Schedule H

Intravenous (IV), Intramuscular (IM)

• Powder for injection: 250 mg, 500 mg, 1 g, 2 g vials (as Cefoperazone sodium)

• Fixed Dose Combinations: Cefoperazone + Sulbactam (500 mg + 500 mg, 1 g + 500 mg, 1 g + 1 g, 2 g + 1 g)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Serious Gram-negative Infections (Intra-abdominal, Respiratory Tract, Urinary Tract, Septicaemia)

Parameter Recommendation

Starting dose 1–2 g IV/IM every 12 hours

Titration Increase based on infection severity and pathogen susceptibility

Usual maintenance dose 2–4 g/day IV in 2 divided doses (every 12 hours)

Maximum dose 12 g/day in life-threatening infections (divided every 6–8 hours)

Duration 7–14 days depending on clinical and microbiological response

Clinical note Add sulbactam if β-lactamase-producing organisms suspected

1. Biliary Tract Infections (Cholangitis, Cholecystitis)

Parameter Recommendation

Starting dose 2 g IV every 12 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 12 hours

Maximum dose 4 g/day for uncomplicated; up to 8 g/day in severe cases

Duration 7–14 days depending on clinical response

Clinical note Preferred cephalosporin for biliary infections due to high biliary excretion (~40%)

1. Surgical Prophylaxis (Abdominal/Colorectal Procedures)

Parameter Recommendation

Starting dose 1–2 g IV single dose

Titration Not applicable

Usual maintenance dose Single preoperative dose

Maximum dose 2 g per single dose

Timing 30–60 minutes before surgical incision

Re-dosing Repeat if procedure duration >3 hours or blood loss >1500 mL

1. Febrile Neutropenia (Empiric Therapy — Combination Regimen)

Parameter Recommendation

Starting dose 2 g IV every 8 hours

Titration Based on culture sensitivity and clinical response

Usual maintenance dose 2 g IV every 8 hours (as part of combination therapy)

Maximum dose 6–8 g/day

Duration Until neutrophil recovery and afebrile for ≥48 hours

Clinical note Combine with aminoglycoside or vancomycin based on institutional protocol; Specialist supervision required

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Melioidosis (severe/septicaemic) — OFF-LABEL 2 g IV every 8 hours (in combination with cotrimoxazole or doxycycline) Intensive phase: 10–14 days minimum Specialist only; based on Indian tertiary care protocols (CMC Vellore, PGI Chandigarh experience)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

Severe Bacterial Infections (Pneumonia, Peritonitis, UTI, Sepsis)

Neonates (<7 days) 20 mg/kg/dose IV 20–40 mg/kg/dose IV Every 12 hours 80 mg/kg/day

Neonates (≥7 days to 28 days) 25 mg/kg/dose IV 25–50 mg/kg/dose IV Every 8 hours 150 mg/kg/day

Infants & Children (>1 month to 12 years) 25–50 mg/kg/dose IV 50–100 mg/kg/day IV Divided every 8–12 hours 200 mg/kg/day

Adolescents (>12 years) Adult dosing Adult dosing — 12 g/day

Clinical Notes:

• Preferred cephalosporin in paediatric biliary infections due to biliary excretion

• Monitor for bleeding complications — consider prophylactic Vitamin K supplementation

• Titration: Not applicable

Biliary Tract Infections (Paediatric)

Parameter Recommendation

Starting dose 50 mg/kg/day IV in divided doses

Titration Not applicable

Usual maintenance dose 50–100 mg/kg/day IV divided every 8–12 hours

Maximum dose 200 mg/kg/day or 4 g/day (whichever is lower)

Secondary Indications — Paediatrics (Off-label)

Indication Dose Duration Notes

Surgical prophylaxis (abdominal/GI procedures) — OFF-LABEL 50 mg/kg IV (max 2 g) 30 minutes before incision Single dose Specialist only; based on institutional paediatric surgery protocols

⚠️ Not recommended in neonates <7 days at high doses or for prolonged courses without specialist supervision due to immature hepatic metabolism and coagulation systems

Combined hepatic + renal impairment Reduce dose by 50%; monitor drug levels if prolonged therapy

Cefoperazone is primarily excreted via bile (~70–80%); renal excretion is secondary (~20–30%)

Risk of hypoprothrombinaemia increases with hepatic impairment due to reduced clotting factor synthesis and impaired drug clearance

• Known hypersensitivity to cefoperazone or any cephalosporin

• History of immediate-type (Type I) hypersensitivity to penicillins (anaphylaxis, angioedema, urticaria)

• Previous cefoperazone-induced severe thrombocytopenia or haemolytic anaemia

• Hepatic impairment — increased risk of coagulopathy; monitor PT/INR

• History of non-immediate penicillin allergy — cross-reactivity risk (~1–2%)

• Pre-existing coagulopathy or concurrent anticoagulant therapy — enhanced bleeding risk

• Malnourished patients — higher risk of Vitamin K deficiency

• Premature neonates — use with caution due to immature hepatic function

• Prolonged therapy (>7 days) — monitor for superinfection and bleeding

Parameter Information

Risk category Generally considered safe (limited human data; no evidence of teratogenicity)

