Mucolytic / Hepatoprotective Antidote
Pregnancy: Safe — recommended in pregnancy; paracetamol overdose in pregnancy requires prompt treatment; acetylcysteine crosses placenta and protects fetus as well as mother
Acetylcysteine (N-acetylcysteine — Paracetamol Overdose)
Brand names: Parvolex
Adult dose
Dose: Three-bag regimen: 150 mg/kg in 200 mL 5% glucose over 1 hour; then 50 mg/kg in 500 mL over 4 hours; then 100 mg/kg in 1000 mL over 16 hours (total 300 mg/kg over 21 hours)
Route: Intravenous infusion (5% glucose diluent — NOT 0.9% saline)
Frequency: Continuous three-stage infusion over 21 hours
Max: 300 mg/kg total dose (adjusted for weight)
Must be commenced within 8 hours of ingestion for maximum hepatoprotection; effective up to 24h; check paracetamol level at 4 hours post-ingestion (or at presentation if >4h); plot on NPIS treatment nomogram
Paediatric dose
Dose: Same weight-based regimen as adults (150 mg/kg → 50 mg/kg → 100 mg/kg) mg/kg
Route: Intravenous
Frequency: Three-stage regimen
Max: As per NPIS nomogram; weight capped at 110 kg for dosing
Paediatric doses same per kg; use smaller volumes; BNFc and NPIS for weight-based calculations; contact NPIS (0344 892 0111) for guidance
Dose adjustments
Renal
No dose adjustment required
Hepatic
No dose adjustment required — used precisely in hepatotoxicity context
Paediatric weight-based calculator
Paediatric doses same per kg; use smaller volumes; BNFc and NPIS for weight-based calculations; contact NPIS (0344 892 0111) for guidance
Clinical pearls
- MHRA 2012 simplified regimen: previous complex multi-bag regimen replaced by 3-bag system administered over 21 hours — same total dose (300 mg/kg), dramatically reduced prescribing errors; current standard is 3-bag Parvolex regimen
- Treatment nomogram: paracetamol level at 4h post-ingestion plotted on NPIS nomogram — single treatment line at 100 mg/L at 4h; treat all patients whose level falls on or above the line regardless of history of risk factors
- Anaphylactoid reaction management: stop infusion immediately → give chlorphenamine 10 mg IV → restart at half rate in 15-30 minutes; most reactions occur during first bag (high concentration) — complete subsequent bags is usually safe; rarely requires discontinuation
- Late presentation (>24h): if paracetamol level undetectable but significant ingestion history with elevated ALT — give acetylcysteine as hepatotoxicity may already be established; contact NPIS for guidance on duration
- Mechanism: acetylcysteine replenishes hepatic glutathione stores — glutathione neutralises NAPQI (toxic paracetamol metabolite N-acetyl-p-benzoquinone imine) which accumulates after cytochrome P450 saturation; prevents hepatocyte necrosis when given early
Contraindications
- Known hypersensitivity to acetylcysteine (anaphylactoid reactions occur in ~15% — manage by slowing/stopping infusion, give antihistamine, restart at lower rate)
Side effects
- Anaphylactoid reactions (15% — most common in first bag, particularly in asthmatics; flushing, urticaria, bronchospasm, hypotension — NOT true anaphylaxis; managed by stopping infusion temporarily)
- Nausea
- Vomiting
- Rash
Interactions
- No clinically significant interactions at standard doses
Monitoring
- ALT/AST, INR, creatinine (at start and after 21-hour course)
- Paracetamol level (4h post-ingestion or at presentation)
- Anaphylactoid reaction signs (first 30 min of each bag)
- INR >2 at 24h = significant hepatotoxicity — contact liver unit
Reference: BNFc; BNF 90; MHRA Parvolex SPC; NPIS TOXBASE; NICE CG16 (Self-harm); Bateman et al. Lancet 2014 (SNAP trial); MHRA 2012 simplified regimen. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.