Schedule H

Oral, Intravenous, Inhalation

• Effervescent tablets: 600 mg

• Oral granules/sachets: 100 mg, 200 mg, 600 mg (for oral solution)

• Injection: 200 mg/mL (10 mL vial — 2000 mg)

• Injection: 200 mg/mL (25 mL vial — 5000 mg)

• Nebuliser solution: 10% w/v (100 mg/mL)

• Nebuliser solution: 20% w/v (200 mg/mL)

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Paracetamol (Acetaminophen) Poisoning — Antidote — Adults

Intravenous Protocol (Preferred — 21-hour regimen):

Phase Dose Diluent Infusion Time

Loading dose 150 mg/kg 200 mL 5% Dextrose Over 1 hour

First maintenance 50 mg/kg 500 mL 5% Dextrose Over 4 hours

Second maintenance 100 mg/kg 1000 mL 5% Dextrose Over 16 hours

Total dose 300 mg/kg — Over 21 hours

Clinical Notes:

• Initiate within 8 hours of ingestion for maximum hepatoprotection; still beneficial up to 24 hours or later if hepatotoxicity present

• Use Rumack-Matthew nomogram to assess need for NAC in acute single ingestion (plot serum paracetamol level against time since ingestion)

• Continue beyond 21 hours if INR elevated, rising transaminases, or ongoing hepatotoxicity — consult toxicology/hepatology

• Dilute ONLY in 5% Dextrose — do not use normal saline

Oral Protocol (Alternative when IV not feasible):

Parameter Recommendation

Starting dose (Loading) 140 mg/kg orally

Titration Not applicable

Usual maintenance dose 70 mg/kg every 4 hours × 17 doses

Maximum dose Total 1330 mg/kg over 72 hours

Clinical Notes:

• Dilute in cola, juice, or water to improve palatability and reduce vomiting

• If vomiting occurs within 1 hour of dose, repeat that dose

• Less preferred due to high emesis rate; reserve for settings where IV unavailable

1. Mucolytic Therapy (Chronic Bronchitis, COPD, Bronchiectasis) — Adults

Oral Route:

Parameter Recommendation

Starting dose 600 mg orally once daily

Titration May increase to twice daily if tolerated and needed

Usual maintenance dose 600 mg once or twice daily

Maximum dose 1200 mg/day

Duration: Long-term use acceptable; reassess efficacy periodically

Inhalation Route (Nebulised):

Parameter Recommendation

Starting dose 3–5 mL of 10% solution OR 1–2 mL of 20% solution via nebuliser

Titration Adjust frequency based on sputum viscosity

Usual maintenance dose 3–5 mL of 10% solution 3–4 times daily

Maximum dose 20 mL of 10% solution per day in divided doses

Clinical Notes:

• Pre-treatment with bronchodilator (salbutamol) recommended to reduce bronchospasm risk

• May be diluted with normal saline if irritation occurs

• Direct instillation via tracheostomy: 1–2 mL of 10–20% solution every 1–4 hours

1. Cystic Fibrosis — Mucolytic — Adults

Parameter Recommendation

Starting dose 3–5 mL of 10% solution via nebuliser twice daily

Titration Adjust frequency based on response

Usual maintenance dose 3–5 mL of 10% solution 2–4 times daily

Maximum dose 20 mL of 10% solution per day

Clinical Notes:

• Use as part of comprehensive airway clearance regimen

• Dornase alfa (rhDNase) is often preferred mucolytic in CF where available

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Contrast-Induced Nephropathy Prevention 600–1200 mg orally twice daily Start 24 hours before contrast; continue for 24–48 hours after OFF-LABEL • Evidence conflicting; benefit uncertain • Not routinely recommended in current guidelines • Consider in high-risk patients (eGFR <45, diabetes) with adequate hydration

Non-Alcoholic Fatty Liver Disease (NAFLD) 600 mg orally twice daily 3–6 months OFF-LABEL • Specialist only • Antioxidant effect • Limited Indian data

Acute Respiratory Distress Syndrome (ARDS) — Adjunct 40–150 mg/kg/day IV in divided doses ICU setting; variable duration OFF-LABEL • Specialist/ICU only • Variable protocols • Limited evidence

PAEDIATRIC DOSING (Specialist Only)

Primary Indications (Approved / Standard in India)

1. Paracetamol Poisoning — Antidote

Intravenous Protocol:

Weight Category Loading Dose First Maintenance Second Maintenance

<20 kg 150 mg/kg in 3 mL/kg 5% Dextrose over 1 hour 50 mg/kg in 7 mL/kg 5% Dextrose over 4 hours 100 mg/kg in 14 mL/kg 5% Dextrose over 16 hours

20–40 kg 150 mg/kg in 100 mL 5% Dextrose over 1 hour 50 mg/kg in 250 mL 5% Dextrose over 4 hours 100 mg/kg in 500 mL 5% Dextrose over 16 hours

