UMEM Educational Pearls

Category: Toxicology

Title: Times When a Subtoxic 4-Hour Acetaminophen Level May Need Repeating

Keywords: acetaminophen, Rumack-Matthew nomogram, diphenhydramine, opioid (PubMed Search)

Posted: 8/8/2012 by Bryan Hayes, PharmD (Emailed: 8/9/2012) (Updated: 8/9/2012)
Click here to contact Bryan Hayes, PharmD

There is a growing recognition of patients who have a subtoxic acetaminophen level at the 4-hour mark, but then still go on to have a toxic level later.

This is concerning in that we usually can exclude the chance for toxicity if the 4-hour, post-ingestion level is < 150 mcg/mL following an acute ingestion (plotted on Rumack-Matthew nomogram).

It still is not clear exactly what subset of patients need to have a second level drawn, but a recurring theme seems to be ingestion of acetaminophen in combination with agents that slow GI motility, such as diphenhydramine or opioids. It may be worth ordering a second APAP level (possibly at 8 hours) in patients ingesting these prodcuts.


Dougherty PP, Klein-Schwartz W. Unexpected late rise in plasma acetaminophen concentrations with change in risk stratification in acute acetaminophen overdoses. J Emerg Med 2012;43:58-63.

Tighe TV, Walter FG. Delayed toxic acetaminophen level after initial four hour nontoxic level. Clin Toxicol 1994;32:431–4.
Ho S, Arellano M, Zolkowski-Wynne J. Delayed increase in acetaminophen concentration after Tylenol PM overdose. Am J Emerg Med 1999;17:315–7.
Schwartz EA, Hayes BD, Sarmiento KF. Development of hepatic failure despite use of intravenous acetylcysteine after a massive ingestion of acetaminophen and diphenhydramine. Ann Emerg Med 2009;54:421–3.
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