Schedule H

Intravenous (IV), Intramuscular (IM)

• Injection: 250 mg vial (as cefepime hydrochloride, powder for reconstitution)

• Injection: 500 mg vial (as cefepime hydrochloride, powder for reconstitution)

• Injection: 1 g vial (as cefepime hydrochloride, powder for reconstitution)

• Injection: 2 g vial (as cefepime hydrochloride, powder for reconstitution)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Febrile Neutropenia (Empirical Therapy) — Adults

Parameter Recommendation

Starting dose 2 g IV every 8 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 8 hours (6 g/day)

Maximum dose 6 g/day

Duration Until neutrophil recovery (ANC >500/µL) and afebrile for at least 48 hours

Clinical note Monotherapy is acceptable; add vancomycin if MRSA suspected; add antifungal if fever persists beyond 4–7 days. Infuse over 30 minutes minimum

1. Hospital-Acquired Pneumonia (HAP) / Ventilator-Associated Pneumonia (VAP) — Adults

Parameter Recommendation

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 7–14 days depending on clinical response and pathogen

Clinical note Add vancomycin or linezolid if MRSA suspected pending cultures; de-escalate once sensitivity available

1. Complicated Urinary Tract Infections / Pyelonephritis — Adults

Parameter Recommendation

Starting dose 1 g IV every 12 hours

Titration Increase to 2 g every 12 hours if severe or poor response

Usual maintenance dose 1–2 g IV every 12 hours

Maximum dose 4 g/day

Duration 7–14 days; switch to oral based on culture sensitivity when clinically stable

Clinical note Covers common uropathogens including Pseudomonas aeruginosa; adjust dose for renal impairment

1. Complicated Intra-abdominal Infections — Adults

Parameter Recommendation

Starting dose 2 g IV every 12 hours

Titration May increase to every 8 hours in severe infection

Usual maintenance dose 2 g IV every 8–12 hours

Maximum dose 6 g/day

Duration 4–7 days with adequate source control; longer if source control delayed or complicated

Clinical note Must combine with metronidazole 500 mg IV every 8 hours — cefepime lacks anaerobic coverage

1. Complicated Skin and Soft Tissue Infections — Adults

Parameter Recommendation

Starting dose 2 g IV every 12 hours

Titration Increase to every 8 hours in severe/necrotizing infections

Usual maintenance dose 2 g IV every 8–12 hours

Maximum dose 6 g/day

Duration 7–14 days depending on clinical response and wound healing

Clinical note Add vancomycin if MRSA suspected; surgical debridement essential in necrotizing infections

1. Sepsis / Severe Gram-negative Infections — Adults

Parameter Recommendation

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 Minimum 7–14 days; guided by source and clinical response

Clinical note Loading dose of 2 g recommended in severe sepsis for rapid therapeutic levels; consider combination with aminoglycoside for synergy in documented Pseudomonas infection

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Bacterial meningitis (Gram-negative, resistant strains) 2 g IV every 8 hours 10–21 days depending on pathogen OFF-LABEL; Specialist only. Reserve for documented susceptible organisms (Pseudomonas, resistant Enterobacterales). Evidence: AIIMS/institutional protocols, international guidelines

Brain abscess (Gram-negative coverage) 2 g IV every 8 hours + Metronidazole 4–8 weeks OFF-LABEL; Specialist only. Neurosurgical consultation essential. Evidence: Indian neurosurgical practice

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

⚠️ Minimum age: 2 months (limited data below 2 months; use only under neonatology/ID specialist supervision)

1. Febrile Neutropenia / Severe Sepsis — Paediatrics (≥2 months)

Weight/Age Dose Frequency Maximum Duration

2 months – 12 years 50 mg/kg/dose IV Every 8 hours 2 g per dose (6 g/day) Until ANC recovery and afebrile ≥48 hours

12 years or >40 kg Adult dosing (2 g IV every 8 hours) Every 8 hours 6 g/day As per adult guidance

1. Complicated Urinary Tract Infections / Pyelonephritis — Paediatrics (≥2 months)

Weight/Age Dose Frequency Maximum Duration

2 months – 12 years 50 mg/kg/dose IV Every 12 hours 2 g per dose 7–14 days

12 years or >40 kg Adult dosing (1–2 g IV every 12 hours) Every 12 hours 4 g/day 7–14 days