40 kg Adult volumes and dosing Adult volumes Adult volumes

Clinical Notes:

• Total dose: 300 mg/kg over 21 hours (same as adults)

• Volume reduction critical in children <20 kg to prevent fluid overload

• Continue if hepatotoxicity evident; consult paediatric toxicology

Oral Protocol (Alternative):

Parameter Recommendation

Starting dose (Loading) 140 mg/kg orally

Usual maintenance dose 70 mg/kg every 4 hours × 17 doses

Maximum dose Total 1330 mg/kg over 72 hours

1. Mucolytic Therapy — Inhalation

Age-Based Dosing:

2–6 years 3 mL of 10% solution via nebuliser 2–3 times daily Specialist supervision; pre-treat with bronchodilator

6–12 years 3–5 mL of 10% solution via nebuliser 2–4 times daily Pre-treat with bronchodilator

12 years Adult dosing 3–4 times daily —

Safety Monitoring:

• Monitor for bronchospasm — have bronchodilator available

• Suction equipment should be available if child cannot expectorate

• Observe for increased sputum production

Secondary Indications — Paediatric (Off-label)

Not applicable — No routinely accepted off-label paediatric uses in Indian practice.

Age Restrictions:

• Nebulised acetylcysteine: Not recommended in children <2 years except under specialist supervision due to risk of bronchospasm and inability to clear increased secretions

• Oral mucolytic use: Limited data in children; avoid routine use below 2 years

• IV antidote use: No minimum age — use for paracetamol poisoning in any age group

No dose adjustment required for any indication.

Notes:

• Acetylcysteine is not significantly renally excreted

• Safe in renal impairment including dialysis patients

• For paracetamol poisoning in dialysis patients: administer as per standard protocol; drug not significantly removed by dialysis

Notes:

• In paracetamol poisoning with hepatic failure, IV fluid volumes may need adjustment to prevent fluid overload

• Continue NAC until INR normalising and transaminases declining

• Known hypersensitivity to acetylcysteine

• Severe uncontrolled asthma (for inhaled route) — risk of severe bronchospasm

• Previous anaphylactoid reaction to IV acetylcysteine requiring permanent discontinuation

Note: For paracetamol poisoning, there are no absolute contraindications — benefit of preventing hepatic failure outweighs risks.

• Bronchial asthma — inhaled and IV routes may trigger bronchospasm; pre-treat with bronchodilator; have emergency treatment available

• History of peptic ulcer disease — oral acetylcysteine may cause GI irritation

• Fluid overload risk — large IV volumes in 21-hour protocol; monitor in cardiac failure, renal failure, or low body weight

• Anaphylactoid reactions — common with IV route (up to 10–20%); usually manageable without stopping infusion

• Inability to protect airway or expectorate — inhaled route may increase secretions dangerously

• Patients <40 kg or <20 kg — adjust IV fluid volumes to prevent hyponatraemia or fluid overload

Parameter Information

Risk Category Generally considered safe (limited human data; animal studies reassuring)

Overall Safety Benefits outweigh risks, especially for paracetamol poisoning

Preferred Alternatives None — acetylcysteine is the treatment of choice for paracetamol overdose in pregnancy

When May Be Used Essential for paracetamol poisoning at any stage of pregnancy; mucolytic use if clearly indicated

Monitoring Maternal LFTs, INR in overdose; standard antenatal monitoring; fetal wellbeing in significant overdose

Note: Untreated paracetamol poisoning carries high fetal and maternal mortality — do not delay NAC due to pregnancy.

Parameter Information

Compatibility Compatible with breastfeeding

Expected Milk Levels Low — minimal systemic absorption with oral mucolytic doses; short half-life

Preferred Alternatives None needed for indicated uses

Decision Continue breastfeeding; no interruption required

Infant Monitoring Observe for irritability, GI upset (unlikely)

Parameter Recommendation

Starting dose Standard adult dosing for all routes

Titration Standard titration

Special considerations Higher risk of fluid overload with IV protocol in patients with cardiac failure

Extra monitoring Fluid balance; renal function; cardiac status during IV infusion

Risk factors Pre-existing cardiac disease; reduced renal reserve

Interacting Drug Effect & Mechanism Management

Activated charcoal Adsorbs oral acetylcysteine — reduces absorption by up to 30% Separate doses by at least 2 hours; if both indicated for paracetamol overdose, give charcoal first, then IV NAC preferred

Nitrates (nitroglycerin, isosorbide) Additive vasodilation — may cause significant hypotension Monitor blood pressure if used concurrently; use with caution

Interacting Drug Effect Management

Carbamazepine Hepatotoxic paracetamol metabolite production may be increased in carbamazepine users — lower threshold for NAC Use standard NAC protocol; may need treatment at lower paracetamol levels

