Label for Your Liver

Acetaminophen toxicity is caused when glucuronidation and sulfation become saturated after an acetaminophen overdose. The saturation of these major metabolic pathways cause the formation of excess NAPQI to be formed by CYP450-mediated N-hydroxylation (AAP, 2001). Two mechanisms can contribute to liver damage. The first of which occurs when NAPQI binds to hepatic cell macromolecules and can progress to necrotic cell death. The second mechanism is the depletion of glutathione which causes oxidative stress and subsequently liver damage and possibly death (AAP, 2001).

Acetaminophen is also one of the most widely used over-the-counter medications. Of particular concern is the ubiquitous statement about liver damage on Tylenol’s label is as follows: This product contains acetaminophen. Severe liver damage may occur if you take *more than 8 gelcaps in 24 hours, which is the maximum daily amount*with other drugs containing acetaminophen* 3 or more alcoholic drinks every day while using this product. The label does not mention that death may result as a consequence of the liver damage, nor how common overdose is associated with acetaminophen. Concurrently, the Tylenol brand has been synonymous with safety and universal applicability. This benign reputation is astounding in light of the 140,000 poisoning cases, 56,000 emergency room visits, 26,000 hospitalizations, and 150 deaths per annum (Bronstein et. al., 2006). These include accidental and intentional overdoses. The inclusion of a statement regarding the potential for death in addition to liver damage is warranted. In addition, encouraging physicians especially in primary care to address acetaminophen usage among their children and themselves would reinforce a cautionary message.



Reference:

American Academy of Pediatrics Committee on Drugs (2001) Acetaminophen toxicity in children. Pediatrics 108:1020–1024


Bronstein AC, Spyker DA, Cantilena LR Jr, Green J, Rumack BH, Heard SE. (2006) Annual Report of the American Association of Poison Control Centers National Poison Data System (NPDS). Clin Toxicol. 45, 815–917.


Schilling, A. (January 2010) Acetaminophen: Old drug, new warnings.Cleveland Clinic Journal of Medicine, 77 (1) 19-27