1. Hospital-Acquired Pneumonia / Severe Lower Respiratory Tract Infections — Paediatrics (≥2 months)

Weight/Age Dose Frequency Maximum Duration

2 months – 12 years 50 mg/kg/dose IV Every 8 hours 2 g per dose 7–14 days

12 years or >40 kg Adult dosing Every 8 hours 6 g/day 7–14 days

Secondary Indications — Paediatrics (Off-label)

Indication Dose Duration Notes

CNS infections / Meningitis (Gram-negative, resistant organisms) 50 mg/kg/dose IV every 8 hours (max 2 g/dose) 10–21 days OFF-LABEL; Specialist only. Paediatric ID/neurology supervision essential. Evidence: Institutional protocols

Neonates (<2 months) 30 mg/kg/dose IV every 12 hours (0–14 days) or every 8 hours (>14 days) As per infection OFF-LABEL; Specialist only. Use only when alternatives unsuitable. Limited safety data

Safety Monitoring in Paediatrics:

• Renal function (serum creatinine, eGFR) at baseline and during therapy

• CBC with differential (weekly in prolonged therapy)

• Neurological status monitoring (especially for signs of encephalopathy)

• Infuse over at least 30 minutes to reduce neurotoxicity risk

• Signs of superinfection (oral thrush, diarrhoea)

≤10 1 g IV every 24 hours; 500 mg every 24 hours for uncomplicated infections

Haemodialysis 1 g loading dose, then 500 mg–1 g every 24 hours; administer after dialysis session (68% removed by HD)

CAPD 500 mg–1 g every 48 hours; limited data

CRRT 1–2 g every 12 hours; adjust based on effluent rate; consult ID/nephrology

• Known hypersensitivity to cefepime, any cephalosporin, or any excipient

• History of immediate/severe hypersensitivity reaction (anaphylaxis, angioedema, severe urticaria) to any penicillin or β-lactam antibiotic

• History of cephalosporin-induced immune-mediated haemolytic anaemia

• History of non-severe penicillin allergy — approximately 1–2% cross-reactivity; can use with monitoring

• Renal impairment (any degree) — mandatory dose adjustment to prevent neurotoxicity

• Pre-existing seizure disorder or CNS pathology — increased risk of cefepime-induced seizures

• Elderly patients — reduced renal reserve even with normal serum creatinine

• History of gastrointestinal disease, especially antibiotic-associated colitis

• Prolonged therapy (>10–14 days) — increased risk of superinfection, C. difficile colitis, haematological abnormalities

• Critically ill patients — consider extended/continuous infusion for enhanced pharmacokinetics

• Concurrent nephrotoxic drugs — additive renal toxicity risk

Aspect Recommendation

Overall safety Limited human data; animal studies show no teratogenicity; use when clearly indicated

Risk category US FDA Category B equivalent

Preferred alternatives Ceftriaxone, Cefotaxime (more extensive pregnancy safety data in Indian obstetric practice)

When to use May be used in second/third trimester when Gram-negative coverage including Pseudomonas is essential and alternatives inadequate

Monitoring Maternal renal function; fetal wellbeing in prolonged use

Aspect Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low (approximately 0.5 mg/L; very small proportion of maternal dose)

Preferred alternatives Ceftriaxone, Cefotaxime, Cefuroxime (if narrower spectrum sufficient)

Infant monitoring GI disturbance (loose stools, diarrhoea), oral thrush, allergic reaction (rare)

• Starting dose: Use standard doses but with mandatory renal function assessment; reduce dose if eGFR <60 mL/min

• Titration: Not applicable; adjust based on renal function

• Special considerations:

• Calculate CrCl/eGFR — serum creatinine alone is unreliable due to reduced muscle mass

• Higher risk of cefepime-induced neurotoxicity (encephalopathy, myoclonus, seizures, coma) — most commonly due to failure to adjust dose in renal impairment

• Increased risk of C. difficile colitis — monitor for new-onset diarrhoea

• Ensure adequate hydration

• Pre-existing cognitive impairment may mask early signs of neurotoxicity

Drug Interaction Management

Aminoglycosides (Amikacin, Gentamicin) Additive nephrotoxicity; synergistic antibacterial effect Monitor renal function daily; synergy is intentional but nephrotoxicity risk significant

Loop diuretics (Furosemide) Increased nephrotoxicity risk Avoid combination if possible; monitor renal function and urine output if unavoidable

Probenecid Reduces renal tubular secretion → increased cefepime levels Generally not clinically significant; monitor for toxicity if high probenecid doses

Drug Interaction Management

Warfarin/Acenocoumarol Cephalosporins may enhance anticoagulant effect (vitamin K reduction) Monitor INR during and after therapy

