New Options for the Use of N-Acetylcysteine in Acetaminophen Overdose

Marcia L. Buck, PharmD, FCCP, FPPAG


Pediatr Pharm. 2016;22(4) 

In This Article

Abstract and Introduction


Acetaminophen remains the most common cause of poisoning reported in the United States. In 2014, the American Association of Poison Control Centers reported 73,347 toxic acetaminophen exposures with 108 fatalities. Of those reports, 23,847 involved children and adolescents.[1] The antidote for acetaminophen overdose, N-acetylcysteine (acetylcysteine), was first approved by the Food and Drug Administration (FDA) in 1963 as a mucolytic to be delivered by nebulization. By the 1970s, it was being widely used to prevent acetaminophen-induced hepatotoxicity.[2] Oral administration of the 20% solution, however, was limited by nausea and vomiting resulting from the inability to mask the drug's odor and taste. An intravenous formulation was approved by the FDA on January 23, 2004 and has subsequently become the primary method for delivery of the antidote.[3]

A new formulation, effervescent tablets to be added to water to form a flavored oral solution, was approved by the FDA on February 9, 2016.[4,5] The solution is designed to be more palatable than the solution for inhalation and allow for rapid administration of acetylcysteine in settings where insertion of an IV catheter is not possible or may delay therapy. The tablets can also be carried by emergency medical personnel for administration in the prehospital setting for known acetaminophen overdoses. In addition to this new formulation, recent publications have described alternative dosing schedules for the IV formulation and the development of a modified form of acetylcysteine that may offer a more potent antidote with fewer adverse effects.