Schedule H

Intravenous (IV), Intramuscular (IM)

Form Strengths

Powder for Injection (IV/IM) 250 mg; 500 mg; 1 g; 2 g per vial

Fixed-Dose Combinations Ceftriaxone + Sulbactam (1 g + 500 mg; 1.5 g combination); Ceftriaxone + Tazobactam (1 g + 125 mg)

Reconstitution Notes:

• IV: Reconstitute with Sterile Water for Injection or compatible IV fluid

• IM: Reconstitute with 1% Lidocaine (without adrenaline) to reduce injection pain — Lidocaine-containing solution must NOT be used for IV administration

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Community-Acquired Pneumonia (CAP)

Adults:

Parameter Recommendation

Starting dose 1 g IV/IM once daily

Titration Increase to 2 g once daily for severe pneumonia

Usual maintenance dose 1–2 g once daily

Maximum dose 4 g/day (given as 2 g every 12 hours if >2 g/day required)

Duration 5–7 days; extend to 10–14 days for severe or complicated cases

Clinical Note: For severe CAP requiring ICU admission, consider combination with macrolide (azithromycin) or fluoroquinolone for atypical coverage.

1. Bacterial Meningitis

Adults:

Parameter Recommendation

Starting dose 2 g IV every 12 hours

Titration Not applicable

Usual maintenance dose 2 g IV every 12 hours (4 g/day total)

Maximum dose 4 g/day

Duration 7 days (meningococcal); 10–14 days (pneumococcal); 21 days (Listeria — add ampicillin)

Clinical Note: Higher doses and shorter dosing intervals essential for adequate CSF penetration. Add dexamethasone before or with first antibiotic dose for suspected bacterial meningitis.

1. Enteric Fever (Typhoid/Paratyphoid)

Adults:

Parameter Recommendation

Starting dose 2 g IV/IM once daily

Titration Not applicable

Usual maintenance dose 2 g once daily

Maximum dose 2 g/day (some protocols allow up to 4 g/day in severe cases)

Duration 10–14 days; minimum until afebrile for 5 days

Clinical Note: Preferred parenteral agent for multi-drug resistant (MDR) and fluoroquinolone-resistant typhoid, which is increasingly common in India. Blood culture before initiation recommended where feasible.

1. Uncomplicated Gonorrhoea (Urethritis/Cervicitis)

Adults:

Parameter Recommendation

Starting dose 250 mg IM as single dose (Indian practice) OR 500 mg IM single dose (per updated guidelines)

Titration Not applicable

Usual maintenance dose Not applicable (single-dose therapy)

Maximum dose 500 mg single dose

Duration Single dose

Clinical Note: Always co-treat with azithromycin 1 g orally single dose (dual therapy) to cover potential chlamydial co-infection and reduce gonococcal resistance emergence. Higher dose (500 mg) increasingly recommended due to rising MICs.

1. Intra-Abdominal Infections (Including Peritonitis, Cholangitis)

Adults:

Parameter Recommendation

Starting dose 1–2 g IV once daily

Titration Not applicable

Usual maintenance dose 2 g once daily

Maximum dose 4 g/day (in severe infections)

Duration 5–14 days depending on source control and clinical response

Clinical Note: Add metronidazole for anaerobic coverage in mixed intra-abdominal infections.

1. Skin and Soft Tissue Infections (Complicated)

Adults:

Parameter Recommendation

Starting dose 1 g IV/IM once daily

Titration Increase to 2 g once daily for severe infections

Usual maintenance dose 1–2 g once daily

Maximum dose 4 g/day

Duration 7–14 days

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Bacterial Meningitis

Neonates (≤28 days):

Parameter Recommendation

Starting dose 50 mg/kg IV once daily

Titration Not applicable

Usual maintenance dose 50 mg/kg once daily

Maximum dose 50 mg/kg/day (do not exceed 2 g/day)

Duration 14–21 days depending on organism

Infants and Children (>28 days to 12 years):

Parameter Recommendation

Starting dose 50 mg/kg IV

Titration Not applicable

Usual maintenance dose 80–100 mg/kg/day divided every 12 hours

Maximum dose 4 g/day

Duration 7–14 days depending on pathogen

1. Community-Acquired Pneumonia (Severe/Hospitalised)

Infants and Children:

Parameter Recommendation

Starting dose 50 mg/kg IV/IM once daily

Titration Not applicable

Usual maintenance dose 50–75 mg/kg once daily

Maximum dose 2 g/day

Duration 5–10 days

1. Enteric Fever (Typhoid)

Infants and Children:

Parameter Recommendation

Starting dose 50 mg/kg IV/IM once daily

Titration Not applicable

Usual maintenance dose 75 mg/kg once daily

Maximum dose 2 g/day

Duration 10–14 days; minimum until afebrile for 5 days

Clinical Note: Preferred parenteral agent for MDR typhoid in children.

