The first data point on the Rumack-Matthew nomogram is at 4 hours
The decision of whether or not to administer the antidote can be made after four hours, based on the acetaminophen level. As long as it is administered within 8 hours of ingestion, the outcome will not be adversely affected.
NAPQI is the prime toxic mediator, which builds up when glutathione stores deplete causing hepatotoxicity.
The first stage of acetaminophen toxicity is largely asymptomatic.
The toxic dose of single-ingestion non-sustained-release formulation is about 140 mg/kg.
Activated charcoal within 4 hours of ingestion
N-acetylcusteine, administered within 8 hours of ingestion
Therapy is guided by the Rumack-Matthew nomogram, provided the ingestion is an acute one involving nonsustained-release preparations.
Acetaminophen levels drawn at hours 4-20 are plotted on the nomogram and guide therapy based on the potential for hepatic (not renal) toxicity
N-acetylcysteine is the antidote and prevents toxicity by inhibiting the binding of NAPQI to hepatocytes.
Treatment with N-acetylcysteine is most effective if started within 10 hours after ingestion.
The FDA-approved recommendation is to continue oral treatment for 72 hours.
In the US only the oral form is FDA-approved
In other countries IV NAC have been safely used for many years, however anaphylaxis is a possible side-effect
Activated charcoal binds acetaminophen and should be given early
Liver function tests are not indicated for trivial acetaminophen ingestions (i.e. "handful of pills") but may be useful in severe ingestions