Normal Acetaminophen Levels
There is no "normal" therapeutic acetaminophen level in clinical practice—acetaminophen levels are only measured and interpreted in the context of suspected overdose using the Rumack-Matthew nomogram. 1
Understanding Acetaminophen Levels in Clinical Context
Therapeutic vs. Toxic Levels
Therapeutic dosing (up to 4 g/day in adults) produces plasma concentrations of 5-20 mcg/mL, which are not routinely monitored and have no clinical significance for treatment decisions 2
Toxic levels are defined by the Rumack-Matthew nomogram, which plots serum acetaminophen concentration against time post-ingestion (4-24 hours after acute ingestion) 1
A level >150 mcg/mL at 4 hours post-ingestion correlates with severe hepatotoxicity risk and mandates N-acetylcysteine (NAC) treatment 2
Levels >200 mcg/mL at 4 hours are associated with even higher risk of liver damage 3
Critical Clinical Pitfalls
Low or undetectable acetaminophen levels do NOT rule out acetaminophen poisoning if the ingestion was remote (>24 hours), occurred over several days, or timing is unknown 4, 1
Patients can present with fulminant liver failure and undetectable acetaminophen levels days after ingestion, particularly with chronic supratherapeutic ingestions 5
Very high aminotransferases (AST/ALT >3,500 IU/L) are highly correlated with acetaminophen poisoning and should prompt NAC treatment even when acetaminophen levels are low or history is lacking 4, 1
When to Measure Acetaminophen Levels
All patients presenting with acute liver failure should have acetaminophen levels drawn, as acetaminophen is the leading cause of acute liver failure in the United States and Europe 4
Levels should be drawn 4-24 hours post-ingestion for acute overdoses to allow proper interpretation using the Rumack-Matthew nomogram 1
For repeated supratherapeutic ingestions, treat with NAC if serum acetaminophen is ≥10 mcg/mL OR if AST/ALT >50 IU/L, regardless of nomogram placement 1