acetylcysteine
antidote· Brands: Parvolex, Mucomyst, Fluimucil, N-A-C, Acetadote, NACIVNEBPO
Mechanism of action
Acetylcysteine acts as a precursor of glutathione, thereby replenishing hepatic glutathione stores. In paracetamol poisoning, it provides sulfhydryl groups that directly detoxify the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). As a mucolytic, it breaks the disulfide bonds in mucoproteins, reducing mucus viscosity.
Pharmacokinetics
Acetylcysteine is rapidly absorbed after oral administration, but undergoes extensive first-pass metabolism, resulting in a low bioavailability of around 10%. It is widely distributed, with peak plasma concentrations occurring 1 to 2 hours after oral ingestion. It is metabolized in the liver, with some renal excretion of metabolites. The elimination half-life is approximately 5 to 6 hours, though it varies with route of administration.
Indications & dosing
Paracetamol overdose
Loading dose over 1 h; then 50 mg/kg over 4 h; then 100 mg/kg over 16 h. Same weight-based 21-hour regimen in children.
- adult · IV: 150 mg/kg once · Loading dose over 1 h; then 50 mg/kg over 4 h; then 100 mg/kg over 16 h. Same weight-based 21-hour regimen in children.
Mucolytic in chronic respiratory disease
For chronic bronchitis and COPD. Alternative: 200 mg three times daily.
- adult · PO: 600 mg once daily · For chronic bronchitis and COPD. Alternative: 200 mg three times daily.
Mucolytic in cystic fibrosis
Nebulised 20% solution, 3-5 mL (600-1000 mg) three to four times daily.
- adult · NEB: 600–1000 mg 3 times daily · Nebulised 20% solution, 3-5 mL (600-1000 mg) three to four times daily.
Prevention of contrast-induced nephropathyoff-label
Off-label use. Give with hydration the day before and day of contrast procedure.
- adult · PO: 600 mg twice daily · Off-label use. Give with hydration the day before and day of contrast procedure.
Contraindications & precautions
- Known hypersensitivity to acetylcysteine · Exclude patients with a history of allergic reactions to acetylcysteine.
- Asthma or allergic bronchospasm · Increased risk of bronchospasm with IV administration; however, benefit in paracetamol overdose usually outweighs risk.
- Ensure resuscitation equipment and appropriate medications (e.g., bronchodilators, antihistamines) are available when administering IV acetylcysteine.
- Use caution in patients with asthma or a history of bronchospasm; monitor closely for signs of respiratory distress.
- Monitor fluid balance and serum sodium, as large volumes of IV fluid may be required for paracetamol overdose.
- Do not delay treatment with acetylcysteine in suspected paracetamol overdose while waiting for serum paracetamol concentration results.
Adverse effects
- Anaphylactoid reaction (bronchospasm, hypotension, angioedema)serious
- Nausea and vomiting
- Flushing
- Rash or pruritus
Monitoring, pregnancy & toxicity
- Serum paracetamol level · At presentation and according to nomogram
- Liver function tests (ALT, AST, bilirubin) · Baseline, then at least 24 hours
- INR · Baseline, then repeat as clinically indicated
- Renal function (serum creatinine, urea) · Baseline, then repeat
- Vital signs · Continuous during infusion
- Signs of anaphylactoid reaction (rash, bronchospasm, hypotension) · Throughout infusion
- Pregnancy: Acetylcysteine is the antidote of choice for paracetamol overdose in pregnancy; standard dosing is used. It should not be withheld due to pregnancy.
- Toxicity: Anaphylactoid reactions (e.g., rash, pruritus, bronchospasm, hypotension) · Stop infusion, administer antihistamines, bronchodilators, and IV fluids; consider restarting at a slower rate if reaction is mild.
- Toxicity: Nausea and vomiting · Slow the infusion rate, administer antiemetics.
- Toxicity: Flushing and urticaria · Usually transient; supportive measures.
Clinical notes
Acetylcysteine is the specific antidote for paracetamol (acetaminophen) poisoning, most effective when given within 8 to 10 hours of ingestion but still beneficial later. It is also used as a mucolytic in chronic respiratory diseases. It can be given orally or intravenously, with the intravenous route preferred in severe poisoning. Adverse effects include anaphylactoid reactions, nausea, and vomiting, particularly with rapid intravenous infusion. Dosing is based on body weight and should follow local protocols.
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BNF; local formulary