Schedule H

Intravenous

Form Strength

Injection 1 g powder for reconstitution (lyophilized vial for IV infusion)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

Note: All uses require hospital setting and infectious disease specialist input. Reserve for confirmed or highly suspected multidrug-resistant (MDR) Gram-negative infections.

▶ Complicated Urinary Tract Infections (cUTI), including Pyelonephritis

Caused by susceptible Gram-negative organisms including carbapenem-resistant strains

Parameter Details

Starting dose 2 g IV every 8 hours

Titration Not applicable (adjust only for renal impairment)

Usual maintenance dose 2 g IV every 8 hours (infused over 3 hours)

Maximum dose 6 g/day

Duration 7–14 days based on clinical response

Key Clinical Notes:

• Reserve for MDR pathogens only; not for empirical use in routine cUTI

• Extended infusion (3 hours) optimizes pharmacodynamics

• Culture-directed therapy mandatory

▶ Hospital-Acquired Pneumonia (HAP) and Ventilator-Associated Pneumonia (VAP)

Caused by susceptible Gram-negative organisms including carbapenem-resistant strains

Parameter Details

Starting dose 2 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 8 hours (infused over 3 hours)

Maximum dose 6 g/day

Duration 7–14 days depending on clinical and microbiological response

Key Clinical Notes:

• Use when resistant to other last-line agents (carbapenems, colistin)

• Preferred for metallo-β-lactamase (MBL) producing organisms

• Combination therapy may be considered for severe Acinetobacter infections

▶ Infections Caused by Carbapenem-Resistant Gram-Negative Organisms (CRE, CRPA, CRAB)

Parameter Details

Starting dose 2 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 8 hours (infused over 3 hours)

Maximum dose 6 g/day

Duration Infection site-dependent; typically 7–14 days

Key Clinical Notes:

• Must confirm susceptibility via culture; resistance can emerge during therapy

• Retains activity against MBL-producing organisms (NDM, VIM, IMP) — key advantage

• Specialist infectious disease input mandatory

Secondary Indications – Adults Only (Off-label):

▶ Bacteraemia caused by CRE or MDR Gram-Negative Bacteria — OFF-LABEL

Parameter Details

Starting dose 2 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 8 hours

Maximum dose 6 g/day

Duration 10–14 days

Supervision Specialist only

Evidence basis Indian case reports support role in salvage therapy; international CREDIBLE-CR trial data

▶ Osteomyelitis due to XDR Gram-Negative Bacilli — OFF-LABEL

Parameter Details

Starting dose 2 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 8 hours

Maximum dose 6 g/day

Duration 4–6 weeks (guided by clinical response and imaging)

Supervision Specialist only; combination therapy recommended

Evidence basis Limited case series; extrapolation from similar beta-lactam use patterns

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

For children ≥3 months with confirmed/suspected MDR Gram-negative infections

Limited safety data available in India; use only under tertiary care infectious disease specialist supervision.

3 months to <2 years 40 mg/kg IV every 8 hours Not applicable 40 mg/kg IV every 8 hours 120 mg/kg/day Infuse over 3 hours; critical care setting only

2 to <12 years 40 mg/kg IV every 8 hours Not applicable 40 mg/kg IV every 8 hours 2 g per dose (max) Monitor renal function; TDM if available

12 to 18 years 2 g IV every 8 hours Not applicable 2 g IV every 8 hours 6 g/day Adult dosing; renal adjustment if required

Safety Monitoring:

• Baseline and periodic renal function assessment

• CBC monitoring during therapy

• Clinical response evaluation at 48–72 hours

• Watch for diarrhoea and hypersensitivity reactions

Minimum Age: 3 months

Secondary Indications – Paediatrics (Off-label):

▶ XDR Bacteraemia or Pneumonia — OFF-LABEL

Parameter Details

Dose As per age bracket above

Duration 10–14 days

Supervision Specialist only

Evidence basis Limited international data; Indian experience minimal

Age Restriction Statement:

Not recommended below 3 months of age except as salvage therapy under strict specialist guidance with documented ethics/institutional approval.

ESRD on Haemodialysis 0.75 g IV every 12 hours Administer after dialysis session on dialysis days

CRRT 2 g IV every 8 hours Close pharmacokinetic monitoring recommended if feasible

Note: All doses to be infused over 3 hours. Cefiderocol is dialyzable.

