Toxicity Associated with Acetaminophen

At a Glance

Clinical presentation of acetaminophen toxicity is dependent on the amount ingested and the time from ingestion. Early symptoms can include nausea, vomiting, and excessive sweating. Twenty-four to forty-eight hours post-exposure, the clinical symptoms decrease but an increase in transaminase levels (LFTs), prothrombin time, and serum bilirubin can be seen. Three to four days after a toxic exposure to acetaminophen is when peak hepatotoxicity occurs. If there has been significant hepatic injury, the patient will display coagulopathy, jaundice, and evidence of renal failure.

What Tests Should I Request to Confirm My Clinical Dx? In addition, what follow-up tests might be useful?

A blood acetaminophen level should be ordered to confirm the clinical diagnosis. Historically, the Rumack-Matthew Nomogram has been used to evaluate blood acetaminophen results. However, this nomogram was developed based on an immediate release, single-drug formulation; it does not apply to extended release formulations or combinations with opiates or other drugs (e.g., Percocet, Tylox). In addition, the nomogram was developed for adult populations, so it does not apply to pediatric populations. An alternative approach is to take serial measurements of blood acetaminophen and calculate the half-life of the drug in the patient; if the half-life is extended beyond that which is typical, that indicates saturation of hepatic metabolism of acetaminophen. Useful follow-up tests to assess hepatic injury include prothrombin time, aspartate aminotransferase (AST), and alanine aminotransferase (ALT).(Table 1)

Table 1

Test Results Indicative of the Disorder
Blood Acetaminophen AST ALT
>100 mg/L >1000 IU/L >1000 IU/L

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

OTC drugs and herbal medications do not typically interfere significantly in commercially available acetaminophen assays. However, these assays are spectrophotometric and rely on measurement of the absorbance (color) at a particular wavelength; excessive hemolysis or lipemia in a specimen can affect the absorbance profile of the specimen and interfere with the result. In addition, depending on the source (manufacturer) of the assay, excessive amounts of bilirubin can also impact the result.

What Lab Results Are Absolutely Confirmatory?

Elevated blood acetaminophen is confirmatory for acetaminophen exposure and intoxication. Proper interpretation of the result requires knowledge (or at least a gross estimate) of the time elapsed between the last acetaminophen ingestion and clinical presentation.

Are There Any Factors That Might Affect the Lab Results? In particular, does your patient take any medications - OTC drugs or Herbals - that might affect the lab results?

Although it is increasingly rare, some clinical laboratories test for acetaminophen using a chromatography-based kit called "Toxi-Lab." In this kit, the presence of acetaminophen can be masked by other early-eluting compounds in the basic extraction and its presence is more reliably detected if neutral or acidic extracts are analyzed.

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