Acetaminophen Intoxication and Length of Treatment: How Long Is Long Enough?

Todd Kociancic, PharmD, and Michael D. Reed, PharmD, FCCP, FCP


Pharmacotherapy. 2003;23(8) 

In This Article

Abstract and Introduction


The currently recommended dosing scheme for treating acetaminophen overdose in the United States consists of a loading dose of oral N-acetylcysteine 140 mg/kg, followed by 70 mg/kg every 4 hours for 17 doses, for a total of 72 hours of oral N-acetylcysteine therapy. This protocol has been both effective and safe. We critically evaluated the evidence that supports reducing the course of N-acetylcysteine therapy from 72 hours to 24 or 36 hours. This shorter regimen offers important benefits for both the patient and the patient's family, such as increased drug tolerability and reduced hospital stay. Patients who intentionally ingested acetaminophen with harmful intent could receive appropriate psychosocial treatment more quickly. In addition, shorter courses of N-acetylcysteine therapy have positive financial ramifications by reducing the hospital stay by 1 or 2 days. Clearly, a shorter treatment regimen would not be appropriate for all patients, particularly those who seek treatment late (> 24 hrs after ingestion) and those with evidence of organ toxicity. In order to provide the necessary evidence to support a change in accepted clinical practice, further investigation on the safety and efficacy of a shorter N-acetylcysteine regimen should be conducted by clinical researchers in a controlled manner.


Acetaminophen is one of the most commonly administered analgesic and antipyretic drugs among children and adults worldwide. The drug is available in many formulations, including a large number of combination products. In acute overdose, acetaminophen is associated with the risk of severe hepatic necrosis and death. In 2001, 64 poison centers across the United States received 112,809 calls concerning exposures to acetaminophen alone or in combination with other drugs.[1] Of the calls with successful follow-up assessment, 59,087 cases were treated in a health care facility, and 238 deaths (0.4% of treated cases and 0.21% of total exposures) were reported. Some deaths resulted from suicide or abuse (43%) and/or coingestion of other drugs with acetaminophen (50%).

Thus, these data document that in acute overdoses of acetaminophen, prompt assessment and specific treatment are very effective in preventing associated mortality. The efficacy of treatment is undoubtedly augmented by increased public awareness of acetaminophen toxicity, the need to treat serious overdoses, and storage of drugs in areas inaccessible to children, all of which decrease the number of large, acute exposures to acetaminophen. More recently, some practitioners have proposed administering a shorter course of antidote therapy than the standard 72 hours for certain acutely poisoned patients. We critically evaluated the evidence supporting such an approach and reconfirm the need for appropriately designed studies to provide the necessary evidence to support a change in accepted clinical practice.


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