• Known hypersensitivity to cefiderocol or any formulation component

• History of severe hypersensitivity (anaphylaxis, angioedema) to any cephalosporin

• Documented severe immediate hypersensitivity reaction to penicillins or carbapenems

• Pre-existing CNS disorders or seizure history — beta-lactams may lower seizure threshold, particularly in renal impairment

• Neutropenia or immunocompromised states — increased risk of treatment-emergent resistance

• Not for empirical use — reserve for confirmed or highly suspected MDR organisms with culture guidance

• Acinetobacter baumannii infections — monotherapy may result in clinical failure; consider combination therapy

• Potential for false-positive direct Coombs test

• Prolonged use (>14 days) — increased risk of Clostridioides difficile infection and superinfection

Parameter Recommendation

Risk category Not formally classified in India; limited human data

Overall safety Use only when clearly needed and no safer alternative exists

Preferred alternatives Meropenem (if organism susceptible)

When may be used Life-threatening MDR infections where alternatives unsuitable; specialist decision

Monitoring Fetal growth surveillance if prolonged use; maternal renal function

Parameter Recommendation

Excretion in milk Expected to be low (based on cephalosporin class pharmacokinetics)

Compatibility Likely compatible; routine breastfeeding acceptable with caution

Preferred alternatives Meropenem or aminoglycosides (if organism susceptible)

Infant monitoring GI disturbances (diarrhoea), rash, oral candidiasis

Parameter Recommendation

Starting dose Same as adult (2 g IV every 8 hours) if normal renal function

Titration Not applicable; dose adjust only for renal impairment

Additional risks Age-related renal decline common — estimate eGFR before dosing

Special considerations Higher risk of Clostridioides difficile infection; CNS toxicity (confusion, seizures) at high doses; monitor hydration status

Interacting Drug/Class Mechanism / Risk Recommendation

Probenecid Inhibits renal tubular secretion; increases cefiderocol levels Avoid concomitant use

Valproic acid / Sodium valproate Risk of reduced serum valproate levels leading to seizure breakthrough Avoid or monitor valproate levels closely; consider alternative anticonvulsant

Other beta-lactam antibiotics (carbapenems, ceftazidime-avibactam) Potential antagonism or unclear benefit of combination Avoid co-administration unless under specialist decision for specific combination strategy

Interacting Drug/Class Mechanism / Risk Recommendation

Aminoglycosides (gentamicin, amikacin) Additive nephrotoxicity Use cautiously; monitor renal function and aminoglycoside levels

Loop diuretics (furosemide) Potential additive nephrotoxicity Monitor renal function, especially in critically ill

Oral iron supplements Theoretical competition due to siderophore mechanism Clinical significance uncertain; no specific avoidance required

Warfarin Infection resolution may alter warfarin response Monitor INR during and after cefiderocol therapy

• Diarrhoea

• Nausea

• Vomiting

• Infusion site reactions (phlebitis, pain)

• Elevated hepatic transaminases

• Hypokalaemia

• Headache

• Rash

Adverse Effect Notes

Clostridioides difficile-associated diarrhoea (CDAD) May occur during or after therapy; requires discontinuation and specific treatment

Seizures Particularly in renal impairment or CNS disorders; dose-related

Anaphylaxis / Severe hypersensitivity Requires immediate discontinuation and emergency management

Treatment-emergent resistance Documented especially with Acinetobacter species during monotherapy

All-cause mortality concern Numerically higher mortality observed in CREDIBLE-CR trial (carbapenem-resistant infections); use with caution in critically ill

During therapy Renal function every 2–3 days; clinical response at 48–72 hours; watch for CNS toxicity in renally impaired

Prolonged therapy (>7 days) LFTs weekly; CBC for neutropenia; monitor for diarrhoea (CDAD)

If available Therapeutic drug monitoring (TDM) in critically ill patients

• Fetcroja (Shionogi — imported via specialty channels)

Note: Limited domestic marketing as of 2024; primarily available through hospital-based procurement, specialty importers, or government facility import licenses. Availability may be inconsistent across regions.

NLEM Status: Not included in NLEM 2022; not under price control

Availability: Extremely high cost limits use to tertiary care centres; available via hospital supply chain or specialty import

• Not for empirical use — reserve exclusively for confirmed or highly suspected MDR/XDR Gram-negative organisms with culture-based susceptibility data

• Key advantage: Retains activity against metallo-β-lactamase (MBL)-producing organisms (NDM, VIM, IMP) where other beta-lactams fail

• Infuse over 3 hours — extended infusion optimizes time-dependent killing and reduces CNS/renal toxicity risk

• Avoid monotherapy for severe Acinetobacter infections — risk of treatment failure and resistance emergence; consider combination with colistin or aminoglycoside

• Resistance surveillance essential — treatment-emergent resistance documented; repeat cultures if clinical response inadequate

• Very limited Indian paediatric experience — use only as salvage therapy under specialist supervision in tertiary centres

cefiderocol; siderophore cephalosporin; MDR Gram-negative; CRE; CRPA; CRAB; cUTI; HAP; VAP; MBL-producer; carbapenem-resistant; ID-specialist; renal-adjust; high-cost

RxIndia v1.0 — 28 May 2025

• CDSCO (regulatory import information)

• ICMR Guidelines for Antimicrobial Resistance Management (2022)

• AIIMS Antimicrobial Stewardship Protocols

• PGIMER Infectious Disease Treatment Guidelines

• Shionogi package insert (India-imported version of Fetcroja)

• Indian Journal of Critical Care Medicine — case series on salvage use (2023)

• IP/NFI: NOT LISTED

• NLEM 2022: NOT LISTED

• CREDIBLE-CR trial (international RCT — used for off-label context only, clearly marked)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (basic pharmacology, supportive)