April 2017

Acetaminophen toxicity is a result of the formation of a reactive intermediate N-acetyl-p-benzoquinonimine (NAPQI), the product of a minor pathway involved in the metabolism of acetaminophen. At therapeutic doses, the majority of acetaminophen metabolism occurs via glucuronidation and sulfation to nontoxic metabolites. In overdose, the nontoxic routes of metabolism become saturated and the metabolism of acetaminophen to NAPQI becomes a major metabolic pathway. The formation of NAPQI occurs primarily via oxidation by hepatic CYP2E1 and, to a lesser extent, by CYP3A4, CYP2A6, and CYP1A2. A fraction of the total NAPQI may be a result of renal CYP2E1 metabolism.

The FDA has issued a Safety Alert restricting the use of codeine and tramadol in children. Children under 12 years and some adolescents younger than 18 years (especially those with certain genetic factors, obesity, or obstructive sleep apnea and other breathing problems) should not use medicines containing these drugs because of increased medical risks, including slowed or difficult breathing and death. The FDA is also recommending against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants, including excess sleepiness, serious breathing problems, or death.