1. Sepsis / Severe Bacterial Infections

Neonates:

Age Dose Frequency Maximum

0–7 days 50 mg/kg Once daily 50 mg/kg/day

8–28 days 50–75 mg/kg Once daily 75 mg/kg/day

Infants and Children:

Parameter Recommendation

Starting dose 50 mg/kg IV

Usual maintenance dose 50–80 mg/kg/day in 1–2 divided doses

Maximum dose 4 g/day

1. Uncomplicated Gonorrhoea (Adolescents ≥45 kg)

Parameter Recommendation

Dose 250–500 mg IM single dose

Duration Single dose

Clinical Note: Co-treat with azithromycin. NACO STI guidelines applicable.

1. Surgical Prophylaxis (Paediatric)

Parameter Recommendation

Dose 50 mg/kg IV (max 1 g) 30–60 minutes before incision

Duration Single dose

Secondary Indications — Paediatrics (Off-label, if any)

10 No dose adjustment required

≤10 (without hepatic impairment) No dose adjustment required; monitor closely

≤10 (with concurrent hepatic impairment) Maximum 2 g/day

Haemodialysis Not significantly removed; no supplemental dose required post-dialysis

Peritoneal dialysis No supplemental dose required

CRRT Standard dosing; monitor clinical response

Clinical Note: Ceftriaxone has dual elimination (hepatic and renal). Dose reduction only needed when both routes are severely impaired.

• Known hypersensitivity to ceftriaxone or any cephalosporin antibiotic

• History of severe (anaphylactic) hypersensitivity reaction to any beta-lactam antibiotic

• Hyperbilirubinaemic neonates, especially preterm infants (<41 weeks postmenstrual age)

• Neonates requiring (or expected to require) calcium-containing IV infusions including parenteral nutrition

• Full-term neonates (<28 days) if concomitant IV calcium administration is anticipated

• Reconstitution with calcium-containing diluents (e.g., Ringer's lactate, Hartmann's solution)

• History of non-severe penicillin allergy — cross-reactivity risk approximately 1–2% (higher with aminopenicillins); observe for allergic reactions

• Prolonged therapy (>14 days) — risk of biliary sludging/gallbladder pseudolithiasis (especially in children, fasting patients, those on TPN)

• Dehydration or restricted fluid intake — increased risk of biliary precipitation

• History of gastrointestinal disease, particularly colitis — risk of Clostridioides difficile-associated diarrhoea

• Concurrent aminoglycoside use — additive nephrotoxicity; administer separately and monitor renal function

• Premature neonates — use cefotaxime preferentially to avoid bilirubin displacement risk

• IM administration — painful injection; use lidocaine 1% for reconstitution (never for IV use)

Parameter Recommendation

Overall safety Generally considered safe; widely used in pregnancy

Risk category Category B (US legacy); no formal India classification; extensive clinical experience supports safety

Preferred alternatives Ceftriaxone is often preferred parenteral cephalosporin in pregnancy for serious infections

When to use For serious infections (typhoid, pneumonia, pyelonephritis, sepsis) when parenteral therapy required

Monitoring Hypersensitivity reactions; CBC and LFTs if prolonged use; standard foetal monitoring

Parameter Recommendation

Compatibility Compatible with breastfeeding

Drug levels in milk Low (approximately 3–4% of maternal dose); clinically insignificant

Preferred alternatives None required; ceftriaxone acceptable during breastfeeding

Infant monitoring Observe for loose stools, oral thrush, or rash (rare)

Parameter Recommendation

Starting dose Standard adult dosing; no age-related reduction required

Titration Not applicable

Specific considerations Assess renal function (serum creatinine may underestimate impairment); ensure adequate hydration to reduce biliary precipitation risk

Additional risks Higher risk of Clostridioides difficile infection; increased susceptibility to biliary complications if malnourished or prolonged fasting

Monitoring Renal function; hepatic function in prolonged therapy; signs of superinfection

Drug Interaction Recommendation

Calcium-containing IV solutions (Ringer's lactate, Hartmann's, calcium gluconate, TPN with calcium) Risk of ceftriaxone-calcium precipitate formation — can be fatal in neonates; lung/kidney precipitation reported CONTRAINDICATED in neonates. In adults/children, administer through separate lines; flush between infusions; do not mix in same bag/syringe

Warfarin/Acenocoumarol Enhanced anticoagulant effect; mechanism includes vitamin K antagonism via gut flora disruption and possible direct effect Monitor INR closely during and for several days after ceftriaxone course; adjust anticoagulant dose as needed

Aminoglycosides (Amikacin, Gentamicin) Additive nephrotoxicity; also physical incompatibility if mixed Administer separately via different lines/sites; monitor serum creatinine and aminoglycoside levels

Drug Interaction Recommendation

Loop diuretics (Furosemide) Theoretical increased nephrotoxicity risk Generally safe; monitor renal function, especially in dehydrated patients

