Schedule H

Oral, Intravenous, Topical (ophthalmic and otic)

• Capsules/Tablets: 250 mg, 500 mg

• Injection: 1 g/vial (powder for reconstitution)

• Eye drops: 0.5% w/v

• Eye ointment: 1% w/w

• Otic drops: 5% w/v (or in combination with lidocaine) — Specialist only

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Typhoid and Paratyphoid Fever (Salmonella enterica)

Parameter Details

Starting dose 50 mg/kg/day orally in 4 divided doses

Titration Not applicable

Usual maintenance dose 50 mg/kg/day orally in 4 divided doses

Maximum dose 4 g/day

Duration 10–14 days

Clinical Notes:

• IV route reserved for severe disease or patients unable to tolerate oral therapy

• Blood cultures should be obtained before initiation

• Response typically seen within 3–5 days; if no improvement, reassess sensitivity

1. Bacterial Meningitis (When Sensitive Organisms Identified and No Alternative Available)

Parameter Details

Starting dose 75–100 mg/kg/day IV in 4 divided doses

Titration Not applicable

Usual maintenance dose 75–100 mg/kg/day IV in 4 divided doses

Maximum dose 4 g/day

Duration 10–14 days; longer if complications present

Clinical Notes:

• Reserve for penicillin/cephalosporin-allergic patients or multidrug-resistant cases

• Specialist infectious disease consultation mandatory

• Monitor CSF parameters for treatment response

1. Rickettsial Infections (e.g., Scrub Typhus) — Alternative to Doxycycline

Parameter Details

Starting dose 50 mg/kg/day orally in 4 divided doses

Titration Not applicable

Usual maintenance dose 50–75 mg/kg/day orally in 4 divided doses

Maximum dose 4 g/day

Duration 7–10 days

Clinical Notes:

• Use when tetracyclines are contraindicated (e.g., pregnancy, children <8 years)

• Specialist discretion advised

• Endemic in parts of India; high index of suspicion required

1. Bacterial Conjunctivitis and Superficial Eye Infections (Topical)

Formulation Dosing Duration

Eye drops (0.5%) 1–2 drops in affected eye(s) every 2–4 hours while awake 5–7 days

Eye ointment (1%) Apply to affected eye(s) 3–4 times daily 5–7 days

Clinical Notes:

• Reassess if no improvement or worsening after 48–72 hours

• Avoid prolonged use beyond recommended duration

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

Indication Dose Duration Notes Evidence Basis

Brain abscess (anaerobic coverage or penicillin-allergic patients) 75–100 mg/kg/day IV in 4 divided doses; Max 4 g/day Based on clinical response; typically weeks OFF-LABEL; Specialist only Indian ID specialist practice when cephalosporins contraindicated

Severe anaerobic infections 50–100 mg/kg/day IV or orally in 4 divided doses; Max 4 g/day Depends on primary site OFF-LABEL; Alternative to metronidazole; use limited by toxicity Specialist practice; reserve for resistant cases

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Typhoid Fever

Children >2 weeks 50 mg/kg/day orally or IV in 4 divided doses Not applicable 50–75 mg/kg/day in 4 divided doses 4 g/day 10–14 days

1. Bacterial Meningitis

Children >2 weeks 75 mg/kg/day IV in 4 divided doses Not applicable 75–100 mg/kg/day IV in 4 divided doses 4 g/day 10–14 days

1. Rickettsial Infections

Children >2 weeks 50 mg/kg/day orally in 4 divided doses Not applicable 50–75 mg/kg/day in 4 divided doses 4 g/day 7–10 days

1. Topical (Eye Infections)

Formulation Dose Duration

0.5% Eye drops 1 drop every 2–4 hours, up to 6 times/day 5–7 days

1% Eye ointment Apply 3–4 times daily 5–7 days

Secondary Indications — Paediatric Doses (Off-label, if any)

Indication Dose Duration Notes Evidence Basis

Neonatal sepsis 15–25 mg/kg/day IV in divided doses Variable; based on clinical response OFF-LABEL; Avoid if possible due to "Gray Baby Syndrome" risk; Specialist NICU supervision mandatory Historical use; superseded by safer agents; reserve for life-threatening infections with no alternatives

⚠️ Not recommended in neonates <2 weeks of age except under specialist supervision in life-threatening situations with no alternative.

Safety Monitoring in Children:

• Weekly CBC mandatory if systemic therapy exceeds 7 days

• Monitor for early signs of bone marrow suppression (pallor, petechiae, unexplained fever)

• Observe for signs of Gray Baby Syndrome in neonates (abdominal distension, vomiting, gray discoloration, cardiovascular collapse)

• No dose modification required in renal impairment

• Drug is not significantly removed by haemodialysis or peritoneal dialysis

• Monitor for accumulation of inactive metabolites in severe renal failure

• Known hypersensitivity to chloramphenicol or any component of the formulation

• Previous history of bone marrow aplasia or blood dyscrasias related to chloramphenicol

• Neonates (especially premature infants) — high risk of Gray Baby Syndrome

• Concurrent use with other bone marrow suppressant drugs (e.g., cytotoxic agents)

• Active bone marrow suppression from any cause

• Hepatic impairment — potential for drug accumulation and enhanced toxicity

• Prolonged systemic use — risk of dose-independent aplastic anaemia (idiosyncratic, potentially fatal)

• Pre-existing haematological disorders — increased susceptibility to bone marrow effects

• G6PD deficiency — use with caution, though not a major oxidant drug

• Renal impairment — monitor for inactive metabolite accumulation

• Concurrent use of drugs affecting haematopoiesis

• Avoid prolonged systemic use when topical alternatives are adequate

Parameter Details

Risk category Category C (based on international data); use with caution

Fetal risks Crosses placenta; risk of fetal bone marrow suppression; Gray Baby Syndrome in late pregnancy/peripartum

Preferred alternatives Azithromycin for typhoid; ampicillin for susceptible organisms; ceftriaxone where applicable

When it may be used Only when benefit clearly outweighs risk (e.g., severe rickettsial infections when tetracyclines contraindicated); specialist input essential

Monitoring Maternal CBC; neonatal monitoring for bone marrow suppression post-delivery

Parameter Details

Compatible with breastfeeding Not recommended during prolonged systemic therapy; topical ophthalmic forms are compatible

Drug levels in milk Moderate; sufficient to cause infant toxicity

Preferred alternatives Azithromycin, amoxicillin, or cephalosporins depending on infection

Infant monitoring Observe for feeding difficulty, pallor, diarrhoea, irritability; monitor for signs of bone marrow suppression if systemic maternal exposure

Parameter Recommendation

Starting dose Initiate at lower end of dosing range (50 mg/kg/day or lower)

Titration Not applicable; avoid dose escalation unless essential

Extra risks Higher risk of cumulative bone marrow toxicity; hepatic impairment common in elderly; monitor CBC and LFT frequently

Monitoring Baseline and weekly CBC; close clinical observation for signs of toxicity

Interacting Drug Effect Recommendation

Rifampicin Induces chloramphenicol metabolism; reduces efficacy; potential antagonism in bacterial killing Avoid combination in treatment of serious infections

Phenytoin Chloramphenicol inhibits CYP2C9; increases phenytoin levels; risk of phenytoin toxicity Avoid or monitor phenytoin levels closely; consider dose reduction

Warfarin Inhibits warfarin metabolism; enhanced anticoagulant effect; bleeding risk Avoid if possible; monitor INR frequently; reduce warfarin dose

Methotrexate Additive bone marrow suppression Avoid concurrent use

Co-trimoxazole Additive haematologic toxicity Avoid concurrent use

Cyclophosphamide and other cytotoxics Additive myelosuppression Avoid concurrent use

Interacting Drug Effect Recommendation

Paracetamol May increase half-life of chloramphenicol Monitor for toxicity with prolonged concurrent use

Oral hypoglycaemics (sulfonylureas) Chloramphenicol may potentiate hypoglycaemic effect Monitor blood glucose; adjust hypoglycaemic dose if needed

Live oral vaccines (typhoid, cholera) Chloramphenicol may reduce immune response Space administration by at least 24 hours; consider inactivated vaccines

