cefiderocol (Rx)

Brand and Other Names:Fetroja
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injection, lyophilized powder of reconstitution

  • 1gram

Urinary Tract Infection

Indicated for complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible gram-negative microorganisms in adults who have limited or no alternative treatment options

2 gram IV q8hr for 7-14 days

Duration of therapy should be dependent on infection severity and patient’s clinical status for up to 14 days

Dosage Modifications

Renal impairment

  • CrCl ≥120 mL/min: 2 gram IV q6hr
  • CrCl 60 to <120 mL/min: No dosage adjustment necessary
  • CrCl 30 to <60 mL/min: 1.5 gram IV q8hr
  • CrCl 15 to <30 mL/min: 1 gram IV q8hr
  • End-stage renal disease (CrCl <15 mL/min) with or without intermittent hemodialysis (HD): 0.75 gram IV q12hr
  • Patients requiring HD: Complete HD at the latest possible time before starting cefiderocol dosing; monitor renal function regularly and adjust dosage accordingly as renal function may change during therapy

Hepatic impairment

  • Effects of hepatic impairment on the pharmacokinetics of cefiderocol have not been evaluated
  • No dosage adjustment necessary in patients with impaired hepatic function

Dosing Considerations

  • To reduce the development of drug-resistant bacteria and maintain effectiveness of cefiderocol and other antibacterial drugs, use only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria
  • When culture and susceptibility information are available, consider selecting or modifying antibacterial therapy
  • In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy

Safety and efficacy not established

Urinary Tract Infection

Indicated for complicated urinary tract infections (cUTI), including pyelonephritis, caused by susceptible gram-negative microorganisms in adults who have limited or no alternative treatment options

2 gram IV q8hr for 7-14 days

Duration of therapy should be dependent on infection severity and patient’s clinical status for up to 14 days

Cefiderocol is substantially excreted by the kidney, and the risk of adverse reactions to this 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 in dose selection and renal function should be monitored

Dosage Modifications

Renal impairment

  • CrCl ≥120 mL/min: 2 gram IV q6hr
  • CrCl 60 to <120 mL/min: No dosage adjustment necessary
  • CrCl 30 to <60 mL/min: 1.5 gram IV q8hr
  • CrCl 15 to <30 mL/min: 1 gram IV q8hr
  • End-stage renal disease (CrCl < 15 mL/min) with or without intermittent hemodialysis (HD): 0.75 gram IV q12hr
  • Patients requiring HD: Complete HD at the latest possible time before starting cefiderocol dosing; monitor renal function regularly and adjust dosage accordingly as renal function may change during therapy

Hepatic impairment

  • Effects of hepatic impairment on the pharmacokinetics of cefiderocol have not been evaluated
  • No dosage adjustment necessary in patients with impaired hepatic function

Dosing Considerations

  • To reduce the development of drug-resistant bacteria and maintain effectiveness of cefiderocol and other antibacterial drugs, use only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria
  • When culture and susceptibility information are available, consider selecting or modifying antibacterial therapy
  • In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy
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Interactions

Interaction Checker

and cefiderocol

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            Adverse Effects

            1-10%

            Diarrhea (4%)

            Infusion site reactions (4%)

            Constipation (3%)

            Rash (3%)

            Candidiasis (2%)

            Cough (2%)

            Elevated liver tests (2%)

            Headache (2%)

            Hypokalemia (2%)

            Nausea (2%)

            Vomiting (2%)

            <2%

            • Blood and lymphatic disorders: Thrombocytosis
            • Cardiac disorders: Congestive heart failure, bradycardia, atrial fibrillation
            • Gastrointestinal disorders: Abdominal pain, dry mouth, stomatitis
            • General system disorders: Pyrexia, peripheral edema
            • Hepatobiliary disorders: Cholelithiasis, cholecystitis, gallbladder pain
            • Immune system disorders: Drug hypersensitivity
            • Infections and infestations: Clostridioides difficile infection
            • Laboratory investigations: Prolonged prothrombin time and prothrombin time international normalized ratio, RBC urine positive, creatine phosphokinase increase
            • Metabolism and nutrition disorders: Decreased appetite, hypocalcemia, fluid overload
            • Nervous system disorders: Dysgeusia, seizure
            • Respiratory, thoracic, and mediastinal disorders: Dyspnea, pleural effusion
            • Skin and SC tissue disorders: Pruritus
            • Psychiatric disorders: Insomnia, restlessness
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            Warnings

            Contraindications

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

            Cautions

            An increase in all-cause mortality was observed in treated patients compared with best available therapy in a multinational, randomized, open-label trial in critically ill patients with carbapenem-resistant gram-negative bacterial infections; reserve use for in patients who have limited or no alternative treatment options for the treatment of cUTI

