failure
• Clostridioides difficile infection
• Hypersensitivity drug reaction
• Hypocalcemia
• Pleural effusions
• Seizure disorder
• Thrombocytosis

More Frequent

• Candidiasis
• Constipation
• Cough
• Diarrhea
• Headache disorder
• Injection site sequelae
• Nausea
• Skin rash
• Vomiting

Rare or Very Rare

• Acute abdominal pain
• Anorexia
• Body fluid retention
• Dysgeusia
• Dyspnea
• Eosinophilia
• Fever
• Insomnia
• Nervousness
• Neutropenic disorder
• Peripheral edema
• Pruritus of skin
• Stomatitis
• Urine discoloration
• Xerostomia

No enhanced messaging available.

Safety and efficacy of cefiderocol have not been established in patients younger than 18 years of age.

There are no data available on use of cefiderocol in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Although available studies cannot definitively establish an absence of risk, published data from prospective cohort studies, case series, and case reports over several decades regarding use of cephalosporins in pregnant women have not identified an association between cephalosporin use during pregnancy and major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Available studies have methodologic limitations, including small sample size, retrospective data collection, and inconsistent comparator groups.

In developmental toxicity studies in rats and mice, there was no evidence of embryofetal toxicity, including drug-induced fetal malformations or reductions in fetal viability, when cefiderocol was administered during organogenesis at dosages providing mean AUCs 0.9 times (rats) or 1.3 times (mice) higher than the daily mean plasma exposure reported in patients with cUTIs receiving 2 g of cefiderocol by IV infusion every 8 hours. In a pre- and postnatal development study, cefiderocol was administered IV at doses up to 1 g/kg daily to rats from day 6 of pregnancy until weaning. No adverse effects on parturition, maternal function, or pre- and postnatal development and viability of the pups were observed.

Cefiderocol crosses the placenta in pregnant rats (less than 0.5% of a dose detected in fetuses).

It is not known whether cefiderocol distributes into human milk, affects breast-fed infants, or affects milk production.

Cefiderocol is distributed into milk in rats (peak concentrations in milk are reported to be approximately 6% of peak plasma concentrations).

The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for cefiderocol and any potential adverse effects on the breast-fed child from cefiderocol or from the underlying maternal condition.

Dosage of cefiderocol should be selected with caution in geriatric patients. Dosage adjustments are not required based on age, but dosage should be adjusted based on renal function.

Of the 148 patients with HABP/VABP who received cefiderocol in a clinical trial, 83 (56.1%) were 65 years of age and older, and 40 (27%) were 75 years of age and older. The incidence of adverse reactions reported in patients 65 years of age or older was similar to that reported in younger adults, and the incidence did not differ between those 65 years of age and older and those 75 years of age and older.

Of the 300 patients with cUTIs who received cefiderocol in a clinical trial, 158 (52.7%) were 65 years of age and older, and 67 (22.3%) were 75 years of age and older. No overall differences in safety or efficacy were observed between these patients and younger adults.

Cefiderocol is known to be substantially excreted by the kidneys, and the risk of adverse reactions to the drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when selecting dosage and it may be useful to monitor renal function. Although dosage adjustments are not required based on age, dosage should be based on renal function.