N-Acetylcysteine (NAC) Indications and Usage

Primary Indication: Acetaminophen Overdose

NAC is the definitive antidote for acetaminophen overdose and should be initiated immediately in all cases of known or suspected overdose, regardless of serum acetaminophen levels or time since ingestion, as recommended by the American College of Medical Toxicology 1, 2
The American Association of Poison Control Centers recommends NAC for acute single ingestion with serum acetaminophen levels plotting above the "possible toxicity" line on the Rumack-Matthew nomogram, and for any presentation within 24 hours of suspected overdose 2, 3
NAC reduces mortality even with late treatment in delayed presentations beyond 24 hours when acetaminophen overdose is suspected, according to the American College of Emergency Physicians 2, 3
The American Academy of Clinical Toxicology recommends NAC for unknown time of ingestion with detectable acetaminophen levels, and for extended-release acetaminophen formulations which demonstrate prolonged absorption 2, 3
NAC is recommended for repeated supratherapeutic ingestions (>4g per 24 hours or ≥6g per 24-hour period for ≥48 hours) by the American College of Medical Toxicology 2, 3
Established acute liver failure with suspected or confirmed acetaminophen toxicity requires NAC, regardless of time since ingestion, as recommended by the American Association for the Study of Liver Diseases 1, 2, 3

NAC improves transplant-free survival and post-transplant survival in acute liver failure from any cause, not just acetaminophen, with a strength of evidence rated as high by the American College of Gastroenterology 1
Transplant-free survival increases from 30% to 41% with NAC treatment, and post-transplant survival improves from 71.4% to 85.7%, according to the American Association for the Study of Liver Diseases 1
Overall survival in adult patients improves from 59% to 76% with NAC, with a moderate strength of evidence, as recommended by the American College of Gastroenterology 1
NAC benefits are most pronounced in patients with grades I-II encephalopathy, suggesting early initiation is critical, according to the American Neurogastroenterology and Motility Society 1

For acetaminophen overdose, the recommended intravenous protocol is a loading dose of 150 mg/kg over 15 minutes, followed by a second dose of 50 mg/kg over 4 hours, and a third dose of 100 mg/kg over 16 hours, as recommended by the American College of Medical Toxicology 2, 3
The oral protocol for acetaminophen overdose consists of a loading dose of 140 mg/kg, followed by maintenance of 70 mg/kg every 4 hours for 17 additional doses, according to the American Association of Poison Control Centers 2

Never delay NAC while awaiting acetaminophen levels if overdose is suspected, as recommended by the American College of Emergency Physicians 2, 3
Low or absent acetaminophen levels do not rule out poisoning if ingestion was remote or occurred over several days, according to the American Academy of Clinical Toxicology 3
Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning and warrant NAC even without confirmatory history, as recommended by the American Association for the Study of Liver Diseases 2, 3