Iron supplements May reduce chloramphenicol efficacy by altering haematologic response Separate administration; monitor clinical response

Vitamin B12 / Folic acid Chloramphenicol may interfere with erythropoietic response Monitor haematologic parameters

• Nausea and vomiting

• Diarrhoea

• Bitter or metallic taste (with oral formulation)

• Skin rash

• Glossitis and stomatitis

• Transient dose-related bone marrow suppression (reversible upon discontinuation)

Adverse Effect Clinical Significance

Aplastic anaemia Idiosyncratic; dose-independent; may occur weeks to months after exposure; potentially fatal; requires immediate discontinuation

Gray Baby Syndrome Circulatory collapse in neonates receiving IV chloramphenicol; presents with abdominal distension, vomiting, gray skin colour, hypothermia, cardiovascular collapse

Optic neuritis Rare; associated with prolonged use; may cause visual impairment

Peripheral neuropathy Rare; prolonged therapy; sensory disturbances

Anaphylaxis Rare; requires immediate cessation and emergency management

Hepatotoxicity Elevated transaminases; jaundice in severe cases

⚠️ Immediate discontinuation required if aplastic anaemia, Gray Baby Syndrome, or hypersensitivity reactions are suspected.

Phase Parameters

Baseline Complete blood count (CBC) with differential and reticulocyte count; liver function tests (LFT); renal function tests

During therapy Weekly CBC mandatory if systemic use exceeds 7 days; LFT every 1–2 weeks in prolonged therapy; clinical monitoring for signs of bone marrow suppression

Long-term/Post-therapy CBC monitoring for up to 2–3 months after therapy cessation (aplastic anaemia can be delayed); neurological assessment if prolonged use

Therapeutic drug monitoring Serum levels in severe infections/ICU settings if available (target trough: 5–15 mcg/mL; peak: 15–25 mcg/mL)

Systemic Formulations:

• Chloromycetin (Abbott)

• Chlorocid (Pfizer)

• Paraxin

• Campicid IV (Injectable)

Topical Ophthalmic Formulations:

• Chlorocol Eye Drops

• Ocupol-C Eye Drops

• Ophthocare Eye Drops/Ointment

• Chloramphenicol Eye Drops (Generic — various manufacturers)

Otic Formulations:

• Otobiotic Ear Drops (combination with polymyxin B)

• Candid Ear Drops (combination formulations)

• Reserve systemic use: Safer alternatives (fluoroquinolones, cephalosporins, azithromycin) are available for most indications; reserve chloramphenicol for resistant organisms or when alternatives are contraindicated.

• Topical use is safe: Ophthalmic chloramphenicol remains a widely useful and low-toxicity first-line option for bacterial conjunctivitis.

• Aplastic anaemia risk: Document clinical reasoning clearly when prescribing systemic chloramphenicol; educate patients about warning signs (unexplained bruising, bleeding, persistent sore throat, fever).

• Avoid in neonates: Gray Baby Syndrome risk is very high in neonates, especially premature infants; avoid unless absolutely essential and under specialist supervision.

• CBC monitoring is mandatory: Even short courses of systemic therapy exceeding 7 days require weekly CBC monitoring.

• Drug interactions matter: Be vigilant with concurrent warfarin, phenytoin, or methotrexate use; consider alternatives or adjust doses with close monitoring.

Chloramphenicol; typhoid; scrub typhus; rickettsial; bacterial meningitis; bone marrow suppression; aplastic anaemia; Gray Baby Syndrome; ophthalmic antibiotic; pregnancy-caution; hepatic-adjustment; NLEM India; Schedule H

RxIndia v1.0 — 28 Mar 2025

• CDSCO Approved Package Inserts

• Indian Pharmacopoeia / National Formulary of India

• National List of Essential Medicines (NLEM) India

• API Textbook of Medicine

• AIIMS Antibiotic Policy (Internal Medicine and Paediatrics)

• IAP Guidelines for Paediatric Infectious Diseases

• WHO Essential Medicines List (supportive reference for paediatric indications)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• Indian specialist clinical practice (Infectious Disease and Paediatric ID consultants)