Pharmacology · Specific antidotes
Acetylcysteine !
The antidote for paracetamol (acetaminophen) overdose: it refills the liver's glutathione so the toxic metabolite is neutralised before it kills liver cells.
Updated 2026-11-01
Also called: N-acetylcysteine (NAC)
Mechanism of action
In overdose, the liver's conjugation pathways saturate and more paracetamol goes through cytochrome P450 to NAPQI, a reactive metabolite normally neutralised by glutathione. When glutathione runs out, NAPQI binds liver proteins and causes centrilobular necrosis. Acetylcysteine is a cysteine donor that restores glutathione, and it can also act as a substitute for glutathione in conjugating NAPQI. It protects best when started early after the ingestion.
- Overdose: more paracetamol becomes toxic NAPQI
- Glutathione runs out and NAPQI damages liver cells
- Acetylcysteine refills glutathione and binds NAPQI
- Less liver necrosis, best if started early
Pharmacokinetics
- Distribution
- Moderate volume of distribution; largely bound to plasma proteins
- Metabolism
- Converted to cysteine and other metabolites, feeding glutathione synthesis
- Elimination
- The kidneys account for roughly a third of its clearance
- Half-life
- About five and a half hours after intravenous use
- Onset and duration
- Maximal liver protection when started within about 8 hours of an acute ingestion; it is still given later
Indications
- Paracetamol (acetaminophen) overdose, guided by the time of ingestion and the serum level on the treatment nomogram Acetaminophen toxicity →
- Repeated supratherapeutic paracetamol use with raised levels or liver enzymes (the nomogram does not apply) Acetaminophen toxicity →
Adverse effects
Common
- Flushing, urticaria and itching, mostly early in the infusion
- Nausea and vomiting
- Tachycardia and oedema
Contraindications
- Previous hypersensitivity reaction to acetylcysteine (relative: in a serious overdose the benefit is weighed against the risk)
Key interactions
- Nitroglycerin
- Acetylcysteine may increase its hypotensive effect
- Activated charcoal (oral acetylcysteine)
- Both are given in early poisoning; the oral antidote and the charcoal are spaced so the charcoal does not adsorb it
What is monitored
- Serum paracetamol level at the right time after ingestion
- ALT/AST and INR, at the start and after the last bag
- Signs of allergic reaction during the first infusion
- Sodium and fluid balance in children and in fluid-restricted patients
Administration and safety
- The intravenous solution is hyperosmolar and must be diluted before use
- Given as a sequence of infusions; volumes are reduced for small children and fluid-restricted patients
- If an allergic reaction occurs, the infusion is stopped, the reaction treated, and the infusion may be restarted carefully
- Treatment is not withheld while waiting for a level when the patient arrives late or the time of ingestion is unknown
Nursing care
- Record the time of ingestion and the amount reported
- Watch skin, breathing and blood pressure closely in the first hour of infusion
- Check the sequence and timing of each infusion bag
- Track liver tests and INR when the course ends
- Ask about suicidal intent and arrange mental-health assessment
Pregnancy and breastfeeding
Data in pregnancy are limited, but delaying treatment of a paracetamol overdose raises maternal and fetal risk, so it is used in pregnancy.
Test yourself
Think of the answer, then tap the question to see it.
Which metabolite of paracetamol damages the liver in overdose?
NAPQI, formed by cytochrome P450 when conjugation is saturated; glutathione normally neutralises it.
How does acetylcysteine protect the liver?
It donates cysteine to rebuild glutathione and can conjugate NAPQI itself.
Why is acetylcysteine started even when the patient arrives late?
Protection is greatest within about 8 hours but some benefit remains, it does not worsen the patient, and the reported time may be wrong.
What is the most common serious reaction during the first infusion?
An anaphylactoid reaction (flushing, urticaria, bronchospasm, hypotension); it is managed and the infusion can often be restarted.
Related drugs
Related conditions
← Back to the class: Specific antidotes
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - ACETYLCYSTEINE injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Guía para el Manejo de Emergencias Toxicológicas (Ministerio de Salud y Protección Social; Organización Panamericana de la Salud, 2017); eEML - Electronic Essential Medicines List (World Health Organization, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.