What is the treatment for acetaminophen (Tylenol) toxicity?

From the Guidelines

The treatment for Tylenol (acetaminophen) toxicity primarily involves administering N-acetylcysteine (NAC), which should be started as soon as possible after ingestion, as it has been shown to be effective in reducing hepatotoxicity and mortality 1.

Treatment Regimen

For oral administration, the standard regimen begins with a loading dose of 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 additional doses. Alternatively, intravenous NAC can be given as a 150 mg/kg loading dose over 60 minutes, then 50 mg/kg over 4 hours, followed by 100 mg/kg over 16 hours.

Treatment Decisions

Treatment decisions are based on the patient's acetaminophen blood level plotted on the Rumack-Matthew nomogram, with treatment indicated if levels fall above the possible toxicity line. Supportive care is essential, including fluid resuscitation and monitoring of liver function tests. Activated charcoal may be administered if the patient presents within 1-2 hours of ingestion to reduce absorption.

Mechanism of Action

NAC works by replenishing glutathione stores in the liver, which are depleted during acetaminophen metabolism and are crucial for detoxifying the harmful metabolite NAPQI that causes liver damage. Early treatment with NAC is critical as it's most effective when given within 8-10 hours of ingestion, though it still provides benefit even when started later.

Special Considerations

In cases of repeated supratherapeutic ingestions or extended-release preparations, the decision to treat with NAC must be individualized, and treatment should be considered if there is any suspicion of hepatotoxicity. The Rumack-Matthew nomogram may not be applicable in these situations, and other factors such as liver function tests and clinical presentation should be taken into account.

Key Points

• NAC should be started as soon as possible after ingestion
• Treatment decisions are based on the Rumack-Matthew nomogram
• Supportive care, including fluid resuscitation and monitoring of liver function tests, is essential
• Activated charcoal may be administered if the patient presents within 1-2 hours of ingestion
• Early treatment with NAC is critical, but it still provides benefit even when started later
• Individualized treatment decisions are necessary in cases of repeated supratherapeutic ingestions or extended-release preparations.

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. The following procedures are recommended:

1. The stomach should be emptied promptly by lavage or by inducing emesis with syrup of ipecac.
2. Administer the loading dose of acetylcysteine, 140 mg per kg of body weight. 5 Determine subsequent action based on predetoxification plasma acetaminophen information.

The treatment for acetaminophen (Tylenol) toxicity is:

• Immediate administration of acetylcysteine solution if 24 hours or less have elapsed from the reported time of ingestion
• Stomach emptying by lavage or inducing emesis with syrup of ipecac
• Loading dose of acetylcysteine, 140 mg per kg of body weight
• Subsequent doses determined by predetoxification plasma acetaminophen level 2

From the Research

Treatment for Acetaminophen (Tylenol) Toxicity

The treatment for acetaminophen (Tylenol) toxicity involves several interventions, including:

• Inhibition of absorption using activated charcoal, gastric lavage, and ipecacuanha 3, 4
• Administration of antidotes, such as N-acetylcysteine (NAC) 3, 4, 5, 6
• Liver transplantation in severe cases of fulminant hepatic failure 3, 4

Reduction of Absorption

Activated charcoal seems to have the best risk-benefit ratio for reducing the absorption of paracetamol 3, 4. Gastric lavage and ipecacuanha can also reduce absorption, but their clinical benefit is unclear 3, 4.

Antidotes

N-acetylcysteine (NAC) is the preferred antidote for paracetamol overdose, with a potential reduction in mortality in patients with fulminant hepatic failure 3, 4, 6. The optimal route of administration for NAC is controversial, with both oral and intravenous routes being effective 6. However, intravenous NAC may be preferable due to concerns over reduced bioavailability of oral NAC by charcoal and vomiting 6.

Special Considerations

In cases of Tylenol Extended Relief overdose, the elimination half-life of acetaminophen is similar to that of immediate-release acetaminophen overdose, but absorption may continue beyond 2-4 hours 5. Therefore, a single 4-hour acetaminophen determination may not be sufficient to recognize patients with potentially toxic ingestions, and additional determinations may be necessary 5.

Concomitant Use of Activated Charcoal and N-acetylcysteine

The concomitant use of activated charcoal and NAC is not recommended due to concerns over adsorption and inactivation of NAC by charcoal 7. However, a study found no significant differences in NAC serum levels when administered with or without activated charcoal 7. Further studies are needed to evaluate the safety and efficacy of concomitant use.