UMEM Educational Pearls

Category: Toxicology

Title: A Simpler IV Acetylcysteine Regimen for Acetaminophen Overdose?

Keywords: acetaminophen, acetylcysteine (PubMed Search)

Posted: 1/7/2016 by Bryan Hayes, PharmD (Emailed: 1/14/2016) (Updated: 1/14/2016)
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The three-bag IV acetylcysteine regimen for acetaminophen overdose is complicated and can result in medication/administration errors. [1] Two recent studies have attempted simplifying the regimen using a two-bag approach and evaluated its effect on adverse effects. [2, 3]

Study 1 [2]

Prospective comparison of cases using a 20 h, two-bag regimen (200 mg/kg over 4 h followed by 100 mg/kg over 16 h) to an historical cohort treated with the 21 h three-bag IV regimen (150 mg/kg over 1 h, 50 mg/kg over 4 h and 100 mg/kg over 16 h).

The two-bag 20 h acetylcysteine regimen was well tolerated and resulted in significantly fewer and milder non-allergic anaphylactic reactions than the standard three-bag regimen.

Study 2 [3]

Prospective observational study of a modified 2-phase acetylcysteine protocol. The first infusion was 200 mg/kg over 4-9 h. The second infusion was 100 mg/kg over 16 h. Pre-defined outcomes were frequency of adverse reactions (systemic hypersensitivity reactions or gastrointestinal); proportion with ALT > 1000 U/L or abnormal ALT.

The 2-phase acetylcysteine infusion protocol resulted in fewer reactions in patients with toxic paracetamol concentrations.

Final word: Two-bag regimens seem to offer advantages compared to the traditional three-bag regimen with regard to reduced adverse drug reactions. Look for more data, particularly on effectiveness, and a potential transition to a two-bag approach in the future.


  1. Hayes BD, et al. Frequency of medication errors with intravenous acetylcysteine for acetaminophen overdose. Ann Pharmacother 2008;42(6):766-70. [PMID 18445707]
  2. Wong A, et al. Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetaml poisoning results in a lower incidence of adverse drug reactions. Clin Toxicol 2015 Nov 23:1-5 [Epub ahead of print, PMID 26594846]
  3. Isbister GK, et al. A prospective observational study of a novel 2-phase infusion protocol for the administration of acetylcysteine in paracetamol poisoning. Clin Toxicol 2015 Dec 22:1-7. [Epub ahead of print, PMID 26691690]

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