            Serious and occasionally fatal hypersensitivity (anaphylactic) reactions and serious skin reactions have been reported; reactions are more likely to occur in individuals with a history of beta-lactam hypersensitivity and/or a history of sensitivity to multiple allergens; discontinue therapy if an allergic reaction occurs

            Cephalosporins may trigger seizures; nonconvulsive status epilepticus, encephalopathy, coma, asterixis, neuromuscular excitability, and myoclonia have been reported with cephalosporins, particularly in patients with a history of epilepsy and/or when recommended dosages of cephalosporins were exceeded due to renal impairment; if CNS adverse reactions including seizures occur, patients should undergo a neurological evaluation to determine whether to discontinue treatment

            Prescribing cefiderocol in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and may increase the risk for development of drug-resistant bacteria

            C difficile-associated diarrhea

            • C difficile-associated diarrhea (CDAD) has been reported
            • CDAD may range in severity from mild diarrhea to fatal colitis
            • Treatment with antibacterial agents alters the normal flora of the colon and may permit overgrowth of C difficile
            • If CDAD is suspected or confirmed, antibacterial drugs not directed against C difficile may need to be discontinued; manage fluid and electrolyte levels as appropriate, supplement protein intake, monitor antibacterial treatment of C difficile, and institute surgical evaluation as clinically indicated

            Drug interaction overview

            • Cefiderocol may result in false-positive results in dipstick tests (urine protein, ketones, or occult blood); use alternate clinical laboratory methods of testing to confirm positive tests
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            Pregnancy & Lactation

            Pregnancy

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

            Available data from published prospective cohort studies, case series, and case reports over several decades with cephalosporin use in pregnant women have not established drug-associated risks of major birth defects, miscarriage, or adverse maternal or fetal outcomes

            Animal data

            • Developmental toxicity studies with cefiderocol administered during organogenesis to rats and mice showed no evidence of embryofetal toxicity, including drug-induced fetal malformations, at doses providing exposure levels 1.4 times (rats) or 2 times (mice) higher than the average observed in cUTI patients receiving the maximum recommended daily dose

            Lactation

            Unknown whether cefiderocol is excreted into human milk; however, cefiderocol-derived radioactivity was detected in the milk of lactating rats that received IV cefiderocol

            When a drug is present in animal milk, it is likely that the drug will be present in human milk

            No information is available on the effects of cefiderocol on the breastfed infant or on milk production

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            A cephalosporin antibacterial with activity against gram-negative aerobic bacteria

            Cefiderocol functions as a siderophore and binds to extracellular free ferric iron

            In addition to passive diffusion via porin channels, cefiderocol is actively transported across the outer cell membrane of bacteria into the periplasmic space using a siderophore iron uptake mechanism

            Cefiderocol exerts bactericidal action by inhibiting cell wall biosynthesis through binding to penicillin-binding proteins

            Absorption

            Peak plasma concentration: 138 mg/L (cUTI patients); 89.7 mg/L (healthy volunteers)

            AUC: 394.7 mg⋅hr/L (cUTI patients); 386 mg⋅hr/L (healthy volunteers)

            Distribution

            Vd: 18 L

            Plasma protein binding, primarily to albumin, of cefiderocol is 40-60%

            Metabolism

            Cefiderocol is minimally metabolized

            Elimination

            Half-life: 2-3 hr

            Clearance: 5.18 L/hr

            Primarily excreted by kidneys

            Excretion: Urine (98.6% [90.6% unchanged]); feces (2.8%)

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            Administration

            IV Incompatibilities

            Compatibility with solutions containing other drugs or other diluents has not been established

            IV Compatibilities

            0.9% NaCl

            Dextrose 5%

            IV Preparation

            Reconstitute vial with 10 mL of either 0.9% NaCl or dextrose 5%; gently shake to dissolve

            Allow vial(s) to stand until foaming on the surface has disappeared (~2 minutes)

            Final volume of the reconstituted solution: 1 gram per 11.2 mL

            Withdraw appropriate volume of reconstituted solution from the vial

            Add withdrawn volume to 100 mL of 0.9% NaCl or dextrose 5%

            Visually inspect for particulate matter and discoloration before administration, whenever solution and container permit

            Infusions are clear, colorless solutions; discard any unused reconstituted solution in the vial

            Preparation of doses

            • 2 grams: 22.4 mL of reconstituted cefiderocol
            • 1.5 grams: 16.8 mL of reconstituted cefiderocol
            • 1 gram: 11.2 mL of reconstituted cefiderocol
            • 0.75 grams: 8.4 mL of reconstituted cefiderocol

            IV Administration

            • IV infusion only
            • Infuse over 3 hr

            Storage

            Unused vials: Refrigerate at 2-8ºC (36-46ºF); protect from light; store in carton until time of use

            Reconstituted vials: Immediately transferred and diluted into the infusion bag; store for up to 1 hr at room temperature; discard any unused reconstituted solution

            Diluted solutions: Stable for up to 4 hr at room temperature

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.