Probenecid Decreases renal tubular secretion of ceftriaxone; increases plasma levels Usually not clinically significant due to hepatic elimination; no dose adjustment typically needed

Oral contraceptives Theoretical reduction in efficacy via gut flora alteration Advise additional barrier contraception during antibiotic course and for 7 days after (precautionary)

Chloramphenicol Potential antagonism (bacteriostatic vs bactericidal) Avoid combination where possible; if used, monitor clinical response closely

• Injection site pain and induration (IM route)

• Phlebitis/thrombophlebitis (IV route)

• Diarrhoea

• Nausea and vomiting

• Skin rash (maculopapular)

• Transient elevation of liver enzymes (AST, ALT)

• Eosinophilia

• Biliary sludging/pseudolithiasis (especially with prolonged use, higher doses, or fasting)

• Positive direct Coombs test (usually without haemolysis)

Adverse Effect Clinical Notes

Anaphylaxis Rare but potentially fatal; discontinue immediately; manage with adrenaline and supportive care

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Very rare; discontinue immediately; requires hospitalisation

Immune haemolytic anaemia Rare; can be severe; discontinue ceftriaxone permanently

Clostridioides difficile-associated diarrhoea (CDAD) May occur during or after therapy; discontinue ceftriaxone if confirmed; treat with oral vancomycin or metronidazole

Biliary obstruction (from pseudolithiasis) Usually reversible upon drug discontinuation; ultrasound for diagnosis

Ceftriaxone-calcium precipitation (neonates) Fatal cardiopulmonary reactions reported; strictly avoid concurrent calcium infusions in neonates

Seizures Rare; reported with very high doses or in renal impairment

Interstitial nephritis Rare; presents with fever, rash, eosinophilia, rising creatinine

Agranulocytosis / Neutropenia Rare; monitor CBC in prolonged therapy

Phase Parameters

Baseline Serum creatinine, LFTs, CBC, allergy history (especially to penicillins/cephalosporins); bilirubin in neonates

During treatment Clinical response; signs of hypersensitivity; GI tolerance; injection site (for phlebitis/pain)

Prolonged therapy (>7 days) LFTs weekly; CBC; renal function; ultrasound abdomen if >14 days (especially in children) to assess for biliary sludging

If on anticoagulants INR monitoring during and after ceftriaxone course

Neonates Bilirubin levels; avoid concurrent calcium; monitor for precipitation-related complications

Brand Name Manufacturer

Monocef Aristo

Ceftriaxone (Generic) Multiple manufacturers

Taxim Alkem

Oframax Ranbaxy/Sun

Xone Alkem

Cefaxone Lupin

LupiCef Lupin

Ceftriax Cadila

Monotax Zydus

Fixed-Dose Combinations:

• Monocef-SB, Magnex (Ceftriaxone + Sulbactam)

• Intacef Tazo (Ceftriaxone + Tazobactam)

Regulatory Note: Listed under NLEM 2022. Prices regulated by NPPA for scheduled strengths. Available through government supply (NRHM, hospital pharmacies) at significantly lower rates.

1. Once-daily dosing advantage: Long half-life (6–8 hours) allows once-daily administration for most indications except meningitis, simplifying inpatient and outpatient parenteral therapy.

1. Calcium contraindication in neonates is absolute: Fatal cardiopulmonary precipitation reported. If ceftriaxone essential, ensure 48-hour gap from any calcium-containing infusion. Cefotaxime is safer alternative in neonates.

1. IM injection technique: Reconstitute with 1% lidocaine (without adrenaline) for IM use to reduce pain. Never use lidocaine-containing solution for IV administration.

1. Biliary sludging is reversible: If gallbladder pseudolithiasis occurs (more common with >14 days therapy or fasting patients), it typically resolves spontaneously after stopping ceftriaxone.

1. Empirical typhoid therapy: Ceftriaxone is preferred parenteral agent in India given high fluoroquinolone resistance. Continue for 10–14 days for optimal cure rates.

1. Not effective against: MRSA, Pseudomonas aeruginosa, Enterococcus species, ESBL-producing Enterobacteriaceae, Acinetobacter. Escalate therapy if these organisms suspected.

ceftriaxone; cephalosporin; third-generation; injectable-antibiotic; meningitis; typhoid; sepsis; surgical-prophylaxis; neonatal-caution; calcium-interaction; NLEM-India; Schedule-H

RxIndia v1.0 — 20 Apr 2025

• CDSCO Drug Database and Product Inserts

• Indian Pharmacopoeia 2022

• National List of Essential Medicines (NLEM) 2022

• API Textbook of Medicine (11th Edition)

• AIIMS Antibiotic Guidelines and Treatment Protocols

• IAP Antimicrobial Guidelines for Paediatric Practice

• ICMR Guidelines for Antimicrobial Use

• NACO STI/RTI Treatment Guidelines

• ILBS/PGI Hepatology Protocols (for SBP)

• WHO Essential Medicines List (supportive reference)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics