(Summary version, Updated November 2021)
N-Acetylcisteine (NAC) is a mucolytic, antioxidant and a glutathione-inducer. It is positioned as the cornerstone antidote for the prevention and treatment of liver toxicity secondary to acetaminophen (APAP) overdose (6, 10, 11, 12, 15, 16), with US-FDA approval for IV, PO and effervescent tablets (9, 13, 14).
Why use NAC:
It has several roles in preventing injury and diminishing ongoing hepatic damage due acetaminophen overdose (1, 3, 5, 6, 11, 15):
Increases sulfation of APAP before it is metabolized to NAPQI.
Detoxifies NAPQI as a glutathione substitute.
Increases available glutathione as a substrate for its synthesis.
Decreases cellular damage secondary to NAPQI toxicity through nonspecific mechanisms (free radical scavenging, enhanced oxygen delivery, increased mitochondrial ATP production, and antioxidant effects).
Election of PO versus IV formulation depends mostly on availability, as they are equally efficacious if successfully administered within 8 hours (the most significant efficacy predictor; with the greatest outcomes achieved when administered within 6-8 hours of APAP ingestion when glutathione stores are depleted around 30% of normal levels)(5, 7, 8, 15).
IV NAC might be preferred in patients who: (i) are seriously poisoned, (ii) presented late at the ED, (iii) are thought to be particularly susceptible to APAP hepatotoxicity, (iv) present nausea and vomiting, and (v) who are unable to take NAC orally. (5). IV formulation carries a significant incidence of mild anaphylactoid reactions, ranging 3.5 to 50% in published series, mostly occurring within the first hour (5), but few events of nausea and vomiting (3%) compared with PO administration (20%)(15).
PO NAC administration on the other hand, besides nausea and vomiting (20%), other mild or serious adverse effects are quite rare. This is a reason why it should be considered in mild and moderate cases of APAP overdose in stable patients without any other immediate risk situations (5).