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LETTER

Use of the Rumack-Matthew Nomogram in Cases of Extended-Release Acetaminophen Toxicity

right arrow Susi Vassallo, MD; Abu N.G.A. Khan, MD; and Mary Ann Howland, PharmD

1 December 1996 | Volume 125 Issue 11 | Page 940


TO THE EDITOR:

A 17-year-old healthy girl presented to the hospital after a suicidal ingestion of 13 g of Extended-Relief Tylenol (McNeil Consumer Products Co., Fort Washington, Pennsylvania). She was asymptomatic, and vital signs and physical examination findings were normal. Acetaminophen levels were obtained 3 hours and 5 hours after ingestion. Both values were below the Rumack-Matthew nomogram (Figure 1). While the patient awaited psychiatric consultation, the acetaminophen level was measured for the third time 11 hours after ingestion. The level was 79.8 µg/mL and was in the toxic range when plotted on the nomogram. Oral N-acetylcysteine therapy was begun, and the patient received the standard 72-hour regimen. Liver function test results were monitored every 12 hours and remained normal for the next 89 hours. Results of serum and urine toxicology screens were negative.



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Figure 1. Acetaminophen levels after suicidal ingestion of 13 g of the drug. NAC = N-acetylcysteine.

 

Extended-relief acetaminophen is available in 650-mg caplets intended to release 325 mg immediately and 325 mg more slowly. Although a few published case reports have described acetaminophen overdose [1, 2], it is unclear how and whether the different toxicokinetics of extended-relief acetaminophen will affect use of the Rumack-Matthew nomogram.

What does the nomogram line represent? Does it indicate the total area under the curve, and is this the important factor in the development of toxicity? Is it some threshold serum value that, when surpassed, results in saturation of sulfation and glucuronidation and depletion of glutathione? Prescott and colleagues' report [3] of hepatic failure in untreated acetaminophen overdoses showed early prolongation of apparent acetaminophen half-lives before hepatotoxicity occurred, probably as a result of saturation pharmacokinetics. Late crossing of the nomogram line after a single acute overdose of extended-relief acetaminophen may simply reflect slow ongoing absorption rather than saturation pharmacokinetics. Unless some threshold value has been reached, toxicity might be unlikely. Further research and a thoughtful rational approach to acetaminophen overdose is needed.


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New York Regional Poison Control Center, New York, NY 10016.


References
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1. Cetaruk EW, Dart RC, Horowitz RS, Hurlbut KM. Extended-release acetaminophen overdose [Letter]. JAMA. 1996; 275:686.

2. Graudins A, Aaron CK, Linden CH. Overdose of extended-release acetaminophen [Letter]. N Engl J Med. 1995; 333:196.

3. Prescott LF, Wright N, Roscode P, Brown SS. Plasma-paracetamol half-life and hepatic necrosis in patients with paracetamol overdose. Lancet. 1971; 1:519-22.

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