Preferred alternatives Ceftriaxone often preferred for obstetric infections in Indian practice

When to use When clearly indicated and benefits outweigh risks; avoid near term if possible

Monitoring LFTs; PT/INR if prolonged course; signs of biliary stasis

Parameter Information

Compatibility Compatible with breastfeeding

Drug levels in milk Low

Preferred alternatives Ceftriaxone or amoxicillin for mild infections if feasible

Infant monitoring Diarrhoea, oral thrush, feeding difficulties (rare)

Parameter Recommendation

Starting dose Standard adult dose unless hepatic impairment present

Titration Not usually required; adjust based on hepatic function

Special risks Higher bleeding risk (especially with poor nutrition, concurrent anticoagulants, or prolonged therapy); age-related decline in hepatic reserve

Monitoring Coagulation parameters (PT/INR) regularly; consider prophylactic Vitamin K (10 mg IM weekly) in frail elderly on prolonged courses

Interacting Drug Effect Recommendation

Alcohol Disulfiram-like reaction (flushing, nausea, tachycardia) due to N-methylthiotetrazole (NMTT) side chain Avoid alcohol during therapy and for 72 hours after last dose

Warfarin / Acenocoumarol Enhanced anticoagulant effect → increased bleeding risk; cefoperazone interferes with Vitamin K metabolism Monitor INR every 2–3 days; may require dose reduction of anticoagulant

Heparin / LMWH Additive bleeding risk Monitor for bleeding; use with caution

Interacting Drug Effect Recommendation

Aminoglycosides Potential additive nephrotoxicity (though cefoperazone itself is not significantly nephrotoxic) Monitor renal function if used concurrently

Loop diuretics (Furosemide) May alter renal clearance kinetics Monitor kidney function

NSAIDs May increase INR/bleeding tendency when combined with cefoperazone Monitor for signs of bleeding

Probenecid Minimal effect on cefoperazone clearance (primarily biliary excretion) No significant interaction

• Diarrhoea

• Injection site pain or phlebitis

• Transient elevation of liver enzymes (AST/ALT)

• Rash, pruritus

• Hypoprothrombinaemia (especially with prolonged or high-dose therapy)

• Positive direct Coombs test (without haemolysis)

Adverse Effect Action Required

Anaphylaxis / Severe hypersensitivity Immediate discontinuation; emergency management

Stevens-Johnson Syndrome / TEN Rare; discontinue immediately; dermatology referral

Severe bleeding episodes Due to Vitamin K-dependent factor depletion; administer Vitamin K; discontinue if severe

Drug-induced hepatitis Discontinue; monitor LFTs

Clostridioides difficile-associated colitis Suspect if severe diarrhoea (≥3 watery stools/day); discontinue and treat appropriately

Haemolytic anaemia Rare; discontinue immediately

Phase Parameters

Baseline CBC, LFTs (AST, ALT, ALP, bilirubin), PT/INR, serum creatinine

During therapy PT/INR every 3–5 days if therapy >5 days or hepatic impairment; LFTs weekly if therapy >7 days

Long-term therapy Consider prophylactic Vitamin K (10 mg IM) every 3–5 days in at-risk patients

Clinical monitoring Signs of bleeding; diarrhoea (consider C. difficile testing if severe); injection site reactions

Cefoperazone (Mono):

• Magnamycin

• Cefoprox

• Operaz

• Cfpaz

• Cefozon

Cefoperazone + Sulbactam (FDC):

• Magnex

• Sulcef

• Supacef-SB

• Cefactum-SB

• Elores

Some sulbactam combinations under NLEM ceiling pricing; prices vary by brand and procurement model

• Biliary excretion advantage: Preferred cephalosporin for biliary tract infections; achieves therapeutic concentrations in bile even with biliary obstruction

• Bleeding risk is real: NMTT side chain inhibits Vitamin K epoxide reductase → monitor PT/INR and supplement Vitamin K in prolonged therapy, malnourished, elderly, or hepatically impaired patients

• Alcohol warning: Counsel patients to avoid alcohol during and for 72 hours after therapy to prevent disulfiram-like reaction

• Renal-safe option: Useful in patients with renal impairment requiring parenteral cephalosporin (no dose adjustment needed)

• Sulbactam combination: Preferred over monotherapy when ESBL-producing or β-lactamase-producing organisms suspected

• Not for CNS infections: Does not adequately penetrate blood-brain barrier

cefoperazone; cephalosporin; third-generation cephalosporin; biliary sepsis; intra-abdominal infection; hepatic excretion; vitamin K deficiency; bleeding risk; renal-safe; injectable antibiotic; NLEM India

RxIndia v1.0 — 06 May 2024

• CDSCO product inserts

• IP/NFI (Indian Pharmacopoeia / National Formulary of India)

• NLEM 2022

• AIIMS Adult Antimicrobial Policy

• API Textbook of Medicine

• ICMR-AMR Surveillance Guidelines

• Hospital Drug Formularies (PGI Chandigarh, CMC Vellore)

• Tertiary care antimicrobial protocols (for melioidosis — CMC Vellore experience)