Feb 26, 2001: Following acetaminophen(APAP) ingestion, when is the Rummack-Mathew nomogram invalid?

Anticonvulsants are currently widely administered  to treat mood disorders.  If a child is taking therapeutic anticonvulsants or is nutritionally depleted (AIDS or cancer), the nomogram should be cut in half.  For example, rather than administering N-acetylcysteine (NAC)to a child  with a four-hour serum APAP concentration of 140 mg/mL, NAC should be administered if the  4-hour concentration is 70 mg/mL.

The parmacokinetics of the drug are the basis for this recommendation.  Normally, only about 4% of APAP is metabolized by the cytochrome P-450 pathway to a toxic intermediate metabolite which is detoxified by glutathione (an amino acid).  In the overdose setting AND when the patient is on CYT P-450 inducers, a much larger amount of the drug is metabolized through this pathway depleting glutathione much earlier. In nutritionally depleted patients, glutathione stores are small resulting in less glutathione available to bind with the toxic metabolite.