Mucolytic / Paracetamol overdose antidote
Pregnancy: Safe at therapeutic doses. Established treatment for paracetamol overdose in pregnancy — paracetamol toxicity is more harmful to mother and fetus than acetylcysteine.
Acetylcysteine
Brand names: Parvolex (IV), NAC, Mucomyst
Adult dose
Dose: Mucolytic (oral): 600 mg OD–TDS. Idiopathic pulmonary fibrosis (off-label): 600 mg TDS. Paracetamol overdose (IV — UK 21-hour SNAP-modified regimen): 100 mg/kg in 200 ml 5% glucose over 2 hours, then 200 mg/kg in 1000 ml over 10 hours (alternative: original 21-hr regimen 150 mg/kg over 1 hr, then 50 mg/kg over 4 hr, then 100 mg/kg over 16 hr).
Route: Oral / IV infusion
Frequency: Variable by indication
For paracetamol overdose, see TOXBASE / MHRA Drug Safety Update Aug 2012 — single 100 mg/L treatment line at 4 hours.
Paediatric dose
Dose: 150 mg/kg
Route: IV infusion
Frequency: Three-bag regimen (paracetamol overdose)
Same mg/kg regimen as adults. Use weight-based fluid volumes (especially under 20 kg) to avoid hyponatraemia: 5% glucose at 7 ml/kg / 14 ml/kg / 28 ml/kg for the three bags. Always TOXBASE.
Dose adjustments
Renal
No dose adjustment. Caution in oliguria — fluid balance.
Hepatic
No reduction needed for paracetamol overdose use (acetylcysteine is the treatment).
Paediatric weight-based calculator
Same mg/kg regimen as adults. Use weight-based fluid volumes (especially under 20 kg) to avoid hyponatraemia: 5% glucose at 7 ml/kg / 14 ml/kg / 28 ml/kg for the three bags. Always TOXBASE.
Clinical pearls
- Paracetamol overdose: in the UK, treat all patients with plasma paracetamol above the single 100 mg/L treatment line at 4 hours post-ingestion (MHRA Aug 2012 — single line replaces previous 'high-risk' line).
- Start NAC empirically within 8 hours if any of: staggered ingestion, unknown timing, OD ≥150 mg/kg, or symptomatic patient — do not wait for level.
- Anaphylactoid reactions are infusion-rate-dependent; the SNAP 12-hour or 21-hour modified regimens (Bateman et al. Lancet 2014) reduce reaction rates without compromising efficacy.
- Asthmatics: pre-treat with nebulised salbutamol if previous reaction; bronchospasm responds to standard asthma management.
- Mucolytic role limited in routine COPD — Cochrane evidence weak. Strongest evidence for adjunctive use in IPF (IFIGENIA trial neutral; PANTHER-IPF found NAC monotherapy did not differ from placebo).
- Useful as antidote for contrast-induced nephropathy prophylaxis is no longer supported (PRESERVE trial NEJM 2018 — no benefit).
Contraindications
- Previous severe anaphylactoid reaction to IV acetylcysteine (rare — usually slow infusion preferred)
- Hypersensitivity to acetylcysteine
Side effects
- Anaphylactoid reaction during IV infusion (~15% — flushing, urticaria, angioedema, bronchospasm; usually within first hour). NOT a true allergy — treat with chlorphenamine ± hydrocortisone, slow/pause infusion, then resume.
- Bronchospasm — particular caution in asthmatics; pre-treat with salbutamol if previous reaction
- Nausea, vomiting (very common with oral; common with IV)
- Rash, pruritus
- Hypotension, tachycardia
- Headache
- Hyponatraemia in small children (relate to fluid volume, not drug)
Interactions
- Activated charcoal: ↓ oral acetylcysteine absorption — separate by 1 hour or give IV instead
- Glyceryl trinitrate / nitroglycerin: potentiates hypotension and headache
- Carbamazepine, phenobarbital, isoniazid, rifampicin: CYP450 inducers — increase paracetamol toxicity threshold; treatment line unchanged in UK
Monitoring
- Paracetamol overdose: paracetamol level and ALT, INR, creatinine at presentation; ALT, INR, creatinine, venous bicarbonate at end of treatment; transfer to liver unit if criteria met (King's College criteria)
- BP and infusion-site observation throughout IV course
Reference: BNFc; BNF 90; BNF for Children 2024; TOXBASE Paracetamol Monograph; MHRA Drug Safety Update Aug 2012 (Paracetamol overdose treatment line); SNAP trial (Bateman et al. Lancet 2014); IFIGENIA trial NEJM 2005;353:2229; PANTHER-IPF NEJM 2014;370:2093; PRESERVE NEJM 2018;378:603. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.