Phenytoin, Phenobarbital Enzyme induction increases toxic metabolite of paracetamol Lower threshold for NAC treatment

Isoniazid Increased paracetamol hepatotoxicity risk Be vigilant; use NAC at lower threshold if overdose suspected

Antitussives May reduce cough reflex needed to clear increased secretions from mucolytic effect Avoid concurrent use with inhaled acetylcysteine

Laboratory Interference:

• May cause false results in colorimetric assays for salicylates, glucose, and uric acid

• Use enzymatic glucose assays in diabetic patients receiving acetylcysteine

Intravenous Route:

• Anaphylactoid reactions (flushing, urticaria, pruritus, angioedema) — up to 10–20%

• Nausea and vomiting

• Hypotension (usually transient)

• Bronchospasm (especially in asthmatics)

Oral Route:

• Nausea and vomiting (common — due to sulfur odour and taste)

• Diarrhoea

• Abdominal discomfort

• Unpleasant sulfurous odour ("rotten egg" smell)

Inhalation Route:

• Bronchospasm

• Cough

• Rhinorrhoea

• Nausea

• Stomatitis

• Increased secretions

Adverse Effect Clinical Action

Anaphylactoid reaction (urticaria, angioedema, bronchospasm, hypotension) Temporarily pause infusion; give IV antihistamine (chlorpheniramine) ± hydrocortisone; restart at slower rate once symptoms controlled — rarely requires permanent discontinuation

Severe bronchospasm Stop infusion/inhalation; bronchodilator therapy; oxygen; consider adrenaline if severe

Severe hypotension Stop infusion; IV fluids; vasopressors if needed

Anaphylaxis (true IgE-mediated — extremely rare) Permanent discontinuation; standard anaphylaxis management

Note: Most IV reactions are anaphylactoid (non-IgE mediated) and do not preclude continued treatment after symptom management.

For Paracetamol Poisoning:

During IV infusion Vital signs (especially for anaphylactoid reactions); hourly during loading dose

Serial monitoring LFTs, INR, creatinine — every 12–24 hours until improving

End of protocol Repeat LFTs, INR — continue NAC if still abnormal

For Mucolytic Therapy:

During therapy Monitor for bronchospasm; sputum clearance; respiratory comfort

Long-term Periodic assessment of symptom improvement

Oral/Effervescent:

• Mucinac (Cipla)

• NAC (Samarth)

• Fluimucil (Zambon)

• Acemiz (Systopic)

• Mucyst (Torrent)

• Nacfil (Cipla)

• Mucox (FDC)

Injectable:

• Mucinac Injection (Cipla)

• NAC Injection (various manufacturers)

• Fluimucil Injection (Zambon)

Nebuliser Solution:

• Mucomix (Cipla)

• Mucinac Respules (Cipla)

• Fluimucil Nebuliser Solution (Zambon)

FDCs Available:

• Acetylcysteine + Ambroxol

• Acetylcysteine + Levosalbutamol

(Use only if specifically indicated; monotherapy preferred for dose titration)

Note: Injection (for paracetamol poisoning) included in NLEM 2022 — may be NPPA price-controlled. Available in government hospitals for toxicology emergencies.

• IV route is preferred for paracetamol poisoning — oral NAC has high emesis rate and erratic absorption after overdose; reserve oral for settings without IV access

• Dilute IV NAC only in 5% Dextrose — not normal saline; ensures stability and prevents precipitation

• Anaphylactoid reactions are common but manageable — do not abandon NAC therapy for mild-moderate reactions; pause infusion, treat with antihistamines ± steroids, and resume at slower rate

• Use Rumack-Matthew nomogram — plot paracetamol level against time post-ingestion (minimum 4 hours) to determine NAC indication; if time of ingestion unknown or staggered overdose, treat empirically

• Don't confuse formulations — injectable acetylcysteine is NOT interchangeable with nebuliser or oral solutions; each has specific concentration and use

• Pre-treat with bronchodilator before nebulised NAC — reduces bronchospasm risk, especially in asthmatics and COPD patients

Acetylcysteine; N-acetylcysteine; NAC; antidote; paracetamol poisoning; acetaminophen overdose; mucolytic; glutathione precursor; emergency medicine; NLEM India; asthma-caution; pregnancy-safe

RxIndia v1.0 — 05 Jan 2025

• CDSCO Approved Drug Formulations Database

• Indian Pharmacopoeia 2022

• National Formulary of India 2021

• NLEM 2022

• AIIMS Emergency Medicine Handbook / Toxicology Protocols

• API Textbook of Medicine, 11th Edition

• ICMR Guidelines for Poisoning Management

• Harrison's Principles of Internal Medicine, 21st Edition

• Goodman & Gilman's The Pharmacological Basis of Therapeutics

• WHO Model List of Essential Medicines

• Indian critical care and pulmonology protocols