From the Guidelines
The recommended dosing of N-acetylcysteine (NAC) for acetaminophen overdose is an intravenous loading dose of 150 mg/kg over 15 minutes, followed by a maintenance dose of 50 mg/kg over 4 hours, and then 100 mg/kg over 16 hours, as this regimen has been shown to be effective in reducing hepatotoxicity and mortality 1.
Key Considerations
- The treatment should be initiated as soon as possible after ingestion, ideally within 8 hours, though it may still be beneficial up to 24 hours post-ingestion.
- For oral administration, a loading dose of 140 mg/kg can be given, followed by 70 mg/kg every 4 hours for a total of 17 doses.
- Treatment decisions should be guided by the patient's acetaminophen level plotted on the Rumack-Matthew nomogram, along with the time since ingestion.
- Patients may experience nausea, vomiting, or anaphylactoid reactions during treatment, which can be managed by slowing the infusion rate or providing antihistamines.
Evidence Summary
- A study published in Hepatology in 2005 found that NAC is effective and safe for the treatment of acetaminophen overdose, and recommended its use in any case of acute liver failure where acetaminophen overdose is suspected or possible 1.
- Another study published in Annals of Emergency Medicine in 2007 recommended administering NAC to patients with possible or probable risk for hepatotoxicity as determined by the Rumack-Matthew nomogram, ideally within 8 to 10 hours postingestion 1.
- A review of the literature published in Annals of Emergency Medicine in 2007 found that the incidence of severe hepatotoxicity and mortality is related to the time to first treatment with NAC, and that treatment within 8 hours of ingestion is associated with the best outcomes 1.
From the FDA Drug Label
DOSAGE AND ADMINISTRATION General Regardless of the quantity of acetaminophen reported to have been ingested, administer acetylcysteine solution immediately if 24 hours or less have elapsed from the reported time of ingestion of an overdose of acetaminophen. 4. Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. 5 Determine subsequent action based on predetoxification plasma acetaminophen information. Choose ONE of the following four courses of therapy.
- Predetoxification plasma acetaminophen level is clearly in the toxic range (See Acetaminophen Assays - Interpretation and Methodology below): Administer a first maintenance dose (70 mg/kg acetylcysteine) 4 hours after the loading dose.
The recommended dosing of N-acetylcysteine (NAC) for acetaminophen overdose is:
- A loading dose of 140 mg/kg of body weight
- Followed by a maintenance dose of 70 mg/kg 4 hours after the loading dose, if the predetoxification plasma acetaminophen level is clearly in the toxic range 2
From the Research
NAC Dosing for Acetaminophen Overdose
- The recommended dosing of N-acetylcysteine (NAC) for acetaminophen overdose varies, with different studies suggesting different protocols 3, 4, 5.
- A common oral regimen consists of a loading dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 doses, totaling 72 hours of therapy 5.
- Intravenous NAC protocols have also been studied, with one regimen consisting of a loading dose of 140 mg/kg, followed by 12 doses of 70 mg/kg every 4 hours, for a total of 48 hours 4.
- Some studies suggest that shorter treatment regimens, such as 24 or 36 hours, may be effective and safe for certain patients, but further research is needed to support this approach 5.
- In cases of massive acetaminophen overdose, higher doses of NAC may be necessary, with some evidence suggesting step-wise increases in dosing in response to high acetaminophen concentrations 6.
- It is essential to carefully monitor patients for signs of NAC overdose, which can include hemolysis, thrombocytopenia, and acute renal failure, especially when administering high doses 7.