Valproic acid Possible reduction in valproate levels; increased seizure threshold interaction Monitor valproate levels; observe for seizure control

Phenytoin Possible altered phenytoin levels Monitor phenytoin levels if prolonged cefepime use

Vancomycin Additive nephrotoxicity Monitor renal function; often used together intentionally

Live oral typhoid vaccine Antibiotics may reduce vaccine efficacy Complete cefepime course before vaccination or delay vaccine by 3 days after last dose

Methotrexate Reduced renal clearance → methotrexate toxicity Avoid combination; monitor methotrexate levels if unavoidable

• Injection site reactions (pain, phlebitis, erythema)

• Diarrhoea and loose stools

• Nausea

• Rash and pruritus

• Headache

• Transient elevation of hepatic transaminases (ALT, AST)

• Positive direct Coombs test (without haemolysis)

• Eosinophilia

• Cefepime-induced neurotoxicity (encephalopathy, altered mental status, confusion, hallucinations, myoclonus, seizures, coma) — risk markedly increased in renal impairment; requires dose reduction or discontinuation; usually reversible within 24–72 hours of stopping

• Anaphylaxis and severe hypersensitivity reactions — discontinue immediately; emergency management required

• Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis — rare; discontinue immediately

• Clostridioides difficile colitis — may occur during or after therapy; discontinue and initiate specific treatment

• Immune-mediated haemolytic anaemia — rare; Coombs-positive; discontinue immediately

• Pancytopenia / Agranulocytosis / Thrombocytopenia — with prolonged therapy; monitor CBC

• Interstitial nephritis — rare; presents with fever, rash, eosinophilia, rising creatinine

During therapy (days 3–5) Clinical response; signs of allergy; neurological status (especially in renal impairment); diarrhoea; injection site

Prolonged therapy (>7 days) CBC with differential (weekly); renal function; LFTs; neurological examination

If on anticoagulants INR at days 3–5 and weekly

ICU/critically ill Daily renal function; neurological status every shift

• Maxipime (BMS/Dr. Reddy's)

• Cepime (Alkem)

• Kefage (Aristo)

• Cefprime (Lupin)

• Monotax (Ranbaxy/Sun Pharma)

• Xylife (Cadila)

• Cefoget (Glenmark)

• Ceftum-4 (GSK — note: different from Ceftum which is cefuroxime)

• Multiple other branded generics available

Fixed-Dose Combinations:

Strength Price Range

• NPPA status: Under price control as per NLEM 2022

• Government supply: Available through public hospital pharmacies at significantly lower rates

• Private sector: Higher end of price range

1. Renal dose adjustment is critical — cefepime-induced neurotoxicity (encephalopathy, seizures, myoclonus) is the most common serious preventable adverse effect and correlates directly with inappropriately high doses in renal impairment

1. Preferred monotherapy for febrile neutropenia — per ICMR/AIIMS protocols, cefepime is acceptable as single-agent empirical therapy in low-risk febrile neutropenia

1. AmpC β-lactamase stable — key advantage over third-generation cephalosporins; effective against organisms producing AmpC (Enterobacter, Citrobacter, Serratia) that may appear susceptible to ceftriaxone/cefotaxime but develop resistance during therapy

1. No activity against MRSA, Enterococci, or anaerobes — always add vancomycin for suspected MRSA; add metronidazole for intra-abdominal/pelvic infections

1. Extended infusion (3–4 hours) may improve outcomes in severe infections — optimises time above MIC; consider for VAP, septic shock, or infections with elevated MIC pathogens

1. Alternative to piperacillin-tazobactam in patients with documented penicillin allergy — cross-reactivity with cephalosporins is lower (1–2%) than historically believed; obtain detailed allergy history before use

cefepime; cephalosporin; fourth-generation cephalosporin; febrile neutropenia; HAP; VAP; Pseudomonas; Gram-negative; injectable antibiotic; neurotoxicity; renal-adjustment; NLEM India; Schedule H

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations List

• Indian Pharmacopoeia (IP)

• NLEM 2022 (National List of Essential Medicines)

• ICMR Guidelines on Antimicrobial Use (2019, 2023)

• AIIMS Antimicrobial Stewardship Guidelines

• API Textbook of Medicine (2022)

• IAP Textbook of Pediatrics (paediatric dosing)

• Goodman & Gilman's Pharmacological Basis of Therapeutics (supportive)

• Harrison's Principles of Internal Medicine (supportive)