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Oral methionine compared with intravenous n-acetyl cysteine for paracetamol overdose

Three Part Question

In a [patient with paracetamol overdose within eight hours] is [methionine as good as or better than n-acetyl cysteine] at [reducing liver damage]?

Clinical Scenario

A 19 year old woman is brought to the emergency department 6 hours after paracetamol overdose. She is fully conscious and admits ingestion of 32 tablets of paracetamol. She is complaining of abdominal discomfort but no nausea or vomiting. Her examination is unremarkable. You arranged blood investigations. IV access and n-acetyl cysteine infusion started as per protocol. You wonder whether oral methionine would have been as effective as n-acetyl cysteine in her treatment.

Search Strategy

Medline 1966-04/03 using the OVID interface.
[exp methionine OR methionine$.mp] AND [exp acetaminophen OR acetaminophen$.mp OR] AND [exp acetylcysteine OR acetylcysteine$.mp OR] LIMIT to human AND English.

Search Outcome

Altogether 39 papers were found, of which 2 were relevant.

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Vale JA et al,
158 patients with paracetamol overdose. Mean age: 26 ys 1:2 M, F ratio High risk patients defined as paracetamol level: >300mg/l at 4 h.Prospective observationalLiver damage:NSDNo randomisation Small study 2 out of the 7 vomited the first dose
Methionine within 10h (n=96)7%
IV n-acetylcysteine within 10h (n=62)2%
In high risk patients methionine within 10 h (n=43)14%
In high risk patients IV n-acetylcysteine within 10 h (n=33)3%
Prescott LF,
104 patients with paracetamol overdose. Mean group 33ys. 1:1.5 M,F Ratio High risk patients defined as paracetamol level: >300mg/l at 4h Prospective observationalLiver damage:NSDNo randomisation Small study
Methionine. Within 10 h (n=42) 57% of them were high risk7%
IV n-acetyl cysteine within 10 h (n=62) 33/62 (53%) of them were high risk2%


There have been no randomised controlled trials and only two prospective observational studies comparing these two drugs. However, patients in these two studies had the antidote within eight hours.

Clinical Bottom Line

IV acetylcysteine (parvolex) is more effective than methionine at preventing liver damage in patients after paracetamol overdose.


  1. Vale JA and Meredith TJ. Treament of Acetaminophen poisoning. Arch Inter Med 1981;141(3 spec no):394-6.
  2. Prescott LF. Treatment of severe Acetaminophen poisoning with intravenous Acetylcysteine. Arch Inter Med 1981;141(3 spec no):386-9.