From the Guidelines
N-acetylcysteine (NAC) is the primary treatment for acetaminophen (Tylenol) poisoning, administered as an IV infusion in a three-step protocol, as recommended by the most recent and highest quality study 1. The protocol involves a loading dose of 150 mg/kg NAC in 5% dextrose over 15 minutes, followed by 50 mg/kg in 5% dextrose over 4 hours, and finally 100 mg/kg in 5% dextrose over 16 hours. This 21-hour protocol is essential for patients with potentially toxic acetaminophen levels or in cases where the ingestion time or amount is unknown but toxicity is suspected. NAC works by replenishing glutathione stores, which are depleted during acetaminophen metabolism, thereby preventing the formation of toxic metabolites that cause liver damage, as supported by studies such as 1 and 1. Some key points to consider when administering NAC include:
- Treatment should be initiated as soon as possible, ideally within 8 hours of ingestion for maximum effectiveness, though it can still provide benefit when started later, as noted in 1.
- Monitor liver function tests, coagulation parameters, and acetaminophen levels throughout treatment.
- Patients may experience anaphylactoid reactions during the initial infusion, which can be managed by slowing the infusion rate and administering antihistamines if needed, as mentioned in 1. It is also important to note that the Rumack-Matthew nomogram may aid in determining the likelihood of serious liver damage, but cannot be used to exclude possible toxicity due to multiple doses over time, or altered metabolism in the alcoholic or fasting patient, as discussed in 1. Given these considerations, administration of NAC is recommended in any case of acetaminophen overdose in which toxicity is suspected, as recommended by 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. ACETYLCYSTEINE IS NOT APPROVED FOR PARENTERAL INJECTION.
The treatment for Tylenol poisoning with IV infusion protocol is not approved. The FDA drug label recommends oral administration of acetylcysteine, with a loading dose of 140 mg per kg of body weight 2. IV infusion is not an approved route of administration.
From the Research
Treatment for Tylenol Poisoning
- The treatment for Tylenol (acetaminophen) poisoning typically involves the administration of N-acetylcysteine (NAC) as an antidote 3, 4, 5, 6, 7.
- NAC can be administered orally or intravenously, with intravenous administration being preferred for most patients due to its faster onset of action and reduced risk of adverse effects 5.
IV Infusion Protocol
- A novel dosing regimen for immediate NAC treatment involves administering 110 mg/kg over the first 5 hours (22 mg/kg/h) followed by the last two phases of the conventional regimen, or 200 mg/kg over 9 hours (22.6 mg/kg/h) followed by the last phase of the conventional regimen 4.
- The updated guidelines for the management of paracetamol poisoning in Australia and New Zealand recommend a two-bag acetylcysteine infusion regimen (200 mg/kg over 4 hours, then 100 mg/kg over 16 hours) 7.
- This regimen has similar efficacy but significantly reduced adverse reactions compared to the previous three-bag regimen 7.
Use of Activated Charcoal
- Activated charcoal is a safe and effective adjunct in the management of acetaminophen overdose, and its use in combination with NAC may improve patient outcomes 3, 6.
- However, the concomitant administration of activated charcoal and NAC may not be recommended due to the potential for adsorption and inactivation of NAC by charcoal 3.
Special Considerations
- Massive paracetamol overdoses that result in high paracetamol concentrations more than double the nomogram line should be managed with an increased dose of acetylcysteine 7.
- All potentially toxic modified release paracetamol ingestions (≥ 10 g or ≥ 200 mg/kg, whichever is less) should receive a full course of acetylcysteine 7.
- Patients ingesting ≥ 30 g or ≥ 500 mg/kg should receive increased doses of acetylcysteine 7.