Friday, September 18, 2026

NAC Regimen


Antidote for paracetamol poisoning is NAC. NAC replenishes cellular glutathione, which protects hepatocytes against injury from the toxic paracetamol metabolite N acetyl p benzoquinone imine (NAQPI). 

21h conventional NAC regimen developed by Prescott has been used since 1970's. The 21h NAC regimen is associated high incidence of anaphylaxis.  The complex regimen can lead to medication errors, frequent treatment interruption, prolonged stays. Since then only a few studies have been done to identify a alternative regimen. 


NAC IV Regime

1. Conventional Three Bag Regime 

  • 150mg/kg in 5D over 15 minutes
  • 50mg/kg in 500ML 5D over 4 hours
  • 100mg/kg in 1L 5D over 16 hours



2. SNAP 12h Regimen ( Scottish and Newcastle Anti emetic Pretreatment for paracetamol poisoning study regimen) 

  • 100mg/kg over 2 h in 200ml D5
  • 200mg/kg over 10h 1L D5
  • Followed by 5% Dextrose over 8h

  • Thanacoody et al (BMC Pharmacology and Toxicology 2013) proposed that adverse effects of 21h regimen was related to high concentration of NAC following loading infusion.   Using the pharmacokinetic data from Prescot they performed a, Monte carlo stimulation to derive expected plasma concentration. Based on this data they estimated that the modified infusion (SNAP) regimen would rise the plasma concentration of 306, 122 and 30 mg/L at 2h, 12h and 20h respectively.
  • SNAP Regimen will achieve a lower peak and a 20h plasma concentration comparable to conventional regimen. Anaphylactoid reaction is assumed to be dose dependent and pharmacokinetic data shows this occurs when NAC >650mg/L. Hence adverse events are believed to be less in the new regime. 
  • Bateman et al (Lancet.2014) did a double blinded RCT to assess whether adverse effect could be reduced with modified regimen. The study found that 12h regimen resulted in lower vomiting and anaphylatoid reaction. 
  • Pettie et al (EClinicalMedicine. 2019) did a study to assess the safety & efficacy of the SNAP 12 hour acetylcysteine regimen for paracetamol poisoning. They compared data of patients treated with 21h conventional regimen (n=1488) to new 12 h SNAP regimen (n=1852) . They found that there was no difference in liver injury or dysfunction in both regimen. Hepatotoxicty (ALT >1000 U/L) occured in 64 (4.3%) and 67 (3.6%) patients, respectively in 21h and SNAP regimen.



3. Simplified Two Bag Regime 
  • 200mg/kg in 500ml D5 over 4 hours
  • 100mg/kg in 1L D5 over 16 hours

  • Wong et al (Clinical Toxicology. 2015 ) did a study to compare incidence of adverse drug events of two bag acetylcysteine regimen with that of traditional three bag regimen. The study found that 2 bag regimen was well tolerated and resulted in significantly fewer and milder adverse effects than 3 bag regimen. 
  • Isbister et al (Clinical Toxicology. 2015 ) did a prospective observational study of a novel 2-phase infusion protocol for administration of acetylcysteine in paracetamol poisoning and found that 2 phase NAC infusion protocol results in fewer reactions. 
  • Cole at al (West J Emerg Med. 2023) did a meta analysis and found 2 bag NAC regimen have similar outcome to the traditional three bag regimen. 
  • Wong et al (Lancet.2020) 2NAC Study did a multicentric observational study done in 9 centres in Australia to compare the rate of ALI after paracetamol overdose in two bag regimen compared to three bag regimen. ALI was observed in 3.1% (21/668) with the two-bag regimen and 2.9% (16/557) with the three-bag regimen (Difference: 0.2%, 95%CI:−1.6 to 2.2). The incidence of hepatotoxicity was: 1.2% (n = 8) with the two-bag regimen and 1.6% (n = 9) with the three-bag regimen (Difference −0.4%, 95%CI −1.75 to 0.91). The incidence of peak INR >2.0 was 0.9% (n = 6) with the two-bag regimen vs 0.4% (n = 2) with the three-bag regimen (Difference: 0.5%, 95%CI −0.33 to 1.41). A two-bag intravenous acetylcysteine regimen was found to be non-inferior to the traditional three-bag regimen with regards to efficacy in preventing acute liver injury for early presentations of paracetamol overdose.

Stopping Criteria

  • Treat with NAC until 
  • Paracetamol levels < 10 mg/L
  • AST or ALT < 100 u/l
  • INR <2
  • Patient is clinically stable and atleast 12h of NAC is given.


Conclusion
  • Both 3 bag and 2 bag regimen is approved by US FDA for treating paracetamol poisoning. 2 bag regimen is recommended by clinical toxicology guidelines of New Zealand and Australia. 


Reference

  • Thanacoody et al. BMC Pharmacology and Toxicology 2013, 14:20 http://www.biomedcentral.com/2050-6511/14/20
  • Pettie JM, Caparrotta TM, Hunter RW, Morrison EE, Wood DM, Dargan PI, Thanacoody RH, Thomas SHL, Elamin MEMO, Francis B, Webb DJ, Sandilands EA, Eddleston M, Dear JW. Safety and Efficacy of the SNAP 12-hour Acetylcysteine Regimen for the Treatment of Paracetamol Overdose. EClinicalMedicine. 2019 May 2;11:11-17. doi: 10.1016/j.eclinm.2019.04.005. PMID: 31317129; PMCID: PMC6610779.
  • Wong A, Isbister G, McNulty R et al. Efficacy of a two bag acetylcysteine regimen to treat paracetamol overdose (2NACstudy). eClinicalMedicine, 2020; 20
  • Wong, A., & Graudins, A. (2016). Simplification of the standard three-bag intravenous acetylcysteine regimen for paracetamol poisoning results in a lower incidence of adverse drug reactions. Clinical Toxicology, 54(2), 115–119. https://doi.org/10.3109/15563650.2015.1115055

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